Trade name Inderal,
Pregnancy category AU: C
Routes of administration by mouth, rectal, intravenous
Propranolol is a non-selective beta receptor antagonist.
Pharmacokinetic data
Bioavailability 26%
Protein binding 90%
Metabolism Liver (extensive) CYP1A2, CYP2D6; minor: CYP2C19, CYP3A4
Elimination half-life 4–5 hours
Excretion Kidney (<1%)
It is used to treat hypertension, some types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, essential tremors, migraine headache prevention, to prevent further heart problems in those with angina or previous heart attacks, portal hypertension, to lower portal vein pressure, prevention of esophageal variceal bleeding, ascites, anxiety, hypertrophic cardiomyopathy
The formulation that is taken orally comes in short-acting and long-acting versions.
Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.
Side effects include nausea, abdominal pain, and constipation.
Propranolol may worsen the symptoms of asthma, and use may be harmful may cause harmful effects for the baby if taken during pregnancy.
Its use during breastfeeding is generally considered to be safe.
It is a non-selective beta blocker which works by blocking β-adrenergic receptors.
An 80 mg capsule of extended-release propranolol
A mixture of 20 mg and 10 mg propranolol tablets
Propranolol is used for treating various conditions, including:
Propranolol is occasionally used to treat performance anxiety.
Its efficacy in managing panic disorder appears similar to benzodiazepines, while carrying lower risks for addiction or abuse.
Its efficacy in treating generalized anxiety disorder and panic disorder remain unestablished.
Some experimentation has been conducted in other psychiatric areas:
Post-traumatic stress disorder (PTSD).
Aggressive behavior of patients with brain injuries.
Treating psychogenic polydipsia.
Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation.
Individuals given propranolol immediately after trauma experience fewer stress-related symptoms and lower rates of PTSD than respective control groups who did not receive the drug.
Memories and their emotional content are reconsolidated in the hours after they are recalled/re-experienced, propranolol can diminish the emotional impact of already formed memories.
Other uses:
Essential tremor.
Migraine and cluster headache prevention and primary exertional headache
Hyperhidrosis
Infantile hemangioma
Glaucoma
Thyrotoxicosis by deiodinase inhibition
Propranolol may be used to treat severe infantile hemangiomas.
This treatment shows promise as being superior to corticosteroids when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.[34]
Propranolol may be contraindicated:
Reversible airway diseases, particularly asthma or chronic obstructive pulmonary disease (COPD)
Slow heart rate (bradycardia) (<60 beats/minute)
Sick sinus syndrome
Atrioventricular block (second- or third-degree)
Shock
Severe low blood pressure
Propranolol should be used with caution in people with:
Diabetes mellitus or hyperthyroidism: hypoglycemia may be masked
Peripheral artery disease and Raynaud syndrome, which may be exacerbated
Pheochromocytoma, as hypertension may be aggravated without prior alpha blocker therapy
Myasthenia gravis, which may be worsened
Other drugs with bradycardic effects.
Propranolol, like other beta-blockers, is classified as pregnancy category C in the United States.
β-blocking agents in general reduce perfusion of the placenta, which may lead to adverse outcomes for the neonate, including lung or heart complications, premature birth, neonatal hypoglycemia and a slower than normal heart rate.
Most β-blocking agents appear in the milk of lactating women.
Propranolol is highly bound to proteins in the bloodstream and is distributed into breast milk at very low levels, and are not expected to pose any risk to the breastfeeding infant.
In overdose, propranolol is associated with seizures.
Cardiac arrest may occur in propranolol overdose due to sudden ventricular arrhythmias, or cardiogenic shock which may ultimately culminate in bradycardic pulseless electrical activity.
Since beta blockers are known to relax the cardiac muscle and constrict the smooth muscle, beta-adrenergic antagonists, including propranolol, have an additive effect with other drugs that decrease blood pressure or decrease cardiac contractility or conductivity.
Significant interactions particularly occur with:
Verapamil Epinephrine (adrenaline)
β2-adrenergic receptor agonists
Salbutamol (albuterol), levosalbutamol, formoterol, salmeterol, clenbuterol
Clonidine
Ergot alkaloids
Isoprenaline (isoproterenol)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Quinidine
Cimetidine
Lidocaine
Phenobarbital
Rifampicin
Fluvoxamine slows the metabolism of propranolol significantly, leading to increased blood levels of propranolol
Propranolol is classified as a competitive non-cardioselective sympatholytic beta blocker: it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors.
It is lipid soluble and also has sodium channel-blocking effects.
It has little intrinsic sympathomimetic activity.
Propranolol can cross the blood-brain barrier and exert effects in the central nervous system in addition to its peripheral activity.
In addition to blockade of adrenergic receptors, propranolol has very weak inhibitory effects on the norepinephrine transporter and/or weakly stimulates norepinephrine release.
It is a weak indirect α1-adrenoceptor agonist in addition to potent β-adrenoceptor antagonist.
It may be involved in the effectiveness of propranolol in the treatment of migraine at high doses.
Propranolol has the ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known membrane stabilizing effect and antiarrhythmic and other central nervous system effects.
Propranolol is a non-selective beta receptor antagonist, it does not have preference to β1 or β2 receptors.
It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the heart.
Blockage of neurotransmitter binding to β1 receptors on cardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibits cAMP synthesis leading to reduced Protein kinase A (PKA) activation.
The above results in less calcium influx to cardiac myocytes through voltage-gated L-type calcium channels meaning there is a decreased sympathetic effect on cardiac cells, resulting in antihypertensive effects including reduced heart rate and lower arterial blood pressure.
It is rapidly and completely absorbed, with peak plasma levels achieved about 1–3 hours after ingestion.
More than 90% of the drug is found bound to plasma protein in the blood.
Coadministration with food appears to enhance bioavailability.
It has a variable bioavailability due to extensive first-pass metabolism.
Hepatic impairment therefore increases propranolol’s bioavailability.
Propranolol can be absorbed along the whole intestine with the main absorption site being the colon.
People who have lost their colon due to surgery may absorb relatively less percentage of propranolol.
The main metabolite 4-hydroxypropranolol, has a longer half-life (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active.
Most of the metabolites are excreted in the urine.
Propranolol is a highly lipophilic drug achieving high concentrations in the brain.
Effective plasma concentrations are between 10 and 100 mg/L.
Toxic levels are associated with plasma concentrations above 2000 mg/L.
Newer, more cardio-selective beta blockers such as bisoprolol, nebivolol, carvedilol, or metoprolol) are used preferentially in the treatment of hypertension.
Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.
It has also been used as a performance-enhancing drug in sports where high accuracy is required, including archery, shooting, golf, and snooker.