Practical pharmacology. Part 1

1.

Practical pharmacology
Part 1

2.

What is pharmacology?
pharma ology
It is science of the drugs
Drug
Science

3.

What is Drug?
It is the chemical that affect
physiological body function
through interaction with
receptors

4.

What is Drug?
It is the chemical that affect
physiological body function
through interaction with
receptors

5.

A
Response

6. Forces involved in D-R interaction

Covalent bonds
Ionic bonds
Hydrogen bonds
Vander waals bonds

7. Forces involved in D-R interaction

Covalent bonds
Ionic bonds
Hydrogen bonds
Vander waals bonds

8. Forces involved in D-R interaction

Covalent bonds
Strong
irreversible
Alkylating agents

9. Forces involved in D-R interaction

Covalent bonds
Ionic bonds
Hydrogen bonds
Vander waals bonds

10. Forces involved in D-R interaction

Ionic bonds
common
Affected by pH

11. Forces involved in D-R interaction

Covalent bonds
Ionic bonds
Hydrogen bonds
Vander waals bonds

12. Forces involved in D-R interaction

Hydrogen bonds
?

13. Forces involved in D-R interaction

Covalent bonds
Ionic bonds
Hydrogen bonds
Vander waals bonds

14. Forces involved in D-R interaction

Vander waals bonds
?

15. Receptors types

On cell membrane
Intracellular
GPCR
Receptor with intrinsic ion channel
Enzyme linked receptors

16. Receptors types

On cell membrane
Intracellular
Transcription factors

17.

18. Drug-Receptor Interaction

D+ R
k1
DR
K1 is association rate constant

19. Drug-Receptor Interaction

DR
k2
D+R
K2 is dissociation rate constant

20. Drug-Receptor Interaction

At equilibrium
D+ R
k1
k2
DR

21. Drug-Receptor Interaction

At equilibrium
[D] [R] k1
= [DR]
k2

22. Drug-Receptor Interaction

At equilibrium
[D] [R] k1
= [DR]
k2

23. Drug-Receptor Interaction

k
2
kd
k1
[R] [D]
=
[DR]
Kd (dissociation equilibrium constant)
is conc. of the drug that
bind 50 % of the receptors

24. kd

• It is a measure of drug affinity
• Its units is conc. units
Drug A
Has higher Kd than
Drug B
Which one has a higher affinity ?

25. Important concepts

• Affinity
• Efficacy
• potency

26. Affinity

• The ability of the drug to bind to the
receptor
• Measured by Kd
• Both agonist and antagonist have
affinity to their receptors

27. Efficacy

• It is the ability of the drugs to elicit
pharmacological effect
• Measured by Emax
• Agonist has efficacy and antagonist has no
efficacy

28. potency

• The ability of the drug to produce
response at lower conc.
• Measured by ED50

29. The drug may be

• Agonist
• Antagonist
• Partial agonist

30. Agonist

• Has affinity and efficacy
• IA=1

31. Antagonist

• Has affinity but no efficacy
• IA=0

32. Partial agonist

• Has affinity and efficacy
• IA=0-1

33. antagonism

• Physical
• Chemical
• Physiological
• Pharmacokinetic
• pharmacodynamic

34. Chemical antagonism

• One drug reacts chemically with an active
drug to form an inactive compound,
It involves precipitation, complexation,
neutralization redox reaction.
Intended treatment of heavy metal
toxicity by complexation with chelators.
Incidental complexatin of tetracycline
calcium in dairy products.

35. Physiological antagonism

• 2 drugs act on different sites in the same
or different system.
• a- Intended Norepinephrine in case of
anaphylaxis.
b-Incidental patient taking barbiturates
for anxiety, co-administration of antitussive (ephedrine).

36. Pharmacokinetic antagonism (ADME)

• a- Intended forced alkaline diuresis in
management of barb Poisoning.
• b- Incidental Barb. + other drugs
Induction of the metabolism of concomitant
drugs, their decrease plasma level.

37. Pharmacodynamic antagonist

Competitive
Reversible
Surmountable antagonism
Ach. + atropine
Non-competitive

38. Pharmacodynamic antagonist

Competitive
Reversible
Non-competitive
Irreversible
Non-surmountable antagonism
Ach. + succinylcholine

39.

X
An
A

40.

An
X
A

41. Dose-Response Curve

• What ?
• Types ?

42.

Response
Hyperbolic curve
Dose

43.

Response
Sigmoidal shaped curve
Log dose

44.

Response
Linear
Log dose

45.

Response
Wide range of doses
Log dose

46.

Response
ED50 can be calculated
ED50
Log dose

47. Graded DRC

• Depends on graded response
• ED50 ?
The dose that give 50% of maximal response

48.

Response
50%
ED50
Log dose

49. Quantal DRC

• Depends on quantal response
• ED50 ?
The dose that give response in 50% of population

50.

%Response
50%
ED50
Log dose

51. ED50

• Compare between potencies of two
drugs
Drug A
Has higher ED50 than
Drug B
Which one is more potent ?

52. ED50

• Calculation of the therapeutic index
LD50
TI
=
ED50
Is a measure of drug safety

53.

Response
50%
LD50
ED50
Log dose
TI

54.

Response
50%
ED50
Log dose
TI
LD50

55.

Drug A
Has higher TI than
Drug B
Which one is more safer ?

56. DRC & antagonists

DRC & antagonists
Response
Competitive reversible antagonist
Log dose

57. DRC & antagonists

DRC & antagonists
Response
Competitive irreversible antagonist
Log dose

58. DRC & antagonists

DRC & antagonists
Response
non-competitive antagonist
Log dose

59. Important notes

Parrallism
Indicate competition

60. Important notes

Emax
Indicate reversibility

61.

Thank you