Propranolol + Hydrochlorothiazide Pharmacology

Propranolol + Hydrochlorothiazide

About Propranolol + Hydrochlorothiazide
Mechanism of Action of Propranolol + Hydrochlorothiazide
Pharmacokinets of Propranolol + Hydrochlorothiazide
Onset of Action for Propranolol + Hydrochlorothiazide
Duration of Action for Propranolol + Hydrochlorothiazide
Half Life of Propranolol + Hydrochlorothiazide
Side Effects of Propranolol + Hydrochlorothiazide
Contra-indications of Propranolol + Hydrochlorothiazide
Special Precautions while taking Propranolol + Hydrochlorothiazide
Pregnancy Related Information
Old Age Related Information
Breast Feeding Related Information
Children Related Information
Indications for Propranolol + Hydrochlorothiazide
Interactions for Propranolol + Hydrochlorothiazide
Typical Dosage for Propranolol + Hydrochlorothiazide
Schedule of Propranolol + Hydrochlorothiazide
Storage Requirements for Propranolol + Hydrochlorothiazide
Effects of Missed Dosage of Propranolol + Hydrochlorothiazide
Effects of Overdose of Propranolol + Hydrochlorothiazide


About Propranolol
A synthetic non-selective beta blocker , Antiarrhythmic,antihypertensive,antianxiety,migraine prophylatic.
Mechanism of Action of Propranolol
Propranolol is a non selective beta receptor antagonist. It have negative chronotropic and negative inotropic effects on heart. It decreases oxygen consumption; cardiac work and aortic pressure It decreases nor adrenaline and renin releases. It decreases central sympathetic out flow.
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.
Pharmacokinets of Propranolol
Absorption: well absorbed orally, bioavailabity is increased by administering along with food.
Distribution: Widely distributed in a plasma protein bound form.
Metabolism: Metabolized in liver.
Excretion: Excreted through urine.

Onset of Action for Propranolol
Duration of Action for Propranolol
Up to 12 hours
Half Life of Propranolol
4 hours
Side Effects of Propranolol
1.Congestive heart failure is precipitated or aggravated
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
10.Gastrointestinal problems
12.Sexual dysfunction
13.Cold extremities
15.Exacerbates prinzmetal`s angina

Contra-indications of Propranolol
1.Hypersensitivity to the drug
2.Second or third degree heart block
3.Congestive heart failure
4.Cardiogenic shock
6.Chronic obstructive pulmonary diseases

Special Precautions while taking Propranolol
1.Peripheral arterial diseases
2.Ischaemic heart disease
3.Congestive heart failure
4.Renal impairment
5.Hepatic impairment
6. Diabetes mellitus
7. The drug should be gradually withdraw with caution
8. Non allergic bronchospastic diseases
9. Thyrotoxicosis
10. Along with other antihypertensive drugs

Pregnancy Related Information
Old Age Related Information
Use with caution
Breast Feeding Related Information
Children Related Information
Use with caution
Indications for Propranolol
1. Hypertension
2. Arrhythmias
3. Anxiety
4. Angina
5. Migraine
6. Prophylaxis of myocardial infarction
7. Tremors
8. Phaeochromocytoma
9. Hypertrophic sub aortic stenosis

Interactions for Propranolol
Quinidine: Orthostatic hypotension.
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.
Typical Dosage for Propranolol
40 to 240mg/day
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.

Schedule of Propranolol
Storage Requirements for Propranolol
Store at controlled room temperature between 20 to 25 degree celcious in a well closed container.
Effects of Missed Dosage of Propranolol
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Propranolol
Treatment is supportive and symptomatic. After ingestion empty the stomach by induced emesis or gastric lavage. Administer activated charcoal. Treat Bradycardia with atropine 0.5 to 1mg.If required administer isoproterinol with caution. Treat hypotension with glucagons and vasopressors like epinephrine. Treat cardiac failure with diuretics and cardiac glycosides. Treat bronchospasm with isoproterinol and aminophylline.


