Propranolol Hydrochloride, Inderal®

Brand name

  • Inderal®

Drug Class

  • Beta-Adrenergic Receptor Blocking Agent
  • Antihypertention

Preparations

  • Tablets: 10 mg, 20 mg, 40 mg
  • Extended-release capsules: 60 mg; 80 mg; 120 mg; 160 mg

Indications

  • Maintenance therapy in the treatment of hypertension and for the prophylaxis of angina pectoris
  • Treatment of anxiety disorders

Pharmacology

  • Propranolol hydrochloride is a non-selective beta-adrenergic receptor blocking drug with no effect on other autonomic nervous system

Metabolism

  • Peak blood levels following the administration of propranolol capsules occur at about 6 hours and the apparent plasma half-life has been reported to be between 10 and 12 hours (i.e., 2 to 3 times that of conventional tablets).

Drug Interactions

  • Anti-arrhythmic drugs
    • Class I  anti-arrhythmic  drugs (e.g.  disopyramide)  and  amiodarone  may  have  a potentiating effect on atrial-conduction time and induce negative inotropic effects.
    • Other cardiac-depressant   anti-arrhythmic   drugs:   prior   administration   of   other antiarrhythmic drugs, such as procainamide and quinidine may potentiate the cardiac- depressant activity of propranolol hydrochloride. Prior digitalization may be indicated and atropine should be at hand to control bradycardia.
  • Thiazide-like diuretics and peripheral vasodilators
    • The combination of propranolol with a thiazide-like diuretic and/or a peripheral vasodilator produces a greater fall in blood pressure than either drug
  • Rizatriptan
    • The simultaneous administration of rizatriptan and propranolol can increase the rizatriptan AUC and Cmax by approximately 70-80%.
    • If both drugs are to be used, a rizatriptan dose of  5 mg has been recommended.
  • Digitalis glycosides
    • In association  with  beta-blockers,  digitalis  glycosides  may  increase atrioventricular conduction time.
  • Verapamil, Diltiazem
    • Beta-blockers combined with calcium channel blockers with negative inotropic effects may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-blocker nor the calcium channel blocker should be administered within 48 hours of discontinuing the other.
  • Nifedipine
    • concomitant therapy  with  dihydropyridine  calcium  channel  blockers (such  as nifedipine) may increase the risk of hypotension and cardiac failure may occur in patients with latent cardiac insufficiency.
  • Epinephrine
    • Concomitant use of sympathomimetic agents, such as epinephrine, may counteract the effects  of  beta-blockers.  Caution  must  be  exercised  when  administering  epinephrine parenterally to patients taking beta-blockers as, in rare cases, vasoconstriction, hypertension and bradycardia may result.
  • Lidocaine
    • administration of propranolol during an infusion of lidocaine may increase the plasma concentration of lidocaine by approximately 30%. Patients already receiving propranolol tend to have higher lidocaine levels than controls. The combination should be avoided.
  • Cimetidine
    • Concomitant use of cimetidine will increase plasma levels of propranolol.
  • Alcohol
    • Concomitant use of alcohol may increase the plasma levels of propranolol.
  • Clonidine
    • Beta-blockers may  exacerbate  the  rebound  hypertension  which  can  follow  the withdrawal of clonidine. If clonidine is co-administered with a beta-blocker, the beta-blocker should  be  withdrawn  several  days  before  stopping  clonidine
    • If  replacing clonidine with beta-blocker therapy, the introduction of the beta-blocker should be delayed for several days after clonidine has been discontinued.
  • Ergotamine, Dihydroergotamine (and  related  compounds)
    • Caution must  be  exercised  if ergotamine, dihydroergotamine or related compounds are given in combination with INDERALLA, since vasospastic reactions have been reported in a few patients.
  • Ibuprofen, Indomethacin
    • Concomitant use of prostaglandin synthetase inhibiting drugs (e.g. ibuprofen and indomethacin) may decrease the hypotensive effects of propranolol
  • Chlorpromazine
    • The concomitant use of propranolol and chlorpromazine may result in an increase in plasma levels of both drugs.
  • Drug-Food Interactions
    • Interactions with food have not been established.
  • Drug-Herb Interactions
    • Interactions with herbal products have not been established.
  • Drug-Laboratory Interactions
    • Propranolol hydrochloride does not interfere with thyroid function tests.
  • Interactions with other laboratory tests have not been established.

