Faculty of Medicine

Department of pharmacology
Faculty of Medicine
Department of pharmacology
Dr. Rawan Ghazwi
Office: M6L0
[email protected]
 Part 1
General Principles of Pharmacology

Contents of Part 1 Topic

1. Introduction and Overview in Pharmacology

2. Routes of drug Administration

3. Pharmacokinetics
4. Pharmacodynamics.
 Definition of
Definition of Drug Pharmacology
A drug is any substance or Pharmacology is the science that
product of known deals with the study of all the
structure, that, when aspects of drugs (study of the
administered to living history, origins, chemical
organisms, produces a structure, preparation,
change in function. administration properties &etc….)

Pharmacology is the study of medications, or chemical

compounds and their interaction with a specific
molecule in the biologic system (the living systems) and
how they affect the body in order to produce a certain
effect through chemical processes either activating or
inhibiting normal body processes.
 Purposes of Drug (Medication or Medicine)

Drugs can be administered for the

following purposes

1.Therapeutic purposes
2.Prophylaxis purposes
3.Diagnostic purposes
Drug Names (Nomenclature)
Drugs have Three Names assigned to them:

1. Chemical Name(‫)االسم الكيميائي‬

All drugs are chemicals, & many have long chemical
names.
Ex: the chemical name for paracetamol is
N-acetyl-para-aminophenol (NAPAP)

2. Generic or approved or official or

non-proprietary name (‫)االسم العلمي‬ Is a
shorter name, Ex: Paracetamol or Acetaminophen

3. When the drug is marketed by a pharmaceutical

company, it is given a third name, known as
Brand or trade or the commercial or
proprietary name (‫)االسم التجاري‬
 Ex: Revanin® 
 1. Chemical Name 2. Generic name 3. Brand (trade) Name 
(‫)االسم الكيميائي‬ (‫)االسم العلمي‬ (‫)االسم التجاري‬
 Is derived from chemical Is Derived from chemical name  Is given by the manufacturer of the
structure of the drug Is given by the international drug (a pharmaceutical company)
 Scientifics usually draw the organization of drug and it is  Is assigned by the manufacturer
structure & name it. World-wide (international) symbol ® after the trade name
acceptance.

 Describes the information  Describes the active ingredient Since several different pharmaceutical
on the drugs molecular of drug companies may market the same
compound & properties. generic drug, there may be several
different trade names for any one drug.
There are different trade names for the
(one) same generic name drug. Ex:
Panadol®, Revanin® , Tylenol ®,
Pandarin ®, & etc  Are a brand name
for generic name~paracetamol
Chemical Name is Generic name is usually short Brand Name  of drug is usually
1.Unsuitable for prescribing short, easy to spell, sounding &
 Is usually long & rarely Generic name given throughout remember it easily.
used. very difficult name to course pharmacology (Usually
pronounce have similar suffix in a group)
2.Commonly Used by
Scientifics, chemists…etc in
scientific studies.
 Drug Sources
Where do drugs come from?

The sources of drugs could be:

1.Natural sources
I. Plant Sources
II. Animal Sources
III. Microorganisms Sources
IV. Inorganic Compounds Minerals Sources

2.Synthetic sources
1. Chemical sources
2. Semisynthetic sources
3. Biosynthetic Sources (Genetically Engineered Drugs)
After a drug is administered, what will happen to the
drug inside our body?
The interaction of drugs within the human body go through two phases:

Branches of Pharmacology:

1. Pharmacokinetic
The action of the body on the drug
2. Pharmacodynamics
The action of drug on the body
 Pharmacokinetics
(PKs)

‘What the body does to the drug’

 Pharmacokinetics describes ‘drug movement’ through the body
from entry to exit by studying the effects of biological systems on
a drug.

 PKs study of the processes of drug ADME

Absorption (A)
Distribution (D)
Metabolism (M)
Elimination
Excretion (E)
 1. The kinetics of Drug Absorption (‫)االمتصاص‬
The first stage of ADME is A, for Absorption.

Absorption occurs by passage of drug

across cell membrane Absorption
It is the process of drug
movement or transport
from the site of
administration (maybe
GIT, skeletal muscles, lung,
skin, or mucous membranes
…etc) to systemic
circulation (major) , or
another site
Absorption occurs after a
drug is administered.
Factors influencing the rate & extent (efficiency) of drug absorption either
related to drug or to body

