alpha receptor antagonists

Question 1

general alpha 1 receptor antagonist

Answer 1

Selective α1 receptor antagonists
• Non-selective α receptor antagonists
• Synthetic compounds
• phenoxybenzamine
• phentolamine
• tolazoline
• Ergot alkaloids
α receptor antagonists
Potential therapeutic interest –hypertension, BPH and pheochromacytoma. 

Selective α1 receptor antagonists cause less tachycardia than the non- selective α-blockers (prazosin, doxazosin terazosin and tamsulosin)

Question 2

phenoxybenzamine (noncompetitive inhibitor, non-selective)

Answer 2

mechanism: links alpha 1 and alpha 2 receptor irreversible and non-competitive
-> irreversible α blocker, long duration of blockade (14-48 hours)
• indication: treatment of pheochromocytoma prior to surgical removal to prevent hypertensive crisis and also for inoperable tumor of such.

adverse affects: postrual hypotension, nasal stiffness and nausea, inhibition of ejaculation and may cause reflex tachycardia.

Question 3

phentolamine

Answer 3

Phentolamine and tolazoline
• reversible α blockers
• phentolamine is strong, used in pheochromocytoma (treatment and
diagnosis)
• tolazoline is a weak blocker, used as a vasodilator in peripheral
vascular diseases (very limited indications)

Question 4

ergot alkaloids

Answer 4

2 major families:
amine alkaloids (ergometrine)- used in postpartum hemorrhage
peptide alkaloids (ergotamine, ergocryptine, ergocrystine, ergocornine)- used in migrane therapy
agonist, partial agonist or antagonist actions on several receptors, especially: α, 5-HT, D.

main actions
• vasoconstriction, vasospasm,
• powerful stimulation of the pregnant uterus,
• CNS actions.

semisynthetic or synthetic, structurally related drugs:
• dihydro-derivatives: more selective for α receptors (antagonists)
• methysergid: more selective for 5-HT receptors (antagonist)
• bromocryptine, cabergoline: more selective for D receptors (agonist)
• lysergic acid diethylamide (LSD): partial agonist at 5-HT receptors in CNS.

• therapeutic indications (ergot alkaloids)
• postpartum hemorrhage (ergometrine, ergotamine);
NEVER before delivery!
• migraine therapy (ergotamine)
• therapeutic indications (ergot derivatives)
• hyperprolactinemia (bromocryptine, cabergoline)
• Parkinson’s disease (bromocryptine, cabergoline)
• migraine therapy (dihydroergotamine, methysergide) • peripheral vascular diseases (dihydro-derivatives)

• possible adverse effects
• nausea, vomiting, diarrhea, prolonged vasospasm, CNS disturbances

Question 5

Drugs with α blocking side effect

Answer 5

Drugs with α blocking side effect
• several (mostly tricyclic) antidepressants
(eg. amitriptyline, imipramine)

• several antipsychotics
(eg. phenothiazines - chlorpromazine)
• may cause hypotension, and reflex tachycardia

• quinidine= antiarrhythmic drug, too rapid iv. injection may cause blood pressure fall

Question 6

prazosin- selective alpha 1 receptor antagonist

Answer 6

• their major advantage over the non-selective α-blockers: less tachycardia
Prazosin
• clinical indications:
• chronic treatment of mild to moderate hypertension
• benign prostate hyperplasia
• orally active, short half-life (3x/day)
• side effects
• first-dose phenomenon (in the beginning of the therapy - severe postural hypotension and syncope)
to avoid: treatment should be started at bedtime, with a low dose
• additional side effects are mild and nonspecific: dizziness, palpitations, headache
α1 blockers are not first line antihypertensive agents, but they can have important advantages: they can be given in case of hyperlipidaemias and diabetes

Question 7

side-effects of alpha 1 blockers

Answer 7

diziness, lack of energy, nasal congestion, headache drowsiness, orthostatic hypotension (less than observed in phenoxybenzamine).

Question 8

terazosin and doxazosin

Answer 8

• prazosin-like drugs with longer half-life

* indications: hypertension, benign prostate hyperplasia

Question 9

tamsulozine and silodosin

Answer 9

• Tamsulozin and silodosin are selective blockers of α1A receptor, whichis expressed mainly in the urinary tract ?
• used for the treatment of benign prostate hyperplasia with less
cardiovascular actions ?

Question 10

urapidil

Answer 10

Urapidil • α1 antagonist, with weak α2 agonist, 5-HT1A agonist and β antagonist
actions
• antihypertensive agent mostly for hypertensive crisis

Question 11

labetalol, carvedilol

Answer 11

α1 and β antagonists

Question 12

yohimbine

Answer 12

alpha 2 selective blockers, used in research mainly nowdays, adverse affect in erectile dysfunction