Antiprotozoal drugs
Dr. Karun Kumar
Senior Lecturer
Dept. of Pharmacology

Antimalarial Drugs
• Aims of using drugs
1. To prevent clinical attack of malaria (prophylactic)
2. To treat clinical attack of malaria (clinical curative)
3. To completely eradicate the parasite from the
patient’s body (radical curative)
4. To cut down human-to-mosquito transmission
(gametocidal)

Classification

• When a person is bitten by an infected mosquito,
Plasmodium sporozoites enter the liver, form tissue
schizonts, and undergo exoerythrocytic schizogony to
produce merozoites
• The merozoites released from the liver invade
erythrocytes and form trophozoites that undergo
erythrocytic schizogony

• Some trophozoites develop into male and female
gametocytes, which must subsequently pass back
into a mosquito before they can develop into
sporozoites and repeat the infection cycle

• Erythrocytic schizontocides  Act on erythrocytic
schizogony
• Tissue schizontocides  Act on preerythrocytic as
well as exoerythrocytic (P. vivax) stages in liver
• Gametocides  Kill gametocytes in blood
• Primaquine blocks exoerythrocytic schizogony (tissue
schizontocide)  Causal prophylaxis
• Symptoms of malaria (fever, chills & rigors)
correspond to erythrocytic stage

Causal prophylaxis
• Pre erythrocytic phase (in liver), which is the cause of
malarial infection and clinical attacks, is the target for
this purpose
• Primaquine ; not used in mass programmes, because
of its toxic potential
• Proguanil for P.f., but not used in India, because of
weak activity against liver stages of P.v., and rapid
development of resistance when used alone

Suppressive prophylaxis
• The schizontocides which suppress the erythrocytic
phase and thus attacks of malarial fever can be used
as prophylactics
• Though the exoerythrocytic phase in case of vivax
and other relapsing malarias continues, clinical
disease does not appear
• Mefloquine & Doxy. are used for malaria prophylaxis
by travellers

Clinical cure
• The erythrocytic schizontocides are used to
terminate an episode of malarial fever
1. High-efficacy drugs  Artemisinin, CQ,
Amodiaquine, quinine, mefloquine, halofantrine,
Lumefantrine and Atovaquone
2. Low-efficacy drugs  Proguanil, pyrimethamine,
sulfonamides, tetracyclines and clindamycin

• The faster acting drugs are preferred, particularly in
falciparum malaria where delay in treatment may
result in death even if the parasites are cleared from
blood by the drug
• The exoerythrocytic phase (hypnozoites) of vivax and
ovale persists which can cause relapses subsequently
without reinfection

• Erythrocytic schizontocides are radical curatives for
falciparum, but not for vivax or ovale malaria
• However, recrudescences occur in falciparum
infection if the blood is not totally cleared of the
parasites by the drug

Erythrocytic schizontocides (cl.cure)
• Kill schizonts in the blood (T/t of acute attacks &
suppressive prophylaxis)  MACHAR Pe attack
• Mefloquine
• Atovaquone
• Chloroquine
• Halofantrine (and Lumefantrine)
• Artemisinins
• ResQ (Quinine)
• Proguanil, Pyrimethamine

T/t of uncomplicated malaria
A. Vivax (also ovale, malariae) malaria
1. Chloroquine 600 mg (10 mg/kg) followed by 300 mg
(5 mg/kg) after 8 hours and then for next 2 days
(total 25 mg/kg over 3 days) + Primaquine 15 mg
(0.25 mg/kg) daily × 14 days
• In CQ resist., Quinine 600 mg (10 mg/kg) 8 hourly × 7
days + Doxycycline 100 mg daily × 7 days or +
Clindamycin 600 mg 12 hourly × 7 days + Primaquine
(as above) or ACT + Primaquine (as above)

B. Chloroquine-sensitive falciparum malaria 
Chloroquine (as above) + Primaquine 45 mg (0.75
mg/kg) single dose (as gametocidal)
C. Chloroquine-resistant falciparum malaria
Artesunate 100 mg BD (4 mg/kg/day) × 3 days +
Sulfadoxine 1500 mg (25 mg/kg) + Pyrimethamine 75
mg (1.25 mg/kg) single dose
• In India (including under NVBDCP) all P.f. cases,
irrespective of CQ-resistance status, are treated with
artemisinin based combination therapy (ACT)

Radical cure
• In case of vivax and ovale malaria, drugs which attack
the exoerythrocytic stage (hypnozoites) given
together with a clinical curative achieve total
eradication of the parasite from the patient’s body
• A radical curative is needed in relapsing malaria,
while in falciparum malaria — adequate treatment of
clinical attack leaves no parasite in the body
• DOC for radical cure of vivax and ovale malaria is
Primaquine 15 mg daily for 14 days

Gametocidal
• Elimination of the male and female gametes of
Plasmodia formed in the patient’s blood
• Gametocidal action is of no benefit to the patient
being treated, but will reduce the transmission to
mosquito
• Primaquine is gametocidal to all species of
Plasmodia, while artemisinins have weak lethal
action on early-stage but not mature gametes

Stage Clinical use
Pre-erythrocytic Causal
prophylaxis
Erythrocytic Cl. Cure & supp.
prophyl.
Exo-erythrocytic Radical cure
Gametocidal Prev. of trans.

