Principles of Drugs Action

8/10/2019 Principles of Drugs Action

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PRINCIPLES OF

DRUGS ACTION

Dr. Nurhidayati


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Targets of drugs action

Receptors

Ion channels Carriers (Transporters)

Enzymes


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RECEPTORS AS

DRUG TARGETS

Types of receptors

1. Surface receptors i.e insulin receptor

The action of drugs acting on this receptor type inminutes

2. Intracellullar receptors Cytosolic and nuclear receptors

The drugs needs to pass through the cell membranefirst to bind to intracellular receptors

Nuclear receptors tends to alter gene transcription

i.e oestrogen receptor

Time scale : slow, taking hours to days to show effects


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3. Receptors linked to Ion channels

The drugs alter the selectivity and opening of thepore

i.e nicotinic Ach receptor ( cholinergic receptors)

Time scale : rapid response

A special subset is a voltage gated ion channel Doesnt require a ligand for its activation

Time course in millisecond

4. Indirect coupling (receptors coupled to G

proteins) Binding of a drug to the receptor causes the

activation of second messenger system

Time course in second


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Structura l mot i fs o f phy s io logical receptors andtheir re lat ionships to s ignal ing pathways.


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If the activation of these receptors

abnormals

activation abnormal response of

activation the cell targets

Disorders/Diseases

activation activation

activation activation

antagonist

agonist

Management


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Examples :

Agonist Adrenaline, Isoproterenol, Fenilefrin adrenergic

receptors

Bethanechol, Pilocarpine, Nicotine Cholinergic receptors

Histamine histamine receptors

Antagonis

Atropine, Scopolamine Cholinergic receptors

Prazosin, Propranolol, Salbutamol Adrenergic receptors Ranitidine, cimetidine, famotidine histamin receptors


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ION CHANNELS AS

DRUG TARGETS

Na Channel Drugs/toxins which affect the Na channel:

Local anaesthetics lignocaine, procain,benzocaine,

Neurotoxins tetrodotoxin, saxitoxin

Drugs / toxins which activate the voltage gatedNa-channelincreaser the ability of the Na

channel open: DDT, scorpion toxin, sea anemonie toxin

veratridine

Ligand gated Na channel

In neuromuscular junction


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INHIBITORS OF RENAL EPITHELIAL NA+

CHANNELS (K+-SPARING DIURETICS)


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The K channel

Ca linked K channel Apamin (found in bee venom)

Charybdotoxin (in scorpion venom)

ATP sensitive K channel

Diazoxide, Pinacidil, Cromakalin

openers

Sulfonylureas (i.e Glibenclamide)

blocker


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The Ca channel

Ca Channel blockers, i.e :Nifedipin

Verapamil

Diltiazem

Felodipine

Nicardipine amiodipine


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Example


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Repl icat ive cycle of HIV-1 show ing the sites of act ionof available antir etrov iral agents


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Replicative cyc les of DNA (A )

and RNA (B) viru ses


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Conversion of acyc lovi r to acyclovi r tr iphosp hate leading toDNA chain terminat ion


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Carriers (Transporters) as

drug targets

2 types :ATP-powered ion pumps

Transporters ATP-powered ion pumps

Proton Pump Inhibitors : omeprazole,lansoprazole

Transporters

Symporters : furosemide (dieuretics)

Antiporters


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INHIBITORS OF NA+-K+-2CL- SYMPORT (LOOP

DIURETICS, HIGH-CEILING DIURETICS)


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INHIBITORS OF NA+-CL- SYMPORT (THIAZIDE AND

THIAZIDELIKE DIURETICS)

Documents

Principles of Drugs Action