About Hydrochlorothiazide
Thiazide derivatibve, Diuretic.
Mechanism of Action of Hydrochlorothiazide
It is thiazide diuretic which exerts its action by acting at site-3(central dilating segment of early distal tubule). It binds to Na+Cl- symporter and inhibits Na+Cl- symport at the luminal membrane. It has additional carbonic anhydrase inhibitory actions in proximal tubules. It increases natriuresis, kaliuresis and diuresis. It decreases Ca2+ excretion and increases Mg2+excretion. It also has minor carbonic anhydrase inhibitory action. It also causes direct arteriolar vasodilatation and decreases total peripheral resistance. The antihypertensive actions of the drug may be attributable to depletion of sodium and subsequent reduction in plasma volume and a decrease in peripheral resistance. Decrease in peripheral resistance is due to either the loss of sodium from the arteriolar wall or a direct action on the vascular bed. It is an effective drug in edema associated with congestive heart failure.
Vertigo: Diuretics are used in vertigo in assumption that vertigo is due to endolymphatic hydrops. They reduce labyrinthine fluid pressure

Pharmacokinets of Hydrochlorothiazide
Absorption: It is absorbed after oral administration.
Metabolism: It is not metabolized in the body.
Excretion: Excreted unchanged in urine.

Onset of Action for Hydrochlorothiazide
1 to 3 hours
Duration of Action for Hydrochlorothiazide
12 to 16 hours
Half Life of Hydrochlorothiazide
5 to 15 hours
Side Effects of Hydrochlorothiazide
1. Dizziness
2. Blurred vision
3. Confusion
4. Tingling fingers
5. Dry mouth
6. Nausea
7. Diarrhoea
8. Constipation
9. Vomiting
10. Weakness
11. Hypokalaemia
12. Hyponatraemia
13. Hyperuricaemia
14. Elevated levels of glucose, calcium and lipids
15. Gastro intestinal disturbances
16. Polyuria
17. Electrolyte imbalance
18. Jaundice
19. Rashes
20. Photosensitivity
21. Fever
22. Itching
23. Myalgia
24. Muscle cramps
25. Arthralgia
26. Blood dyscrasias
27. Ototoxicity

Contra-indications of Hydrochlorothiazide
1. Hyper uricaemia
2. Hyper calcaemia
3. Renal impairment
4. Hepatic impairment
5. Anuria
6. Hypersensitivity to the drug
7. Hyper sensitivity to sulfonamides
8. Fluid and electrolyte imbalance

Special Precautions while taking Hydrochlorothiazide
1. Gout
2. Diabetes mellitus
3. Renal impairment
4. Hepatic impairment
5. Monitor and correct Fluid and electrolyte imbalance
6. Hyper parathyroidism
7. Cirrhosis

Pregnancy Related Information
Old Age Related Information
Use with caution
Breast Feeding Related Information
Children Related Information
May be used
Indications for Hydrochlorothiazide
1. Hypertension
2. Oedema associated with heart failure
3. Oedema due to renal and hepatic diseases
4. Diabetes insipidus
5. Idiopathic hypercalciurea.
6. Vertigo
Interactions for Hydrochlorothiazide
Cholestyramine & Colestipol: decrease absorption of hydrochlorothiazide.
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.
Chlorpropamide: Hypokalaemia.
Propantheline: Bioavailability of hydrochlorothiazide increased.
Metoclopramide: Bioavailability of hydrochlorothiazide decreased.
NSAIDs: Natriuretic effect of hydrochlorothiazide decreased.
Typical Dosage for Hydrochlorothiazide
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

Schedule of Hydrochlorothiazide
Storage Requirements for Hydrochlorothiazide
Store at room temperature in a well closed container and protected from light.
Effects of Missed Dosage of Hydrochlorothiazide
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose.Continue the regular schedule.Do not double the dose.
Effects of Overdose of Hydrochlorothiazide
Treatment is supportive and symptomatic. Remove drug from the body by induced emesis and gastric lavage. Monitor and assist respiratory, cardiovascular, and renal function as indicated. Monitor and support fluid and electrolyte balance.

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