Ramipril + Hydrochlorothiazide Pharmacology

Ramipril + Hydrochlorothiazide

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

About Ramipril
Angiotensin - converting enzyme inhibitor, Antihypertensive.
Mechanism of Action of Ramipril
It is a prodrug and converted in to active Ramiprilat; which 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. The drug does not compromise renal, cerebral, and coronary blood flow. 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 Ramipril
Absorption: Absorbed orally up to 60%, Distribution: Widely distributed in the tissues, Metabolism: Metabolized in the body in to active metabolite, Ramiprilat. Excretion: Excreted mainly through urine and also excreted through faeces.
Onset of Action for Ramipril
1 to 2 hours
Duration of Action for Ramipril
24 hours
Half Life of Ramipril
8 to 48 hours
Side Effects of Ramipril
1.Cough
2.Angioedema
3.Hypotension
4.Chest pain
5.Hyperkalemia
6.Rashes
7.Urticaria
8.Swelling of lips, mouth, nose, and larynx
9.Fetopathic in later half of pregnancy
10.Headache
11.Diarrhoea
12.Fatigue
13.Dizziness
14.Nausea
15.Neutropenia
16.Thrombocytopenia
17.Acute renal failure is precipitated in renal artery stenosis


Contra-indications of Ramipril
1.Hypersensitivity to the drug
2.Renal artery stenosis
3.Aortic stenosis
4.Coarctation of aorta

Special Precautions while taking Ramipril
1.Renal impairment
2.Hepatic impairment
3.Use cautiously in patient at high risk of cardiogenic shock, severe heart failure etc
4.Anaesthesia and surgery

Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Contraindicated
Indications for Ramipril
1.Hypertension
2.Heart failure

Interactions for Ramipril
Antacids: May decrease bioavailability of ramipril.
Phenothiazines: Pharmacologic effects enhanced by phenothiazines.
Allupurinol: Higher risk of hypersensitivity reactions.
Digoxin: Increases plasma digoxin levels.
Potassium preparations & Potassium sparing diuretics: Hyperkalaemia and increased risk of renal failure.
Lithium: Toxicity due to increased serum concentration of lithium.
Typical Dosage for Ramipril
Starts with 1.25mg once daily. Increases the dose to 2.5 to 5mg once daily; depending on patient`s response.
Maximum dose: 10mg once daily.
In CHF patients starts the dosage with 1.5mg once daily dosage and gradually increases at 2 to3 weeks` intervals to usual dosage.

Schedule of Ramipril
H
Storage Requirements for Ramipril
Store at a temperature range of 15 to 30 degree C. in a well closed container and protect from moisture.






Effects of Missed Dosage of Ramipril
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 Ramipril
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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