2. General pharmacology
By
Mohamad-Hesham Daba,MD,PhD
Associate professor of
Clinical pharmacology
3. PHARMACOGENETICS
• Pharmacogenetics refers to the study of
inherited differences (variation) in drug
metabolism and response.
• Pharmacogenomics refers to the general
study of all of the many different genes
that determine drug behavior.
• N.B.The distinction between the two terms is considered
arbitrary, however, and now the two terms are used
interchangeably.
4. A. Heritable conditions causing
increased or toxic drug response
1. Hereditary methemoglobinemia
2. Glucose -6- phosphate
dehydrogenase deficiency
3. Malignant hyperthermia
4. Pseudo cholinesterase deficiency
5. Acetylator phenotypes
5. Hereditary methemoglobinemia
• It is due to deficiency of
methemoglobin reductase
enzyme responsible for
reduction of oxidized Hb
(methemoglobin) to reduced
Hb.
• When the affected individual
takes oxidizing drug (e.g.
nitrates), much of his Hb is
converted to methemoglobin
and accumulates in his blood
→ cyanosis.
•
6. Glucose -6- phosphate dehydrogenase
deficiency
• G-6-PD is an important source of
reduced NADPH which maintains
glutathione in the RBCs in its
reduced form. Reduced
glutathione keeps Hb in the
reduced (ferrous) form.
• Individuals with deficiency in G-6-
PD enzyme may suffer acute
hemolysis if they are exposed to
oxidizing drugs e.g. nitrates,
antimalarial drugs, and others.
7. Malignant hyperthermia
• It is rare genetic disorder of
skeletal ms characterized by
sudden release of stored Ca2+
from the sarcoplasmic
reticulum
• when the patient is exposed to
certain types of general
anesthetics leading to
generalized ms rigidity, high
fever, and lactic acidosis
• (could be treated by dantroline)
8. Pseudocholinestrase deficiency
• Succinylcholine is a neuromuscular
blocker metabolized by pseudo-
cholinestrase enzyme.
• Some individuals have deficient PsChE,
when they take succinylcholine, severe
ms paralysis and death from paralysis of
respiratory ms may occur due to lack of
succinylcholine metabolism
(succinylcholine apnea).
Treated by plasma transfusion*
9. Acetylator phenotypes
• Two types of abnormal acetylators could be
detected; Rapid acetylators and slow acetylators:
• Isoniazide (first line antituberculus drug)
causes two distinct forms of toxicity :
- peripheral neuropathy whose incidence is greater in
slow acetylators due to interference with pyridoxine
metabolism
- acute hepatocellular necrosis occurs more commonly in
rapid acetylators and is related to formation of a
hepatotoxic metabolite.
10. B. Heritable conditions causing
:decreased drug response
• Resistance to
cumarin
anticoagulant
• Resistance to Vit. D
• Resistance to
mydriatics:
11. Resistance to cumarin anticoagulant
• Those patients have a
variant of the enzyme that
converts Vit.K to its
reduced (active) form.
Cumarins normally
inhibits this step.
• Presence of this variant
of the enzyme
antagonizes the effect of
cumarines and these
patients needs 20 times
the usual dose to get the
response.
12. Resistance to Vit. D
• True end organ
resistance due to
mutation of vit D
receptors.
• Individuals who
exhibit this condition
develop rickets that
responds only to huge
doses of Vit. D.
14. Pharmacogenetics
• The risk of neurotoxicity from
isoniazid ( used for tuberculosis)
is higher in Egyptians than in Eskimo
populations.
Questions:
• Give an explanation?
• What is proper treatment for neurotoxicity?
• When hepatotoxicity occur?
15. Pharmacodynamics
• A 70-year –old man has been taking
beta-blockers for many years for his
angina (stable). He develops severe
intermittent claudication and his legs
were cold, and his doctor stops the
B.B suddenly. His angina worsens
within days, and he is admitted to
hospital with myocardial infarction.
• Give an explanation?
16. Pharmacodynamics
• A 30-year-old man has been
abusing heroin for many years.
Gradually, the dose needed to
achieve the desired effect has
increased. He was found dead in
the street.
• Give an explanation?
17. Match the following
• A-Median lethal dose (LD50)
• b-Therapeutic index (T.I)
• c- Full agonist
• d- Partial agonist
• 1- LD50 / ED50 ratio(…..)
• 2-maximum response obtained from tissue(…..)
• 3-can not produce maximal response(…..)
• 4-can produce maximal response(…..)
• 5-Dose kills 50% of experimental animals (…..)
