antimalarial agents

1. Antimalarial drugsAntimalarial drugs
Malaria is cause by four species of protozoaMalaria is cause by four species of protozoa::
 Plasmodium malariae.Plasmodium malariae.
 P. falciparum.P. falciparum.
 P. vivax.P. vivax.
 P. ovale (rare).P. ovale (rare).
The plasmodium transmitted to human by theThe plasmodium transmitted to human by the
bite of an infectedbite of an infected female anopheles mosquito.female anopheles mosquito.

3. Malaria transmission life cycleMalaria transmission life cycle::
SporozoitesSporozoites  tissue schizonts (in liver)tissue schizonts (in liver)
 merozoites infect RBC (bloodmerozoites infect RBC (blood
schizonts)schizonts) rupture of RBC (clinicalrupture of RBC (clinical
attack)attack)  new crops of merozoitesnew crops of merozoites
Sexual formSexual form: some merozoites: some merozoites
differentiate into male & femaledifferentiate into male & female
gametocytesgametocytes  ingested by a mosquitoingested by a mosquito
where they formwhere they form SporozoitesSporozoites humanhuman

4. P. malariae & p. falciparumP. malariae & p. falciparum havehave oneone
cyclecycle of liver invasion and end by the 4thof liver invasion and end by the 4th
week i.e. no relapse occurs.week i.e. no relapse occurs.
P.ovale & p. vivaxP.ovale & p. vivax have dormant stageshave dormant stages
((hypnozoiteshypnozoites) in the liver. These) in the liver. These
hypnozoites may rupture months or yearshypnozoites may rupture months or years
later causing relapse of the attacks.later causing relapse of the attacks.

5. Blood SchizonticidesBlood Schizonticides
Chloroquine (4- aminoquinoline derivative)Chloroquine (4- aminoquinoline derivative)
Mechanism of actionMechanism of action::
Inhibits synthesis of DNA and RNA in theInhibits synthesis of DNA and RNA in the
plasmodium.plasmodium.
Increases pH of the vacules in the parasite, soIncreases pH of the vacules in the parasite, so
prevent its utilization of erythrocyte hemoglobin.prevent its utilization of erythrocyte hemoglobin.
Uses:Uses:
Acute attack 600 mg base (4 tab.) then 300 mgAcute attack 600 mg base (4 tab.) then 300 mg
after 6 h. then 150 mg bid for two more days.after 6 h. then 150 mg bid for two more days.
Add 100 mg proguanil/ day (2 tab.) inAdd 100 mg proguanil/ day (2 tab.) in
chloroquine-resistant area.chloroquine-resistant area.

6. Chemoprophylaxis:Chemoprophylaxis:
300 mg base (2 tab.) / week,300 mg base (2 tab.) / week,
one week before entering the endemicone week before entering the endemic
areaarea
& 4 weeks after leaving.& 4 weeks after leaving.

7. Other uses:Other uses:
Amebic liver abscess (as chloroquine isAmebic liver abscess (as chloroquine is
concentrated in the liver).concentrated in the liver).
Anti-inflammatory in autoimmune diseases e.g.Anti-inflammatory in autoimmune diseases e.g.
rheumatoid arthritis (unknown mechanism).rheumatoid arthritis (unknown mechanism).
A/EA/E: GIT upset, rash, headache, peripheral: GIT upset, rash, headache, peripheral
neuritis, cardiac depressant, retinal damageneuritis, cardiac depressant, retinal damage
((don’t use chloroquin> 5 years without regulardon’t use chloroquin> 5 years without regular
ophthalmic examination),ophthalmic examination), toxic psychosis andtoxic psychosis and
precipitates porphyria.precipitates porphyria.

