Interacting Drugs- summary

Digitalis glycosides 

Albuterol                                                                                                                      enhanced skeletal muscle binding of dogoxin

Betablockers                                                                                                                           AV modal conduction can result in complete heart block 

Disopyramide                                                                                                                      alter pharmacolgic effects of digoxin, 

Non deploarising muscle relaxants-succinylcholine                                                            when administered with digitalis glycosides, toxicity  ( cardiac arrhythmias) of either agents increased 

Potas. sparing diuretics- spironolactone-                                                                              increase or decrease toxic effects of digitalis glycosides diuretics. Monitoring  is required. Spironolactone may interfere with some digoxin assays Amiloride decrease inotropic effects of digoxin Triamterene increase its pharmacologic effects 

Sympathomimetics - concomittant use with digoxin can increase the risk of cardiac arrhythmias 

Thiazide loop diuretics - Amphotericin B                                                                               increase urinary potassium loss , hypokalemia may increase diuretics } effects of toxicity of digitalis glycosides . Observe fot clinical signs of fluid or electrolytes imbalance. Replace electrolyte as appropiate 

Thyroid hormones /Thioamines                                                                                           may decrease therapeutic effects of digitalis glycosides .Thioamines increase        therapeutic and toxic effects

Congestive heart failure, atrial fibrillation, atrial flutter, paroxysmal tachycardia, cardiogenic shock.

Death due to digitalis toxicity due to cardiac arrhythmias in combination with heart block. Extrabeats,anorexia,nausea and vomiting.

Diarrhoea in elderly, confusion, dizziness, restlessness, nervousness, agitation, amnesia, visual disturbances.

Gynaecomastia and allergy skin rash, eosinophillia, thrombocytopenia and vasculitis, sexual dysfunction, and sweating can occur but are rare.

Digitalis toxicity,ventricular tachycardia/fibrillation,obstructive cardiomyopathy.

Special precautions:

Cardiac dysarrhythnmias, hypokalemia, hypertension,IHD, hyperkalaemia, hypomagnesaemia, elderly patients, elctroconversion, renal/thyroid dysfunction.

Electrolyte imbalance- Potassium- hypokalemia sensitizes the myocardium to digitalis and may reduce the positive inotropic effect of digitalis.

Toxicity can occur even with normal serum glycoside levels. Calcium- calcium particularly when administered rapidly IV, may produce serious arrhythmias in digitalized patients. Hypercalcemia from any cause predisposes the patient to digitalis toxicity.

Magnesium- hypomagnesimia may predispose to digitalis toxicity. If low magnesium levels are detected in a patient receiving digoxin, institute replacement therapy.

Thyroid dysfunction- digoxin requirements are reduced in hypothyroidism, digoxin responses in patients with compensated thyroid disease are normal.

Laboratory tests- perform periodic detreminations of heart rate, electrolytes, especially potassium, ECG, and renal function BUN or serum creatinine. Digoxin may produce false ST-T changes in ECG during excercise testing.

Serum digoxin concentration- it may also be useful to measure glycoside serum concentration periodically especially if digitalis intoxification is suspected.

Warnings-

Long term use in CHF- the drug is continued after heart failure is aboished unless some other known precipitating factors is corrected. If digoxin is discontinued, regluarly monitor for clinical evidence of recurrent heart failure.

Obesity- digitalis alone or with other drugs has been promoted for use in treatment of obesity. Potentially fatal arrhythmias or other advrese effects make the use of these drugs in treating obesity dangerous and unwarranted.

Digitalis toxicity- if digitalis intoxification cannot be excluded cardiac glycosides should be withheld temporararily if the clinical situation permits.

Detremination of drug serum levels may be helpful.

Severe carditis- patients with severe carditis suchas carditis associated with rheumatic fever or viral myocarditis are sepecially sensitive to digoxin-induced disturbances.

Cardiovascular disease- patients with acute myocardial infarction (MI) severe pulmonary disease severe carditis, eg carditis associated with rheumatic fever or viral myocarditis ) or advanced heart failure may be more sensitive to digitalis and more prone to disturbances of rhythm . If heart failure devolops, digitilaztion may be tried with relatively low doses and cuatiously increased until a beneficial effect is obtained. If the therapeutic trial does not result in improvement, discontinue the drug

 Renal function improvement- renal insufficiency delays excetion of of dogoxin, adjust dosage in patients with renal disease.

