Mechanisms of Drug Actions by
Drugs act within the cell by modifying normal biochemical reactions. Enzyme
inhibition may be reversible or non reversible; competitive or non-competitive.
Antimetabolites may be used which mimic natural metabolites. Gene functions may
1_Direct Enzyme Inhibition:
Inhibition caused by drugs may be either reversible or irreversible.
Reversible inhibitors bind to enzymes with non-covalent interactions such as
hydrogen bonds, hydrophobic interactions and ionic bonds.
It is divided into:
Competitive inhibitors are often similar in structure to the real substrate ,the
substrate and inhibitor cannot bind to the enzyme at the same time.
This type of inhibition can be overcome by sufficiently high concentrations of
The inhibitor can bind to the enzyme at the same time as the enzyme's
is a form of mixed inhibition where the binding of the inhibitor to the enzyme
reduces its activity Irreversible inhibition
irreversible inhibitors usually covalently modify an enzyme, and inhibition cannot
therefore be reversed. Irreversible inhibitors often contain reactive functional
groups such as: nitrogen mustards, aldehydes, haloalkanes, alkenes, Michael
acceptors, phenyl sulfonates fluorophosphonates
Irreversible inhibitors are generally specific for one class of enzyme and do not
inactivate all proteins.
And these are examples of drugs that inhibit different enzymes:
Substrate Enzyme Products Inhibitor Uses
Acetylcholine Acetylcholine Choline; Neostigmine Myasthenia gravis and to
esterase acetate reverse neuromuscular
Arachidonate Cyclooxygenase Prostanoids Aspirin Heart disease and
Angiotensin (AT)I AT converting AT II Captopril Hypertension, heart failure,
Hypoxanthine Xanthine oxidase Uric acid Allopurinol Gout
HMG-CoA HMG-CoA Mevalonic Simvastatin To lower blood cholesterol
Folate Dihydrofolate Tetrahydrof Trimethoprim With cotrimoxazole as
reductase olate antibacterial
Thymidine Viral reverse Zidovudine HIV infection
Deoxyribonucleotides DNA polymerase DNA Cytarabine Anticancer drug
Example: Inhibition of cyclooxygenase enzyme
by some drugs.
Cyclooxygenase enzyme: responsible for production of prostaglandins
from arachidonic acid .
There are three isomers of it:
Control most of physiological function: renal function,gastric function,platelet
Responsible for production of allgesic and inflammatory prosta glandins.
Selectively inhibited by paracitamol.
Drugs acting on cyclooxygenase enzyme.
1_Non Steroid Anti Inflammatory
They are non selective inhibitors of cox1 and cox2.
So they are used as analgesic,anti inflammatory,antiplatelet aggregation and
antipyretic.but their disadvantage is Pseudoallergy,gastritis,nephrotoxicity.
Selective cox2 inhibitor.so they are used as analgesic and anti inflammatory
only.they do not cause side effects.
Selective cox3 inhibitor.it is used as analgesic,antipyretic.
b) Suppression of Gene Function:
Many drugs act as suppressors of gene function including antibiotics, fungicides,
antimalarials and antivirals. Gene function may be suppressed in several steps of protein
synthesis or inhibition of nucleic acid biosynthesis. Many substances which inhibit nucleiacid
biosynthesis are very toxic since the drug is not very selective in its action between the
parasite and host
The strategy of chemotherapy consists of exploiting the biochemical differences
between the host and parasite cells. Metabolites are any substances used or
produced by biochemical reactions. A drug which possesses a remarkably close
chemical similarity (mimic) to the normal metabolite is called an antimetabolite. The
antimetabolite enters a normal synthetic reaction by "fooling" an enzyme and
producing a counterfeit metabolite. The counterfeit metabolite inhibits another
enzyme or is an unusable fraudulent end product which cannot be utilized by the cell
for growth or reproduction. Such antimetabolites have been used as antibacterial or
Mechanism of drug action by
Various substances, including some drugs, stimulate in vivo the
activity of hepatic oxidative enzymes which metabolize drugs and
certain endogenous compounds, such as steroids and fatty acids.
An increase in the rate of metabolism of these compounds by the
so-called "drug-metabolizing enzymes" often results in an increased
rate of their elimination with a concomitant decrease in their
There are also indications that a stimulation of the
(drug-metabolizing enzymes) may have therapeutic possibilities.
For instance, in the case of infants unable to dispose of bilirubin
because of inadequately developed enzyme system, the stimulation
of the formation of the enzyme would be beneficial. The mechanism
of action of the drug-metabolizing enzymes and the mode of
stimulation of their activity by drugs are not adequately understood.
However, rapid progress is being made toward the understanding of
these complex problems.