8. QuinineQuinine::
Mechanism of actionMechanism of action::
Inhibits DNA strand separation.Inhibits DNA strand separation.
Inhibits transcription and protein synthesis.Inhibits transcription and protein synthesis.
Uses:Uses:
Chloroquine-resistantChloroquine-resistant P. falciparumP. falciparum (orally).(orally).
Cerebral malaria (i.v infusion 10 mg/kg over 4 h.). itCerebral malaria (i.v infusion 10 mg/kg over 4 h.). it
could repeated at an intervals of 8-12 h. until patient cancould repeated at an intervals of 8-12 h. until patient can
take the drug orally.take the drug orally.
A/E:A/E:
CinchonismCinchonism i.e. headache, dizziness, & tinnitus.i.e. headache, dizziness, & tinnitus.
Inhibits cardiac conductivity, hemolysis in G-6-P D andInhibits cardiac conductivity, hemolysis in G-6-P D and
black water fever (intravascular hemolysis).black water fever (intravascular hemolysis).

9. Quinidine:Quinidine:
It is the dextro-isomer of quinine.It is the dextro-isomer of quinine.
It is used when quinine is not available.It is used when quinine is not available.
Mefloquine:Mefloquine:
Its mechanism of action is unknown.Its mechanism of action is unknown.
UsesUses::
treatment & prophylaxis oftreatment & prophylaxis of chloroquine-resistantchloroquine-resistant
P. falciparum.P. falciparum.
A/EA/E: GIT upset, headache, dizziness, syncope,: GIT upset, headache, dizziness, syncope,
extrasystoles & seizures.extrasystoles & seizures.

10. Halofantrine:Halofantrine:
Unknown mechanism of action.Unknown mechanism of action.
UsedUsed only by oral routeonly by oral route in P. falciparumin P. falciparum
cerebral malaria.cerebral malaria.
NoNo parenteral preparation.parenteral preparation.
NotNot used for prophylaxis.used for prophylaxis.
NotNot used during pregnancy unless benefitused during pregnancy unless benefit
outweighs the risk.outweighs the risk.

11. QinghaosuQinghaosu ((ArtemisininArtemisinin):):
It is a Chinese herbal medicine was used asIt is a Chinese herbal medicine was used as antipyreticantipyretic..
It is a blood schizonticide againstIt is a blood schizonticide against all types of malariaall types of malaria
including chloroquine-resistant p. falciparum.including chloroquine-resistant p. falciparum.
Unknown mechanism of action.Unknown mechanism of action.
Uses:Uses:
P. falciparumP. falciparum cerebral malariacerebral malaria (oral & parenteral).(oral & parenteral).
NotNot usedused prophylactically.prophylactically.
NotNot used inused in pregnancypregnancy as it is emberytoxic in rats.as it is emberytoxic in rats.

12. Antifolates (sulfonamides & sulfones):Antifolates (sulfonamides & sulfones):
Synergistic blockade of folic acid synthesisSynergistic blockade of folic acid synthesis
SulfonamideSulfonamide inhibits dihydropteroateinhibits dihydropteroate
synthetase, so inhibits folic acid synthesis.synthetase, so inhibits folic acid synthesis.
Pyrimethamine and proguanilPyrimethamine and proguanil inhibitinhibit
dihydrofolate reductase, so inhibitdihydrofolate reductase, so inhibit
tetrahydrofolate (folinic acid synthesis).tetrahydrofolate (folinic acid synthesis).

13. Fansidar:Fansidar:
It is a combination ofIt is a combination of sulfadoxin and pyrimethamine.sulfadoxin and pyrimethamine.
It is used inIt is used in chloroquine-resistant p. falciparumchloroquine-resistant p. falciparum..
NotNot used forused for prophylaxisprophylaxis as it causesas it causes agranulocytosis &agranulocytosis &
Stevens-Johnson syndrome.Stevens-Johnson syndrome.
A.E:A.E:
SulfonamideSulfonamide: rashes, kidney damage, hemolysis & GIT: rashes, kidney damage, hemolysis & GIT
upset.upset.
PyrimethaminePyrimethamine: folic acid deficiency, agranulocytosis &: folic acid deficiency, agranulocytosis &
Stevens-Johnson syndrome.Stevens-Johnson syndrome.
DisadvantagesDisadvantages:: slow blood schizonticide activity, drugslow blood schizonticide activity, drug
resistance & numerous & serious adverse effects.resistance & numerous & serious adverse effects.
C/I:C/I: pregnancy & nursing women, G-6-PD, renalpregnancy & nursing women, G-6-PD, renal
impairment & children under 2 months of age.impairment & children under 2 months of age.

