Propranolol + Hydrochlorothiazide Pharmacology
Propranolol + Hydrochlorothiazide
In sympathetic over activity, it prolongs systole by retarding conduction. It increases oxygen supply and exercise tolerance in angina patients. It decrease automaticity and abbreviates refractory period of myocardial fibers and decreases rate of depolarization in SA node, Purkinje fibers, and other ectoptic foci. Prolong effective refractory period of AV node and AV conduction is delayed. At higher doses direct depressant membrane stabilizing action is exerted. The drug decreases BP in hypertensive individuals. Initially total peripheral resistance increases due to blockade of beta mediated vasodilatation and decrease in cardiac output; so little change in BP. But when treatment is continued due to adaptation of resistance vessels to decreased cardiac output total peripheral resistance decreases and systolic and diastolic BP falls.
Antimigraine action: Propranolol is useful in migraine due to its beta blockade action. Through beta blockade action it inhibits vasodilation and relieves migraine.
Distribution: Widely distributed in a plasma protein bound form.
Metabolism: Metabolized in liver.
Excretion: Excreted through urine.
2.Decreases coronary blood flow
5.Decreases exercise capacity
6.Decreases carbohydrate tolerance
7.Decrease insulin release
8.Increases free fatty acid levels and increase LDL to HDL ratio
9.Worsens chronic obstructive lung diseases
15.Exacerbates prinzmetal`s angina
2.Second or third degree heart block
3.Congestive heart failure
6.Chronic obstructive pulmonary diseases
2.Ischaemic heart disease
3.Congestive heart failure
6. Diabetes mellitus
7. The drug should be gradually withdraw with caution
8. Non allergic bronchospastic diseases
10. Along with other antihypertensive drugs
6. Prophylaxis of myocardial infarction
9. Hypertrophic sub aortic stenosis
Rifampicin, Phenobarbital, NSAIDs, Thyroid hormones, Smoking: Decrease antihypertensive action of propranolol.
Corticosteroids: Antagonism of hypotensive effect.
Sympathomimetics: Marked hypertension and bradycardia.
Insulin: Hypoglycemic effects prolonged by propranalol and masking of symptoms of hypoglycemia in diabetes.
Lidocaine: Increased levels of lidocaine may occur resulting in toxicity.
Calcium channel blockers: Severe bradycardia especially in those with impaired LV function.
Phenothiazines: Chlorpromazine increases plasma levels of propranolol.
Reserpine: Additive effect resulting in vertigo, syncope or postural hypotension.
Clonidine: May increase the postural hypotension. Severity of rebound hypertension caused by abrupt withdrawal of clonidine enhanced.
Haloperidol: Severe hypotension.
Prazosin: May increase first dose response (acute postural hypotension) of prazosin.
Theophylline: Propranolol antagonises effect of theophylline.
Alcohol: Enhanced hypotensive effect.
ACE inhibitors: Enhanced hypotensive effect.
Lab tests: May interfere with Glaucoma screening test due to reduction in intraocular pressure.
Hypertension: Starts with 80mg once daily or in 2 divided doses and gradually increases up to 320mg/day based on patient`s response in divided doses 12th hourly or 8th hourly.
Maximum daily dose: 640mg.
Sustained release formulations: 120 to 160mg/day. Once daily.
Children: 1mg/kg/day gradually increases to 4mg/kg/day based on patient`s response in 4 divided doses
Maximum dose: 5mg/kg/day.
Arrhythmias & Anxiety: 30mg to 150mg/day in 3 to 5 divided doses.
Children: 0.5 to 4mg/kg/day in 3 to 4 divided doses.
Angina: 40 to 80mg two times daily to 4 times daily.
Migraine: 80 to 120mg/day in divided doses in 12th hourly to 8th hourly. And gradually increases at 1 week intervals to 160mg/day.
Children: 1mg/kg/day four times daily and gradually increases up to 5mg/kg/day based on patient`s response.
Prophylaxis of myocardial infarction: Initiate the therapy with 20mg dose 5days after myocardial infarction. Then give doses of 40mg thrice daily and gradually increases at weekly intervals up to 80mg based on patients response.
Vertigo: Diuretics are used in vertigo in assumption that vertigo is due to endolymphatic hydrops. They reduce labyrinthine fluid pressure
Metabolism: It is not metabolized in the body.
Excretion: Excreted unchanged in urine.
2. Blurred vision
4. Tingling fingers
5. Dry mouth
14. Elevated levels of glucose, calcium and lipids
15. Gastro intestinal disturbances
17. Electrolyte imbalance
24. Muscle cramps
26. Blood dyscrasias
2. Hyper calcaemia
3. Renal impairment
4. Hepatic impairment
6. Hypersensitivity to the drug
7. Hyper sensitivity to sulfonamides
8. Fluid and electrolyte imbalance
2. Diabetes mellitus
3. Renal impairment
4. Hepatic impairment
5. Monitor and correct Fluid and electrolyte imbalance
6. Hyper parathyroidism
2. Oedema associated with heart failure
3. Oedema due to renal and hepatic diseases
4. Diabetes insipidus
5. Idiopathic hypercalciurea.
Diazoxide: Additive action - may cause hyperglycemia, hyperuricaemia and hypotension.
Digitalis: Diuretics induced hypokalaemia may precipitate digitalis toxicity.
Lithium: Hydrochlorothiazide potentiates therapeutic and toxic effects by increasing its renal excretion.
Frusemide: Synergy leading to profound diuresis and greater than predicted electrolyte loss.
Non-depolarizing muscle relaxants: Diuretics induced hypokalaemia enhances efficacy.
Sulfonylureas: Efficacy decreased due to hydrochlorothiazide induced glucose intolerance.
Propantheline: Bioavailability of hydrochlorothiazide increased.
Metoclopramide: Bioavailability of hydrochlorothiazide decreased.
NSAIDs: Natriuretic effect of hydrochlorothiazide decreased.
Hypertension: 25mg once daily or in divided doses. Increased to 50mg if required; depending up on the patient`s response.
Children: 1mg/kg single daily dose.
Starts with 25 to 50mg. Increased the dose until desired response is obtained.
Maximum dose: 200mg/day
Maintenance dosage: 25 to 100mg daily or on alternate days.
Children: 1mg/kg single daily dose or 1 to 3mg/kg/day in two divided doses
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