'''Penbutolol''' (brand names '''Levatol''', '''Levatolol''', '''Lobeta''', '''Paginol''', '''Hostabloc''', '''Betapressin''') is a [[medication]] in the class of [[beta blocker]]s, used in the treatment of [[hypertension|high blood pressure]].<ref name=label>FDA [http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf Penbutolol label] Last updated Dec 2010</ref> Penbutolol is able to bind to both [[Beta-1 adrenergic receptor|beta-1 adrenergic receptors]] and [[beta-2 adrenergic receptors]] (the two subtypes), thus making it a non-selective β blocker.<ref name=Katzung>Katzung, Bertram G. Basic and Clinical Pharmacology (13th ed.) McGraw-Hill Education, 2015. {{ISBN|9780071826419}}</ref>{{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.<ref name=Frishman>{{cite journal | vauthors = Frishman WH, Covey S | year = 1990 | title = Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism | url = | journal = Journal of Clinical Pharmacology | volume = 30 | issue = 5| pages = 412–21 | pmid = 2189902 }}</ref>
'''Penbutolol''' (brand names '''Levatol''', '''Levatolol''', '''Lobeta''', '''Paginol''', '''Hostabloc''', '''Betapressin''') is a [[medication]] in the class of [[beta blocker]]s, used in the treatment of [[hypertension|high blood pressure]].<ref name=label>FDA [http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf Penbutolol label] Last updated Dec 2010</ref> Penbutolol is able to bind to both [[Beta-1 adrenergic receptor|beta-1 adrenergic receptors]] and [[beta-2 adrenergic receptors]] (the two subtypes), thus making it a non-selective β blocker.<ref name=Katzung>Katzung, Bertram G. Basic and Clinical Pharmacology (13th ed.) McGraw-Hill Education, 2015. {{ISBN|9780071826419}}</ref>{{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.<ref name=Frishman>{{cite journal | vauthors = Frishman WH, Covey S | year = 1990 | title = Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism | url = | journal = Journal of Clinical Pharmacology | volume = 30 | issue = 5| pages = 412–21 | pmid = 2189902 | doi=10.1002/j.1552-4604.1990.tb03479.x}}</ref>
It was approved by the FDA in 1987<ref name=FDAapp>FDA [http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=018976&DrugName=LEVATOL&ActiveIngred=PENBUTOLOL%20SULFATE&SponsorApplicant=AUXILIUM%20PHARMS%20INC&ProductMktStatus=3&goto=Search.Label_ApprovalHistoryApproval History NDA 018976]</ref> and was withdrawn from the US market by January 2015.<ref name=FDAstop>FDA notice in the Federal Register. Jan 9, 2015 [https://www.federalregister.gov/articles/2015/01/09/2015-00116/determination-that-tagamet-cimetidine-tablets-and-other-drug-products-were-not-withdrawn-from-sale Determination That TAGAMET (Cimetidine) Tablets and Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness]</ref>
It was approved by the FDA in 1987<ref name=FDAapp>FDA [http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=018976&DrugName=LEVATOL&ActiveIngred=PENBUTOLOL%20SULFATE&SponsorApplicant=AUXILIUM%20PHARMS%20INC&ProductMktStatus=3&goto=Search.Label_ApprovalHistoryApproval History NDA 018976]</ref> and was withdrawn from the US market by January 2015.<ref name=FDAstop>FDA notice in the Federal Register. Jan 9, 2015 [https://www.federalregister.gov/articles/2015/01/09/2015-00116/determination-that-tagamet-cimetidine-tablets-and-other-drug-products-were-not-withdrawn-from-sale Determination That TAGAMET (Cimetidine) Tablets and Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness]</ref>
Line 63:
Line 63:
===Pharmacokinetics===
===Pharmacokinetics===
Penbutolol is rapidly absorbed from the gastrointestinal tract, has a [[bioavailability]] over 90%,<ref name=Vallner>{{cite journal | vauthors = Vallner JJ ''et al.'' | year = 1977 | title = Plasma level studies of penbutolol after oral dose in man | url = | journal = Journal of Clinical Pharmacology | volume = 17 | issue = 4| pages = 231–23 | pmid = 14976 }}</ref> and has a rapid onset of effect. Penbutolol has a [[half life]] of five hours.<ref name=Katzung/>{{rp|Table 10-2, p 252}}
Penbutolol is rapidly absorbed from the gastrointestinal tract, has a [[bioavailability]] over 90%,<ref name=Vallner>{{cite journal | vauthors = Vallner JJ ''et al.'' | year = 1977 | title = Plasma level studies of penbutolol after oral dose in man | url = | journal = Journal of Clinical Pharmacology | volume = 17 | issue = 4| pages = 231–23 | pmid = 14976 | doi=10.1177/009127007701700407}}</ref> and has a rapid onset of effect. Penbutolol has a [[half life]] of five hours.<ref name=Katzung/>{{rp|Table 10-2, p 252}}
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.[1]
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.[1]
Side effects
Penbutolol has a low frequency of side effects.[1][7] These side effects include dizziness, light headedness, and nausea.[1][8]
Pharmacology
Pharmacodynamics
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.[2]: Table 10-2, p 252 Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.[3]
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.[2]: 213–214 Penbutolol blocks this and decreases heart rate, which lowers blood pressure.[10]: 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.[3] 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.[11]: 221
Penbutolol is rapidly absorbed from the gastrointestinal tract, has a bioavailability over 90%,[8] and has a rapid onset of effect. Penbutolol has a half life of five hours.[2]: Table 10-2, p 252
Society and culture
Availability
Penbutolol was approved by the FDA in 1987.[4] 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.[5]
^ abcdKatzung, Bertram G. Basic and Clinical Pharmacology (13th ed.) McGraw-Hill Education, 2015. ISBN 9780071826419
^ abcFrishman WH, Covey S (1990). "Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism". Journal of Clinical Pharmacology. 30 (5): 412–21. doi:10.1002/j.1552-4604.1990.tb03479.x. PMID2189902.
^Schoenberger, J. A. Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group. Am J Cardiol. 1989 Jun 1;63(18):1339-42. PMID2658525
^ abVallner JJ, et al. (1977). "Plasma level studies of penbutolol after oral dose in man". Journal of Clinical Pharmacology. 17 (4): 231–23. doi:10.1177/009127007701700407. PMID14976.
^Berdeaux A, Duhaze P, Giudicelli JF (1982). "Pharmacological analysis of beta adrenoceptor blockade-induced coronary blood flow redistribution in dogs using l-penbutolol". The Journal of Pharmacology and Experimental Therapeutics. 221 (3): 740–747. PMID6123586.
^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
^Finkel, Richard; Clark, Michelle A.; Cubeddu, Luigi X. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition Lippincott Williams & Wilkins, 2009. ISBN 9780781771559
^Langlois M, Brémont B, Rousselle D, Gaudy F (1993). "Structural analysis by the comparative molecular field analysis method of the affinity of beta-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors". Eur. J. Pharmacol. 244 (1): 77–87. doi:10.1016/0922-4106(93)90061-d. PMID8093601.
^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