L15 Dynamics Of Drug Action Flashcards
What is major target of drug action
Cell surface receptors or intracellular and sometimes some membrane transporters
Explain mechanism of Drugs modulating ligand gated ion channels (metabotroptic receptors)
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)
Explain mechanism of drugs modulating G protein coupled receptors
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
What are drugs modulating G protein coupled receptors mainly triggered by
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
Explain mechanism of drugs modulating enzyme linked receptors
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
Drug affinity
Shows how well a drug recognizes and binds to its receptor
Drug potency
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
Drug efficacy
Measure effectiveness of a drug to elicit a max achieved response when given at highest practical concentration
Antagonist
When drug fails to elicit any desired response and meanwhile prevents endogenous ligand from binding to the receptor
Agonist
When a drug binds to its receptor and formed bound complex elicits a desired response (has affinity and efficacy)
When is s shaped curve called
Graded dose response curve
What is Max concentration called and what does it show
E max
Efficacy
Half maximal response
EC50
When is potency of drug considered high
If effect of a given intensity is evoked by a small dose of a drug
Types of agonists
Full
Partial
Inverse
What is a full agonist
Mimics response of ligand (has same efficacy)
What is a partial agonist
Incapable of reaching response of ligand (has lower efficacy) and is giving sub maximal response
What is an inverse agonist
Stabilizes a spontaneously activated receptor setting it back to its inactive state
Types of antagonists
Competitive reversible
Competitive irreversible
Non competitive antagonist
Whats a competitive reversible antagonist
Binding is non permanent and can be overcome by increasing concentration of agonist relevant to it
What is a competitive irreversible antagonist
Binding is permanent because it forms a covalent bond with the active site
Cannot be overcome by inc concentration
What is a non competitive antagonist
Blocking agonist ability to activate its receptor by binding to a diff site (allosteric site)
Whats physiological antagonism
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)
What is chemical antagonism
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)
