L15 Dynamics Of Drug Action

Question 1

What is major target of drug action

Answer 1

Cell surface receptors or intracellular and sometimes some membrane transporters

Question 2

Explain mechanism of Drugs modulating ligand gated ion channels (metabotroptic receptors)

Answer 2

Bind instead of ligand and alter flow of ions passing in to channels

a) inhibition of influx of NA and efflux of K in response to activation of nicotinic receptors(help in muscle relaxation during operations)
b) stimulation of influx of chloride in response to GABA receptor A to suppress neuronal functions (help in convulsions)

Question 3

Explain mechanism of drugs modulating G protein coupled receptors

Answer 3

Bind instead of ligand
Ignite or switch off transduction cascade
Cascade is initiated by specific G protein and 2ndry messengers and affect many downstream hormones

Question 4

What are drugs modulating G protein coupled receptors mainly triggered by

Answer 4

Gs proteins linked to B2 adrenergic receptors to activate adenylate cyclase and inc cAMP to activate protein kinase A to induce bronchodilation in bronchial asthma

Gi linked to a2 adrenergic receptors to inhibit AC and dec cAMP and inhibit PKA reducing blood pressure in hypertension

Gq linked to a1 adrenergic receptors to activate PLC Increasing IP3 and DAG activating PKC to inc blood pressure in hypotension

Question 5

Explain mechanism of drugs modulating enzyme linked receptors

Answer 5

They can:
Bind to receptor instead of ligand to activate or inhibit down stream receptor activation of exogenous insulin to stimulate intrinsic tryosine kinase receptor (controls type 1 more than type 2)

Bind to ligand itself to prevent activation of receptors during use of anti-TNFa(mAb) to control rheumatoid or IBD

Bind to downstream signaling of the receptor directly as when immune modulators is used to treat some cancers

Question 6

Drug affinity

Answer 6

Shows how well a drug recognizes and binds to its receptor

Question 7

Drug potency

Answer 7

Measures the required amount of drug necessary to produce an effect of a given intensity when reaching and binding with variable affinity to its receptor

Question 8

Drug efficacy

Answer 8

Measure effectiveness of a drug to elicit a max achieved response when given at highest practical concentration

Question 9

Antagonist

Answer 9

When drug fails to elicit any desired response and meanwhile prevents endogenous ligand from binding to the receptor

Question 10

Agonist

Answer 10

When a drug binds to its receptor and formed bound complex elicits a desired response (has affinity and efficacy)

Question 11

When is s shaped curve called

Answer 11

Graded dose response curve

Question 12

What is Max concentration called and what does it show

Answer 12

E max

Efficacy

Question 13

Half maximal response

Answer 13

EC50

Question 14

When is potency of drug considered high

Answer 14

If effect of a given intensity is evoked by a small dose of a drug

Question 15

Types of agonists

Answer 15

Full
Partial
Inverse

Question 16

What is a full agonist

Answer 16

Mimics response of ligand (has same efficacy)

Question 17

What is a partial agonist

Answer 17

Incapable of reaching response of ligand (has lower efficacy) and is giving sub maximal response

Question 18

What is an inverse agonist

Answer 18

Stabilizes a spontaneously activated receptor setting it back to its inactive state

Question 19

Types of antagonists

Answer 19

Competitive reversible
Competitive irreversible
Non competitive antagonist

Question 20

Whats a competitive reversible antagonist

Answer 20

Binding is non permanent and can be overcome by increasing concentration of agonist relevant to it

Question 21

What is a competitive irreversible antagonist

Answer 21

Binding is permanent because it forms a covalent bond with the active site
Cannot be overcome by inc concentration

Question 22

What is a non competitive antagonist

Answer 22

Blocking agonist ability to activate its receptor by binding to a diff site (allosteric site)

Question 23

Whats physiological antagonism

Answer 23

Achieving antagonistic effect by acting on a diff receptor (ex: adrenaline that induces vasoconstriction by action a1 adrenergic receptors to antagonize vasodilator action of histamine produced by its action of H1 receptors)

Question 24

What is chemical antagonism

Answer 24

Achieving antagonistic effect by reacting chemically to form an inactive complex
(Ex: protamine sulphate that forms an inactive complex with heparin when there is no need to stop hemorrhage induced by it)