Interacting drugs- summary

+ Disopyramide-

Antiarrhythmics      -      Procainamide,Lidocaine have been used, along with disopyramide, QT prolongation may occur

 Erythromycin        -      plasma levels of disopyramide increased -

Hydantoin             -       Disopyramide and half-life may be decreased

 Rifampicin           -       Disopyramide serum levels decreased

 Anticoagulants     -     decreased prothrombin time after disopyramide discontinuation may occur

 Digoxin                -       serum Digoxin may be increased, a beneficial effect has been reported -

 Disopyramide + Quinidine    -   increased disopyramide level or decreased quindine levels. This may  result in disopyramide toxicity or dereased response to quinidine

Quinidine + Disopyramide     result in decreased response to quinidine

 Flecainide            -    disopyramide has negative inotropic properties, do not use with flecainde unless benefits outweigh risks

 Beta blockers     -  difficult to predict, disopyramide clearance may be decreased, adverse effects may occur (sinus bradycardia, hypotension) or there may be no occurance of synergistic or adverse negative inotropic effects

 Reduced efficacy with administration of phenytoin.

Potentiates adverse negative chronotopic and initropic effect produced by beta-blckrs and verapramil.

Potentiates inhibitory effect on the conduction system produced by digitalis.

Potentiates QT interval prolongation produced by tricyclic antidepressants and aminodarone.Avoid other anti-arrhythmias except life threatening arrhythmias.

Ventricular arrhythmias.

DISOPYRAMIDE-

CARDIOVASCULAR -  Palpitations 5.8% Chest pain  5.8% Angina like pain 1.4 %

CNS                               Dizziness/lightheadedness 2.9%  Tremor 3.8%

                                       Coordination difficulties 1.3%
                                       Changes in sleep habits 8.7%  Weakness 2.9%

                                       Nervousness 5.8%  Fatigue 1%  Depression  1.4%
     
GI                                   Nausea/Vomiting/ heartburn 14% Diarrhea 8%

                                      Constipation 11.6%

MISCELLANEOUS        Blurred vision 7%  Headache 4% Rash 2% Dyspnea 3% 

                                     Dry mouth 14.5%   Arthalgia 2%

In controlled trials, the most frequent adverse reactions were upper GI distress ( 41% ),
tremor ( 12.6 ) lightheadedness ( 10.5% ) and coodrination difficulties ( 10.2 % ).
these reactions were generally serious. these were dose related and were reversible if the
dosage was reduced, if the drug was taken with food or antacids or if it was discontinued.
however they  still led to discontinuation in 40% 

Lab test abnormalities-
Abnormal liver function tests, positive ANA, thrombocytopenia, leukopenia,
 including neutropenia, and agranulocytosis,myelofibrosis
 

L.V.F 2nd 3rd degree block or sinus node disease in absence of pacemaker.

Cardiomyopathy. Cardiogenic shock.

Hypersens to the drug.

Children. Hypotension.

Special precautions:

Digitalise first in atrial flutter/fibrillation or blocked supraventricular tachycardia Digitalis intoxication.

Myasthenia gravis.

Pregnancy,

Hepatic failure.Glaucoma,urinary retension.

Prostatic hypertrophy. Correct significant potassium defecit ,digitalis toxicity.

Potassium imbalance- disopyramide may be ineffective in hypokalemia and its toxic efects may be enhanced in hyperkalemia and its toxic effects may be enhanced in hyperkalemia. Correct any potassium deficit before instituting therapy.

Warnings-

Proarrhythmic effects- because of proarrhythmic effects ,use with lesser arrhythmias is generally not recommended

Symptomatic ventricular premature contractions- avoid treatment of patients with this condition.

Survival- antiarrhythmic drugs have not been shown to enhance survival in patients in patients with ventricular arrhythmias.

Negative inotropic properties- Heart failure /hypertension- may cause or aggravate CHF to produce severe hypotension, especially in patients with depressed systolic function.

Do not use in patients with uncompensated or marginally compensated CHF or hypotension secondary to cardiac arrhythmias.

