1. General pharmacology
By
Mohamad-Hesham Daba,MD,PhD
Associate professor of
Clinical pharmacology
2. Intended learning outcomes
• Define pharmacodynamics
• Recognise targets for drug actions
• Classify drug receptors
• Identify agonist, antagonist and partial ag
• Describe graded and quantal dose response
curves
• Compare bet. affinity, potency and efficacy
• Define therapeutic index
• Discuss the clinical importance of drug
combination
3. Drug-body interactions
• Pharmacodynamic
interactions:
the effects of the drugs on the body
• Pharmacokinetic interactions:
the way in which the body handles the
drugs.
4. PHARMACODYNAMICS
• Mechanisms of drug
action:
• Body control
systems:
• Receptors
• Ion channels
• Enzymes
• Carrier molecules
5. Receptors
• Definition:
• Receptors are
• protein macromolecules on the surface or
within the cell
• that combine chemically with small
molecules (ligands)
• and produces physiological regulatory
functions.
9. • Ligand: is any molecule that can combine
with the receptors. A ligand that activates
the receptor is called agonist. A ligand that
blocks the receptor is called antagonist.
• Affinity: it is the empathy of the receptor
to the ligand. It determines the ability of the
drug to bind to receptors.
• Efficacy: it is the ability of the drug to give
certain Emax. It means the ability of the drug
to induce effevt
10. Agonist means a drug that activates the
receptors upon binding
11.
12. Pharmacologic antagonist:
means a drug that binds without activating its
receptors and thereby prevents activation by
an agonist
Receptor block may be:
Reversible antagonism (Competitive antagonism)
the antagonist effect can be overcome by increasing the
concentration of agonist
Irreversible antagonism (Non-competitive antagonism)
the antagonist effect cannot be overcome by increasing the
concentration of agonist
13. Partial agonistmeans a drug that binds to its receptor but
produces a smaller effect at full dosage than a full agonist
14. Dose response relationship curves and their
importance
• A. Graded dose-response
• Importance: 1 Calculation of the ED50 - Potency
- Equieffective doses
- Relative sensitivity
2 Calculation of the Emax. - Efficacy (intrinsic activity)
15. • Calculation of the ED50:
• ED50 is the dose that produces 50% of the maximal response in
one animal.
• Value of knowing the ED50:
• Comparing the potencies of multiple drugs.
• Comparing the equieffective doses of multiple drugs.
• Calculation of drug efficacy:
• Efficacy is the maximal response (Emax) obtained by a drug.
• Value of knowing the Emax:
• Knowing the maximal responding capacity of the organ.
• Differentiation between full agonists and partial agonists.
16. • Potency versus efficacy:
• ►Potency: it is the effect of drug in relation to its dose.
• ►Efficacy: it is the ability of the drug to give certain Emax.
• Efficacy is more important than potency because it is the
major determinant of drug effectiveness while potency has
little clinical importance because simply you can increase the
dose of a less potent drug to obtain the effect of a more potent
one (provided that it is not toxic)
17. :B. Quantal dose-response curve
• Importance:
Calculation of the ED50
(the dose that gives specific
effect in 50% of treated
group of animals)
Calculation of the LD50
(the dose that kills 50% of
treated animals)
Determination of the therapeutic
index
T.I.=LD50/ ED50
(it must be >1)
18. • The therapeutic index (also
known as therapeutic ratio) is
a comparison of the amount of a
therapeutic agent that causes the
therapeutic effect to the amount
that causes death (in animal
studies) or toxicity (in human
studies).
So, in humans
therapeutic index or ratio
=TD50/ ED50
19. Quick quiz
1.Which branch of pharmacology studies the
way drugs work in living organism?
C. Pharmacotherapeutics
D. Pharmacokinitics
E. Pharmacogenitics
F. Pharmacodynamics
G. Pharmacovigilance
20. Quick quiz
• A 55-year-old woman with congestive heart failure is to
be treated with a diuretic drug. Drugs X and Y have the
same mechanism of diuretic action. Drug X in a dose of
5mg produces the same magnitude of diuresis as 500 mg
of drug Y. This suggests that:
A. Drug Y is less efficacious than drug X.
B. Drug X is about 100 times more potent than drug Y.
C. Toxicity of drug X is less than that of drug Y.
D. Drug X is a safer drug than drug Y.
E. Drug X will have a shorter duration of action than drug Y
because less of drug X is present for a given effect.
