Alpha adrenergic blockers
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Transcript of Alpha adrenergic blockers
ALPHA-ADRENERGIC BLOCKERS
Dr. K. R. Prabhakar,Resident.
CLASSIFICATION
α-Adrenoceptor Antagonists
Non-selective
block α1 & α2
Selective Miscellaneous•Ergot alkaloids
Reversible•Phentolamine•Tolazoline(priscoline)
Irreversible
•Phenoxyben-zamine
α1-blockers•Prazosin•Terazosin•Doxazosin•Alfuzosin & Bunazosin•Tamsulosin &Silodosin
α2-blockers•Yohimbine •Idazoxan
General effects of α blockersBlood vesselsα1-blockade→reduces peripheral resistance
Fall in BP
Postural hypotensionα2-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.
Heart Reflex tachycardia due to:-
fall in mean arterial pressureBlockade of presynaptic α2 receptors- ↑ NA release.
Nose: nasal stuffiness
Eye: miosis
GIT: intestinal motility ↑se
Kidney: Hypotension
↓se GFR NA+ & H2O reabsorption
Urinary bladder
α1A blockade- ↓se tone of smooth muscle in trigone, sphincter & prostrate.
Improved urine flow, used in BPH.
Reproductive systemContraction of vas deferens result in ejaculation
through α receptors.Blockade results in impotence.
Irreversible non-selective α- blockersPhenoxybenzamine Cyclizes spontaneously to highly reactive
ethyleniminium intermediate.Binds covalently to α-receptors- irreversible or non-
equilibrium 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 compartment-
relaxation of postcapillary vessels.
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.
Reversible non-selective α-blockersTolazoline 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.
SEN, V, cramps, diarrhoea, nervousness, chillsTachycardia, Exacerbation of MI, peptic ulcer.
Use PVDPulmonary HT of newborn.
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.
Reversible, selective α1- blockers
PrazosinHighly selective α1-blocker , α1: α2 selectivity 1000:1Fall in BP with only mild tachycardia.Dilates arterioles more than veinsPostural hypotension occurs as 1st dose effect,
minimized by starting with low doses at bed time.Also inhibits PDE- ↑se cAMP in smooth muscle.
PKEffective orally, BA- 60%.Highly bound to plasma proteins (α1 acid glycoprotein).
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 diseaseBPHScorpion sting
Terazosin &Doxazosin
Long acting( t1/212 & 18hr) congener of prazosin.
Used in HTN & BPH as single daily dose.
Tamsulosin & SilodosinUroselective 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.
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.
α2-receptor blockers
YohimbineNatural alkaloid from Pausinystalia yohimbe.No established clinical role.
Idazoxan Has membrane stabilizing action.
Ergot alkaloids Ergotamine & DihydroergotamineCompetitive α-receptor blockers.Principal use is migraine.
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-
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.
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.
CHFShort term benefit, leads to Na+ & H2O retension.
Migraine Ergotamine more effective
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.
Side effects of α-blockersPalpitationPostural hypotensionNasal blockadeDiarrheaFluid retentionInhibition of ejaculation & impotence.
Thank you