penbutolol

Penbutolol is used to treat mild to moderate high blood pressure. Like other beta blockers it is not a first line treatment for this indication.NICE [https://www.nice.org.uk/guidance/cg127/chapter/1-guidance Hypertension guidance] Last updated 2013

It should not be used or only used with caution in people with heart failure and people with asthma. It may mask signs of low blood sugar in people with diabetes and it may mask signs of hyperthyroidism.

Animal studies showed some signs of potential trouble for women who are pregnant, and it has not been tested in women who are pregnant. It is not known if penbutolol is secreted in breast milk.

Penbutolol has a low frequency of side effects.{{cite journal | vauthors = Schoenberger JA | date = Jun 1989 | title = Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group | journal = Am J Cardiol | volume = 63 | issue = 18| pages = 1339–42 | pmid = 2658525 | doi = 10.1016/0002-9149(89)91045-x }} These side effects include dizziness, light headedness, and nausea.

Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors (the two subtypes), thus making it a non-selective β blocker.{{rp|Table 10–2, p 252}} Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.

Blocking β adrenergic receptors decreases the heart rate and cardiac output to lower arterial blood pressure. β blockers also decrease renin levels, which ultimately results in less water being reabsorbed by the kidneys and therefore a lower blood volume and blood pressure.{{cite journal | vauthors = Berdeaux A, Duhaze P, Giudicelli JF | year = 1982 | title = Pharmacological analysis of beta adrenoceptor blockade-induced coronary blood flow redistribution in dogs using l-penbutolol | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 221 | issue = 3| pages = 740–747 | pmid = 6123586 }}

Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by a catecholamine, they stimulate a coupled G protein which activates adenylyl to convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP ultimately alters the movement of calcium ions in heart muscle and increases heart rate.{{rp|213–214}} Penbutolol blocks this and decreases heart rate, which lowers blood pressure.Dent, M. R., Singal, T., Tappia, P. S., Sethi, R., Dhall, N. S. (2008). β-Adrenoceptor-Linked Signal Transduction Mechanisms in Congestive Heart Failure. Chapter 2, pp 27-49 in Signal transduction in the cardiovascular system in health and disease, Eds Srivastava, Ashok K., Anand-Srivastava, Madhu B. Springer Science & Business Media, 2008 {{ISBN|9780387095523}}{{rp|40}}

The ability of penbutolol to act as a partial agonist proves useful in the prevention of bradycardia as a result of decreasing the heart rate excessively. Penbutolol binding β1 adrenergic receptors also alters kidney functions. Under normal physiological conditions, the enzyme renin converts angiotensinogen to angiotensin I, which will then be converted to angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal gland, causing a decrease in electrolyte and water retention, ultimately increasing water excretion and decreasing blood volume and pressure.Finkel, Richard; Clark, Michelle A.; Cubeddu, Luigi X. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition Lippincott Williams & Wilkins, 2009. {{ISBN|9780781771559}}{{rp|221}}

Like propranolol and pindolol, it is a serotonin 5-HT_1A and 5-HT_1B receptor antagonist;{{cite journal | vauthors = Langlois M, Brémont B, Rousselle D, Gaudy F | title = Structural analysis by the comparative molecular field analysis method of the affinity of beta-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors | journal = Eur. J. Pharmacol. | volume = 244 | issue = 1 | pages = 77–87 | year = 1993 | pmid = 8093601 | doi = 10.1016/0922-4106(93)90061-d}} this discovery by several groups in the 1980s generated excitement among those doing research on the serotonin system as such antagonists were rare at that time.Glennon RA. Strategies for the Development of Selective Serotonergic Agents. Chapter 4 in The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics. Ed. Bryan L. Roth. Springer Science & Business Media, 2008 {{ISBN|9781597450805}}{{rp|111–14}}

Penbutolol is rapidly absorbed from the gastrointestinal tract, has a bioavailability over 90%,{{cite journal | vauthors = Vallner JJ et al. | year = 1977 | title = Plasma level studies of penbutolol after oral dose in man | journal = Journal of Clinical Pharmacology | volume = 17 | issue = 4| pages = 231–23 | pmid = 14976 | doi=10.1177/009127007701700407| s2cid = 31794332 }} and has a rapid onset of effect. Penbutolol has a half life of five hours.{{rp|Table 10–2, p 252}}

Penbutolol was approved by the FDA in 1987. In January 2015 the FDA acknowledged that the penbutolol was no longer marketed in the US, and determined that the drug was not withdrawn for safety reasons.

{{Reflist|2}}

{{Endothelial antihypertensives}}

{{Adrenergic receptor modulators}}

{{Serotonin receptor modulators}}

Category:5-HT1A antagonists

Category:5-HT1B antagonists

Category:Beta blockers

Category:N-tert-butyl-phenoxypropanolamines

Category:Withdrawn drugs

Category:Cyclopentyl compounds