ACE inhibitors include-

Benazepril, Captopril, Enalapril, Enalaprilat, Fosinopril, Lisonopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril

Refer Captopril

Interacting drugs-

Summary

+ACE Inhibitors

  Antacids +

  bioavailability of ACEIs decreased, more likely with captopril. Separate the adminindstration times by 1 to 2 hours

 Capsicin +

 capsicin cause or exacerbate coughing associated with ACEI treatment and vice versa

 Indomethicin +

 reduced hypotensive effect of ACEIs . more prominent in low-resin or volume dependent hypertensives patients

Phenothiazines + 

pharmacologic effects of ACEIs increased

 Probenecid + 

 increased catopril blood levels and decreased total clearance Capotopril have occurred.

 Rifampicin + Enalapril  

  pharmacologic effects of enalapril decreased

 ACEIs +

 Allopurinol  - 

  higher risk of hypersensitivity reaction possible when these drugs are given concurrently

 Digoxin - 

  increased plasma digoxin levels

 Lithium -

increased lithium levels and symptoms of toxicity occur

 Pot prepn/ Pot sparing diuretics  - 

coadministration result in elevated serum potasium concen. 

 Quinapril + Tetracycline  -

  tetracycline absorption reduced by 28% to 37% possibly due to Tetracycline the high magnesium content of quinalapril tabs

Risk of bone marrow depression increased with concomittant therapy with immunosuppressant drugs.

Hyperkalaema may result if used along with ACE inhibitors especially if renal function is impaired.

FIXED DOSE COMBINATIONS APPROVED BY DCG(I)

Hypertension

ACE inhibitors include-

Benazepril, Captopril, Enalapril, Enalaprilat, Fosinopril, Lisonopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril

Refer Captopril

Adverse reactions summary-

   
                        Adverse reactions by the ACEIs  % 
                       
CAPTOPRIL -
------------------
Adverse Reactions -

CARDIOVASCULAR -      Chest pain, Tachycardia 1 %,
 

 CNS -                                Insomnia/sleep disturbances, Parathesias , Headache,
                                           Dizziness, Fatigue,  Malaise  2%

 GI/GU                                Dysgeusia 4%, Abdominal pain, Vomiting,
                                           Nausea, Diarrhea, Anorexia, Constipation, Dry mouth, 2%

RESPIRATORY                Cough, Dyspnea   2%,

DERMATOLOGIC             Rash  5%, Pruritus, Alopecia   2%   

RENAL-
Captopril- proteinuria, renal insufficiency, nephrotic syndrome, polyuria, urinary frequency, intestial nephritis,

HEMATOLOGIC-
Catopril- neurtropenia. agranulocytosis, thrombocytopenia, pancytopenia

DERMATOLOGIC-
Captopril- rash often pruritus uusually occurs during the first 4 weeks of therapy. The rash is usually maculopapular, rarely urticarial and disaaperas with a few days of dosage reduction,short-term antihistamine treatment or discontinuation of therapy

Lab test abnormailities- elevated liver enzymes, serum bilirubin, uric acid and blood glucose.

MISCELLANEOUS- anaphtlaoid reaction have occured

Captopril- eosinophilic pneumonitis, gynaecomastia, myasthenia, rhinitis

Known hypersensitivity to the drug.Aortic stenosis

.Renal impairment.

Pregnancy & lactation.

Special precautions:

Patients on diuretics & in sod depleted cases, diuretics should be stopped or sod intake increased before starting therapy.

Monitor WBC count & urinary protein before and during therapy. In CCF diuretics,digitalis must be given concurrently as appropiate. Titrate to lowest effective dose.

Hyperkalemia- risk factors for development of hyperkalemia may include renal insufficiency, diabetes mellitus,and concurrent use of agents for treatment of hyperkalemia. Hyperkalemia also ocurred with captopril.

Surgery/anesthesia- in patients undergoing major surgery or during anesthesia with agents that produce hypertension.

ACEIs will block angiotension II formation secondary to renin release.

Cough- chronic cough has occurred with the use al ACEIs presumambly due to the inhibition of the degradation of endogenous bradykinin Characterstically the cough is nonproductive, persistent and resolves within 1 to 4 days after therapy discontinuation.

Warnings-

Neutropenia- discontinuation of captopril has generally led to prompt return of the normal WBC count, upon confirmation of neutropenia, withdraw the drug and closely observe the patient

Anaphylaoid and possibly related reactions- patients receiving ACEIs may be subject to variety of adverse reactions some of them serious

Hypotension- minimize the possibility of hypotension either by discontinuing the diuretic or increasing salt intake approximately 1 week prior to initiating ACEIs,or initiate with small doses.

Alternately, provide medical supervision for at least 2 hours after the intial dose and until blood pressure has stabilized for at least an additionl hour.