21. Quick quiz
1. In the absence of other drug, pindolol causes an increase
in heart rate by activating beta adrenoceptors. In the
presence of highly effective beta stimulants, however,
pindolol causes a dose-dependent, reversible decrease in
heart rate. Therefore pindolol is probably:
A. An irreversible antagonist.
B. A physiologic antagonist.
C. A chemical antagonist.
D. A partial agonist.
E. A Spare receptor agonist.
22. Quick quiz
1. Which of the following provides
information about the variation in
sensitivity to the drug within the
population studied?
A. Maximal efficacy.
B. Therapeutic index.
C. Drug potency.
D. Graded dose-response curve.
E. Quantal dose-response curve.
23. Quick quiz
5. Which of the following provides
information about the largest response a
drug can produces, regardless of dose?
.A. Drug potency
.B. Maximal efficacy
.C. Mechanism of receptor action
.D. Therapeutic index
.E. Therapeutic window
24. HYPOREACTIVITY TO
DRUGS
• Tolerance: decreased response to the same dose of
the drug. The same response could be obtained by
higher doses. It occurs over a long period
• Tachyphylaxis: it is a type of tolerance, which occurs
very rapidly.
Probable mechanisms:
• Change in receptors (desensitization):
• Loss of receptors (down-regulation):
• Exhaustion of mediators:
• Increased metabolic degradation:
• Physiological adaptation:
25. HYPERREACTIVITY TO DRUGS
overshoot phenomena or hypersusceptibility or
intolerance
Up-regulation means increase number of receptors
due to prolonged exposure to the antagonist or
prolonged deficiency of the natural agonist. When the
antagonist is suddenly withdrawn, severe reaction
occurs in the form of rebound or withdrawal effects
e.g. severe tachycardia & arrhythmia can occur after
sudden stoppage of beta-blockers.
26. DRUG COMBINATION
• Summation and addition: combined effects of two drugs are
equal to the sum of their individual effects.
• Synergism or potentiation: combined effects of drugs may be
greater than the sum of their individual effects.
• Antagonism:
- Chemical antagonism:
- Physical antagonism:
- Physiological antagonism:
- Competitive antagonism:
- Non-competitive antagonism
27. • Which of the following terms best
describes the antagonism of leukotriene’s
bronchoconstrictor effect (mediated at
leukotriene receptors) by terbutaline
(acting at adrenoceptors) in a patient with
asthma?
2. Pharmacologic antagonist.
3. Partial agonist.
4. Physiologic antagonist.
5. Chemical antagonist.
6. Noncompetitive antagonist.
28. • Many drugs produce effects by
interaction with receptors. Other
cellular components with which drugs
interact to produce effects include:
2. Nucleic acids.
3. Structural proteins.
4. Enzymes.
5. Proteins involved in transport processes.
6. All of the above.
29. • Which of the following chemical
compounds produce their major
effects by binding to intracellular
receptors that bind to nuclear DNA?
2. Insulin.
3. Succinylcholine.
4. Catecholamines.
5. Opioid peptides.
6. Steroids.
30. The term that refers to the rapid
diminution of responsiveness
following administration of a drug
is:
2.hyporeactivity
3.idiosyncratic drug response
4.tolerance
5.drug inactivation
6.tachyphylaxis
31. MATCH the pharmacologic term in the answers below with the most
:appropriate definition of the term in the items
• Efficacy
• Potency
• Tolerance
• Therapeutic index
• Intolerance
A) Decreased response to the same dose of the drug.
B) When the antagonist is suddenly withdrawn, severe reaction occurs in the
form of rebound or withdrawal effects
C) This is the maximal response obtainable by a drug treatment
D) This is the ratio of the toxic dose to the therapeutic dose
E) This is the amount of drug required to produce a desired effect
