Adrenergic blocking agent

Last updated

Adrenergic blocking agents are a class of drugs that exhibit its pharmacological action through inhibiting the action of the sympathetic nervous system (SNS) [1] in the body. The sympathetic nervous system is an autonomic nervous system that we cannot control by will. It triggers a series of responses after the body releases chemicals named noradrenaline (norepinephrine) and adrenaline (epinephrine). [1] These chemicals will act on adrenergic receptors, with subtypes alpha-1, alpha-2, beta-1, beta-2, and beta-3, which ultimately allow the body to trigger a fight-or-flight response to handle external stress. [1] These responses include vessel constriction in general vessels whereas there is vasodilation in vessels that supply skeletal muscles or in coronary vessels. [1] Additionally, heart rate and contractile force increases when the SNS is activated, which may be harmful to cardiac function as it increases metabolic demand. [1]

Contents

Adrenergic blocking agents treat certain diseases through blocking the adrenergic receptor, [2] [3] preventing it from being activated by noradrenaline and adrenaline. As a result, it stops the body from producing the fight-or-flight response.

Medical uses

There are drugs that are approved by the US Food and Drug Administration (FDA), whereas there are some off-label uses as well.

Alpha-1 blocker

The alpha blockers mostly act in our smooth muscles, especially the ones that control the size of vessels. [3] Thus, alpha1 blockers can dilate blood vessels and decrease the blood pressure. [3] Depending on its site of action, it can be used to treat different diseases. [3] They can be used to treat signs and symptoms of benign prostatic hyperplasia, hypertension (but not as first line agent), pheochromocytoma, extravasation management and reversal of local anesthesia. [3]

benign prostatic hyperplasia BPH.png
benign prostatic hyperplasia
Manifestation of Raynaud phenomenon Raynaud's Phenomenon (front).jpg
Manifestation of Raynaud phenomenon

There are some off- label use as well, such as chronic prostatitis and lower urinary tract symptoms in males, ureteral calculus expulsion, ureteral stent-related urinary symptoms. [3] It can be used in post-traumatic stress disorder, Raynaud phenomenon, hypertensive crisis, extravasation of sympathomimetic vasopressors, problem with urine related to neurogenic bladder, functional outlet obstruction and partial prostate obstruction. [3]

Alpha-2 blocker

Alpha-2 blockers reduce the transmission of neurotransmitters circulating around the body, which contributes to contraction of smooth muscle. [4] Instead of treating diseases, they are used as antidotes for reversing overdose of alpha-2 agonist, reducing the toxic effect of the agonist. [4] Only limited indications are present for this drug. More research is in progress to investigate the possible use of alpha2 blockers. [4]

Beta-1 blocker

Myocardial infarction (heart attack) Depiction of a person suffering from a heart attack (Myocardial Infarction).png
Myocardial infarction (heart attack)

Since beta-1 receptors are mainly located in the heart, most beta-1 blockers take abnormalities associated with the heart as the target. [5] It treats medical conditions like hypertension, arrhythmias, heart failure, chest pain, and myocardial infarction. It treats other symptoms unrelated to heart like migraines and anxiety. [5]

Beta-2 blocker

Beta-2 blockers promote vasodilation in some tissues as mentioned above (arterioles in skeletal muscles or ciliary muscle in the eye etc.). Currently, there is no beta-2 blocker with FDA approval. [6] Butoxamine, an example of beta-2 blocker, has no clinical use but is used in research. [6]

Beta-3 blocker

Due to the relatively limited study on the beta-3 receptor, there is not much development of beta-3 blockers. Therefore, beta-3 blockers has no clinical use. [7]

Adverse effects

Selectivity

Some drugs, being non-selective, can exert actions on 2 or more different receptors. Examples include non-selective beta blocker, which block both beta-1 receptor and beta-2 receptor as well. [2]

Non-selective alpha blocker

The adverse effects of non-selective alpha blockers are caused by the autonomic response to the systemic changes induced by the adrenergic blocking agents. [3] The common adverse effects of alpha blockers are due to the blockade of alpha-1 adrenergic receptors in tissue that requires high level of alpha adrenergic sympathetic input such as arterial resistance, vascular capacitance and the outflow tract of the urinary bladder. [8] The undesirable symptoms are mentioned in the following 'selective alpha-1 blocker' part.

