Download presentation
Presentation is loading. Please wait.
1
Alpha Adrenergic receptor blockers
SYMPATHOLYTIC AGENTS..2 Alpha Adrenergic receptor blockers
2
ALPHA BLOCKERS Several agents Chemically heterogeneous and with different specificities According to nature of action : Two Groups, Competitive & Irreversible According to selectivity : Three Groups, 1 > 2; 1 = 2; 2 > 1
3
Classification - RECEPTOR antagonist 1- SELECTIVE competetive
1 > 2 2- SELECTIVE competetive 2 > 1 NON-SELECTIVE Competetive 1 = 2 NON-SELECTIVE Irreversible 1 = 2 Prazosin Yohimbine Phentolamine Phenoxy- Terazosin Idazoxan Tolazoline benzamine Doxazosin Mianserin Dibenamine Tamsulosin
4
Pharmacological actions
Major actions on Blood pressure Other effects based on role of receptors in different tissues selectivity of the agent (2 vs 1)
5
CVS Vasodilatation – arteriolar and venous BP PVR
Magnitude dependent on symp. activity at that time More in erect that in supine position – postural hypotension More marked if hypovolaemia is present Baroreflex activation – reflex tachycardia – tends to oppose the fall by HR and CO
6
Reflex tachycardia more marked with non selective agents – WHY?
Compensatory salt and water retention with long term use Prevent pressor response to usual doses of agonists Convert pressor response of Adrenaline to depressor – Dale’s reversal Vascular 2 receptors also vasoconstrictor but activated by circulating and not synaptic NA --no marked effects of 2 blockers 2 blockers can NA release (presynaptic action) – CV effects
7
OTHER EFFECTS ↓contraction of trigone and sphincter in bladder urine flow insulin secretion from islet cells (2 blockers) Miosis Nasal stuffiness adrenergic sweating
8
α1 – blockers : Clinical uses
Reduce blood pressure Hypertensive emergencies Long term treatment Phaeochromocytoma Vasodilatation Peripheral vascular insufficiency To reverse vasoconstrictor excess Improve urine flow Benign prostatic hyperplasia
9
α1 – blockers : Adverse effects
Postural hypotension ( less with α1 selective - venodilatation is less) Reflex tachycardia ( less with α1 selective) Salt and water retention Nasal stuffiness Miosis Failure of ejaculation
10
Specific Agents Ergot alkaloids (ergotamine): Partial agonist & blocking property Also affect other receptors (eg. 5-HT, ) Therapeutic effects (migraine, uterus) not related to blockade. Uses: Migraine (acute attack) Uterotonic – (methylergonovine) in PPH
11
Phenoxybenzamine: 1 > 2 ;
Irreversible : Covalent binding with receptor Long duration of action ( hrs) Also blocks 5-HT, ACh & H1 receptors -- ? significance Inhibits neuronal & extra-neuronal uptake of NA Absorbed from GIT, low bioavailability
12
Phenoxybenzamine Clinical use: Phaeochromocytoma Control of BP Prior to surgery Adverse effects: Postural hypotension, Tachycardia, Nasal stuffiness, ejaculation
13
PVR – blockade + direct (non adrenergic)
Phentolamine : 1 = 2 PVR – blockade + direct (non adrenergic) HR – Reflex + 2 presynaptic on cardiac symp. terminals Poorly absorbed orally Clinical use: Phaeochromocytoma Local vasoconstrictor excess Adverse effects: Cardiac stimulation : tachycardia, arrhythmia, angina GIT Stimulation : - diarrhoea; gastric acid secretion
14
Tolazoline: Similar to phentolamine Slightly less potent Better absorption from GIT Rapidly excreted in urine Limited clinical application: peripheral vasospastic disease
15
1 Selective Agents Prazosin & Terazosin: 1 >>>> 2
