A-Adrenergic Antagonists

Question 1

Phenoxybenzamine (Dibenzyline)

Answer 1

a1 and a2 antagonist
irreversible – covalent binding
long lasting effects (at least 3 days)
Used for: pre-op treatment of pheochromocytoma to block potential hypertensive crisis during surgery, sweating and HTN caused by pheochromocytoma, certain vasospastic disorders, and frostbite therapy
Side Effects: dizziness, decreased ejaculation ability, fatigue, miosis, orthostatic hypotension, tachycardia
Half-life is approx. 24 hours, and the drug takes several hours after initial dosing to see effects. Care must be taken with other drugs given even upon cessation of therapy, as blockade may still be present for 7 days after the last dose.
Oral dosing

Question 2

Phentolamine (Regitine)

Answer 2

a1 and a2 competitive antagonist
shorter duration of action than PBZ (phenoxybenzamine)
Used for: pheochromocytoma diagnosis, pheochromocytomectomy, MAO induced hypertensive crisis, impotence
Side Effects: dizziness, decreased ejaculation ability, flushing, hypotension, sinus tachycardia
Given parenterally due its short acting

Question 3

Prazosin (Minipress)

Answer 3

Selective a1 antagonist
Used for: treating HTN
Side Effects: dizziness, headaches, drowsiness, palpitations, tachycardia, orthostatic hypotension
Because it doesn’t block a2 receptors, there is no excessive release of NE from neurons, and less of a risk of reflexive tachycardia seen with other alpha blockers
Oral dosing

Question 4

Terazosin (Hytrin)

Answer 4

Selective a1 antagonist
Closely related to Prazosin, but less potent
More water soluble and higher bioavailability that Prazosin, and also has a longer t1/2 (12 hours), and can be used qD.
Used mainly for treatment of hypertension and BPH (benign prostatic hyperplasia)
Oral dosing

Question 5

Doxazosin (Cardura)

Answer 5

Selective a1 antagonist
Also closely related to Prazosin
Similar bioavailability as Prazosin, but has a longer t1/2 (20 hrs), and can be used qD.
Used mainly for treatment for HTN and BPH (benign prostatic hyperplasia)
Oral dosing

Question 6

Alfuzosin (Uroxatral)

Answer 6

Selective a1 antagonist
Also closely related to Prazosin
Similar bioavailability as Prazosin, but with a slightly longer t1/2 (3-5 hrs)
Used for: treatment of BPH (benign prostatic hyperplasia - relaxes smooth muscle in bladder neck and prostate
Available as an extended release oral dose form

Question 7

Tamsulosin (Flomax)

Answer 7

Selective a1A antagonist (but limited a1B activity, which controls vascular smooth muscle)
Therefore, somewhat more selective as treating BPH, with little effect on BP
t1/2 of 5-10 hours
Metabolized mainly by P-450 system
Oral dosing

Question 8

Yohimbine

Answer 8

Selective competitive a2 antagonist
Blocks central a2 receptors leading to increased BP and HR (decreased parasympathetic outflow, and increased sympathetic outflow), possible aphrodisiac properties, due to peripheral a2 blockade and parasympathetic override
Side Effects: antidiuretic effects, CNS excitation, hypertension, tachycardia, increased motor activity, nervousness, irritability, N/V
Local injections into penile shaft to increase erections