ANTIPROTOZOAL DRUGS

Halia Wanadiatri, dr., M.Si.

• Malaria cases occur via infection from:
• Female anopheles mosquitoes in endemic regions
• Acquired congenitally or via transfusions/needles
• P. Falciparum: the majority  severe disease
• P. Malariae: relatively uncommon
• P. Vivax, p. Ovale: hypnozoites  potential for relapse
• P. Knowlesi:
• Previsiously: zoonotic malarial parasite
• Now: human malaria sometimes lethal
• Although all may cause significant illness, P. Falciparum is
responsible for nearly all serious complications & deaths
• Drug resistance is important therapeutic problem, most notably with
p. falciparum

MALARIA
• Treatment of the acute blood stage infection is necessary for
malaria caused by all malaria species.
• in p. Falciparum & p. Malariae infection, only one cycle of
liver cell invasion & multiplication occurs, & liver infection
causes spontaneously in less than 4 weeks  blood
schizonticides.
• In p. Vivax & p. Ovale infections, a dormant hepatic stage,
the hypnozoite, is NOT eradicated by most & subsequent
relapses can therefore occur after therapy directed against
erythrocytic parasites  eradication of both erythrocytic &
hepatic parasites is required to cure these infections.

ANTIMALARIA DRUG
 Gol. Quinoline:
Chloroquine, Hydroxycloroquine, Quinine,
Quinidine, Amodiaqiune, Pyronaridine,
Mefloquine, Halofantrine, Lumefantrine,
Piperaquine, Atovaquone, Primaquine
Gol. Artemisinin:
Artemether, Artesunate, Dihidroartemisinin
Antifolat:
Sulfadoxine, Pyrimethamine, Proguanil
Antimicrobial:
Tetracycline, Doxycycline, Clindamycin

ANTIMALARIA
• The active component of an herbal medicine that has
been used as an antipyretic in China
• The semisynthetic artemisinins have been formulated:
• Artesunate (water-soluble)
• Artemether (lipid-soluble)
• Dihydroartemisinin

ARTEMISININ
• Rapid & potent activity against even MDR-parasites
• Reduction in the parasite population each 48-h cycle of
intraerythrocytic invasion, replication & egress. 3 to 4
cycles (6-8 d)  to remove all the parasites from the
blood
• Tx < 5 days  recurrent parasitemia (several weeks)
• Should NOT be used for chemoprophylaxis: short T ½
 recrudescence ↑

ARTEMISININ
• Artemisinin-based combinaton therapies (ACTs) for the first-
line tx (T ½ ↑ & different MOA)  efficacy ↑ & resistance ↓:
• Artemeter + Lumefrantine: COARTEM (structural ~ mefloquine &
halofantrine {prolongantion QTc intervals}); is the most widely
used; T ½ = 2-4 d; cardiotoxicity (-); (+) high-faat meal  abs ↑;
sweetened dispersible formulation  for children)
• Artesunate + Amodiaquine (T ½ 9-18d; no longer recommended
 agranulocytosis & hepatotoxicity)
• Artesunate + Mefloquine
• Dihydroartemisinin + Piperaquine (is potent & well-tolerated; has
the longest plasma T ½ . 5 w  be effective introducing rates of
reinfection)

ARTEMISININ
• AE:
• Dose related & reversible, reticulocyte ↓ & neutrophil
counts↓ & transaminase levels ↑  allergic rx (1:3000)
• No systemic neurological changes were attributable to
threatment in px > 5 yo.
• CI: < 5 kg or TM I (animals: embryo lethality or
malformations)

ARTEMISININ
• Has declined across most malaria-endemic regions of the
world because of the spread of chloroquine-resistant P.
Falciparum  replaced by ACTs.
• EXCEPT in areas where resistant strains of p.vivax 
effective in chemoprophylaxis or treatment of acute attacks of
malaria caused by p. Vivax, p. Ovale, p. Malariae
• 24-48 h  febris (-); 48-72 h  parasitemia (-)
• Chloroquine: 1 g orally immediatlly, followed by 500 mg at 6,
24, 48 h.
• Chloroquine & its analogs  to treat hepatic amebiasis

