Patient with compensated cardiac failure, Prinzmetal angina, 1st degree atrioventricular block, peripheral vascular disease, Raynaud’s syndrome, thyroid/parathyroid disease, history of psychiatric illness, bronchospastic disease, history of allergy or asthma, COPD, pre-diabetes or diabetes mellitus, moderate to high cholesterol level, myasthenia gravis, SLE, psoriasis, untreated phaeochromocytoma. Hepatic and renal impairment. Pregnancy and lactation. Avoid abrupt withdrawal and dose reduction.
Significant: Hypersensitivity reactions (e.g. anaphylaxis), electrolyte disturbances (e.g. hypokalaemia, hyponatraemia, hypomagnesaemia, hypochloroaemic alkalosis, hypercalcaemia), transient myopia, acute angle-closure glaucoma, exacerbation of arterial insufficiency, psoriasis and SLE; CNS depression. Rarely, photosensitivity. Cardiac disorders: Bradycardia, atrioventricular conduction disturbances, heart failure exacerbation. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, loss of appetite. General disorders and administration site conditions: Fatigue, feeling cold, asthenia. Metabolism and nutrition disorders: Hyperglycaemia, hyperuricaemia. Musculoskeletal and connective tissue disorders: Muscle cramps. Nervous system disorders: Headache, dizziness, numbness in extremities, muscle weakness. Psychiatric disorders: Insomnia. Respiratory, thoracic and mediastinal disorders: Bronchospasm Vascular disorders: Orthostatic hypotension.
Monitor blood pressure, heart rate, renal function including creatinine and urea, uric acid, serum glucose, serum lipids including cholesterol and triglycerides, fluid and serum electrolytes especially for K, Na and Ca ions. Monitor for signs and symptoms of fluid and electrolyte disturbances; arterial obstruction.
Symptoms: Cardiac insufficiency, bradycardia, hypotension, bronchospasm, hypoglycaemia, fluid and electrolyte disturbance manifested by dizziness, somnolence, nausea, hypovolaemia, hypotension, hypokalaemia. Management: Symptomatic and supportive treatment. May give IV atropine for bradycardia; vasopressors and IV fluids for hypotension; isoprenaline for 2nd or 3rd degree atrioventricular block; β2 agonist and aminophylline for bronchospasm; IV glucose for hypoglycaemia; IV diuretics, inotropic and vasodilating agents for acute worsening of heart failure.
May increase toxicity with other antihypertensive agents (e.g. reserpine), calcium channel blockers (e.g. verapamil).
Bisoprolol: May potentiate AV conduction time and may increase negative inotropic effect with class I antiarrhythmic drugs (e.g. quinidine, disopyramide, propafenone). Concomitant catecholamine-depleting drugs (e.g. reserpine, guanethidine) may produce excessive sympathetic activity. May exacerbate rebound hypertension upon discontinuance of clonidine treatment. Increased risk of bradycardia with digitalis glycosides. Reduced hypotensive effect with NSAIDs.
Hydrochlorothiazide: Increased hypokalaemic effect with corticosteroids, ACTH, amphotericin, carbenoxolone, salicylic acid derivatives, and other kaliuretic diuretics. Thiazide- induced hypokalaemia or hypomagnesaemia favours the onset of digitalis-induced arrhythmia. Impaired absorption with anionic exchange resins (e.g. cholestyramine, colestipol). May potentiate the effect of nondepolarizing skeletal muscle relaxant (e.g. tubocurarine). May enhance the hyperglycaemic effect of β-blockers and diazoxide. May increase the risk of adverse effects of amantadine. May reduce the excretion of cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. Increased bioavailability with anticholinergic agents (e.g. atropine, biperiden). May enhance hypercalcaemic effect of Ca-containing medicinal products.
Hydrochlorothiazide: Reduced bioavailability with food. Increased risk of hypotension with alcohol.
Hydrochlorothiazide: May interfere with tests for thyroid and parathyroid function.
Description: Bisoprolol is a selective competitive inhibitor of β1-adrenergic receptors. It has no significant membrane stabilising or intrinsic sympathomimetic activities.
Hydrochlorothiazide is a diuretic acting mainly at the beginning of the distal tubules. It increases the excretion of Na and Cl ions, and consequently of water, by reducing electrolyte reabsorption from the renal tubules. Onset: Bisoprolol: 1-2 hours.
Hydrochlorothiazide: Approx 2 hours. Duration: Hydrochlorothiazide: 6-12 hours. Pharmacokinetics: Absorption: Bisoprolol: Rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability: Approx 80%. Time to peak plasma concentration: 2-4 hours.
Hydrochlorothiazide: Well absorbed from the gastrointestinal tract. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours. Distribution: Bisoprolol: Widely distributed, with highest concentration in the heart, liver, lungs and saliva. Plasma protein binding: Approx 30%.
Hydrochlorothiazide: Crosses the placenta and enters breast milk. Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%. Metabolism: Bisoprolol: Undergoes significant first-pass metabolism in the liver (approx 20%). Excretion: Bisoprolol: Mainly via urine (50% as unchanged drug, 50% as inactive metabolites); faeces (<2%). Plasma elimination half-life: 10-12 hours.
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: Approx 6-15 hours.