Practical pharmacology. Part 3. Drug response

1.

Practical pharmacology
Part 3

2.

Drug response

3. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

4. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

5.

A
Response

6. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

7.

Side effects
A
Response
Side effects

8. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

9. Intolerance

Exaggerated response
(magnified pharmacological response)
resembling an overdose of a drug but at normal dose.
It is commonly observed in children

10. Causes

Pharmacokinetic
Renal insufficiency patients taking digoxin
Infants due to underdeveloped renal, hepatic function,
immature BBB, or low level of plasma proteins

11. Causes

Pharmacodynamic
Thyrotoxic patients, epinephrine

12.

Thyroxine

13.

Toxicity

14. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

15. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

16. Idiosyncrasy

Genetically determined
abnormal response to a drug

17. Example 1

Succinyl choline in
pseudocholine esterase deficiency subjects

18. Example 2

Chloroquine, salicylates, sulfa drugs in
glucose 6-phosphate dehydrogenase
deficiency subjects

19.

The Glutathione Redox System
x
Glutathione (GSH)
SH
SH
FAD
Glutathione
Reductase
x
NADPH + H+
NADP+
Glucose6-phosphate
Glutathione disulfide (GSSG)
x
Glucose-6-P
Dehydrogenase
6-Phospho
gluconolactone

20. Example 3

Isoniazide in slow, fast acetylators

21.

Slow acetylator
Isoniazide
Isoniazide
metabolites
Fast acetylator

22. Drug reponse

Normal therapeutic response
Side effects
Exaggeration of pharmacological effect
Toxicities
Abnormal response
Tolerance

23. Tolerance

Decreased therapeutic efficacy
on repeated administration over
days or months.

24. Tachyphylaxis (desensitization)

Rapidly developing tolerance

25. Resistance (Refractoriness)

Loss of therapeutic efficacy

26. Types of tolerance

Acquired
Congenital

27. Acquired tolerance

• Due to repeated administration of a
drug
Pharmacokinetic
Pharmacodynamic

28. Pharmacokinetic tolerance

barbiturates cause tolerance
of
concomitantly administered drugs

29. Pharmacodynamic tolerance

• Conformational changes in receptor
due to long use of agonist, or
disruption of receptor effectors
linkage, or down regulation of
receptor
• Exhaustion of mediators in case of
amphetamine

30.

EFFECTOR
RESPONSE

31. Congenital tolerance

Natural inborn tolerance to certain drug
which has been never used before

32. Congenital tolerance

Racial
Ephedrine is not effective mydriatic in
black colored people

33. Congenital tolerance

Species
Rabbits
tolerate large quantities of
atropine without toxicity

34. Congenital tolerance

Individual

35.

Kymograph

36.

Organ bath
Drum
Water bath

37. Conditions

Physiological solution
Temperature
Aeration

38. Physiological solution

NaCl & KCl
CaCl2
Mg salt
NaHCO3
NaH2PO4
Glucouse
For isotonicity

39. Physiological solution

NaCl & KCl
CaCl2
Mg salt
NaHCO3
NaH2PO4
Glucouse
Contractility

40. Physiological solution

NaCl & KCl
CaCl2
Mg salt
NaHCO3
NaH2PO4
Glucouse
Contractility

41. Physiological solution

NaCl & KCl
CaCl2
Mg salt
NaHCO3
NaH2PO4
Glucouse
Buffering action

42. Physiological solution

NaCl & KCl
CaCl2
Mg salt
NaHCO3
NaH2PO4
Glucouse
Nutrition

43. Temperature

36-37˚C

44. Aeriation

Pure O2
Carbogen (90% O2 + 10% CO2)
Air

45. Our isolated organ

• Rabbit intestine
• Tyrode‘s solution
• Temperature 37˚C
• Aeration by air pump

46.

47.

Myogenic contraction
0.1
wash
0.2
0.3
0.4

48.

Donot forget

49.

50.

Thank you