Digitoxin toxicity also develops more frequently and lasts longer in renal impairment because of decreased digitoxin excretion.

Hepatic function impairment- impaired hepatic function does not appear to significantly alter transformation or effects of digoxin, however reduction in dosage may be necessary.

Elderly- excercise care in elderly patients because their body mass tends to be small and renal, clearance is likely to be reduced.

Pregnancy- use only when clearly needed and when the potential benefits outweigh the potential hazards to the fetus.

Lactation- ecercise caution while administering to a nursing woman.

Children- carefully titrate dose. ECG monitoring may be necessary to avoid intoxification.

Indications:

Congestive heart failure, atrial fibrillation, atrial flutter, paroxysmal tachycardia, cardiogenic shock..

Dosage:

Peak body digoxin stores of 8 to 12mcg/kg should provide therapeutic effect.Larger stores (10 to 15mcg/kg are often required for control of ventricular rate in patients with atrial flutter or fibrillation.

Overdosage-

Symptoms GI- anorexia,nausea, vomting and diarrhea CNS- headache, weakness, apathy, drowsiness, visual disturbances, blurred , yellowvision, halo effect, confusion, restlessness, disoreintation, seizures, ECG abnormalities Cardiovascular- ventricular tachycadia

Treatment 1. Discontinue digitalis until all signs of toxicity are abolished.

Missed dose-

1. If you miss a dose of this medicine, and you remember it within 12 hours, take it as soon as you remember

2. However, if you do not remember until later, do not take the missed dose at all and do not double the next one.

3. Instead go back to yourregular dosing schedule.

4. If you have any questions about this or if you miss doses for 2 or more days in a row check with your doctor.

For Availability/supplies 

List of entries

1. Congestive Heart failure (CHF)

2. Artial fibrillation

3. Artial flutter

1. Heart Failure ( 1035 )

 Heart failure is charaterized by well known symptoms and physical signs. Heart failure is considered 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,.

2. Atrial fibrillation ( 1055 )

 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 contractions in the untreated patient are usually rapid and irregularly irregular.

3. Atrial flutter ( 1054 )

 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

1.Take the medicine exactly as directed by the physician.

2.Do not change the dose of digitoxin unless your doctor tells you to do so.

3. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to digitalis other related medicines. Also tell your doctor if youn are allergic to any other substances such as foods, preservatives or dyes.

4. Pregnancy-Studies on efects of pregnancy has not been done. However make sure that your doctor knows if you are pregnant or if you may become pregnant before taking digitalis.

5. Breast feeding- although small amounts of digitalis medicines pass into the breast milk they have not been reported to cause problems in nursing babies.

6. Children- this medicine has not shown to cause different side effects or problems than it does in adults.

7. Elderly- signs and symptoms of overdose may be especialy likely to occur in elderly patients

8. Other medicines-

Tell your doctor if you are taking any of the following- Amiodarone or Amphetamines Appetite suppressants or Digitalis medicine other than heart medicine Medicines for asthma or other breathing problems or Medicines for cold, sinus problems or hay fever or other allergies - may increase the risk of heart rhythm problems

9.Other medical problems-

Tell your doctor if you have any other medical problems- Heart disease or Lung disease - heart may be more sensitive to the efects ofdigitalis Heart rhythm problems - digitalis glycosides may make certain herat rhythm problems worse Kidney disease or Liver disease - effects may be increased because of slower removal of digitalis medicines from the body Thyroid disease- patients with low or high thyroid gland activity may be more or less sensitive to the efects of digitalis glycosides

10. 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.

Pharmacology:

The influence of digitalis glycoside on the myocardium is dose related and involves both a direct action on cardiac muscle and the specialised conduction system,and indirect actions on the cardiac systems medicated by the autonomus nervous system. Pharmcokinetics: Digitoxin is well absorbed. Digitoxin tablets are absorbed 60 to 80%,the elixir is absorbed 70 to 85%,and a solution filled capsule is 90 to 100%. When oral digitoxin is taken after meals,the rate of absorption is slowed,but total amount absorbed is unchanged.

Delayed absorption. When oral digoxin is taken after meals, the rate of absorption is slowed but total amount absorbed is usually unchanged. When taken with bran fiber, the amount absorbed may be reduced

Pregnancy-

Use only when clearly needed and when the potential benefits outweigh the potential hazards to the fetus.

Lactation- Exercise caution while administering to a nursing woman.

Children- Carefully titrate dose. ECG monitoring may be necessary to avoid intoxification.