Pharmacology of Quinidine

Anti-Arrhythmic Drugs

• Quinidine: • 85% protein bound; eliminated by hepatic metabolism • Suppresses the conversion of T4 to T3; helpful in patients with thyrotoxicosis • Therapeutic range: 2.3 – 5 ug/ml • Toxic range: >5 ug/ml • Half-life: 6-8 hours • Common formulations: quinidine sulfate and quinidine gluconate • Peak serum level: 2 hours after an oral dose (sulfate); 4-5 hours for gluconate • Toxic effects: nausea, vomiting, abdominal discomfort, cardiovascular toxicity

• Amiodarone (Cordarone): • Iodine-containing drug that can cause hypothyroidism or hyperthyroidism • Used to treat ventricular arrhythmias • Therapeutic range: 1 – 2.5 ug/ml • Toxic effects: bradycardia, hepatitis, photodermatitis • Blocks several channels (e.g., K+ and inactivated Na+ channels) and β-adrenoceptors • Often effective when other drugs have failed, but should be used sparingly due to serious side effects (e.g., photosensitivity, thyroid disorders, neuropathy, and pulmonary alveolitis)

Class 3 Anti-Arrhythmic Drug

• Sotalol: • Has both Class III and Class II (β-blocking) actions, but lacks the side-effects of amiodarone • Has the side-effects of β-blockers (e.g., increased ANA)

Calcium Channel Blocker

• Verapamil: • Used to treat angina, hypertension, and supraventricular arrhythmias • Blocks L-type Ca channels, especially on the AVN, where conduction is entirely dependent on Ca2+ spikes • Therapeutic range: 80-400 ng/ml • Toxic effects: hypotension, peripheral edema, ventricular fibrillation

Other Anti-Arrhythmic Drugs

• Disopyramide (Norpace): • Used to treat cardiac arrhythmias; used as a substitute for quinidine • Therapeutic range: 2-5 ug/ml • Toxic effects: nausea, vomiting, abdominal discomfort, cardiovascular toxicity • Half-life: 6-8 hours • Protein binding: 20-30%

• Procainamide (Pronestyl, Procanbid, Procan SR): • Sodium channel blocker • Used to treat cardiac arrhythmia • Oral administration is the common route • GIT absorption is rapid and complete • 20% protein bound; eliminated by renal filtration and hepatic metabolism • Hepatic metabolite: N-acetylprocainamide (NAPA) • Therapeutic range: 4-8 ug/ml • Toxic effects: reversible lupus-like syndrome (Increase ANA), nephrotic syndrome, urticaria

Anticonvulsant Drugs

• Phenytoin: • Used to control seizures (tonic-clonic, simple partial seizures) and as a short-term prophylactic agent in brain injury • Decreases sodium and calcium influx into hyperexcitable neurons • IV administered; GIT absorption is incomplete • 87-97% protein bound; eliminated by hepatic pathway • Therapeutic range: 10-20 ug/ml • Toxic range: >20 ug/ml • Half-life: 6-24 hours • Major toxicity: initiation of seizures, teratogenic action (cleft lip & palate), vitamin D deficiency, folate deficiency

• Ethosuximide (Zarontin): • Drug of choice for controlling petit mal (absence) seizure • Orally administered • Not protein bound • Therapeutic range: 40-100 ug/ml • Half-life: 40-60 hours • Toxic effects: GI disturbances, ataxia, SLE, aplastic anemia, pancytopenia

Other Anticonvulsant Drugs

• Felbamate (Felbatol): • Indicated for use in severe epilepsies – mixed seizure disorder, Lennox-Gaustat syndrome, adults with epilepsy • Orally administered – complete absorption of GIT • Half-life: 14-22 hours • Eliminated by renal and hepatic metabolism • Therapeutic dose: 30-60 ug/mL • Toxic effects: fatal aplastic anemia and hepatic failure

• Other Anti-epileptic Drugs: • Therapeutic dose: 5 mg/dL • Side Effects: GI disturbances, interference with platelet aggregation • Toxic dose: >30 mg/dl • Toxic effects: mixed acid-base disturbance (metabolic acidosis and respiratory alkalosis), hypoglycemia, Reye syndrome

Therapeutic Drug Monitoring (TDM)

• Sample Collection: • Serum or plasma – specimen of choice • Timing of specimen collection: the single most important factor in TDM • Trough concentration drawn right before the next dose • Peak concentration drawn one hour after an orally administered dose (except digoxin)

• Methods: • Immunochemical Methods (immunoassays) • Provides rapid analyses of blood and urine samples • Can detect drug levels in the nanomolar ranges