FUNDAMENTAL

PHARMACEUTICAL
TRAINING

CLINICAL
PHARMACOLOGY
To calculate the precise effect that a drug will
have in the body, Clinical Pharmacology has
three components

♦ Pharmacokinetics
Absorption
Distribution
Metabolism
Exceretion
♦ Pharmacodynamics
Clinical effects
Mechanism of action
♦ Drug delivery system
Drug form
Drug formulation
route of administration
 Oral cavity
Mouth

Pharynx
Tongue

Salivary
glands
Esophagus

Liver
Stomach

Pyloric
sphincter
Stomach
Gall-
bladder
Small
Pancreas intestine

Large
intestine

Rectum
Anus
Pharmacokinetics is the study of
distribution and movement of a drug to
the various compartments of the body
after absorption and its metabolism
and excretion
▼ Bioavailability of a medicinal product may be
regarded as the quantity of administered dose
which arrive in a therapeutic form at the site
where it will exert its biological action’
▼ Bioavailability of active ingredient of
medicinal product is dependent on it
Absorption, Distribution, Metabolism, and
Excretion.
Bioavailability is often expressed in
%age of oral Vs IV & IV =100%)
▼ Absorption may be ▼ Metabolism the drug may
influenced by the drug then be chemically changed by
formulation or factors as the body into other, usually
acidity alkalinity and gut smaller, molecules, or
metabolites before excretion.
movement. Sometimes these metabolites are
▼ Distribution drug vary active in their own right.

in speed in which they ▼ Excretion most drugs are

penetrate cells and in the excreted in the urine, usually as
extent to which they bind metabolites. Some however, may
be eliminated in the bile, from
to blood proteins. Some are the gut wall, or, in the case of
more concentrated in some anesthetics from lungs
certain tissues.
 Bile

Liver

Gall- Stomach
bladder

Bile

Duodenum of Acid chyme

small intestine

Pancreas
 FIRST PASS EFFECT
▼ the first pass effect can be influence a drug’s bioavailability. when a
drug is absorbed orally the greater part is first carried to the liver via
portal circulation. if the drug is one that is normally broken down in
the liver, by the time it reaches the systemic circulation the amount
available at the site of action is considerably less than that absorbed.
This is known as (first pass) effect and must be taken into account
when considering relative dosage.
▼ With highly bioavailable drug, a good amount of administered dose
reaches the blood, increasing the chance of an optimum therapeutic
effect.
▼ The peak serum drug concentration is the maximum amount of drug
achieved in the blood and must reach therapeutic levels to have an
effect. In chronic conditions the aim of dosing regimes is to achieve
a steady state concentration maintaining serum drug concentrations
at a therapeutic level
 T½ HALF - LIFE
▼ The half-life of a drug is the time taken for the
concentration to fall by 50% from peak values. It is a
resultant of distribution , metabolism and excretion and
may be complex.

oR
▼ Half –life time required for one half of the concentration of drug in
the blood to be eliminated from the body.
▼ Precise knowledge of bioavailability and pharmacokinetics may be
critically important for antibiotics used in the treatment of life-
threatening infections but it is of less consequence for mild
analgesics used for symptomatic relief of pain. It is particularly
important in designing dosage schedules and avoiding unnecessary
peaks ad troughs in blood concentrations
 PHARMACODYNAMICS

▼ It is the study of the activity of a drug both in

nature and size of response once it reaches the
site of action.
▼ Plasma monitoring of drug levels is critical for products with narrow
therapeutic index.
▼ Many drugs are thought to produce their effects by combining with
some enzymes, cell membranes or other cell components. this
interaction is thought to alter the function of the cell, thereby
starting a series of biochemical and physiological changes by which
the drug is characterized. The initial interaction is the action of drug,
the subsequent events are correctly termed the drug’s effects.
 MODE OF ACTION OF DRUGS

