Antiarrhythmic agents include-

Group I A  -  Moricizine, Quinidine, Procainamide, Disopyramide,
            I B -  Lidocaine, Phenytoin, Tocainide, Mexiletine
            I C     Flecanide,  Propafenone   
Group II - Propranolol, Esmolol, Acebutol
Group III - Bretylium, Amiodarone, Solatol
Group IV - Verapramil, Digoxin, Adenosine

Interacting drugs - Summary

+  Quinidine-               
       
 Amiodarone +
  increased quinidine levels, with possible potentially fatal cardiac dysrhythmias
       
  Antacids + 
  increase serum quinidine levels and toxicity
        
  Barbiturates + 
  quinidine serum levels and elimination half-life decreased
        
  Cholinergic drugs+
 concurrent cholinergic agents may result in failure to terminate paroxymal
   supraventricular tachycardia
      
  Cimetidine   +
   quinidine serum levels may be increased
       
  Hydantoins + 
  a decrease in the therapeutic effect of quinidine may occur
      
  Nifedipine   + 
  serum levels and action of choline lower than predicted by the dosage
      
  Rifampicin  + 
   increased metabolism of quinidine associated with reduction of
   therapeutic effects
       
   Sucralfate   +  
   serum quinidine level reduced, decreased therapeutic  effects
       
    Urinary alkalinzr + 
     urinary elimination of quinidine is reduced, serum con. increased,
       increased pharmacologic effects
      
     Verapramil  + 
    quinidine clearance reduced, half-life prolonged, resulting in hypotension
     bradycardia, ventricular tachycardia

     Quinidine +
  
      Anticholinergic drugs
    concurrent use may cause additive vagolytic effect
      
     Anticoagulants  
     anticoagulation potentiated, haemorrhage occur
      
      Betablockers 
     effects of metoprolol or propranolol increased
      
     Cardiac glycosides  -Digitoxin, Digoxin
    plasma levels of cardiac glycosides increased. Pharmacologic  effects increased and toxicity occur
         
     Quinidine + Disopyramide or Disopyramide + Quinidine
      increased disopyramide levels or decreased   quinidine levels occur
        
      Nondepolarising neuromuscular blockers
      nondepolarizing neuromuscular blockers effects enhanced       
        
       Procainamide
      pharmacologic effects of procainamide increased, toxicity occurs
        
       Propafenone 
       serum propafenone levels increased , increasing pharmacol effect
        
       Succinyl chloride
       neuromuscular blockade produced by succinyl choline prolonged
         
        Tricyclic antidep
       clearance of tricylic antidepressant  reduced, increased pharmacol effect

Paroxymal atrial(supraventricular) tachycardia,,atrial flutter.

Antiarrhythmic agents include-

Group I A  -  Moricizine, Quinidine, Procainamide, Disopyramide,
            I B -  Lidocaine, Phenytoin, Tocainide, Mexiletine
            I C     Flecanide,  Propafenone   
Group II - Propranolol, Esmolol, Acebutol
Group III - Bretylium, Amiodarone, Solatol
Group IV - Verapramil, Digoxin, Adenosine
 

Adverse reactions-

QUINIDINE-
---------------
CARDIOVASCULAR -  Palpitations 4.6% Chest pain  4.6% Angina like pain 1.9%
                                        Increased ventricular arrhythmias 2.7%

CNS                               Dizziness/lightheadedness 14.1%  Tremor 2.3 %

                                        Coordination difficulties 1.1%
                                       Changes in sleep habits 2.7 % Weakness  5.3%

                                        Nervousness 1.9%  Fatigue 6%
                                       Numbness 2.3% Tinnitus 1.5% Depression  1.1%

GI                                   Nausea/Vomiting/ heartburn 21% Diarrhea 33%
                                       Changes in appetite 2%

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

                                        Dry mouth 2%
                                        Arthalgia 2%  Fever 3%

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. but  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
 

Hypersentivity  to the drug orother cinchona derivatives manifested by throombocytopenia,
skin eruptions, or febrile reactons, myastenia gravis, history of thrombocytopenic purpura associated  with quinidine administration.

Special precautions:

Monitoring- perform periodic blood counts and liver and kidney functions tests.Discontinue use if blood dysacrasis or signs of hepatic or reanl disorders occur.

