PHENTOLAMINE AND TOLAZOLINE
Alpha 1 receptor blockade at the periphery
STIMULATION OF BETA 1 RECEPTORS OF
EPISODES OF POSTURAL HYPOTENSION
Due to absence of efficient peripheral
vasoconstriction in erect posture due to alpha 1
blockade → peripheral pooling of blood → cerebral
DALE’S VASOMOTOR REVERSAL
PHENOMENON - Prior treatment with alpha1
blocker prevents pressor response of epinephrine
,hence the unopposed vasodilating beta 2 effect is
Nasal stuffiness – vasodilatation & congestion of
Miosis – Due to loss of tone of radial muscles of
Improved urine flow rates-due to smooth muscle
relaxation of bladder neck & prostate
Failure of ejaculation & impotence-due to
inhibition of contraction of vas deferens &
Administered as IV
For diagnosis & management of
PHEOCHROMOCYTOMA - If after giving 5mg of
phentolamine,BP falls by 25-35mm of Hg,it is a
potential case of pheochromocytoma & if it is less it is
a case of essential hypertension.
PVD- Raynaud’s syndrome & frostbite
To prevent dermal necrosis – can be used
locally(S.C.)to prevent dermal necrosis after incidental
extravasation of NE from IV infusion.
To treat HYPERTENSIVE CRISIS that follows abrupt
withdrawal of clonidine or those resulting from
interaction of ingested tyramine containing food with
Binds covalently to alpha 1 & alpha 2 receptors
causing irreversible blockade for longer
Also inhibit reuptake of release noradrenaline by
adrenergic nerve terminals
Preferred drug for pheochromocytoma
Marked postural hypotension with initial first few
doses – first dose phenomenon,tolerance
Other toxic effects- reversible inhibition of
ejaculation,salt & water retention,cardiac
arrhythmias,sedation,fatigue & nausea.
Treatment of pheochromocytoma- controls
episodes of severe hypertension during surgical
manipulation.- 1mg/kg as i.v infusion.
PVD-Raynauds phenomenon & frostbite.
REVERSIBLE SELECTIVE ALPHA
Less tachycardia as it lacks alpha 2 receptor
blocking actions,decreases cardiac preload,it
suppresses sympathetic outflow from CNS.
Potent inhibitor of cyclic phosphodiesterase
enzyme causing rise in cAMP
Causes rise in HDL & adecrease in LDL & TGL
Relaxes smooth muscle in bladder
neck,prostatic capsule &prostatic urethra &
improves urine flow in BPH.
Well absorbed orally.
Treatment of hypertension- initial dose -1mg at
Treatment of BPH- 1-5mg orally BD
Treatment of Raynauds disease.
TERAZOSIN & DOXAZOSIN
Long duration of action
Terazosin 2-5mg orally OD
Doxazoin 1 – 4 mg OD
More effective than fenasteride due to faster action
to decerease urine flow.
Combination is better as it decreases prostate
BUNAZOSIN & ALFUZOSIN
Both are orally effective
Alfuzosin – 2.5mg TID,has to be avoided in patients
with hepatic impairment.
Bunazosin- longer t1/2
TAMSULOSIN & SILODOSIN
Selective alpha 1A receptor antagonist which are
primarily located on bladder neck & urethra.
More effective for treatment of BPH.
Better bioavailability than prazosin
Side effect – abnormal ejaculation & intra – operative
floppy iris syndrome.
ALPHA 2 BLOCKERS
YOHIMBINE & IDAZOXAN
Yohimbine – natural alkaloid from Pausinystalia
No established clinical role.
Although efficacy not clearly established ,can be
used to treat male sexual dysfunction , diabetic
neuropathy & postural hypotension.
Drug can abruptly reverse antihypertensive effect
of alpha 2 agonist like clonidine which is an
important drug interaction.
Ergotamine & dihydroergotamine
Competitive alpha receptor blocking activity
Also act as partial agonist at alpha receptors and
at 5HT2 receptors.
Some of these are oxytocics or dopamine