Alpha-1 blockers (also called alpha-adrenergic blocking agents ) are drugs that block alpha-1-adrenergic receptors in the arteries, smooth muscles, and central nervous system. network. By blocking alpha-1 receptors causes the muscles and fine arteries to dilate. It is mainly used to treat benign prostate hyperplasia (BPH), hypertension and post-traumatic stress disorder.
Over the last 40 years, various drugs have been developed from non-selective alpha-1 blockers to selective alpha-1 inhibitors. The first drug used was a non-selective alpha blocker, named phenoxybenzamine and used to treat BPH. Today tamsulosin is the first-line treatment for BPH and is a selective alpha-1 inhibitor.
Enlarged prostate gland can cause serious pain and contraction of the prostate gland causing less urination. Alpha-1 blockers are used to treat these symptoms.
Video Alpha-1 blocker
Medical use
Benign prostatic hyperplasia
Benign prostatic hyperplasia (BPH) is an enlarged prostate gland. Alpha-1 blockers are the most common drug used to treat BPH. Alpha-1 blockers are the first-line treatment for BPH symptoms in men. Doxazosin, terazosin, alfuzosin and tamsulosin have all been well established in the treatment to reduce the symptoms of lower urinary tract (LUTS) caused by benign prostatic hyperplasia. They are all believed to be equally effective for this purpose. First-generation alpha-1 inhibitors, such as prazosin, are not recommended for treating lower urinary tract symptoms as their effects lower blood pressure. Second and third generation are highly recommended. In some cases alpha-1 blockers have been used in combination therapy with 5-alpha reductase blockers. Dutasteride and tamsulosin are on the market as a combined therapy and the results show that they improve symptoms significantly compared to monotherapy.
Hypertension
Alpha-1 blockers are used as second-line treatment for high blood pressure. They are not considered good as first-line treatment because some are more selective, although they can be good for treating men with hypertension and BPH. Doxazosin has been shown to improve the symptoms of BPH in the elderly and reduce blood pressure at the same time. BPH is very common in men over 60 years and hypertension as well. Terazosin is also safe and effective for use against hypertension and BPH but is the first generation while doxazosin is the second generation alpha-1 blocker.
Post-traumatic stress disorder (PTSD) and nightmare
Post-traumatic stress disorder is a deactivation condition that can be caused by after several types of life-threatening trauma. This is common in veteran soldiers who have experienced some kind of trauma. Prazosin is commonly used as an antihypertensive but because of alpha-1 adrenergic activity of Prazosin, the activity has been linked to fear and a surprising response. Prazosin has been established as an effective and safe alpha-1 adrenergic receptor antagonist. It can be used to overcome the trauma of nightmares, sleep disorders and chronic PTSD.
Maps Alpha-1 blocker
Adverse effects
Since Alpha-1-a blocker affects BPH symptoms more specifically than Alpha-1 blockers, adverse effects seem to be more related to the reproductive system while minimizing the effects on the blood pressure system. Hypotension and its complications (such as weakness and dizziness) are a constant risk, however, although selective alpha-1a inhibitors are used. It is therefore important when starting treatment with alpha-1 inhibitors to monitor blood pressure to minimize the risk of adverse effects associated with low blood pressure.
By reducing the alpha-1-adrenergic activity of the blood vessels, these drugs can cause hypotension (low blood pressure) and interfere with baroreflex response. Thus, they can cause dizziness, dizziness, or fainting when risen from a lying or sitting position (known as orthostatic hypotension or postural hypotension). For this reason, it is generally recommended that alpha blockers be taken at bedtime. The risk of a first dose phenomenon can be reduced or eliminated by a gradual dose titration, since the adverse effects of Prazosin are associated with the dose. This is also the case for Tamsulosin and it can be assumed that the other alpha-1 blockers work in the same way, because Tamsulosin is an alpha-1-a blocker and Prazosin is an alpha-1 blocker. The risk of iris sliced ​​floppy syndrome during cataract surgery increases when the patient uses an alpha-1 blocker. This is particularly the case for Tamsulosin and other alpha-1-a blockers, since alpha-1-a receptors are present in the dilator iris muscle, allowing uninterrupted action of the iris nerve muscle constrictors that are preserved and iris loss. However this can be treated if the eye surgeon is experienced and has knowledge of the use of alpha-1 blockers.