▼ DRUG STRUCTURE AND ACTIVITY: The actions

of drugs are closely tied up with their molecular structure, very often slight
molecular changes result in major changes in the drug’s properties. Research
into variations in the drug structures has often lead to valuable new drugs.
▼ RECEPTORS: the part of cell on which the drug acts is
known as receptor. amongst the best known are the alpha and beta-
adrenergic receptors. Receptors may not necessarily be present on the
surface of cell; they may well be an internal component.
▼ SITE OF ACTION: some drugs act only on certain cells, tissues or
organs and their effect is localized. others act on most cells of the body in a
general way. this can be explained by selective distribution through out the
body, but this is by no means always the reason. drugs can act
extracellularly, at the surface cell , or intracellularly. drugs may produce
their effect indirectly by blocking the action of another substance.
drugs can act directly on effectors cells. for example, blood pressure may be
lowered directly by inhibition of vascular smooth muscle.
▼ BIOCHEMISTRY OF DRUG ACTION:
The detailed biochemical action of many drugs is not
known. in some however it is. Antibiotics and
chemotherapeutic agents act by selectively toxic to
bacteria. In infectious diseases the cause is invasion of the
body by microorganisms. Fortunately the biochemistry of
the microbial cell is sufficiently different drugs to be
given which destroy the invader, but don’t harm the host.
▼ The use of drugs with a selective action on abnormal
rapidly dividing cells offers an approach to the problem of
alleviating the malignant disease. These are sometime
referred to as cytotoxic drugs. Drugs presently available
tends to attack normal growing cells as well as cancerous
cells. Their scope is therefore limited as toxic effect
(death to normal cell) limits their therapeutic use.
 MEASURING THE DRUG EFFECTS

▼ A SPECFIC DRUG’S EFFECT CAN BE MEASURED

BY PLOTTING A DOSE-RESPONSE CURVE. THIS
ILLUSTRATES THE INTENSITY OF EFFECT, OR
EFFICACY, AT DIFFERENT DOSES AND ALSO
IDENTIFIES THE POTENCY OF A DRUG – THE
REALTIVE AMOUNT IS REQUIRED TO PRODUCE A
SPECFIC EFFECT.
▼ THE MINIMUM EFFCETIVE DOSE IS THE LOWEST
DOSE THAT WILL PRODUCE AN APPRECIABLE
EFFECT.
▼ THE MINIMUM EFFECTIVE DOSE IS REACHED
WHEN INCREASING THE DOSE FAILS TO
INCREASE THE CLINICAL EFFCET.
▼ DOSE RESPONSE CURVE PROVIDE A USEFUL
BASIS FOR COMAPRING DRUGS WITH SIMILSR
EFFECTS TO ASSESS RELATIVE POTENCY AND
EFFICACY.
 ADVERSE REACTIONS
▼ The choice of appropriate pharmacological
therapy is based on drug efficacy and drug safety.
Drugs exert their beneficial effects by altering
biological processes within the body. this can
lead to unwanted, or non-therapeutic effects. Side
effects of drug other than those required for
therapeutic purposes which occur in normal
dosage range. toxic effects are usually dangerous
which normally occur outside the normal
therapeutic range.
▼ The therapeutic index or therapeutic ratio is used
to describe the relative safety vs. efficacy of a
drug.
 Following are the examples of factors ,
which may cause adverse reaction
▼ Variation in therapeutic response
Body weight
Individuals at the extreme of age (infants, elderly)
▼ Extreme susceptibility to drugs
salicylates
▼ Abnormally in patient causing relative over dosage,
either from physiological change, or enhancement of
effect.
▼ Normal but unpleasant pharmacological effects.
▼ Undesirable local effects
▼ Secondary effects: these occur as an indirect
consequence of the activity of the drug.
▼ hypersensitivity and allergy
▼ genetic abnormalities.
▼ direct toxic effects e.g. hepatotxicity and
nephrotoxicity: because drugs are concentrated in the
liver and the kidney.
▼ Teratogenic effects are those which cause
adverse effects to the developing fetus in a drug
which crosses from the maternal to fetus
circulation.
▼ Other toxic effects on the foetus and the new
born.
▼ Drug interaction resulting from the introduction
of more powerful drugs and increasing use of
combining therapy. When two drugs are given
together, the action of one drug upon the other
may lead to an increase, reduction or
modification of effect, sometime with more
serious results.
These interactions may cause by alterations to the
absorption, metabolism or excretion of one or
both drugs