Captopril + Hydrochlorothiazide Pharmacology

Captopril + Hydrochlorothiazide

About Captopril + Hydrochlorothiazide
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Mechanism of Action of Captopril + Hydrochlorothiazide
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Pharmacokinets of Captopril + Hydrochlorothiazide
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Onset of Action for Captopril + Hydrochlorothiazide
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Duration of Action for Captopril + Hydrochlorothiazide
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Half Life of Captopril + Hydrochlorothiazide
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Side Effects of Captopril + Hydrochlorothiazide
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Contra-indications of Captopril + Hydrochlorothiazide
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Special Precautions while taking Captopril + Hydrochlorothiazide
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Pregnancy Related Information
Contraindicated
Old Age Related Information
N/A
Breast Feeding Related Information
Contraindicated;since Hydrochlorthiazide is contraindicated in breast feeding the combination generic cannot be used in breast feeding mother
Children Related Information
N/A
Indications for Captopril + Hydrochlorothiazide
It is a combination of ACE inhibitor Captopril and Thiazide diuretic Hydrochlorothiazide.
1.Hypertension
Interactions for Captopril + Hydrochlorothiazide
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Typical Dosage for Captopril + Hydrochlorothiazide
Adult: 1 tablet to be taken once daily
Schedule of Captopril + Hydrochlorothiazide
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Storage Requirements for Captopril + Hydrochlorothiazide
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Effects of Missed Dosage of Captopril + Hydrochlorothiazide
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Effects of Overdose of Captopril + Hydrochlorothiazide
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Captopril

About Captopril
A specific competitive Angiotensin-Converting Enzyme (ACE) Inhibitor, Antihypertensive.
Mechanism of Action of Captopril
It is an angiotensin converting enzyme inhibitor prevents the conversion of angiotensin-1 to angiotensin-2 and abolishes the pressor actions of angiotensin. It decreases aldosterone secretion, sodium and water retention, and total peripheral resistance, leads to fall in BP. The arterioles dilate and the compliance of larger arteries is increased. Both systolic and diastolic BP is lowered. It has no effect on cardiac output and cardiovascular reflexes. And there is little dilatation of capacitance vessels; so postural hypotension is not a problem. The drug does not compromise renal, cerebral, and coronary blood flow. BP lowering depending up on sodium status and renin angiotensin activity. So greater fall in BP occurs in Reno vascular accelerated and malignant hypertension. The drug also increases plasma kinin levels and potentiate the hypotensive action of exogenously administered bradykinin. It is used for treatment of systolic heart failure, because it improves symptoms, decrease mortality and reduce ventricular hypertrophy. It reduces both preload and after load and thus increasing cardiac out put in patients with heart failure.
Pharmacokinets of Captopril
Absorption: Well absorbed orally, food reduces absorption. Distribution: Widely distributed, but poor brain penetration. Metabolism: About 50% is metabolized in liver, Excretion: Excreted mainly through urine and a small amount is excreted through faeces.
Onset of Action for Captopril
15 minutes
Duration of Action for Captopril
6 to 12 hours
Half Life of Captopril
2 to 3 hours
Side Effects of Captopril
1.Cough
2.Angioedema
3.Hypotension
4.Hyperkalemia
5.Rashes
6.Urticaria
7.Swelling of lips, mouth, nose, and larynx
8.Dysguesia
9.Fetopathic in later half of pregnancy
10.Headache
11.Dizziness
12.Nausea
13.Granulocytopenia(rare)
14.Proteinuria(rare)
15.Acute renal failure is precipitated in renal artery stenosis
16.Transient increase in liver enzymes.
Contra-indications of Captopril
1.Hypersensitivity to the drug
2.Renal impairment
3.Aortic stenosis.
Special Precautions while taking Captopril
1.Renal impairment
2.Severe autoimmune diseases
3.Sodium depletion should be corrected before starting therapy
4.Anaesthesia
5.Use cautiously along with drug that affects WBC counts or immune response
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Use with caution
Children Related Information
Use with caution
Indications for Captopril
1.Hypertension
2.Heart failure
3.Left ventricular dysfunction after myocardial infarction
4.Diabetic nephropathy
Interactions for Captopril
Antacids: Decrease efficacy of Captopril.
Indomethacin: Reduces hypotensive effect.
Digoxin: Increases plasma digoxin levels.
Potassium preparations & Postassium sparing diuretics: Hyperkalaemia and increased risk of renal failure.
Lithium: Toxicity due to increased serum concentration of Lithium.
Immunosuppressive Drugs: Increased risk of bone marrow depression.
Antidepressants, Diuretics, b-Blockers, Phenothiazines: Enhance hypotensive effect.
Morphine: Enhanced analgesic effect and respiratory depression.
Typical Dosage for Captopril
25mg 12th hourly or 8th hourly. Increases the dose after 1 to 2 weeks to 50mg 8th hourly. If patient`s response is inadequate, a diuretic may be added. Dosage may further increases to 100mg 8th hourly based on patient`s response if required.
Maximum dose: 450mg/day
Children:0.15mg/kg/day once daily or in 3 to 6 divided doses.
Heart failure: 25mg 8th hourly. Increases to 25 to 50mg 8th hourly if required. In patients on diuretic therapy starts the therapy with an initial dosage of 6.25 to 12.5 mg 8th hourly.
Left ventricular dysfunction after myocardial infarction: Give 6.25mg orally as a single dose 3days after myocardial infarction. Then 12.5mg 8th hourly and gradually increases
to 25mg or50mg 8th hourly.
Diabetic nephropathy: 25mg 8th hourly.
Schedule of Captopril
H
Storage Requirements for Captopril
Store at controlled room temperature at a range of 15 to 30 degree C.
Effects of Missed Dosage of Captopril
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 Captopril
Treatment is supportive and symptomatic. To remove drug from the body perform induced emesis and gastric lavage. Administer activated charcoal to reduce absorption In severe cases haemodialysis is considered if required. Treatment includes I.V. infusion of normal saline solution

Hydrochlorothiazide

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
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
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
Adults:
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.
Oedema:
Adults:
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
G
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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