Альфа-1 блокаторлар: қолданылуы, қасиеттері және емдеудегі рөлі

Class of compounds

Alpha 1 blockers (also called alpha adrenergic blocking agents or alpha 1 antagonists) constitute a variety of drugs that block the effect of catecholamines on alpha 1 adrenergic receptors. They are mainly used to treat benign prostatic hyperplasia (BPH), hypertension and post traumatic stress disorder. whereas tamsulosin is a selective antagonist for all alpha 1 subtypes. Drugs that act as selective antagonists at specific alpha 1 adrenergic receptor subtypes have also been developed.

Benign prostatic hyperplasia (BPH) is an enlarged prostate gland. Alpha 1 blockers are the most commonly used medicine to treat BPH. Alpha 1 blockers are first line treatment for the symptoms of BPH in men. In some cases alpha 1 blockers have been used in combined therapy with 5 alpha reductase blockers. Dutasteride and tamsulosin are on the market as combined therapy and results have shown that they improve symptoms significantly versus monotherapy.

Alpha 1 blockers are used as second line treatment for high blood pressure. They are not thought to be good as first line treatment because there are other more selective agents, although they can be good for treating men with hypertension and BPH. Doxazosin has been shown to improve symptoms of BPH in the elderly and reduce blood pressure at the same time. BPH and hypertension are both very common in men over 60 years old. In patients with neurogenic hypertension who fail in achieving blood pressure control with angiotensin converting enzyme inhibitors (ACEi), Angiotensin receptor blockers (ARB) and calcium channel blockers (CCB), alpha and beta adrenergic receptor blockers constitute the main treatment options. This is supported by studies that show surprisingly though consistently that neither alpha nor beta blocker mono therapy reduces sympathetically mediated blood pressure reactivity to acute experimental stressors. Studies of combined oral alpha and beta blockade using an alpha blocker (e. g., doxazosin or terazosin) in combination with a nonlipophilic beta blocker with more reliable bioavailability (e. g., betaxolol, bisoprolol, atenolol and others) have shown a larger antihypertensive effect. This approach also enables separate titration of alpha and beta blocking effects. In these studies, doxazosin was prescribed at the low dose of 1–2 mg.

Post traumatic stress disorder is a disabling mental condition that can develop following a traumatic experience; for example, it is especially common in military veterans and sexual assault survivors. Prazosin is commonly used as an anti hypertensive, but because alpha 1 adrenergic activity has been connected to fear and startle responses, it sees use as a PTSD treatment. Prazosin has been established as an effective and safe centrally active alpha 1 adrenergic receptor antagonist. It can be used to treat trauma nightmares, sleep disturbance and chronic PTSD.

Contraindication : Allergies or hypersensitivity to alpha 1 blockers or any of the active ingredient, that includes angiodema induced by the drug. Patients with a history of orthostatic hypotension or severe hepatic impairment. Interactions : No interactions were recorded when administered with atenolol (beta blocker), enalapril (ACE inhibitor) and theophylline. Some drugs; such as Fluoxetine, Paroxetine and Ritonavir are strong inhibitors of the CYP2D6 enzyme and therefore it is not recommended to use at the same time as tamsulosin, as it may increase plasma levels of tamsulosin and increase the risk of adverse effects. Warfarin and diclofenac can increase the elimination rate for tamsulosin, but has not shown an effect on alfuzosin hydrochloride. Co administration of alpha 1 inhibitor can cause hypotension.

Absorption: Bioavailability of tamsulosin and terazosin is around 90% during oral administration in fasting state. Food can have effect on absorption for tamsulosin if it has been ingested shortly before, Tmax for fasting state is 2,9–5,6 hours compared to 5,2–7 hours in fed state. Food has no effect on absorption of terazosin but can delay plasma level concentration for 1 hour, peak plasma level are around 1–2 hours. Alfuzosin bioavailability under fed state is around 49%. Tmax is 8 hours in fed state.

Alpha 1 blockers inhibit the activation of post synaptic alpha 1 receptors by norepinephrine thus opposing blood vessel contraction. Alpha 1 blockers have no effect on renin release or cardio output.

Alpha 1 blocker, blocks alpha receptors and it relaxes the smooth muscles in the bladder. It helps the urine to flow smoothly and it can lessen the pain caused by the bladder pressing on the prostate. Selective alpha 1 blockers are better tolerated than non selective alpha blockers in the body and therefore works better on BPH. Terazosin, tamsulosin and doxazosin are prime drug for BPH because they have a long half life and modified release formulation. Tamsulosin is primarily used because it doesn't affect the blood pressure and the side effects of vasodilation is minimum. Alpha 1 blockers have a good effect on lipoproteins in plasma, insulin resistance and it causes the glucose levels in blood to lower.

By changing the furan ring in prazosin to tetrahydrofuran ring (as in alfuzosin) the half life is greatly increased, allowing once a day dosing. Silodosin is the most selective for alpha 1a receptors. The affinity and selectivity for alpha 1 receptors seems to be determined by structure between the quinazoline and the furan ring. Piperazine is present in prazosin, terazosin and doxazosin which seems to contribute to the non selective inhibition of alpha 1 receptors. Doxazosin 2,4 diamino 6,7 dimethoxyquinazoline variations for in vitro and in vivo performance. A key factor in these structures were the derivations from 2,4 diamino 6,7 dimethoxyquinazoline nucleus that was replaced for norepinephrine. And N 1 which protonated quinazoline was also a key factor. Tamsulosin is most potent alpha 1 blocker and has the most selectivity for alpha 1a receptors. It has no beta blocking activity.

The first effective treatment for benign prostatic hyperplasia (BPH) was a non selective alpha blocker phenoxybenzamine which was irreversible. Dibenzyline was the first brand name marketed. Today phenoxybenzamine is not the first choice due to many side effects like lowering blood pressure. Terazosin was the first long lasting alpha 1 blocker approved by FDA to treat BPH. Doxazosin and Tamsulosin were approved after. The first line treatment choice today to treat BPH is tamsulosin. It is not better tolerated, nor does it have greater efficacy than the previous drugs, however, it requires minimal dose titration in comparison. Alfuzosin SR (sustained release) was the fourth alpha 1 selective blocker to be approved by FDA and requires no dose titration.