Notes in Pharmacology

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PHARMACOLOGY
- came from the Greek word "Pharmakon" which means "Drug" and "Logos" which means
"Discourse" / "Logia" (Latin) - "Study".
- it is a science that deals with the chemical and physical properties of drugs, their sources,
effects, biotransformation and excretion.
- it is the study of the effects of chemical substances upon living tissues.
HISTORY OF PHARMACOLOGY
Pharmacologic thought had its beginning when early humans began to wonder why the
chewing of certain plant roots or leaves altered their awareness or functions. As experience in
root and leaf chewing progressed into therapeutic berry picking and smoke smelling, the
experiences were spread and shared. As time progressed, some individuals became more
astute in observing and remembering that plant products produced predictable effects. Thus,
the first pharmacologist was born. Clearly this humble beginning has evolved through the
years into a huge industrial and academic community that is concerned with the study and
development of drugs. Drugs that evolved are then prescribed and dispensed through the
practice of medicine, dentistry, and pharmacy. (for continuation - refer to Holroyd)
The history of pharmacology can be divided into 2 periods: the early period dates back to
antiquity and is characterized by empirical observations in the use of crude drugs. It is
interesting that even primitive people could discover relationships between drugs and disease.
The use of drugs has been so prevalent throughout history that Sir William Osler stated (1894)
with some justification that man has an inborn craving for medicine.
In contrast to this ancient period, modern pharmacology is based on experimental
investigations concerning the site and mode of action of drugs. The application of the
scientific method to studies on drugs was initiated in France by Francois Magendie and was
expanded by Claude Bernard (1813-1878). The name of Oswald Schiemie Debug (1838
1921) is commonly associated with the development of Experimental Pharmacology - in
Germany and John Jacob Abel (1857-1938) played a similar role in the U.S.
The growth of pharmacology was greatly stimulated by the rise of synthetic organic
chemistry which provided new tools and new therapeutic agents. More recently,
pharmacology has benefited from developments of other basic sciences and in turn has
contributed to their growth.
Some of the greatest changes in medicine that have occurred during the last few decades
are directly attributable to the discovery of new drugs.
Claude Bernard - expanded application in scientific method.

Alexander Fleming - discovered penicillin.
Hippocrates - father of medicine
John Jacob Abel - development of experiments in pharmacology
Oswald Schieme Debug - development of experimental pharmacology
Joseph Lister - antiseptic technique
BRANCHES OF PHARMACOLOGY
1. Pharmacokinetics - concerned with the absorption, distribution, biotransformation, and
excretion of drugs.
- movement of drugs in the body. "How the body handles the drug?"
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2. Pharmacodynamics - deals with the effects of drugs in the body; deals with the mechanism
of action/effect of a drug in living organisms and their corresponding responses and the
physiologic and biochemical effects of the drug. "How the drug produces its effect?" "What
the drug does to the body?"
3. Pharmacognosy - identification and procurement of crude and naturally occurring drugs.
Former name: "Materia Medica"
4. Pharmacy - procurement, preparation and dispensing of drugs.
5. Pharmacogenetics - effects of drug on people with congenital abnormalities of metabolism.
e.q. Eskimos - hydrolyze isoniazid = faster than other races.
barbiturates - geriatrics = stimulation instead of depression
6. Posology - study of dosage of drugs.
7. Toxicology - study of the adverse effects of drugs.
8. Biochemorphology - alteration of the chemical structure of drugs to produce a different effect.
9. Developmental pharmacology - effects of drugs in fetal development.
e.q. Thalidomide babies - teratogenic.
10. Pharmacotherapeutics - "clinical pharmacology' - the uses/application of drugs in the
treatment of disease; the art and science of using drugs in the diagnosis, treatment, and
prevention of disease.
11. Descriptive pharmacology - qualitative effects of drugs in man.
12. Clinical Pharmacology – the study of the effects of drugs in man.
13. Molecular pharmacology – the study of drug effects at the molecular level.
IMPORTANCE OF PHARMACOLOGY TO DENTISTRY

1. To be able to cure diseases
2. To be able to prescribe drugs to the patient appropriate for his condition.
3. To be able to communicate with the medical staff and practitioners.
***The dentist should be able to obtain the maximal advantage while producing the minimal
disadvantages.
***The prescriber should be aware of how drugs may modify the physiology of the patient.
DRUGS - any chemical substance that affects / modifies the biologic system.
- chemical necessary for the maintenance of life processes by their ability to act
selectively in biologic systems to accomplish a desired effect.
- a single entity that may be one of the constituent of medicine.
Medicine - may contain one or more active constituents (drugs) together with additives to
facilitate administration.
*** "All medicines are drugs, but not all drugs are medicine."
SOURCES OF DRUGS
1. Natural
a. Animals - glandular products are the chief medicinal currently obtained form animal
sources. e.q. thyroid hormone, insulin from pancreas of cattle and pigs,
epinephrine and ACTH.
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b. Plants - crude drugs maybe obtained from any part of various plants used medicinally.
E.q Leaves - Pito-pito, Alagaw, Banaba, etc.; digitalis from foxglove plant.
c. Minerals - iron, commonly used in the form of ferrous sulphate
2. Synthetic/Chemical Substances - done in the laboratory by chemists.
a. Pure drugs and other simple substances
b. Products of complex synthesis (antibiotics, sulfonamides and adrenocorticosteroids).
STAGES IN THE DEVELOPMENT OF A DRUG

Evolution of a New Drug
Drug development Strategies
Experimental Pharmacology
Toxicological Assessment
Clinical Evaluation
Marketing and Promotion
STRATEGIES
* Serendipity (luck and intuition)
* Molecular Roulette (random clinical synthesis)
* Program Basic Research with Synthesis of Specific Chemicals.
* Clinical Observation of Drug Action in the Practice.
PRINCIPAL INDIVIDUAL(S) STAGES IN THE DEVELOPMENT OF A DRUG

CONCERNED
Various Ideas
Chemist Natural or synthetic chemical compounds
Pharmacologists Pharmacological Tests
Biochemists Performs "biologic assays"
Toxicologists Acute toxicity Chronic toxicity tests
Mutagenicity Teratogenesis Carcinogenecity
Pharmacists Pharmaceutical formulation / Clinical trials
Clinical Pharmacologists Phase 1: A pilot investigation made in a small number
Normal Volunteers of normal volunteers
Dentist/Doctor/Patients Phase 2: An open clinical trial carried out in a small
Clinical Pharmacologists number of patients
Nurse Patients Statistician Phase 3: Large scale clinical trial
Practicing Dentists/Doctors Phase 4: Monitored release and post- marketing
and their patients surveillance of new drug
Accepted drug
CLINICAL EVALUATION
Phase I
* A pilot study that uses small numbers of human volunteers
* Initially, low doses of drug that are gradually increased are used and the toxic or exaggerated
effects are monitored
Phase II
* The drug is tested in limited numbers of hospitalized patients with the disease the drug is
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intended to treat
* The test drug is compared to established drugs and placebo
Phase III
* Testing is intended to large group of outpatients to permit evaluation of the drug under
conditions that may exist if the drug is marketed.
* If the drug is safe and effective for its intended use, the FDA may approve the drug for
marketing.
Phase IV
* A new drug is usually marketed only after a few hundreds, or at most few thousand patients have
been exposed to it for a relatively short period of time.
* Post-marketing surveillance is necessary to assess efficacy and toxicity of a new drug on a
larger scale.
* 3 MAJOR PHASES IN A PRE-CLINICAL TESTS

1. Acute Toxicity Test
2. Sub-acute (prolonged) Toxicity Test
3. Chronic Toxicity Test
PRINCIPLES OF DRUG ACTION

1. Cure disease
2. Alleviate symptoms
3. Replace deficiencies
FUNDAMENTAL ACTION OF DRUGS

1. STIMULATION - drugs that increases the overall activity of specialized organs, tissue, or cell.
e.q. caffeine (coffee - CNS stimulant; can cause tachycardia (inc. heart activity).
2. DEPRESSION - drugs that decreases the overall functional activity of cells, tissues, or organs.
e.q. alcohol, barbiturates.
3. IRRITATION - either inc. or dec. but it is said that stimulation is pushed too far to the point
of injuring the cell.; manifested as nausea, vomiting, itchiness, redness.
4. REPLACEMENT / SUPPLEMENT - drugs that can be used as substitutes for what is lacking
in the body. e.q. vitamins.
5. ANTIMICROBIAL / ANTIBACTERIAL - when the action of the drug is directed towards
the invading microorganism in the body. e.q. antibiotics.
6. ANESTHETIC - a solution that tends to produce a temporary block or nerve conduction.
7. PROPHYLACTIC - to prevent any untoward occurrences/illnesses in the body. e.q. DPT,
polio vaccines, etc.
*All drugs exert some effect on a biologic system

* In most instances, a given effect can be related to drug dosage in a quantitative fashion.
*Two important expressions of drug action can be demonstrated: POTENCY and EFFICACY.
Potency - amount/strength of a drug required to produce the desired effect or action

- is a measure of drug activity in terms of the amount required to produce an effect of
given intensity.
Efficacy - ability of the drug to elicit its maximum inherent physiologic effect.
- the "Maximum Intensity of Effect" of a certain drug.
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* For example, one drug (drug A) produces complete eradication of premature ventricular
contractions (PVCs) at a dose of 10 mg. A second drug (drug B) produces complete
eradication of PVCs at a dose of 20 mg. Therefore, both drugs have the same efficacy
(complete eradication of PVCs), but drug A is more potent than drug B. It takes less of drug A
to produce the same effect. A third drug (drug C) can reduce the PVCs by only 60%, and it
takes a dose of 50 mg. to achieve the effect. Therefore, drug C has less efficacy and less
potency in the reduction of PVCs compared with both drug A and drug B.
CHARACTERISTICS OF DRUG ACTION

1. According to Biochemical Action
E.q. Hypoglycemic agents; Hemostatic agents
2. According to Physiologic Effects
E.q. Muscle relaxants; Anti-hypertensive agents
3. According to the Organ System on which they exert their Therapeutic Action
E.q. CNS stimulants
USES OF DRUGS
1. Diagnosis - e.q. barium enema
2. Prevention - e.q. DPT vaccine
3. Contraception - e.q. pills, deprovera, etc.
4. Treatment - e.q. analgesics, antibiotics
MECHANISM OF DRUG ACTION

1. Action on a Receptor
2. Action on an Enzyme
3. Action on Membrane Ionic Channels
4. Cytotoxic action
I. ACTION ON A RECEPTOR
Receptor - a specific macromolecule usually a protein to which a specific group of drug
or naturally occurring substances such as neurotransmitter or hormone can
bind.
RECEPTORS INVOLVED IN THE ACTION OF COMMONLY USED DRUGS
RECEPTOR MAIN ACTION OF NATURAL AGONISTS
ADRENOCEPTOR
1 Vasoconstriction
2 Hypotension ; Sedation
B1 Heart Rate
B2 Bronchodilation
Vasodilation
Uterine Relaxation
CHOLINERGIC
Muscarinic Heart Rate
Secretion
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Gut Motility
Bronchoconstriction
Nicotinic Contraction of Striated Muscle
HISTAMINE
H1 Bronchoconstriction
Capillary Dilation
H2 Increased Gastric Acid
DOPAMINE CNS Neurotransmitter

OPIOD CNS Neurotransmitter
II. ACTION ON ENZYME

Enzyme - protein macromolecule with which substances interact to produce “activation”
or “inhibition”.
*Drugs in clinical use which exert their effect thru enzyme action generally do so by
“inhibition”.
E.q. Aspirin inhibits platelet cyclo-oxygenase; Allopurinol inhibits xanthene oxidase.
III. ACTION ON MEMBRANE IONIC CHANNELS

The conduction of impulse in nerve tissues and electrochemical coupling in muscles
depends on the movement of ions particularly sodium, calcium, and potasium through
membrane channels.
*Several group of drugs that interfere with these processess: Antiarrythmic drugs,
General and local anesthesia, Anticonvulsant.
IV. CYTOTOXIC ACTIONS

This mechanism have been defined in terms of effects on specific receptors or enzymes.
But in other cases, chemical action (Alkylation) damages DNA or other macromolecules
and results in cell death or failure of cell division.
E.q. Drugs used in cancer or in treatment of infection may kill malignant cells or
Microorganisms.
PUBLICATIONS IN PHARMACOLOGY
U.S.P. United States Pharmacopoeia

- Representatives from school of medicine and pharmacy
- American medical Association
- American Pharmaceutical Association
- State Medical Societies
- American Chemical Society
- Other scientific organization and federal agencies
Purpose of U.S.P. : It sets the official chemical and physical standards that relate
essentially to strength and purity of drug.
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N.F. National Formulary

- issued every 5 years
- establishes official standards for drugs not described in the U.S.P.
- described extent of drugs' use and therapeutic value
British Pharmacopoeia
- English equivalent of U.S.P. (Great Britain and Canada)
Pharmacopoeia Internationalis
- issued by W.H.O.
A.D.T. Accepted Dental Therapeutics

A.D.R. Accepted Dental Remedies
- biennial publication of the Council on Dental Therapeutics (CDT) of the American Dental
Association
- drugs of recognized value that are labeled and advertised in accordance with CDT are
included.
- Primarily a handbook of dental pharmacotherapeutics and intended to assist the dental
practitioner in the selection of drugs.
P.D.R. Physician's Desk Reference

- a handbook published annually by some 200 manufacturers
Special Value:
1. Published annually and therefore includes relatively up to date information
2. It is cross-indexed to include the use of proprietary names
Disadvantages:
1. Products or drugs are arranged by manufacturers rather than by pharmacologic class
2. Information may be "biased".
* REPUBLIC ACT 6675 - known as the GENERIC ACT OF 1988

- an act to Promote, Require and Ensure the production of an adequate supply,
distribution, use and acceptance of drugs and medicines identified by their generic names.
AIM:
1. To promote, encourage and require the use of generic terminology in the importation,
manufacturing, distribution, marketing, advertising and promotion, prescription and
dispensing of drugs.
2. To ensure the adequate supply of drug with generic names through a rational system of
procurement and distribution.
3. To encourage the extensive use of drug with generic names through a national system of
procurement and distribution.
Importance of R.A. 6675

1. For health professionals to become more aware and cognizant of their therapeutic effectiveness.
2. To provide drugs to indigent patients at the lowest possible cost.
3. To have healthy competition among drug manufacturers
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Who Shall Use Generic Terms?

All government health agencies
All medical, Dental and Veterinary practitioners
All drug establishments
All drug outlets
Penalty for NOT complying to R.A. 6675

First Offense
Reprimand which will be recorded in the Professional Regulation Commission Book.
Second Offense
Fine : Not less than P2,000.00 but not greater than P5,000.00.
Third Offense
Fine : Not less than P5,000.00 but not greater than P10,000.00.
Fourth and Succeeding
Fine : Not less than P10,000.00 and suspension of license to practice for one year.
DRUG NOMENCLATURE
1. CHEMICAL NAME
"FIRST NAME" given to compound of known composition
- conveys the chemical structure of the compound.
E.q. N-Acetyl p-aminophenol
CODE DESIGNATION - convenient means of referring to the compound before it has been
assigned either a generic or trade name.
2 Types of Code Designation

1. A letter and number combination e.q. SH 567
letter/s - research laboratory involved
number/s - arbitrarily assigned
2. Letter combination e.q. AZT - Azothymidine
TPA - Tissue Plasminogen Activator
ASA - Acetyl Salicylic Acid
2. TRADE NAME (Commercial Name; Proprietary Name; Brand Name)

- name of the company who manufactured the drug
- gives no or little information about the drug itself
BRAND NAME - name of the company marketing the product

- distinguishes its product from others.
- E.q. Biogesic, Ponstan, Flanax, Amoxil,
Two Important Disadvantages of Trade Name:

1. Makes the problem of drug identification more complex
2. Deprive the patient to avail of a less expensive generic preparations.
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Advantages of Trade Names:

1. They are convenient and saves time when writing prescriptions for multiple-entity drugs
2. Trade names are usually shorter and easier to remember than generic names.
3. The use of trade names demands the product of a specific manufacturer in whose
manufacturing practices the practitioner may have special confidence.
3. GENERIC NAME - "Official" name of the drug; "Non-Proprietary name.
Advantages of using Generic Names

1. Healthy competition among drug manufacturers
2. Provides a wide selection of drugs
3. It is universally accepted.
Disadvantages of using Generic Names

1. Not all preparations are prepared as they should be.
2. It is hard to remember.
3. It is inconvenient when written.
E.g.
Chemical : 2-diethylamino 2,6 acetoxylidide : N-acetyl p-aminophenol
Generic : Lidocaine : Acetaminophen
Trade Name : Xylocaine : Tylenol
Dolicaine : Tempra
Octocaine : Valadol
L-caine : Datril
*** How to use the PIMS / MIMS
PIMS - Philippine Index for Medical Specialties

MIMS - Monthly Index for Medical Specialties. It is a global term for a therapeutic index.
Brand Name /Manufacturer / Distributor

Contents (C)
Indication/s (I)
Dosage (D)
Contraindications ( C/I )
Special Precautions ( SP )
Adverse Reactions ( AR )
Drug Interactions ( DI )
Presentation / Price ( P/P )
Example: (Based from MIMS Dental Phils. 2002 page 68)
ATMOSE Morishita-Seggs Rx (Atmose is the proprietary name of the

(Metro Drug) drug;
C. Mefenamic Acid Morishita-Seggs is the name of the
I. Relief of mild to moderate pain including company who manufactured the drug
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headache, dental pain, post-op and postpartum Metro Drug is the name of the
pain, dysmenorrhea, osteoarthritis and RA. company marketing the product
D. Adult and children > 14 yr. Initially 500 mg. Rx means this drug needs prescription
then 250 mg 6 hrly. P/P. Atmose is available in capsule
CI. Peptic ulceration or inflammatory bowel disease. form at a dosage of 500 mg.;
SP. Hepatic or renal impairment; epilepsy. X100 means in one box there are
AR. GI disturbances; peptic ulceration, GI bleeding; 100 capsules that costs
drowsiness; dizziness; nervousness; visual Php357.63
disturbances; skin rash; urticaria; blood dyscrasias.
DI. Enhances the effects of the coumarin anticoagulants.
P/P. Cap 500 mg X 100’s (P357.63)
PHARMACOLOGICAL CLASSIFICATION INDEX

Pharmacological Classes and Sub-classes
(based on MIMS Dental Phils 2002)
I. ALIMENTARY SYSTEM
1. Antacids and Antiulcerants
2. GIT regulators, Antiflatulents and Anti-Inflammatories
3. Antispasmodics
4. Antidiarrheals
5. Laxatives, Purgatives
6. Digestives
7. Cholagogues, Cholelitholytics and Hepatic Protectors
II. CARDIOVASCULAR AND HEMATOPOIETIC SYSTEM

1. Cardiac Drugs
2. Anti-anginal Drugs
3. ACE Inhibitors
4. Beta Blockers
5. Calcium Antagonists
6. Diuretics
7. Antidiuretics
8. Peripheral Vasodilators and Cerebral Activators
9. Vasoconstrictors
10. Migraine Drugs
11. Haemostatics
12. Anticoagulants, Antithrombotics and Fibrinolytics
13. Haemorrhoidal, Phlebitis and Varicose Preparations
14. Haemorrheologicals
15. Haematopoetic Agents
16. Other Cardiovascular Drugs
III. RESPIRATORY SYSTEM

1. Respiratory Stimulants
2. Antiasthmatic Preparations
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3. Cough and Cold Remedies

4. Decongestants and other Nasal Preparations
5. Other drugs acting on Respiratory System
IV. NEUROMUSCULAR SYSTEM

1. Anti-inflammatory Enzymes
2. Analgesics and Antipyretics
3. Antirheumatic, Anti-inflammatory Analgesics
4. Gout Preparations
5. Minor Tranquilisers
6. Major Tranquilisers
7. Hypnotics and Sedatives
8. Anticonvulsants
9. Antidepressants
10. CNS Stimulants
11. Nootropics and Neurotonics
12. Antiemetics and Antivertigo Drugs
13. Neurodegenerative Disease Drugs
14. Antiparkinsonism Preparations
15. Neuromuscular Disorder Drugs
16. Muscle Relaxants
V. HORMONES
1. Androgens and Related Synthetic Drugs
2. Oestrogens and Progesterones and Related Synthetic Drugs
3. Combined Sex Hormones
4. Corticosteroid Hormones
5. Trophic Hormones and Related Synthetic drugs
6. Anabolic Agents
7. Other Hormone Related Drugs
VI. CONTRACEPTIVE AGENTS

1. Depot Contraceptives
2. Oral Contraceptives
3. Other Contraceptives
VII. ANTIBIOTICS
1. Aminoglycosides
2. Cephalosphorins
3. Chloramphenicols
4. Macrolides
5. Penicillins
6. Quinolones
7. Tetracyclines
8. Antifungals
9. Antibacterial Combinations
10. Other Antibiotics
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VIII. OTHER CHEMOTHERAPEUTICS

1. Antituberculous Agents
2. Sulphonamides
3. Antiamoebics
4. Anthelmintics
5. Antileprotics
6. Antivirals
7. Antineoplastics
8. Antimalarials
9. Leishmaniacides, Trypanocides
10. Filaricides
IX. GENITO-URINARY SYSTEM

