Pharmacology -receptor theory about regulations of receptors

1. Regulation of receptors(pharmacodynamics)
Presented by
THIRUPPANESH S
B.PHARM(FOURTH SEM:_)
DATE:01/08/2023
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2. Coming up in this slides,
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Regulation
of receptors
1.Definition
2.How it
takes
place?
4.Clinical
importance

3.  Definitions:
Up regulation(super sensitivity):
 In upregulation (i.e., increase in the number of recepters)
the activity of the receptors is lower than usual (e.g., due
to long -term administration of an antagonist.
Down regulation(desensitization):
 Downreguation (i.e., decrease in the number ) is the
inverse of upregulation.
 It occurs due to repeated or long-term administration of
an agonist

4. -Receptor
-Agonist
-Antagonist
TARGET
CELL
TARGET
CELL
TARGET
CELL
Internalization of receptor
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5. Drug(down
regulation)
receptors Modulation of
action
 Isoprenaline  Beta2-
adrenoreceptors
in bronchial muscle
 Reduce response to
salbutamol
 Levodopa  DA receptor in basal
ganglia
 Decrease therapeutic
effect in parkinsonism
 morphine  Opiate receptor in
CNS
 Tolerance to analgesic
effect
 diazepam  BZD-GABA receptor
complex in CNS
 Sedative effect
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6. -Receptor
-Agonist
-Antagonist
TARGET
CELL
TARGET
CELL
TARGET
CELL
externalization of receptor
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7. • By the definition more the receptor, more
the cell respond to it.
• Enzyme inducers bind the liver cell and
increase CYT450 enzyme which increase
the degradation of molecule
Up regulation
• When the signal molecule(agonist) bind to
the receptor for long time result in down-----
regulation also called desensitization.
• Down regulation either leads to
tachyphylaxis or tolerance
Down regulation
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8. Prolonged use of antagonist
Up regulation of receptor
Sudden withdrawal of antagonist
Increase in receptor and its sensitivity
Exaggeration of antagonist mediated response
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9. Some examples of up regulation:
Clinical relevance in clonidine /CNS depressant /opioid withdrawal
syndrome ,sudden discontinuation of propranolol in angina pectoris
etc.,
This mechanism involved may be unmasking of receptors or their
proliferation or accentuation of signal amplification by the transducer
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10. Prolonged use of agonist
Down regulation of receptor
Decreased effectiveness of agonist mediated clinical response
(TOLERANCE) due to,
1. Masking or internalization of the receptor (it became inaccessible
to the agonist )
2. Decreased synthesis /increased destruction of the receptor
refractiveness develops over week or months or slowly
Receptor down regulation particularly shown by the
TYROSIN KINASE RECEPTOR
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11. For downregulation:
clinical examples are bronchial asthma patient treated with beta
adrenergic agonist and parkinsonian patient treated with high doses
of levodopa gradually became less responsive.
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12. References:
1. KD-TRIPATHI-ESSENTIALS OF MEDICAL PHARMACOLOGY-
2013 (page no:53-55)
2. LECTURI-PHARMACODYNAMICS _BLOGS.
3. RECEPTOR THEORIES BY BHAVANI PENTELA –LECTURE 11
FROM_ AKTU.
4. REGULATION OF RECEPTOR BY DR.DARSHAN J. DAVE.
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