Renal function impairment- monitor renal function in hypertensive patients with renal disease particularly those with severe artery stenosis during the first few weeks of therapy.

Dosage reduction or discontinuation of the diuretic may be required.

Hepatic function impairment- since ramipril and fosinopril are primarily metabolized to their active metabolites , patients with impaired liver function could develop markedly elevated plasma levels of unchanged fosinopril or ramipril.

Elderly- no overall differences were observed between elderly patients receiving fosinopril , moxepril, or benezapril and younger patients., however greater sensitivity of some older individuals cannot be ruled out.

Pregnancy- when pregnancy is detected discontinue ACEIs as soon as possible.

Lacation- decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children- safety and efficay have not been established.

Indications:

Hypertension

Dosage:

Individualise dose. Administer 1 hour before meals. If possible discontinue previous antihypertensive drug,before treatment with Captopril. 25mg 2 or 3 times a day.

Increase to 50mg 2 or 3 times a day,if necessary after 1 or 2 weeks. Higher doses require diuretic. Do not exceed daily of 450mg.

Overdosage- Symptoms

Hypotension is most common. Systolic blood pressure of 95 mmd 80mm Hg have occured following lisonopril and captopril overdosage, respy

Treatment

1. Treatment includes usual supportive measures

2. The primary concern is correction of hypotension.

3. Volume expansion with an IV infusion of normal saline is te treatment ofchoice to restore blood pressure

4. Captopril, enalaprilat and lisonopril may be removed by hemodialysis.

5. Benazeprilat can be removed by dialysis, but this intervention should rarely,if ever be required.

 Missed dose-

 1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

List of entries-

1.Congestive Heart Failure (CHF)

2. Atrial fibrillation

3. Atrial flutter

4. Evidence Based Medicine (MIMS March 2003) -

Heart failure

 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 Classification:

1. Take captopril 1 hour before meals. Take moexipril in the fasting state

2. Do not interupt or discontinue medication without consulting physician

3. Notify physician if any of the following occur- sore throat, fever, swelling of hands or feet, irregular heart beat , chest pains, signs of angioedema, excessive prespiration, dehydration, vomiting and diarrhea may lead to a fall in blood pressure.

4. May cause dizziness, fainting or lightheadedness, especially during the first days of therapy; avoid sudden changes in posture. If syncope occurs, discontinue drug until physician has been contacted. Heart failure patients should avoid rapid increases in physical activity.

5. May cause skin rash or impaired taste perception. Notify physician if these persist.

6. Do not use salt substitutes containing potassium without consulting a physician

7. A persistent dry cough may occur and usually does not subside unless the medication is stopped. If this effect become bothersome, consult a physician.

8. Allergies- Tell your doctor if you have ever allergies to benazepril, captopril, enalapril, fosinopril, lisonopril, quinapril or ramipril.

9. Pregnancy- use of ACE inhibitors during pregnancy especially in the second and third trimesters (after three months) can cause low blood pressure, severe kidney failure, too much potassium or even death in the newborns.

10.Breast feeding- benazapril, captopril, and fosinopril pass into breat milk. Enalapril, lisonopril, quinapril or ramipril - not known whether these medicines pass into breast milk. These medicines have not been reported to cause problems in nursing babies.

11.Children- children are sensitive to the blod pressre lowering efect of ACE inhibitors, and increase side effects or other problems during treatment.

12 Elderly- not shown to cause different side effects in elderly.

13. Other medicines- certain medicines should not be taken together. Tell your doctor if you are taking the following- Diuretics Potassium containg medicines or supplements Salt substitutes Low salt milk

14. Other medical problems- presence of other medical problems affect the use of ACE inhibitors- Diabetic melitus- Heart or blood pressure vessels Heart attack Kidney disease Liver disease. Previous reactions to any ACE inhibitors- horaesness, swelling of face, mouth, hands, or feet, sudden trouble in breathing, -reactionis more likely to occur again.

15. Dosing- Follow doctors instructions

16. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

17. Storage- Keep the medicines out of reach of children Store the medicines away heat and direct light Do not store tablets or capsules in the bath room, in damp places near the kitchen sink Heat and dampness will cause the medicines to break down

Food signifiacntly reduces bioavailability of captopril. Food intake reduces Cmax and AUC of moxepril by about 70% and 40% respy. after a low-fat breakfast. After high-fat take moxepril in the fasting state.

The rate and extent of quinapril absorption are diminished moderately when administredly during a high-fat meal.

The rate but not extent of of ramipril and fosionopril is reduced by food. Food does not reduce the GI absorption of benezapril,enalapril and lisonopril

Pregnancy-

When pregnancy is detected discontinue ACEIs as soon as possible.

Lacation-

Decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children- Safety and efficay have not been established.