Perindopril co-administered with potassium supplements or potassium sparing diuretics may increase the serum potassium levels. Indomethicin reduces its antihypertensive effect Co-administration with diuretics can cause hypotension Lithium concentration may be incre4ased when co-administered

Hypertension

ACE inhibitors include- Benazepril, Captopril, Enalapril, Enalaprilat, Fosinopril, Lisonopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril Refer Captopril

Cough , back pain, sinusitis, viral infection, upper extremity pain, dyspepsia, fever, proteinuria, otic infection, palpitation, dizziness, headache, asthenia.

History of angioedema related to previous ACE inhibitor treatment. Hypersensitivity

Special precautions:

Patient with volume and salt depletion secondary to salt restriction, prolonged diuretic therapy, dialysis, diarrhea or vomitting, CCF, ischemic cardiovascular or cerbrovascular disease, undergoing surgery, anesthesia, pre-existing renal impairment. Concomittant diuretic therapy should be cautiously treated. Hypokalemia can develop in those with renal impairment To be used with caution in pregnancy and lactation

Date of Approval       September 1991

Indications:

Hypertension

Dosage

2mg once daily increased upto a maximum of 8mg /day.

Congestive Heart Failure (CHF) Heart failure is charaterized by well known symptoms and physical signs. Heart failure is coinsidered to be pathophysiological state in which an abnormal cardiac function is responsible for the failure of the heart to pump blood at a rate communsurate with the requirement of the metabolizing tissues. Heart failure is frequently but not always caused by a defect in myocardial contraction, and then the term myocardial failure is appropiate,. Increased cardiac output results in in diuresis and general amelioration of disturbances characteristic of fight heart failure (venous congestion, edema) and left heart failure ) dyspnea, orthopnea, cardiac asthma). Digitalis is generaly most effective in "low output" failure and less effective in "high output " failure ) bronchopulmonary insufficiency, artriovenous fistula, anemia, hyperthyroidism.

Atrial fibrillation This is a dysrhythmia in which the effective contraction of the atria is abolished and the AV node and the ventricles are bombarded with a very rapid and irregular series of stimuli. Many of these impulses are blocked at the AV node, but many are passed through, so that the ventricular contracrtions in the untreated patient are usually rapid and irregularly irregular.

Digitalis rapidly reduces ventricular rates and eliminates the pulse deficit. Palpitation,precordial distress or weakness are relieved and concomittant congestive failure ameliorated.

Continue digitalis in doses necessary to maintain the desired ventricular rate, both ar rest and in response to excercise and other clinical effects. Atrial flutter The dysrhythmia is less common than artial fibrillation. There is a considerable controversy regarding its mechanism.

A reciprocating rhythm or circus current movement is most likely. The atria contracts at a rate of 250 to 350 rates per minute. AV block is almost always present and its ratio is usually even numbered. Digitalis slows the heart; normal sinus rhythm appear. Digitalis slows the ventricular rate, by decreasing the degree of AV block, and commonly converts flutter to fibrillation. When the drug is withdrawn , the atrial flutter will frequently revert spontaneosuly to normal sinus rhythm. If this not occur quinidine may be employed to restore sinus rhythm.

Heart failure Evidence Based Medicine (MIMS March 2003) Beneficial ACE inhibitors such as captopril, enalapril,lisonopril,and perindopril Digoxin Appropriate use of beta-blockers Spironolactoone in severe cases Likely to be beneficial Multidisciplinary intereventions (nutrition, counselling) Excercise Angiotensin II receptor blockers Amiiodarone Implatable cardiac defibrillators Unlikely to be beneficial Calcium channel blockers Likely to beineffective or harmful Positive inotropes(non-digitalis) Non-amiodarone antiarrhythmic drugs

Key Points

1. There is conflicting evidence of the efficacy of multidisciplinary approach

2. Pescribed excercise training improves functional capacity and quality of life and reduces the rate of adverses cardiac events

3. Ace inhibitors reduce mortality, admission to hospital for heart failue and ischaemic events in patients with heart failure but are still under-used.

4. One critical trial has found that angiotensin II receptor blockers are at least as effective as ACE inhibitors for reducing clinical events(death or admission to hospitals). They confer no advantage over ACE inhibitors but can be useful if ACE inhibitors are not tolerated

5. Positve inotropic drugs improve symptoms but do not reduce mortality

6. Adding beta-blocker to ACE inhibitors decreases the rate of death and admission to hospitals

7. One clinical trial has found that in severe heart failure, adding an aldosterone receptor antagonist to an ACE inhibitor reduces mortality compared with ACE inhibitors alone.

8. ACE inhibitors delay the onset of symptoms and reduce cardiovascular events in patients with asymtomatic left ventricular systolic dysfunction

ACE inhibitors include- Benazepril, Captopril, Enalapril, Enalaprilat, Fosinopril, Lisonopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril Refer Captopril

Pharmacology: Perinopril is converted to its active diacid metabolite perinoprilat by de-esterification. Perindoprilat, the active metabolite is more potent that its prodrug. It reversibly inhibits the angiotrensin converting enzyme, thus preventing the conversuion of angiotensin I to angiotensin II .

Pharmacokinetics: Perindopril is converted to perindoprilat primarily in the liver, although some hydrolysis occurs in plasma and the intestinal wall. Perinodpril undergoes first pass metabolism to form perindopril glucoronide, which is subsequently hydrolysed to perindoprilat glucoronide. Perindopril and perinodprilat are renally cleared. Following oral administration 75% is recovered in urine over 96hours and 25% in the feces.

To be used with caution in pregnancy and lactation