CHLOROQUINE
• Safe
• The Pruritus is transient (dark-skinned persons), lasting 48-72
h, & is NOT responsive to Ahs
• Acute chloroquine toxicity: most frequently or doses ↑ are
administered too rapidly by parenteral routes:
cardio/neuromyo/retinopathy  evaluations every 3-6 mo
• Po, > safer
• Avoid lethal toxicity, parental:
• Slowly by constant iv infusion
• In small divided doses by the sc / im route

CHLOROQUINE
• > toxic, < effective than chloroquine
• Quinidine (iv), a stereoisomer of quinine; > potent & >
toxic than quinine (orally)
• Parenteral solutions are highly irritating:
• Should NOT be given sc; may cause abscesses (im),
thrombophlebitis (iv infused)
• For chemoprophylaxis: NOT used ~ toxicity & t ½ ↓
• In sever illness, the prompt use of loading doses of iv
quinidine can be lifesaving

QUININE, QUINIDINE
• Qunine: a triad of dose-related toxicities when given at full
therapeutic or excessive dose:
• Cinchonism (tinnitus, high-tone deafness, visual disturbances,
headache, dysphoria, nausea, vomitting & postural hypotension)
• Hypoglycemia (can be life threatning if NOT tx promptly w/ iv
glucose)
• Hypotension (is rare; ~ excessively rapid iv infusions)
• Quinidine, > cardiotoxic (Qtc prolongation, fatal cardiac
dysrhythmias) than quinine  monitoring
• “blackwater fever” (rx hypersensitivity) – the triad of massive
hemolysis, hemoglobinemia & hemoglobinuria leading to anuria,
renal failure & in some instances death.
• The action of quinine at NMJ enhances the effect of neutomuscular
blocking agents & opposes the action of Ach inh.

QUININE, QUINIDINE
• 750 mg as initial dose  2-4 x 250 mg, po
• CI:
• Cardiac conduction abnormal
• Psychiatric or seizure disorders
• Do NOT administer if patient has received related drugs
(chloroquine, qunine, quinidine) < 12 h ago

MEFLOQUINE
• Screening G6PD def. Prior to tx
• (+) a blood schizonticide: to eradicate erythrocytic stages
of thes plasmodia & reduce the possibility of emerging
drug resistance
• Doses:
• 0,25 mg/kgBB/d ~ 14d (p.vivax/ovale)
• Relaps 0,5 mg/kgBB/d

PRIMAQUINE
• AE:
• Abdomen distress  taking at mealtime
• Methemoglobinemia: congenital def. of NADH methemoglobin
reductase
• Acute hemolysis & hemolytic anemia: G6PD def.
• If daily dose > 30mg  blood count
• Is generally well tolerated when taken for > 1 year
• CI:
• Pregnant, lactating mother
• Use in acutely-ill patients who have a tendency to develop
granulocytopenia (RA, SLE)
• (+) other tx causing hemolytic anemia or myeloid bone marrow
suppression.

PRIMAQUINE
• Slow-acting ~ delayed death mechanism
• Typically paired with fast-acting antimalarials (Quinine,
Artesunate)
• Used alone for short-term chemoprophylaxis in the areas
w/ chloroquine- & mefloquine-resistant malaria
(Doxycycline, T ½)
• Clindamycin (po, iv): 3 x 20 mg/kg/d po ~ 7d; safe in
children & pregnant
• Doxycycline (po, iv): 2 x 100 mg po ~ 7 d
• Tetracycline (po, iv): 4 x 250 mg po ~7 d

ANTIMICROBIAL
• The diagnose of malaria must be considered for patients
presenting w/acute febrile illness after returning from
malaria-endemic region is crucial
• The oral route of drug administration is preferred, but iv
preparations may be administeres until oral medication
can be taken
• Avoid starting tx on an empty stomach
• Vomiting & diarrhea  abs ↓  tx failure 
readministration within an hour may still be effective

CHEMOTHERAPY
• Within 48-72 hr of initiating tx, px should show marked
clinical improvement (especially clearence of fever) & a
substantial decrease in parasitemia as monitored by daily
thin & thick blood smears
• Hypnozoite resistance to Primaquine is difficult to assess:
• Parasitemia within the first 4-6 weeks of an initial infection
may be due to failure of the blood stage treatment,
inadequate adherance, or primaquine failure
• Chloroquine sensitve p. Falciparum:
• Chloroquine
• Chloroquine resistance p. Falciparum:
• ACT
• Plus Primaquine : gametocidal & hipnozoidal ~first day
(p. Falciparum)
• Pregnant women should be urged NOT to travel to
endemic areas if possible
• Should NOT be used during pregnancy because of:
• Lack of safety data (antifolates, atovquone)
• Potential risks for fetus (tetracycline, doxycycline,
primaquine, mefloquine)
• Pregnant px w/ p. Vivax or p. Ovale inf. Should be kept
under chloroquine chemoprophylaxis until delivery.