Factors which enhanced drug Factors which decreased drug

absorption absorption

1. Dosage forms:
• absorption is rapid for Gases forms > 1.The presence of food/other
Liquid forms > solid form medications in the stomach (Drug food
• Absorption is rapid for solution > interaction)
suspension > capsule > tablet 2.Highly increased Intestinal motility
2. High dose (concentration) of a medication (diarrhea)
3. Low Molecular Weight & small Particle
2. Chemical instability of Some drugs
size
in gastric pH & enzyme
3. The larger the surface area & the high the
blood supply where the drug is being 3. Diseases of the gut.
absorbed.
4. The ability of the drug to cross cell
membranes.
Un-ionized drugs (non-polar) are more lipid
soluble  are absorbed faster  The
more easily a drug crosses a cell
The first-pass metabolism/effect or Pre-systemic Effect for oral drug
and Drug Bioavailability (F)

 The first-pass (Pre-systemic)  Bioavailability (F)

metabolism (First-Pass Effect)  Measure of the fraction
Refers to metabolism of a drug (proportion or percentage) of
during its passage from the site chemically unchanged or un-
of absorption into the systemic metabolized of administered
circulation. drug that are absorbed &
After oral drug administration & transported to reaching the
before it enters the systemic systemic circulation following
circulation drugs are exposed to administration by any route
drug metabolizing enzymes in (Except IV route)
the GIT lumen or Gut wall ,
 By definition, I.V doses have
portal circulation, or liver.
100% bioavailability F =1
Highly fraction (proportion or
In general, the First-pass
percentage) % of drug reaches the
Metabolism  Decreases Drug systemic circulation  Highly
Bioavailability bioavailability.
 First-Pass Effect is an important feature for:

1. An orally administered drugs 2. Rectally administered drugs

which are highly affected by first-pass metabolism (GIT which are partially affected by first-pass
lumen or Gut wall portal circulation, or liver )are metabolism (liver) are absorbed via the lower
absorbed mainly in the upper small intestine and enters intestinal mucosa.
the splanchnic circulation supplying that mucosa.

Note: Other routes of drug administration are NOT affected by

first-pass metabolism.
Note: The first-pass metabolism is the reason that oral medication
dosages are much higher than IV medication dosages.
 Some Methods for Delaying Some Methods for Enhancing
drug Absorption drug Absorption

1. Vasoconstrictors
 Add vasoconstrictors drug to some
parenteral drug for delay its 1. Formulation rapidly
absorption Ex: add adrenaline to absorbed drug
local anesthetic (L.A) drugs for  Administer Drug Sublingually
specific reasons.  May dissolved drug in water.
2. Massage the area
2. Formulation (by diff. way) ex:
1. Administer Drug by transdermal
route.
2. Administer Drug in oily
preparations.
3. Drug prepared as slow releasing
(SR) preparations as extended oral
drug
 2. Thekinetics of Drug Distribution(‫)انتشار الدواء في الجسم‬
The second stage of ADME is D, for Distribution

Distribution
Is the second processes after drug
absorption
Defined as the process or the way by
which a drug reversibly move from or
leaves the blood circulation (plasma) &
distributed into the extracellular fluid
and/or the cells of the tissues to reaches
the site of its action or target cells.

Factors influence 1. Highly lipid-soluble drugs

2. High Blood flow to organs
the effective
3. Capillary structure permeability
distribution of &Passage drug Across Barriers
medication
 Medication accumulates and forms a
reservoir called pooling
There are two types of pooling:
1. Protein-binding:
 Protein-binding occurs when a medication binds to plasma proteins.
 Many drugs bind to plasma proteins, including albumin, on reaching
the circulation

2. Tissue-binding:
 Tissue-binding occurs when medication binds to tissues, ex: lipid
soluble drugs are bound highly to adipose tissue. Other drugs
accumulated in bone.
 1. Binding drug to plasma protein

In the systemic circulation, the Drug may be found in

Two States

1. The free (unbound) 2. Binding of Drugs to

fraction of the drug Plasma Proteins

Reversible
binding

Drug is reversible & tightly bound with protein (When the

concentration/level of free drug in plasma decreases, bound drug is
dissociates very slowly from protein to become free)
 1. Binding drug to plasma protein

In the systemic circulation, the Drug may be found in Two States

1. The free (unbound) 2. Binding of Drugs to

fraction of the drug Plasma Proteins
Characteristic of Drug-Protein complex
Characteristic of free drug
1.Drugs protein-complex serves as temporary
store (reservoir) of drug.
1. Is pharmacologically active 2.Drugs protein-complex delays drug elimination
or excretion as result prolongs the duration of
action of the drug in body
2. Only the free fraction (unbound)
of drug is available for 3.Drugs protein-complex (bound drugs)
pharmacological action, 1. Are relatively large size & pharmacologically inactive
metabolism & excretion 2. Are not metabolized Delays drug metabolism
3. Are not excreted  Delays drug excretion
4. can’t cross the cell membranes & can’t enter into
capillaries & then into tissues to its site of action.
 Reversible binding

