Adrenergic Antagonists_Lect 15_2010BbF

Adrenergic Antagonists_Lect 15_2010BbF - Adrenergic...

Info iconThis preview shows pages 1–8. Sign up to view the full content.

View Full Document Right Arrow Icon
Adrenergic Antagonists
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Lecture Objectives I. Review requirements/role for effective sympatholytics II. Examine Direct Antagonists A. Non-Selective a Adr B. Selective : a 1 vs a 2 C. Non-Selective b Adr D. Selective b 1 vs b 2 E. Examine Indirect Antagonist ( Non-Selective) Focus: Mechanism of Action Therapeutic Use Side-Effects/Drug Interactions
Background image of page 2
I. The role for sympatholytics Efficacy as therapeutics related to R selectivity Widely prescribed class of drugs Effective antagonism determined by Expression receptor subtypes Anatomical Level Relative [] of Ag vs ANT at target tissue (WHY?) Relative affinities Duration of Block competitive/non-competitive reversible Irreversible antagonism reversal requires de novo synthesis Duration ~ dissociation rate and t 1/2
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
IIA. Non-selective a Adr R ANT 1. Phenoxybenzamine ( dibenzyline ) Irreversible (similar to nitrogen mustards) Decreasing but persistant block 3 days post exposure D-R curve shifts right and Emax decreased ( WHY? ) Dirty drug H1R, 5HT R, mAChR Enhances NE via reuptake block & blocks a 2 inhibition of release Results CV : ↓TPR, ↓DP,↓ VR and reflex tachycardia Hypotensive response greater in HT patients Used to treat pheochromocytoma Metabolic: insulin secretion (unmasking b 2 effects with no a inhibition of insulin release), lipolysis
Background image of page 4
Others: Tolazoine ( Priscoline ) & Phentolamine ( Rogitine ) Reversible & competitive inhibitors slightly higher affinity for a 1R Blocks serotonin (5HT) at high [ ] (1/1000 affinity as a - AdrR) CV effects similar to phenoxybenzamine but transient Used for short-term HT treatment pheochromocytoma tyramine-rich diets of those taking MAO-I
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
IIB. Selective a 1 R ANT Prazosin ( Minipress ) At therapeutic dose- selective a 1R ANT (100X greater affinity) Similar potency for a 1A, B, D subtypes Clinically used for mild to moderate HT, CHF No adverse effects associated with non-selective a ANT Tachycardia via baroR feedback may occur Tachycardia associated with nonselective a ANT does NOT occur due to autoinhibition ( a 2 R) intact with a 1 ANT ↓TPR, ↓DP, ↓VR (may have large vein pooling), ↓pre -after load, ↓pulmonary congestion and ↑CO First dose phenomenon- orthostatic hypotension Oral absorption, extensive plasma-protein binding, biotransformed
Background image of page 6
Terazosin ( Hytrin ) Treat mild/moderate HT and benign prostatic hyperplasia (BPH) Tamsulosin ( Flomax ) High affinity for a 1A and a 1D receptor subtypes >70% a AdrR are a 1A in prostate and sphincter of bladder Symptomatic treatment of BPH ( a 1A overexpression) Less postural hypotension and CV effects (no a 1B binding)
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 8
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 28

Adrenergic Antagonists_Lect 15_2010BbF - Adrenergic...

This preview shows document pages 1 - 8. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online