Adrenergic Receptor Blocking Agent
Adrenergic receptor antagonists are drugs that bind to α or β
adrenergic receptors and prevent or block the responses produced by
catecholamines or sympathomimetic drugs.
Source: Encyclopedia of Neuroscience, 2009
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-
science/adrenergic-receptor-blocking-agent
Alpha adrenergic blockers
1. 1. Dr. K. R. Prabhakar, Resident.
2. 2. CLASSIFICATION α-Adrenoceptor Antagonists Non-selective block α1 & α2 Selective
Miscellaneous •Ergot alkaloids Reversible Irreversible α1-blockers α2-blockers
•Phentolamine •Phenoxyben- •Prazosin •Yohimbine zamine •Terazosin •Tolazoline
•Idazoxan •Doxazosin (priscoline) •Alfuzosin & Bunazosin •Tamsulosin &Silodosin
3. 3. General effects of α blockers Blood vessels α1-blockade→reduces peripheral resistance
Fall in BP Postural hypotension α2-blockade in brain ↑se vasomotor tone. Block pressor
action of adrenaline, fall in BP due toβ2. action- “vasomotor reversal of Dale” Actions of
selective α-agonists supressed.
4. 4. Heart Reflex tachycardia due to: fall in mean arterial pressure Blockade of
presynaptic α2 receptors- ↑ NA release. Nose: nasal stuffiness Eye: miosis GIT: intestinal
motility ↑se Kidney: Hypotension ↓se GFR NA+ & H2O reabsorption
5. 5. Urinary bladder α1A blockade- ↓se tone of smooth muscle in trigone, sphincter &
prostrate. Improved urine flow, used in BPH. Reproductive system Contraction of vas
deferens result in ejaculation through α receptors. Blockade results in impotence.
6. 6. Irreversible non-selective α- blockers Phenoxybenzamine Cyclizes spontaneously to
highly reactive ethyleniminium intermediate. Binds covalently to α-receptors- irreversible or
nonequilibrium competitive block. Blockade is slow onset & longer duration (3-4 days).
Also inhibits reuptake of NE. Shifts blood from pulmonary to systemic circuit. Shift fluid
from extravascular to vascular compartmentrelaxation of postcapillary vessels.
7. 7. PK Preferred ROA- i.v. Lipid soluble penetrates brain. Mainly excreted through urine
in 24 hrs. Accumulates in adipose tissue on ch. Administration. Dose 20-60 mg/d oral
1mg/kg/1hr slow i.v infusion. Uses Pheochromocytoma, occasionally 2oshock, PVD.
8. 8. Reversible non-selective α-blockers Tolazoline Block is modest & short lasting. Direct
vasodilator & stimulates the heart. Also blocks 5-HT receptors, histamine like gastric
secretagouge & Ach like motor action on intestine. SE N, V, cramps, diarrhoea,
nervousness, chills Tachycardia, Exacerbation of MI, peptic ulcer. Use PVD Pulmonary
HT of newborn.
9. 9. Phentolamine More potent α-blocker than tolazoline. Other actions are less marked.
Duration of action is shorter (min). Equally blocks α1 & α2 receptors- NA release ↑sed.
Uses ∆sis & intraop.management of pheochromocytoma. 5mg i.v- B.P falls by
25(D)or35(S)mmHg. HTN due to clonidine withdrawl, cheese reaction. Dermal necrosis
due to extravasated i.v NA/DA. Given S.C as local infiltration.
10. 10. Reversible, selective α1- blockers Prazosin Highly selective α1-blocker , α1: α2
selectivity 1000:1 Fall in BP with only mild tachycardia. Dilates arterioles more than veins
Postural hypotension occurs as 1st dose effect, minimized by starting with low doses at
bed time. Also inhibits PDE- ↑se cAMP in smooth muscle. PK Effective orally, BA- 60%.
Highly bound to plasma proteins (α1 acid glycoprotein).
11. 11. Metabolized in liver, 1o excreted in bile. t1/2 – 2-3hrs, effect lasts for 6-8hrs. Uses
Primarily as antihypertensive. LVF not controlled by diuretics & digitalis. Raynaud’s
disease BPH Scorpion sting
12. 12. Terazosin &Doxazosin Long acting( t1/212 & 18hr) congener of prazosin. Used in
HTN & BPH as single daily dose. Tamsulosin & Silodosin Uroselective α1A blocker α1A
–bladder base, prostrate. α1B- blood vessels. Don't cause significant changes in BP & HR.
t1/2- 6-9hr, MR cap(0.2-0.4 mg) can be taken OD. Efficacious in Rx of BPH. SE:
retrograde ejaculation, dizziness,, floppy iris syd. Silodosin weaker(4-8mg/d) but longer
acting.
13. 13. Bunazosin & Alfuzosin Orally effective α1 blockers similar to prazosin. Alfuzosin t1/2
4hrs (2.5mgTDS or 10mg SR OD). CI in hepatic impairment, metabolized in liver.
Bunazosin slightly longer t1/2. Primarily used in BPH.
14. 14. α2-receptor blockers Yohimbine Natural alkaloid from Pausinystalia yohimbe. No
established clinical role. Idazoxan Has membrane stabilizing action. Ergot alkaloids
Ergotamine & Dihydroergotamine Competitive α-receptor blockers. Principal use is
migraine.
15. 15. Uses of α-Blockers Pheochromocytoma Tumor of adrenal medullary cells-excess Cas.
Cause intermittent or persistent hypertension. Diagnosed by- ↑se urinary VMA,
normetanephrine. phentolamine test can also be performed. Rx Phenoxybenzamine
Definitive therapy for inoperable or malig.tumors. Preoperative- orally x 2wks, i.v during
surgery as-
16. 16. 1. Normalizes blood volume & body H2O distribution. 2. During surgery excess release of
CAs in to blood. Phentolamine drip can also be used. Hypertension Selective α1 blocker
prazosin is preferred. 2o shock Fluid loss leads to vasoconstriction. Should not be given
without fluid replacement.
17. 17. Peripheral vascular disease Little benefit in Buerger’s disease & int.claudication.
More useful in Reynaud's disease & acrocyanosis where vasoconstriction is prominent.
Prazosin or phenoxybenzamine are useful. CHF Short term benefit, leads to Na+ & H2O
retension. Migraine Ergotamine more effective
18. 18. Benign prostrate hypertrophy Two classes of drugs are available. 1. α1-blockers- ↓
tone of prostrate and bladder neck. 2. 5-α reductase inhibitors: finasteride & dutasteride.
arrest growth/reduce size of prostrate. α1-blockers gives faster and greater symptomatic
releif than finasteride. Effect of α1-blockers decline after several years of use, must be
combined with fiasteride. Terazosin, doxazosin, tamsulosin are preferred.
19. 19. Side effects of α-blockers Palpitation Postural hypotension Nasal blockade
Diarrhea Fluid retention Inhibition of ejaculation & impotence.
20. 20. Thank you