Chloroquine
• Rapidly acting erythrocytic schizontocide against all
species of plasmodia; controls most clinical attacks in
1–2 days with disappearance of parasites from
peripheral blood in 1–3 days
• Actively concentrated by sensitive intraerythrocytic
plasmodia; higher concentration is found in infected
RBCs than in noninfected ones
• DOC for T/t & prophyl. of non-falciparum malaria &
CQ sensitive P. falciparum malaria

Mechanism of action
• By accumulating in the acidic vacuoles of the parasite
and because of its weakly basic nature, it ↑ vacuolar
pH and thereby interferes with degradation of
haemoglobin by parasitic lysosomes
• Polymerization of toxic haeme generated from
digestion of haemoglobin to nontoxic parasite
pigment haemozoin is inhibited by the formation of
CQ-haeme complex

• Haeme itself or its complex with CQ then damages
the plasmodial membranes
• Clumping of pigment and changes in parasite
membranes follow
• Other related antimalarials like quinine, mefloquine,
lumefantrine, pyronaridine appear to act in an
analogous manner

Other uses (RED LIP Mahatma Gandhi)
1. Rheumatoid arthritis
2. Extraintestinal amoebiasis
3. Discoid lupus erythematosus
4. Lepra reaction
5. Infectious mononucleosis
6. Photogenic reactions
7. Malaria (DOC in pregnant women)
8. Giardiasis

Adverse effects
• Nausea, vomiting, anorexia, uncontrollable itching,
epigastric pain, uneasiness, difficulty in
accommodation and headache are frequent and
quite unpleasant
• Prolonged use of high doses can result in blindness
due to retinal damage

Mefloquine
• Fast acting erythrocytic schizontocide, but slower
than CQ or quinine due to prolonged absorption
after oral ingestion.
• Effective against CQ-sensitive as well as resistant
plasmodia
• A single dose controls fever and eliminates
circulating parasites in infections caused by P.
falciparum or P. vivax

• However, relapses occur frequently subsequently in
vivax malaria
• Also an efficacious suppressive prophylactic for
multiresistant P. falciparum and other types of
malaria
• Bitter in taste
• S/E  Dizziness, nausea, vomiting, diarrhoea,
abdominal pain, sinus bradycardia and Q-T
prolongation

Use
• MDR P. falciparum
• Due to potential toxicity, cost and long t½, use is
restricted
• In combination with artesunate as ACT for
uncomplicated falciparum malaria, including CQ-
resistant and CQ + sulfa-pyrimethamine (S/P)
resistant cases
• For prophylaxis of malaria among travellers to areas
with multidrug resistance

Sulfonamide-Pyrimethamine (S/P)
• Pyrimethamine has high affinity for the plasmodial
DHFRase enzyme
• Sulfadoxine and sulfamethopyrazine are ultralong
acting sulfonamides — attain low blood
concentrations, but are able to synergise with
pyrimethamine which also has long t½

• Combination has the potential to cause serious
adverse effects (exfoliative dermatitis, Stevens
Johnson syndrome, etc.) due to the sulfonamide
• Use is restricted to single dose t/t of uncomplicated
CQ-resistant falciparum malaria
• 1st line ACT regimen used under NVBDCP in India

Primaquine
• Has a marked effect on primary as well as secondary
hepatic phases of the malarial parasite
• Highly active against gametocytes and hypnozoites
• A/E  Abd. pain, g.i. upset, weakness or uneasiness
in chest (S/E); can be minimized by taking the drug
with meals. CNS and CV symptoms are infrequent.
• Leucopenia occurs rarely with larger doses.
• Most imp. toxic potential is dose related haemolysis,
methaemoglobinaemia, tachypnoea and cyanosis

Use
1. Vivax malaria  Radical cure of relapsing (vivax)
malaria. G-6-PD status of the patient should be
tested before giving 14 day primaquine course. It is
to be taken with food to reduce g.i. side effects.
2. Falciparum malaria  Single 45 mg dose is given
with the curative dose of CQ or ACT to kill the
gametes and cut down transmission to mosquito

Artemisinin derivatives
• Fastest acting drugs against malaria
• Used for t/t of MDR malaria & cerebral malaria
• Short acting drugs, monotherapy needs to be
extended beyond the disappearance of the parasites
to prevent recrudescence
• Recrudescence can be totally prevented by
combining 3 day artemisinin with a long acting drug

• A/E  N, V, abd. pain, itching and drug fever.
Headache, tinnitus, dizziness, bleeding, dark urine, S-
T segment changes, Q-T prolongation subside when
the patient improves or drug is stopped
• Use  Uncomplicated falciparum malaria (CQ-
resistant as well as sensitive). DCGI has prohibited
use of oral artemisinins as single drugs. FDCs are
encouraged
• Severe and complicated falciparum malaria 
Artesunate (i.v. or i.m.) OR Artemether (i.m.) OR
Arteether (i.m.) given till the patient is fit to take oral
medication, followed by 3 day oral ACT

ACT regimens for uncomplicated
falciparum malaria
1. Artesunate-mefloquine (AS/MQ)  Artesunate 100
mg BD (4 mg/kg/day) × 3 days + mefloquine 750 mg
(15 mg/kg) on 2nd day and 500 mg (10 mg/kg) on
3rd day (total 25 mg/kg)
2. Artesunate-sulfadoxine + pyrimethamine (AS/S/P)
 Artesunate 100 mg BD (4 mg/kg/day) × 3 days +
sulfadoxine 1500 mg (25 mg/kg) and
Pyrimethamine 75 mg (1.25 mg/kg) single dose

Summary

Antiamoebic drugs
• Drugs useful in infection caused by the anaerobic
protozoa Entamoeba histolytica
• Diloxanide furoate  DOC for asympt. Intest.
Amebiasis & carriers
• Metronidazole  DOC for amoebic liver abscess &
intestinal wall disease

Classification

EXAM DIAGRAM