This document summarizes the classification, mechanisms of action, pharmacokinetics, and clinical uses of α-adrenergic receptor antagonists (α-blockers). It discusses non-selective α-blockers that block both α1 and α2 receptors like phentolamine and phenoxybenzamine, as well as selective α1-blockers like prazosin, doxazosin, tamsulosin, and selective α2-blockers like yohimbine. The major uses of α-blockers include treatment of pheochromocytoma, hypertension, peripheral vascular disease, benign prostatic hyperplasia, migraine, and congestive heart failure. Common side effects include hypotension

1. Dr. K. R. Prabhakar,
Resident.

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

4. 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.

5. 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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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).

12.  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

13. 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.

14. 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.

15. 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.

16. 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-

18. 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.

19. 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

20. 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.

23. Side effects of α-blockers
 Palpitation
 Postural hypotension
 Nasal blockade
 Diarrhea
 Fluid retention
 Inhibition of ejaculation & impotence.

24. Thank you