Effective in management of hypertension Low affinity for 2 Relative absence of tachycardia ↓ Triglycerides & LDL, ↑ HDL (favourable) Both are extensively metabolized by liver Prazosin shows high 1st Pass effect (50%) Oral absorption - good Terazosin :Bioavailability >90%; >18 h action Uses: Hypertension and BPH Adverse effects First dose effect Postural hypotension Salt & water retention ( long term use)
16
Doxazosin: Similar to Prazosin but longer t ½ (22 Hr) Alfuzosin : similar to prazosin Tamsulosin Selective α1 anatgonist Has greater selectivity for α1A subtype Has greater efficacy for BPH Relatively smaller effects on blood vessels USE: BPH
17
Indoramin & Urapidil : Newer 1-selective agents Have some utility in hypertension
18
2 selective Yohimbine Hardly used clinically Idazoxan Mianserin : Used as an antidepressant; 2 – blocking action within CNS contributes to its effect. Other receptor actions also (eg. 5-HT) Labetalol : 1 +
19
Clinical Uses Of Blockers
Pheochromocytoma Hypertensive emergencies Chronic hypertension – non selective blockers are not used Peripheral vascular diaease – spastic (Raynauds), not morphological Local vasoconstrictor excess – phentolamine useful- local infiltration Urinary obstruction – BPH – prazosin, terazosin, tamsulosin CHF α2- selective antagonists do not have any recognised clinical use
20
Some neuroleptic agents (eg
Some neuroleptic agents (eg. chlorpromazine, haloperidol) used in psychiatry possess α receptor blocking activity (in addition to Dopamine receptor antagonism) which may lead to cardiovascular adverse effects with these agents.
21
ADRENERGIC NEURON BLOCKERS
Inhibit the function of peripheral, post-ganglionic adrenergic neurons Guanethidine - Antihypertensive Guanadrel Antihypertensive Reserpine Antihypertensive Bretylium Anti-arrhythmic Not used now
22
Guanethidine : Sympathoplegic, Taken up and concentrated by neurons Blocks NE release (LA like action on terminal) Displaces NE from granules IV : initial release – initial mimetic actions Does not cross BBB Widespread sympatholytic effects Leads to several adverse effects Chronic use causes effector supersensitivity Guanadrel: Similar to Guanethidine
23
Bretylium : Inhibits release of NE from terminals Also has direct anti-arrhythmic activity Reserpine : Blocks vesicular uptake of NE – depletes vesicles Displaces NE from terminal – initial mimetic actions Crosses BBB – CNS effects: Depression ,suicidal tendency Adverse effects due to non specific sympatholysis These drugs rarely used now for Hypertension
24
Autonomic Drugs Used for Glaucoma:
Cholinomimetics Muscarinic agonists Pilocarpine AChE inhibitors Physostigmine, Increased outflow Ecothiophate Alpha agonists Non – selective Epinephrine Increased outflow Dipevefrine Selective α Apraclonidine Decreased aqueous Brimonidine secretion Beta Blockers Timolol, betaxolol Decreased aqueous secretion Other drugs Carbonic anhydrase inhibitors – acetazolamide – ↓ formation Prostaglandins – lanatoprost – ↑ outflow
25
Targets for Pharmacological Interference
Tyrosine hyhroxylase MPT NA DOPA decarboxylase Methyldopa Pseudotransmitter* Dopamine hydroxylase Disulfiram Release of NA Tyramine Sympathomimetic Amphetamine Release of NA Guanethidine Sympatholytic Bretylium Reuptake Cocaine, effect of NT Imipramine indirect mimetics Reuptake into granules Reserpine Release Depletion
26
Targets for Pharmacological Interference
Presynaptic 2 Catecholamines release Presynaptic 2 Catecholamines release Presynaptic M ACh release MAO Several metabolism Extrasynaptic uptake PBZ, Steroids Effect COMT Pyrogallol Talcapone Entacapone
27
Dale’s Reversal Phenomenon
Mean arterial blood pressure PBZ Adr Back
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.