Selective alpha-1 blocker

With the vasodilation and smooth muscle relaxation caused by alpha-1 blockers, [9] around 10 to 20% of patients present undesirable effects of asthenia(weakness), dizziness, faintness and syncope. [8] Other adverse outcomes that are even more uncommon include headache, drowsiness, palpitations, urinary incontinence and priapism. [8] Mild body weight gain of 1–2 kg, which may be associated with secondary hyperaldosteronism, is also observed in some patients. [8]

Demonstration of orthostatic hypotension Orthostatic Hypertension demonstration.gif
Demonstration of orthostatic hypotension

The alpha-1 blockers are associated with the first-dose effect, which refers to the tachycardia response and orthostatic hypotension that caused by the systemic vasodilation at the initial administration of alpha-1 blockers. [3] After the first administration, patients may experience a short period of orthostatic hypotension with a sensation of intense faintness, which is aggravated by upright posture, intravascular volume depletion or concurrent administration of other antihypertensive medications. [8]

Selective alpha-2 blocker

Apart from increasing the noradrenaline release, the selective alpha-2 blockers have the potential to bind with other receptors such as the 5-HT receptor. [10] However, the serotonin receptor antagonism has side effects such as weight gain and impaired movement. [11] Hence, alpha-2 blockers are not used clinically due to its extensive binding.

Similar to the alpha-1 blocker, the alpha-2 family will also present the first-dose effect, but it is generally less pronounced compared with the alpha-1 blockers. [3]

Non-selective beta blocker

The Central Nervous System (CNS) side effects of beta blockers including sleep impairment, dreaming, nightmares and hallucinations are generally small. Also, the effects on short-term memory are minimal. [12]

Selective beta-1 blocker

heart failure Depiction of a person suffering from heart failure.png
heart failure

The cardio-selective beta-1 blockers could cause adverse effects including bradycardia, reduced exercise ability, hypotension, atrioventricular nodal blockage and heart failure. [5] Other possible adverse effects include nausea and vomiting, abdominal discomfort, dizziness, weakness, headache, fatigue, and dryness in mouth and eye. [5] Sexual impairment, memory loss, and confusion are regarded as rare side effects. [5] For diabetic patients, there is an extra risk of masking hypoglycemia-induced tachycardia, while a continuous hypoglycemia could cause acute brain damage. [5]

Selective beta-2 blocker

Demonstration of thickening of airway Asthma attack-airway (bronchiole) constriction-animated.gif
Demonstration of thickening of airway

The blockade of beta-2 receptors will result in vasoconstriction and smooth muscle constriction, [6] and the effects are similar to the agonism of alpha-1 receptors. The side effects include hypertension, tachycardia, arrhythmia and subcutaneous ischemia at the site of injection. [3] Other possible side effects include Raynaud phenomenon, hypoglycemia during exercise, muscle cramps, and increase of airway resistance. [6]

Selective beta-3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, there is limited information on the adverse effects caused by beta-3 blocker.

Contraindications

Alpha-1 blocker

As alpha 1 blocker will dilate blood vessels, it lowers the blood pressure. [3] Thus, it contraindicate to patients with a history of orthostatic hypotension and in current use of phosphodiesterase inhibitors. [3] Moreover, alpha 1 blocker should not be given to patients with heart failure since it expands blood volume. [13]

Alpha-2 blocker

There are limited information about the contraindication of alpha-2 blocker, since it has limited clinical uses.

