1. Introduction to Pharmacology
อ. ภญ. ปวิตรา พูลบุตร
Pawitra Pulbutr
B.Pharm (Hon.), M.Sc in Pharm (Pharmacology)

2. Objectives เข้าใจความหมายของเภสัชวิทยา
อธิบายความหมายของเภสัชจลนศาสตร์และเภสัชพลศาสตร์
เข้าใจถึงการออกฤทธิ์ของยาโดยการจับกับ Receptor, ความหมายของAffinity และ Efficacy
เข้าใจความหมายของ Agonist, Partial agonist และ Antagonist พร้อมทั้งแยกความแตกต่างได้
อธิบายการเกิด Antagonism และ Enhancement of drug effectsในรูปแบบต่างๆ
เข้าใจ Quantal dose-response curve และ Graded dose response relations

3. What is Pharmacology?
Pharmacology can be defined as the study of the manner in which the functions of the living systems is affected by chemical agent

4. Mechanism of drug action
DRUGS
Interaction
Chemical agents
Living System
Drug fate in the body
Mechanism of drug action
Absorption
Distribution
Metabolism
Elimination
Pharmacologic effect
Physiological
Biochemical
Desired
Treatment
Prophylaxis
Undesired
Side effect
Toxicity

5. Medicine What is drug? Chemicals Alters biological functions
Do not create new functions
Interact with “specific molecule” (target) in the body
Intrinsic substance OR Xenobiotics

6. Drug - Body Interactions
Pharmacodynamics
เภสัชพลศาสตร์
What drug does to the body
Pharmacokinetics
เภสัชจลนศาสตร์
What body does to the drug

7. (Adverse drug reaction; ADRs)
Pharmacodynamics
What drug does to the body
How do drugs act ?… Mechanism of action
Drug-Target Interactions
Dose response relationship
Mechanism of action
Desired effects
(Clinical response)
Undesired effects
(Adverse drug reaction; ADRs)

8. Target for drug action Protein Other eg. DNA RNA, Tubulin Receptors
Ion channels
Enzymes
Carrier molecules

9. Pharmacokinetics Drug concentration at sites of actions
What body does to the drug
Drug fate in the body
Absorption
Distribution
Metabolism
Excretion
Drug concentration
at sites of actions
Elimination
Drug action
Onset & Duration of action

10. Dose of drug administered
absorption
Drug concentration
In systemic circulation
Drug in tissues or distribution
distribution
Pharmacokinetics
distribution
Drug concentration
at site of action
Elimination
Drug metabolized or excreted
Pharmacologic effect
Pharmacodynamics
Clinical response
Toxicity
Efficacy
Figure 1.1 Schematic representation of the pharmacokinetic and pharmacodynamic processes that link the administration of drugs to its effects

11. Ligand can either stimulate or block receptor
Drug acts at receptor
Ligand can either stimulate or block receptor
Stimulate … “Agonist”
Block … “Antagonist”
Drug or Ligand
Receptor

12. KA = drug concentration which have 50% occupancy at equilibrium
KA indicates Affinity; ความชอบจับของยากับ receptors
High KA ; Low Affinity
MODEL
50 % occupancy
Low KA ; High Affinity

13. Theoretical relationship between occupancy and ligand concentration
KA = drug concentration which have 50% occupancy at equilibrium
KA indicate affinity

15. Concentration Effect Curve
Concentration effect curve is not equal to occupancy concentration curve
Can not indicate the affinity … response is not related to affinity

16. Agonists VS Antagonists Ligand = Agents that bind to receptor
Drugs act at receptor (one type of drug target)
Ligand = Agents that bind to receptor
Agonists
Bind receptor Physiological response
Maximal response “ Full agonist”
Submaximal response “ Partial agonist”

17. Figure 1.4 Theoretical occupancy and response curve for full and partial agonist
Response full agonist
A= Full agonist
Occupancy
Response
Response
B= Partial agonist
Response partial agonist
Occupancy
0.5
1.0
Concentration

18. A & C = Full agonist
B & D = Partial agonist

19. Agonist has both “Affinity & Efficacy” Antagonist has only “Affinity”
Bind receptor No physiological response
Block receptor
Prevent endogenous ligand or agonist binding
Agonist has both “Affinity & Efficacy”
Antagonist has only “Affinity”
Agonist + Antagonist
Pharmacologic antagonism

20. Drug antagonism
Pharmacologic antagonism
Physiologic antagonism
Chemical antagonism

21. Agonist + Competitive reversible antagonist

22. Agonist + Irreversible antagonist

23. Enhancement of drug effect
Additive effect 1+1 = 2
Paracetamol + Ibuprofen
Synergism 1+1 > 2
Sulfamethoxazole + Trimethoprim
Potentiation 0+1 > 1
Penicillin + Probenecid

24. Quantal dose response curve
Quantal response = All or none response
Count the number of subjects who response

25. Figure 1.6 Quantal dose effect curves
Median effective dose = ED50
Median lethal dose = LD50
Therapeutic index (T.I.) = LD50 / ED50
More safety… High therapeutic index
Figure 1.6 Quantal dose effect curves

26. Graded dose response relations
Different response when increasing the dose
Respiratory arrest
Drug A
Anesthesia
Efficacy … A = B
Potency… A > B
sedation
Drug B
dose
Figure 1.7 Graded dose-response comparison of 2 sedative-hypnotic drugs
Efficacy ประสิทธิภาพ …Maximum effect (Emax)
Potency ความแรง ...Dose to give the same response (Lower dose; Higher potency)

27. Key words of the day Pharmacology Pharmacokinetics Pharmacodynamics
Affinity … KA
Concentration – Occupancy curve
Concentration response curve
Ligand… Agonist-Antagonist
Antagonism
Enhancement
Quantal dose response relationship
Therapeutic index/ Standard margin of safety
Efficacy VS Potency

28. Don't be Panic!
Q&A