| Indication |
For the treatment of malaria and leg cramps |
| Pharmacodynamics |
Quinine is used parenterally to treat life-threatening
infections caused by chloroquine-resistant Plasmodium falciparum
malaria. Quinine acts as a blood schizonticide although it also has
gametocytocidal activity against P. vivax and P. malariae. Because it is
a weak base, it is concentrated in the food vacuoles of P. falciparum.
It is thought to act by inhibiting heme polymerase, thereby allowing
accumulation of its cytotoxic substrate, heme. As a schizonticidal drug,
it is less effective and more toxic than chloroquine. However, it has a
special place in the management of severe falciparum malaria in areas
with known resistance to chloroquine. |
| Mechanism of action |
The theorized mechanism of action for quinine and related
anti-malarial drugs is that these drugs are toxic to the malaria
parasite. Specifically, the drugs interfere with the parasite's ability
to break down and digest hemoglobin. Consequently, the parasite starves
and/or builds up toxic levels of partially degraded hemoglobin in
itself. |
| Absorption |
76 - 88% |
| Volume of distribution |
- 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]
- 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]
- 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]
|
| Protein binding |
Approximately 70% |
| Metabolism |
Hepatic, over 80% metabolized by the liver. |
| Route of elimination |
Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine. |
| Half life |
Approximately 18 hours |
| Clearance |
- 0.17 L/h/kg [healthy]
- 0.09 L/h/kg [patients with uncomplicated malaria]
- 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]
- 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]
- Oral cl=0.06 L/h/kg [elderly subjects]
|
| Toxicity |
Quinine is a documented causative agent of drug induced
thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in
the blood. Quinine induces production of antibodies against
glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more
rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased
antibodies against these complexes increases platelet clearance, leading
to the observed thrombocytopenia. |