Beta-1 blocker

Damaged alveoli of a chronic obstructive pulmonary disease patient Depiction of a woman suffering from Emphysema, a type of Chronic Obstructive Pulmonary Disease.png
Damaged alveoli of a chronic obstructive pulmonary disease patient

Traditionally, Beta-1 blocker has several contraindications, including, recent history of fluid retention without use of diuretics, and complete or second degree of heart block. [5] Whilst some studies suggest that there are only minor differences in terms of adverse effect between asthma patients and non-asthma patients, beta-1 blockers are generally not prescribed to asthma patients or patients with chronic obstructive pulmonary disease, due to its potential blockage of beta 2 receptors. [5] Additionally, beta1 blocker should not be given to patients with peripheral vascular diseases, diabetes mellitus, since blockage of beta-2 receptors may lead to vasoconstriction and delayed response to hypoglycemia respectively. [5]

Beta-2 blocker

Beta 2 blocker should be avoided for patients with asthma, COPD as it causes bronchoconstriction. [6] It may also increase the chance of hypoglycemic comas in diabetic patients. [6]

Beta-3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, beta-3 blocker has no clinical use. The contraindications of beta-3 blocker can not be observed.

Overdose

Alpha-1 blocker

Overview of Parasympathetic Nervous System Blausen 0703 Parasympathetic Innervation.png
Overview of Parasympathetic Nervous System

Overdose of alpha-1 blocker will lead to an unopposed parasympathetic activity. [3] Symptoms include bradycardia, hypotension, miosis and sedation.

Alpha-2 blocker

There is a lack of information regarding toxicity caused by overdose of alpha-2 blocker, due to its limited clinical uses.

Beta-1 blocker

Toxicity of beta-1 blocker will contribute to symptoms including bradycardia, hypotension, due to its extensive blockage of beta-1 receptor. [5] Moreover, overdose of beta-1 blocker may lead to the loss of their selectivity and bind to beta-2 receptor, causing bronchopulmonary symptoms. [5] Overdose of lipophilic beta-1 blocker can disturb neurologic functioning, which eventually lead to altered mental states. [5]

To mitigate the toxicity of Beta-1 blocker, glucagon, salts like calcium and sodium bicarbonate, magnesium sulfate are used to reverse beta-1-blocker effect and treating hypotension respectively. [5]

Beta-2 blocker

Similar to alpha-2 blocker, there is a lack of information about beta-2 blocker's toxicity, due to its limited clinical uses.

Beta-3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, there is not much information regarding the toxic effect of beta-3 blocker.

Drug interactions

Alpha-1 blocker

CYP3A4 inhibitors

Alpha-1 blockers such as alfuzosin, doxazosin, tamsulosin, and silodosin involve CYP450 enzyme metabolism, particularly by CYP3A4. [14] Alpha-1 blockers will conjugate in glucuronidation during metabolism. CYP3A4 inhibitors inhibit glucuronidation and hence reduce the glucuronide-conjugated metabolite. [15] Hence, potent CYP3A4 inhibitors can potentially increase their exposure to those alpha blockers. However, there are no clinically significant evidence supporting the drug interaction between alpha-1 blocker and CYP3A4 inhibitors. [16]

Alpha-2 blocker

Since alpha-2 blocker has limited clinical uses, there is a lack of information on drug interaction regarding alpha-2 blocker.

Beta-1 blocker

Antihypertensive drugs

Additional hypotensive effects may occur when patients are taking beta-1 blockers with other antihypertensive drugs such as nitrates, PDE inhibitors, ACE inhibitors and calcium channel blockers. [17] The combination of beta blockers and antihypertensive drugs will work on different mechanism to lower blood pressure. [17] For example, the co-administration of beta-1 blocker atenolol and ACE inhibitor lisinopril could produce a 50% larger reduction in blood pressure than using either drug alone. [18]

Hypertensive drugs

Ibuprofen as an NSAID, can cause drug interaction with beta-1 blocker 200mg ibuprofen tablets.jpg
Ibuprofen as an NSAID, can cause drug interaction with beta-1 blocker

Antihypertensive drugs and hypertensive drugs affect blood pressure in an opposite way. [19] The most common hypertensive drugs in the UK are NSAIDs and steroids. [19] NSAIDs inhibit the synthesis of prostaglandin, which increases the blood pressure and potentially reduce the efficacy of several antihypertensive drugs. [20]

Beta-2 blocker

Since beta-2 blocker has limited clinical uses, there is a lack of information on drug interaction regarding beta-2 blocker.

