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)