Introduction to

pharmacology -
Pharmacokinetics

Assist. Prof. Dr. Dyary Hiewa, Ph.D.

dyary.othman@univsul.edu.iq
Objectives
 Introduction to pharmacology

 Definition of pharmacokinetics

 Illustration of the processes involved in

pharmacokinetics of drugs
Pharmacology is the study of chemicals
—drugs—on living tissues and how those
chemicals help diagnose, treat, cure, and
prevent disease or correct the
pathophysiology of living tissues
Pharmacology
Derived from two Greek words:
 Pharmakon = drugs
 Logos = science
Drug
A chemical substance used in the treatment,
cure, prevention, or diagnosis of disease or
used to otherwise enhance physical or mental
well-being.
Major areas of study in
pharmacology
Pharmacology

1. Pharmacokinetics = what the body does to the

drug

2. Pharmacodynamics = what the drug does to the

body
pharmacokinetics
Studies:
1. Absorption
2. Distribution
3. Metabolism
4. Excretion

ADME
 Routes of drug administration

Enteral Parenteral Topical

Oral
Intravenous
Sublingual
Intramuscular

Rectal Subcutaneous

Inhalation

Epidural
Intraperitoneal
Routes of drug administration
Determined by:
 properties of the drug (e.g., water or lipid
solubility, ionization)

 therapeutic objectives (e.g., the desirability of a

rapid onset, the need for long-term treatment,
or restriction of delivery to a local site)
Absorption of drugs
 The transfer of a drug from the site of
administration to the bloodstream.

 Routes of administration other than

intravenous may result in partial absorption
and lower bioavailability.
The rate and extent of absorption depend on:
1. The environment where the drug is absorbed
2. Chemical characteristics of the drug
3. The route of administration
Mechanisms of drug
absorption

1. Passive diffusion

2. Facilitated diffusion

3. Active transport

4. Endocytosis and exocytosis

 Factors influencing drug absorption
1. pH
2. Blood flow to the absorption site
3. Total surface area available for absorption
4. Contact time at the absorption surface
Effect of pH on drug absorption
Most drugs are either weak acids or weak bases:

 Acidic drugs (HA) release a proton (H+), causing

a charged anion (A−) to form:

 Weak bases (BH+) can also release an H+.

However, the protonated form of basic drugs is
usually charged, and loss of a proton produces
the uncharged base (B):
 pKa (ionization constant)

 The pH at which the protonated and non-protonated

(ionized and non-ionized) forms are equal

concentration of ionized form = concentration of non-ionized

form
Ionization constants (pKa) of some common
drugs

Weak acids Weak bases

Drug pKa Drug pKa

Ampicillin 2.5 Atropine 9.7
Aspirin 3.5 Epinephrine 8.7
Furosemide 3.9 Lidocaine 7.9
Henderson Hasselbalch Equation
 The lower the pKa of a drug, the more acidic
it is. Conversely, the higher the pKa, the more
basic is the drug.
Blood flow to the absorption site
 The intestines receive much more blood flow
than the stomach, so absorption from the
intestine is favored over the stomach.
 Total surface area available for
absorption

The intestine has a surface area about

1000-fold that of the stomach,
making absorption of the drug across
the intestine more efficient
Contact time at the absorption
surface

If a drug moves through the GI tract

very quickly, as can happen with severe
diarrhea, it is not well absorbed.
Bioavailability
 It is the rate and extent to which an
administered drug reaches the
systemic circulation.

 For example, if 100 mg of a drug is

administered orally and 70 mg is
absorbed unchanged, the
bioavailability is 70%.
Determination of bioavailability
 Factors influencing bioavailability

1. First-pass hepatic metabolism

2. Solubility of the drug

3. Chemical instability

4. Nature of the drug formulation

 DRUG DISTRIBUTION
It is the process by which a drug
reversibly leaves the bloodstream
and enters the interstitium
(extracellular fluid) and the tissues
 DRUG DISTRIBUTION
The distribution of a drug from the plasma to the
interstitium depends on:

1. Cardiac output and local blood flow

2. Capillary permeability

3. The tissue volume

4. The degree of binding of the drug to plasma and tissue

proteins

5. The relative lipophilicity of the drug

Volume of distribution
the fluid volume that is required to
contain the entire drug in the body
at the same concentration measured
in the plasma
 Drug half-life
 It is the time a drug takes to
reduce the plasma drug
concentration by half.

 Drugs with higher Vd have a

longer half-life and extended
duration of action.
 DRUG METABOLISM

 Metabolism leads to formation of products with

increased polarity, which allows the drug to be
eliminated.
Reactions of drug metabolism
 Phase I : oxidation, reduction, hydrolysis, etc.

 Phase II: conjugation with glucuronic acid, acetic acid,

etc.
Kinetics of drug
metabolism
 Zero-order kinetics

 First-order kinetics
DRUG CLEARANCE (ELIMINATION)

 the most important route of elimination is the

kidney

 Patients with renal dysfunction are at risk for drug

accumulation and adverse effects

 Drug clearance may also occur via the intestines,

bile, lungs, and breast milk, among others
THANK YOU