Propranolol

Last updated on: 29.10.2020

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Synonym(s)

beta-adrenergic receptor antagonist; CAS number: 525-66-6

Definition
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Propanolo is a non-cardioselective beta-adrenoceptor antagonist. These are also called "beta blockers/betarezptor blockers" (the term "beta blocker" is incorrect in that this group of substances only blocks channels or transporters, but not the receptors).

All beta-adrenoceptor antagonists are competitive antagonists and (with the exception of timolol and sotalol) have a common basic structure (see figure).

Propanolol is used in cardiovascular diseases such as hypertension, arrhythmia and coronary heart disease (CHD).

Further indications of propranolol are primary anxiety syndrome, migraine prophylaxis, essential tremor and hyperthyroidism as symptomatic therapy.

Pregnancy/nursing period
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Propranolol may only be given during pregnancy after strict indication and weighing of the benefit-risk ratio. Attention must be paid to possible triggering of contractions and to undesirable effects on the fetus (intrauterine growth retardation, bradycardia). Therefore, the therapy must be terminated at least 48 - 72 hours before the calculated date of birth. If this is not possible, the newborns must be carefully monitored in the first 48 - 72 hours after birth.

Lactation period: As propranolol is one of the lipophilic beta-blockers, it may enter the breast milk. Breastfeeding is therefore not recommended.

Dosage and method of use
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Propranolol can be administered orally as well as parenterally. The film-coated tablets should be taken before meals and the retarded tablets (in the morning) unchewed with sufficient liquid. The intravenous injection should be administered slowly, corresponding to 1 ml of injection solution per minute, with continuous monitoring of pulse, blood pressure and ECG. It should only be used until the heart rhythm disturbances are under control.

Oral form of administration:

Arterial hypertension: Initially 80 - 120 mg propranolol hydrochloride per day, divided into 2-3 EDs, is recommended. The daily dose can be increased to 160 - 240 mg propranolol hydrochloride. If necessary, the dosage can be increased to 320 mg propranolol hydrochloride, divided into 2 single doses as a film-coated tablet or a single dose in the morning as a retarded capsule.

Coronary heart disease, tachycardic arrhythmias: The starting dose is 120 mg propranolol hydrochloride, divided into 3 EDs. If necessary, the daily dose can be increased to 160 - 240 mg propranolol hydrochloride, divided into 2-3 EDs or 1x in the morning or evening 160 mg propranolol hydrochloride retard capsules.

Reinfarction prophylaxis: Treatment should be started between the 5th and 21st day after myocardial infarction: Dosage: initially 120 mg propranolol hydrochloride, divided into 3 EDs, over 2 - 3 days. Then 80 - 160 mg propranolol hydrochloride, divided into 2-3 EDs as a film-coated tablet or 1 ED as a retardation capsule.

Hyperkinetic heart syndrome: 30 - 120 mg propranolol hydrochloride, divided into 3 EDs, for 2 - 3 days.

Migraine prophylaxis, essential tremor, symptomatic therapy of primary anxiety syndrome: initial dose 80 - 120 mg propranolol hydrochloride (divided into 2-3 EDs).

Hyperthyroidism (symptomatic therapy as a supplement or until specific measures take effect): The recommended dose is 30 - 160 mg propranolol hydrochloride divided into 3-4 EDs.

Arrhythmias in children and adolescents: Individual dosage. The orientation dose is 0.25 - 0.5 mg/kg body weight 3-4 times/day.

Restricted liver or kidney function: In case of severely restricted liver or kidney function the elimination of propranolol is reduced. A reduction of the dose may be necessary.

Proliferative infantile hemangiomas (oral solution): Therapy should be started in infants between 5 weeks and 5 months of age. The initial dose is 0.5 mg/kg propranolol (base) twice daily for the first week. There should be an interval of at least 9 hours between the individual doses. An increase in dose (up to the therapeutic dose) should only be made under medical supervision:

  • Week 2: 2x/day 1 mg/kg
  • Week 3: 2x/day 1,5 mg/kg as maintenance dose
  • The treatment duration: =/> 6 months.

Intravenous application (acutely threatening supraventricular and ventricular arrhythmias):

Adults: Initially, 1 mg propranolol hydrochloride (corresponds to 1 ml injection solution, i.e. 1 ampoule) is injected slowly intravenously over 1 minute. If necessary, the injection may be repeated with the same dose at intervals of 2 minutes until the effect is felt or until the maximum dose is reached. The maximum dose is 10 mg for adults with retained consciousness and 5 mg for adults under anaesthesia.

Children and adolescents: Intravenous injection is intended exclusively for the emergency treatment of cardiac arrhythmias. The recommended dosage is 0.025 - 0.05 mg/kg. If necessary, the dose can be repeated every 6 - 8 hours.

Undesirable effects
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The most common side effects of propranolol are based on its effect on the autonomic nervous system. Headache, gastrointestinal discomfort with diarrhea, vomiting, nausea or constipation as well as fatigue, dizziness and sweating.

Also: restlessness, nervousness, confusion or sleep disturbances, drop in blood pressure, cardiac arrhythmia, increased heart failure. Rare are itchy exanthema, diffuse alopecia.

Interactions
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MAO inhibitor: excessive blood pressure drop

calcium antagonists of the verapamil or diltiazem type: hypotension, bradycardia or other cardiac arrhythmia

Amiodarone: Enhanced cardiodepressive effects

Insulin and oral antidiabetics: Increased and prolonged hypoglycemia

Other antihypertensive drugs: Increased blood pressure reduction

Alphamethyldopa, guanfacine, cardiac glycosides, clonidine: Stronger decrease of heart rate or delay of the transition Excessive increase of blood pressure

Cimetidine: Enhancement of the propranolol effect

Contraindication
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Hypersensitivity to propranolol

AV block II and III degree and sick sinus syndrome in patients without pacemakers

Higher degree sinuatrial block

Bradycardia

Untreated heart failure (NYHA III and IV)

Prinzmetal Angina

Shock

Hypotension

Pulmonary Hypertension

bronchial asthma or bronchospasm

Psoriasis: In psoriatics, the use of beta-receptor blockers should only be used after careful risk-benefit analysis.

Allergies: Beta-receptor blockers can increase sensitivity to allergens and the severity of anaphylactic reactions, i.e. acute general allergic reactions. For this reason, a strict indication is required for patients with a history of severe hypersensitivity reactions and for patients undergoing therapy to weaken or eliminate the allergic reaction (desensitization therapy; caution: excessive anaphylactic reactions).

Chronic obstructive respiratory diseases

Simultaneous treatment with MAO inhibitors and other adrenergic impulse enhancing drugs

Simultaneous treatment with calcium antagonists with negative inotropic effects such as verapamil and diltiazem

After a long food ration

Uremia

Metabolic acidosis

Severe peripheral circulatory disorders(pAVK)

Patients with a tendency to hypoglycaemia or patients who have fasted for a longer period

Untreated pheochromocytoma.

Infants under 5 weeks

Preparations
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Dociton® 10 mg film-coated tablets

Dociton® 40 mg film-coated tablets

Note(s)
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Taking the drug Propranolol can lead to positive results in doping tests.

Patientinformation
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Particularly at the beginning of treatment, the individual's ability to react can be altered to such an extent that the ability to actively participate in road traffic and to operate machinery is impaired.

Literature
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  1. Al-Majed AA et al (2017) Propranolol. Profiles Drug Subst Excip Relat Methodol 42:287-338.
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Last updated on: 29.10.2020