Propranolol videos and info

Propranolol is a non-selective beta blocker, that is, it blocks the action of epinephrine on both β₁- and β₂-adrenergic receptors. It has little intrinsic sympathomimetic activity (ISA) but has strong membrane stabilizing activity (only at high blood concentrations, eg overdosage). Only L-propranolol is a powerful adrenoceptor antagonist, whereas D-propranolol is not. However, both have local anesthetic (termed topical) effect.

Pharmacokinetics

Propranolol is rapidly and completely absorbed, with peak plasma levels achieved approximately 1–3 hours after ingestion. Co-administration with food appears to enhance bioavailability. Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment will therefore increase its bioavailability. The main metabolite 4-hydroxypropranolol, with a longer half-life (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active.

Propranolol is a highly lipophilic drug achieving high concentrations in the brain. The duration of action of a single oral dose is longer than the half-life and may be up to 12 hours, if the single dose is high enough (e.g., 80 mg). Effective plasma concentrations are between 10–100 ng/mL.

Clinical use

Indications

Propranolol is indicated for the management of various conditions including:^[1]

While once first-line treatment for hypertension, the role for beta-blockers was downgraded in June 2006 in the United Kingdom to fourth-line as they perform less well than other drugs, particularly in the elderly, and evidence is increasing that the most frequently used beta-blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes. ^[7]

Propranolol is often used by musicians and other performers to prevent stage fright.

Precautions/contraindications

Adverse effects

Pregnancy and lactation

Propranolol, like other beta blockers, is classified as Pregnancy category C in the United States and ADEC Category C in Australia. Beta-blocking agents in general reduce perfusion of the placenta which may lead to adverse outcomes for the neonate, including pulmonary or cardiac complications, or premature birth. The newborn may experience additional adverse effects such as hypoglycemia and bradycardia.

Most beta-blocking agents appear in the milk of lactating women. This is especially the case for a lipophilic drug like propranolol. Breastfeeding is not recommended in patients receiving propranolol therapy.

Interactions

Beta blockers, including propranolol, have an additive effect with other drugs which decrease blood pressure, or which decrease cardiac contractility or conductivity. Clinically-significant interactions particularly occur with:^[1]

Dosage

The usual maintenance dose ranges for oral propranolol therapy vary by indication:

Research into role against malaria

Propranolol along with a number of other membrane-acting drugs have been investigated for possible effects on P. falciparum and so the treatment of malaria. In vitro positive effects until recently had not been matched by useful in vivo anti-parasite activity against P. vinckei,^[13] or P. yoelii nigeriensis.^[14] However a single study from 2006 has suggested that propranolol may reduce the dosages required for existing drugs to be effective against P. falciparum by 5- to 10-fold, suggesting a role for combination therapies.^[15]

References

^ ^a ^b ^c ^d Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
^ Kornischka J, Cordes J, Agelink MW (April 2007). "[40 years beta-adrenoceptor blockers in psychiatry]" (in German). Fortschr Neurol Psychiatr 75 (4): 199–210. doi:10.1055/s-2006-944295. PMID 17200914.
^ Vieweg V, Pandurangi A, Levenson J, Silverman J (1994). "The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia". Int J Psychiatry Med 24 (4): 275–303. PMID 7737786.
^ Kishi Y, Kurosawa H, Endo S (1998). "Is propranolol effective in primary polydipsia?". Int J Psychiatry Med 28 (3): 315–25. PMID 9844835.
^ Kramer MS, Gorkin R, DiJohnson C (1989). "Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study". Hillside J Clin Psychiatry 11 (2): 107–19. PMID 2577308.
^ Thibaut F, Colonna L (1993). "[Anti-aggressive effect of beta-blockers]" (in French). Encephale 19 (3): 263–7. PMID 7903928.
^ Sheetal Ladva (2006-06-28). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=567178. Retrieved on 2006-09-30.
^ "Doctors test a drug to ease traumatic memories - Mental Health - MSNBC.com". http://www.msnbc.msn.com/id/10806799/. Retrieved on 2007-06-30.
^ Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK (2007). Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. pp. 503. doi:10.1016/j.jpsychires.2007.05.006. PMID 17588604.
^ "Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder". http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T8T-4P1G931-2&_user=10&_coverDate=06%2F22%2F2007&_alid=594818882&_rdoc=1&_fmt=summary&_orig=search&_cdi=5095&_sort=d&_docanchor=&view=c&_ct=1&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=cff0ee031b688b5fbc74a7de54915c38.
^ van Harten J (1995). "Overview of the pharmacokinetics of fluvoxamine". Clin Pharmacokinet 29 Suppl 1: 1–9. PMID 8846617.
^ *Joint Formulary Committee. British National Formulary, 47th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2004.
^ Ohnishi S, Sadanaga K, Katsuoka M, Weidanz W (1990). "Effects of membrane acting-drugs on plasmodium species and sickle cell erythrocytes". Mol Cell Biochem 91 (1-2): 159–65. doi:10.1007/BF00228091. PMID 2695829.
^ Singh N, Puri S (2000). "Interaction between chloroquine and diverse pharmacological agents in chloroquine resistant Plasmodium yoelii nigeriensis". Acta Trop 77 (2): 185–93. doi:10.1016/S0001-706X(00)00133-9. PMID 11080509.
^ Murphy S, Harrison T, Hamm H, Lomasney J, Mohandas N, Haldar K (December 2006). "Erythrocyte G protein as a novel target for malarial chemotherapy". PLoS Med 3 (12): e528. doi:10.1371/journal.pmed.0030528. PMID 17194200.

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