PROPRANOLOL HYDROCHLORIDE

PROPRANOLOL HYDROCHLORIDE
(proe-pran'oh-lole)
Apo-Propranolol , Inderal, Inderal LA, InnoPran XL, Novopranol 
Classifications: beta-adrenergic antagonist; antihypertensive agent; antiarrhythmic, class ii;
Therapeutic: antihypertensive
; antiarrhythmic, class ii
Pregnancy Category: C

Availability

10 mg, 20 mg, 40 mg, 60 mg, 80 mg, 90 mg tablets; 60 mg, 80 mg, 120 mg, 160 mg sustained release capsules; 4 mg/mL, 8 mg/mL, 80 mg/mL solution; 1 mg/mL injection

Action

Nonselective beta blocker of both cardiac and bronchial adrenoreceptors that competes with epinephrine and norepinephrine for available beta-receptor sites. In higher doses, exerts direct quinidine-like effects, that depresses cardiac function including contractility and arrhythmias. Lowers both supine and standing blood pressures in hypertensive patients. Mechanism of antimigraine action unknown but thought to be related to inhibition of cerebral vasodilation and arteriolar spasms.

Therapeutic Effect

Blocks cardiac effects of beta-adrenergic stimulation; as a result, reduces heart rate, myocardial irritability (Class II antiarrhythmic), and force of contraction, depresses automaticity of sinus node and ectopic pacemaker, and decreases AV and intraventricular conduction velocity. Hypotensive effect is associated with decreased cardiac output, suppressed renin activity, as well as beta-blockade; decreases platelet aggregation.

Uses

Management of cardiac arrhythmias, myocardial infarction, tachyarrhythmias associated with digitalis intoxication, anesthesia, and thyrotoxicosis, hypertrophic subaortic stenosis, angina pectoris due to coronary atherosclerosis, pheochromocytoma, hereditary essential tremor; also treatment of hypertension alone, but generally with a thiazide or other antihypertensives.

Unlabeled Uses

Anxiety states, migraine prophylaxis, essential tremors, schizophrenia, tardive dyskinesia, acute panic symptoms (e.g., stage fright), recurrent GI bleeding in cirrhotic patients, treatment of aggression and rage.

Contraindications

Greater than first-degree heart block; CHF, right ventricular failure secondary to pulmonary hypertension; ventricular dysfunction; sinus bradycardia, cardiogenic shock, significant aortic or mitral valvular disease; bronchial asthma or bronchospasm, severe COPD, pulmonary edema, allergic rhinitis during pollen season; concurrent use with adrenergic-augmenting psychotropic drugs or within 2 wk of MAO inhibition therapy; abrupt discontinuation; major depression; peripheral vascular disease, Raynaud's disease; pregnancy (category C).

Cautious Use

Peripheral arterial insufficiency; history of systemic insect sting reaction; patients prone to nonallergenic bronchospasm (e.g., chronic bronchitis, emphysema); major surgery; cerebrovascular disease, stroke; renal or hepatic disease; pheochromocytoma, vasospastic angina; older adults; diabetes mellitus; patients prone to hypoglycemia; hyperthyroidism, thyrotoxicosis; surgery; myasthenia gravis; Wolff-Parkinson-White syndrome; lactation.

Route & Dosage

Hypertension
Adult: PO 40 mg b.i.d., usually need 160–480 mg/d in divided doses; InnoPran XL dose 80 mg qhs, may increase to 120 mg hs
Child: PO 0.5–1 mg/kg/d in 2 divided doses (max: 16 mg/kg/d)
Neonate: PO 0.25 mg/kg q6–8h (max: 5 mg/kg/d) IV 0.01 mg/kg slow IV push over 10 min q6–8h prn (max: 0.15 mg/kg q6–8h)

Angina
Adult: PO 80–320 mg mg/d in divided doses

Arrhythmias
Adult: PO 10–30 mg q6–8h IV 0.5–3 mg q4h prn
Child: PO 0.5–1 mg/kg/d in divided doses, titrate up to daily dose of 2–6 mg/kg/d (max: 16  mg/kg/d) IV 0.01–0.1 mg/kg/min over 10 min (infant max: 1 mg, child max: 3 mg)

Acute MI
Adult: PO 180–240 mg/d in divided doses

Migraine Prophylaxis
Adult: PO 80 mg/d in divided doses, may need 160–240 mg/d


Hemodialysis: No supplemental dose needed

Administration

  • Do not give within 2 wk of a MAO inhibitor.
  • Note that InnoPran XL should be given hs.
  • Be consistent with regard to giving with food or on an empty stomach to minimize variations in absorption.
  • Take apical pulse and BP before administering drug. Withhold drug if heart rate <60 bpm or systolic BP <90 mm Hg. Consult physician for parameters.
  • Ensure that sustained release form is not chewed or crushed. Must be swallowed whole.
  • Reduce dosage gradually over a period of 1–2 wk and monitor patient closely when discontinued.
Intravenous

Note: Verify correct IV concentration and rate of infusion for neonates with physician.

PREPARE: Direct: May be given undiluted or dilute each 1 mg in 10 mL of D5W.  Intermittent: Dilute a single dose in 50 mL of NS.  

ADMINISTER: Direct for Adult: Give each 1 mg or fraction thereof over 1 min.  Direct for Neonate Child: Give each dose slowly over 5 min.  Intermittent: Give each dose over 15–20 min.  