Adverse Effects

  • Cardiovascular
    • Congestive heart failure
    • heart failure deterioration
    • precipitation of heart block
    • vertigo
    • lightheadedness
    • decreased renal perfusion and rarely
    • postural hypotension
    • intensification of AV block and hypotension
    • severe bradycardia
    • claudication and cold extremities
    • Raynaud’s phenomenon
    • dyspnoea
    • palpitations
    • precordial pain
  • Central Nervous System
    • Dizziness, lethargy, weakness, drowsiness, headache,  insomnia,  fatigue  and/or  lassitude, anorexia, anxiety, mental depression, poor concentration, reversible amnesia and catatonia, vivid dreams  with  or  without  insomnia,  nightmares,  hallucinations,  psychoses,  mood  changes, confusion, paresthesia, incoordination.
  • Nervous System
    • Isolated reports of myasthenia gravis-like syndrome or exacerbation of myasthenia gravis.
  • Gastrointestinal
    • Nausea, vomiting, epigastric distress, anorexia, bloating, mild diarrhoea, constipation
  • Respiratory
    • Bronchospasm (may  occur  in  patients  with  bronchial  asthma  or  a  history  of  asthmatic complaints,  sometimes  with  fatal  outcome);  laryngospasm  and  respiratory  distress (see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS).
  • Blood
    • Thrombocytopenia
  • Dermatologic
    • Erythematous rashes
    • Urticaria
    • Exfoliative psoriasiform eruption
    • Stevens-Johnson Syndrome
    • Toxic epidermal necrolysis
    • Exfoliative dermatitis
    • Erythema multiforme.
  • Endocrine
    • Hypoglycaemia in  elderly  patients,  patients  on  haemodialysis,  patients  on  concomitant antidiabetic therapy, patients with prolonged fasting and patients with chronic liver diseases
  • Allergic
    • Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.
  • Others
    • Reduction or loss of libido; reversible alopecia
    • Rarely: diminution and loss of hearing; tinnitus; visual  disturbances;  diminished  vision;  conjunctivitis;  dry  eyes,  thrombocytopenic purpura; pharyngitis; agranulocytosis; fever combined with aching and sore throat; flushing of the face

Contraindications

  • Hypersensitivity
  • Patients with a history of or current reports of bronchial asthma or bronchospasm
  • Allergic rhinitis during the pollen season
  • Sinus bradycardia and greater than first degree block
  • Cardiogenic shock
  • Right ventricular failure secondary to pulmonary hypertension
  • Congestive heart failure unless the failure is  secondary to a tachyarrhythmia treatable with propranolol hydrochloride
  • Patients prone to hypoglycaemia and after prolonged fasting
  • As with other beta-blockers, INDERAL- LA must not be used in patients with bradycardia, hypotension, metabolic acidosis, severe peripheral arterial circulatory disturbance, sick   sinus syndrome, untreated phaeochromocytoma, uncontrolled heart failure, Prinzmetal’s angina.

Pregnancy and Breastfeeding

  • Propranolol should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Propranolol is excreted in human milk. Breast feeding is therefore not recommended when Propranolol is administered to nursing women.

Warning

  • Propranolol is intended for the maintenance therapy of hypertension and for prophylaxis of angina pectoris. It is not indicated for initial or emergency treatment of these conditions. It should be substituted for conventional propranolol hydrochloride tablets only when the dose requirement is suitable.
  • In  Patients  Without  a  History  of  Cardiac  Failure,  continued  depression  of  the myocardium over a period of time can, in some patients, lead to cardiac failure.
  • Although contraindicated  in  severe peripheral arterial circulatory disturbances, propranolol as  with  other  beta-blockers, may also  aggravate less  severe peripheral  arterial circulatory disturbances.
  • Dizziness and/or fatigue may occasionally occur with  beta-blocker administration and this should be taken into account.
  • Oculomucocutaneous  Syndrome:  Various  skin  rashes  and  conjunctival  xerosis  have  been reported in patients treated with beta-blockers, including propranolol hydrochloride. A severe oculomucocutaneous  syndrome,  whose  signs  include  conjunctivitis  sicca  and  psoriasiform rashes, otitis, and sclerosing serositis has occurred with the long-term use of one beta-adrenergic blocking agent.

