upregulation and downregulation.pptx

Pharmacology -receptor theory about regulations of receptors

1. Regulation of receptors(pharmacodynamics) Presented by THIRUPPANESH S B.PHARM(FOURTH SEM:_) DATE:01/08/2023 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 1

2. Coming up in this slides, 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 2

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 Downregulation : TARGET CELL TARGET CELL Internalization of receptor 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 4

5. Regulation of receptor by drugs: 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 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 5

6. - Receptor -Agonist -Antagonist TARGET CELL Upregulation : TARGET CELL TARGET CELL externalization of receptor 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 6

7. Regulation of receptors: 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 7

8. Clinical importance of up regulation : Prolonged use of antagonist Up regulation of receptor Sudden withdrawal of antagonist Increase in receptor and its sensitivity Exaggeration of antagonist mediated response 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 8

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 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 9

10. Clinical importance of down regulation : Prolonged use of agonist Down regulation of receptor Decreased effectiveness of agonist mediated clinical response (TOLERANCE) due to, Masking or internalization of the receptor (it became inaccessible to the agonist ) 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 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 10

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. 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 11

12. References: KD-TRIPATHI-ESSENTIALS OF MEDICAL PHARMACOLOGY-2013 (page no:53-55) LECTURI-PHARMACODYNAMICS _BLOGS. RECEPTOR THEORIES BY BHAVANI PENTELA –LECTURE 11 FROM_ AKTU. REGULATION OF RECEPTOR BY DR.DARSHAN J. DAVE. 7/31/2023 thiruppanesh s//kmchcop/pharmacology-1 12

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