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Pharmacology and General
principles
Asmaa A.H.
Outline
• General Pharmacology.
• Source of Drugs.
• How drugs act: molecular aspects.
Receptor
Enzyme
Ion channels
Transporters
• Intrinsic activity.
Pharmacology
Pharmacology is the study of drugs and its origin, chemical
structure, preparation, administration, action, metabolism
and excretion.
The study of drugs that alter functions of living organism.
A drug is a chemical applied to physiological system that
affect its function in a specific way.
Pharmacokinetic: it mean movement of drug within body it
include; absorption, distribution, metabolism, excretion.
Pharmacodynamics: it is study of drugs-their mechanism
of action, pharmacological action, adverse effects.
Source of Drugs
The different sources of drugs are:
a. Plant:
i. Alkaloids :e.g. morphine, atropine
ii. Glycosides: e.g. Digoxin
b. Animals: Insulin, heparin.
c. Minerals: Ferrous sulphate.
d. Microorganism: Penicillin.
e. Semisynthetic: Hydromorphone.
f. Synthetic: e.g. aspirin, paracetamol.
Drugs are also produced by genetic engineering (DNA
recombinant technology) e.g human insulin, Growth hormone.
How drugs act: molecular aspects
It is a special form of drug delivery system where the
pharmacologically active agent or medicament is
selectively targeted or delivered only to its site of
action. The therapeutic response of a drug depend upon
the interaction of drug molecule with cell on cell
membrane related biological events, primary drug
targets :
• Receptor.
• Enzyme.
• Carrier protein.
• Ion channel.
ReceptorAre the sensing elements in the system of chemical
communications that coordinates the function of all the
different cells in the body.
Receptors form a key part of the system of chemical
communication that all multicellular organisms use to
coordinate the activities of their cells and organs.
Types of the receptors
1-Ligand-gated ion channels (Ionotropic receptors).
2-G-Protien Coupled receptors (Metabotropic).
3-Kinase-linked receptors.
4-Nuclear receptors.
EnzymesMany drugs are targeted on enzymes, the drug molecule
is a substrate analogue that act as competitive inhibitor
of the enzyme (e.g. Captopril, acting on ACE). In other
cases the binding is irreversible and non-competitive
(e.g. Aspirin, acting on Cox). Some drugs may require
enzymatic degradation to convert them from an
inactive form (prodrug) to an active form (e.g. Enalapril
is converted by esterase to enalaprilat which its inhibit
ACE). On the other hand enzymatic conversion of the
drug metabolite to a reactive metabolite (e.g.
Paracetamol causes liver damage).
Ion channels
Ion channel are essentially gateways in the cell
membranes that selectively allow the passage of
particular ions and that are induce to open or close by a
variety of mechanism. Two important types are ligand-
gated ion channel and voltage- gated channels. When
one or more agonist are bound, since agonist binding is
needed to activate them. Voltage-gated channels are
gated by changes in the transmembrane potential rather
than by agonist binding.
Transporters
The movement of small organic molecules across cell
membranes through transport protein because permeating
molecules are often too polar (i.e insufficiently lipid-
soluble) to penetrate lipid membranes on their own. Many
such transporters are known: those responsible for transport
of ions and many organic molecules across renal tubule,
intestinal epithelium and BBB, transport of Na+ and Ca+2
out of cells, the uptake of NT precursors (such as choline)
or of NT themselves (such as amines and amino acids) by
nerve terminals and the transport of drug molecules and
their metabolite across cell membrane and epithelial
barriers.
• Agonist: Agent which activates a receptor to produce an effect similar to that of the physiologic signal molecule (e.g. Phenylpherine).
• Partial agonist: Agent which activates a receptor to produce a sub maximal effect (e.g. Buspirone).
• Inverse agonist: Agent bind on same receptor of agonist produce an effect in the opposite direction to that of the agonist (e.g. Benzodiazepine).
• Antagonist: Agent which prevents the action of an agonist on a receptor but doesn’t have any effect of its own receptor (e.g. amlodipine).
• Competitive antagonist: If both agonist and antagonist bind to the same binding site on the receptor they are said to be competitive so prevent an agonist from binding to its receptor. (e.g. Naloxone).