Note

This document was prepared by the “Mental Health for All” team and was edited by Dr. Siavash Jafari (MDm MHSc, FRCPC, ABAM). This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

References:

  • Shand D.G. Pharmacokinetics of Propranolol: A Review, Postgraduate Med. J. 1976; 52  (Suppl. 4): 22.
  • Johnsson G, Regardh C.G. Clinical Pharmacokinetics of Beta-Adrenoreceptor Blocking Drugs. Clin. Pharmacokin. 1976; 1: 233-263
  • Walle T, Conradi E.C., Walle U.K., Fagan T.C., Gaffney T.E. Propranolol Glucuronide Cumulation During Long-Term Propranolol Therapy: A Proposed Mechanism for Propranolol. Clin. Pharm. Ther.1979; 26: 686-695
  • Black J.W., Duncan W.A.M., Shanks R.G. Comparison of Some Properties of Pronethalol and Propranolol. Br. J. Pharmacol. & Chemother. 1965; 25: 577
  • Shanks R.G. The Effect of Propranolol on the Cardiovascular Responses to Isoprenaline, Adrenaline and Noradrenaline in the Anesthetized Dog. Br. J. Pharmacol. & Chemother. 1966; 26: 322
  • Shanks R.G. The Peripheral Vascular Effects of Propranolol and Related Compounds. Br. J. Pharmacol. & Chemother. 1967; 29: 204-217
  • Epstein S.E., Robinson B.F., Kahler R.C., Braunwald E. Effects of Beta-Adrenergic Blockade on the Cardiac Response to Maximal and Sub-maximal Exercise in Man. J. Clin. Invest. 1965; 44: 1745 – 1753
  • Barrett A.M., Cullum V.A. The biological Properties of the Optical Isomers of Propranolol and Their Effects on Cardiac Arrhythmias. Br. J. Pharm. 1968; 34: 43-55
  • Lucchesi B.R., Whitsitt L.S., Brown N.L. Propranolol in Experimentally Induced Cardiac Arrhythmias. Can. J. Physiol. And Pharmacol. 1966; 44: 543
  • Conolly M.E., Kersting F, Dollery C.T. The Clinical Pharmacology of Beta-Adrenoceptor-Blocking Drugs. Prog. Cardiovasc. Dis. 1976; Vol. XIX, No. 3
  • McDevitt D.G. The Assessment of Beta-Adrenoceptor Blocking Drugs in Man. Br. J. Clin. Pharmac. 1977; 4: 413-425
  • Beumer H.M. Adverse Effects of Beta-Adrenoreceptor Blocking Drugs on Respiration. Cardiovascular Drugs. 1977; Vol. 2: Beta-Adrenoceptor Blocking Drugs. G.S. Avery, Ed., ADIS      Press, Sydney
  • Tivenius L, Nyberg G. Effect of Alprenolol and Propranolol on ventilatory function. A comparative Study in Patients With Chronic Obstructive Lung Disease. Pharmacologia Clinica. 1969; 2: 51
  • Nickerson M, Collier B. Propranolol and Related Drugs. The Pharmacological Basis of Therapeutics, 5th Edition,  N.Y.:  L.S.  Goodman  and  A.  Gilman,  Eds.,  MacMillan Publishing Co., Inc., 1975
  • Greenblatt D.J., Shader R.I. On the Psychopharmacology of Beta-Adrenergic Blockade. Curr. Ther. Res. 1972; 14: 615-625.
  • Saelens D.A., Walle T., Privitera P.J. et al. Central Nervous System Effects and Metaboli Disposition of Glycol Metabolite of Propranolol. J. Pharmacol. Exp. Ther. 1974; 188: 86-92
  • Gibson D.G.: Pharmacodynamic Properties  of  Beta-Adrenoceptor  Blocking Drugs  in Man.  Cardiovascular Drugs,  1977;  Vol.  2:  Beta-Adrenoceptor  Blocking Drugs. G.S. Avery, Ed., ADIS Press, Sydney
  • Dollery C.T., Patterson J.W., Conolly M.E. Clinical Pharmacology of Beta-Receptor- Blocking Drugs. Clin. Pharm. Ther. 1969; 10: 765
  • Meyler’s Side Effects of Drugs. Amsterdam-Oxford American Elsevier Publishing Co.  Inc. Excerpta Medica. New York; 1975. Vol. 8 p.443
  • Winkler G.F., Young R.R. Efficacy of Chronic Propranolol Therapy in Action Tremors of the Familial, Senile or Essential Varieties, N. Engl. J. Med. 1974; 290: 984-988
  • Murray T.J. Essential Tremor. Can. Med. Assoc. J. 1981; 124: 1559-156
  • Dvornik D et al. Relationship between Plasma Propranolol Concentrations and Dose of Long-Acting Propranolol (Inderal-LA). Current Therapeutic Research. 1983 Oct; Vol. 34 (4):599
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