Beta-3 blocker

Since beta-3 blockers are still under development, there is a lack of information on drug interactions.

Mechanism of action

Alpha-1 blocker

Mechanism of Action of Alpha -1 blocker Alpha 1 Receptor Signaling Cascade.gif
Mechanism of Action of Alpha -1 blocker

Alpha 1 blocker exerts its action on alpha-1 receptor, dilating the smooth muscles. [3] Alpha-1 receptor is a Gq type G-protein coupled receptor. [3] When it is activated, it will lead to activation of phospholipase C, raising the intracellular level of IP3 and DAG. [3] As a result, a higher intracellular concentration of Calcium is achieved, contributing to smooth muscle contraction and glycogenolysis. [3] Alpha 1 blockers, in contrast, bind to and act as inhibitors of alpha-1 receptors, hence preventing the downstream action mentioned(increase of phospholipase C, IP3 and DAG hence increase of Ca Concentration). [3] As a result, the contraction of smooth muscle is suppressed.

Mechanism of Action of Alpha-2 blocker A2 receptor signaling.gif
Mechanism of Action of Alpha-2 blocker

Alpha-2 blocker

The alpha-2 blocker acts on alpha-2 receptors. The alpha-2 receptor is a G-protein coupled receptor as well, which exert its action by Gi function, leading to an inhibition of adenylyl cyclase and thus reducing synthesis of cAMP. [3]  It lowers the amount of calcium inside the cell. [3] Ultimately, release of noradrenaline and epinephrine will be inhibited and smooth muscles tend to dilate. [3] Alpha-2 blocker stops the downstream signaling pathway (inhibit adenylyl cyclase, reduce cAMP and Ca), thus lead to release of the mentioned neurotransmitters(noradrenaline and epinephrine) and contraction of smooth muscle eventually. [3]

Beta-1 blocker

Beta-1 blocker will stop the action of beta-1 receptor via occupying the beta-1 receptor without any activation. [5] The beta-1 receptor is a G-protein-coupled receptor with Gs alpha subunit as its main communication method. [5] By signaling Gs, adenylyl cyclase is recruited to activate a cAMP pathway, which potentiates the receptor. [5] This kind of receptor is located at the heart, kidney and adipose tissue. [5] Eventually, a higher cardiac output(or an increased amount of perfusion to organs) will be resulted. [5] Moreover, more renin is released from the kidney to produce more angiotensin II, increasing the blood volume. [5] Moreover, it encourages lipolysis in adipose tissue. Beta-1 blocker blocks the beta-1 receptor and stops the action mentioned above. (signaling Gs, thus activate cAMP pathway by recruiting adenylyl cyclase, leading to higher cardiac output, renin release and lipolysis)

Beta-2 blocker

Beta-2 blockers cease action of beta-2 receptor by blocking the receptor and preventing it from being activated. [6] Similar to beta-1 receptor, the activated beta-2 receptor will lead to the detach of alpha subunit of Gs protein and attachment of adenylate cyclase. [6] Adenosine triphosphate(ATP), is then catalyzed to form cAMP. [6] cAMP will facilitate release of protein kinase A as well as reduction of intracellular calcium level, relaxing the smooth muscles. [6] Beta-2 blockers stops the above-mentioned signaling pathway, (formation of cAMP, release of protein kinase A, reduction of intracellular calcium level) by blocking the receptor.

The alpha-1 receptor has an opposite action when it is compared with beta 2 receptor. However, the location of the two receptors differs in different tissues, which gives rise to different action of smooth muscle. [21] For example, in the eye, under stimulation of sympathetic nervous system, radial muscles of the iris contract through activation of alpha-1 receptor to allow more light to enter, while the ciliary muscle in the eye relaxes through activation of beta-2 receptor to allow far vision. [21] In the arterioles of skeletal muscle, there is only mild constriction under activation of SNS, due to the balance between alpha-1 and beta-2 receptors. [21] [1]

