Transcript ISHIK UNIVERSITY FACULTY OF DENTISTRY

ISHIK UNIVERSITY
FACULTY OF DENTISTRY
Drug Receptors
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The drug receptors are macromolecular sites which
are situated on the surface or inside the effector
cells with which specific agonist combines to
produce its response.
Antagonist prevents the action of an agonist on a
receptor, but does not have any effect of its own
Drug-receptor interaction
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Each drug requires a target within the body called
a receptor.
Binding of drugs to receptor is:
Reversible : Effect for short time (reversible bonding
forces)…most drugs
Irreversible: Effect is prolonged (Covalent bonding
forces) : aspirin cause irreversible inhibition of PG
synthesis.
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Drugs act by antagonize or inhibit:
Cell surface Receptors
Ion Channels
Enzyme Inhibition
Transport Inhibitors
Nuclear Receptors
1)Action of a receptor :
 A spesific macromolecule, usually a protein to which
a specific group of drugs or naturally occurring
subtances (neurotransmitters or hormones) can bind.
 The biochemical evets that result from a drureceptor interaction and which produce effect, are
complex.
 The binding of drug to receptor result formation of :
Drug-Receptor Complex…Then the effect.
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Drug + Receptor  Drug-receptor complex  effect
Types and subtypes of receptors
Receptor
Subtype
Main Actions of
Naturale agonist
Agonist Drug
Antagonist Drug
Adrenoceptor
α1
α2
β1
β2
Vasoconstruction
Hypotension
Sedation
Increase HR
Bronchodilation
Noradrenaline
Clonidine
Dopamine
Salbutamol
Prazosin
Atenolol
Cholinergic
Muscarinic
Heart rate
Atropine
Histamine
H1
H2
Bronchoconstruction
Increase gastric acidity
Chlorpheniramine
Ranitidine
• Are Drugs That Anatgonize Cell Surface Receptors Clinically Useful?
 Angiotensin receptor blockers (losartan, valsartan) for high blood pressure, HF
 Beta-adrenoceptor Blockers (propranolol, Atenolol) for angina, MI, HF, HBP
Functions of a receptor may be
briefly summarized as follows:
1.
2.
3.
Receptors largely determine
the quantitative relations
between dose or concentration
of drug and pharmacologic
effects.
Receptors are responsible for
selectivity of drug action.
Receptors mediate the actions
of both pharmacologic
agonists and antagonists.
2) Action on an enzyme
Enzymes, like receptors; are protein macromolecules
which subtrates interact to produce activation or
inhibition
 Examples: Enalapril (inhibits ACE-Anti-HTN)
3) Transport Inhibitors: Sodium pump inhibitors . Such
as:
 Digoxin inhibits the membrane bound
Na+/K+ATPase (Used in HF)
 Diuretics (Loop DU) inhibit the Na+/Cl- cotranporter in the kidney
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4) Actions on membrane ion channels
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The conduction of impulses in nerve tissues and
electromechanical coupling in muscle depend on the
movement of ions particularly sodium, calcium, and
potassium, through membrane channels.
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Several groups of drugs interfere with these processes:
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Antiarrythmic drugs (Quanidine: Na Channel blockers)
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Local anesthetics as (Lidocaine: Sodium channel Blocker)
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Anti-HTN: amlodipine (Ca channel blockers)
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Oral Anti-DM: Sulphonylureas block ATP-sensitive potassium channels in
pancreatic B-cells
5) Drugs work by antagonizing Nuclear receptors:
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Lipid soluble ligand can easily diffuse across cell
membrane and move to the nucleus of the cell where
it binds to nuclear receptors (DNA) and then activate
the transcription of spesific gene.
Estrogen receptor antagonists for the prevention and treatment of
breast canser (Tamoxifen)
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Agonists: Drugs that binds to receptor and
stimulates or activates the receptor to produce an
effect (salbutamol at beta-1 receptor).
Antagonists are drug that binds to receptors and
prevents the action of an agonist but does not have
any effect itself (losartan at the angiotensin II
receptor)
Have only the affinity but no intrinsic activity.
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Drug Tolerance is seen when the same dose of drug
given repeatedly loses its effect or when greater
doses are required to obtain previous effect.
Eg. Tolerance of Glyceryl trinitrate occurs in
treatment of angina pectoris when given
repeatedly so a drug free time of 8-12 h is
advised.
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Up-Regulation : Continouse or repeated exposure
to antagonists initially can increase the receptors
and with chronic exposure to antagonist, the number
of receptors on cell membrane surface increase.
Eg. Β-blockers (propranolol) should not be stopped
promptly in people with ischemic heart disease (IHD)
because it presipitates unstable angina or mycardial
infarction ( avoid sudden withdrawal)
Combined effect of drugs
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SYNERGISM
When two drugs are given simultaneously, and the
action of one drug is increased by the other, they
are treated as synergistic. In the synergism, the
drugs can have action in the same direction or when
given alone, one may be inactive. Synergism can be
additive or supradditive in nature.
Drug Antagonism
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COMPETITIVE ANTAGONISM
In competitive antagonism, the
antagonist binds with the same
receptor as agonist. If the log dose
response curve with agonist is
obtained in the presence of
antagonist, it will be found that
antagonist has no effect of its own
and there is parallel rightward shift
in the dose response curve of
agonist with no change in shape,
slope or maximum response.
Eg. Acetylcholine (as agonist) – atropine (as
antagonist).
NON-COMPETITIVE ANTAGONISM
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Antagonist binds to another
site or receptor. The
antagonist is not displaced
by a high concentration of
the agonist on the same
receptor and the doseresponse curve is flattened
and its slope and maximum
response will be decreased.
Eg. Noradrenaline--- Phenoxybenzamine