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-
17.
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.
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22.
23. Side effects of α-blockers
Palpitation
Postural hypotension
Nasal blockade
Diarrhea
Fluid retention
Inhibition of ejaculation & impotence.
