Plasmodium parasites cause malaria in humans. They are transmitted via mosquito bites. Antimalarial drugs include blood schizonticides like chloroquine and quinine that act on erythrocytic parasites, tissue schizonticides that eliminate liver forms, and gametocides that prevent transmission. Chloroquine is commonly used but resistance has emerged. Other options include quinine, mefloquine, and artemisinin derivatives. Proper classification and combination of drugs is needed to achieve radical cure of the infection. Metronidazole is the treatment of choice for intestinal amebiasis caused by Entamoeba histolytica, while diloxanide furoate can

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

3. Malaria transmission life cycle:
• Sporozoites  tissue schizonts (in liver) 
merozoites infect RBC (blood schizonts)
rupture of RBC (clinical attack)  new crops
of merozoites
• Sexual form: some merozoites differentiate
into male & female gametocytes  ingested
by a mosquito where they form Sporozoites
human

4. • P. malariae & p. falciparum have one cycle of
liver invasion and end by the 4th week i.e. no
relapse occurs.
• P.ovale & p. vivax have dormant stages
(hypnozoites) in the liver. These hypnozoites
may rupture months or years later causing
relapse of the attacks.

5. Drug Classification
• Classified by their selective actions on
different phases of the parasite life cycle:
1. Tissue schizonticides: eliminate developing or
dormant liver forms.
2. Blood schizonticides: act on erythrocytic
parasites.
3. Gametocides: kill sexual stages and prevent
transmission to mosquitoes.
• No one available agent can reliably effect a
radical cures.

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

7. Chemoprophylaxis:
• 300 mg base (2 tab.) / week,
• one week before entering the endemic area
• & 4 weeks after leaving.

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

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

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

11. Halofantrine:
• Unknown mechanism of action.
• Used only by oral route in P. falciparum
cerebral malaria.
• No parenteral preparation.
• Not used for prophylaxis.
• Not used during pregnancy unless benefit
outweighs the risk.

12. Qinghaosu (Artemisinin):
• It is a Chinese herbal medicine was used as antipyretic.
• It is a blood schizonticide against all types of malaria including
chloroquine-resistant p. falciparum.
• Unknown mechanism of action.
Uses:
• P. falciparum cerebral malaria (oral & parenteral).
• Not used prophylactically.
• Not used in pregnancy as it is emberytoxic in rats.

13. Antifolates (sulfonamides & sulfones):
Synergistic blockade of folic acid synthesis
• Sulfonamide inhibits dihydropteroate
synthetase, so inhibits folic acid synthesis.
• Pyrimethamine and proguanil inhibit
dihydrofolate reductase, so inhibit
tetrahydrofolate (folinic acid synthesis).

14. Fansidar:
• It is a combination of sulfadoxin and pyrimethamine.
• It is used in chloroquine-resistant p. falciparum.
• Not used for prophylaxis as it causes agranulocytosis &
Stevens-Johnson syndrome.
A.E:
• Sulfonamide: rashes, kidney damage, hemolysis & GIT upset.
• Pyrimethamine: folic acid deficiency, agranulocytosis &
Stevens-Johnson syndrome.
Disadvantages: slow blood schizonticide activity, drug resistance
& numerous & serious adverse effects.
C/I: pregnancy & nursing women, G-6-PD, renal impairment &
children under 2 months of age.

15. Atovaquone:
• Unknown mechanism of action.
• Used alone for treatment of pneumocytosis and
toxoplasmosis in patients with AIDS.
• Atovaquone + proguanil (malarone) for treatment &
prophylaxis of chloroquine-resistant P. falciparum.
A/E: fever, rashes, cough, nausea, vomiting, diarrhea,
headache & insomnia.

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

17. Mefloquine
• A synthetic 4-quinoline methanol that is chemically
related to quinine.
• Pharmacokinetics
– Only be given orally because severe local irritation occurs
with parenteral use.
– Well absorbed.
– Highly protein-bound, extensively distributed in tissues,
and eliminated slowly. t1/2 is 20 days.
• Pharmacological Effects:
– Strong blood schizonticidal activity against P falciparum
and P vivax, but not active against hepatic stages or
gametocytes.

