Unit I General Pharmacology
Unit I General Pharmacology
Unit I General Pharmacology
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Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 1
UNIT – I: General Pharmacology
B. Chemistry
Chemical structures of drugs can provide information about mechanism of action, pharmacokinetics,
stability, and metabolic fate.
1. Structure-Activity Relationship: A modification of the chemical structure of a drug may accentuate or
diminish its pharmacological effects, often providing clues as to the mechanism of action. A picture of the
biological reactive site (the receptor) can be developed in such studies. Also, drugs are metabolized by
body systems, which may convert the parent drug to a more active or a less active form. The drug structure
can be modified to enhance or diminish the rate of metabolic conversion.
2. Sites of Action: The organ or cellular target of drug action.
3. Drug Receptors: Macromolecules in cells or cell membranes with which drugs interact to exert their
effects. Usually the interacting forces are reversible ionic and Van der Waals bonds of relatively low energy,
but sometimes covalent bonds are formed (e.g. organophosphate insecticides).
C. Pharmacodynamic
The effect of the drug on the body. Pharmaco-dynamics is the study of the relationship of drug
concentration and the biologic effect (physiological or biochemical).
For most drugs it is necessary to know the site of action and mechanism of action at the level of the
organ, functional system, or tissue. For example, the drug effect may be localized to the brain, the
neuromuscular junction, the heart, the kidney, etc. Often the mechanism of action can be described in
biochemical or molecular terms. Most drugs exert effects on several organs or tissues, and have
unwanted as well as therapeutic effects. There is a dose-response relationship for wanted and
unwanted (toxic) effects.
Patient factors affect drug responses - age, weight, sex, diet, race, genetic factors, disease states, trauma,
concurrent drugs, etc.
D. Pharmacokinetics
The effect of the body on the drug. To produce its characteristic effects, a drug must be present in
appropriate concentrations at its sites of action. Thus, it is important to know the interrelationship of
the absorption, distribution, binding, biotransformation, and excretion of a drug and its concentration
at its locus of action.
1. Absorption (oral or parenteral): A drug must be absorbed and achieve adequate concentration at its site of
action in order to produce its biological effects. Thus, when a drug is applied to a body surface (e.g., G.I.
tract, skin, etc.), its rate of absorption will determine the time for its maximal concentration in plasma and
at the receptor to produce its peak effect.
2. Distribution: The blood, total body water, extracellular, lymphatic and cerebrospinal fluids are involved in
drug movement throughout the body. Depending upon its chemical and physical properties, the drug may
be bound to plasma proteins or dissolved in body fat, delaying its progress to its sites of action or excretory
mechanism.
3. Metabolism: This is how certain drugs are handled by the body in preparation for their elimination and
includes the fate of drugs-biotransformation (e.g., hydrolysis, conjugation, oxidation-reduction).
4. Excretion: The kidney is the most important organ for drug excretion but the liver, lung and skin are also
involved in drug elimination. Drugs excreted in feces are mostly derived from unabsorbed, orally ingested
drugs or from metabolites excreted in the bile and not reabsorbed by the intestine. The physical and
chemical properties, especially the degree of ionization of the drug, are important in the rate of excretion.
5. Biological Factors Modifying Pharmacokinetic Aspects: Normal variations occur in population
pharmacokinetic constants (absorption rates, elimination rates). Other factors include age, weight, obesity,
edema, concurrent diseases, other drugs (various interactions including effects on protein binding or
metabolic rate), diet, dose interval and route of administration, genetic variations in elimination rate.
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UNIT – I: General Pharmacology
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UNIT – I: General Pharmacology
G. Pharmacovigilence
The area of Pharmacovigilence that focuses on the effects of drugs on patient safety.
It involves the characterization, detection, and understanding of adverse events associated with drug
administration, including adverse drug reactions, toxicities, and side effects that arise as a consequence
of the short- or long-term use of drugs.
Adverse drug reactions, including drug-drug interactions, are estimated to be a major cause of
mortality of inpatients and also lead to significant increases in duration of hospitalization. No drug is
free of toxic effects. Some untoward effects of drugs are trivial, but others are serious and may be fatal.
Side effects often are predictable from knowledge of the pharmacology of a particular drug.
Examples of chemicals or drug-induced toxicities are given below:
1. Allergic reactions: The number of serious allergic reactions to drugs involving antigen-antibody reactions
is low but when they occur the physician must have sufficient knowledge to manage these problems.
2. Blood dyscrasias: These are very serious and sometimes fatal complications of drug therapy. They
include: agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia and defects in clotting
factors.
