7. Prostrate:
Prostrate & lower urinary tract exhibit high
proportion of α 1a receptors.
α 1 receptor blockers alleviate some symptoms
of BPH
Antagonism of α 1 receptors permits relaxation
of smooth muscles of prostrate & neck &
bladder.
Decreased resistance to urine outflow.
8. Phentolamine:
Potent competetive antagonist at α 1 & α 2
receptors.
Cardiac stimulation d/t antagonism of
presynaptic α 2 receptors.
Minor inhibitory effects at serotonin
receptors, agonist effects at muscarinic & H1
& H2 histamine receptors.
Adverse effects: severe tachycardia,
arrhythmias & myocardial ischemia.
9. Phenoxybenzamine:
Binds covalently to α receptors l/t irreversible
blockade of long duration (14-48 hrs).
Inhibits reuptake of released NE by presynaptic
adrenergic nerve terminals.
Blocks H1, Ach & serotonin receptors.
Attenuation of catecholamine induced
vasoconstriction.
Reduces blood pressure when sympathetic tone
is high.
10. Cardiac output may increase: reflex effects
& some blockade of presynaptic receptors in
cardiac sympathetic nerves.
Major therapeutic use: pheochromocytoma.
Adverse effects: orthostatic hypotension &
tachycardia.
Nasal stuffiness & inhibition of ejaculation.
11. Prazosin:
Piperazinyl quinazoline with ~ 1000 fold
greater affinity for α 1 than α 2 receptors in
arterioles & veins.
Relatively potent inhibitor of cyclic nucleotide
phosphodiesterases.
Leads to fall in peripheral vascular resistance
& venous return without increasing heart rate.
Does not promote release of NE from
sympathetic nerve endings in heart.
Appears to depress baroreflex function in
hypertensive patients
Relaxes smooth muscles in prostrate
12. Favorable effects on serum lipids: decreases
LDL & triglycerides. Increases HDL
concentrations
Well absorbed after oral absorption.
Bioavailability ~ 50~70%.
Tightly bound to plasma proteins.
Peak plasma concentration 1-3 hrs.
Extensively metabolized in liver; plasma half
life 1~3hrs.
Duration of antihypertensive action 7-10 hrs.
Marked postural hypotension (first dose
phenomenon)
13. Terazosin & Doxazosin:
Structural analogs of prazosin, highly
selective for α 1 receptors.
Longer half life & duration of action than
prazosin (Terazosin t1/2~ 12 hrs, DOA- 18 hrs;
Doxazosin t1/2~ 20 hrs, DOA- 36 hrs)
Induce apoptosis in prostrate smooth muscles.
May lessen symptoms associated with chronic
BPH by limiting cell proliferation.
14. Tamsulosin & Silodosin:
Selective α 1a receptor antagonists.
Tamsulosin: relatively greater potency inhibiting
prostrate smooth muscle versus vascular smooth
muscle.
Tamsulosin: well absorbed, high bioavailability,
extensively metabolized by CYPs, t1/2 5-10 hrs.
A/E: Retrograde ejaculation, IFIS in patients
undergoing cataract operation (billowing of
flaccid iris, propensity for iris prolapse,
progressive intraoperative pupillary constriction
Silodosin: Weaker longer acting analog of
Tamsulosin
