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RESPONSE
To alter their biochemical &/or biophysical activity DepressActivateReplace Irritate DestroyPHARMACODYNAMICSPHARMACODYNAMICS
AbsorbDistributeMetabolizeExcrete
PHARMACOKINETICSPHARMACOKINETICS
Interacts with body’s biological moleculesTARGETS Of Drug Action
The body
The DRUG
MOLECULAR MECHANISMS OF DRUG ACTION
ilos By the end of this lecture you will be able to :
Differentiate between their patterns of
action; agonism versus antagonism
Identify different targets of drug action
Elaborate on drug binding to receptors
ByProf. Omnia NayelAssoc. Prof. Osama Yousif
TARGETS
STRUCTURAL
CARRIER MOLECULE
ENZYME ION CHANNEL
RECEPTOR
REGULATORY
PHARMACODYNAMICSPHARMACODYNAMICS
Tubulin Tubulin are
Vincristine Colchicine
Tubulin
Structure
STRUCTURAL PROTEINTARGETS
Examples of drugs acting on:
TARGETS
ENZYME The drug competes with the natural substrate for the enzyme
REVERSIBLE
IRREVERSIBLEOrganophosphates irreversibly competes with ACH for cholinestrase
Neostigmine reversibly compete with ACH for cholinestrase at MEP
REGULATORY PROTEIN
Examples of drugs acting:
CARRIER MOLECULE
Responsible for transport of ions and small organic molecules between intracellular compartments,
through cell membranes or in extracellular fluids.
The drug binds to such molecules altering their transport ability
Cocaine blocks transport of catecholamines at synaptic cleft in CNS
On a Passive Transporter
TARGETS REGULATORY PROTEIN
Examples of drugs acting:
On an Active Transporter
Digitalis blocks efflux of Na by Na pump
ION CHANNEL
Responsible for influx or out-flux of ions through cell membranes along their concentration gradients.
They are activated by alteration in action potential and are controlled by gating machinery.
Local Anesthetics block Na influx through Na channel in nerve fibers.They are Na channel Blockers.
TARGETS REGULATORY PROTEIN
Drugs can act as a:*Channel blocker or *Channel modulator
Sulfonylurea drugs block K+ out flux via the K channels in pancreatic cells . They are K Channel Modulator
Drugs bind and alter R signal transduction machinery.
Responsible for selectively sensing & binding of a stimulus (ligand) & its coupling to a response via a set of signal transduction machinery
A
B
RR
R
AR*A
B
PharmacologicalRESPONSE
NO RESPONSE
LRL Physiological
RESPONSELR*
ENDOGENOUSLIGAND
RECEPTOR
BindOccupy
InitiateActivate
Agonist
Antagonist
ACh
Tubocurarine
AFFINITY EFFICACY
A drug that possesses both affinity and efficacy
A drug that possesses an affinity but no efficacy
TARGETS REGULATORY PROTEIN
The tendency of a drug to bind to the receptors is governed by its affinity.
Is that inherent property intrinsic to the agonist that determines how "good" an agonist is.
Agonist
Antagonist
A drug that possesses both affinity and efficacy
A drug that possesses an affinity but no efficacy
high intrinsic efficacy↓
a full agonist
low intrinsic efficacy ↓
a partial agonist.
The ability for it, once bound, to activate the receptor is denoted by its efficacy.
AFFINITY
EFFICACY
Has Agonistic-Antagonistic Potentials
PindololPindolol,, is a partial agonistpartial agonist, produces less decrease in heart rate than pure antagonists such as propranolol.
PindololPindolol,, is a partial agonistpartial agonist, produces less decrease in heart rate than pure antagonists such as propranolol.
High intrinsic efficacy↓
Max response
Low intrinsic efficacy ↓ Submax response
A Full Agonist
A PartialAgonist
AgonistLigand
Ligand
Quiz?
• Vincristine binds to:
A) a structural proteinB) an ion channelC) an enzymeD) a carrier molecule
Quiz?
• Local anaesthetics are:
• A) Reversible enzyme inhibitorsB) Irreversible enzyme inhibitors C) Channel blockersD) Channel modulators
Quiz?
• An agent that can bind and maximally activate the receptor .
• A) Reversible antagonist B) Full agonist C) Partial agonistD) Irreversible antagonist