Propranolol
Proprated®
Category
Beta-Adrenergic Blocking Agent. (USPDI)
Chemistry
(±)-1-isopropylamino-3-(1-naphtyloxy) propan-2-ol hydrochloride.(Martindale)
Mechanism of action/Pharmacokinetics
Proprated® as Beta-adrenergic blocking agent blocks the adrenergenic effect of the sympathetic neurotransmitters by competing for receptor binding sites at both Beta1 and Beta2 adrenoceptors. Proprated® also possesses moderate membrane-stabilizing (quinidine-like) activity.(USPDI)
Pharmacokinetic Properties
Absorption Almost completely
Distribution Widely distributed
Protein binding 90%
Biotransformation Hepatic to active and inactive metabolites
Time to peak concentration 1-2 Hours
Half life 3-6 Hours
Peak plasma Concentration Vary greatly with individuals
Elimination Hepatic
Hemodialysis Is not effective
(Martindale)
Indications
Proprated® is used in management of Hypertension, pheochromocytoma, Angina pectoris, myocardial infarction, cardiac arrhythmias, Hypertrophic Cardiomyopathy, anxiety disorders, tremor, prophylaxis of migraine and upper GI bleeding in patients with portal Hypertension.
(Martindale)
Contraindications
Except under special circumstances, this medication should not be used when the following medical problems exist: Cardiac failure, Cardiogenic shock, Heart block, Sinus bradycardia, Hypotension.
Risk-benefit should be considered when the following medical problems exist Allergy, Asthma, Emphysema or nonallergic bronchitis, Congestive heart failure, Diabetes mellitus, Hepatic function impairment, Hyperthyroidism, Mental depression, Myasthenia gravis, Pheochromocytoma, Psoriasis, renal function impairment, Raynaud`s syndrome.
(USPDI)
Warnings and precautions
There has been reports of exacerbation of angina and, in some cases, myocardial infarction, following abrupt discontinuance of proprated® therapy. Therefore when discontinuance of propranolol is planned, the patients should be cautioned against interruption or cessation of therapy without a physician's advice. If proprated® therapy is interrupted exacerbation of angina occurs, it's usually advisable to reinstitute proprated® therapy and take other measures appropriate for the management of angina pectoris.
(Facts)
Pregnancy
Beta-adrenergic blocking agents cross the placenta. The safety of this agents in pregnancy is not fully established. Fatal and neonatal bradycardia, hypotension, hypoglycemia, and respiratory depression have been reported with beta blockers in pregnant women. However other reports seem to indicate successful treatment of maternal, hypertension during pregnancy with no apparent effects on the fetus or neonate.
FDA Pregnancy category C.
(Martindale, USPDI)
Breast-feeding
Proprated® is distributed into breast milk. It is calculated that the maximum dose likely to be ingested by a breast-fed infant would be less than 0.1% of the maternal dose. No adverse effects have been reported in breast-fed infants whose mothers were receiving proprated® and therefore it considers to be compatible with breast feeding.
Although the risk appears to be small, breast-fed infants should be monitored for signs of beta-adrenergic blocked, especially bradycardia, hypotension, respiratory distress and hypoglycemia.
(Martindale, USPDI)
Drug Interactions
Allergen immunotherapy or the allergenic extracts for skin testing (increase the potentials of serious systemic reactions). Amiodarone (add depressant effects on conduction and negative inotropic effects). Anesthetics (increase the risk of myocardial depression and hypotension). Antidiabetic agents, oral or insulin (glycemic control impairment, increased risk of hyperglycemia, impair recovery from hypoglycemia), Beta Blocker may mask certain symptoms of developing hypoglycemia NSAID`s (may reduce the anti hypertensive effects). Calcium channel blockers or clonidine or diazoxide or Guanabenz or reserpine, (altered antihypertensive response may be observed, symptomatic bradycardia, with or without serious hemodynamic effects with verapamil and diltiazem). Cimetidine (reduction of hepatic clearance of beta blockers). Cocaine (inhibition of therapeutic effects). Contrast media, iodinated (increased risk of anaphylaxis). Estrogens(decrease the antihypertensive effect). Flecainide, lidocaine, MAO Inhibitors, Neuromuscular blocking agents, Nicotine, Nitroglysirine, Phenothiazines, Phenytion, Phenoxybenzamine, Phentolamin, Propafenone, Sympathomimetics, Xanthines, also have interactions with Proprated®.
(USPDI)
Adverse reactions
Bradycardia, symptomatic, bronchospasm, congestive heart failure, mental depression, reduced peripheral circulation, Allergic reaction, arrhythmias, back pain or joint pain, chest pain, confusion, hallucinations, hepatotoxicity, leucopenia, orthostatic hypotension, psoriasiform eruption, thrombocytopenia, decreased sexual ability, drowsiness, trouble in sleeping, unusual tiredness or weakness, anxiety, constipation, diarrhea, nasal congestion, nausea or vomiting, stomach discomfort, changes in taste, dry, sore eyes, frequent urination, itching of skin, nightmares and vivid dreams, numbness and/or tingling of fingers, toes or skin especially the scalp.
(USPDI)
Overdosage
Bradycardia, dizziness, or fainting, hypotension, irregular heartbeat, difficulty breathing, bluish-color fingernails, palms, hands or seizures.
Treatment of overdosage is based on decreased absorption (gastric lavage and activated charcoal) and other specific treatments (like Atropine, Diazepam, dobutamine, dopamine, glucagons, transvenous pacing,..).
(USPDI)
Dosage and Administration
-Antianginal:
Oral, 80 to 320 mg per day in two, three or four divided doses.
-Antiarrhythmic:
Oral, 10 to 30 mg per day in three or four times daily.
-Antihypertensive:
Oral, 40 mg two times a day (the dosage being increased gradually as
needed and tolerated.)
-Hypertropic Cardiomyopathy:
20 to 40 mg three to four times a day.
-Myocardial infarction:
180 to 240 mg a day in divided doses
-pheochromocytoma:
20 to 40 mg three times a day
-Vascular headache prophylactic:
20 mg four times a day, up to 240 mg a day
-Antitremor agent:
40 mg two times a day up to 320 mg daily
-Antianxiety as adjunct therapy:
10 to 80 mg thirty to ninety minutes prior to the anxiety provoking activity.
-Thyrotoxicosis as adjunct therapy:
10 to 40 mg three to four times daily.
-Usual pediatric dose:
-Antiarrhythmic/Antihypertensive:
-Initial:
Oral, 500 mcg (0.5 mg) to 1 mg per kg of body weight per day in two to four divided doses has been used as an initial dose and being adjusted afterward.
(USPDI)
Storage
Store below 30˚ c and away from humidity and direct light.
How supplied
proprated® tablets are supplied as film coated tablets of 10 mg (pink), 20 mg (pink), 40 mg (pink) in white opaque blisters of 10`s outered in boxes of 100`s.
References
1-USP DI 2006
2-Martindale 2007
3-USP DI 2004
4-Drug facts 2004