Beta-3 blocker

Beta-3 blocker will inactivate beta-3 receptor and stops the following action. [7] Beta 3 receptor is a G-protein coupled receptor, similar to beta-1 and beta-2 receptors. [7] The receptor is involved in G-as activation. [7] The receptor will also stimulate adenylyl cyclase. [7] Eventually, it will lead to effects like increase of tryptophan and 5-hydroxytryptamine level, increase of lipolysis in adipose tissue. [7] Beta-3 blocker will antagonize the receptor, which will stop the signaling pathway(G-as activation, stimulation of adenylyl cyclase). [7]

History

Alpha blockers

In 1978, a successful alpha blocker, phenoxybenzamine was confirmed to be clinically beneficial through a randomized, placebo-controlled study. [22] It was the first alpha blocker which was used for treating Benign Prostatic Hyperplasia. [22]

Another Alpha Blocker Prazosin, which was the first drug selective to alpha 1 receptor, was developed in 1987 [22] for the therapy of Benign Prostatic Hyperplasia. Other alpha blockers are then introduced for several diseases. [22]

Beta blockers

The first beta blocker, propranolol, was introduced in the early 1960s by the winner of The Nobel Prize in Physiology or Medicine 1988- Sir James W. Black. [23] The drug was originally developed in order to induce a calm effect on the heart by blocking the beta receptor for adrenaline, treating a range of cardiovascular disorders. [23]

Beta-3 blockers

Unlike other subtypes of receptor, beta 3 receptors were more recently discovered in 1989. [7] Therefore, Beta 3 blockers are still under development.

Agents

The following examples are the common adrenergic blocking agents used clinically.

Drug Chemical structure Drug classClinical usesBrand Name
Phenoxybenzamine
Prazosin.svg
Non-selective alpha blocker Paroxysmal hypertension, pheochromocytoma-induced sweating [24] Dibenzyline [25]
Phentolamine
Phentolamine.svg
Non-selective alpha blocker Reversal agent for unnecessary prolonged local analgesia [26] Regitine [27]
Prazosin
Prazosin.svg
Selective alpha-1 blocker Hypertension, benign prostatic hyperplasia, PTSD associated nightmares and Raynaud phenomenon [28] APO-PRAZO [29]
Tamsulosin
Tamsulosin.svg
Selective alpha-1 blocker Benign prostatic hypertrophy [30] HARNAL D [31]
Yohimbine
Yohimbine structure.svg
Selective alpha-2 blocker Not used clinically, but available for treatment of male erectile dysfunction [32] PMS-YOHIMBINE [33]
Propranolol
Propranolol-skeletal.svg
Non-selective beta blocker Migraine prophylaxis [34] APO-PROPRANOLOL [35]
Timolol
Timolol structure.svg
Non-selective beta blocker Glaucoma and ocular hypertension [36] APO-DORZO-TIMOP [37]
Atenolol
Atenolol structure.svg
Selective beta-1 blocker Hypertension, angina and acute myocardial infarction [38] ALONET [39]
Metoprolol
Metoprolol Structure.svg
Selective beta-1 blocker Angina, heart failure, myocardial infarction, atrial fibrillation and hypertension [40] BETALOC [41]
Butaxamine
Butaxamine.svg
Selective beta-2 blocker Not used clinically, use in animal and tissue experiments [42] (not used clinical)