Clinical 1. Competition between drugs for the same

Significance of plasma protein-binding sites may increase
the “drug free fraction’’
Plasma Protein 2. Chronic renal failure & liver disease
Binding
 2. Binding to tissues & plasma protein
1. Drug Tissue-binding: Tissue-binding occurs when some
medications are concentrated or accumulated in tissues or some organs of the
body, which can lead to toxicity on chronic use or to produce beneficial
effect.
Characteristic of Drug Tissue Binding
1. Drug is pharmacologically ACTIVE
2. Tissue acts as temporary store of drug (reservoir)
3. Extensive tissue binding delays drug elimination or excretion as result prolongs
the duration of action of the drug in body
For example,
1. Heavy metals as lead and arsenic in hair and skin
2. Fat -soluble medications are bound highly to adipose tissues.
3. Tetracyclines are concentrated & accumulate in bones and teeth  cause:
 Teeth discoloration (brownish to yellowish)
 Hypoplasia of teeth
Due to that Tetracycline should not be used (contraindicated) in children & pregnancy
 The kinetics of Drugs Elimination
(The removal of drugs from the body)
3. The kinetics of Drugs Metabolism
The third stage of ADME is M, for Metabolism

Metabolism
After the drug has been distrusted, the next phase is metabolism. This is where the
drug is broken down. It is the process of biochemical alteration of the drug in the
body by proteins called enzymes, which creates metabolites (Is the end result of
form drug metabolism)

Sites of Drug Metabolism

(Biotransformation)

The liver is the primary & major

site for drug metabolism
The kinetics of Drugs Elimination
(The removal of drugs from the body)
 What is the aim of the process of drug metabolism?
The major function of drug Metabolism is
1.Inactivation the drug: ???? The main function of drug metabolism is Reducing drug
lipid solubility by convert drug from its Active form or convert the lipid-soluble drugs
(lipophilic, uncharged, nonpolar, unionized compounds)  into Inactive Metabolite (form)
or into water-soluble (Hydrophilic, Polar, Charged, ionized compounds)  To enhance
their excretion in urine by kidneys
Note: Liver enzymes are largely targeted lipid-soluble drugs  because they are
typically very difficult to eliminate

Other minor function is Alteration the biological activity of some drugs

1. Maintain activation of some drugs (means increase the activity of some active drugs)
Covert Drug from its Active form  To more active Metabolite (form)
Note: When the metabolite is active, the duration of action gets prolonged
2. Toxification : Convert Active Drug  To Toxic metabolite
Note: In case of some drugs, the active metabolite may be toxic (May Increased
drug toxicity
3. Activation or bio-activation : Convert of In-Active Drug  into an active pharmacological
agent in the body by normal metabolic processes (as liver or target site of action) is converted
to its active "active pharmacological agent ‘’
Note: prodrug means An inactive form of a drug.
 Pro-drug

An inactive precursor of a drug. Conversion of an "inactive" drug into an

"active pharmacological agent ‘’ in the body by normal metabolic process.

1. Prodrug is designed to improve drug bioavailability

2. Prodrug is designed to achieve longer duration of
action
3. Prodrug is designed to improve the taste.
4. Prodrug is designed to drug delivery For site-specific
 The kinetics of Drugs Elimination
(The removal of drugs from the body)
4. The kinetics of Drug Excretion
The Last stage of ADME is E, for Excretion

Excretion: Sites of Drug excretion

Is the process by which drugs or their
metabolites are irreversibly exit the
body, through renal or non-renal Kidneys are the primary &
route. major site of drug
excretion

 kidney failure may increase risk of

toxicity of drugs?
 How can we decrease risk of toxicity?
 In drug overdose or poisoning from
(weak or basic drugs)

Ion trapping
This process is clinically useful to manage drug
overdose or acute drug toxicity by increasing their
renal excretion in urine & minimize the amount of drug
of back-diffusion (decrease reabsorption) through
changing the pH of urine to allow the drug
(either acidic or basic) in ionized form
 Alkalinization of Urine Acidification of Urine

It means changing the pH of urine to It means changing the pH of urine to

basic environment to acidic environment to
Trapped acidic drugs (get ionized in Trapped basic drugs (get ionized in
alkaline urine) acidic urine)

Alkalinization of urine → increases Acidification of urine → increases

ionization of weak acids → increases ionization of weak bases → increases
renal elimination. renal elimination

Weak Acidic Drug is better excreted in Weak Basic Drug is better excreted in
basic media. acidic media.

