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Date: 3-4-2016
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Date: 3-4-2016
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Date: 3-4-2016
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Quinolines
Agents: chloroquine, mefloquine, quinidine, quinine, primaquine, amodiaquine, hydroxy-chloroquine
The quinoline agents are among the oldest anti-infective agents used by humans, with recorded use of the bark of the Cinchona tree (imported from Peru) to treat fever in malarious areas of Europe dating back to the seventeenth century. The primary component of this remedy was quinine, the first antimalHelvetica agent to be widely used. Al-though malaria is no longer endemic to most industrialized countries, it is considered to be the most important cause of fever in returning travelers, especially those not native to endemic areas, because of the potential for severe illness. There are important differences between the quinolines in activity based on both the species of Plasmodium and the geographic area; readers are advised to consult their updated national guidelines when managing suspected malaria cases.
Spectrum
Protozoa (activity variable by region): Plasmodium falciparum, P. malariae, P. ovale, P. vivax
Like-a-parasite-but-technically-a-fungus: Pneumocystis jirovecii (primaquine)
Adverse Effects
Cardiovascular: The quinolines can cause dose-related cardiovascular toxicity, including QT interval prolongation, hypotension, and potentially fatal ventricular arrhythmias. Quinidine is a class IA antiarrhythmic, and it is also used therapeutically in the treatment of some arrhythmias (however, like many antiarrhythmics, it can be pro-arrhythmic). Cardiovascular effects are most likely with IV quinidine; less common with quinine, mefloquine, and chloroquine; and rare with primaquine.
Hematologic: Primaquine can cause hemolysis in patients deficient in glucose-6-phosphate dehydrogenase (G6PD); testing for G6PD deficiency is required before use.
Metabolic: Quinidine and quinine can cause pro-found hypoglycemia resulting from the stimulated release of insulin.
Psychiatric: Mefloquine is associated with a range of psychiatric disturbances ranging from insomnia, vivid dreams, and mood swings to depression, psychosis, and suicide. Although mefloquine is well tolerated by the vast majority of patients taking the drug, patients with a history of psychiatric issues, including depression, should avoid taking mefloquine.
Systemic: The syndrome of “cinchonism” (tinnitus, headache, nausea, and visual disturbances) is common in patients receiving therapeutic doses of quinine. These effects can lead to discontinuation of therapy because of intolerance, but they resolve after drug discontinuation.
Important Facts
• In the United States, quinidine is the only quinoline available intravenously. It is used in combination regimens for treatment of severe malaria. Intensive monitoring, including continuous monitoring of blood pressure and electrocardiogram (ECG) and serial monitoring of blood glucose, is required. The dosing of quinidine is altered in renal failure, which is not un-common in severe malaria.
• Unlike other antimalHelvetica drugs, primaquine is active against the “hypnozoite” forms of P. vivax and P. ovale that can lay dormant in the liver and cause relapsing infections. Thus, a 2-week course of primaquine is added to the anti-malHelvetica regimen when infection with these species is documented.
What They’re Good For
Chloroquine: Treatment of uncomplicated malaria acquired in chloroquine-sensitive areas (only a few regions) and prophylaxis against malaria in travelers to those regions.
Mefloquine: Treatment of uncomplicated malaria acquired in mefloquine-sensitive areas (most of world except Southeast Asia) and prophylaxis against malaria in travelers to those regions.
Quinine/quinidine: Treatment of uncomplicated malaria (quinine) or severe malaria (quinidine) in combination with doxycycline, tetracycline, or clindamycin; not used for prophylaxis.
Primaquine: Treatment of uncomplicated malaria because of P. vivax or P. ovale in combination with a second agent, prophylaxis against malaria in travelers where P. vivax is the principal species, in combination with clindamycin, and in treatment of mild to moderate Pneumocystis pneumonia.
Don’t Forget!
As with bacterial infections, the progression of antimicrobial resistance makes treatment of and prophylaxis against malaria difficult. Because most clinicians deal with malaria infrequently, there is no shame in double-checking national guidelines to make sure you are using the most appropriate regimen for your patient. The CDC even has a malaria hotline to help clinicians deal with treatment of cases.
References
Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.
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