1. Preparations for Vaginal Conditions
2. Urinary Antiseptics
3. Drug acting on Uterus
4. Other Drugs Acting on Genito-Urinary System
X. METABOLISM
1. Insulins
2. Oral Antidiabetic Agents
3. Thyroid Preparations
4. Antithyroids
5. Antihyperlipidaemic Agents
6. Other Agents Affecting Metabolism
XI. VITAMINS AND MINERALS

1. Vitamins A, D, E
2. Vitamin B’s / with C
3. Vitamin C
4. Calcium / with Vitamins
5. Multivitamins / with Minerals
6. Vitamins with Hormones / Geriatric Preparations
7. Pediatric Vitamins and Minerals
8. Electrolytes and Minerals
9. Antianemics / Pre and Post Natal Vitamins
XII. NUTRITION
1. Infant / Follow-On Formulae
2. Enteral / Nutritional Products
3. Parenteral Nutrition
4. Tonics
5. Appetite Stimulants
6. Antiobesity Agents
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XIII. EYE, EAR, MOUTH / THROAT
*EYE
1. Eye Anti-infectives and Antiseptics
2. Eye corticosteroids
3. Eye Antiseptics with Corticosteroids
4. Mydriatic Drugs
5. Miotic Drugs
6. Glaucoma Preparations
7. Other Eye Preparations
*EAR
1. Ear Anti-infectives and Antiseptics
2. Ear Corticosteroids
3. Ear Antiseptics with corticosteroids
4. Other Ear Preparations
*Mouth / Throat
1. Mouth / Throat Preparations
XIV. DERMATOLOGICALS
1. Topical Anti-infectives
2. Topical Anti-infectives with Corticosteroids
3. Topical Corticosteroids
4. Acne Treatment Preparations
5. Antiseptics and Disinfectants
6. Medicated Surgical Dressings
7. Topical Fungicides and Antiparasites
8. Psoriasis, Seborrhea and Ichthyosis Preparations
9. Topical Antivirals
10. Keratolytics
11. Skin Protectives
12. Topical Antihistamines / Antipruritics
13. Topical Analgesics and Anti-inflammatories
14. Other Dermatologicals
XV. ANAESTHETICS
1. Local Anesthetics
2. General Anesthetics
XVI. DIAGNOSTIC AGENTS
1. Urinalysis Agents
XVII. ALLERGY AND IMMUNE SYSTEM

1. Antihistamines and Antiallergies
2. Vaccines, Antisera and Immunologicals
3. Immunosuppressants
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XVIII. ANTIDOTES AND DETOXIFYING AGENTS
XIX. INTRAVENOUS AND OTHER STERILE SOLUTIONS
XX. MISCELLANEOUS
Different Factors Affecting Response:

Routes of Drug Administration
Passage of Drug Across Body Membranes
Molecular Mechanism of Action
Absorption
Distribution FATE of a DRUG
Metabolism
Excretion
ROUTES OF DRUG ADMINISTRATION
ENTERAL
Oral
Rectal
PARENTERAL
Hypodermic Routes
Intravenous
Intramuscular
Subcutaneous
Intradermal
Intrathecal
Intraperitoneal
Additional Routes
Topical
Inhalation
Sublingual
Transdermal
LOCAL ROUTE
Topical
Intradermal
Intrathecal
Intranasal
Intraconjuctival
Intra-oral
Intra-articular
Intra-arterial
Other special routes
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SYSTEMIC ROUTES
Enteral
Parenteral
*** Locally administered drugs may be absorbed at a rate and to an extent sufficient to result in
the production of systemic effects.
ENTERAL ROUTES - drug is placed directly into the GIT from where absorption occurs.
A. ORAL ROUTE
- simplest and most convenient for self administration.
Contraindication for Oral Route

1. Patients with gastrointestinal intolerance
2. Patients preparing for anesthesia
3. Patients with gastrointestinal surgery
4. Precluded in coma
Disadvantages of Oral Route

1. Irritant drugs cannot always be given by mouth for it may cause sickness.
2. It is not feasible to give drugs by this route to patients who are vomiting or moribund.
3. Many drugs are destroyed by the action of the digestive ferments before they can be
absorbed.
4. Intestinal absorption may be irregular due to other substances in the git.
5. Intestinal absorption may be affected by changes in gastric emptying which may
increase or decrease the rate of absorption.
"First Pass Effect" - refers to the metabolism of a drug en route from the gut lumen to
the systemic circulation.
- a process that rapidly deactivate some drugs in the liver that was
given orally and was initially perfused into the hepatic portal
circulation.
Some drugs do not go directly into the systemic circulation following absorption
but pass from the intestinal lumen to the liver, by the portal vein. In the liver, most of
the drug is metabolized to an inactive drug form for excretion, reducing the amount of
active drug.
Importance of First Pass Metabolism

1. It is one of the reasons for the apparent differences in drug absorption between
individuals.
2. In patients with severe liver disease, first-pass metabolism may be dramatically
reduced leading to the absorption of greater amounts of parent drug.
Drugs with High First Pass Metabolism

Analgesics
Aspirin
Morphine
Paracetamol
Pentazocine
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Pethidine
Respiratory Drugs
Salbutamol
Terbutaline
Drugs Acting on Central Nervous System
Chlormethiazole
Chlorpromazine
Imipramine
Levodopa
Nortriptyline
Oral Contraceptives
Cardiovascular Drugs
Glyceryl Trinitrate
Isoprenaline
Nifedipine
Prazosin
Propanolol
Verapamil
Lignocaine
Metropolol
RECTAL ROUTE
- drugs are given via the rectum. E.q. solid form – suppositories; liquid form – enemata.
- used when oral administration is impossible.
- avoids the acidity and enzymes of the gastric juice and first pass metabolism.
- Both local and systemic effects are obtained but absorption of many drugs are often
irregular and incomplete. Indications: Pediatrics / Geriatrics
PARENTERAL ROUTES - generally chosen when speed or reliability are specially desired.
A. Injection – essential if the drug is to be absorbed in active form.
- absorption is usually more predictable and more rapid
- requires special skill; drugs cannot be withdrawn easily.
Disadvantages
1. Difficult for the patients to perform the injection by themselves.
2. Strict asepsis must be maintained to avoid infection
3. Usually more costly and less safe.
4. Can cause pain.
TYPES OF INJECTION
Intravenous (IV)
- route of choice for emergency cases
- Most rapid route / method to elicit drug response.
Advantages
1. Rapid action
2. Can be used for drugs which are irritant by IM injection.
3. Useful for ill, hospitalized patients when a slow IV infusion provides a steady flow
without disturbing the patient
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Disadvantages
1. Tend to produce more immediate adverse reactions.
2. Too high concentration of the drug is readily obtained when injected rapidly.
3. The chance of penetration into an artery instead of a vein is a possibility.
Complications:
1. Drug Shock
2. Acute, serious, allergic responses
3. Phlebitis
4. Necrosis around the injection site.
Intradermal (cutaneous) - E.q. skin testing.
Action:
- local effect
- small amount is injected into the epidermis of the skin so that volume does not interfere
with wheal formation or cause a systemic reaction.
- used for observation of an inflammatory (allergic) reaction to foreign proteins.
- rarely employed except in certain Diagnostic and test procedures (screening for
allergic or local irritant responses).
- takes the longest time for drug absorption.
Sites:
- Locations are chosen so that inflammatory reaction can be observed. Preferred areas
are lightly pigmented, thinly keratinized, and hairless such as ventral mid-forearm,
clavicular area of chest, scapula area of back, and medial aspect of thighs.
Equipment:
Needle: 26 – 27 gauge
Syringe: 1 ml. calibrated in 0.01 ml. increments
Usually 0.01 – 0.1 ml. injected.
Technique:
Cleanse area using circular motion; observe sterile technique.
Hold skin taut.
Insert needle, bevel up, at a 15 degree angle; outline of needle under the skin should be
visible.
Inject medication slowly to form a wheal (blister or bleb).
Remove needle slowly.
Make a mark or encircle the bleb with a pen.
Do not massage area; instruct client not to do so.
Assess for allergic reaction in 24 – 72 hours; measure diameter of local reaction.
Subcutaneous - for drugs which are not irritant to tissues. E.q. morphine sulphate,
adrenaline, and insulin.
- volume is usually 1 ml. or less; seldom exceeds 2 ml.
- cutaneous blood flow is slower compared to IM
- sustained effect can be obtained by placing a pellet of drug subcutaneously; e.q.
18
Estradiol plants.
- drug is injected in the subcutaneous layer into the alveolar connective tissue just below the
skin.
Action:
- Systemic effect
- Sustained effect; absorbed mainly through capillaries; usually slower in onset than with
intramuscular route.
- Used for small doses of non-irritating water-soluble drugs.
Sites:
- Locations for subcutaneous injection are chosen for adequate fat pad size and include the
abdomen, upper hips, upper back, lateral upper arms, and lateral hips.
Equipment:
½ - 5/8 in. in length
Syringe: 1 – 3 ml.
Usually 0.5 – 1.5 ml. injected.
Insulin syringe measured in units for use with insulin only.
Technique:
Cleanse area with circular motion using sterile technique
Pinch the skin.
Insert needle at angle appropriate to body size. 45 to 90 degrees.
Release skin.
Aspirate, except with heparin.
Inject medication slowly.
Remove needle quickly.
Gently massage area, unless contraindicated with heparin.
Apply plaster if needed.
Advantages:
1. Spread the action out over a number of hours.
2. Avoid too intense or too short response
3. Avoid frequent injections.
Layer of skin and site of injections:
Epidermis
Cutaneous
Dermis
Membrane
Fascia
Subcutaneous
Muscle
19
Intramuscular (IM)
- more dangerous than IV; better for irritant tissues.
Action:
- systemic effect.
- Usually more rapid effect of drug than with subcutaneous.
- Used for irritating drugs, aqueous suspensions, and solutions in oils.
- indicated when an immediate effect is not required but a prompt effect is desirable.- 10 –
30 minutes absorption.
Sites:
Locations are chosen for adequate muscle size and minimal major nerves and blood
vessels in the area. Preferred locations include ventrogluteal, dorsogluteal, deltoid, and
vastus lateralis.
Equipment:
1 – 1.5 in. in length
Syringe: 1 –3 ml.
Usually 0.5 – 1.5 ml. injected
Technique:
Same as for subcutaneous injection except that needle is inserted at 90 degree angle into
the muscle.
Figure: Angles for injections. (A) IM 90 (B) (C) (D) SC 90 , 60 , 45 (E) ID 10=15 .
Intraperitoneal – injected into the peritoneal cavity by absorption of messenteric veins
Intrapleural - introduce into the pleural cavity; for aspiration of fluids.

20
Intrathecal / Intraspinal - for spinal analgesia into the spinal subarachnoid space.
- administered into the cerebrospinal fluid at any level of the cerebrospinal axis.
Intraneural - used in trigeminal neuralgia.
Intrasternal - drugs which normally do not cross the blood brain barrier.
BUCCAL and SUBLINGUAL route

- an enteral route infrequently used but useful in drugs with first pass hepatic metabolism.
E.q. glyceryl trinitrate for angina attack but ineffective when swallowed as its first pass
metabolism approaches 100 per cent
- drugs that are susceptible to degradation by the GIT and even the liver are safely
administered sublingually.
INHALATION - E.q. inhalation anesthetics, aerosol inhalation for asthma.

- inhalation is via the mouth; absorption occurs in the small bronchioles. E.q. disodium
cromoglycate via a “Spinhaler”.
- drug is absorbed through the pulmonary endothelium at the alveoli to gain rapid access
to the general circulation.
Reasons for rapid absorption

1. Alveolar and vascular epithelial membranes of the lungs are quite permeable.
2. Blood flow is abundant.
3. There is al large surface for absorption.
Particle Size
1. Particles greater than I um in diameter - tend to settle in the bronchi.
2. Particles less than 0.5 um - fail to settle; mainly are exhaled.
TOPICAL
- least effective.
- drug is applied to the skin and other epithelial surfaces with glove, tongue blade, or
cotton-tipped applicator.
- utilized for local drug effect.
- Use appropriate technique to remove medication form container and apply to clean, dry
skin, when possible. Do not contaminate medication in container, use gloves or an
applicator.
Methods of enhancing drug absorption via the Topical route

1. Ionotophresis - uses galvanic current
2. Inunction - mechanical rubbing of drug into the skin.
TRANSDERMAL
- stored in a patch placed on the skin and absorbed through skin, having systemic effect
- Transdermal drugs provide more consistent blood levels and avoid GI absorption
associated with oral products.
21
PHARMACEUTICAL PREPARATIONS AND DOSAGE FORMS

Pharmaceutical preparations are the forms in which drugs are prepared by the pharmacist or
pharmaceutical chemist for administration in the treatment of the sick.
SOLID PREPARATIONS
Aerosols - packed with compressed gas under pressure for topical application. Upon release, the
aerosol takes the form of a fine mist, foam, semisolid fluid or solid.
Ampules - are hermetically sealed glass containers for medicinal substances containing a sterile
solution for parenteral use.
Capsules - small gelatin receptacles of various sizes for oral administration. Generally dissolve
in the stomach except the enteric capsules which dissolves in the intestines. They
maybe of firm or flexible consistency.
Carpules - are glass tubes enclosed on both ends with rubber stoppers, one acting as a plunger,
the other as a diaphragm. Contain a drug in solution and designed for parenteral
medication
Confections - medicinal substances formed into a mass with sugar, honey, and water as
confection of rose.
Effervescent Salts - powdered drug which give off CO2 gas and go into solution when added to
water.
Konseals - (rice flour capsules) or wafers (thin sheets of dried flour paste) – sometimes used to
enclose drug powders.
Papers - paper impregnated with medicinal substances. E.q. mustard paper
Pills - small spherical masses of drugs intended for swallowing covered with various substances
as gelatin, salol, sugar, chocolate, etc. and generally colored; powdered drugs mixed
with adhesive substances like glucose or honey and molded in spherical or ovoid forms.
Suppositories - solid bodies of various weights and shapes adapted for introduction into orifices
(vagina, rectum, urethra, etc.) of the human body and usually melting,
softening, or dissolving at body temperature. For urethral use, they are called
bougies.
Rectal Suppositories - conical or bullet-shaped, usually weigh about 2 grams.
Used to produce local and systemic effects and to produce catharsis.
Vaginal Suppositories - conical or spherical in shape and weigh from 4 – 10
grams. Used to confer antisepsis, to combat various infections, and as
spermatocides.
Urethral Suppositories - pencil-shaped and weigh for 2 – 4 grams. Used mainly
for local treatment of the female urethra
Tablets - solid dosage forms containing granulated or powdered drugs that are compressed or
molded into round or discoid shapes.contains medicinal substances with or without
suitable diluents. They vary in shape, size and weight. It may be classed according to
the method of manufacture, as molded tablets or compressed tablets.
Troches - lozenges intended to be dissolved in the mouth for local effect on the mucous
membrane of the mouth and throat.
SEMI-SOLID PREPARATIONS
Cerates - unctuous preparations having for their bases the simple cerate. Similar to ointments in
consistency but do not melt at body temperature. E.q. Cantharides cerate.
Creams - semi-solid emulsions of either the oil-water or the water in oil type for topical
22
application.
Extracts - concentrated preparation of vegetable or animal drugs. Made in 3 forms: 1) Semi
liquids or liquids of syrupy consistency 2) Plastic masses (pilular or solid extracts)
and 3) Dry powders (powdered extracts.
Ointments - for external application. Medicinal substances are combined with a base of
sufficient softness which tend to fall into two groups: hydrophilic such as the
lanolin and the lipophilic, such as the petrolatum. E.q. ZOE ointment
Pastes - comprise two classes of ointment-like preparations intended for external application:
1)Hydrogels – such as hydrated pectin; and 2) Fatty pastes – such as ZOE paste, which
consist of thick, stiff ointments which do not ordinarily flow at body temperature and
therefore serve as protective coatings over the areas they are applied.
Plasters - adhesive, fatty or resinous compounds spread on textile fibers, leather, muslin, etc.,
Either soft or dry and intended for local application. E.q. Belladone plaster, etc..
Poultices (Cataplasma) - semi-liquid mixtures of such substances as flaxseed, elm bark, or
bread, etc., with hot water or milk, spread upon cloth and used as a means for applying
heat and moisture or stimulation to the body surfaces. E.q. Cataplasma Kaolini.
Triturations - powders consisting of an active remedy triturated with sugar or milk, usually of
10% strength. E.q. Triturations of Elaterin.
LIQUID PREPARATIONS
Aromatic waters - saturated (0.2%) aqueous solutions of volatile substances, usually volatile
oils. Generally used as vehicle for water-soluble drugs. E.q. peppermint
water.
Collodions - liquid preparations having for their base a solution of guncotton (pyroxylin) in a
mixture of ether and alcohol. E.q. Flexible collodion.
Collyria - Medicinal eyewashes.
Decoctions - solutions of vegetable substances prepared by boiling with water in a closed
container for 15 minutes and strained – as decoction of coffee and sarsaparilla.
Elixirs - clear, sweetened, hydroalcoholic liquids intended for oral use. Contains flavoring
substances. Because of alcoholic content, they are miscible with tinctures.
Two types:
1. Aromatic elixir - used mainly for diluting other liquid preparations
2. Medicated elixirs - include Phenobarbital elixir, Diphenhydramine Hydrochloride
Elixir, and Terpin Hydrate and Codeine elixir.
Emulsions - aqueous preparations in which oils, oleoresins, balsams, resins, or other substances
which are insoluble in water are suspended by means of gum or other viscid
excipients. E.q. Cod liver oil emulsion, milk and eggyolk.
Fluid extracts - liquid extractions of drugs prepared by percolation. Concentrated tinctures in
which 1 g. of the drug corresponds to 1 ml. of the finished product. E.q. Ergot
fluid extract.
Gargles - mixtures or hydroalcoholic solutions for application to the pharynx and mouth.
Gels - suspension in a water medium, of insoluble drugs in hydrated form wherein particle size
approaches or attains colloidal dimensions.
Glycerites - mixtures or solutions of medicinal substances with or in glycerin. E.q. Tannic acid
glycerite.
Honeys - solutions of drug in clarified honey. E.q. Honey of rose.
Injections - sterile preparations for parenteral use. Comprise of 1) Solutions for injection 2)
Dry solids, which upon the addition of suitable solvents yield solutions conforming
23
in all respects to the requirements for injections 3) Solids suspended in a suitable

fluid medium which are not to be injected IV or into the spinal canal 4) dry solids,
which upon the addition of suitable vehicles, yield preparations conforming to the
requirements for sterile suspensions and 5) emulsions of fluids in fluid media,
suitable for parenteral administration, but are not to be injected in the spinal canal.
Liniments - liquid ointments applied with friction to the skin.
Lotions - mixtures or solutions of medicinal agents intended for external application with
soothing and protective effect.
Milks - suspension of poorly soluble drugs in water medium and distinguished from gels mainly
in that the suspended particles are larger. They tend to separate on standing and must be
shaken well before use. E.q. Milk of magnesia.
Mixtures - suspension of drugs in an aqueous vehicle. E.q. Brown mixture.
Oleates - solutions of metallic salts or alkaloids in oleic acid. E.q. Oleate of Mercury.
Solutions - liquid preparations that contain one or several soluble chemical substances (non
volatile) in water.
Spirits or Essences - volatile substances dissolved in alcoholic solution. Many are flavoring
agents. E.q. Peppermint spirit –also used as a carminative. Aromatic
Ammonia Spirit – a medicated spirit used as a reflex stimulant.
Suspensions - finely divided drugs either intended for suspension in some suitable liquid vehicle
prior to use or already in suspension in a liquid vehicle.
Syrups - highly concentrated solutions of sugar such as sucrose in water, carrying flavors or
medicinal substances – as syrup of Orange, Syrup of Wild cherry. Syrups serves as
vehicle or preservatives. Some contain active therapeutic agents.
2 Classes of Syrups:
1. Flavored syrups - employed to mask the taste of unpleasant tasting drugs and
to add stability to preparations. E.q Acacia syrup, Cocoa syrup.
2. Medicated syrups - E.q Ipecac syrup (emetic, expectorant); Chloral Hydrate
syrup (hypnotic), contain some added medicinal substances.
Tinctures - hydroalcoholic solutions of medicinal substances usually obtained by extractin of
vegetable drugs; generally alcoholic extracts of vegetable or animal drugs obtained
by percolation. E.q. Belladona tincture; Vanilla tincture (used as flavoring agents);
Iodine tincture (used as antiseptic).
Waters - may be a natural product, as tap water, or distilled and de-ionized to form a more
purified and sterile product. E.q. Water for injection.
SYSTEMS OF MEASUREMENT
Three systems of measurement (metric, apothecary, and household) are used in measuring
drugs and solutions. The metric system developed in the late eighteenth century, is the
internationally accepted system of measure. It is replacing the apothecary system, which dates
back to the middle ages and had been used in England since the 17th century. It is proposed that
the apothecary system will phase out by the end of this century. Household measurement is
commonly used in community and home settings.
I. METRIC - to measure based on decimals and Arabic numbers; the official system used in
the USP.
24
Units: Meter (m) = for length