18. • Clinical Uses
– Chemoprophylaxis:
– Treatment: mainly for chloroquine-resistant
falciparum malaria.
• Adverse Effects and Cautions
– Nausea, vomiting, diarrhea, abdominal pain——
dose-dependent
– Neuropsychiatric toxicities: dizziness, headache,
behavioral disturbances, psychosis, seizures.

19. Pyrimethamine
• Pharmacokinetics
– Slowly but adequately absorbed from the gastrointestinal tract.
– Slowly eliminated and excreted from urine.
• Pharmacological Effects
– Kill schizonts of primary exoerythrocytic stage.
– Act slowly against premature schizonts of erythrocytic stage.
– No action against gametocytes, but can inhibit development of
plasmodium in mosquito.
– Inhibit plasmodial dihydrofolate reductase → inhibiting
breeding of plasmodium.

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

21. Alternative therapy
• Mefloquine 20 mg base/kg up to a maximum of 1.5 g
in two divided doses 8 hours apart.
• Mefloquine is contraindicated in pregnancy.
Cerebral malaria:
• Quinine 10 mg/kg i.v infusion over 4 h. could be
repeated at intervals of 8-12 h. until patient can take
drug orally.
• Or Halofantrine: orally only
• Or Qinghaosu (Artemisinin): oral & i.v

22. Chemoprophylaxis of malaria
Chloroquine-sensitive area:
• Chloroquine 150 mg base ( 2 tab/week)
Chloroquine-resistant area:
• Chloroquine ( 2 tab/week) plus proguanil
100 mg (one or two tab/ day)
or
• Mefloquine 250 mg (one tab./ week)

23. Anti-amebiasis Drugs
• Amebiasis is infection with Entamoeba
histolytic.
• Amebiasis is transmitted through
gastrointestinal tract.
• Ameba has two stages of development: cyst
and trophozoite.
Cysts → small intestine → little trophozoites (ileocecum)

24. Metronidazole
• A nitroimidazole . The nitro group of metronidazole
is chemically reduced in anaerobic bacteria and
sensitive protozoans. Reactive reduction products
appear to be responsible for antimicrobial activity.
• Pharmacokinetics
– Oral metronidazole is readily absorbed and permeates all
tissues by simple diffusion.
– Protein binding is low (<20%)
– Through blood brain barrier
– Metabolizing in liver.
– Excreted mainly in the urine.

25. • Pharmacological Effects and Clinical Uses
1. Anti-amebiasis: kills E histolytic trophozoites but
not cysts. Treatment of all tissue infections with
E histolytic. No effection against luminal
parasites and so must be used with a luminal
amebicide to ensure eradication of the infection.
2. Anti-trichomoniasis:
3. Anti-anaerobic bacteria:
4. Anti-giardiasis:

26. • Adverse Effects and Cautions
– Nausea, headache, dry mouth, a metallic taste in
the mouth.
– Infrequent: vomiting, diarrhea, rash, insomnia,
neutropenia, ……
– Rare: severe central nervous system toxicity
( ataxia, encephalopathy, seizures)——drug
withdrawal
– Has a disulfiram like effect, so that nausea and
vomiting can occur if alcohol is ingested during
therapy.

27. Emetine and Dehydroemetine
• Emetine, an alkaloid derived from ipecac, and
dehydroemetine, a synthetic analog, are effective
against tissue trophozoites of E histolytic .
• Because of major toxicity concerns they have
been almost completely replaced by
metronidazole.
• Administered subcutaneously (preferred) or i.m.
(but never i.v.) because oral preparations are
absorbed erratically.

28. • Pharmacological Effects and Clinical Uses
• kills E histolytic trophozoites of histolytic tissues
but no effection against luminal trophozoites. a
luminal amebicide should also be given.
• Rapidly alleviate severe intestinal symptoms,
used to treat amebic dysentery for the minimum
period because of toxicity.
• Occasionally as alternative therapies for amebic
liver abscess.

29. s
Inhibiting peptidyl-tRNA transposition →
inhibiting elongation of peptide chain
→inhibiting protein synthesis → interfering
cleavage and breeding of trophozoites

30. Diloxanide furoate
• Diloxanide furoateis a
dichoroacetamide(derivative.
• Effective luminal amebicide but is not active
against tissue trophozoites.
• The unabsorbed diloxanide in the gut is the active
antiamebic substance.
• Effective for asymptomatic luminal infections.
• It is used with a tissue amebicide, usually
metronidazole.
• Adverse Effects: flatulence, nausea, abdominal
cramps, rashes, abortion.