3. Hepatotoxicity and nephrotoxicity: Because many chemicals and drugs are eliminated and metabolized
by the liver and kidney, damage to these organs is seen commonly.
4. Teratogenic effects: The thalidomide tragedy dramatically emphasized that drugs may adversely
influence fetal development.
5. Behavioral toxicity: This is a term used to describe suppression of normal anxiety, reduction in
motivation, impairment of memory and learning, distortion of judgement, impairment of reflexes, adverse
effects on mood, etc.
6. Drug dependence and drug abuse: The repeated administration of some chemicals may lead to drug
dependence. Drugs likely to be abused and upon which drug dependence may develop are the various
psychopharmacological agents such as opiates, barbiturates, amphetamines, nicotine and ethanol.
Dependence on tobacco (nicotine) is also well known.
7. Carcinogenesis: Carcinogenesis is a delayed type of toxicity with a latency of many years.
8. Pharmacogenetic toxicities: Certain genetically-predisposed individuals have a markedly toxic reaction
to certain otherwise safe drugs. Examples are prolonged apnea after succinylcholine, or malignant
hyperthermia associated with anesthetics.
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UNIT – I: General Pharmacology
(B) Routes of administration of drugs
Definition
- A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other
substance is taken into the body.
- Most of the drugs can be administered by different routes. Drug- and patient-related factors determine the
selection of routes for drug administration. The factors are:
1. Characteristics of the drug.
2. Emergency/routine use.
3. Site of action of the drug—local or systemic.
4. Condition of the patient (unconscious, vomiting, diarrhoea).
5. Age of the patient.
6. Effect of gastric pH, digestive enzymes and first-pass metabolism.
7. Patient’s/doctor’s choice (sometimes).
- Before consider the various routes of drug administration, let study of how drugs move within the body:-
(Schematic diagram showing the various pharmacokinetic processes following administration of a drug. D drug, P protein, R receptor)
Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 5
UNIT – I: General Pharmacology
1. LOCAL ROUTES
- It is the simplest mode of administration of a drug at the site where the desired action is required. Systemic side
effects are minimal.
i. Topical: Drug is applied to the skin or mucous membrane at various sites for local action.
a) Oral cavity: As a suspension, e.g. nystatin; as a troche, e.g. clotrimazole (for oral candidiasis); as a
cream, e.g. acyclovir (for herpes labialis); as ointment and jelly, e.g. 5% lignocaine hydrochloride (for
topical anaesthesia); as a spray, e.g. 10% lignocaine hydrochloride (for topical anaesthesia).
b) GI tract: As tablet that is not absorbed, e.g. neomycin (for sterilization of gut before surgery).
c) Rectum, Vaginal and anal canal:
As an enema (administration of drug into the rectum in liquid form):
- Evacuant enema (for evacuation of bowel): For example, soap water enema—soap acts as a lubricant
and water stimulates the rectum.
- Retention enema: For example, methylprednisolone in ulcerative colitis.
As a suppository (administration of the drug in a solid form into the rectum), e.g. bisacodyl—
for evacuation of bowels.
Advantages
- Used in children.
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any surgical or radiological
procedure.
Disadvantages
- Inconvenient.
- Drug absorption is slow and erratic.
- Irritation or inflammation of rectal mucosa can occur.
d) Eye, ear and nose: As drops, ointments and sprays (for infection, allergic conditions, etc.), e.g.
gentamicin eye/ear drops.
e) Bronchi: As inhalation, e.g. salbutamol (for bronchial asthma and chronic obstructive pulmonary
disease). Gases, volatile liquids and solids (in the form of finely divided powders) are inhaled for
systemic and local effects. Inhalation of solids is called insufflation.
Advantages
- Rapid absorption of the drug due to large surface area.
- First pass effect is avoided.
- Rapid local effects.
Disadvantages
- Only few drugs can be administered.
- May produce irritation of pulmonary mucosa.
- Inconvenient procedure.
- Chances of cardiotoxicity.
f) Skin: As ointment, cream, lotion or powder, e.g. clotrimazole (antifungal) for cutaneous candidiasis.
g) Transdermal: Transdermal patches can provide prolonged or controlled (iontophoresis) drug
delivery. Systemic absorption (Transdermal) is better with low dose, low MWt, lipid soluble drugs
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UNIT – I: General Pharmacology
ii. Intra-arterial route: This route is rarely employed. It is mainly used during diagnostic studies such as
coronary angiography and for the administration of some anticancer drugs, e.g. for treatment of malignancy
involving limbs.
iii. Administration of the drug into some deep tissues by injection, e.g. administration of triamcinolone
directly into the joint space in rheumatoid arthritis.