Liter (l) = for capacity
Gram (gm.) = for weight
Metric Tables:
Table of Length Table of Capacity Table of Weight
1 km. = 1,000 m. 1 kl. = 1,000 l. 1 kg. = 1,000 gm.
1 hm. = 100 m. 1 hl. = 100 l. 1 hg. = 100 gm.
1 dkm = 10 m. 1 dkl = 10 l. 1 dkg = 10 gm.
1 dm. = 0.1 m. 1 dl. = 0.1 l. 1 dg. = 0.1 gm.
1 cm. = 0.01 m. 1 cl. = 0.01 l. 1 cg. = 0.01 gm.
1mm. = 0.001 m. 1ml. = 0.001 l. 1mg. = 0.001 gm.
Procedure for Conversion Between Units of the Metric System:

1. To change milligrams to grams, milliliters to liters, or grams to kilograms,
divide by 1000.
2. To change liters to milliliters, grams to milligrams, kilograms to grams,
multiply by 1000.
Examples:
a. 64 mg. = ? gm.
1000 mg. : 1 gm. = 64 mg. : x gm.
1000 x = 64
x = . 64 .
1000
= 0.064 gm.
b. 325 ml. = ?L
1000 ml. : 1L. = 325 ml. : x L.
1000 x = 325
x = . 325 .
1000
= 0.325 L
II. APOTHECARIE’S OR ENGLISH SYSTEM - In this older system, Roman numerals

and common fractions are used to designate units. Also, the units of measure precede the
numeral in correct form. e.q the correct way to signify 20 grains would be “gr.xx.” A
line is often written above the numerals, and a dot is placed above the numeral I to
distinguish more clearly between the two I’s and a V or X hastily written. When using the
apothecary system in calculations, however, the Arabic numbers are used.
Procedure for Conversion Within the apothecary System

1. Write the equivalent between the terms to be converted as the first two terms of the
proportion.
25
2. Being careful to keep the units in the last two terms in the same order as they occur
in the first, write the known quantity and the unknown equivalent as the third and
fourth terms of the proportion.
Examples:
a. 6 drams = ? ounces
8 drams : 1 ounce = 6 drams : X ounces
8x = 6
x = . 6 . = . 3 . ounce
8 4
b. 2 drams = ? minims
60 minims : 1 dram = x minims : 2 drams
1 x = 120
x = 120 minims
TABLE OF WEIGHT
60 grains = 1 dram
8 drams = 1 ounce
12 ounces = 1 lb.
TABLE OF CAPACITY
60 minims = 1 fluidram
480 minims or 8 fluidrams = 1 fluid ounce
7680 minims or 16 fluid ounces = 1 pint
2 pints = 1 quart
4 quarts = 1 gallon
III. HOUSEHOLD SYSTEM - The household system of measurement is not as accurate as

the metric system because of the lack of standardization of spoons, cups, and glasses.
The measurements are approximate.
HOUSEHOLD UNITS OF MEASUREMENT

60 drops (gtt) = 1 teaspoon
3 teaspoon = 1 tablespoon (tbs)
6 teaspoon = 1 ounce
2 tbs = 1 oz.
6 oz. = 1 tea cup
8 oz. = 1 glass
8 oz. = 1 measuring cup
OTHER EQUIVALENTS
1,000 cc. = 1 L = 1 quart
500 cc. = 1 pint
30 cc. = 1 fluidounce = 2 tbsp.
5 cc. = 1 fluidram = 60 minims = 1 tsp.
1 cc. = 15 minims
1 kg. = 1000 gms. = 2.2. lbs.
26
4 gms. = 1 dram = 60 grains
TEMPERATURE CONVERSION
Celsius to Farenheit: ( C ) (9/5) + 32
Farenheit to Celsius: ( F – 32 ) (5/9)
METRIC DOSES with APPROXIMATE APOTHECARY EQUIVALENTS

( by Musser/O’Neil * reprinted from USP XVI)
LIQUID MEASURE
Approximate Approximate
METRIC APOTHECARY METRIC APOTHECARY
equivalents equivalents
1000 ml. 1 quart 3 ml. 45 minims
750 ml. 1 ½ pints 2 ml. 30 minims
500 ml. 1 pint 1 ml. 15 minims
250 ml. 8 fluid ounces 0.75 ml. 12 minims
200 ml. 7 fluid ounces 0.6 ml. 10 minims
100 ml. 3 ½ fluid ounces 0.5 ml. 8 minims
50 ml. 1 ¾ fluid ounces 0.3 ml. 5 minims
30 ml. 1 fluid ounce 0.25 ml. 4 minims
15 ml. 4 fluid drams 0.2 ml. 3 minims
10 ml. 2 ½ fluid drams 0.1 ml. 1 ½ minims
8 ml. 2 fluid drams 0.06 ml. 1 minim
5 ml. 1 ¼ fluid drams 0.05 ml. ¾ minim
4 ml. 1 fluid drams 0.03 ml. ½ minim
WEIGHT
Approximate Approximate
METRIC APOTHECARY METRIC APOTHECARY
Equivalents equivalents
30 Gm. 1 ounce 30 mg. ½ grain
15 Gm. 4 drams 25 mg. 3/8 grain
10 Gm. 2 ½ drams 20 mg. 1/3 grain
7.5 Gm. 2 drams 15 mg. ¼ grain
6 Gm. 90 grains 12 mg. 1/5 grain
4 Gm. 60 grains (1 dram) 8 mg. 1/8 grain
1.5 Gm. 22 grains 4 mg. 1/15 grain
0.6 Gm. 10 grains 1.5 mg. 1/40 grain
0.5 Gm. 7 ½ grains 1.2 mg. 1/50 grain
27

75 mg. 1 ¼ grains 0.2 mg. 1/300 grain
50 mg. 1 grains 0.15 mg. 1/400 grain
60 mg. ¾ grain 0.12 mg. 1/500 grain
40 mg. 2/3 grains 0.1 mg. 1/600 grain
APPROXIMATE HOUSEHOLD EQUIVALENTS

HOUSEHOLD APOTHECARY METRIC
1 drop (gt) 1 minim (m or min) 0.06 milliliter (ml.)
15 drops (gtt) 15 min 1 ml. (cc.)
1 teaspoon (tsp) 1 fluidram (60 minims) 5 or 4 ml. *
1 tablespoon (tbsp) 4 fluid dram 15 ml.
2 Tbs. 1 fluid ounce 30 ml.
1 ounce 1 fluid ounce 30 ml.
1 tea cup 6 fluid ounce 180 ml.
1 glass 8 fluid ounce 240 ml.
1 measuring cup 8 fluid ounce 240 ml.
2 measuring cups 1 pint (pt) 500 ml.
DOSE CALCULATIONS
Children are not able to tolerate adult doses of drugs. There are several formulas for
graduating dosage according to age and weight. The recommended dosage for kg. or lb. of body
weight is more accurate than calculating dosage according to age. Other factors beside age and
weight enter into dosage for children. For this reason, some physicians, use the :body surface
area” method to estimate the dosage for children. Charts are available to determine the body
surface area in square meters according to height and weight.
For Infants and Preschool children
Clark’s Rule
Weight (lbs.) X Adult dose

---------------------------------- = Infant dose
150
28
Fried’s Rule
- sometimes used in calculating dosages for infants less than 2 years old.
Age (mos.) X Adult dose

--------------------------------- = Infant dose
15
For Preschool to Adolescent years:
Young’s Rule
- not valid after 12 years of age. If the child is small enough to warrant a reduced
dose after 12 years of age, the reduction should be calculated on the basis of
Clark’s rule.
Age (yr.) X Adult dose

---------------------------------- = Child dose
Age (yr.) + 12
Cowling’s Rule
Age (at next b-day) X Adult dose

------------------------------------------- = Child dose
24
Calculation based on Body Surface Area (BSA) :

- considered to be the most accurate way to calculate the drug dose for infants,
children, older adults, and clients who are on antineoplastic agents or whose body
weight is low. The BSA, in square meters is determined by where the person’s height
and weight intersect the nomogram scale.
Surface area X Adult dose

----------------------------------- = Child dose
2.00
OR
Multiply the drug dose ordered by the number of square meters.
Example:
Order: Cyclophosphamide (Cytoxan) 100 mg. / m2 / day, PO
Patient is 5 ft. 10 in. (70 in.) tall and weighs 160 lbs.
a. 70 in. and 160 lbs. intersect the nomogram at 1.97 m2 (BSA)
b. 100 mg. x 1.97 = 197 mg.
Answer: Administer Cyclophosphamide 197 mg. or 200 mg./day.

29
30
31
PRESENTLY USED DOSE CALCULATION:
Weight: (Ideal Body Weight)
At Birth: 3000 Grams
Less than 6 months: Weight In Grams

Age in Months X 600 + Birth Weight
6 – 12 Months: Weight in Grams

Age in Months X 500 + Birth Weight
1 – 6 Years: Weight in Kilograms

Age in Years X 2 + 8
7 – 12 Years: Weight in Kilograms

Age in Years X 7 - 5
2
Suggested Dose:
Age 13 – 18 years = 250 mg.
19 – above = 500 mg.
Example:
Given: Age of child = 2 years old
Recommended dose = 10 mg.
Available dose: 250mg./5ml. x 30 ml.
Formula: Age in years X 2 + 8

Solution: 2 X 2 + 8 = 12 kg.
10 mg. X 12 Kg. = 120 mg. (dose needed by a 2-year old child)
What part of 250 mg. is 120 mg.?

To compute for the exact dose/ml., multiply 120 mg. to 5ml. and 250mg.
to X(ml.) then divide to 250mg.
250mg. / 5ml. = 120mg / X(ml.)
5ml. X 120mg. = 600mg./ml.

250mg. X ?ml = 250mg.
Then divide:
600mg./ml.
250 mg.
= 2.4 ml.
*120mg. computed dose of the child is 2.4ml. in a 250mg./5ml. preparation of the drug.
32
DOSE CALCULATION ACCORDING TO KEE AND HAYES

Basic Formula:
D
------ X V = A
H
Where: D = is the desired dose; drug dose ordered by the physician

H = is the on hand dose; drug dose on label of container (bottle, vial).
V = is the vehicle; drug form in which the drug comes (tablet, capsule, liquid)
A = is the amount calculated to be given to the client.
Example:
Order: Ampicillin (Polycillin) 0.5 g., PO, bid
Available (drug label): Polycilin 250 mg./capsule
Solution: The unit of measure that is ordered, grams, and the unit on the bottle,
milligrams, are from the same system of measurement, the metric system.
Conversion to the same unit is necessary to work the problem. Since the
bottles is in milligrams, convert grams to milligrams. To convert grams
(large value) to milligrams (small value), move the decimal point three
spaces to the right.
0.5 G. = 0.500 mg. or 500 mg.
D 500 mg. 500

------ x V = --------- x 1 capsule = ------- = 2 capsules
H 250 mg. 250
RATIO AND PROPORTION:

- the oldest method currently used in calculating drug dosage.
Known Desired
H : V : : D : x
means
extremes
x =
Example:
Order: Ampicillin 100 mg., PO, qid
Available: Ampicillin (Polycillin) 250 mg./5ml.
Solution: Conversion is not needed since both are expressed in the same unit
of measure.
33
H : V :: D : x
250 mg. : 5 ml. :: 100 mg. : x ml.
means
extremes
250x = 500
x = 2 ml.
Answer: Ampicillin 100 mg. = 2 ml.
DRUG LIST:
NARCOTIC ANALGESICS
1. MEPERIDINE HCL (DEMEROL)
Elixir: 50mg/5ml.
Tablet 50,100 mg.
Injection 100 mg./ml.
Dose: 6mg./kg./Day or 0.5 – 1.0 mg./Kg./Dose
2. NALBUPHINE (NUBAIN)
Injection 10 mg./ml.
Dose: 0.1 – 0.2 mg./Kg./Dose
NON-NARCOTIC ANALGESIC
1. ASA (ASPIRIN)
60, 81, 200, 300, 600, mg. Tablet
Dose: 6.5 mg./Kg./Day
2. ACETAMINOPHEN
Afebrin, Tempra, Tylenol, Calpol, Rexidol, Naprex, Panadol
100 mg./5ml., 120mg./5ml., 250mg./5ml. Syrup
60mg./0.6 ml. Drops
Dose: 10 – 20 mg./Kg./Dose
3. MEFENAMIC ACID
Ponstan, Dolfenal
50 mg./5ml. Suspension
250, 500 mg. Tablet, Capsule
Dose: 6.5 mg./Kg./Dose (Pedia)
34
BETA-LACTAM ANTIBIOTICS
PENICILLIN G
1. PENICILLIN G BENZATHINE
Usual Dose: Newborn(NB), Infants (IN): 50,000 – units/kg/single dose IM
Children (CH) (>60 lbs.) and Adults (A): 600000-1200000 units IM q
3 weeks for rheumatic fever prophylaxis
2.4 million units IM once (divided into 2 injection sites at one visit) for
three treatment of early syphilis, weekly X 3 doses for syphilis of more
than one year duration.
Preparation: (Penadur L-A): 1.2 M units and 2.4 M units/vial.
2. CRYSTALLINE PEN G (BENZYLPENICILLIN)

Usual dose: NB - 25,000 U/Kg. q 6, 8, 12
IN, CH - 100,000 – 250,000 U/Kg. div. q4h.
Preparation: Pen G: 1 M units/vial and 5 M units/vial
3. PHENOXYMETHYLPENICILLIN (PENICILLIN V)
Usual Dose: IN, CH - 25-50 mg./Kg./Day or 25,000-100,000 U/Kg./Day
div.q6-8 h, PO
1-2 g/d or 1.6-3.2 million u/d div.q6h, PO
Preparation: Oral - 250, 500, 625 mg. capsule
125 mg./5ml; 25mg./5ml, suspension 60 ml.
Note: Administer on empty stomach (1-2 hours after meal)
BROAD SPECTRUM PENICILLINS

1. AMOXICILLIN
Usual Dose: IN, CH- 20-40 mg./kg./day div.by 3 doses (q8h) PO
Adults- 750-1500 mg./day div. q8h, PO
Preparations: Drops - 100mg./ml. Granules/Powder for suspension, 10ml. drops
125, 250 mg./5ml. 60-70 ml.
Capsule- 250, 500 mg.
Injection- 250,500mg./vial
2. AMPICILLIN
Usual Dose: NB- 25-50 mg./kg. Q6-12 IV
IN, CH- 100-200 mg./kg./day div.q4-6 h.
A- 2-12 Grams infusion div. q6h.
(Ampicin, Amopen drops: 100 mg/ml.; suspension 125, 250 mg./5ml.;
capsule- 250,500mg.; Injection- 100, 250, 500 mg./vial)
COMBINATION OF A PENICILLIN AND BETA-LACTAMASE INHIBITOR

1. BACAMPICILLIN
Usual Dose: IN, CH - 25-50 mg./kg./day div.by 2 doses (q12) PO
A- 800-1600 mg. bid
(Penglobe susp. 200mg./5ml.; Tablet- 200, 400, 800 mg.
2. CO-AMOXICLAV
35
Usual Dose: NB- not recommended

IN, CH- 40 mg./kg./day div. q8h PO and IV.
A- 750 – 1.5 Grams/d div.q8 PO and IV.
Preparations: 156.25 mg./5ml (30-60 ml)
375, 625 mg. tablet
600,1200 mg./vial
PENICILLINASE RESISTANT PENICILLIN

1. CLOXACILLIN
Usual Dose: IN, CH - 50-100 mg./kg./day div.q6h (4 doses) PO
Adults - 2-4 Grams/day div.q6 PO
Preparations: Suspension - 125 mg./5ml x 60 ml.
Capsule - 250 mg., 500 mg.
Injection - 250, 500 mg./ vial
CEPHALOSPORINS
First Generation
A. CEPHALEXIN
Usual Dose: IN, CH - 25-50 mg./kg./day div.q6h, PO
Adults - 1-4 Grams/day div.q6h, PO
Preparations: 125 mg./ 5ml. Granules/Powder for Suspension (50-70 ml).
100 mg./ 5 ml. Granules/Powder for drops (10 ml.)
Capsule - 250, 500 mg.
B. CEPHAZOLIN
Usual Dose: NB - 20 mg./kg. q12h
IN, CH - 50-100 mg./kg./day div. q8h, IM or IV
Adults - 1-6 Grams/day div.q8h, IM or IV.
Preparation: 1 Gram vial
Second Generation
A. CEFACLOR
Usual Dose: IN, CH - 20-40 mg./kg./day q8-12h, PO
Adults - 750 – 1500 mg./day div.q8-12 h, PO
Preparations: Suspension 125mg./5ml. Granules/ Powder for suspension
Puvule 250, 500 mg.
50 mg./ml. Granules/Powder for drops (20ml.)
B. CEFUROXIME
Usual dose - 30-50 mg./kg./day
Injection 250-750 mg./vial
Third Generation
A. CEFTRIAZONE
Usual Dose: 50-100 mg./kg./day
Injection 250, 500 mg., 1 G / vial
36
B. CEFTAZIDIME
Injection 250, 500 mg., 1 G./ vial
AMINOGLYCOSIDES
1. GENTAMYCIN SULFATE
Usual Dose: IN, CH, A - 3.5-8 mg./kg./day div.q8 IM or IV
Preparation: Injection - 20, 40, 80 mg./ml. (vial)
2. AMIKACIN SULFATE
Usual Dose: IN,CH,A - 15mg./kg./day loading, 10mg./kg./day maintenance
Preparation: Injection - 50, 125, 250 mg./ml. (vial)
DRUGS THAT ACT ON 30 S RIBOSOMAL SUBUNIT

TETRACYCLINE
Usual Dose: CH(>8years) - 25-50 mg./kg./day div. q6h, PO
Adults - 1-2 Grams / day div.q6h, PO
Preparations: Oral - 250, 500 mg. capsules
Other preparations: Doxycycline - 2-4 mg./kg./day
Doxin capsule - 100 mg.
Minocycline (Minocin) - capsule: 50 mg., 100 mg.
DRUGS THAT ACT ON 50 S SUBUNIT

CHLORAMPHENICOL
Usual Dose: IN, CH - 50-100 mg./kg./day div.q6h, PO, IM, IV
Adults - 50-100 mg./kg./day div.q6h, PO, IM, IV
Preparations: Oral - 125 mg./5 ml., 60 ml. suspension
250, 500 mg. capsules
Injection - 1 Gram vials
ERYTHROMYCIN
Usual Dose: IN, CH - 30-50 mg./kg./day, div. q6h PO, IV
Adults - 1-2 Grams/day div. q6 PO, IV
Preparations: 250, 500 mg. tablet; 500 mg. capsules; 100mg./2.5 ml. (30 ml. drops);
200, 400 mg./5ml. (60 ml. suspension)
CLINDAMYCIN
Usual Dose: IN, CH - 10-25 mg./kg./day, div. q6h PO, IV
Adults - 600-1800 mg./day div. q6 PO
Preparations: Oral - 150, 300 mg. capsule; 75 mg./5 ml. x 30 ml. suspension
TRIMETHOPRIM - SULFAMETHOXAZOLE
(COTRIMOXAZOLE)
Usual Dose: IN, CH - 8 mg. TMP and 40 mg. SMX/kg./d div.q12h PO
Adults - 320 mg. TMP and 1600 SMX/d div.q12h PO
Preparations: Oral - 100,000 units/ml. 30 ml. suspension; 500,000 units per tablet
Vaginal - 100,000 units tablets
37
KETOCONAZOLE
Usual Dose: CH - 5-10 mg./kg./day div. q12-24 h, PO
Adults - 200 – 400 mg. qd PO
Preparations: Oral - 200 mg. tablets
ISONIAZID
Preparation: Syrup - 150 mg./5ml.
Tablet - 400 mg.
METRONIDAZOLE
Usual Dose: For amoebiasis and Anaerobic Infections:
IN, CH - 35-50 mg./kg./d div. q8h, PO
Adults - 750 mg. tid, PO
Preparations: Oral - 250, 500 mg. tablets; 125 mg./5ml. (60 ml. suspension)
Injection - 5mg./ml. 100 ml. vial
Rectal - 1 G Suppository
QUINOLONES
Usual Dose: Adults - 400-800 mg./day divq12h, PO, IV
Preparations: Ofloxacin (Inoflax), Ciprofloxacin (Coprobay) - 200, 400 mg. tablets
RIFAMPICIN
Usual Dose: 10-20 mg./kg./day PO
Preparations: Syrup - 100 mg./ml. and 200 mg./5ml. (50-60 ml. suspension)
Capsule - 150, 300, 450, 600 mg.
ANTIFUNGALS
AMPHOTERECIN B
Usual Dose: IN, CH - 0.1-0.25 mg./kg./day (single IV dose)
Adults - 0.25-1 mg./kg./day
Preparation: Injection - 5 mg./ml. (10 ml. vial)
NYSTATIN
Usual Dose: NB - 400,000 units/day div.q4-6 h PO
IN, CH - 400,000-800,000 units / day div.q4-6 h PO
Adults - 800,000 – 2,000000 units/day div. q4-6 h PO
PRINCIPLES OF PRESCRIPTION ORDER WRITING
Prescription - a written order for medicines written by a qualified Medical, Dental or Veterinary
practitioner to the pharmacist for a patient.
“Simple” - if containing only one ingredient.