Interactions and contraindications
Contraindications: Allergy or hypersensitivity to alpha-1 blockers or any of the active ingredients, including drug-induced angiodema. Patients with a history of orthostatic hypotension or severe liver disorder.
Interactions: No interactions were recorded when administered with atenolol (beta blocker), enalapril (ACE inhibitor) and theophylline. Furosemide has a decreasing effect on plasma levels for tamsulosin, and increased plasma levels with cimetidine. There is no dose adjustment that needs to be done when the level is within the normal range. Drugs that inhibit CYP3A4 eg itraconazole, ketoconazole and ritonavir may increase exposure to drugs for tamsulosin, alfuzosin, doxazosin and silodosin. Grapefruit is also a strong inhibitor of the CYP3A4 enzyme, so concurrent use is not recommended as it can increase plasma levels of Alpha-1 blockers metabolized by the CYP3A4 enzyme. Some medications; such as Fluoxetine, Paroxetine and Ritonavir are strong inhibitors of the CYP2D6 enzyme and therefore are not recommended to be used in conjunction with tamsulosin, as it can increase plasma tamsulosin levels and increase the risk of side effects.
Warfarin and diclofenac may increase the rate of elimination for tamsulosin, but have not shown any effect on alfuzosine hydrochloride. Co-administration of alpha-1 inhibitors can cause hypotension.
Because alpha-1 blockers can cause orthostatic hypotension, co-administration with antihypertensives and vasodilators should be evaluated with respect to risk-benefit because the risk for low blood pressure is greatly increased.
By reducing? 1 -adrenergic vascular activity, these drugs can cause hypotension (low blood pressure) and interfere with baroreflex response. Thus, they can cause dizziness, dizziness, or fainting when risen from a lying or sitting position (known as orthostatic hypotension or postural hypotension). For this reason, it is generally recommended that alpha blockers be taken at bedtime. In addition, the risk of a first dose phenomenon can be reduced by starting with a low dose and titration up as needed.
Because these drugs can cause orthostatic hypotension, as well as low blood pressure in general, these agents can interact with other drugs that increase the risk for low blood pressure, such as antihypertensives and other vasodilators.
As discussed above, tamsulosin may have a lower risk for low blood pressure and orthostatic hypotension because of its selectivity for? 1a -adrenergic receptor. On the other hand, drugs (a) increase the risk of iris floppy syndrome, and (b) may indicate adverse drug side effects (ADRs) of sulfa-related drugs.
List of alpha-1 blockers
Silodosin exhibits high affinity and selectivity for alfa-1a adrenergic receptors found in the prostate that ensure that it works quickly and effectively to relieve symptoms of BPH. Low affinity Silodosin for alpha-1b receptor in blood vessels is considered to be reflected in the low incidence of orthostatic side effects and vasodilation.
Pharmacokinetics
Absorption Ã,: Bioavailability of tamsulosin and terazosin is about 90% during oral administration in a fasting state. Food may have an effect on absorption for tamsulosin if it has been digested shortly before, Tmax for fasting state is 2.9 to 5.6 hours compared with 5.2-7 hours under feeding. Food has no effect on terazosin absorption but can delay plasma concentration for 1 hour, peak plasma levels of about 1-2 hours. Alfuzosine bioavailability under feeding conditions was about 49%. Tmax 8 hours under feeding conditions. Tamsulosin Cmax ranged from 13.9-18.6 ng/mL fastest and in a feeding state of 7.2-15.6 ng/mL, Cmax for alfuzion was 13.6 mg/mL.
Distribution: Tamsulosin is 99% bound to plasma and low distribution volume 0.2l/kg. Alfuzosine is 90% bound to plasma and distribution volume 2.5l/kg. Terazosin 90-94% is bound to plasma.