Non-selective alpha blocker

Selective alpha-1 blocker

Selective alpha-2 blocker

Non-selective beta blocker

Selective beta-1 blocker

Selective beta-2 blocker

Selective beta-3 blocker

References

  1. 1 2 3 4 5 6 Waxenbaum, Joshua A.; Reddy, Vamsi; Varacallo, Matthew (2021), "Anatomy, Autonomic Nervous System", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30969667 , retrieved 2021-03-31
  2. 1 2 Alhayek, Soubhi; Preuss, Charles V. (2021), "Beta 1 Receptors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30422499 , retrieved 2021-03-31
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Taylor, Bryce N.; Cassagnol, Manouchkathe (2021), "Alpha Adrenergic Receptors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30969652 , retrieved 2021-03-31
  4. 1 2 3 Crassous, Pierre-Antoine; Denis, Colette; Paris, Hervé; Sénard, Jean Michel (2007). "Interest of alpha2-adrenergic agonists and antagonists in clinical practice: background, facts and perspectives". Current Topics in Medicinal Chemistry. 7 (2): 187–194. doi:10.2174/156802607779318190. ISSN   1873-4294. PMID   17266605.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Tucker, William D.; Sankar, Parvathy; Theetha Kariyanna, Pramod (2021), "Selective Beta-1-Blockers", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   29763157 , retrieved 2021-03-31
  6. 1 2 3 4 5 6 7 8 9 10 Abosamak, Nour Eldin R.; Shahin, Mohamed H. (2021), "Beta 2 Receptor Agonists/Antagonists", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32644495 , retrieved 2021-03-31
  7. 1 2 3 4 5 6 7 8 Schena, Giorgia; Caplan, Michael J. (2019-04-16). "Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask)". Cells. 8 (4): 357. doi: 10.3390/cells8040357 . ISSN   2073-4409. PMC   6523418 . PMID   30995798.
  8. 1 2 3 4 5 Carruthers, S. G. (1994-07-11). "Adverse effects of alpha 1-adrenergic blocking drugs". Drug Safety. 11 (1): 12–20. doi:10.2165/00002018-199411010-00003. ISSN   0114-5916. PMID   7917078. S2CID   195124733.
  9. ↑ "Alpha 1 Adrenergic Receptor Antagonists", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID   31644028 , retrieved 2021-03-15
  10. ↑ Haddjeri, N.; Blier, P.; de Montigny, C. (1996-05-01). "Effect of the alpha-2 adrenoceptor antagonist mirtazapine on the 5-hydroxytryptamine system in the rat brain". The Journal of Pharmacology and Experimental Therapeutics. 277 (2): 861–871. ISSN   0022-3565. PMID   8627568.
  11. ↑ Casey, Austen B.; Canal, Clinton E. (2017-06-21). "Classics in Chemical Neuroscience: Aripiprazole". ACS Chemical Neuroscience. 8 (6): 1135–1146. doi:10.1021/acschemneuro.7b00087. ISSN   1948-7193. PMC   5495458 . PMID   28368577.
  12. ↑ McAinsh, J.; Cruickshank, J. M. (1990). "Beta-blockers and central nervous system side effects". Pharmacology & Therapeutics. 46 (2): 163–197. doi:10.1016/0163-7258(90)90092-g. ISSN   0163-7258. PMID   1969642.
  13. ↑ Grimm, Richard H.; Flack, John M. (2011-09-13). "Alpha 1 adrenoreceptor antagonists". Journal of Clinical Hypertension (Greenwich, Conn.). 13 (9): 654–657. doi:10.1111/j.1751-7176.2011.00510.x. ISSN   1751-7176. PMC   8108949 . PMID   21896145. S2CID   40129624.
  14. ↑ Troost, Joachim; Tatami, Shinji; Tsuda, Yasuhiro; Mattheus, Michaela; Mehlburger, Ludwig; Wein, Martina; Michel, Martin C (2011-08-01). "Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin". British Journal of Clinical Pharmacology. 72 (2): 247–256. doi:10.1111/j.1365-2125.2011.03988.x. ISSN   0306-5251. PMC   3162654 . PMID   21496064.
  15. ↑ Rossi, Maxime; Roumeguère, Thierry (2010-10-27). "Silodosin in the treatment of benign prostatic hyperplasia". Drug Design, Development and Therapy. 4: 291–297. doi: 10.2147/DDDT.S10428 . ISSN   1177-8881. PMC   2990389 . PMID   21116335.
