Page 933 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 52 Antiprotozoal Drugs 919

H 2 N
CH 3
C 2 H 5 N Cl
NH CH CH 2 CH 2 CH 2 N
C 2 H 5 Cl NH 2
N
Cl Cl
C 2 H 5
Cl
N Pyrimethamine (folate antagonist)
Chloroquine (4-aminoquinoline)
HO
H 3 C CH 3 N CH 3
CH 3
HC N
NH OH Lumefantrine (phenanthrene methanol)
Cl NH NH 2
C 2 H 5 Cl
CH 2 N N
C 2 H 5 H 2 N
Cl
N Proguanil (folate antagonist)
Amodiaquine (4-aminoquinoline) O
N CH CH 2
N CH 2
N N OH
CH 2
HO CH N O
Atovaquone (quinone)
N CH 3 O
Cl
CH 3
N
Cl N Quinine (quinoline methanol) H 3 C O
Piperaquine (4-aminoquinoline) O O
HO
HC
O
CH 3 O CH 3
N
H R 2 R 1
Artemisinins (endoperoxides)
(multiple structures)
N
N CF 3
NH CH CH 2 CH 2 CH 2 NH 2
CF 3
Mefloquine (quinoline methanol) N
CH 3
Primaquine (8-aminoquinoline)
OH
CH 2 CH 2 CH 2 CH 3
HOCHCH 2 CH 2 N
CH 2 CH 2 CH 2 CH 3
N
N N Cl
O O HN
S N
N OCH 3 OCH 3
H
OCH 3
H 2 N F 3 C Cl
Cl
Sulfadoxine (folate antagonist) Halofantrine (phenanthrene methanol) N
Pyronaridine
FIGURE 52–2 Structural formulas of some antimalarial drugs.
of the hemoglobin breakdown product, heme, into hemozoin, and malaria. It rapidly terminates fever (usually in 24–48 hours) and
thus eliciting parasite toxicity due to the buildup of free heme. clears parasitemia (in 48–72 hours) caused by sensitive parasites.
Resistance to chloroquine is now very common among strains of Chloroquine has been replaced by other drugs, principally arte-
P falciparum and uncommon but increasing for P vivax. In P falciparum, misinin-based combination therapies, as the standard therapy to
mutations in a putative transporter, PfCRT, are the primary mediators treat falciparum malaria in most endemic countries. Chloroquine
of resistance. Chloroquine resistance can be reversed by certain agents, does not eliminate dormant liver forms of P vivax and P ovale, and
including verapamil, desipramine, and chlorpheniramine, but the clini- for that reason primaquine must be added for the radical cure of
cal value of resistance-reversing drugs is not established. these species.

2. Chemoprophylaxis—Chloroquine is the preferred che-
Clinical Uses moprophylactic agent in malarious regions without resistant
1. Treatment—Chloroquine is the drug of choice in the treat- falciparum malaria. Eradication of P vivax and P ovale requires a
ment of uncomplicated nonfalciparum and sensitive falciparum course of primaquine to clear hepatic stages.