Perindopril + Indapamide Pharmacology

Perindopril + Indapamide

About Perindopril + Indapamide
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Mechanism of Action of Perindopril + Indapamide
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Pharmacokinets of Perindopril + Indapamide
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Onset of Action for Perindopril + Indapamide
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Duration of Action for Perindopril + Indapamide
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Half Life of Perindopril + Indapamide
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Side Effects of Perindopril + Indapamide
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Contra-indications of Perindopril + Indapamide
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Special Precautions while taking Perindopril + Indapamide
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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 Perindopril + Indapamide
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Interactions for Perindopril + Indapamide
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Typical Dosage for Perindopril + Indapamide
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Schedule of Perindopril + Indapamide
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Storage Requirements for Perindopril + Indapamide
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Effects of Missed Dosage of Perindopril + Indapamide
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Effects of Overdose of Perindopril + Indapamide
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Perindopril

About Perindopril
A long-acting Dicarboxylate-containing ACE inhibitor, Antihypertensive.
Mechanism of Action of Perindopril
It is a prodrug and converted in to active Perindoprilat; which is a long acting 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. The drug restores the reduced elastic properties of arteries and heart in hypertensive individuals. 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 Perindopril
Absorption: Well absorbed orally, Distribution: It is distributed in to the body, Metabolism: Metabolized in the body in to active metabolite, Perindoprilat; and other inactive metabolites Excretion: Excreted mainly through urine.
Onset of Action for Perindopril
60minutes
Duration of Action for Perindopril
24 hour
Half Life of Perindopril
N/A
Side Effects of Perindopril
1.Cough
2.Angioedema
3.Chest pain
4.Hyperkalemia
5.Rashes
6.Urticaria
7.Swelling of lips, mouth, nose, and larynx
8.Fetopathic in later half of pregnancy
9.Headache
10.Dizziness
11.Depression
12.Sleep disturbances
13.Diarrhoea
14.Anorexia
15.Nausea
16.Vomiting
17.Fatigue
18.Decreased haemoglobin count
19.Infections
20.Elevated liver enzymes
21.Acute renal failure is precipitated in renal artery stenosis


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

Special Precautions while taking Perindopril
1.Renal impairment
2.Hepatic impairment
3.Ischaemic heart disease
4.Severe heart failure
5.Collagen vascular diseases
6.Angioedema
7.Cerebrovascular diseases
8.Lower dosage is needed for elderly

Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Contraindicated
Indications for Perindopril
1.Hypertension
2.Congestive heart failure
Interactions for Perindopril
Nitrates, Diuretics, Beta-blockers, Anti-depressants, Alcohol, Calcium channel blockers: Enhanced hypotensive effect.
Potassium sparing diuretics: Hyperkalaemia.
Sex hormones: Oestrogens and combined oral contraceptives antagonise hypotensive effect.
Typical Dosage for Perindopril
Starts with 4mg; orally once daily. Increases the dose to 8mg once daily or in two divided doses; after one month of therapy depending on patient`s response.
Maximum dose: 16mg/day
In CHF patients starts the dosage with 2mg once daily dosage and gradually increases at 1 to2 weeks` intervals to 4mg or further increase in dose depends up on patient`s response.

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

Effects of Missed Dosage of Perindopril
N/A
Effects of Overdose of Perindopril
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 to treat hypotension. Treat dehydration and maintain electrolyte balance.

Indapamide

About Indapamide
Thiazide-related(a non-thiazide sulphonamide) drug, Diuretic, Antihypertensive.
Mechanism of Action of Indapamide
It exerts thiazides like diuretic 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 increases natriuresis, kaliuresis and diuresis. It decreases Ca2+ excretion and increases Mg2+excretion.
It causes vasodilatation by Ca channel blockade. It decreases total peripheral resistance and exerts anti hypertensive action. 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.


Pharmacokinets of Indapamide
Absorption: It is compleately absorbed orally.
Distribution: Widely distributed
Metabolism: Extensively metabolized inside the body, and a small portion reaches tubular fluid.
Excretion: Excreted mainly through urine and rest is excreted through faeces.
Onset of Action for Indapamide
1 to 2 hours
Duration of Action for Indapamide
24 to 36 hours
Half Life of Indapamide
N/A
Side Effects of Indapamide
1. Dizziness
2 Headache
3. Orthostatic hypotension
4. Back pain
5. Infection
6. Rhinitis
7. Pharyngitis
8. Sinusitis
9. Vertigo
10 Nausea
11. Diarrhoea
12. Vomiting
13. Constipation
14. Muscle cramps
15. Peripheral edema
16. Polyuria
17. Weakness
18. Hypochloremia
19. Hypokalaemia
20. Hyponatraemia
21. Hyper urecaemia
22. Elevated levels of glucose calcium and lipids
23. Gastro intestinal disturbances
24. Impotence
25. Visual impairment
26. Electrolyte imbalance
27.Ototoxicity
Contra-indications of Indapamide
1. Hepatic impairment.
2. Hypersensitivity to the drug
3. Hypersensitivity to Sulfonamides
4. Anuric renal failure
5. Cerebro vascular accidents

Special Precautions while taking Indapamide
1. Renal impairment
2. Progressive Liver diseases
3. Hyper urecaemia and Gout
4. Diabetes mellitus
5. Fluid and electrolyte imbalance
6. Cirrhosis
7. Hyper calcaemia
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Contraindicated
Indications for Indapamide
1. Hypertension
2. Oedema
Interactions for Indapamide
Diazoxide: Synergistic action - may cause hyperglycemia, hyperuricaemia and hypotension.
Digitalis: Diuretic induced hypokalaemia may precipitate digitalis toxicity.
Frusemide: Synergy leading to profound diuresis and greater than predicted electroyte loss.
Sulfonylureas: Hypoglycaemic effects enhanced.
Chlorpropamide: Hypokalaemia.
Propantheline: Bioavailability of indapamide increased.
Metoclopramide: Bioavailability of indapamide decreased.
NSAID`s: Natriuretic effect of indapamide decreased.
Typical Dosage for Indapamide
Hyper tension: 1.25mg single daily dose. Increased to 2.5mg if required after 4 weeks.
Maximum dose: 5mg/day
Edema: 2.5mg single daily dose. Increased to 5mg if required after 1 week.

Schedule of Indapamide
G
Storage Requirements for Indapamide
Store at a cool dry place; and at a temperature below 30 degree C. in a well closed container. Keep out of reach of children.
Effects of Missed Dosage of Indapamide
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 Indapamide
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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