Alpha blockers also are known as α-blockers or α-adrenoreceptor antagonists are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors). Alpha blocker drug that blocks receptors in arteries and smooth muscle. This action relaxes the blood vessels and leads to an increase in blood flow and a lower pressure for the control of hypertension. The action in the urinary tract enhances urinary flow in prostatic hypertrophy (enlarged prostate).
Alpha-blockers were used as a tool for pharmacologic research to develop a greater understanding of the autonomic nervous system. Using alpha blockers, scientists began characterizing arterial blood pressure and central vasomotor control in the autonomic nervous system. Today, they can be used as clinical treatments for a limited number of diseases.
Types /Classification of Alpha Blockers
- α1-blockers act on α1-adrenoceptors
- α2-blockers act on α2-adrenoceptors
Schematic of G Protein-Coupled Receptor Signaling, representing Gi GPCR signaling, Gs GPCR signaling, and Gq GPCR signaling.
When the term “alpha-blocker” is used without further qualification, it can refer to an α1 blocker, an α2blocker, a nonselective blocker (both α1 and α2 activity), or an α blocker with some β activity. However, the most common type of alpha blocker is usually an α1 blocker.
Non-selective α-adrenergic receptor antagonists include:
- Phenoxybenzamine
- Phentolamine
- Tolazoline
- Trazodone
Selective α1-adrenergic receptor antagonists include:
- Alfuzosin
- Doxazosin
- Prazosin (inverse agonist)
- Tamsulosin
- Terazosin
- Silodosin
Selective α2-adrenergic receptor antagonists include:
- Atipamezole
- Idazoxan
- Mirtazapine
- Yohimbine
Details classification of alpha blockers
| α1 or Alpha-1 Blockers |
- Agonists: 6-FNE
- Amidephrine
- Anisodine
- Buspirone
- Cirazoline
- Corbadrine
- Desglymidodrine
- Dexisometheptene
- Dipivefrine
- Dopamine
- Droxidopa
- Ephedrine
- Epinephrine
- Etilevodopa
- Ethylnorepinephrine
- Indanidine
- Isometheptene
- L-DOPA (levodopa)
- L-Phenylalanine
- L-Tyrosine
- Melevodopa
- Metaraminol
- Methoxamine
- Methyldopa
- Midodrine
- Naphazoline
- Norepinephrine
- Octopamine (drug)
- Oxymetazoline
- Phenylephrine
- Phenylpropanolamine
- Pseudoephedrine
- Synephrine
- Tetryzoline
- Tiamenidine
- Antagonists: Abanoquil
- Adimolol
- Ajmalicine
- Alfuzosin
- Amosulalol
- Arotinolol
- Atypical antipsychotics (e.g., brexpiprazole,
- clozapine, olanzapine, quetiapine, risperidone)
- Benoxathian
- Buflomedil
- Bunazosin
- Carvedilol
- Corynanthine
- Dapiprazole
- Domesticine
- Doxazosin
- Ergolines (e.g., ergotamine, dihydroergotamine, lisuride, terguride)
- Fenspiride
- Hydroxyzine
- Indoramin
- Ketanserin
- Labetalol
- Mepiprazole
- Metazosin
- Naftopidil
- Neldazosin
- Niaprazine
- Nicergoline
- Niguldipine
- Phendioxan
- Phenoxybenzamine
- Phentolamine
- Phenylpiperazine antidepressants(e.g., hydroxynefazodone,
- nefazodone, trazodone, triazoledione)
- Prazosin
- Quinazosin
- Quinidine
- Ritanserin
- Silodosin
- Spiperone
- Talipexole
- Tamsulosin
- Terazosin
- Tiodazosin
- Tolazoline
- Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin)
- Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, imipramine, trimipramine)
- Trimazosin
- Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine)
- Zolertine
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| α2 Blockers |
- Agonists: (R)-3-Nitrobiphenyline
- Apraclonidine
- Brimonidine
- Cannabivarin
- Clonidine
- Corbadrine
- Detomidine
- Dexmedetomidine
- Dihydroergotamine
- Dipivefrine
- Dopamine
- Etilevodopa
- Ephedrine
- Ergotamine
- Epinephrine
- Etilefrine
- Ethylnorepinephrine
- L-DOPA (levodopa)
- L-Phenylalanine
- L-Tyrosine
- Lofexidine
- Medetomidine
- Melevodopa
- Methyldopa
- Mivazerol
- Naphazoline
- Norepinephrine
- Oxymetazoline
- Phenylpropanolamine
- Piperoxan
- Pseudoephedrine
- Rezatomidine
- Rilmenidine
- Romifidine
- Talipexole
- Tasipimidine
- Tetrahydrozoline
- Tiamenidine
- Tizanidine
- Tolonidine
- Urapidil
- Vatinoxan
- Xylazine
- Xylometazoline
- Antagonists: 1-PP
- Adimolol
- Aptazapine
- Atipamezole
Atypical antipsychotics (e.g., asenapine, brexpiprazole, clozapine,
lurasidone, paliperidone, quetiapine, risperidone, zotepine)
- Azapirones (e.g., buspirone, gepirone, ipsapirone, tandospirone)
- Buflomedil
- Cirazoline
- Efaroxan
- Esmirtazapine
- Fenmetozole
- Fluparoxan
- Idazoxan
- Mianserin
- Mirtazapine
- Olanzapine
- Pardoprunox
- Phentolamine
- Phenoxybenzamine
- Setiptiline
- Spiroxatrine
- Sunepitron
- Tolazoline
- Typical antipsychotics (e.g., chlorpromazine, fluphenazine,
- loxapine, thioridazine)
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Mechanism of action of Alpha Blockers
Alpha blockers work by blocking the effect of nerves in the sympathetic nervous system. This is done by binding to the alpha receptors in smooth muscle or blood vessels. α-blockers can bind both reversibly and irreversibly.