QRS widening- although unusual may occur, discontinue use in such cases. QTc prolongation- and worsening of arrhythmias including ventricular tachycardia and fibrillation may occur.

Atrial tachyarrhythmias- digitalize patients with atrial flutter or fibrillation prior to administrartion to ensure that enhancement of AV conduction does not increase ventricular rate beyond acceptable limits.

Conduction abnormalities- use caution in patients with sick sinus syndrome ,Wolff-Parkinsons -White (WPW) syndrome or bundle barnch block.

Heart block- if first degree heart block develops reduce dosage. If the block persists, drug discontinuation must depend upon the benefit compared to risk of higher degree of heart block.

Concomitant antiarrhythmic therapy- reserve concomitant use to disopyramide with other class IA antiarrhyythmics or propranolol for life-thraetening arrhthmias unresponsive to a single agent.

Hypoglycemia- has been reported in rare instances.

Monitor blood glucose in patients with CHF , chronic malnutrition hepatic disease and in those taking drugs which could compromise normal gluoregulatory mechanisms in the absence of food ( eg. beta-adrenoreceptor blockers, alcohol).

Anticholenergic activity- do not use in patients with urinary retention, glaucoma, or myastenia gravis unless overiding measures are taken.

Renal functin impairment- reduce dosage in impaired renal function.

Carefully monitor ECG for prolongation of PR interval , evidence ofQRS widening or other signs of over dosage

Hepatic function impairment- heaptic function impairment increases plasma half life ,therefore reduce dosage in such patients.

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

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

Approved by FDA in 1977 Indications:

Ventricular arrhythmias.

Dosage:

Individualise dose. Adults- 400 to 800mg/day.

Recommended dose 600mg/day.

Children- Divide daily dose and administer every 6 hours.

Overdosage

Symptoms  -Overdose may be followed by apnea, loss of consciousness cardiac arrhyhtmias, loss of spontaneous respiration and death. Toxic plasma levels produce excessive widening of the QRS cpmplex and QT interval, worsening of CHF, hypotension, varying conduction disturbances, bradycardia, and finally asystole.

Anticholinergic effects may be observed

Treatment

1. Prompt,vigorous treatment is necessary even in absence of symptoms.

2. Such treatment may be life saving and may be followed by activated charcoal by mouth or stomach tube

3. Administaration of isoproternol,dopamine, cardiac glycosides, diuretics, intraaortic ballon, counterpulsation,mechanical ventilation, hemodialysis or charcoal hemoperfusion may be used.

4. Monitor ECG.

5. If progressive AV block develops,implement endocardial pacing.

6. In case of impaired renalfunction,mesures to increase the GFR may reduce the toxicity.

7.Altering the urinary pH does nor affect plasma half-life or the amount of disopyramide excreted in the urine.

8. Anticholinergic effects may be reversed by neostigmine.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible unless the dose is less than 4 hours.

2. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Bladder dysfunction-

Drugs causing adverse reactions-

1. Anticholinergics

2. Monoamine oxidase inhibitors

3. Tricyclic antidepressants

4. Disopyramide

1.May cause dry mouth, difficult urination, dizziness, breathing difficulty, constipation or blurred vision. Inforn doctor if symptoms persist.

2.Do not break or chew sustained released tablets.

3. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to disopyramide or 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- disopyramide passes into breast milk

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

7. Elderly- side effects such as difficult urination and dry mouth may be especially likely to occur in elderly patients

8. Other medicines- tell your doctor if you are taking any of the following- Other heart medicine - effects on the heart may be increased Pimozide-

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

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.

11. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

12. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Pharmacology:

Disopyramide is an antiarrhythmic agent pharmacologically similar to but unrelated to procainamide and quinidine. It decreases the rate of diastolic depolarisation,decreases the upstroke velocity, increases the action potential duration of normal cardiac cells and prolongs the refractory period.

Pharmacokinetics:

Following oral admin of immediate release disopyramide, the drug is rapidly and almost completely absorbed. Peak plasma levels usually occur within 2 hours.

None reported.

Pregnancy:

Use only when clearly needed

Lactation:

Use with caution.