“Compound” - if containing more than one ingredient.
38
Drugs may be combined in prescriptions for the following reasons:

1. To obtain the conjoint effect of two or more active substances.
2. To diminish or annul undesirable effects produced by one or more of the active
ingredients.
3. To increase the solubility or aid in the dispensing of the active substances.
4. Occasionally, to produce a new compound.
PARTS OF AN IDEAL PRESCRIPTION
________Doctor’s Name_________
_____________Address______________
________Tel. No.________
----------------------------------------------------------------------------------------------------------------------
Patient’s name: __________________________________ Date:_____________

Address:________________________________________________________________________
Tel. No. __________________ Age: ______ Sex: ______
Rx
Generic name of drug, dosage form and amount .
(Brand name of drug)
Direction to the pharmacist .
Direction to the patient .
__________________ D.M.D.
Prescriber’s Signature
PRC License Number
P.T.R. Number .
Narcotic License Number ( S-2)
T.I.N. Tax Identification Number
____________________
39
Refill Information
Parts of the Prescription

Superscription : Patient’s name, address, and age; date and the symbol Rx.
Inscription : Name of drug, dosage form, and amount.
Subscription : Directions to the pharmacist
Transcription / Signature : Direction to the patient
HEADING
Name, address and phone number of the prescriber.
Name, address, age, and phone number of the patient, and date
BODY
The symbol Rx
Name and dosage unit or concentration (liquids) of the drug.
Amount to be dispensed
Directions to the patient
CLOSING
Prescriber’s signature
Space for DEA number
Refill instructions
“Please place name of drug on label”
Importance of placing the name of the drug on label:

1. In case of overdose or adverse reactions, the drugs’ identity can be quickly obtained.
2. Other practitioners can identify drugs the patient is taking.
3. In most cases, the patient has the right to know what drug he or she is taking.
Hints for Prescription Writing

1. Write legibly in ink or have it typewritten
2. Use the metric system
3. Avoid abbreviations
4. Keep a copy of each prescription or transcribe the information to the patient’s record.
5. Include complete information for the patient.
a. Never use “take as directed” unless a written instruction sheet is provided.
b. Include the intended purpose.
c. Use precautions to remind a patient of a drug’s side effects. E.q. “Caution: Sedation
or drowsiness.”
d. Add reminder phrases to increase the patient’s compliance. E.q. “Take until all are
gone.”
6. It must contain the following particulars:
a. The address and usual signature of the practitioner giving it.
b. The date on which it was signed by the practitioner.
c. An indication of whether the practitioner is a dentist, doctor, or veterinary surgeon.
d. The name, address, age (if under 12) of the person whose treatment is given.
7. The prescription shall not be dispensed not later than six months after the date of
signature.
40
Considerations in Drug Administration / Prescribing

1. Tolerance – the ability of a client to respond to a particular dose of a certain drug may
diminish after days or weeks of repeated administration. A combination of drugs may be
given to decrease or delay the development of tolerance for a specific drug.
2. Pathologic State / Pre-existing Disease State - Liver, kidney, heart, circulatory and
gastrointestinal disorders are examples of preexisting states that can affect a response to a
drug. For instance, diabetics should not be given elixirs or syrups than contain sugar.
3. Age - The age of a patient will affect his or her response to drugs. Children and elderly
persons are more sensitive to drugs; they require less than the usual adult dose.
4. Weight - the more a person weighs, the more dilute the drug will become and a smaller
amount will accumulate in the tissues. On the other hand, the less a person weighs, the
greater accumulation in the tissues and a more powerful drug effect is produced.
5. Sex - Women are more susceptible to the action of certain drugs and are usually given
smaller doses.
6. Drug-Drug Interaction - the effects of a combination of drugs may be greater then, equal
to, or less than the effects of a single drug. Some drugs may compete for the same
receptor sites. An adverse reaction may lead to toxicity or complication such as
anaphylaxis.
7. Psychological factors / Emotional factors - A person’s personality often plays an
important part in his response to drugs; comments about the drug and its side effects may
influence its effects.
8. Genetic factors - drug idiosyncrasy is an abnormal susceptibility of some individuals that
causes them to react differently than most people. This intolerance to small amounts of
some drugs is thought to be due to genetic factors. If your mother or father has an adverse
reaction to a drug, you may also.
9. Environmental factors - the setting in which the drugs are given and the attitude of the
person giving the medication may influence the effects of drugs.
10. Method of administration - generally, larger doses are ordered when a medication is
given by mouth or by rectum and smaller doses when the parenteral route is used.
11. Blood level curves and dosing regimens
12. Pregnant and breastfeeding mothers - Administration of medication in the early weeks of
pregnancy may cause damage to the fetus. During the third trimester, there is the
possibility of premature labor caused by drugs that may stimulate muscular contractions.
LATIN PHRASES and ABBREVIATIONS
Used in PRESCRIPTION WRITING
41
Abbreviations Latin English
a. ante before
aa ana of each
a.c. ante cibum before meals
ad ad to, up to
ass. adde, addantur add, let them be added
ad lib. ad libitum at pleasure
acq. acqualis equal
agit. agita shake
aq. aqua water
aq. dest. aqua distilata distilled water
amp. --- ampule
b. bis twice
bene bene well
b.i.d. bis in die twice a day
c cibum meal
c. cum with
cap. capsula capsule
co. ; comp. compositus compound
coch. mag. cochleare magnum a tablespoonful
coch. med. cochleare medium a dessertspoonful
coch. parv. cochleare parvum a teaspoonful
cong. congium a gallon
d. dies a day
da da give
d. in p. acq. dividatur in partes acquales let it be divided into equal parts
d.t.d. dentus tales doses give such doses
dieb alt. diebus alternis every other day
dil dilitus dilute
disp. dispensa, dispensetur dispense
div. divide divide
dos. dosis a dose
E.C. --- enteric coated
elix. elixir elixir
Et et and
Ex ex out of
Ext extractum extract
ex aq. ex aqua with water
e.m.p. ex modo prescripto after the manner prescribed
f. fiat, fiant make, let be made
Fac face make
fl. or fld. fluidus fluid
Ft. fiat make
gm. --- gram
gr. --- grain
gtt. gutta, guttae a drop, drops
h hora hour
h.s. hora somni at bedtime(hour of sleep)
42
DRUG THERAPY
Pharmaceutical Process
Pharmacokinetics Process
Pharmacodynamics Process
Therapeutic Process
PHARMACEUTICAL PROCESS
Is the drug getting into the patient?
Approximately 80% of drugs are taken by mouth; therefore, the pharmaceutic phase is the
first phase of drug action. In the gastrointestinal tract, drugs need to be in solution to be
absorbed. A drug in solid form (tablet or pill) must disintegrate into smaller particles in order
for it to dissolve into a liquid.
Disintegration is the breakdown of the tablet or pill into smaller particles.

Dissolution is the dissolving of smaller particles in gastrointestinal fluid for absorption.
Rate Limiting is the time it takes for the drug to disintegrate and become available for the
body to absorb it.
Factors to consider
1. Particle size - the smaller the particle size, the faster it can be absorbed in the body.
2. Excipients of drug - fillers and inert substances are used in drug preparation to allow the
drug to take on a particular size and shape and to enhance dissolution of the drug. Some
additives such as K and Na in penicillin K and penicillin Na, increase the absorbability of
the drug.
3. Coating material - Enteric-coated (EC) drugs resist disintegration in the gastric acid in
the stomach, so disintegration does not occur until the drug reaches the alkaline
environment in the small intestine.
PHARMACOKINETIC PROCESS
Is the drug getting into its site of action?
- is the process of drug movement to achieve drug action.
- concerned with the absorption, distribution and elimination (metabolism and excretion)
of drugs.
ABSORPTION
- process by which drug molecules are transferred form the site of administration in the body
to the circulating fluids
Factors Affecting Absorption

1. Physico-chemical factors
2. Site of absorption / Blood flow at the site
3. Drug Solubility
4. Effects of food
a. Blood flow
b. Gastric emptying
43
 the non-ionized portion behaves as a non-polar lipid soluble compound which readily
traverses body membranes.
 The amount of ionization that any weak electrolytes undergoes depend on the pH at the
drug site in the tissues and its dissociation characteristics.
 Increase pH (weak acids) - the greater the degree of ionization
Decrease pH (weak bases) – the greater the degree of ionization.
Oral absorption – depends on the dosage form of drugs.

Absorption on injection sites - depends on the solubility of drug and the blood flow at the
site; also affected by dosage form. E.q. drugs in suspension are absorbed much ore
slowly than those in solution.
Effects of food on drug absorption

- by affecting the blood flow and gastric emptying. E.q. liquid glucose meal decreases
flow and a meal rich in protein increases flow.
- some drugs are irritating to the stomach mucosa, so fluids or food are necessary to
dilute drug concentration
- there are drugs that are absorbed easily in the presence of food.
Factors that Modify the Rate of Absorption

1. Drug Concentration at the Site
2. Circulation to the Site of Absorption
3. Area of Absorptive surface
FACTORS GOVERNING THE FATE OF A DRUG

1. Molecular Weight
- substances with high molecular weight are not usually absorbed intact except in minute
quantities.
- they are absorbed by enzymatic actions. E.q. insulin is a protein – it undergoes
enzymatic breakdown in the git and is not absorbed.
2. Chemical Stability
- unstable drugs maybe inactivated in the git. E.q. Benzylpenicillin in unstable in acid
medium and cannot be effective if given by mouth. Phenoxymethylpenicillin is more
stable in acid medium.
3. Lipid Solubility
- if the drug is lipid soluble, it can easily pass through the membrane.
4. Degree of Ionization
- the unionized portion of a drug is lipid soluble and so is readily absorbed; ionized
portion is lipid insoluble.
THE CELL MEMBRANE

Composition:
Lipids (40%) phospholipids
- makes membrane relatively impermeable to ions and polar molecules
Proteins (50-60%)
- make up the structural components of the membrane
- acts as enzyme during transport
44
Carbohydrates (remainder) Oligosaccharide

- linked covalently to form complexes of glycoproteins and glycolipids
*PRINCIPAL MECHANISMS INVOLVED IN THE PASSAGE OF DRUGS

ACROSS CELL MEMBRANE
1. Lipid Diffusion (Simple Diffusion)

- drug molecules dissolves in the membrane to penetrate through the other side.
Can take place either via:
Lipoprotein membrane
Paracellular spaces
2. Aqueous Diffusion (Filtration through Pores)
- the size of the drug molecule is relative to the size of the pores.
- water soluble drugs with molecular weight less than 100 Daltons are able to cross
the cell membrane by passing through the polar pores. E.q. Ethanol (46); Urea (60)
3. Specific Carrier Mediated Transport System
Active Transport
- process by which a substance is transported against a concentration gradient.
Drug molecules are mediated by transport “carrier” that furnish energy for the
transportation of drug from lower concentration through higher concentrations.
E.q. Na, K, Ca, Fe, amino acids, and glucose.
3 Features
1. Ability to work against concentration gradient, osmotic, electrical, or
hydrostatic gradient
2. Specificity – ability to concentrate a selected substance on one side of the cell
membrane.
3. Each system require an energy source (ATP), to which it is directly coupled.
Facilitated Diffusion
- a passive process whereby drugs can move across cell membranes more rapidly
than simple diffusion.
- involves the action of a specific but saturable carrier system
- can only work in the presence of an appropriate concentration gradient.
DISTRIBUTION
- the passage of drug into various body fluids compartments such as plasma, intestinal fluids
and intracellular fluids; process by which the drug becomes available to body fluids and
body tissues.
Factors affecting Distribution

1. Blood flow
2. Affinity to the tissue
3. Protein binding
Forms of Drug inside the Body

1. Free / Unbound state - free active drug
45
2. Bound - inactive drug

Binding to Plasma Proteins - e.q. salicylic acid and warfarin bind to Albumin
Basic drugs bind to acid glycoproteins and lipoproteins
Binding to Cells - drugs become bound onto the surface or inside the cells.
*Only free drugs or drugs not bound to protein are active and can cause a
pharmacologic response. As the free drug in the tissues decreases, more bound drug is
released from the protein to maintain the balance of free drug.
Checking the protein-binding percentage of all drugs administered is important in
order to avoid possible drug toxicity. E.q. Drug accumulation and toxicity can result if
two highly protein-bound drugs are given concurrently because they will compete for protein
binding sites causing more free drug to be released into the circulation; Also, a low protein
level decreases the number of protein binding sites, causing an increase in the amount of
free drug in the plasma. Drug overdose may result because drug dosage is prescribed
according to the percentage in which the drug binds to protein.
STORAGE DEPOT (Non-specific Site) - helps prevent prolong the action or areas for
transient storage.
AFFINITY TISSUES - maybe sites of action or areas for transient storage; some drugs
accumulate in particular tissues such as fat, bone, liver, eye, and muscle.
E.g.
Guanethidine - binds to heart and skeletal muscle
Quinacrine - binds to liver and skeletal muscles
Tetracycline - bone and enamel
Thiopental - adipose tissue
METABOLISM
- Liver – main organ of metabolism
- most drugs are inactivated by liver enzymes and are then converted by hepatic enzymes to
an inactive metabolite or water soluble substance for excretion. However, some drugs are
transformed into active metabolites causing an increased pharmacologic response.
Example of liver disease that affects metabolism - cirrhosis and hepatitis.
1. Excretion in the original form e.q. Hexamethonium – a highly ionized antihypertensive

compound excreted in the urine unchanged.
2. Transformation into one or more Metabolites
Other organs: G.I.T., Lung, kidney, skin and placenta.
BIOTRANSFORMATION - a process wherein parent drug is converted by enzymes

into drug metabolites ready to perform its action.
Biotransformation of Drugs has Two Effects

1. It alters the pharmacological activity, usually decreasing it but sometimes converting
the drug to a compound similar or greater activity (potency) than the original.
2. Results in metabolites that are more water-soluble and less lipid soluble than the parent
compounds and therefore more readily excreted in the urine.
46
* Two General Types of Chemical Reaction

Phase 1 (Non-Synthetic reaction)
1. Oxidation - Diazepam
2. Reduction - Nitrazepam, Cortisone
3. Hydrolysis - Suxamethonium, Amethocaine
Phase 2 (Synthetic (Conjugation) Reaction)

-It involves conjugation to form one or more of the following:
1. Glucoronide e.g. Morphine, Paracetamol
2. Sulphate e.g. Isoprenaline
3. Acetate e.g. Isoniazid, Hydralazine
4. Glutathione e.g. Paracetamol
BIOLOGIC HALF-LIFE (t1/2) - is the time it takes for one half of the drug concentration to
be eliminated.
- a drug goes through several half-lives before more than 90% is eliminated.
Example: 650 mg. of Aspirin t1/2 = 3 hours
Number (t1/2) Time of Elimination(h) Dosage Remaining (mg) %left

1 3 325 50
2 6 162 25
3 9 81 12.5
4 12 40.5 6.25
5 15 20 3.1
6 18 10 1.55
- it takes three hours for the first half-life to eliminate 325 mg and the second half-life
(6h) for an additional 162 mg. to be eliminated, and so until the 6th half-life (18h)
when 10 mg. of aspirin is left in the body.
- a short half-life is 4-8 hours.
- a long half-life is 24 hours or longer (e.q Digoxin 36 hours); it takes several days until
the body completely eliminates the drug.
Factors Affecting Drug Metabolism

1. Age
2. Sex
3. Liver Disease
4. Environmental Factors
5. Genetic Factors
6. Route of Administration
MICROSOMAL DRUG METABOLIZING SYSTEM - the most important of the many

biochemical system in the body involved in biotransformation.
- located primarily in the smooth Endoplasmic Reticulum of hepatic cells.
47
CYTOCHROME P450 - the most important enzyme in the microsomal enzyme system
involved in the oxidative transport processes.
EXCRETION
- major way by which the activity of the drug is terminated
- mainly in the Kidney; some via the (Extra Renal Route) .Bile, Skin (sweat), Lungs
(expired air), Saliva, Feces
and Breast Milk
- expressed in terms of “Renal Plasma Clearance” – the volume of plasma effectively cleared
of the drug by the kidney in unit time.
RENAL EXCRETION - most important route of drug elimination

*3 Processes Implicated in Renal Excretion
1. Glomerular Filtration
- depends upon the plasma concentration of drugs and molecular weight.
- 125 ml./min.
2. Tubular Reabsorption / Active Secretion in the Proximal tubule
3. Tubular Secretion / Passive Re-absorption in the distal tubule
PHARMACODYNAMICS
Is the Drug producing the required Pharmacological Effect?
- study of a drug’s effect on cellular physiology and biocehmistry and the drug’s mechanism
of action.
I. Drugs which act via Pharmacological Receptors:

1. Act at low concentration
2. React with specific receptors
3. Show structure activity relation
4. Can be antagonized by specific antagonist
e.q. acetylcholine; adrenaline; noraduraline and histamine
e
II. Drugs which DO NOT act via Pharmacological Receptors:
f 1. Act at higher concentrations
g 2. Do not react with specific receptors
h 3. Tend to show structure-activity relationships
i 4. Do not have specific antagonists
e.q. General anesthetics and non-specific destructants of cell membranes such as
detergents.
DRUG-RECEPTOR INTERACTION
Receptor - a macromolecule with special sites to which specific substances binds.
(Drug/Ligands – Receptor).
SITES OF RECEPTORS
1. On or within Cell Membranes
2. Inside Cells
48
Most receptors, protein in structure, are found on cell membranes. Drugs act through
receptors by binding to the receptor to produce (initiate) a response or block (prevent) a
response. The activity of many drug is determined by the ability of the drug to bind to a
specific receptor. The better the drug fits at the receptor site, the more biologically active
the drug is. It is similar to the fit of the right key in a lock.
Figure: Two drug agonists attach to the receptor site. The drug agonist that has an
exact fit is a strong agonist and is more biologically active than the weak agonist.
Agonist - a drug (hormone or neurotransmitter) which combines with its specific receptor,
activates it and initiates a sequence of effects.
E.q. Isoproterenol stimulates the beta1 receptor.
Antagonist - a drug which interferes with the action of an agonist but does not have any
effect itself unless it possess partial agonist activity.
E.q. Cimetidine blocks the H2 receptor thus preventing excessive gastric
secretion.
Partial Agonist - a drug that act on a receptor with an intrinsic activity or efficacy of < 1.
Mixed Agonist-Antagonist - a drug that act simultaneously on a mixed group of

receptor with an agonist action on one set and an antagonist action on another.
***DRUG ANTAGONISM - occurs when their biological effect is less than the expected sum of
their individual effects.
Pharmacological Antagonism:
1. Reversible Competitive / Equilibrium Antagonism
- substances are competing dynamically for the same pharmacological receptor
2. Irreversible Competitive / Non-Equilibrium Antagonism
- drugs form very strong bonds
Non-Competitive Antagonism - block action of an agonist not at the receptor level but at
some point between receptor and effector that leads to the action of the agonist.
Physiological Antagonism - occurs when two drugs that act on different receptors produce
opposite effects. E.q. Adrenaline antagonizes the effects of histamine on bronchial
smooth muscle.
Chemical Antagonism - occurs when one drug combines chemically with another to
produce inactive product.
49
Pharmacokinetic Antagonism - occurs when one drug effectively reduces the

concentration of another at its site of action by altering its absorption, distribution or
elimination.
***Relationship Between the Dose of Drug and the Effect it produces:

Two Types of Relationship:
1. Quantitative (Graded) responses or effects
- the effect increases as the dose is increased until the maximum is reached. Beyond
this point, any increase in the dose is not accompanied by an increase in effect or
response.
Graded - refers to that characteristic of an effect which begins at some low level and
increase through progressive stages until it reaches some higher level.
2. Quantal responses or effects

- “All or None” response. E.q. In toxicity test, a dose could either kill or not.
Definition of Terms:
Onset of Action - begins when the drug enters the plasma and lasts until it reaches minimum
effective concentration (MEC).
Peak Action - occurs when the drug reaches its highest blood or plasma concentration.
Duration of Action - is the length of time the drug has a pharmacologic effect.
Time-response-curve - evaluates three parameters of drug action: the onset of drug, peak action,
and duration of action.
Biologic Variation - connotes the sum total of all the sources of variation that combine to
cause one biologic unit to vary from one another.
Threshold Dose - lowest case of a drug that will produce a measurable response.
Plateau - endpoint/terminal point in a graded dose response curve.
Therapeutic Index - the difference between the dose which will produce the desired effect
and that which will cause adverse effect.
- estimates the margin of safety of a drug by using a ration that measures the
effective therapeutic dose in 50% of animals (ED50) and lethal dose in 50%
of animals (LD50). The closer the ratio is to 1, the greater the danger of
toxicity.
- a figure that gives measure as to the amount by which therapeutic dose
made exceeded before eliciting a toxic effect. For clinical situation, a
better measure would be adverse effect dose ED50 in which a specific
adverse effect is considered, rather than the lethal median dose.
Median Effective Dose (ED 50) - smallest dose causing the given pharmacologic effect in
50% of the individuals of a sample.
Relative Safety - dose of the drug required to produce the desired therapeutic effect
relative to the dose of the drug required to produce toxic or lethal effects.
Therapeutic Effects - desirable clinical action of a drug.
"Risk - Benefit Ratio" - toxicity taken into consideration --- "the risk of treatment weighed
against the risk of disease" e.q. the use of known highly toxic drugs
such as those used in the treatment of cancer applies this principle.
50
THERAPEUTIC PROCESS
Is the Pharmacological effect being translated into a desired therapeutic effect?
Factors which Determine the Relationship Between

Prescribed Drug Dosage and DRUG Effect
Dosage Pathway Influences on Drug Effect
Prescribed dose Patient compliance

