(c) Propranolol

Propranolol 80 mg three times daily did not affect the pharmacokinetics of

a single 20-mg dose of quinapril in 10 healthy subjects.3 The pharmacokinetics
of ramipril 5 mg daily were unaffected by propranolol 40 mg
twice daily.4 Similarly, the manufacturer of fosinopril reports that the
bioavailability
of fosinoprilat, its active metabolite, was not altered by propranolol.
5,6 Another study found no significant pharmacokinetic
interaction between cilazapril 2.5 mg daily and propranolol 120 mg daily
in healthy subjects, but the reductions in blood pressure were about doubled
and long-lasting in healthy subjects and in patients with hypertension
Indications

Listed in Dosage.

Dosage

Adult : PO HTN As conventional tab or oral soln: Initial: 40-80 mg

bid. Usual range: 160-320 mg/day. Max: 640 mg/day. As extended
release cap: Initial: 80 mg once daily. Usual range: 120-160 mg
once daily. Max: 640 mg/day. Phaeochromocytoma As
conventional tab or oral soln: 60 mg/day in divided doses given 3
days pre-op w/ -blocker. If tumour is inoperable, 30 mg/day in
divided doses may be given. Angina pectoris As conventional
tab or oral soln: Initial: 40 mg bid or tid. Usual range: 120-240
mg/day. Max: 320 mg/day. As extended release cap: 80 mg once
daily, may be increased to 160 mg once daily. Max: 240
mg/day. MI As conventional tab or oral soln: 40 mg 4 times daily
for 2-3 days followed by 80 mg bid. Doses are given w/in 5-21
days of MI. Cardiac arrhythmias As conventional tab or oral
soln: 30-160 mg/day in divided doses. Hypertrophic
cardiomyopathy As conventional tab or oral soln: 10-40 mg, 3-4
times/day. Hyperthyroidism As conventional tab or oral soln: 1040 mg, 3-4 times/day. As extended release cap: 80 mg once daily,
may be increased to 160 mg once daily. Max: 240
mg/day. Anxiety As conventional tab or oral soln: 10-40 mg bid
or tid. As extended release cap: 80 mg once daily. Max: 160 mg
once daily. Essential tremor As conventional tab or oral soln:
Initial: 40 mg bid or tid. Usual range: 120-240 mg/day. As
extended release cap: 80 mg once daily, may be increased to 160
mg once daily. Max: 240 mg/day. Migraine prophylaxis As

conventional tab or oral soln: Initial: 40 mg bid or tid. Usual

range: 120-240 mg/day. As extended release cap: 80 mg once
daily, may be increased to 160 mg once daily. Max: 240
mg/day. Portal HTN As conventional tab or oral soln: Initial: 40
mg bid increased at wkly intervals up to 160 mg bid. As extended
release cap: 80 mg once daily, may be increased to 160 mg once
daily. Max: 320 mg/day. IV Emergency treatment of cardiac
arrhythmias 1 mg given over 1 min, repeated every 2 min if
needed. Max: 10 mg in conscious patients and 5 mg in patients
under anaesth.
Dosage Details

Intravenous
Emergency treatment of cardiac arrhythmias
Adult: 1 mg given over 1 min, repeated every 2 min if needed.
Max: 10 mg in conscious patients and 5 mg in patients under
anaesth.
Oral
Phaeochromocytoma
Adult: As conventional tab or oral soln: 60 mg/day in divided
doses given 3 days pre-op w/ -blocker. If tumour is inoperable,
30 mg/day in divided doses may be given.
Child: As conventional tab or oral soln: 0.25-0.5 mg/kg 3-4 times
daily.
Oral
Hypertension
Adult: As conventional tab or oral soln: Initially, 40-80 mg bid.
Usual range: 160-320 mg/day. Max: 640 mg/day. As extended
release cap: Initially, 80 mg once daily. Usual range: 120-160 mg
once daily. Max: 640 mg/day.
Child: As conventional tab: Initially, 1 mg/kg/day in 2 divided
doses. Usual range: 2-4 mg/kg/day in 2 divided doses. Max: 4
mg/kg/day in 2 or 3 divided doses.
Oral
Myocardial infarction
Adult: As conventional tab or oral soln: 40 mg 4 times daily for 23 days followed by 80 mg bid. Alternatively, 180-240 mg/day in

divided doses. Doses are given w/in 5-21 days of MI.

Oral
Portal hypertension
Adult: As conventional tab or oral soln: Initially, 40 mg bid
increased at wkly intervals up to 160 mg bid. As extended release
cap: 80 mg once daily, may be increased to 160 mg once daily.
Max: 320 mg once daily.
Oral
Prophylaxis of migraine
Adult: As conventional tab or oral soln: Initially, 40 mg bid or tid.
Usual range: 120-240 mg/day. As extended release cap: 80 mg
once daily, may be increased to 160 mg once daily. Max: 240
mg/day.
Child: As conventional tab or oral soln: 12 yr 10-20 mg bid or
tid. >12 yr Initially, 40 mg bid or tid increased to wkly intervals up
to 160 mg/day. Max: 240 mg/day.
Oral
Cardiac arrhythmias
Adult: As conventional tab or oral soln: 30-160 mg/day in divided
doses.
Child: As conventional tab or oral soln: 0.25-0.5 mg/kg 3-4 times
daily.
Oral
Essential tremor
Adult: As conventional tab or oral soln: Initially, 40 mg bid or tid.
Usual range: 120-240 mg/day. As extended release cap: 80 mg
once daily, may be increased to 160 mg once daily. Max: 240
mg/day.
Oral
Anxiety
Adult: As conventional tab or oral soln: 10-40 mg bid or tid. As
extended release cap: 80 mg once daily. Max: 160 mg once daily.