There are several α receptors throughout the body where these drugs can bind. Specifically, α1 receptors can be found in most vascular smooth muscle, the pupillary dilator muscle, the heart, the prostate, and pilomotor smooth muscle. On the other hand, α2 receptors can be found in platelets, cholinergic nerve terminals, some vascular smooth muscle, postsynaptic CNS neurons, and fat cells.
The structure of α receptors is a classic G protein-coupled receptors (GPCRs) consisting of 7 transmembrane domains, which form three intracellular loops and three extracellular loops. These receptors couple to heterotrimeric G proteins composed of α, β, and γ subunits. Although both of the α receptors are GPCRs, there are large differences in their mechanism of action. Specifically, α1 receptors are characterized as Gq GPCRs, signaling through Phospholipase C to increase IP3 and DAG, thus increasing the release of calcium. Meanwhile, α2 receptors are labeled as Gi GPCRs, which signal through adenylyl cyclase to decrease cAMP.Because the α1 and α2 receptors have different mechanisms of action, their antagonists also have different effects. α1 blockers can inhibit the release of IP3 and DAG to decrease calcium release, thus, decreasing overall signaling. On the other hand, α2 blockers prevent the reduction of cAMP, thus leading to an increase in overall signaling.
Indications of Alpha Blockers
It may be used as an adjunct in the treatment of hypertension, as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone, for differential diagnosis of pheochromocytoma in hypertensive patients, prophylaxis of vascular migraine headaches, treatment of severe dysmenorrhea, management of vasomotor symptoms associated with menopause, rapid detoxification in the management of opiate withdrawal, treatment of alcohol withdrawal used in conjunction with benzodiazepines, management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, and in the treatment of attention-deficit hyperactivity disorder (ADHD).
Contra-Indications of Alpha Blockers
Side Effects of Alpha Blockers
The most common
More common
Rare
Drug Interactions of Alpha Blockers
Alpha blockers may interact with the following drugs, supplements, & may change the efficacy of drugs
- alpha-1 blockers (e.g., doxazosin, prazosin, tamsulosin)
- alpha-2 blockers (e.g., clonidine, dexmedetomidine, methyldopa)
- angiotensin-converting enzyme inhibitors (ACEIs; e.g., captopril, ramipril)
- angiotensin II receptor blockers (i.e., irbesartan, losartan, valsartan)
- antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
- atorvastatin
- azole antifungals (e.g., itraconazole, ketoconazole, posaconazole)
- barbiturates (e.g., phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-agonists (e.g., formoterol, salbutamol, salmeterol)
- other beta-blockers (e.g., propranolol, metoprolol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- cyclosporine
- dexamethasone
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide)
- duloxetine
- levodopa
- lidocaine
- MAO inhibitors (e.g., phenelzine, moclobemide, selegiline)
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- nilotinib
- nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen)
- other beta-blockers (e.g., atenolol, metoprolol, propranolol)
- pentoxifylline
- phosphodiesterase-5-inhibitors (e.g., sildenafil, tadalafil)
- selective serotonin reuptake inhibitors (SSRI; e.g., fluoxetine, paroxetine, sertraline)
- sunitinib
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
Alternative alpha blockers, such as prazosin, tamsulosin, doxazosin, or terazosin can have adverse interactions with beta blockers, erectile dysfunction drugs, anxiolytics, and antihistamines. Again, these interactions can cause dangerous hypotension. Furthermore, in rare cases, drug interactions can cause irregular, rapid heartbeats or an increase blood pressure.
Yohimbine can interact with stimulants, hypertension drugs, naloxone, and clonidine. Interactions with such drugs can cause either an unintended increase in blood pressure or potentiate an increase in blood pressure.
References
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