Medication errors
Administered dose Rate and extent of absorption
Body size and composition
Distribution in body fluids
Binding in plasma and tissues
Rate of elimination
Concentration at locus of action Physiological variables
Pathological factors
Genetic factors
Interaction with other drugs
Development of tolerance
Intensity of effect Drug receptor interaction
Functional state
Placebo effects
PHARMACOLOGY OF INFLAMMATION
- a reaction of the vascular and supporting elements of a tissue to injury which results in a
protein-rich exudate, provided the injury has not been so severe as to destroy the area.
CLINICAL SIGNS OF INFLAMMATION

1 Rubor - Redness
2. Tumor - Swelling
3. Calor - Hotness
4. Dolor - Pain
5. Functio Laesa - Loss of function
CLINICAL MEDIATORS
HISTAMINE
- a vasoactive amine found in most tissues of the body
- formed by the decarboxylation of the amino acid histidine.
PHARMACOLOGICAL PROPERTIES OF HISTAMINE
- relaxation of the vascular smooth muscle
- contraction of the bronchi and gut wall
- secretion of exocrine glands
- production of pain and itch
- acts as neurotransmitter in the CNS (control of thirst, secretion of antidiuretic hormone,
control of blood pressure, and pain perception).
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TYPES OF HISTAMINE RECEPTORS

H1 = primarily related to smooth m. activity
H2 = primarily involved with the stimulation of gastric secretions
H3 = mediates CNS effects of histamine on histaminergic nerve terminals
Effects of Histamine:
Heart - increase heart rate & force of contraction which results in an increase in cardiac
output
- increase histamine may cause arrhytmias due to slowing of A-V conduction
- dilation of small b.v leads to flushing, lowered peripheral resistance, and a drop in
blood pressure.
Smooth muscles - “Bronchial muscle’

- activation of H1 receptor results to bronchoconstriction.
- Patients who suffer from asthma are particularly sensitive to the action of histamine on
the bronchial musculature however, antihistamines are of no value in the treatment of
asthma.
Gastric secretion - even a slow concentration can cause copious secretion of the gastric
juices mediated by H2 receptor.
Pain and Itch - caused by direct stimulation of free nerve endings when injected.
- Subcutaneous injection of histamine causes sharp pain of short duration like a wasp’s
sting but when injected into a more superficial layer of the skin, causes itching.
ANAPHYLAXIS AND ALLERGY

Anaphylactic reaction – most dangerous acute allergic reaction occurring hour after drug
administration.
- histamine will be released due to an antigen combining with specific antibody attached
to the surface of mast cells (DEGRANULATION) causing the extrusion of histamine
from the secretory granules in the mast cells.
- e.q. of substances that can cause anaphylaxis and allergy: Penicillin, animal fur,
pollen.
Adverse Effects - undesirable clinical action of a drug; a range of untoward effects

(unintended and occurring at normal doses) of drugs that cause mild to
severe side effects, including anaphylaxis; Always undesirable.
Side Effects - are physiologic effect not related to desired rug effects; Maybe desirable or
undesirable and are predicted.
Toxic Effects - adverse effects of an unexpected nature resulting from the direct action
of a drug.
Allergy - altered capacity of the body to react to various antigens.
Idiosyncracies - covers unusual or bizarre drug effects that cannot readily be explained in an
individual recipient.
AUTOCOIDS – derived from the Greek word “autos” (self) and ‘akas” (remedy). It refers
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substances which have local hormone-like activity at or near the site of

production.
EICOSANOIDS – a term that denotes the metabolites of certain 20-carbon

polyunsaturated fatty acids, mainly arachidonic acid.
- products of arachidonic acid metabolism are divided into two main groups on the
basis that they are ultimately derived from the action of one of the two enzymes
systems (cyclo-oxygenase or lipoxygenase) on arachidonic acid.
ARACHIDONIC ACID - a 20 - polyunsaturated fatty acid

Two sources :
1. Metabolic pool - endogenous synthesis of arachidonic acid
2. Cell membrane pool - stimulated synthesis such as trauma; major source of the
eicosanoid precursor in inflammation.
Arachidonic acid -----metabolized------ results to metabolites (eicosanoids - a term…) by the

action of the 2 enzyme (cyclo-oxygenase and lipoxygenase)
*In most cells and tissues, phospolipids are thought to be the major source of arachidonic acid.
1. The first step in eicosanoid synthesis: liberation of the Arach. Acid from cell membrane
phospolipids by the action of a group of enzymes known as the phospolipases particularly
phospolipase A2 responsible for its bulk.
2. The second step : formation of cyclo-oxygenase on free arachidonic acid ( results in the
insertion of 2 oxygen molecules into the fatty acid carbon chain to form PGG2 which is
rapidly transformed by the peroxydase-like activity of cyclo-oxygenase into the
hydroxyperoxide, PGH2). This is followed by the formation of one of the three groups
depending on the particular cell and circumstances involved, the prostaglandins,
thromboxane, and prostacyclin.
CYCLO-OXYGENASE PRODUCTS:
PROSTAGLANDIN - 1st identified in 1930 but their structure and function were
elucidated until 1960.
- occur in every tissue and body fluid.
– vasodilators = fall in blood pressure
2 Types: PGE and PGF series
THROMBOXANE AND PROSTACYCLIN

THROMBOXANE A2 - Main synthesis in platelets plays an important role in platelet
aggregation
PROSTACYCLIN - a potent vasodilator and acts as an antagonist of platelet
aggregation; main synthesis in vessel walls.
*T and P are biologically opposite poles of the mechanism for regulating the platelet
vessel wall interaction and the formation of hemostatic plug. Both are unstable,
with very short half lives.
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LIPOXYGENASE PRODUCTS:
LEUKOTRIENES - has potent chemotactic properties; probably involved in the

process of cellular infiltration that accompanies
inflammation. Types: LTA4; LTB4; LTC4; LTD4; LTE4
PLATELET ACTIVATING FACTOR

- a lipid autocoid synthesized mainly by platelets, leukocytes, and endothelial cells.
- action includes vasodilation, inc. in vascular permeability, white blood chemotaxis,
and the release of lysosomal enzymes.
- a potent stimulator of platelet aggregation.
- may also be important in the pathogenesis of asthma.
Arachidonic Acid Metabolism Product
Cyclo-oxygenase product Lipoxygenase product
Prostaglandins Leukotrienes
Thromboxanes Compounds based on
Prostacyclin eicosatetraenoic acid
BRADYKININ AND KALLIDIN

- Polypeptides formed from the plasma alpha globulins by a complex series of
proteolytic reactions.
- Potent vasodilators
- Increase capillary permeability = oedema
- Cause bronchoconstriction
- Bradykinin: 10X active than histamine; effects are brought by: Kinin Receptors : B1
and B2
5-HYDROXYTRYPTAMINE (5-HT)
j - amine formed by the hydroxylation of tryptophan stored in gastric mucosa
k - dilatation of arteries and constriction of veins via receptors 5HT1 ; 5HT2 ; 5HT3
l - high concentrations are found in platelets.
- pharmacologic properties: role in inflammation is uncertain and maybe insignificant;
dilation of arteries and constriction of veins.
CYTOKINES - Proteins secreted by cells that have effects on other cells
LYMPHOKINES - cytokines produced by sensitized T lymphocytes and to a lesser

extent by B lymphocytes in response to antigenic challenge
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Actions of Lymphokines:
1. Chemotactic for macrophages
2. Macrophage activation
3. Macrophage inhibition
4. Chemotactic for other mononuclear WBC
5. Mutagenic for other lymphocytes
6. Increased vascular permeability
7. Activation of osteoclasts.
INTERLEUKINS
- cytokines from macrophages and lymphocytes during inflammation and immune
response.
- exerts a number of inflammatory actions which include the stimulation of PG and
collagenase production, chemoattraction for WBC and enhancement of the hepatic
synthesis of acute phase proteins.
- Has 8 types: Interleukins 1 – 8.
COMPLEMENT
- consist of a series of protein that react in a cascade fashion
ANTIHISTAMINES
- antagonize histamine at the receptor sites; do not alter the formation or release of histamine
from tissues or mast cells.
- classified as H1 or H2 receptor blockers (antagonists)
H1 Receptor Antagonists
- interact with H1 receptor on cell membranes - results in a decrease in the availability of
these receptors for the action of histamine; well absorbed from the git; therapeutic effects
can be observed within 15-30 min. after dosage; widely distributed in the body and broken
down in the liver.
- Therapeutic uses: Treatment and prevention of a variety of allergic conditions (e.q. rhinitis,
hay fever, and certain allergic dermatoses such as acute urticaria). Topical application is
useful in relieving the itching associated with insect bites; widely used as common cold
remedies usually combined with decongestants (e.q. Actifed).
- no effect on bronchospasm or severe hypotension associated with anaphylactic shock; no
value in the treatment of asthma.
Unwanted effects: Sedation; may cause stimulation; dryness of the mouth; variety of g.i
disturbances.
*** Alcohol should be avoided while taking H1 blockers as it enhances the sedative effect.
H2 Receptor Antagonists
- antagonizes the action of histamine at H2 receptor.
- commonly used are Cimetidine and Ranitidine.
- reduce gastric secretion; Treatment of duodenal ulcers and gastric hypersecretion.
Unwanted effects: slight such as headache, dizziness, constipation or diarrhea, and skin
rashes
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5-HT ANTAGONISTS - Ergot alkaloids are a group of compounds that are antagonists for
5-HT, Ergotamine.
CORTICOSTEROIDS - have potent anti-inflammatory properties; widely used in the treatment

of recurrent oral ulceration and other oral mucosal lesion such as erosive lichen planus,
erythema multiforme, and pemphigus. E.q. 0.1% Triamcinolone (topical) ; hydrocortisone
sodium succinate 2.5 mg. ; Bethamethasone 17-valerate (topical spray) ; etc.
- pulpal inflammation; TMJ pain; Bell’s palsy; post-operative pain and swelling after dental
surgery; Anaphylactic and allergic reactions.
PHARMACOLOGY OF PAIN
Pain - an unpleasant sensory and emotional experience associated with actual or potential tissue
damage, or described in terms of such damage.
Analgesia - absence of pain in response to stimulation which would normally be painful.
Hyperalgesia - an increased response to a stimulus which is normally painful
Neuralgia - pain in the distribution of a nerve.
Neuritis - inflammation of a nerve or nerves.
Nociception - activity in a nerve fiber which arises as the result of stimulation of nociceptors.
If nociception reaches consciousness, it is perceived as pain.
Nociceptor - a receptor preferentially sensitive to a noxious stimulus or to a stimulus which
would become noxious if prolonged.
Pain threshold - the least stimulus intensity at which a subject perceives pain.
Pain tolerance level - the greatest stimulus intensity causing pain that a subject is prepared to
tolerate.
Allodynia - pain due to a stimulus which does not normally provoke pain.
Causalgia - a syndrome of sustained burning pain, allodynia and hyperpathia after a traumatic
nerve lesion, often combined with vasomotor dysfunction and later trophic changes.
Hyperaesthesia - increased sensitivity to stimulation excluding special senses.
Hyperpathia - a painful syndrome characterized by increased reaction to a stimulus, especially
repetitive stimulus, as well as an increased threshold.
Neuropathy - a disturbance of function or pathological change in a nerve; in one nerve,
mononeuropathy; in several nerves, mononeuropathy multiplex; if diffuse and
bilateral, polyneuropathy.
Two Main Types of NOCICEPTORS

1. High Threshold Mechanoreceptor
2. Polymodal Nociceptor
THEORIES OF PAIN
1. SPECIFICITY Theory - concerned primarily with the sensory discriminative aspects of
pain and its quality, location on the skin, intensity and duration.
2. CENTRAL SUMMATION (PATTERN) Theory – pain is not a separate entity, but
results from over stimulation of other primary sensations.
3. SENSORY INTERACTION Theory – stresses inhibition as an important physiological
mechanism in pain transmission.
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4. GATE CONTROL Theory - stressed the importance of both descending control

mechanism and activity in large sensory fiber in modulating the pain experience.
PERIPHERAL MEDIATORS OF PAIN

1. BRADYKININ
2. HISTAMINE
3. EICOSANOIDS
Four Main Groups of Eicosanoids

1. Prostaglandin
2. Prostacyclin
3. Thromboxane
4. Leukotrienes
CENTRAL MEDIATORS OF PAIN

1. Amino Acids
2. Peptides
METHODS TO RELIEVE PAIN

1. Remove peripheral stimulus
2. Interrupt nociceptive input
3. Stimulate nociceptive inhibitory mechanism
4. Modulate central appreciation of pain and/or emotional concomitants
5. Block or remove secondary factors maintaining pain.
I. NON – NARCOTIC ANALGESICS

General Characteristics
1. Relieves pain without altering consciousness.
2. Safer than narcotics.
3. Produce fewer side effects.
4. Not addicting.
5. Act principally on peripheral nerve endings.
6. Inhibits the synthesis of prostaglandins.
PharmacologicAction
1. Analgesia
2. Antipyresis
3. Antiinflammatory
SALICYLATES – extracts of willow bark containing the bitter glycoside salicin.

Therapeutically Useful SALICYLATES
1. Salicylic Acid - parent compound., toxic internally, topical fungicide, keratolytic agent.
2. Sodium Salicylate - internal use as an analgesic, less effective than aspirin, may be
used in patients allergic to aspirin.
3. Methyl Salicylate (oil of wintergreen) – external use as a counterirritant, flavoring in
cooking.
4. Acetylsalicylic acid - widespread use as an analgesic, antipyretic and antirheumatic
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5. Salicylamide – internal use as an analgesic; less effective than aspirin; less G.I.
irritation.
6. Difflunisal – an investigational salicylate; possibly better tolerated , effective at lower
doses; apparent therapeutic advantage over aspirin and perhaps other inflammatory
agents.
ASPIRIN
- absorbed from the git; partly from stomach but mainly in the upper small intestine
Pharmacological Properties
- Analgesic (mild analgesic) – due to inhibition of the synthesis of PGE.
Suitable regimen: 600-1200mg. every 4-6 hours.
- Anti-inflammatory – inhibit synthesis of eicosanoids; High concentrations can inhibit
the function and activity of PMN leukocytes
- Antipyretic – lowers an elevated body temp. (pyrexia) due to infection, tissue damage,
malignancy or other disease states; due to inhibition of prostaglandin
production in the hypothalamus.
- Antithrombotic effect
Unwanted effects
- Gastrointestinal – epigastric pain, nausea, gastric erosions leading to blood loss
- Haemostatic effects – prolongs bleeding time; inhibiting the synthesis of platelet
thromboxane.
- Tinnitus – hearing loss due to rise in labyrinth pressure
- Uricosuric effect – increase plasma uric acid. Should Not be given to patients with
gout(a disorder of uric acid metabolism).
- Effects on kidney – decrease renal blood flow; also enhances sodium and water
retention.
Aspirin Hypersensitivity – from rhinitis to life threatening laryngeal edema.

Aspirin Overdose – 10-30 gm. can be fatal.
Aspirin and Reye”s Syndrome – an acute encephalopathic illness and fatty degeneration
of the viscera, especially the liver that arises after an infectious illness such as
chickenpox or influenza.
- interaction between aspirin and the viral infection leads to damage of cell mitochondria
in genetically susceptible individuals.
PARA-AMINOPHENOLS
A. Acetaminophen (paracetamol, N-acetyl)
B. Phenacetin (acetophenetidin)
ACETAMINOPHEN
Pharmacologic Properties
1. Analgesic
2. Antipyretic
3. Antiinflammatory (not clinically significant)
4. Do not produce gastric bleeding
5. Do not affect platelet adhesiveness
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6. Do not affect uric acid excretion

7. Enhances water transport in the kidney.
8. Peak plasma concentration usually occur 30 minutes. After dosage, and the half life
is usually 2 hours.
9. Conjugated in the liver and excreted in the urine.
Adverse Effect:
1. Methemoglobinemia (Phenacetin)
- condition that results from conversion of the iron in hemoglobin to an oxidized state
that cannot effectively carry oxygen.
Signs: 1. Cyanosis
2. Dyspnea on exertion
3. Anemia
2. Hemolytic Anemia
- Hemolysis is caused by minor metabolites that oxidize glutathione in the RBC and
thereby labilize the erythrocyte membrane to oxidative destruction.
Signs: 1. Abdominal or lower back pain
2. Jaundice
3. Hemoglobinuria
4. Anemia
3. Hepatic Necrosis
- may occur after ingestion of a single dose of 10 to 15 Grams.
4. Nephrotoxicity
Adult dose: 325 to 500 mg. or 2 tablets or capsules; not more than 4 Grams in 24
hours.
Unwanted effects: few; most serious is hepatoxicity

Paracetamol Overdose: 10-15 gm. – acute liver damage – manifests between 2-6 days
after overdose 25 gm. – fatal
Treatment: Gastric lavage provided it is in the first hour after dosage; <12 hrs. – N
acetylcysteine; after 24 hrs. – the success of treatment depends on the
magnitude of the initial dose. (px will suffer a slow and distressing death).
- In postoperative dental pain, efficacy is NOT dose-related.
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

- share many of aspirin’s pharmacological properties.
- anti-inflammatory and analgesic because they can inhibit the synthesis of eicosanoids.
- produce unwanted effects similar to those of aspirin.
A. PHENYLPROPIONIC ACID DERIVATIVES – Ibuprofen, Naproxen, Flurbiprofen and

Fenoprofen
Pharmacologic Properties
1. The mechanism of action appears to be related to inhibition of prostaglandin
synthetase.
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2. Analgesic, antipyretic, and anti-inflammatory.

3. Indicated for the symptomatic treatment of rheumatoid arthritis.
Adverse Reaction
1. Gastointestinal upset
2. CNS effects such as dizziness, headaches, drowsiness and tinnitus.
Naproxen: t1/2 13 hours.

Ibuprofen – peak plasma concentration – 1.5 hrs. after dosage and the plasma half life is
2 hours; broken down in the liver; excreted in the urine; has similar
unwanted effects as aspirin.
B. INDOLEACETIC ACID
1. Indomethacin
- most potent inhibitors of cycloxygenase
- analgesic, antipyretic, powerful anti-inflammatory agent.
- used in rheumatoid arthritis.
- first drug of choice to treat gout.
Adverse reaction:
- GI complaints
- CNS - dizziness, headache, tinnitus, vertigo, confusion – unknown, but may be
due to PG inhibition
2. Sulindac
- has analgesic, antipyretic effect.
- treatment of rheumatoid arthritis.
C. PYRROLACETIC ACID
Tolmentin
Zomepirac
D. FENAMIC ACID DERVIATIVES (FENAMATES)

1. Mefenamic acid
- treatment of pain, dysmenorrhea
- sedation can occur
- absorbed after oral dose; peak plasma concentrations – after 2 hrs.; half-life is 3-4
hours.
- metabolized in liver, half of metabolites excreted in the urine, half in the feces.
- Diarrhea occurs in 25% of patients
- as active as aspirin;
- incidence of unwanted effects esp. GI disturbance is high.
2. Meclofenamate
- treatment of arthritis
- dose: initial – 500 mg. followed by 250 mg. every six hours.
E. PYRAZOLONES
Phenylbutazone
Oxyphenbutazone
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F. DIFFLUNISAL
- a difluorophenyl derivative of salicylic acid; has similar pharmacologic properties as
aspirin
- long plasma half-life – 8 hrs. (only b.i.d.)
II. NARCOTIC ANALGESIC

Similarities: They all produce:
1. Potent analgesia
2. Addiction
3. Respiratory depression
4. Sedation
5. Emesis
6. Constipation
CLASSIFICATION
1. OPIUM ALKALOIDS
2. SEMISYNTHETIC DERIVATIVES
3. SYNTHETIC DERIVATIVES
I. OPIUM ALKALOIDS
- opium is the dried juice obtained from the unripe seed capsules of the poppy plant
(Papaver somniferum)
A. Morphine
– most potent analgesic in use
– named after Morpheus (Greek God of Dreams)
– undergoes extensive first pass metabolism in the liver.
– Parenteral solutions of morphine sulfate and oral preparations are available.
– t1/2 = 3 hours
– Dosage: Adult – 10 to 15 mg. subcutaneously every 4-6 hours.
Children – 0.1 to 0.2 mg/kg/dose
Maximum dose: 15 mg.
1. Analgesia - effective against continuous dull pain.
2. GIT – used to treat diarrhea and dysentery; produce degree a degree of
constipation.
3. Cough suppression - effective antitussive.
4. Cardiovascular - cause the release of histamine.
Unwanted Effects
2. Dependence
3. Nausea and Emetic effect
4. Cause constriction of the pupil (MIOSIS)
5. Actions on the bladder.
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B. Codeine or Methyl Morphine

- Dose: Adult – 15-60 mg (1/4 to 1 grain)
1. Effective when taken by mouth
2. Use in treating mild to moderate pain
3. Very effective antitussive.
Unwanted Effects
1. Nausea, vomiting, sedation, dizziness
2. Can depress respiration
3. Can cause constipation
C. Heroin
- produced by acetylation of morphine
- 2 to 5X as potent as morphine as an analgesic.
- highly euphoric and addicting drug
II. SEMISYNTHETIC DERIVATIVE OF MORPHINE OR CODEINE