Vagolytic effects- because quinidine has vagolytic activity on the atrium and AV node administration  of cholinergic drugs or any other procedure to enhance vagal activity may fail to terminate paroxymal  supraventricular tachycardia

Potassium balance- the effect of quinidine is enhanced by potassoium and reduced if hypokalemia  is present. The risk of drug-induced torsade de pointes is increased by concomitant hypokalemia.

Malaria- (P falciparum) - dosing schedule known to be effective have been asociated with hypotension,  increased QRS and corrected QT intervals and chinchonism. Closely monitor ECG and blood pressure  

Warnings-

Hepatotoxicity- (including granulomatous  hepatitis) due to quinidine hypersentivity has occured.  Monitor liver functions during the first 4 to 8 weeks of therapy. 

Atrial flutter or fibrillation- although quinidine reduces recurrence of atrial fibrillation after cardioversion, it may be associated with an increase in mortality.

Cardiotoxicity- specialists recommend quinidine be initiated only in hospitalized patients with ECG  monitoring. However, this is reserved for patients receiving large doses or who are at high risk.

Parentral therapy- the dangers of parentral use of quinidine are increased in the presence of AV block  or absence of atrial activity. Administration is more hazardous in patients with extensive myocardial  damage.

Syncope- occassionally occurs in patients on long-term quinidine therapy. usually resulting from  ventricular tachycardia  or fibrillation.

Renal / hepatic or cardiac insuficiency- during the first few of therapy,although rare, consider hypersentivity  to quinidine including anaphylactoid reactions (eg angioedema, purpura, acute  asthmatic episode, vascuar collapse)

Test dose- administer a single 200mg dose tablet of quinidine sulfate or 200mg IM quinidine
gluconate prior to initiation of treatment to detremine whether the patient has idiosyncracy to quinidine. 

Pregnancy- safety for use during pregnancy is not established. Use only when clearly needed  and when potential benefits outweigh potential hazards to the fetus.

Lactation- The American Academay of Pediatrics considers quinidine to be compatible with breast  feeding.

Children- safety and efficacy have not been established.

Indications:
Paroxymal atrial(supraventricular) tachycardia,atrial flutter.

Dosage:
Premature atrial and ventricular contractions- 200 to 300mg 3 to 4 times daily

Paroxymal supraventricular tachycardias - 400 to 600mg every 2 or 3 hours until the paroxysm    is terminated

Conversion of atrial fibrillation - 200mg every 2 to 3 hours for 5 to 8 doses with subsequent daily   increases until sinus rhythm is restored or toxic effects occur. Do not exceed a total daily dose   of 3 to 4g in any regimen Prior to quinidine admininstration , control the ventricular rate and CHF  ( if present ) with digoxin

Maintenance therapy - 200 to 300mg 3 to 4 times daily. Other patients may require larger doses
 or more frequent admin.than  the usually recommended schedule

Sustained released forms-  300 to 600mg every 8 to 12 hours. Since the rate of absorption from various  sustained release forms may be markedly different, and since the anhydrous quninidine content is different, do not consider them interchangeable 

Children-  the following doses has been suggested-
   oral - quinidine sulfate - 30mg/kg/24 hours  or 900mg/m2 /24 hours in 5 divided doses
   IV - quinidine gluconate - 2 to 10mg/kg dose  every  3 to 6 hours as needed, however this route is    not recommended

Overdosage- Symptoms              

                                                 
Severe quinidine intoxification may be associated with depressed mental function, even in
hemodynamically stable patients.
The patient progresses from lethargy to coma,including respiratory arrest, recurent generalized     motor seizures may occur.
The onset of CNS manifestations  may be substantrially delayed beyond the onset of cardiovascular  toxicity, conversely recovery from coma is often  delayed                                                                  
                                                                                             
CNS- lethargy, confusion, coma, respiratory depression or  arrest, seizures, headache, parathesia,  vertigo                
                                                                                               
GI- vomiting, abdominal pain, diarrhea, nausea.               
                                                                                                 
