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Mr Thabiso Tlaila
MSc Pharmacology
Department of Pharmacology
Discipline of Pharmaceutical Sciences
University of KwaZulu-Natal
tlailat@ukzn.ac.za
INTRODUCTION TO PHARMACOLOGY
Drug receptors:
■ Molecular components of the body with which a drug
interacts to bring about its effect
Drug Metabolism
In order to reach its receptor and bring about a
biological effect, a drug molecule must travel from the
site of administration to the site of action.
a) Absorption of drugs
■ Drugs usually enter the body at sites remote from
the target tissue or organ and thus require transport
by the circulation to the intended site of action. To
enter the blood stream, a drug must be absorbed
from its site of administration (unless if its
administered IV)
Drug Metabolism cont…
b) Transport of a drug from the GIT
■ Depending on their chemical properties, drugs may
be absorbed from the GIT by either passive diffusion
or active transport.
c) Distribution of drugs
■ Following absorption or systemic administration into
the bloodstream, a drug distributes into interstitial
and intracellular fluids
Drug Metabolism cont…
CNS Distribution
■ Distribution of drugs into the CNS from the blood is
unique, brain capillary endothelial cells have
continuous tight junctions- this is called the blood
brain barrier (BBB). Thus, drug penetration into the
brain depends on transcellular transport.
■ Lipid solubility of a drug is an important determinant
of its uptake by the brain
■ The more lipophilic a drug: the more likely it is to
cross BBB
Drug Metabolism cont…
CNS Distribution
Drug Metabolism cont…
Distribution to the Placenta
■ The transfer of drugs across the placenta is of critical
importance because drugs may cause anomalities in
the developing fetus.
■ Lipid solubility, extent of plasma binding and degree of
ionization of weak acids and bases are important
general determinants in drug transfer across the
placenta
■ The placenta is not an absolute barrier to all drugs as a
number of influx transporters are present- the fetus is
thus to some extent exposed to all drugs taken by the
mother
Drug Metabolism cont…
d) Metabolism of drugs
■ The lipophilic characteristics of drugs that promote
their passage through biological membranes and
subsequent access to their site of action also serve
to hinder their excretion from the body
■ The metabolism of drugs into more hydrophilic
metabolites is essential for their elimination from
the body, as well as for termination of their biological
and pharmacological activity
Drug Metabolism cont…
d) Metabolism of drugs
■ Metabolism of a drug sometimes terminates its
action – metabolized to biologically inactive
derivatives
■ Orally administered drugs are metabolized before
they enter systemic circulation – first-pass effect
Drug Metabolism cont…
d) Metabolism of drugs
Drug Metabolism cont…
Pro-drugs
■ are inactive when administered and must be
metabolized in the body to become active
■ Many drugs are active when administered and also
have active metabolites.
■ Some drugs are not modified by the body and
continue to act until they are excreted.
Drug Metabolism cont…
Drug Metabolism cont…
e) Elimination of drugs
■ Drugs are eliminated either unchanged by the process of
excretion or converted to metabolites
■ Excretory organs eliminate polar compounds (more
hydrophilic) efficiently than lipophilic compounds
■ Lipophilic drugs are not readily eliminated until they are
metabolized to more polar compounds
■ The kidney is the most important organ for excreting drugs
and their metabolites
■ Substances excreted in the feces are principally unabsorbed
orally ingested drugs or drug metabolites excreted either in the
bile or secreted directly into the intestinal tract and not
reabsorbed
Drug Metabolism cont…
e) Elimination of drugs
■ Excretion of drugs in breast milk is important as
drugs are potential sources of unwanted
pharmacological effects on the baby.
■ Excretion from the lung is important for the
elimination of anesthetic gases.
■ Excretion of drugs into sweat, saliva, and tears is
quantitatively unimportant
Pharmacokinetics
Pharmacokinetics is the effect of biological systems on drugs. It
deals with the processes of absorption, distribution and
elimination.
a) Dosage regimens
■ A dosage regimen is a plan for drug administration over a
period of time.
■ An appropriate dosage regimen results in the achievement of
therapeutic levels of the drug in the blood without exceeding
the minimum toxic concentration
■ Ideally, the dosing plan is based on knowledge of both the
minimum therapeutic and minimum toxic concentrations of
the drug as well as the clearance and volume of distribution
Pharmacokinetics cont…
Loading dose:
■ If the therapeutic concentration must be achieved
rapidly and the volume of distribution is large, a loading
dose may be needed at onset of therapy
Maintenance dose:
■ If it is important to maintain a concentration above the
minimum therapeutic level at all times, either a larger
dose may be given at long intervals or smaller doses at
more frequent intervals.
■ If the difference between the toxic and the therapeutic
concentration is small, then smaller doses should be
administered more frequently
Pharmacokinetics cont…
b) Adjustment of dosage when elimination is altered by disease
■ Renal disease or reduced cardiac output often reduces the
clearance of drugs that depend on renal function
■ Impairment of hepatic clearance occurs when liver blood flow is
reduced as in heart failure.