Elimination: The elimination half-life for alfuzosine is about 8 hours, alfuzosine is metabolized primarily through the liver. 75-91% are excreted in the feces and 35% in unchanged form. The volume of distribution and excretion increased with renal impairment did to bind the protein less, but the part-time elimination rate did not change. therefore no dose adjustment is required for low to moderate renal impairment. Delayed part-time elimination, peak concentrations in double plasma and bioavailability change in patients with liver disorders. Alfuzosin should not be used for patients with renal impairment. Tamsulosin is excreted through the urine and 9% of the unchanged in its active form, the elimination half-life for tamsulosin is between 9-13 hours for healthy volunteers. The elimination half-life for the target patient is about 14-15 hours. No dose adjustment is required for patients with renal impairment and moderate liver disorders. 10-20% of terazos are excreted unchanged in urine and feces during oral administration. 40% are eliminated in urine and 60% in stool. Elimination of the half-life for terazosin is between 8-13 hours. No dose adjustment required for patients with renal impairment. Terazosin is metabolized by the liver and excreted by bilary channels, so patients with moderate liver disorders should receive a dose of ditazed terazosine magician. Patients with severe liver disorders should not take terazosin due to lack of clinical data.
Action mechanism
Alpha-1 blockers inhibit norepinephrine that inhibits blood vessels from contraction. This occurs because the alpha 1 blocker inhibits the activation of the post-synaptic alpha-1 receptor by releasing catecholamines and/or neural circulation. Alpha-1 blockers have no effect on release of renin or cardio output.
Benign prostatic hyperplasia
Alpha-1 blockers, block alpha receptors and relax the smooth muscles in the bladder. This helps urine flow smoothly and can reduce pain. of the bladder pressing the prostate. Selective alpha-1 inhibitors are more tolerable than non-selective alpha blockers in the body and therefore work better on BPH. Terazosin, tamsulosin and doxazosin are the main drugs for BPH because they have a long and modified release formulation. Tamsulosin is primarily used because it does not affect blood pressure and the side effects of vasodilation are minimal.
Hypertension
Alpha-1 blockers lower blood pressure by blocking alpha-1 receptors so that norepinephrine can not bind to receptors and cause dilated blood vessels. Without obstacles in the blood vessels, blood flows more freely. Alpha-1 blockers have a good effect on lipoproteins in plasma, insulin resistance and cause blood glucose levels to be lower.
By changing the furan ring on the prazosin ring to tetrahydrofuran (as in alfuzosin) the half-life is greatly increased, allowing once-daily dosing. Silodosin is the most selective for alpha-1a receptors. The affinity and selectivity for alpha-1 receptors appears to be determined by the structure between quinazoline and the furan ring. Piperazine is present in prazosin, terazosin and doxazosin which seem to contribute to the inhibition of non-selective alpha-1 receptors.
Doxazosin 2,4-diamino-6,7-dimethoxyquinazoline variation for in vitro and in vivo performance. A key factor in this structure is the derivation of 2,4-diamino-6,7-dimethoxyquinazoline nuclei that is replaced for norepinephrine. And the protonated N-1 quinazoline is also a key factor.
Tamsulosin is the most powerful alpha blocker and has the most selectivity for alpha 1a blockers. It does nothing for beta-adrenoceptors because it does not have a beta-hydroxyl group and therefore can not block beta-receptors.
History
The first effective treatment for benign prostatic hyperplasia (BPH) is non-selective alpha non-selective alpha blocker fensterbenzamine. Dibenzyline is the first brand name to be marketed. Today phenoxybenzamine is not the first choice because of many side effects such as lowering blood pressure.
The first selective alpha-1 blocker approved for treating hypertension is prazosin. Prazosin was synthesized in 1974 when Constantin and Hess tried to find vasodilators that had minimal effects on cardiac activity. Prazosin is a much better tolerated drug than phenoxybenzamine but the problem that remains is to lower blood pressure to many.
Terazosin is the first long-lasting alpha 1 blocker approved by the FDA to treat BPH. Doxazosin and Tamsulosin were approved thereafter. The first-line treatment option today to treat BPH is tamsulosin. Not because it is better tolerated or has greater efficacy than previous medicines. Just because the titration of doses is minimal. Alfuzosin SR (continuous release) is the fourth alpha-selective barrier approved by the FDA. It is used to treat BPH and the good thing about Alfuzosin SR, it does not require dose titration. Over 30 years of increasing alpha 1 blockers for BPH has focused primarily on tolerance and good usage.
References
External links
- DrugDigest - Alpha blocker
- RxList.com - Tamsulosin
- alpha-Adrenergic Blockers in the US National Library of Medicine's Medical Subject Headings (MeSH)
Source of the article : Wikipedia
0 Comments