Pharmacodynamics-2

Dr.U.P.Rathnakar
MD.DIH.PGDHM

Potency-A>B

Potency & efficacy of C <A&B

Efficacy-A=B

Potency & efficacy

Effect on pain [efficacy]

Drug B
[Pethidine]

E Max
Severe

Drug A
[Morphine]

Drug C
[Aspirin]

Moderate

Mild

50mg Dose [potency] 2mg 4mg 8mg 15mg 25mg 300mg

Drug potency & Efficacy

Potency- Amount of drug required to obtain a particular response[More potent less dose] Efficacy-The ability of a drug to elicit a maximal response Aspirin is less potent[300mg] & less efficacious than morphine[10mg]

Pethidine is less potent[100mg] equally efficacious as morphine[10mg]

Dose-response curves

Response

10mg

100mg

1000mg

Dose-response curves
X is more potent than Y or Z

X & Z are equally efficacious But X is more potent

Y is less efficacious than X and Z

Dose-response [potency & effect]curve[DRC]

100%

E max

50%

EC50

Dose-response curves determine how much of a drug (X-axis) causes a particular effect, or a side effect, in the body (Y-axis).

Graded dose response curves

[Single subject- Continuous]

Linear [Simple]dose response curve

Log dose response curve

Advantages of Log-dose curve Large no.of doses can be plotted on a small graph paper Comparison of two or more drugs easier as middle portion is straight line

Quantal dose response curve

Quantal or all or none: frequency with which any drug evokes a all or none response in a population
97% 85% 35% 35% 100%

50% 11% 12% 3% 15% 4% 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0

LD50 & ED50

4%

Cumulative DRC

Therapeutic index [TI]

LD50=Dose which kills 50% of sample population ED50=Dose which produces desired effect in 50% of sample

TI=

Median lethal dose[LD50 ]or Toxic Dose50]

Median effective dose[ED50]

Wider the TI-More safe the drug Eg.Penicillin -wide TI , Digoxin narrow TI
Certain safety factor = LD1/ED99 LD1=Lethal dose for 1% population ED99=Effective dose for 99% of population

Therapeutic index
TI=10/5=2
TI=100/5=20

100%

TI Narrow TI WIDE ED50 50% LD[TD]50 ED50

10mg

5mg 5mg 100mg

Therapeutic range
Therapeutic range: Range between dose which produces minimal Th.effect and Max.acceptable adverse effect

Acceptable-ADE

Min.Th.Effect

Therapeutic range

Combined effect of drugs

When 2 drugs are administered together:1. They may be Indifferent to each other 2. One may increase the action of the otherSynergism 3. Action may be decreased or abolished Antagonism

Combined effect of drugs

Indifferent

Synergism Physical

Antagonism

Chemical Additive One facilitates the action of other Physiological One opposes the action of other

Supra-additive [Potentiation]

Receptor

Competitive
[Equilibrium & Non-equilibrium]

Non-competitive

Agonists snd antagobists

Synergism
Two drugs One increases or facilitates the action of the other

Additive Drug A + Drug B = Effect of A+B [1 + 1 = 2] Advantage: Side effect may not add up Dose of both can be reduced Eg. Aspirin + Paracetamol Nitrous oxide +Halothane Amlodipine+Atenolol

Supra-additive (Potentiation) Effect of combination is more than individual effect of 2 drugs 1 + 1 = 3 OR 1 + 0 = 2 One drug may be inactive Levodopa+Carbidopa[Inacti ve alone][1 + 0 = 2] Sulfamethaoxazole+Trimeth oprim[Both active] [1+1= 3]

Antagonism [Effect of one drug is decreased]

1. Physical Charcoal adsorbs alkaloids 2. Chemical KMno4 oxidizes Alkaloids BAL chelates arsenic Protamine neutralizes heparin Na.Thiopentone+ Succinylcholine 3. Physiological Histamine and Adrenaline [Functional] Glucagon and Insulin Hydrochlorothiazide and triamterene 4. Receptor:

Antagonism [Receptor]
One[Antagonist] blocks the receptor action of the other[Agonist]

Competitive[surmountable] Binds with the same site on the receptor Resembles the agonist Surmountable by increasing the concn. Of agonist Rightward shift of DRC 5. Eg. Ach atropine Morphine - Naloxone

Non-competitive[unsurmountable] Binds to another site or same site covalently No resemblance Not surmountable Flattening of DRC Eg. Diazepam Bicuculline PhenoxybenzamineNoradrenaline

Competitive and non-competitive antagonism

Flattening of DRC

Rightward shift of DRC

Competitive

Non-competitive

Factors modifying fuel efficiency??? Factors modifying drug action

New
Driver Mfr.defect Bad road Over loaded Engine problem

[Age?]
[M or F] [Genetic?] [Envn.] [Obesity?] [Patho.states]

Tarffic congestion [DI, polypharmacy]