Quinolines

Question 1

Quinolines

Answer 1

Chloroquine 
Mefloquine 
Quinidine 
Quinine 
Primaquine 
Amodiaquine 
Hydroxychloroquine 

Among oldest anti-infective agents
17th century in Europe- bark of Cinchona tree (imported from Peru) to treat fever in malarious areas; primary component was quinine

Most important cause of fever in returning travelers, especially those not native to endemic areas, because of potential for severe illness

Important differences between quinolines in activity based on both species of Plasmodium and the geographic area

Question 2

Quinolines MOA

Answer 2

Incompletely understood

Chloroquine, quinine, and quinidine appear to interfere with the ability of the malaria parasite to detoxify hemoglobin metabolites

Primaquine appears to affect parasitic mitochondrial function

Question 3

Quinolines Spectrum

Answer 3

Protozoa (activity variable by region)
Plasmodium falciparum, malariae, ovale, vivax

Like a parasite but technically a fungus
Pneumocystis jirovecii (primaquine)

Question 4

Quinolines Adverse Effects

Answer 4

CV
Dose related CV toxicity (QT interval prolongation, hypotension, potentially fatal ventricular arrhythmias)
Quinidine is a class IA anti-arrhythmic- used in the therapy of some arrhythmias (many antiarrhymthics can be proarrhythmic)
CV effects most likely with IV quinidine; less common with quinine, mefloquine, and chloroquine; rare with primaquine

Hematologic
Primaquine can cause hemolysis in patients with G6PD- glucose-6-phosphate-dehydrogenase; test for G6PD deficiency before use

Metabolic
Quinidine and quinine can stimulate release of insulin- causing profound hypoglycemia

Psychiatric
Mefloquine- range of psych disturbances (insomnia, vivid dreams, mood swings, depression, psychosis, suicide; the drug is well tolerated by most patients; patients with history of psych illness should avoid

Systemic
Cinchonism- tinnitus, HA, N, visual disturbances; common in patients on therapeutic doses of quinine
Can lead to discontinuation because of intolerance; effects resolve after discontinuation

Question 5

Quinolines Important Facts

Answer 5

In US, only quinidine available IV
Used in combo regimens for severe malaria
Intensive monitoring required- continuous BP and ECG; serial monitoring of blood glucose
Dosing is altered in renal failure (not uncommon in severe malaria)

Unlike others, primaquine active against “hypnozoite” forms of P. vivax and P. ovale that can lay dormant in the liver and cause relapsing infection; 2 week course of this added to regimen of these species are documented

Question 6

Quinolines Good For

Answer 6

Chloroquine
Treatment of uncomplicated malaria from chloroquine sensitive areas (only a few regions)
Prophylaxis against malaria in travelers to those regions

Mefloquine
Treatment of uncomplicated malaria in mefloquine sensitive areas (most of the world except SE Asia)
Prophylaxis against malaria in travelers to those regions

Quinine/quinidine
Treatment severe malaria (quinidine) in combo with doxycycline, tetracycline, or clindamycin; not used for prophylaxis

Primaquine
Treatment uncomplicated malaria due to P. vivax or ovale in combo with a second agent
Prophylaxis against malaria in travelers where P. vivax is principal species, in combination with clindamycin, treatment of mild-moderate Pneumocystis pneumonia

CDC has malaria hotline
Business hours: 855-856-4713
After hours: 770-488-7788