Cardiovascular- tachyarrhythmias (sinus tachycardia, ventricular tachycardia, ventricular fibrillation,  torsade de pointes) depressed automaticity and conduction ( QRS and QT prolongation, bundle brach block,sinus bradycardia, sinoatrial block,sinus arrest, AV block, ST depression,   T inversion ) hypotension (depressed contractility and cardiac output, vasodilation) syncope, heart  failure                    

Other- cinchonism, hypokalemia, visual.auditory disturbances
tinnitus, acidosis

  Treatment

1. If ingestion of quinidine is recent, gastric lavage,emesis or administration of activated charcoal   may reduce absorption.
 2. Management of overdosage includes-  symptomatic treatment, ECG blood gases, serum  electrolytes and blood pressure, monitoring, cardiac  pacing if indicated,acidification of  the urine

 3. Avoid alkalization of urine.
4. Mechanical ventilation and other supportive  measures may be required

 5. IV Infusion of 1/6 molar sodium lactate reportedly reduces cardiotoxic effects of quinidine

 6. Since marked CNS depresssion may occur even in the presence of convulsions, do not give CNS   depressants

7.Hypotension may treated if necessary with  metaraminol or norepinephrine after adequate
     fluid volume replacement.

8. Tachydyshythmias should respond to phenytoin or lidocaine.

 9. Hemodialysis has been effective in overdosage

Missed dose-

1. If you miss a dose of this medicine and remember within 2 hours of missed dose take it as soon as   possible.
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.

Thrombocytopenia- ( 1555 )

The normal platelet count ranges from 150,000 to 400,000 per cubic millimeter. A platelet count of less than 100,000 per cubic meter is generally constitute thrombocytopenia. There is an approximate relationship between the plastelet count and severity of bleeding. A sudden drop in platelet count ,fever, ans anemia aggravate the hemostatic defect of thrombocytopenia

Drugs causing adverse reactions- ( 385 )

1. Quinidine

2. Quinine

3. Furosemide

4. Chlorthalidone

5. Thiazides

6. Gold salts

7. Cotrimoxazole

8. Aspirin

9. Indomethicin

10. Phenylbutazone

11. Oxyphenbutazone

12. Chlorpropamide

13. Acetazolamide

14. Phenytoin and other hydantoin

15. Methyldopa

16. Carbamazepine

17. Digitoxin

18. Novobiocin

1.Swallow the tablets as a whole

2.Do not break,crush,or chew before swallowing

3.Take quinidine exactly as directed by your doctor,even though you may feel well.

4. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to quinidine or quinine. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

5.Pregnancy - studies on effects of pregnancy have not been done in either humans or animals. However, a closely related medicine has been shown to shown to cause birth defects of the nervous system. Quinine may also cause contractions of the uterus.

6.Breast feeding- quinidine passes into the breast milk. However it has not been reported cause problems in nursing babies

7. Children - no specific information available comparing use of this medicine in children with use in other age groups.

8. Elderly- not expected to cause different side effects or problems in older people than in younger adults.

9. Other medicines - Anticoagulants - risk of bleeding may be increased Other heart medicine - effects on the heart may be increased Pimozide - risk of heart rhythm problems may be increased Urinary alklalinisers - effects may be increased because levels of quinidine in body may be increased

10. Other medical problems - Tell your doctor if you have any other medical problems especially - Asthma - possible allergic reaction Blood disease Infection Kidney disease or Liver disease - efects may be increased because of slower removal of quinidine from the body. Myasthenia gravis - muscle weakness may be increased Overactive thyroid Psoriasis

11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. 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.

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

14. AVOID CONCURRENT USE WITH ERYTHROMYCIN

Group I A  -  Moricizine, Quinidine, Procainamide, Disopyramide,
            I B -  Lidocaine, Phenytoin, Tocainide, Mexiletine
            I C     Flecanide,  Propafenone   
Group II - Propranolol, Esmolol, Acebutol
Group III - Bretylium, Amiodarone, Solatol
Group IV - Verapramil, Digoxin, Adenosine

Pregnancy-
Safety for use during pregnancy is not established. Use only when clearly needed. and when potential benefits outweigh potential hazards to the fetus.

Lactation-
The American Academay of Pediatrics considers quinidine to be compatible with breast feeding.

Children-
Safety and efficacy have not been established.