A. Hydromorphone
- more potent than morphine.
- principal use is for acute pain.
B. Hydrocodone (Codone, Dicodid)
C. Oxymorphone
- extremely addicting and a potent respiratory depressant.
- Dose: Adult - 1mg. subcutaneously.
- Available only for parenteral use.
III. SYNTHETIC NARCOTICS
A. Meperidine (Demerol)
- most common narcotic abused by professionals.
- Dose: Adult – 50 to 100 mg. orally, subcutaneously, or intramuscularly.
- Preparation: Tablets, elixir, and solutions for injections.
- available in combination with acetaminophen or promethazine.
Adverse Effect
1. Sedation
3. Increased tone and secretions of GIT
4. Produces addiction
5. Tolerance develops.
B. Alpaprodine
C.
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D. Anileridine
- Dose: usual Adult dose – 25 to 50 mg. every six hours.
- can be give orally, intramuscularly or subcutaneously.
- available in tablets and injection.
OPIOID ANTAGONIST
Naloxone
- mainly used to treat opioid overdose, particularly the effects on respiration.
- must be given intravenously.
- 0.4 to 0.8 mg for immediate effect
- t1/2 1 hour
COMPREHENSIVE DRUG ABUSE PREVENTION and CONTROL ACT OF 1970
SCHEDULE 1 SUBSTANCES
 Drugs with a high potential for abuse and no currently accepted medical use.
 Not for prescription use but may be obtained for research purposes.
E.q. Heroin Ketobemidone
Marijuana Benzylmorphine
Peyote Nicomorphine
Mescaline Methaqualone
LSD Dihydromorphine
Nicodeine Racemoramide
Morphine methylsulfonate
Levomoramide
SCHEDULE II SUBSTANCES
 Drugs with a high potential for abuse with severe liability to cause psychic or physical
dependence.
 Consists of certain opioid drugs and drug containing amphetamines or metaamphetamines as
the single active ingredient or in combination with each other.
 Categorized as “Class A Narcotic Drugs.”
E.g. Opium Morphine
Codeine Hydromorphone
Amobarbital Methadone
Meperidine Cocaine
Oxycodone Pentobarbital
Diphenoxylate Phemetrazine
Methylphenidate Secobarbital
Methamphetamine Dextroamphetamine
Etorphine hydrochloride
SCHEDULE III SUBSTANCES

 Drugs with a potential for abuse that is less than those in schedules I and II substances.
63
 Their abuse may lead to moderate or low physical dependence or high psychological
dependence.
 Drugs included was formerly known as “Class B Narcotic drugs” plus a number of non-
narcotic agents.
E.q. Chlorhexadol Gluthethimide
Methylprylon Sulfodiethylmethane
Sulfonmethane Nalorphine
Benzphetamine Chlorphentermine
Phendimetrazine
Certain barbiturates except those listed in another schedule.
SCHEDULE IV SUBSTANCES
 Drugs with low potential for abuse that leads only to limited physical or psychological
dependence relative to drugs in Schedule III.
E.q. Barbital Phenobarbital
Ethinamate Paraldehyde
Phentermine Methohexital
Fenfluramine Methylphenobarbital
Chloral betaine Chloral hydrate
Meprobamate Propoxyphene
Benzodiazepines Mebutamate
Ethchlorvynol
SCHEDULE V SUBSTANCES
 Drugs have a lower potential for abuse than those in Schedule IV for which there is currently
accepted medical use in the U.S.
 Drugs are categorized as “Exempt Narcotics.”
HEMOSTATICS
Locally applied substances that are employed to arrest excessive bleeding or hemorrhage.
Sympathomimetics
- reduce bleeding by local vasoconstriction. E.q. Epinephrine
Styptics and Astringents

- precipitates the tissue proteins in the immediate area.
E.q. Zinc Chloride, Aluminum Chloride, Ferric Sulfate
Mechanical Agents
- acts as matrices in which blood cells / fibrin can be entrapped.
E.q. Gel foam, Oxidized Cellulose, Oxidized Regenerated Cellulose.
Thrombin
- normal constituent of the blood coagulation scheme, combines with fibrinogen.
HEMOSTASIS AND HEMOSTATIC AGENTS

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Factors in the Arrest of Hemorrhage

1. Vessel wall contraction
- of short duration (5-20 minutes)
- can be prolonged by topical or local infiltration of Adrenaline.
2. Adhesion and Aggregation of Platelets
- Platelets are non-nuclear cells with a cytoplasm rich in granules.
- normal count: 150,000 – 4000,000 cells/ml.
- half life is 7 to 10 days
- releases Adenosine Diphosphate (ADP) and Thromboxane A2
- forms Platelet PLUG
3. Ability of blood to coagulate

Stage I - Activation of Factor X --- Xa
Stage II – Prothrombin (II) --- Thrombin
Stage III - Fibrinogen (I) --- Fibrin --- Clot
Stage IV - Fibrin Clot - Lysed fibrin and fibrin peptides.
4. Fibrinolysis (The breakdown of blood clot)

- can be influenced by age, sex, diet, smoking, altitude, exercise.
VITAMIN K - fat soluble vitamin that is essential for the normal hepatic biosynthesis of
several factors required for blood clotting. (II, VII, IX, X)
ANTICOAGULANTS
- they directly or indirectly interfere with the normal clotting mechanism of blood.
- patients receiving are those with a history of myocardial infarction, cerebrovascular
thrombosis, venous thrombosis, and pulmonary embolism.
A. Heparin
- enhances the activity of antithrombin III (neutralizes several of the activated clotting
factors Ixa, Xa, Xia, and XIIa. It also inactivates prothrombin by forming an
irreversible complex with it).
- must be administered parenterally.
- half life is between 1 to 5 hours (the higher the dose, the higher the half life)
- Unwanted effects: Heamorrhage and Thrombocytopenia.
- the effect can be reversed by the specific antagonist (Protamine Sulphate) at eh dose
regimen of 1 mg. of protamine for every 100 units of heparin.
B. Coumarin Anticoagulants
- Oral anticoagulants
- includes Warfarin Sodium and Phenindione.
- antagonist to vitamin k
- reduces synthesis of vitamin K dependent clotting factors (II, VII, IX, X).
- affected by diet, bowel disease, pyrexia, age, pregnancy, liver disease.
ANTIPLATELET DRUGS
- Antithrombotic
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- decrease thrombin formation

E.q. Aspirin, Diprydamole, Sulphin Pyrazone.
FIBRINOLYTIC DRUGS
- promotes the breakdown of thrombi by activation of plasminogen to form plasmin.
E.q. Streptokinase, Urokinase, Tissue Plasminogen Activator.
ANTIFIBRINOLYTIC DRUGS
- these encourage the stabilization of fibrin by inhibiting plasminogen activator.
E.q. Tranexamic acid
- effects: Nausea, diarrhea, hypotension.
DENTAL MANAGEMENT OF PATIENTS WITH HEMOSTATIC PROBLEMS

1. Impaired Platelet Function
- due to reduction in platelet count or impaired aggregation due to drug therapy.
- Treatment: Low platelet count – Platelet transfusion before surgery.
Thrombocytopenia due to immune destruction of platelet – Administration
of corticosteroid
- it is a wise precaution to suture and pack the socket to minimize the risk of post
extraction hemorrhage.
- drugs that impair platelet aggregation and increase bleeding time includes Aspirin,
NSAID’s, Sodium Valproate, and Phenytoin.
2. Vascular Defects
- associated with vitamin C deficiency and long term corticosteroid therapy.
- patients have increased capillary fragility which can cause bleeding problems after
surgery.
- can be controlled by pressure, suturing, and packing.
3. Impaired Coagulation
A. Haemophilia
- sex-linked; affects only males.
- patients have reduced factor VIII activity.
- can be corrected by replacement therapy of freeze-dried factor VIII
(cryoprecipitate).
- drugs used in conjunction with factor VIII include anti-fibrinolytic agents, epsilon
aminocaproic acid which should be started pre-operatively.
B. Christmas Disease
- associated with a deficiency of factor IX (derived from plasma but not present in
cryoprecipitate).
- Replacement therapy.
C. Von Willebrand’s disease

- inherited disorder associated with both prolonged bleeding time and deficiency of
factor VIII.
- replacement therapy is necessary.
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LOCAL ANESTHETICS
- reversible Blockade of Peripheral Nerve Conduction; drugs that have little or no irritating
effects when injected into the tissues and that will temporarily interrupt conduction when
absorbed into the nerve.
Autonomic Losses in the usual order

1. Sense of Cold
2. Warmth
3. Pain
4. Touch
5. Pressure
6. Vibration
7. Proprioception
8. Motor function
Components of Local Anesthetics

A. Anesthetic Drug
B. Vasoconstrictor
e.g. epinephrine, levonordefrin
Role of Vasoconstrictor in Local Anesthetics

Prolong Local Block
Delay Systemic Absorption
Limit Toxicity
C. Antioxidant
e.g. Sodium Bisulfite or Sodium Pyrosulfite
D. Antiseptics
m methylparaben
n
Ideal Properties of Local Anesthetics
1. Potent Local Anesthesia
2. Reversible Local Anesthesia
3. Absence of Local Reactions
4. Absence of Systemic Reactions
5. Absence of Allergic Reactions
6. Rapid Onset
7. Satisfactory Duration
8. Adequate Tissue Penetration
9. Low Cost
10. Stability in Solution (long shelf life)
11. Sterilization by Autoclave
12. Ease of Metabolism and Excretion
Two Groups: ESTER group and AMIDE group

67
CHEMISTRY OF LOCAL ANESTHETICS
Aromatic Nucleus Linkage Amino Group
ESTER
O R3
R1 ------ -- C – O – R2 -- ------ N
R4
____________________ o r ____________________________
AMIDE
H O R3
R1 ------ -- N – C – R2 -- ------ N
R4
Absorption: Increase vasodilation = Increase speed of circulation

Distribution: Brain, liver, kidneys, lungs, spleen.
Metabolism: Ester – hydrolyzed in plasma by plasma cholinesterase.
Amide – Liver
Prilocaine – Lungs
Excretion: Kidney
Pharmacologic Effects
1. Reversible peripheral nerve conduction
2. Smooth muscle effects – relaxation of smooth muscle because sensory receptors are
depressed.
3. Analgesic effect
4. Anticonvulsant effects.
Most Local Anesthetics are Synthetic except Cocaine

1. An Aromatic, Lipophilic Group
2. An Intermediate Chain (Ester or Amide Linkage)
3. A Hydrophilic 2º or 3º amino group, which forms water soluble salts when
combined with acids.
Generally almost without exception, Drugs thus formed are:

White and Odorless
Viscid Liquids or Amorphous Solids
Fat Soluble but relatively Insoluble in water
All are Bases and form Water Soluble Salts with Acids
Toxicity of Local Anesthetics: Descending stimulation of the C.N.S. followed by

68
DEPRESSION of certain areas of the brain
Classic Progression:
1. Restlessness, Apprehension and Tremors progressing to Excitement and Convulsions
2. Increase Blood Pressure and Pulse Rate
3. Increase Respiratory Rate
o 4. Respiratory and cardiovascular depression with Loss of reflexes and consciousness.
Characteristics of Lidocaine Toxicity:

DEPRESSION, generally the cause of Death, may appear without initial stimulation.
GENERAL ANESTHESIA
- the drug induced absence of the perception of all sensation allowing surgery or other painful
procedures to be carried out.
- depresses the CNS; alleviate pain and cause a loss of consciousness.
HISTORY
Nitrous Oxide “laughing Gas” described by john Priest
Horace Wells observed its effects as anesthetics.
Ether – by T.G. Morton and C.T. Jackson
Highly flammable, volatile, pungent odor.
Chloroform - volatile liquid; by J.Y. Simpson
THEORIES ON MECHANISM OF ACTION OF G.A.

1. Lipid or Meyer Overton Theory
2. Inhibition of biochemical Action
3. Molecular theories
Pharmacologic Effects
1. CNS depressants
2. CVS depression
3. Urine output is reduced
4. May produce liver damage.
5. Release of ACTH, antidiuretic hormone, sympathetic neurotransmitters.
STAGES OF ANESTHESIA (Guedel’s Classification)

Stage I : ANALGESIA
- from administration of anesthesia – loss of consciousness
Analgesia
Euphoria
Perceptual distortions
Amnesia
Stage II : DELIRIUM
- loss of consciousness – beginning of surgical anesthesia
Excitement
Involuntary muscular activity (Increase muscle tone)
Irregular breathing
69
Hypertension
Tachycardia
Stage III : SURGICAL ANESTHESIA

- state of analgesia associated with majority of surgical procedures
- spontaneous respiration ceases
* 4 Planes based on:

Respiration
Size of pupils
Reflex characteristics
Eyeball movement
Stage IV : MEDULLARY DEPRESSION / RESPIRATORY PARALYSIS

- begins with cessation of respiration – circulatory collapse
- Pupils fixed and dilated
- No lid or corneal reflexes
 If not reverse immediately, Death occurs.
PHASES OF ANESTHESIA
(Flagg)
INDUCTION
- encompasses all the preparation and medication necessary for a patient up to the time the
surgeon is ready to begin.
MAINTENANCE
- begins with the patient at a depth of anesthesia sufficient to allow surgical manipulation
and continues until completion of procedure.
RECOVERY
- begins with the termination of the surgical procedure and continues through the post
operative period until the patient is fully responsive to the environment.
CLASSIFICATION OF G.A. BY ROUTE OF ADMINISTRATION
Inhalation Intravenous Agents
Gases Volatile liquids
Nitrous Oxide Halogenated Hydrocarbon Neuroleptics

Chloroform Fentanyl with Droperidol
Ethyl Chloride (Innovar)
Cyclopropane Trichloroethylene
70
(Trilene, Trimar) Dissociative

Ethylene Halothane (Fluothane) Ketamine
(Ketalar, Ketaject)
Halogenated Ether Barbiturates
Methoxyflurane Methohexital
(Penthrane) (Brevital)
Enflurane Thiamylal Sodium
(Enthrane) (Surital)
Isoflurane Thiopental Sodium
(Forane) (Pentothal)
Ether Narcotics
Diethyl Ether Fentanyl (Sublimaze)
(Ether) Morphine
Vinyl Ether
(Vinethene)
“BALANCED ANESTHESIA”
- PRE-ANESTHETIC MEDICATION-
- INDUCTION-
- NEUROMUSCULAR BLOCKING -AGENT
- ANESTHETICS-
G OAL:
ANALGESIA
SLEEP
MUSCLE RELAXATION
ABOLITION OF REFLEXES
PREMEDICATION
Features Required of PREMEDICATION Agents
1. Alleviate pre-operative anxiety.
2. Provide some degree of post-operative amnesia esp. in children.
3. Make the induction and maintenance anaesthesia easier.
4. Reduce the amount of anaesthetic agents required by enhancing their effects
5. Provide additional analgesia.
6. Reduce salivary and bronchial secretions.
7. Reduce activity in the parasympathetic nervous system.
PREMEDICATION AGENTS
OPIOIDS - e.q. Morphine, Pethidine, Papaverum
Therapeutic Effects: Analgesic, Sedative, Euphoriant, Respiratory depression,
Suppression of cough reflex
71
Unwanted Effects: Nausea, Vomiting
ANXIOLYTICS - e.q. Benzodiazepines

- used orally to provide post-operative sedation.
ANTIPSYCHOTICS (Neuroleptics) e.q. Penothiazines derivatives – promethazine and

Trimeprazine.
- pre-anaesthetic sedatives; anti-emetic; for patients who fear or has predisposition to
post-operative vomiting; depresses respiration: cause varying amount of hypotension.
ANTICHOLINERGIC Atropine Sulphate; Hyoscine; Glycopyrrolate

- reduce secretions; prevent overactivity of the parasympathetic nervous system.
Atropine Sulphate - commonly used to reduce salivary and bronchial secretions

during anesthesia by antagonizing the actions of acetylcholine at muscarinic
receptors.
Hyoscine - antagonizes the effect of endogenous acetylcholine at muscarinic receptors;

given IM 30-60 minutes before induction anesthesia; a CNS depressant – causes
drowsiness and depression of the vomiting center -anti-emetic. Athigh doses, it may
act as stimulant of the CNS. Both atropine and hyoscine block the action of
acetylcholine released from the vagal nerve endings which gives some protection
against vagal stimulation.
Glycopyrrolate - a quarternary ammonium; produces prolonged and good control of

salivary and pharyngeal secretions; less effect on the cardiovascular system; used as
preoperative or intraoperative antimuscarinic to attenuate or prevent the
intra-operative bradycardia sometimes associated with the use of suxamethonium or
due to cardiac vagal reflexes..
NEUROMUSCULAR BLOCKING AGENTS

- by specific blockage of the neuromuscular junction, they enable light levels of anesthesia
to be used with adequate relaxation of the muscles of the abdomen and diaphragm;
produce relaxation of the abdominal muscles, and paralysis of the respiratory muscles;
relaxes the vocal cords allowing the passage of a tracheal tube.
Two Types of Neuromuscular Blocking Agents

I. NON DEPOLARIZING MUSCLE RELAXANTS(competitive)
Tubocurarine - highly ionized; given IV ; produce paralysis of all voluntary muscles;

action commences 3-4 mins. and lasts up to 40 mins.; used as an adjunct to G.A.;
action may be reversed by administration of neostigmine ; a weak ganglion blocker
– causes the release of histamine -- peripheral vasodilation - - will lower the b.p. ;
may also cause flushing and bronchospasm due to the release of histamine;
does not cross the blood brain barrier or the placenta.
Pancuronium - more potent than Tubocurarine but has a shorter action; acts by
competitive block but does not normally block transmission in autonomic ganglia
72
and so does not significantly alter the blood pressure. However, if rapidly injected
IV, it may cause a rise in bp due to vagal blocking and tachycardia; does not cause
histamine to be released; may also be used to produce relaxation in a number of
pathological conditions such as tetanus; also used extensively in ICU.
Atracurium and Vecoronium - most often used at the present time; have little effect
on the cardiovascular system; may release little of histamine; more advantageous
to patient’s with renal or hepatic impairment.
II. DEPOLARIZING MUSCLE RELAXANTS

Suxamethonium - depolarizes the postsynaptic membreane and maintains this state so
that the adjacent m. fibers are electrically inexcitable; injected IV; produces
complete muscular relaxation in half a minute; has a number of muscarinic action
including increase in salivary secretion, muscle injury occasionally due to direct
action on the muscle or may follow K depletion from muscles.; may cause
malignant hyperpyrexia – maybe treated by rapid cooling, inhalation of 100%
oxygen and IV of Dantrolene 1 mg/kg of body weight.
* MUSCLE CONTRACTION
action potential ---- travels down the motor nerve---- release of packets of acth (quanta-
millions of acth molecules) ----- acth crosses the synaptic cleft and interacts with the
cholinergic receptors on the end plate of a muscle fiber ---- surge of acth brings a massive
increase in the permeability of the post-synaptic membrane to Na ions and to a < extent to
K ions (Na ions enter and generate a local end plate potential (depolarization) until it
reaches a critical threshold --- triggers off a muscle action potential propagated along the
muscle fiber causing it to contract.
Acth is then broken down by cholinesterase in the neuromuscular junction; the motor end
plate polarizes and is then ready to be stimulated again.
INDUCTION AGENTS (IV ANESTHETIC AGENTS)

- widely used to induce anaesthesia
Sodium Thiopentone - an ultra short acting barbiturate; given IV; produces loss of
consciousness in 10-20 seconds. Max. depth occurs 40 secs. ; px becomes conscious 2-3
mins. after dosage; provide anes. for short operative procedures; induce unconsciousness
prior to inhalation anaesthesia; rapidly enters the brain; 85% bound to plasma protein;
metabolized in the liver; excreted in the kidney; depresses many of the functions of CNS;
no analgesic properties; low doses may increase sensitivity to pain; an anticonvulsant;
often associated with laryngospasm; bronshospasm; cough; extravascular injection may
cause pain and necrosis when the concentration is > 2.5%; endothelial and deeper layer
may be damaged when inadvertently injected into an artery; must not be given to patients
with porphyria no effect on the uterus but can cross the placenta and depress the fetal
cardiovascular system; there is transient drop in blood pressure.
Methohexitone - an ultra short acting barbiturate;

Pharmacological properties – same with Thiopentone
Unwanted effects - pain on injection, involuntary movements, cough, and laryngospasm;
has convulsant properties
73
Etomidate - a carboxylated imidazole derivative; rapid recovery and lack of “hangover’

effect may be due to short plasma half life; does not release histamine; painful, cause
involuntary movements; prolonged use may cause adrenocortical suppression in ICU;
has little or no effect on the cardiovascular system.
Ketamine - given IV but can be given IM; associated with profound sedation and
analgesia; produces dissociation but not sedation and so airway reflexes are maintained;
vivid hallucinations and nightmares; raises b.p. and pulse rate; useful in management of
mass casualties.
Propofol - a new phenolic IV induction agent and maintenance anaesthesia provided the
surgical procedure does not exceed 1 hour.; recovery is usu. rapid and often accompanied
by euphoria; sexual fantasies can also occur; highly lipophilic; More expensive.
Unwanted effects - cardiac respiratory depression; apnea and marked hypotensive effect;
pain on injection.
INHALATION ANAESTHESIA
- most widely used form of maintenance anaesthesia
INHALATION ANAESTHETIC AGENTS

