Penbutolol
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| Trade names | Levatol |
| AHFS/Drugs.com | Consumer Drug Information |
| MedlinePlus | a601091 |
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| Chemical and physical data | |
| Formula | C18H29NO2 |
| Molar mass | 291.435g·mol−1 |
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Penbutolol(brand namesLevatol,Levatolol,Lobeta,Paginol,Hostabloc,Betapressin) is amedicationin the class ofbeta blockers,used in the treatment ofhigh blood pressure.[1]Penbutolol is able to bind to bothbeta-1 adrenergic receptorsandbeta-2 adrenergic receptors(the two subtypes), thus making it a non-selective β blocker.[2]: Table 10–2, p 252 Penbutolol is asympathomimetic drugwith properties allowing it to act as a partial agonist at β adrenergic receptors.[3]
It was approved by the FDA in 1987[4]and was withdrawn from the US market by January 2015.[5]
Medical uses
[edit]Penbutolol is used to treat mild to moderatehigh blood pressure.[1]Like otherbeta blockersit is not a first line treatment for this indication.[6]
It should not be used or only used with caution in people withheart failureand 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
[edit]Penbutolol has a low frequency of side effects.[1][7]These side effects include dizziness, light headedness, and nausea.[1][8]
Pharmacology
[edit]Pharmacodynamics
[edit]Penbutolol is able to bind to both beta-1 adrenergic receptors andbeta-2 adrenergic receptors(the two subtypes), thus making it a non-selective β blocker.[2]: Table 10–2, p 252 Penbutolol is asympathomimetic drugwith properties allowing it to act as a partial agonist at β adrenergic receptors.[3]
Blocking β adrenergic receptors decreases the heart rate andcardiac outputto lowerarterial blood pressure.β blockers also decreasereninlevels, which ultimately results in less water being reabsorbed by the kidneys and therefore a lowerblood volumeandblood pressure.[9]
Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by acatecholamine,they stimulate a coupledG proteinwhich activates adenylyl to convertadenosine triphosphate(ATP) tocyclic 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 apartial agonistproves useful in the prevention ofbradycardiaas 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 convertsangiotensinogentoangiotensin I,which will then be converted toangiotensin II.Angiotensin II stimulates the release ofaldosteronefrom theadrenal gland,causing a decrease inelectrolyteand water retention, ultimately increasing water excretion and decreasing blood volume and pressure.[11]: 221
Likepropanololandpindolol,it is aserotonin5-HT1Aand5-HT1Breceptorantagonist;[12]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.[13]: 111–14
Pharmacokinetics
[edit]Penbutolol is rapidly absorbed from the gastrointestinal tract, has abioavailabilityover 90%,[8]and has a rapid onset of effect. Penbutolol has ahalf lifeof five hours.[2]: Table 10–2, p 252
Society and culture
[edit]Availability
[edit]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]
References
[edit]- ^abcdefFDAPenbutolol labelLast updated Dec 2010
- ^abcdKatzung, Bertram G. Basic and Clinical Pharmacology (13th ed.) McGraw-Hill Education, 2015.ISBN9780071826419
- ^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.S2CID12950442.
- ^abFDAHistory NDA 018976
- ^abFDA notice in the Federal Register. Jan 9, 2015Determination That TAGAMET (Cimetidine) Tablets and Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness
- ^NICEHypertension guidanceLast updated 2013
- ^Schoenberger JA (Jun 1989). "Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group".Am J Cardiol.63(18): 1339–42.doi:10.1016/0002-9149(89)91045-x.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.S2CID31794332.
- ^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, 2008ISBN9780387095523
- ^Finkel, Richard; Clark, Michelle A.; Cubeddu, Luigi X. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition Lippincott Williams & Wilkins, 2009.ISBN9780781771559
- ^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, 2008ISBN9781597450805