14. Atovaquone:Atovaquone:
Unknown mechanism of action.Unknown mechanism of action.
Used alone for treatment of pneumocytosis andUsed alone for treatment of pneumocytosis and
toxoplasmosis in patients with AIDS.toxoplasmosis in patients with AIDS.
Atovaquone +Atovaquone + proguanilproguanil (malarone)(malarone) forfor
treatment & prophylaxistreatment & prophylaxis of chloroquine-resistantof chloroquine-resistant
P. falciparumP. falciparum..
A/EA/E: fever, rashes, cough, nausea, vomiting,: fever, rashes, cough, nausea, vomiting,
diarrhea, headache & insomnia.diarrhea, headache & insomnia.

15. Tissue SchizonticideTissue Schizonticide
Primaquine (8- aminoquinoline derivative):Primaquine (8- aminoquinoline derivative):
It is a tissue schizonticide.It is a tissue schizonticide.
It has a cellular oxidant activity and possibly interferesIt has a cellular oxidant activity and possibly interferes
with mitochondria function.with mitochondria function.
Gametocide, so inhibits infection transmission byGametocide, so inhibits infection transmission by
mosquito.mosquito.
Uses:Uses:
Eradication of liver stages (hypnozoites) ofEradication of liver stages (hypnozoites) of P.vivaxP.vivax && P.P.
ovaleovale, after standard chloroquine therapy to prevent, after standard chloroquine therapy to prevent
relapse.relapse.
It should not be given if there is risk of reinfection.It should not be given if there is risk of reinfection.
A/E:A/E: GIT upset, pruritis, headache, methemoglobinemia,GIT upset, pruritis, headache, methemoglobinemia,
hemolysis especially in G-6-PD.hemolysis especially in G-6-PD.

16. Treatment of malariaTreatment of malaria
P. vivax, P. ovale & P. malariae:P. vivax, P. ovale & P. malariae:
ChloroquineChloroquine
NBNB: It is also allowed in pregnancy.: It is also allowed in pregnancy.
P. FalciparumP. Falciparum (most cases are chloroquine-resistant):(most cases are chloroquine-resistant):
Quinine 600 mg salt/8hQuinine 600 mg salt/8h till patient become better andtill patient become better and
blood is free of parasites (usually in 3-5 days).blood is free of parasites (usually in 3-5 days).
Followed by a single dose ofFollowed by a single dose of fansidar (3 tablets).fansidar (3 tablets).
In pregnancy 7-day course of quinine alone shouldIn pregnancy 7-day course of quinine alone should
be givenbe given..

17. Alternative therapyAlternative therapy
Mefloquine 20 mg base/kg up to a maximum ofMefloquine 20 mg base/kg up to a maximum of
1.5 g in two divided doses 8 hours apart.1.5 g in two divided doses 8 hours apart.
Mefloquine is contraindicated in pregnancy.Mefloquine is contraindicated in pregnancy.
Cerebral malaria:Cerebral malaria:
Quinine 10 mg/kg i.v infusion over 4 h. could beQuinine 10 mg/kg i.v infusion over 4 h. could be
repeated at intervals of 8-12 h. until patient canrepeated at intervals of 8-12 h. until patient can
take drug orally.take drug orally.
OrOr Halofantrine:Halofantrine: orally onlyorally only
OrOr QinghaosuQinghaosu ((ArtemisininArtemisinin):): oral & i.voral & i.v

18. Chemoprophylaxis of malariaChemoprophylaxis of malaria
Chloroquine-sensitive area:Chloroquine-sensitive area:
Chloroquine 150 mg base ( 2 tab/weekChloroquine 150 mg base ( 2 tab/week))
Chloroquine-resistant area:Chloroquine-resistant area:
Chloroquine ( 2 tab/week) plus proguanilChloroquine ( 2 tab/week) plus proguanil
100 mg (one or two tab/ day)100 mg (one or two tab/ day)
oror
MefloquineMefloquine 250 mg (one tab./ week)250 mg (one tab./ week)