Nitrous Oxide - E.q. Entonox colorless, odorless gas; weak anaesthetic; an adjunct to
other inhalation agents; may produce severe hypoxia when used alone; an excellent
analgesic agent; a direct myocardial depressant; stimulates sympathetic nervous
system; may cause nausea, vomiting, (megaloblastic anemia and neuropathy in
animals); suppresses spermatogenesis and production of WBC and RBC in bone
marrow; Uses: changing painful dressing, an aid to post-operative physiotherapy and
emergency ambulances.
Halothane - a halogenated hydrocarbon; colorless at room temperature; has pleasant
smell;not inflammable; non explosive; causes dose-related reduction in b.p.,slowing of
heart rate; severe dysrhythmia; bronchodilation ; depresses respiration; no analgesic
property and does not produce a degree of relaxation; may cause hepatic necrosis.
Enflurane - a halogenated ether; colorless at room temperature; non flammable with a
mild sweet odor; alters electrical activity in the brain; 80% excreted unchanged in
expired gases, 2.5 % metabolized in the liver and excreted in the kidney; produces a
dose-related reduction in b.p.; causes respiratory depression; twitching of the limbs,
jaws, face and neck but self limiting; no significant effect on the liver
Isoflurane - isomer of enflurane; a halogenated methylethyl ether; physical properties
similar to enflurane; reduction in b.p. but has little or no effect on cardiac output;
increase in heart rate but no arrythmias; depresses respiration and stimulates airway
reflexes causing increased secretion, coughing and laryngospasm.
Ether - one of the earliest and safest volatile liquids irritating to the mucus membrane;
inflammable and explosive; often associated with nausea and vomiting; now rarely
used.
ANAESTHETIC EMERGENCIES
1. Respiratory Obstruction
2. Hypersensitivity reaction
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ANTISEPTICS AND DISINFECTANTS

- substance that kill or prevent the growth of microorganism
Antiseptics - used on living tissues.
Disinfectants – applied on inanimate objects.
1. ALCOHOLS
A. Ethyl Alcohol and Isopropyl Alcohol
B. Chlorhexidine and Iodine
C. Surgical Spirits – mixture of ethyl/methyl alcohol
2. ALDEHYDES
A. Formaldehyde – bactericidal activity on bacteria, fungi, and viruses; action is very slow
– 0.5% will take 12 hrs.; 2-8% concentrations to disinfect inanimate objects.
B. Glutaraldehydes – acts against all microorganisms; less viruses, odor; 2% concentration;
for cold sterilization; for articles contaminated by hepatitis B virus that cannot be heat
sterilized; 1 – 12 hour exposure.
C. Chlorhexidine (Hibitane) – antiseptic and disinfectant
p 1. Hibiscrub ICI – pre-operative preparation of skin and hand disinfection.
q 2. Hibisol ICI – disinfection of sin and hands.
r 3. Corsodyl ICI – in dental gel; mouthwash 0.2% solution.
s
t Hibitane Obstetric cream (ICI) – pre-operative preparation of hands and skin of
u midwife/doctor.
v Hibitane Concentrate – general purpose antiseptic
w
3. DYES – complex organic substances from coal tar e.q. aniline dyes, gentian violet, brilliant
green, acnidine dyes, acriflavin and proflavine.
4. HALOGENS – reacts with bacterial proteins.
5. CHLORINE – has a rapid, potent and brief action; effective against most bacteria, some
fungi, yeast, and viruses; in the form of hypochlorites, organic chloramines, chlorinated
isocyanurates; inactivated by organic matter.
6. IODINE – acts as much the same way as chlorine but not readily inactivated by organic
matter; bactericidal and fungicide; present in weak solution of 2.5% iodine in potassium
iodine, water and alcohol; stains skin.
7. IODOFORM – mild antiseptic E.q. whiteheads varnish incorporated into ribbon gauze for
infected sockets and dressing for surgical removal; contains iodoform with benzoin,
storax, and balsam of tolu in solvent ether; Kri-paste- used as root canal filler; Kri
liquid - sterilize root canals.
8. IODOPHORS – combination of iodine and surface active detergents; effective against

gram + - organisms after 15 secs.; doesn’t stains skin. E.q. Povidone Iodine
75
9. OXIDIZING AGENTS – liberates oxygen which oxidizes proteins of bacteria and tissue
proteins.
Hydrogen Peroxide – mild antiseptic; 30% aqueous solution to bleach discolored root
filled teeth; mouthwash in acute ulcerative gingivitis.
Sodium Perborate – treatment of acute ulcerative gingivitis; liberates oxygen when in

contact with organic matter.
10. PHENOLS, CREOSOLS and their derivatives
Phenol - 80% in water; irritant and caustic producing a burning pain; produces feeling of
anesthesia
CMCP (Camphorated para-aminophenol) – 35% in camphor; medicament in root canals.
Cresol – 3x bacteridal potency of phenol; also toxic E.q. Metacrsyl acetate (Cresatin) –
irrigation of root canals; not irritant to periapical tissues.
Chloroxylenols – less effective than phenolic agents; activity reduced in the presence of
organic matter. E.q. Dettol (5% chloroxylenol).
Hexachloropane – excellent disinfectant; for gram + cocci; not very irritant to tissues but
has neurotoxic effects on babies (dusting powders).
11. SURFACE ACTIVE AGENTS

Classification according to ionic charge:
CATIONIC - positive charge; includes quarternary ammonium compounds such as:
1. Benzalkonium chloride (Zepiran)
2. Cetylpyridinium (Ceepryn)
3. Cetrimide (Cetavlon)
- bactericidal against some gram + and some gram negative bacteria; little effect on tubercle
bacilli, spore forming microbes and psuedomonas aeruginosa;
ANIONIC - negative charge; not bactericidal, only enhances physical removal of bacteria;
effective against gram + microorganism; E.q. Sodium lauryl sulfate and green soap.
DENTAL USES OF ANTISEPTICS

1. Skin preparation before surgery or injection
2. Pre-operative preparation of the oral mucosa
3. Sometimes as an ingredient of dentrifices
4. Inhibition of dental plaque
5. Cleaning of operating areas
6. Cold sterilization of instruments and equipment
7. Storage of sterilized surgical equipment
8. Preparation of surgeon’s hand
9. Irrigation of root canals in endodontics.
DEFINITION OF TERMS
76
Antimicrobial Agents – substances that kill or suppress the growth or multiplication or prevent
the action of microorganisms
Anti-infective Agents – substances that act against or tend to destroy infection.
Antibacterial Agents – substances that destroy or suppress the growth or multiplication of
bacteria.
Antiviral Agents – substances that destroy or suppress the growth or multiplication of viruses.
Anti-fungal Agents – substances that destroy or suppress the growth or multiplication of fungi.
Antibiotic Agents – chemical substances produced by microorganisms that have the capacity, in
dilute solutions, to destroy or suppress the growth or multiplication of
organisms or prevent their action.
Antibacterial (Antimicrobials) – are obtained from natural sources or are manufactured

Antibiotic – chemicals that are produced by one kind of microorganism that inhibit or kill another
kind of organism.
* The difference between antibiotic and synthetic antibacterial agents is that antibiotics are
produced by microorganisms and the antibacterial agents are made in the laboratory.
Classification of Antibacterials According to its ACTION
1. Bacteriostatic
– inhibit or retard the multiplication or growth of bacteria but does not kill them.
E.q. Tetracyclines, sulfonamides, chloramphenicol
- bacteria can grow again when drug is withdrawn.
- Host defense mechanism (e.q. phagocytosis) are required to kill the microorganism.
2. Bactericidal – drugs that kill bacteria.
E.q. Penicillin, Cephalosphorins, Aminoglycosides, Vancomycin, Metronidazole,
Imipenem.
- best choice in treatment especially in life threatening infections, endocarditis and in
patients whose leukocyte count is <500μ/L
* some drugs may be bacteriostatic at low concentrations and bactericidal at high

concentrations against the same or different microorganisms; In patients with impaired
defense mechanism, a bactericidal is preferred over a bacteriostatic agent because the body’s
ability to fight infection is compromised.
Classification According to RANGE OF ACTIVITY

Spectrum – the range of activity of a drug.
1. Narrow Spectrum – acts against either gram positive or gram negative organisms.
one type of organism; only selective. E.q. Penicillin and
erythromycin – gram + bacteria.
2. Broad Spectrum – acts against a wide variety of organisms – effective on both gram +
and gram – bacteria as well as some viruses; treats infection not
identified by culture and sensitivity test.
E.q. Tetracylcine and Cephalosphorins.
77
INFECTION – invasion of the body by pathogenic microorganism and the reaction of the
tissues to their presence and to the toxins generated by them.
Principal factors that determine a microorganism causing an infection

1. Virulence of the microorganism
2. Number of organisms present
3. Resistance of the host
How do Microorganism cause an infection?

1. Infectivity (must enter the right portal of entry)
2. It must be able to multiply on the body of the susceptible host.
3. Invasiveness (effective mechanism for transmission)
4. It must be able to produce toxins, enzymes and other metabolites that affect the cell
or toxigenecity.
Two Goals to be achieved to prevent infection

1. Reduce the number of bacteria in the surgical wound.
2. Enhance the host’s defenses so as to prevent the bacteria that entered the wound from
causing clinically evident infection.
INDICATION FOR ANTIMICROBIAL AGENTS
A. Prophylactic Indications
- used for high risk patients whose immune system are weak. E.q. in rheumatic or
congenital heart disease, Renal dialysis patients, or the presence
of a heart prosthesis. Any dental procedure may precipitate a bacteremia, therefore,
prophylactic antibiotics must be given to prevent bacterial endocarditis.
B. Therapeutic Indication
- for the treatment of infection.
“Does this particular patient need the assistance of antimicrobial agents to resolve
this particular infection?"
* NOT ALL INFECTIONS REQUIRE ANTIBIOTIC THERAPY, it all depends on:

1. The patient. “host responses”
- Defense mechanism is considered.
- The presence or absence of systemic manifestation such as fever, malaise, and
lymphadenopathy are indicators of how well the patient is doing without
antimicrobial therapy.
2. The Infection.
- The virulence and invasiveness of the etiologic microorganism are important in
determining the acuteness, severity, and spreading tendency of the infection
which is obviously need to be treated with antimicrobial agents.
Five Basic Principles in the Use of Antibiotics / Antimicrobials

1. Infection must be present or imminent - consider the signs of inflammation.
2. Identify the organism - accomplished through culturing, gram stain or educated guesses.
Purpose: To determine the specific type of antimicrobial sensitive to the specific type of
microorganism.
3. Choose the specific type of antibiotic
---------------------------------------------------------------------------------------------------------
78
Antibiotics G- & G+ G-
--------------------------------------------------------------------------------------------------------
Phenoxymethyl Penicillin ++++ +
Penicillin G ++++ +
Ampicillin +++
Erythromycin +++ ++
Clindamycin +++ +
Cephalosporins +++ +
Tetracycline ++ +++
Aminohlycoside + ++++
----------------------------------------------------------------------------------------------------------
4. Administer antibiotics properly

5. Prevent and minimize toxicity and hypersensitivity.
a. right dose
b. right dose interval
c. right dose form
d. right duration of therapy
Duration of dosage:
- An antimicrobial agent should be continued long enough to prohibit a regrowth of the
causative microorganism, but not so long to induce toxic drug symptoms or alter the
normal flora to the extent that superinfection results
** It should continue 48 hours after the symptoms of infection are absent. If beta
hemolytic streptococci are the causative organisms, usually penicillin should be
continued for at least 10 days. For osteomyelitis, it should be continued for 14 days after
fever and tenderness are absent and drainage has ceased. In patients with a depressed
immune system or history of prolonged healing, coverage usually needs to be continued
longer than in normal patient.
MECHANISM OF ACTION OF ANTIBACTERIALS

1. Inhibition of cell wall synthesis
a. Inhibition of cross linking (transpeptidation) of peptidoglycan. e.q. Penicillins;
Cephalosporins.
b. Inhibition of other steps in peptidoglycan synthesis. e.q. Vancomycin,
Cycloserin, Bacitracin.
2. Inhibition of protein synthesis
x a. Action on 50S ribosomal subunit e.g. Chloramphenicol, Erythromycin,
y Clindamycin.
z b. Action on 30S ribosomal subunit. e.q. Tetracyclines and Aminoglycosides.
3. Inhibition of nucleic acid synthesis
aa a. Inhibition of nucleotide synthesis e.q. Sulfonamides and trimethoprim
bb b. Inhibition of DNA synthesis e.q. Quinolones (Ofloxacin)
cc 4. Alteration of cell membrane function
a. Antibacterial activity e.q. Polymyxin
b. Antifungal activity e.q. Amphotericin B, Nystatin, ketoconazole.
5. Uncertain mechanisms
E.g. Isoniazid, Metronidazole.
79
Resistance – ability of a microorganism to be unaffected by an antimicrobial agent.

Natural resistance – occurs when an organism has always been resistant to the antimicrobial
Agent; occurs without previous exposure to the drug.
Acquired resistance – occurs when the organism that was previously sensitive to an
antimicrobial agent develops resistance/ caused by prior exposure to
the drug.
Cross Resistance - occurs with antibacterials that have similar actions. E.q. Penicillin;
Cephalosporins.
Genetic recombination including conjugation, transformation , and transduction, can result

in the passing on of resistance from one bacterial strain to another. The second strain
becomes resistant to the same antibiotics as the first strain without having been exposed to
the antibiotic.
**Action depends on depends on several variables:

1. Usual therapeutic concentration of that agent
2. Type of organism
3. The mechanism of action of that agent.
GENERAL ADVERSE REACTIONS TO ANTIBACTERIALS
1. Allergy / Hypersensitivity - may be mild to severe. E.q rash, pruritus, hives-treated
with antihistamine.
2. Anaphylactic Shock - shortness of breath is the first symptom; treatment is
epinephrine bronchodilators and antihistamines.
3. Superinfection, Suprainfection - infection caused by proliferation of microorganisms
that are different than those causing the original infection.
- a secondary infection that occurs when the normal microbial flora of the body are
disturbed during antibiotic therapy. E.q. Fungal infections.
- often caused by broad spectrum antibiotics such as tetracycline
CULTURE AND SENSITIVITY TESTS

- only way in which one can reasonably ensure that a particular drug will kill or inhibit the
growth of an infecting microorganism. However, it will not show the potency of the drug
nor differentiate between bactericidal and bacteriostatic effects, they will only show
which drug adversely affect the growth of the microorganism on the culture plate.
Culture – a sample from the infected site is taken and grown on culture media. After the
pathogen is grown, sensitivity test can be conducted.
Sensitivity – after the organism is identified, it is again grown on culture media and the
effect of different antimicrobial agents on the organism is tested. One to two
days are required before the result of this test are available
Advantages of Culture and Sensitivity tests

1. An early correction of therapy is possible if the drug selected is ineffective against the
microorganism causing the infection
2. Pathogens grown on culture before antibiotic therapy is begun can be more easily
identified than after a therapeutic failure has occurred.
80
Blood level – the concentration of the antibacterial agent present in the blood or serum; an
important index to drug dosage, since certain concentration of the drug is required
in the body fluids to inhibit or kill the microorganism.
Synergism – effect when a combination of two antibiotics is more rapidly bactericidal than either
drug used alone. Combinations of antibiotic that are bactericidal generally are
synergistic. Combinations of those that are bacteriostatic are merely additive.
Antagonism – effect when the bactericidal rate for the combination of two drugs is less than that
for either drug used alone; often exhibited when a bateriostatic and a bactericidal
agent are used in combination.
DENTALLY USEFUL ANTI-INFECTIVE AGENTS

1. PENICILLINS
- can be divided into three groups
A. Penicillin G and V
B. Penicillinase-resistant penicillins
(Methacillin, Cloxacillin, Nafcillin, Floxacillin, Dicloxacillin)
C. Extended-Spectrum penicillins
(Ampicillin-like agents, carbenicillin-like agents and amino-penicillin group.
Administration and Body handling

- can be administered orally or parenterally.
- should not be applied topically because of its allergenecity.
- Penicillin V is better absorbed orally than penicillin G
- degraded by the gastric fluid-it should be administered one hour before meals or 2
hours after meals.
- crosses placental barrier and a small amount appears to be excreted in the milk and
saliva.
Spectrum:
- very potent bactericidal agent that acts by interfering with the synthesis of the
bacterial cell wall.
- its narrow spectrum of activity includes gram positive aerobic and facultative
organism(cocci: Streptococcus,and Staphylococcus; rods: Bacillus,
Corynebacterium and Clostridium; Spirochetes:Treponema pallidium; and certain
gram negative aerobic cocci: Neisseria gonorrhea and N. meningitidis)
Adverse reactions :
- most common cause of drug allergies.
1. Toxicity
- large doses of penicillin G have been associated with renal damage manifested as
fever, eosinophilia, rashes, albuminuria.
- gastrointestinal irritation can manifest itself as nausea with or without vomiting.
2. Allergy and Hypersensitivity
Immediate - less than 30 minutes includes anaphylaxis.
Accelerated - 2 to 48 hours includes serum sickness and laryngeal edema.
81
Late - 3 or more days includes rashes, oral lesions, and other symptoms.
Uses:
- for dental infections
a. ANUG – penicillin V
b. Periodontal abscess - penicillin V
c. Abscess, cellulitis, pericoronitis – penicillin V
d. Osteomyelitis - penicillin V
e. Rheumatic heart disease - penicillin V.
2. ERYTHROMYCIN
- administered orally; available in tablets and capsules, oral suspensions and IV and IM
forms.
- formulated as enteric-coated tablet, capsule or insoluble ester to reduce degradation by
the stomach acid.
- it should be administered 2 hours before meals or several hours after meals.
Activity and Spectrum:

- usually bacteriostatic but may be bactericidal at normal therapeutic doses.
- used against gram positive bacteria.
- also a drug of choice for whooping cough, diphteria, syphilis, and gonorrhea.
- cross-resistance has been reported between erythromycin and clindamycin.
- poor second choice to treat dental infections.
Adverse Effect:
1. Gastrointestinal Effects
- include stomatitis, abdominal cramps, nausea, vomiting and diarrhea.
2. Cholestatic Jaundice
- symptoms include nausea, vomiting and abdominal cramps followed by jaundice
and elevated liver enzyme levels.
3. Allergy
- very uncommon.
Drug Interaction:
- patients taking Theophylline chronically for asthma or acutely for bronchitis may
exhibit a drug interaction with erythromycin.
- has been implicated in the failure of oral contraceptive efficacy.
Uses:
- drug of first choice in patients allergic to penicillin.
- indicated certain situations for the prophylaxis of rheumatic heart disease.
- usual adult dose is between 250 and 500 mg qid.
- for bacterial prophylaxis- 1 gm 1 hour before the dental appointment
3. TETRACYCLINE
- broad spectrum antibiotics affecting a wide range of microorganisms.
- most commonly given by mouth.
- secreted in the saliva and milk of lactating mothers.
82
- stored in the dentin and enamel of unerupted teeth.

