Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia) in theheart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.
Mechanism
Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inwardsodium current (INa). Quinidine's effect on INa is known as a use dependent block. This means that at higher heart rates, the block increases, while at lower heart rates the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of thecardiac action potential to decrease (decreased Vmax).
Quinidine also blocks the slowly inactivating tetrodotoxin-sensitive Na current, the slow inwardcalcium current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito.
At micromolar concentrations, quinidine inhibits Na⁺/K⁺-ATPase by binding to the same receptor sites as the digitalis glycosides such as ouabain.
The effect of quinidine on the ion channels is to prolong the cardiac action potential, thereby prolonging the QT interval on the surface ECG.
Other ECG effects include a wide notched P wave, wide QRS complex, depressed ST segment, and U waves. These are the results of both slowed depolarization and repolarization.
The effects of quinidine on atrial fibrillation are said to have been discovered by a Danish Merchant seaman with AF who took quinine for malaria prophylaxis during trips to India India
Elimination
The half life of oral quinidine is 6 to 8 hours, and it is eliminated by the cytochrome P450 system in the liver. About 20% is excreted unchanged via the kidneys.
Side effects
Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of lidocaine, Beta blockers, opioids, and some anti-depressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have CNS side effects such as respiratory depression if the two drugs are co-administered.[1]
Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, andtorsades de pointes and for that reason is not used much today. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system, and may lead to thrombocytic purpura.
Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonismwith tinnitus (ringing in the ears) being among the most characteristic and common symptoms of this toxicity syndrome.
Other uses
Intravenous quinidine is also indicated for treatment of Plasmodium falciparum malaria. However, quinidine is not considered the first line therapy for P. falciparum. The recommended treatments for plasmodium falciparum according to the Toronto Notes 2008 are quinine (not to be confused with "quinidine") + doxycycline combination or atovaquone/proguanil (Malarone TM).
Quinidine sulfate is used in the treatment of atrial fibrillation in the horse.
Quinidine-based ligands are used in AD-mix-β for Sharpless asymmetric dihydroxylation.
Disopyramide
Disopyramide (INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication. It is a Class Ia antiarrhythmic (sodium channel blocker) used in the treatment of ventricular tachycardias. It has no effect on alpha or beta adrenergic receptors. It resembles Quinidine but it has a marked anti-muscarinic effect on the heart, for this reason, it is not considered as a drug of 1st choice. It is also used in ventricular arrhythmia and supraventricular arrhythmia that might follow myocardial infarctions.
Cardiac adverse effects
§ Severe hypotension
Extracardiac effects
§ Dry mouth
§ Blurred vision
§ Glaucoma
§ Rash
disopyramide possibly enhances hypoglycaemic effect of
§ gliclazide,
§ insulin and
§ metformin
§
Procainamide
ocainamide (INN, pronounced /proʊˈkeɪnəmaɪd/; trade names Pronestyl, Procan,Procanbid) is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.
History
Procainamide was introduced in 1951.
Mechanism
It blocks open sodium (Na+) channels and prolongs the cardiac action potential (outwardpotassium (K+) currents may be blocked). This results in slowed conduction, and ultimately the decreased rate of rise of the action potential, which may result in widening of QRS onelectrocardiogram (ECG).
Uses
This drug is used for both supraventricular and ventricular arrhythmias. For example, it can be used to convert new-onset atrial fibrillation, though it is suboptimal for this purpose. It can also be used to treat Wolf-Parkinson-White syndrome by prolonging the refractory period of the accessory pathway. Typically use is secondary to lidocaine in patients who are allergic to lidocaine or dysrhythmias that are refractory to lidocaine.
Administration
Procainamide is administered intravenously or orally. When administered intravenously, aloading dose should first be given, though care should be taken not to cause hypotension. Procainamide's major active metabolite is N-acetyl procainamide (NAPA NAPA
Side effects
Adverse effects include rash, myalgia, hypersensitivity reactions (fever, agranulocytosis), Drug-Induced Lupus Erythematosus (particularly in slow-acetylators), and proarrhythmic effects (e.g., torsades de pointes). Treatment with procainamide can cause antibody production against cellular components, accounting for the systemic lupus erythematosus-like adverse reactions.
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