31. Paromomycin
• Aminoglycoside antibiotic.
• Not significantly absorbed from the
gastrointestinal tract.
• Only as a luminal amebicide and has no effect
against extraintestinal amebic infections.
• inhibiting protein synthesis → kill
trophozoites;
• inhibiting symbiosis flora → indirectly
inhibiting ameba protozoa.

32. • Chloroquine reaches high liver
concentrations → treatment of amebic liver
abscess.
• Not effective in the treatment of intestinal
or other extrahepatic amebiasis.
• Anti-trichomoniasis Drugs
• Metronidazole
• Acetarsol

33. Anthelmintic Drugs
• Classification of Helminth
a. Roundworms (nematodes) —— epidemic in
China
b. Tapeworms
c. Flukes (trematodes)

34. Mebendazole
• A synthetic benzimidazole that has a wide spectrum
of anthelmintic activity and a low incidence of
adverse effects.
• Pharmacokinetics
– Oral absorption ＜ 10 ％
– First pass elimination is high.
– Protein-binding ＞ 90 ％
– Excreted mostly in the urine, a portion of absored drug
and its derivatives are excreted in the bile.
– Absorption is increased if the drug is ingested with a fatty
meal.

35. • Pharmacologic Effects
– Inhibits microtubule synthesis in nematodes , thus
irreversibly impairing glucose uptake. Intestinal parasites
are immobilized or die slowly.
– Kills hookworm, ascaris , and trichuris eggs.
• Clinical Uses
– Pinworm infection
– Ascaris lumbricoides , Trichuris trichiura , Hookworm, and
Trichostrongylus.
– Other infections: intestinal capillariasis), trichinosis,
taeniasis, strongyloidiasis , dracontiasis, et al.

36. • Adverse Effects and Cautions
– Low-dose: nearly free adverse effects.
– Diarrhea, abdominal pain is infrequent.
– High-dose: pruritus, rash, eosinophilia, reversible
neutropenia, musculoskeletal pain, fever,
transient liver function abnormalities, alopecia,
glomerulonephritis, agranulocytosis

37. Albendazole
• A benzimidazole carbamate
• A broad-spectrum oral anthelmintic for
treatment of hydatid disease and
cysticercosis(, pinworm infection, ascariasis,
trichuriasis, strongyloidiasis, and infections
with both hookwormspecies.
• Effect better than Mebendazole.

38. • Clinical Uses
– Administered on an empty stomach when used
against intraluminal parasites but with a fatty
meal when used against tissue parasites.
1. Ascariasis, Trichuriasis, and Hookworm and
Pinworm infections.
2. Strongyloidiasis
3. Hydatid Disease
4. Neurocysticercosis
5. Other infections: cutaneous larva migrans,
gnathostomiasis

39. Piperazine
• Treatment of ascariasis.
• No longer recommended for treatment of
pinworm infection, because a 7-day couse of
treatment is required.
• Not useful in hookworm infection, trichuriasis, or
strongyloidiasis
• Causes flaccid paralysis of ascaris by blocking
acetylcholine at the myoneural junction.
• Neurotoxic adverse effects.

40. Pyrantel
• A tetrahydropyrimidine derivative.
• A broad-spectrum anthelmintic
• Highly effective for the treatment of pinworm,
ascaris, and Trichostrongylus orientalis infections.
• Moderately effective against both species of
hookworm but less so against N americanus.
• Not effective in trichuriasis or strongyloidiasis
• Oxantel, an analog of pyrantel, is effective
against in trichuriasis; the two drugs have been
combined for their broad-spectrum anthelmintic
activity.

41. • Effective against mature and immature forms of
helminths within the intestinal tract but not
against migratory stages in the tissues or against
ova.
• Inhibition of cholinesterase —— a depolarizing
neuromuscular blocking agent → spastic paralysis
• Used with caution in patients with liver
dysfunction.
• No combination with piperazine because of
antagonistic action.