Alpha-1 adrenergic receptors antagonists or alpha-1-blocking drugs
General features
By reducing the stimulation of peripheral alpha-1 receptors, alpha-1 antagonists induce :
- decrease of arterial and venous vasoconstriction and consequently decrease of peripheral resistance and lowering of arterial pressure,
- decrease of platelet aggregation,
- facilitation of bladder evacuation.
By reducing stimulation of central alpha-1 receptors, alpha-1 antagonists which cross the blood-brain barrier have a sedative effect.
Alpha-1 a ntagonists have vascular or urologic therapeutic uses according to their preferential impact. However, this selectivity is not complete and they can be at the origin of various beneficial or adverse effects .
Alpha-1 antagonists with vascular therapeutic uses
The principal alpha-1 antagonists with vascular therapeutic uses are prazosin, urapidil, ifenprodil and buflomedil. Prazosin is the drug of reference of this group.
- Prazosin
The principal effect of prazosin is vasodilation by alpha-1 antagonism. As it does not inhibit the presynaptic alpha-2 receptors, endogenous norepinephrine present in the synaptic cleft inhibits its own release.
It is indicated in the treatment of arterial hypertension, congestive heart failure and Raynaud syndrome .
Its main adverse effects are postural hypotension with lipothymia, dizziness (especially at the beginning of treatment), edema, tachycardia and palpitations of reflex origin, as well as digestive disorders. Urinary incontinence and erectile dysfunction have been reported. Prazosin hardly crosses the blood-brain barrier and has little sedative effect.
The sustained-release formulation regularizes its hypotensive effect and reduces frequency and importance of adverse effects.
To reduce adverse effects, it is necessary to start the treatment with low doses taken in the evening, to increase doses gradually and to stop them gradually.
Prazosin |
PRAZOSIN Capsules |
- Urapidil
Urapidil, in addition to its alpha-1 blocking effect which is predominant, has a 5HT1A agonist effect and central actions. Urapidil is prescribed in the treatment of arterial hypertension.
Its adverse effects are dizziness, headache, postural hypotension.
- Ifenprodil
Ifenprodil is alpha-1 and alpha-2-blocking agent (blocking of presynaptic alpha-2 receptors increases noradrenaline release).
It is proposed in the treatment of arteritis.
- Buflomedil
Buflomedil has an alpha-1 blocking effect and possibly a calcium-channel blocking effect. Buflomedil is prescribed in the treatment of arteriopathies and Raynaud syndrome. In case of poisoning, it can cause seizures and heart rhythm disorders.
- Raubasine
Raubasine is an alpha-1-blocking agent which is proposed as cerebral anti-ischemic agent.
- Ergot derivatives
Nicergoline and dihydroergotoxine are ergot derivatives with alpha-1-blocking effects. Dihydroergotoxine is a combination of 3 compounds dihydroergocornine, dihydroergocristine, dihydroergocryptine. They have been proposed in the treatment of cerebral ischemia and cerebral disorders of senescence.
- Indoramin
Indoramin is an alpha-1 antagonist and a H1antihistamine; it is moreover an antagonist of certain effects of serotonin, dopamine and prostaglandins. It has been used in prophylactic treatment of migraine.
- Moxisylyte
Moxisylyte, also called thymoxamine is proposed in the treatment of vascular disorders of senescence.
Notice
Many neuroleptics and antidepressants have alpha-1 blocking properties, partially responsible for their sedative and hypotensive effects.
Alpha-1 antagonists with urologic uses
Alpha-1 adrenergic antagonists used to relieve urinary symptoms of benign prostatic hyperplasia are afluzosin, tamsulosin, terazosin and doxazosin. They act preferentially on alpha-1 adrenergic receptors of vesical trigone muscle, urethra and prostate. They improve functional symptoms of prostatic adenoma without acting on the adenoma itself.
They can induce various adverse effects: lipothymic tendency, decrease of blood pressure, tachycardia, asthenia, drowsiness.
- Alfluzosin
Alfuzosine was one of the first alpha-1 antagonists having an urologic specificity to be released on the market.
Tamsulosin has alpha-1-blocking properties quite similar to those of afluzosin, with perhaps a better urologic selectivity.
Tamsulosin |
FLOMAX* Capsules |
- Terazosin
Chemical structure and properties of terazosin are quite similar to those of prazosin. Its plasma half-life is longer than that of prazosin.
Terazosin |
HYTRIN* Capsules |
- Doxazosin
Doxazosin and trimazosin are also alpha-1-blockers close to prazosin. Doxazosin, compared with chlorthalidone in the treatment of arterial hypertension, was effective as an hypotensive, but there were more cardiovascular adverse effects in doxazosin group than in chlorthalidone group.
Doxazosin |
DOXAZOSIN Tablets |
- Prazosin
Prazosin, generally used as an antihypertensive drug, can also be used in the supportive treatment of urinary functional disorders caused by prostatic adenoma (see higher).
In an patient presenting simultaneously an arterial hypertension and functional symptoms of benign prostatic hyperplasia, the prescription of an alpha-1 blocker seems a solution likely to improve the two disorders.
Notice
Moxisylyte is a product marketed for many years for the treatment of senescence disorders (see higher). Used with higher dosage (tablets of 120 mg) in the treatment of the prostatic functional disorders, it induced dose-dependant hepatotoxicity and was withdrawn from the market.
Moxisylyte was reintroduced because of its vasodilatator effect in another therapeutic use, induction of erection in patients with erectile dysfunction, where it is used by intracavernous route in a discontinuous way and in lower dosage.
Inhibitors of type V phosphodiesterases such as silfénadil, active by oral route ( See “NO-mimetic”. ), are used preferentially to drugs which require a local injection.
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