- also concentrated in the gingival crevicular fluid.
Types:
1. Doxycycline - excreted in the feces
2. Tetracycline – eliminated by glomerular filtration,
- oral absorption is decreased by administration of food with high calcium content,
dairy products, oral iron supplements or antacids.
3. Minocycline - metabolized in the liver and excreted in urine.
dd - may be given to patients with renal dysfunction
Spectrum:
Bacteriostatic and interfere with the synthesis of bacterial protein
Broad spectrum
Adverse Reactions:
1. Gastrointestinal effects
- anorexia, nausea, vomiting, diarrhea, gastroenteritis, glossitis, stomatitis,
xerostomia, and superinfection (moniliasis)
2. Hepatoxicity - large dose of parenteral tetracycline
3. Renal toxicity
4. Hematologic effects - hemolytic anemia, leukocytosis, thrombocytopenic purpura
5. Effects on teeth and bones
6. Superinfection
7. Photosensitivity– exaggerated sunburn
8. Allergy
Uses:
1. Alternative drug to treat chlamydial and rickettsial infections
2. Used to treat cholera, acne, and pulmonary infections
3. Doxycycline is used to treat travelers diarrhea
4. Indicated for the treatment of periodontitis
5. Mixture of equal parts of tetracycline syrup and lidocaine viscous for the
management of recurrent aphthous stomatitis
6. ANUG may also be treated with tetracycline
4. CLINDAMYCIN
- bacteriostatic antibiotic effective primarily against gram-positive organisms.
- administered orally, intramuscularly, or intravenously.
ee - food does not interfere with absorption
ff - cross-resistance between Clindamycin and tetracycline (competition for binding site)
Adverse Reaction:
1. Gastrointestinal effects (Pseudo Membranous Colitis- PMC )
-severe, persistent diarrhea and the passage of blood and mucus in the stool
2. Superinfection
3. Allergy
83
Uses:
1. Should be used only when specifically indicated
2. Mixed infections insensitive to penicillin- anaerobes
5. METRONIDAZOLE
- taken orally
- bactericidal and penetrates all bacterial cells.
Adverse Reactions:
1. Gastrointestinal effects - nausea, anorexia, diarrhea and vomiting, epigastric
distress and abdominal cramping
2. Oral effects - unpleasant metallic taste; altered taste of alcohol; glossitis,
stomatitis and a black furred tongue; dryness of the mouth
3. Effects on CNS - headache, dizziness, vertigo, ataxia, confusion, depression,
weakness, insomnia, and convulsive seizures
4. Renal toxicity - cystitis, polyuria, dysuria, incontinence
5. Disulfiram-like reaction - alcohol should be avoided; symptoms include
nausea, abdominal cramps, flushing, vomiting or headache
Uses:
1. Treatment of trichomoniasis, amebiasis
2. Not the drug of choice for any dental infections (alternative drug)
3. Shown to be effective for the treatment of B. fragilis infections following
mandibular fracture
6. CEPHALOSPHORINS
- chemically related to penicillin
- bactericidal agents
- can be administered orally, intramuscularly, or intravenously.
Adverse Reactions:
1. Gastrointestinal effects
2. Nephrotoxicity
3. Superinfection
4. Local reaction
5. Allergy
6. Cross sensitivity with penicillin
Uses:
1. For infections that are sensitive to these agents but resistant to penicillin
7. VANCOMYCIN
- administered only intravenously
- bactericidal
- narrow spectrum of action against many gram positive cocci.
Adverse Reactions:
1. Ototoxicity
84
2. Nephrotoxicity
3. Anaphylaxis
4. Superinfection
Uses:
1. Useful in the prophylaxis of infective endocarditis for patients with prosthetic heart
valves who are allergic to penicillin.
2. Used orally to treat PMC.
8. AMINOGLYCOSIDES
(Neomycin, Streptomycin, Kanamycin, Gentamycin, Tobramycin, Amikacin, Netilmicin)
- bactericidal
- have a broad antibacterial spectrum
- poorly absorbed after oral administration & so must be administered by IM or IV
injection for a systemic effect
- used for the treatment of aerobic gram-negative infections
Adverse Reaction:
1. Ototoxicity
- toxic to the 8th cranial nerve, which can lead to auditory and vestibular
disturbances. Patients may have difficulty in maintaining equilibrium and can
develop vertigo.
2. Nephrotoxicity - can cause kidney damage
3. Neuromuscular blockade - act as weak neuromuscular blocking agents,
potentially producing apnea
Uses:
- reserved for hospitalized patients with the serious gram-negative infections
Gentamicin is used in dentistry to prophylaxis patients with prosthetic heart valves
9. CHLORAMPHENICOL
- broad spectrum
gg - bacteriostatic
- active against a large number of gram-positive and gram negative organisms,
rickettsiae, and some chlamydiae. Particularly active against Salmonella typhi.
- has serious side effects like fatal blood dyscracias (aplastic anemia, and
thrombocytopenia)
- “Grey baby syndrome” occurs when infants given cannot conjugate it.
- Antibiotic of first choice in the treatment of life-threatening influenza and typhoid
fever.
SULFONAMIDES
- cannot be classified as an antibiotic because they are not produced by living organisms.
- bacteriostatic against many gram positive and gram negative bacteria.
Adverse Reaction:
1. Allergic reaction (rash, urticaria, pruritus, fever, fatal exfoliative dermatitis).
2. Nausea, vomiting, abdominal discomfort, headache and dizziness.
85
3. Liver damage, depressed renal function, blood dyscrasias.

Uses:
- used when antibiotics are ineffective or cannot be used.
- should not be used topically for oral lesions
ANTIFUNGAL DRUGS
1. NYSTATIN
- effective against candida albicans
- not absorbed from the skin or mucuos membranes.
- used for local effects in the treatment of candidiasis on the skin or any part of the
alimentary tract.
- has a very unpleasant taste.
Uses:
a. Thrush
b. Denture stomatitis
c. Antibiotic stomatitis
d. Some forms of mucocutaneous candidiasis.
2. AMPHOTERICIN B
- poorly absorbed from the GIT and probably not all from the unbroken skin.
- used locally to treat conditions for which nystatin could be used.
- available in intravenous injection.
3. IMIDAZOLE AGENTS
(Miconazole, Ketoconazole)
- used in the treatment of systemic fungal infections and candidiasis
----------------------------------------------------------------------------------------------------------------------------------------------
GENERAL REFERENCES
Ansel, H.C., Popovich, N.G., and Allen, L.V.: “Pharmaceutical Dosage forms and Drug Delivery
Systems”, Sixth edition, William and Wilkins, USA, 1995.
Asperheim, M. K.: “Pharmacology AN INTRODUCTORY TEXT”, Seventh Edition

W.B. Saunders Company, Philadelphia, Pennsylvania, USA, 1992.
Grajeda-Higley, L.: “Understanding Pharmacology: A Physiologic Approach”, Appleton and

Lange, Stanford, USA 2000.
Kee, J.L. and Hayes, E.R.: “Pharmacology: A Nursing Process Approach”, 1st edition, W.B.
86
Saunders Company, Philadelphia, Pennsylvania, USA.
Musser, R. D. and O’Neil, J. J.: “Pharmacology and Therapeutics”, 4th edition. The McMillan
Company, London, 1969.
Mycek , M. J., Harvey, R. A., and Champe, P. C.: “Lippincott’s Illustrated Reviews:
Pharmacology”, 2nd edition, Lippincott-Raven Publishers, Inc. New York 1997
Olson, J.: “Clinical Pharmacology Made Ridiculously Simple”, international editions 2000,
McGraw-Hill Book Company, Singapore, 1997.
Stringer, J.L.: “Basic Concepts in Pharmacology”, A Student’s Survival Guide, 2nd edition,
McGraw-Hill Companies, Inc., Singapore, 2001.
Walton, J. G., Thompson J. W., and Seymour, R. A.: “Textbook of Dental Pharmacology and
Therapeutics”, Second edition, Oxford University Press, New York, 1994
----------------------------------------------------------------------------------------------------------------------
CENTRO ESCOLAR UNIVERSITY

College of Dentistry
Course Title: PHARMACOLOGY
Course Number: PHA100/PHA100L
Units: Lecture – 2 Hours / Week: Lecture – 2 hours/week

Laboratory – 1 Laboratory – 3 hours/week
Pre-requisites: Anesthesiology
Course Description:
The course presents the principles in the use of drugs for the diagnosis, prevention, and
treatment of diseases. Each drug is considered according to its indication, mechanism of action,
pharmacokinetics, contraindications and precautions, unwanted effects and drug interactions. The
course deals more on the commonly prescribed drugs used and related in the practice of Dentistry.
General Objectives:
1. To explain the basic and clinical pharmacology upon which drug therapy is based with
particular emphasis on drugs used in Dentistry.
2. To demonstrate the physical and biological behavior of some drugs in order to familiarize
students with the actual effects of drugs.
3. To expose students to the type of questions they will encounter in the licensure
examinations.
87
COURSE PLAN:
Suggested
Course Teaching Time Allotment Evaluative Measures
Content Specific Objectives Methodology/ (no. of hours) and Requirements
Strategy and
Materials
Introduction To introduce the Lecture Lec. = 4 Recitation/Quizzes
to general principles of Lab. = 3 Laboratory Manual
Pharmacology pharmacology
Drug To identify drugs Lecture Lec. = 2 Recitation/Quizzes
Nomenclature according to their Lab. = 3 Laboratory Manual
generic, chemical, and MIMS
trade names
Drug Therapy To know and Lecture Lec. = 4 Recitation/Quizzes
understand the
different processes
involved in drug
therapy.
Route of Drug To effectively apply Lecture Lab. = 3 Practical exercise
Administration drugs according to its demonstration Lab. = 3 Quizzes
A. IM/ route of administration method
Subcutaneous
B. Cutaneous
Dosage Forms To familiarize students “Show and Lab. = 6 Written Report
on the different dosage Tell Method” Oral Report
forms of drugs; Laboratory Manual
differentiating one Practical/Written Quiz
from the other
Drug To interpret different Lecture Lab. = 3 Interpretation of
Literature drug literature literatures
Laboratory Manual
Systems of To know how to Lecture Lec. = 2 Exercise/Quizzes
Measurement convert units and Board Lab. = 3 Laboratory Manual
Conversion doses of drugs exercises
Computation To know how to Lecture Lec. = 2 Exercise/Quizzes
of a child’s properly compute for a Board Lab. = 3 Laboratory Manual
dose child’s dose. exercises
Prescription To equip students with Lecture Lec. = 2 Quizzes
Writing and the knowledge of Board Lab. = 6 Laboratory Manual
Prescription prescription writing. exercises
Orders To learn how to
interpret prescription
order.
Pharmacology To know the different Lecture Lec. = 2 Recitation
of Pain and processes involved Quizzes
Inflammation with pain.
To know the different
88
mediators of
inflammation.
Analgesics To know the Lecture Lec. = 4 Recitation
mechanism of action Prescription Quizzes
and application of the Writing
different groups of exercises
analgesics.
Antihistamines To know the Lecture Lec. = 2 Recitation
pharmacokinetics and Quizzes
pharmacodynamics of
antihistamines
Hemostasis / To know the Lecture Lec. = 2 Recitation
Hemostatic mechanism of action Test for Lab. = 3 Quizzes
agents of hemostatic agents bleeding Laboratory Manual
and its importance in time/clotting
Dentistry. time of white
mice
Anesthetic To describe the Lecture Lec. = 2 Recitation
agents pharmacokinetics and Tests the Lab. = 3 Quizzes
pharmacodynamics of effects on Laboratory Manual
these drugs. white mice
Antimicrobials To know the different Lecture Lec. = 4 Recitation
types of antimicrobials Inoculation Lab. = 3 Quizzes
and its corresponding of bacteria Practical exercises
mechanism of action. Culture and Laboratory manual
To apply through sensitivity
prescription writing Test
the antimicrobials
learned.
Antiseptics and To know the Lecture Lec. = 2 Recitation
Disinfectants pharmacokinetics and Lab. = 3 Quizzes
pharmacodynamics of Laboratory manual
these drugs.
Drugs acting on To describe the Lecture Lec. = 2 Recitation
the Central mechanism of action Lab. = 3 Quizzes
Nervous of sedative-hypnotics Laboratory manual
System
Therapeutic To familiarize students Lecture Lec. = 6 Research papers
Measures of with common dental Lab. = 9 Recitation
Common diseases and its Quizzes
Dental therapeutic measures. Laboratory manual
Conditions and To understand the
Emergency
proper management of
Drugs.
some dental office
emergencies.
To understand the
pharmacologic
89
orientation of AIDS
and Hepatitis.
Suggested References:
Textbook of Dental Pharmacology and Therapeutics by: John G. Walton

Pharmacology by: Goodman and Gillman
Pharmacology by: Katzung
Clinical Pharmacology in Dental Practice by: Sam V. Holroyd
LABORATORY TOPICS MANUAL TOPICS LECTURE TOPICS
1. Introduction and definition 1. Introduction to 1. Introduction and definition

of terms Pharmacology of terms
2. Demonstration of Routes of 2. Drug Nomenclature 2. Drug Nomenclature
Administration
3. Skin Testing 3. Routes of Drug 3. Drug Therapy
Administration
4. Interpretation of Drug 4. Skin Testing 4. Routes of Drug
Inserts Administration
5. Conversion of doses and 5. Drug Dosage Forms 5. Dosage Forms
measurements
6. Prescription Writing 6. Drug Literatures 6. Drug Literatures
7. Prescription Orders 7. System of measurements 7. System of Measurements
PRELIM EXAM 8. Conversions 8. Prescription Writing /
Orders
8. Narcotics and Non- 9. Prescription Writing 9. Analgesics
Narcotics Analgesics
9. Histamine and 10. Prescription Orders 10. General Anesthetics
Antihistamines
10. Hemostasis and 11. Analgesics 11. Local Anesthetics
Hemostatic Agents
11. General Anesthetics 12. Antihistamines 12. Histamines and
Antihistamines
12. Local Anesthetics 13. Hemostasis and 13. Hemostasis and hemostatic
Hemostatics Agents Agents
90
13. Antimicrobials – culture 14. General Anesthetics 14. Antimicrobials

and Sensitivity
15. Local Anesthetics 15. Antiseptics / Disinfectants
14. Sedative – Hypnotics 16. Antimicrobials 16. Sedative-Hypnotic Drugs
15. Antiseptics and 17. Sedative-Hypnotic Drugs 17. Office Emergencies
Disinfectants
16. Common Oral Diseases 18. Antiseptics / Disinfectants 18. Common Oral diseases
17. Office Emergencies 19. Common Dental Diseases 19. AIDS / Hepatitis
18. AIDS and Hepatitis 20. Office Emergencies
21. AIDS and Hepatitis
OUTLINE OF TOPICS IN PHARMACOLOGY
PRELIM
LECTURE
1st Meeting
Orientation
2nd Meeting
Definition of terms
Introduction
History of pharmacology
Branches of Pharmacology
Importance of Pharmacology to dentistry
Fundamental action of drugs
Uses of Drugs
Drug Nomenclature
Drug Publications
Quiz
3rd Meeting
91
Stages in the development of a drug

Introduction to Drug Therapy
Quiz
4th meeting
Process of Drug Therapy
Quiz
5th meeting
Continuation of Drug Therapy
Quiz
LECTURE PRELIM EXAM
LABORATORY
1st Meeting
Orientation
2nd Meeting
Exercise 2 & 3
*Exercise 1 will be given as a quiz
How to use MIMS
Quiz
3rd Meeting
Exercise 4
Routes of Drug administration
Quiz
4th meeting
Exercise 5
Quiz
LABORATORY PRELIM EXAM
General Principles / Factors / Terminologies

1. Factors affecting Patient's Reaction to Drugs
A. Routes of Drug Administration
1. Enteral
2. Parenteral
B. Passage of Drug Across Body Membrane
1. Active Transfer
2. Passive Transport
C. Fate of Drug
1. Absorption
92
2. Distribution
3. Metabolism / Biotransformation
4. Excretion / Elimination
2. Considerations in Drug Administration

A. Tolerance
B. Pathologic State
C. Age and Weight
3. Action vs. Effect
Anaphylaxis
Placebo
Immunity
Idiosyncrasy
Tolerance
Tachyphylaxis
Drug Resistance
Refractory
Hyporeaction
Hyper-reaction
Hypersensitivity
Supersensitivity
88888888888888888888
3rd Meeting
General Anesthetics
Local Anesthetics
Locally Acting Medication: Antimicrobials, Hemostatics and Protectives
4th Meeting
Diuretics and Antihypertensive

Sedative Hypnotics
Psychotherapeutic
5th Meeting
Central Nervous System Stimulants

Anticonvulsant
Antineoplastic
Adrenocorticosteroids
FINALS
93
* SPECIAL TOPICS
1st Meeting
Emergency Drugs
2nd Meeting
Pharmacologic Considerations
3rd Meeting
Disease Status of Common Interest
4th Meeting
Pharmacologic Management of Certain Common Oral Disease Entities
5th Meeting
Drug Interactions
Predictable Reaction:
1. Excess pharmacological activity
2. Rebound response upon discontinuation
Excessive Pharmacological Effects:

1. Respiratory depression in severe bronchitic patients given morphine or benzodiazepine
hypnotics
2. Hypotension resulting in stroke, myocardial infarction or renal failure in patients receiving
excessive doses of antihypertensive drugs.
3. Bradycardia in patients receiving excessive DIGOXIN
Withdrawal Symptoms:
1. Extreme agitation, tachycardia, confusion, delirium and convulsions may occur following the
discontinuation
of long-term CNS depressants such as barbiturates, benzodiazepine and alcohol.
2. Acute Addisonian crisis may be precipitated by the abrupt cessation of corticosteroid therapy.
3. Severe hypertension and symptoms of sympathetic overactivity may arise shortly after
discontinuing
clonidine therapy.
4. Withdrawal symptoms after narcotic analgesics.
Allergic Responses:
Allergy - altered capacity of the body to react to various antigens with which it comes in
contact.
* 2 Types of Hypersensitivity:
94
1. Immediate
- antibody is circulating or fixed to certain tissues.
- Antigen reacts to antibody.
2. Delayed
- a reaction of T-cells that have been stimulated by antigen to react against targets such as
infectious agents.
- Antibody is not involved.
Genetically Determined effects - major toxicity of some drugs is restricted to individuals with
particular
genotype or genetic make-up.
DEFECT TOXIC DRUG SYMPTOMS
Pseudocholinesterase
Deficiency Succinylcholine Paralysis
Apnea
Glucose-6-Phosphate
Dehydrogenase deficiency Sulfonamides
Quinidines Hemolysis
Primaquine
Acetylator-Polymorphism Procainamide Systemic Lupus
Hydralazine
Isoniazid Neuropathy
Hepatic Porphyria Barbiturates Symptomatic prophyria
Idiosyncratic Drug Reaction:

Idiosyncracy - used primarily to cover unusual, unexpected, bizarre drug effects that cannot
readily explained or predicted in individual recipients.
*DRUG INDUCED MALIGNANT DISEASE IS FORTUNATELY RARE...
PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM:

- generally, all drugs influence blood pressure, heart rate, potassium pump
Diversity of ANS on Body functions specific to Dentistry:

1. Practical application of vasoconstrictors in local anesthetic solutions.
2. Agents that reduces salivary flow
3. Alterations of the ANS mechanism both centrally and peripherally antihypertensive drug.
4. Significant peripheral changes in ANS activity produced by antipsychotic phenothiazines and
antidepressants.
5. Entire concept of chemical neurotransmitters and receptors are founded on the principles of the
ANS.
*2 Divisions of the ANS

1. Sympathetic
95
2. Parasympathetic
* Both are regarded as peripheral in modes of action and drug reactions even though these cell
bodies are
located within the CNS and receive considerable CNS input.
Autonomic Nervous System - concerned with the maintenance of a constant internal environment
to provide
for optimal cellular function and survival.
Functions:
Reflex vasodilation
Regulates Body temperature
Blood glucose level
Cardiac Rate
Water Balance
SYMPATHETIC DIVISION - designed to cope with sudden emergencies. E.q. Fright and flight
phenomenon
PARASYMPATHETIC DIVISION - conservation of bodily processes E.q. Reflex slowing of

the heart
Action Potential - bioelectric signals / self propagated impulses along the nerves.
Neurotransmitters - chemical mediators that transmit signals across nerve to nerve, or nerve
to effector tissue.
Acetylcholine - specific chemical mediator at all autonomic ganglia and parasympathetic post
ganglionic synapses.
- transmitter substance of the neuromuscualr junction in skeletal muscle.
Norepinephrine - principal chemical mediator of the sympathetic postganglionic neuron.
Epinephrine - major mediator released by the adrenal medulla.
Cholinergic - nerves releasing acetylcholine.
Adrenergic - nerves releasing norepinephrine.

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1

Claude Bernard - expanded application in scientific method.

IMPORTANCE OF PHARMACOLOGY TO DENTISTRY

STAGES IN THE DEVELOPMENT OF A DRUG

PRINCIPAL INDIVIDUAL(S) STAGES IN THE DEVELOPMENT OF A DRUG

* 3 MAJOR PHASES IN A PRE-CLINICAL TESTS

PRINCIPLES OF DRUG ACTION

FUNDAMENTAL ACTION OF DRUGS

*All drugs exert some effect on a biologic system

Potency - amount/strength of a drug required to produce the desired effect or action

CHARACTERISTICS OF DRUG ACTION

MECHANISM OF DRUG ACTION

RECEPTORS INVOLVED IN THE ACTION OF COMMONLY USED DRUGS

RECEPTOR MAIN ACTION OF NATURAL AGONISTS

DOPAMINE CNS Neurotransmitter

II. ACTION ON ENZYME

III. ACTION ON MEMBRANE IONIC CHANNELS

IV. CYTOTOXIC ACTIONS

U.S.P. United States Pharmacopoeia

N.F. National Formulary

A.D.T. Accepted Dental Therapeutics

P.D.R. Physician's Desk Reference

* REPUBLIC ACT 6675 - known as the GENERIC ACT OF 1988

Importance of R.A. 6675

Who Shall Use Generic Terms?

Penalty for NOT complying to R.A. 6675

2 Types of Code Designation

2. TRADE NAME (Commercial Name; Proprietary Name; Brand Name)

BRAND NAME - name of the company marketing the product

Two Important Disadvantages of Trade Name:

Advantages of Trade Names:

3. GENERIC NAME - "Official" name of the drug; "Non-Proprietary name.

Advantages of using Generic Names

Disadvantages of using Generic Names

*** How to use the PIMS / MIMS

PIMS - Philippine Index for Medical Specialties

Brand Name /Manufacturer / Distributor

Example: (Based from MIMS Dental Phils. 2002 page 68)

ATMOSE Morishita-Seggs Rx (Atmose is the proprietary name of the

PHARMACOLOGICAL CLASSIFICATION INDEX

II. CARDIOVASCULAR AND HEMATOPOIETIC SYSTEM

III. RESPIRATORY SYSTEM

3. Cough and Cold Remedies

IV. NEUROMUSCULAR SYSTEM

VI. CONTRACEPTIVE AGENTS

VIII. OTHER CHEMOTHERAPEUTICS

IX. GENITO-URINARY SYSTEM

XI. VITAMINS AND MINERALS

XIII. EYE, EAR, MOUTH / THROAT

XVI. DIAGNOSTIC AGENTS

XVII. ALLERGY AND IMMUNE SYSTEM

XVIII. ANTIDOTES AND DETOXIFYING AGENTS

XIX. INTRAVENOUS AND OTHER STERILE SOLUTIONS

Different Factors Affecting Response:

ROUTES OF DRUG ADMINISTRATION

Contraindication for Oral Route

Disadvantages of Oral Route

Importance of First Pass Metabolism

Drugs with High First Pass Metabolism

Patient’s name: ______________________ Date:_