Example: Example:
Overdose or toxicity from Weak acid Overdose or toxicity from Weak basic
drugs (ex: aspirin) is managed by drug (ex: amphetamines) is managed
administration of basic compounds (e.x. by administration of acidic compounds
sodium bicarbonate) to alkalinize urine (ex: Ammonium chloride or vitamin C)
(inc. pH of urine) to acidify urine (dec. pH of urine)
 How long does it take for a drug to reach
maximum therapeutic effect (peak) & How
long it take for a drug to leave the body?

Fundamental Principles of PK.

1. The therapeutic Drug Range (Window)

2. Drug Plasma half-life =Elimination Half Life (T ½ )
3. Steady-State concentration (Css)
4. Loading dose.
5. Maintenance dose.
 Paracetamol
500 mg
6 x1

Paracetamol:

half-life about 4 hours

To reach steady state ??
It is eliminated from the body within…………????
 If your doctor prescribe paracetamol 5oo mg
four times /day
As analgesic for your headache. When you
should take these doses ?

There are two terms are important

Paracetamol to determine that :
500 mg
4X1 1- Onset of drug action ‫بدء عمل الدواء‬
It is the Time needed for agent to start it
action (a therapeutic response) in the site of
action.

2- Duration of drug action ‫مدة فعالية الدواء في‬

‫الجسم‬

Is the length of time that a drug is completely

effective to determine or how long does
drug last in the body
Indications or Therapeutic uses (‫)استخدامات الدواء‬
The diseases for which the drug is prescribed to treat or prevent,
e.g. paracetamol is analgesic and antipyretic effect .
Is Indicated relief pain and fever

Analgesic & antipyretic

Mechanism Of Action
(MOA)
( ‫)الية عمل الدواء‬
How drug work in the body to Therapeutic Dose ((‫الجرعة العالجية‬
produce its therapeutic effect It is the amount of a substance to
produce the required effect in most
patients.
 1. The Therapeutic Drug Range (Window)
Is the range of drug levels in the blood that will give the desired effect without
causing serious side effects. (The Safe blood level for optimal action)
Located in between the MEC and the level of MTC

Minimum Toxic Concentration

(MTC) The Minimum plasma level
(MTC) Minimum Toxic Concentration of drug concentration where toxic
effects start to occur.

Minimum Effective Concentration

(MEC) The minimum level of drug
concentration needed for the
desired therapeutic effect to be
present or starts.
 2. Drug Plasma Half-life (t ½)
~Elimination Half-life t½
Drug Plasma half-life (t½) Is the time taken for the plasma
concentration (amount) of a drug to be decreased to half (50% ) it’s
original value in the plasma.

Example: A patient is taking 100 mg of a drug that has a half life of 4 hours.
You are trying to determine when a 100-mg dose of the drug will be gone from
the body.
If a drug’s half-life is 4 hours, means every 4 hours the level of the drug that is
present in the body will decrease by 50 %.

4hrs 4hrs 4hrs 4hrs

4hrs
t½ 3t½ 4t½ 5t
2t½
100 mg 50 mg 25 mg 12.5 mg 6.25 mg 3.125
 3. Steady-State Concentration (Css)
‫ثبات الدواء بالدم‬
‘Steady-state’’ or plateau level is a constant serum drug level
& where expect maximum drug effect or maximum therapeutic
response or A drug’s peak effect (The highest plasma concentration)
How much the doses and When the steady state is achieved to keep the drug
within therapeutic range ?

When the steady state is

achieved?

It’s usually about after the 4th or

5th doses the steady state is
achieved or reached  Its takes
4-5 half-lives for the plasma
concentration to reach the
plateau
 4. Loading dose 5. Maintenance dose
A loading dose is an initial single high Maintenance dose is Lower dose than
dose (often maximum dose) is given to loading dose, that is given continuously
allow the drug rapidly reach the steady (at regular intervals) to keep the drug
state (A big jump in serum concentration) blood level at a steady state in order to
that is followed by with smaller doses maintain the desired therapeutic effect

When used Loading dose?

1.In drugs with long half-lives  coz
the time is taken by a drug to reach the
target steady state concentration is high.
2.In situations (in acute conditions) to
achieve a fast therapeutic effect.

We do this often times with

antibiotics, particularly in the case of really
severe infections  A loading/ bolus dose of
the drug should be administered at the
beginning of the treatment to raise the plasma
concentration of the drug within the target
range in a shorter time.
EXAMPLE :
T ½ of digoxin 36 hrs. (long T ½ )
Calculate the time need to reach Maximal therapeutic effect & the
time need for the drug to eliminate from body?
5 t ½ x36 hrs =180 hrs.
 Regular doses from digoxin around 125 -250 microgram

 In emergency cases as pt. with Herat failure & atrial fibrillation:

 Administer IV loading dose from digoxin equal 1.5 mg to rapidly reach

therapeutic levels

Remember digoxin is narrow therapeutic effect Need carful

monitoring