Oral
Angina pectoris
Adult: As conventional tab or oral soln: Initially, 40 mg bid or tid.
Usual range: 120-240 mg/day. Max: 320 mg/day. As extended
release cap: 80 mg once daily, may be increased to 160 mg once
daily. Max: 240 mg/day.
Oral
Hypertrophic cardiomyopathy
Adult: As conventional tab or oral soln: 10-40 mg, 3-4 times
daily.
Oral
Hyperthyroidism
Adult: As conventional tab or oral soln: 10-40 mg, 3-4 times
daily. As extended release cap: 80 mg once daily, may be
increased to 160 mg once daily. Max: 240 mg/day.
Child: As conventional tab or oral soln: 0.25-0.5 mg/kg 3-4 times
daily.
Hepatic
Impairment

Oral:
Severe: 20 mg tid.
HTN, Angina pectoris, Hyperthyroidism, Anxiety, Essential
tremor, Portal HTN:
As extended release cap: 80 mg once daily or 160 mg every other
day.

Administration

Tab: Should be taken on an empty stomach. Take before meals.

Cap: May be taken with or without food. Take consistently either
always w/ or always w/o meals.

Contraindicatio
ns

Sinus bradycardia, cardiogenic shock, sick sinus syndrome,

Raynaud's syndrome, 2nd and 3rd degree heart block, overt CHF,
bronchial asthma, COPD, untreated phaeochromocytoma,
Prinzmetal's angina; severe peripheral arterial disease, metabolic
acidosis. Concomitant use w/ thioridazine.

Special
Precautions

Sinus node dysfunction, DM, history of nonallergic bronchospasm

(e.g. chronic bronchitis, emphysema), myasthenia gravis, 1st

degree heart block. May mask signs of hyperthyroidism and

hypoglycaemia. Renal or hepatic impairment. Abrupt withdrawal
may exacerbate angina symptoms or precipitate MI in patients w/
coronary artery disease. Elderly. Pregnancy and lactation.
Adverse Drug
Reactions

Bradycardia, hypotension, syncope, shock, angina pectoris.

Lightheadedness, giddiness, ataxia, dizziness, irritability,
sleepiness, hearing loss, and visual disturbances to vivid dreams,
hallucinations, and confusion. Epigastric distress, abdominal
cramping, nausea, vomiting, diarrhoea, constipation, and
flatulence. Hypoglycaemia, skin rash, transient eosinophilia,
thrombocytopenic and nonthrombocytopenic purpura; elevated
levels of K, transaminases, and BUN. Rarely, Peyronie's disease
and dry eyes.

Pregnancy
Category (US
FDA)

Parenteral/PO: C, D (in 2nd & 3rd trimesters)

Patient
Counselling

Avoid cigarette smoking.

Monitoring
Parameters

Monitor ECG, heart rate and BP.

Overdosage

Symptoms: Hypotension, bradycardia, pulmonary oedema,

cardiogenic shock, syncope, bronchospasm, drowsiness, seizures,
loss of consciousness. Management: For recent ingestion,
evacuate gastric contents. Admin atropine or isoproterenol IV for
bradycardia. Glucagon may be useful for the treatment of
hypotension or depressed myocardial function. Bronchospasm
can be treated w/ isoproterenol and aminophylline IV.

Drug
Interactions

May cause additive negative chronotropic and/or inotropic effect

w/ amiodarone, disopyramide, quinidine, flecainide and Ca
channel blockers. May cause additive hypotensive effect w/
phenothiazines. -adrenergic stimulating effects of
sympathomimetic agents are antagonised. Concomitant admin w/
catecholamine-depleting drugs (e.g. reserpine) may cause
additive effects and potentiate depression. Reduced
antihypertensive effect w/ aluminium and NSAIDs.
Coadministration w/ warfarin increases its bioavailability and
prothrombin time. Altered antidiabetic response when used w/
antidiabetic agents and insulin. Increased risk of hypotension and

attenuation of the reflex tachycardia w/ anaesth drugs.

Potentially Fatal: Increased risk of QT interval prolongation and
torsades de pointes w/ thioridazine.
Food
Interaction

BP control may be altered w/ alcohol. Protein-rich foods may

increase bioavailability.

Lab
Interference

May alter thyroid function test results. May interfere w/ glaucoma

screening tests.

Mechanism of
Action

Description: Propranolol is a non-cardioselective -blocker that

competitively blocks 1- and 2-receptors resulting in decreased
heart rate, myocardial contractility, BP and myocardial oxygen
demand. It has membrane-stabilising properties.
Onset: 1-2 hr (oral).
Pharmacokinetics:
Absorption: Almost completely absorbed from the GI tract.
Bioavailability: Approx 25%. Time to peak plasma concentration:
Approx 1-2 hr (oral).
Distribution: Widely distributed, enters breast milk, crosses
blood brain barrier and placenta. Volume of distribution: 4 L/kg.
Plasma protein -binding: Approx 90%.
Metabolism: Undergoes hepatic metabolism via CYP2D6
isoenzyme, and CYP1A2 to 4-hydroxypropranolol (biologically
active).
Excretion: Via urine (96-99% as metabolites and <1% as
unchanged drug). Elimination half-life: Approx 3-6 hr.

Storage

Store between 20-25C.