INCOMPATIBILITIES Y-site: Amphotericin B cholesteryl complex, diazoxide.

  • Store at 15°–30° C (59°–86° F) in tightly closed, light-resistant containers.

Adverse Effects (≥1%)

Body as a Whole: Fever; pharyngitis; respiratory distress, weight gain, LE-like reaction, cold extremities, leg fatigue, arthralgia, anaphylactic/anaphylactoid reactions. Urogenital: Impotence or decreased libido. Skin: Erythematous, psoriasis-like eruptions; pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, urticaria. Reversible alopecia, hyperkeratoses of scalp, palms, feet; nail changes, dry skin. CNS: Drug-induced psychosis, sleep disturbances, depression, confusion, agitation, giddiness, light-headedness, fatigue, vertigo, syncope, weakness, drowsiness, insomnia, vivid dreams, visual hallucinations, delusions, reversible organic brain syndrome. CV: Palpitation, profound bradycardia, AV heart block, cardiac standstill, hypotension, angina pectoris, tachyarrhythmia, acute CHF, peripheral arterial insufficiency resembling Raynaud's disease, myotonia, paresthesia of hands. Special Senses: Dry eyes (gritty sensation), visual disturbances, conjunctivitis, tinnitus, hearing loss, nasal stuffiness. GI: Dry mouth, nausea, vomiting, heartburn, diarrhea, constipation, flatulence, abdominal cramps, mesenteric arterial thrombosis, ischemic colitis, pancreatitis. Hematologic: Transient eosinophilia, thrombocytopenic or nonthrombocytopenic purpura, agranulocytosis. Metabolic: Hypoglycemia, hyperglycemia, hypocalcemia (patients with hyperthyroidism). Respiratory: Dyspnea, laryngospasm, bronchospasm.

Diagnostic Test Interference

beta-adrenergic blockers may produce false-negative test results in exercise tolerance ECG tests, and elevations in serum potassium, peripheral platelet count, serum uric acid, serum transaminase, alkaline phosphatase, lactate dehydrogenase, serum creatinine, BUN, and an increase or decrease in blood glucose levels in diabetic patients.

Interactions

Drug: phenothiazines have additive hypotensive effects. beta-adrenergic agonists (e.g., albuterol) antagonize effects. Atropine and tricyclic antidepressants block bradycardia. diuretics and other hypotensive agents increase hypotension. High doses of tubocurarine may potentiate neuromuscular blockade. Cimetidine decreases clearance, increases effects. antacids, ascorbic acid may decrease absorption. Herbal: Black pepper may increase plasma levels.

Pharmacokinetics

Absorption: Completely from GI tract; undergoes extensive first-pass metabolism. Peak: 60–90 min immediate release; 6 h sustained release; 5 min IV. Distribution: Widely distributed including CNS, placenta, and breast milk. Metabolism: Almost completely in liver (CYP1A2, 2D6). Elimination: 90–95% in urine as metabolites; 1–4% in feces. Half-Life: 2.3 h.

Nursing Implications

Assessment & Drug Effects

  • Obtain careful medical history to rule out allergies, asthma, and obstructive pulmonary disease. Propranolol can cause bronchiolar constriction even in normal subjects.
  • Monitor apical pulse, respiration, BP, and circulation to extremities closely throughout period of dosage adjustment. Consult physician for acceptable parameters.
  • Evaluate adequate control or dosage interval for patients being treated for hypertension by checking blood pressure near end of dosage interval or before administration of next dose.
  • Be aware that adverse reactions occur most frequently following IV administration soon after therapy is initiated; however, incidence is also high following oral use in the older adult and in patients with impaired kidney function. Reactions may or may not be dose related.
  • Lab tests: Obtain periodic hematologic, kidney, liver, and cardiac functions when propranolol is given for prolonged periods.
  • Monitor I&O ratio and daily weight as significant indexes for detecting fluid retention and developing heart failure.
  • Consult physician regarding allowable salt intake. Drug plasma volume may increase with consequent risk of CHF if dietary sodium is not restricted in patients not receiving concomitant diuretic therapy.
  • Fasting for more than 12 h may induce hypoglycemic effects fostered by propranolol.
  • If patient complains of cold, painful, or tender feet or hands, examine carefully for evidence of impaired circulation. Peripheral pulses may still be present even though circulation is impaired. Caution patient to avoid prolonged exposure of extremities to cold.

Patient & Family Education

  • Learn usual pulse rate and take radial pulse before each dose. Report to physician if pulse is below the established parameter or becomes irregular.
  • Be aware that propranolol suppresses clinical signs of hypoglycemia (e.g., BP changes, increased pulse rate) and may prolong hypoglycemia.
  • Understand importance of compliance. Do not alter established regimen (i.e., do not omit, increase, or decrease dosage or change dosage interval).
  • Do not discontinue abruptly; can precipitate withdrawal syndrome (e.g., tremulousness, sweating, severe headache, malaise, palpitation, rebound hypertension, MI, and life-threatening arrhythmias in patients with angina pectoris).
  • Be aware that drug may cause mild hypotension (experienced as dizziness or lightheadedness) in normotensive patients on prolonged therapy. Make position changes slowly and avoid prolonged standing. Notify physician if symptoms persist.
  • Do not drive or engage in potentially hazardous activities until response to drug is known.
  • Consult physician before self-medicating with OTC drugs.
  • Inform dentist, surgeon, or ophthalmologist that you are taking propranolol (drug lowers normal and elevated intraocular pressure).

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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