PREGNANCY
• Chloroquine are the preferred agents
• Atovaquone is NOT recommended unless breast-feeding
infant weight > 5 kg
• The breast-feeding infant should be shown to have a
normal G6PD level before receiving Primaquine

LACTATING MOTHERS
• Artesunate im/iv dgn kombinasi obat
• Quinidine (tidak boleh iv bolus, dosis max 2000mg/hr)
• Cegah & tangani komplikasi
• Pertimbangkan pertukaran tranfusi untuk
hiperparasitemia.
• Ganti ke terapi oral bila biov dapat diandalkan

MALARIA BERAT
• Rawat jalan
• Hari ke 3, 7, 14, 21, 28
• Pemeriksaan klinis dan hapusan darah secara mikroskopis
• Apabila ada perburukan gejala segera datang ke dokter
• Rawat inap
• setiap hari sampai tidak ditemukan parasit 3 hari berturut-
turut
• Kemudian mengikuti seperti terapi rawat jalan

PEMANTAUAN
 CHEMOPROPHYLAXIS
Chloroquine (may exacerbate psoriasis) 1-2w -4w
Hydroxychloroquine 1-2w -4w
Mefloquine 1-2w -4w
Atovaquone + proguanil 1-2d -1w
Doxycycline (CI: < 8 yo; pregnant) 1-2d-4w
Primaquine: • 1-2d -1w
• Prophylaxis for short-duration travel to • For 14d after
areas p.vivax departure
• Anti-relaps tx (terminal prophylaxis)
Bed nets & insect repellents (avoid exposure at dusk & dawn)
• Take weekly at the same day of the week
• Take daily at the same time each day
• Nitroimidazole
• T½=8h
• Penetrates well into bady tissue & fluids (saliva, breast milk, CSF),
except placenta.
• inexpensive & versatile drug w/ efficacy a broad spectrum of
anaerobic & microaerophilic bacteria.
• AE:
• Headache, nausea, dry mouth, a metalic taste
• Disulfiram-like effect if they drink alcoholic beverages during or within 3
d of tx w/ this drug (abdominal distress, nausea, vomitting, flushing, or
headache, tachycardia, hyperventilation)
• + disulfiram or disulfiram-like drugs  should NOT be taken together 
confusional & psychotic states
• Caution: active ds of the CNS  potential neurotoxicity
• Pregnant trimester 1, NOT advised.

METRONIDAZOLE
• An aminoglicoside
• The drug is NOT abs from the GIT thus the actions of an
oral dose are confined to the GIT
• AE are rare w/ oral usage: abd pain & cramping,
epigastric pain, steatorrhea, diarrhea
• Has been advocated as a tx for Giardiasis in pregnant
women, when metronidazole is CI & as an alternative
agent for metronidazole-resitant isolates G. intertinalis

PAROMOMYCIN
• Entamoeba histolytica.
• This organism can cause asymptomatic intestinal
infection, mild to moderate colitis, severe intestinal
infection (dysentery), ameboma, liver abscess, and other
extraintestinal infections

AMEBIASIS
• DOC:
• Tinidazole 2 gr once
• Or metronidazole 3 x 250mg ~ 5d
• Alternative drugs:
• Furazolidone 4x100mg ~ 7d
• Albendazole 1x400mg ~ 5d
• Paromomycin: pregnant women to avoid any possible
mutagenic effect of the other drugs
• Nitazoxanide & tinidazole: in immuno-competent < 12 yo

GIARDIASIS
• These conditions have a significant impact on public
health in the form of disabling pruritus, secondary
infection & in the case of the body louse (pediculosis,
scabies), transmission of life-threatning illnesses such as
typhus
• Topical (permetrin, lindanel, sulfur, crotamiton)
• Oral (ivermectine)

ECTOPARASITES
TERIMA KASIH
&
SELAMAT BELAJAR