Quinine is a derivate of the bark of the South American cinchona tree. Quinidine is a stereoisomer of quinine; it is a "class 1a antiarrhythmic drug" and also an antimalarial agent.
As an "Antiarrhythmic":
Note: The use of quinidine for the above indications has mostly been replaced by better pharmacological therapies such as amiodarone and procainamide.
Plasmodium Falciparum Malaria, Quinidine gluconate is acknowledged as an effective treatment of severe and complicated Malaria both alone as a therapy or in combination with exchange transfusion. EKG monitoring for prolongation of QT interval and QRS changes along with CBC, liver and renal function testing should be done on a routine basis when giving Quinidine as an IV infusion or for a prolonged period.
Antiarrhythmic: Class 1a antiarrhythmic agents (example - quinidine, procainamide, disopyramide, ajmaline) work by inhibiting the fast inward sodium current, depressing the phase 0 of the action potential hence dampening the excitability of cardiac muscles which in turn prolongs the action potential and decreases automaticity. Quinidine's effect on fast inward sodium current is known as a 'use-dependent block' - this means at higher heart rates, the block increases, while at lower heart rates, the block decreases. Quinidine has also been shown to decrease potassium efflux during repolarization, inhibition of slow delayed rectifier potassium current and shows a "reverse use dependence" pattern (less current suppression at more frequent depolarizations) and calcium transport across cell membranes.
Antimalarial: It works as an antimalarial agent by having activity against the erythrocytic stage of the Plasmodium species, and it acts by building up in the parasites food vacuole, it forms a complex with heme which prevents crystallization in the parasites food vacuole. Cytotoxic-free heme accumulates secondary to inhibited heme polymerase activity.
Quinidine also has anticholinergic activity.
Quinidine is available as both parenteral and oral preparations.
Pharmacodynamics and Pharmacokinetics:
Quinidine is well known for its toxicity causing QT prolongation and in severe cases a pleomorphic arrhythmia a.k.a "Torsades de Pointes." This condition can be fatal and times, and the management of the situation includes discontinuation of the drug, institution of cardiac and electrolyte (potassium and magnesium) monitoring, management of hypoxia. Prompt management of torsades de pointes can be done by giving magnesium sulfate and terminating prolonged episodes by electrical cardioversion, in refractory cases isoproterenol or transvenous pacing is an option.
Quinidine is one of the oldest drugs known for the management of arrhythmias, and still has utility in the management of early repolarization syndrome, Brugada syndrome and idiopathic ventricular fibrillation, and certain infections such as Plasmodium falciparum malaria. A team approach is necessary amongst physicians, nurses, cardiologist, rheumatologist, a pharmacist for early detection and management of the drug toxicity which can be fatal at times (cardiology - as an antiarrhythmic/proarrhythmic, rheumatologist - known to cause lupus-like syndrome, infectious disease specialist - used in severe malaria), nurses for adverse effect monitoring and proper drug administration, pharmacists for correct drug dosing. The choice of the patient for the treatment is also essential for deciding therapy with quinidine, such as dose adjustment may be required in neonates, elderly, patients with CHF, hepatic or renal dysfunction and patients who are on other drugs such as digoxin and the ones known to prolong the QT interval. While inpatient consults with the cardiologist and intensivist about ICU care and monitoring while in the hospital are indicated. As all these interactions and responsibilities demonstrate, an interprofessional healthcare team approach is necessary for effective and safe therapy with quinidine. [Level 5]
|||Yang F,Hanon S,Lam P,Schweitzer P, Quinidine revisited. The American journal of medicine. 2009 Apr; [PubMed PMID: 19249010]|
|||Starmer CF,Grant AO,Strauss HC, Mechanisms of use-dependent block of sodium channels in excitable membranes by local anesthetics. Biophysical journal. 1984 Jul; [PubMed PMID: 6331543]|
|||Yao JA,Trybulski EJ,Tseng GN, Quinidine preferentially blocks the slow delayed rectifier potassium channel in the rested state. The Journal of pharmacology and experimental therapeutics. 1996 Nov; [PubMed PMID: 8930193]|
|||Taggart WV,Holyoak W, Steady-state bioavailability of two sustained-release quinidine preparations: quinidine gluconate versus quinidine sulfate. Clinical therapeutics. 1983; [PubMed PMID: 6871920]|
|||Roden DM,Thompson KA,Hoffman BF,Woosley RL, Clinical features and basic mechanisms of quinidine-induced arrhythmias. Journal of the American College of Cardiology. 1986 Jul; [PubMed PMID: 2423573]|
|||Benton RE,Sale M,Flockhart DA,Woosley RL, Greater quinidine-induced QTc interval prolongation in women. Clinical pharmacology and therapeutics. 2000 Apr; [PubMed PMID: 10801251]|
|||Ochs HR,Greenblatt DJ,Lloyd BL,Woo E,Sonntag M,Smith TW, Entry of quinidine into cerebrospinal fluid. American heart journal. 1980 Sep; [PubMed PMID: 7405805]|
|||Burckart GJ,Marin-Garcia J, Quinidine dosage in children using population estimates. Pediatric cardiology. 1986; [PubMed PMID: 3725633]|
|||Ochs HR,Greenblatt DJ,Woo E,Smith TW, Reduced quinidine clearance in elderly persons. The American journal of cardiology. 1978 Sep; [PubMed PMID: 356577]|
|||Crouthamel WG, The effect of congestive heart failure on quinidine pharmacokinetics. American heart journal. 1975 Sep; [PubMed PMID: 1163425]|
|||Leahey EB Jr,Bigger JT Jr,Butler VP Jr,Reiffel JA,O'Connell GC,Scaffidi LE,Rottman JN, Quinidine-digoxin interaction: time course and pharmacokinetics. The American journal of cardiology. 1981 Dec; [PubMed PMID: 7304462]|
|||Hager WD,Fenster P,Mayersohn M,Perrier D,Graves P,Marcus FI,Goldman S, Digoxin-quinidine interaction Pharmacokinetic evaluation. The New England journal of medicine. 1979 May 31; [PubMed PMID: 431681]|
|||Spinler SA,Cheng JW,Kindwall KE,Charland SL, Possible inhibition of hepatic metabolism of quinidine by erythromycin. Clinical pharmacology and therapeutics. 1995 Jan; [PubMed PMID: 7828386]|
|||Data JL,Wilkinson GR,Nies AS, Interaction of quinidine with anticonvulsant drugs. The New England journal of medicine. 1976 Mar 25; [PubMed PMID: 1250281]|
|||Hardy BG,Schentag JJ, Lack of effect of cimetidine on the metabolism of quinidine: effect on renal clearance. International journal of clinical pharmacology, therapy, and toxicology. 1988 Aug; [PubMed PMID: 3220613]|
|||Thomas SH,Behr ER, Pharmacological treatment of acquired QT prolongation and torsades de pointes. British journal of clinical pharmacology. 2016 Mar; [PubMed PMID: 26183037]|