- Typical Plot of Concentration versus Time after Topical Administration
Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 7
UNIT – I: General Pharmacology
2. a) Systemic Routes (Enteral)
Drugs administered by this route enter blood and produce systemic effects. Enteral Routes It includes (i) Oral
route, (ii) Buccal or Sublingual route and (iii) Rectal route.
i. ORAL ROUTE
It is the most common and acceptable route for drug administration. Dosage forms are tablet, capsule, syrup,
mixture, etc., e.g., paracetamol tablet for fever, omeprazole capsule for peptic ulcer are given orally.
Advantages:
- Convenient - portable, safe, no pain, can be self-administered.
- Cheap - no need to sterilize (but must be hygienic of course)
- Variety of dosage forms available - fast release tablets, capsules, enteric coated, layered tablets, slow
release, suspensions, mixtures
- Convenient for repeated and prolonged use.
Disadvantages:
- Sometimes inefficient :- high dose or low solubility drugs may suffer poor availability, only part of the dose
may be absorbed. Griseofulvin was reformulated to include the drug as a micronized powder. The
recommended dose at that time was decreased by a factor of two because of the improved bioavailability.
- First-pass effect :- drugs absorbed orally are transported to the general circulation via the liver. Thus drugs
which are extensively metabolized will be metabolized in the liver during absorption. e.g. the propranolol
oral dose is somewhat higher than the IV, the same is true for morphine. Both these drugs and many others
are extensively metabolized in the liver.
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UNIT – I: General Pharmacology
Advantages:
- Quick onset of action.
- Action can be terminated by spitting out the tablet.
- Bypasses first-pass metabolism.
- Self-administration is possible.
Disadvantages
- It is not suitable for bitter tasting and unpalatable drug.
- It is not suitable for Irritant and lipid-insoluble drugs.
- cannot give to unconscious patient.
- Large quantities cannot be given.
- Cannot be given in severe vomiting.
Typical Plot of Concentration versus Time after Buccal Administration
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UNIT – I: General Pharmacology
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UNIT – I: General Pharmacology
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UNIT – I: General Pharmacology
i. INTRAVENOUS (IV)
Drugs may be given into a peripheral vein over 1 to 2 minutes or longer by infusion, or Drugs are injected
directly into the blood stream through a vein.
Drugs are administered as:
a) Bolus: Single, relatively large dose of a drug injected rapidly or slowly as a single unit into a vein. For
example, i.v. ranitidine in bleeding peptic ulcer.
b) Slow intravenous injection: For example, i.v. morphine in myocardial infarction.
c) Intravenous infusion: For example, dopamine infusion in cardiogenic shock; mannitol infusion in
cerebral oedema; fluids infused intravenously in dehydration.
Advantages
- Bioavailability is 100%.
- Quick onset of action; therefore, it is the route of choice in emergency, e.g. intravenous diazepam to control
convulsions in status epilepticus.
- Large volume of fluid can be administered, e.g. intravenous fl uids in patients with severe dehydration.
- Highly irritant drugs, e.g. anticancer drugs can be given because they get diluted in blood.
- Hypertonic solution can be infused by intravenous route, e.g. 20% mannitol in cerebral oedema.
- By i.v. infusion, a constant plasma level of the drug can be maintained, e.g. dopamine infusion in cardiogenic
shock.
Disadvantages
- Once the drug is injected, its action cannot be halted.
- Local irritation may cause phlebitis.
- Self-medication is not possible.
- Strict aseptic conditions are needed.
- Extravasation of some drugs can cause injury, necrosis and sloughing of tissues.
- Depot preparations cannot be given by i.v. route.
Precautions
- Drug should usually be injected slowly.
- Before injecting, make sure that the tip of the needle is in the vein.
Typical Plot of Concentration versus Time during an IV Infusion Administration
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UNIT – I: General Pharmacology
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UNIT – I: General Pharmacology
v. INTRA-ARTICULAR ROUTE
Drug is injected directly into the joint space, e.g. hydrocortisone injection for rheumatoid arthritis. Strict aseptic
precautions should be taken. Repeated administration may cause damage to the articular cartilage.
Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 14
UNIT – I: General Pharmacology
v. TRANSDERMAL ROUTE
The drug is administered in the form of a patch or ointment that delivers the drug into the circulation for
systemic effect.
For example, scopolamine patch for sialorrhoea and motion sickness, nitroglycerin patch/ointment for angina,
oestrogen patch for hormone replacement therapy (HRT).
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