  16. ↑ Bensalah, N.; Garcia, S.; Rose, F. X.; Bedouch, P.; Conort, O.; Juste, M.; Roubille, R.; Allenet, B.; Tod, M.; Charpiat, B. (2017-04-27). "[How to act when an alpha-blocker is associated with a potent inhibitor of CYP3A4]". Progrès en Urologie. 27 (5): 275–282. doi:10.1016/j.purol.2017.02.003. ISSN   1166-7087. PMID   28365198.
  17. 1 2 Laurent, Stéphane (2017-07-26). "Antihypertensive drugs". Pharmacological Research. 124: 116–125. doi:10.1016/j.phrs.2017.07.026. ISSN   1096-1186. PMID   28780421. S2CID   251991.
  18. ↑ Wing, L. M.; Chalmers, J. P.; West, M. J.; Russell, A. E.; Morris, M. J.; Cain, M. D.; Bune, A. J.; Southgate, D. O. (1988). "Enalapril and atenolol in essential hypertension: attenuation of hypotensive effects in combination". Clinical & Experimental Hypertension, Part A. 10 (1): 119–133. doi:10.3109/10641968809046803. ISSN   0730-0077. PMID   2832102.
  19. 1 2 Elliott, William J. (2006-10-01). "Drug interactions and drugs that affect blood pressure". Journal of Clinical Hypertension (Greenwich, Conn.). 8 (10): 731–737. doi:10.1111/j.1524-6175.2006.05939.x. ISSN   1524-6175. PMC   8109496 . PMID   17028488. S2CID   11714409.
  20. ↑ Polónia, J. (1997). "Interaction of antihypertensive drugs with anti-inflammatory drugs". Cardiology. 88 Suppl 3 (3): 47–51. doi:10.1159/000177507. ISSN   0008-6312. PMID   9397294.
  21. 1 2 3 Alshak, Mark N.; M Das, Joe (2021), "Neuroanatomy, Sympathetic Nervous System", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   31194352 , retrieved 2021-03-31
  22. 1 2 3 4 Lepor, Herbert (2007). "Alpha Blockers for the Treatment of Benign Prostatic Hyperplasia". Reviews in Urology. 9 (4): 181–190. ISSN   1523-6161. PMC   2213889 . PMID   18231614.
  23. 1 2 "The Nobel Prize in Physiology or Medicine 1988". NobelPrize.org. Retrieved 2021-03-15.
  24. ↑ Yoham, Athina L.; Casadesus, Damian (2021), "Phenoxybenzamine", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32809502 , retrieved 2021-03-15
  25. ↑ "Dibenzyline (Phenoxybenzamine): Uses, Dosage, Side Effects, Interactions, Warning". RxList. Retrieved 2021-03-31.
  26. ↑ Grover, Harpreet Singh; Gupta, Anil; Saksena, Neha; Saini, Neha (2015-10-01). "Phentolamine mesylate: It's[sic] role as a reversal agent for unwarranted prolonged local analgesia". Journal of Indian Society of Pedodontics and Preventive Dentistry. 33 (4): 265–268. doi: 10.4103/0970-4388.165646 . ISSN   1998-3905. PMID   26381625. S2CID   24722104.
  27. ↑ "Regitine, OraVerse (phentolamine) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Retrieved 2021-03-31.
  28. ↑ "Prazosin - Search Results - PubMed". PubMed. Retrieved 2021-03-15.
  29. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  30. ↑ "Tamsulosin", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID   31643349 , retrieved 2021-03-15
  31. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  32. ↑ Tam, S. W.; Worcel, M.; Wyllie, M. (2001-09-01). "Yohimbine: a clinical review". Pharmacology & Therapeutics. 91 (3): 215–243. doi:10.1016/s0163-7258(01)00156-5. ISSN   0163-7258. PMID   11744068.
  33. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  34. ↑ Ha, Hien; Gonzalez, Annika (2019-01-01). "Migraine Headache Prophylaxis". American Family Physician. 99 (1): 17–24.
  35. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  36. ↑ Barnes, James; Moshirfar, Majid (2021), "Timolol", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   31424760 , retrieved 2021-03-15
  37. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  38. ↑ Rehman, Baryiah; Sanchez, Daniela P.; Shah, Saumya (2021), "Atenolol", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30969666 , retrieved 2021-03-15
  39. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  40. ↑ "Metoprolol - Search Results - PubMed". PubMed. Retrieved 2021-03-15.
  41. ↑ "Drug Office | 藥 物 辦 公 室". www.drugoffice.gov.hk. Retrieved 2021-03-31.
  42. ↑ PubChem. "Butaxamine". pubchem.ncbi.nlm.nih.gov. Retrieved 2021-03-15.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.