PHARMACOLOGY
ANTI-MALARIAL DRUGS
Leon Caculitan, MD
CHEMOTHERAPY FOR MALARIAMarch 2019
Anti-Protozoal Drugs
Drug Classification:
1. Tissue Schizonticides: Drugs that eliminate developing or dormant liver forms.
2. Blood Schizonticides: Drugs that act on erythrocytic parasites.
DRUG
CHLOROQUINE
- is a synthetic 4
aminoquinoline formulated as
the phosphate salt for
oral use.
PHARMACOKINETICS:
Chloroquine is a rapidly and
completely absorbed
following oral administration.
It concentrates in erythrocytes
and some tissues. Thus it has a
very large apparent volume of
distribution.
The drug also penetrates into
the CNS and traverses the
placenta.
Chloroquine is dealkylated by
the hepatic mixed function
oxidase system and is
principally excreted in the
urine.
QUININE
- is derived from the bark of
the cinchona tree. Quinidine is
the
dextrorotatory stereoisomer of
quinine. Taken orally, Quinine
is well distributed
throughout the body and can
reach the fetus.
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ANTI-MALARIAL ACTION
Chloroquine is a highly effective
blood Schizonticide. It's also
moderately effective
against gametocytes of P. vivax,
P. ovale and P. malariae.
Chloroquine is not active against
liver stage parasites.
Quinine is a rapidly acting, highly
effective blood schizonticide. It's
gametocidal
against P. vivax and P. ovale. It's
NOT effective against liver stage
parasites.
3. Gametocides: Drug that kill sexual stages and prevent transmission to
mosquitoes.
Radical Cure: Elimination of both hepatic and erythrocytic stages.
NOTE: No one available agent can reliably affect a radical cure.
MODE OF ACTION
After traversing the erythrocytic and
plasmodial membranes, Chloroquine
is
concentrated in the organism's
acidic food vacuoles. Chloroquine
specifically binds to heme released
from the digestion of the host cells'
hemoglobin, preventing its
polymerization to hemozin (a
pigment). The increased pH and
accumulation of the
toxic heme result in oxidative
damage to the membranes, leading
to lysis of both the
parasite and the RBC.
Quinine and quinidine interfere with
heme polymerization resulting in the
death of
the erythrocytic form of the
plasmodial parasite.
CLINICAL USE
1. Parenteral treatment of
severe falciparum malaria.
Quinine or quinidine is the
treatment of choice for
severe falciparum malaria.
2. Oral treatment of
falciparum malaria. Quinine
is appropriate first line
therapy
for uncomplicated
falciparum malaria. Quinine
is commonly used with
doxycycline to shorten
quinine's duration of use and
limit toxicity.
SPUP MEDICINE
EXIMIUS
2021
ADVERSE EFFECTS OTHERS
At high doses, some toxic effects RESITANCE:
occur such as gastro-intestinal Chloroquine resistant P.
upset, pruritis, falciparum exhibit
headache and blurred vision. multigenic alternations
Discoloration of the nail beds and that confer a
mucous membranes high level of resistance.
may be seen on chronic When a chloroquine
administration. Rare reactions resistant organism is
include hemolysis in G6PD encountered,
deficient persons, seizures, therapy usually consists of
agranulocytosis and ECG an orally administrated
changes. Patients with psoriasis combination of quinine,
or porphyria should not be pyrimethamine and a
treated with chloroquine, sulfonamide,such as
because an acute attack may be sulfadoxine
provoked.Chloroquine is
considered safe in pregnancy.
1. Cinchonism: A syndrome
causing nausea, vomiting, tinnitus
and vertigo is the
major adverse effect. These
effects are reversible and are not
considered to be
reasons for suspending therapy.
2. Positive Coombs test for
hemolytic anemia. Quinine
treatment should be
suspended.
3. Hemolysis with G6PD
deficiency.
4. Potentiation of neuromuscular
blocking agents and elevation of
digoxin levels
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EXIMIUS
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PRIMAQUINE 1. Eradicates primary - Primaquine is a tissue 1. Drug induced hemolytic Contraindications

- Primaquine is a synthetic 8-
aminoquinoline. It's well
absorbed on oral
administration and is not
concentrated in tissues. It's
rapidly oxidized to many
compounds.
exoerythrocytic forms of P.
falciparum and P. vivax.
2. Eradicates secondary
exoerythrocytic forms of
recurring malarias (P. vivax
and
3. P. ovale). Primaquine is the
only agent that can lead to
radical cures of P. vivax and
P. ovale malaria, which may
remain in the liver after the
erythrocytic form of the
disease is eliminated.
4. Destroys in the blood the
gametocytic forms of all 4
plasmodia.
5. It is not effective against the
erythrocytic stage of
malaria.
schizonticide. Anemia in patients with
- Metabolites of it are believed to genetically low levels of
act as oxidants that are glucose 6 phosphate
responsible for the schizonticidal dehydrogenase.
action as well as for the 2. Abdominal discomfort
hemolysis and especially when administrated in
methemoglobinemia combination with
encountered as toxicities. chloroquine.
3. Occasional
methemoglobinemia.
4. Rarely granulocytopenia and
agranulocytosis
1) Patients should be
tested for G6PD
deficiency before
primaquine is prescripted.
When the patient is
deficient in G6PD,
treatment strategies may
consist of (1)
withholding therapy, (2)
treating patients with
standard dosing for 14
days (3)
treating with weekly
primaquine for 8 weeks.
2) During pregnancy
Inhibitors of Folate
synthesis:
36.8

PYRIMETHAMINE  Against erythrocytic forms of - Pyrimethamine inhibits 1. Fansidar is used to treat

- adequately absorbed,
bound to plasma proteins and
has an
elimination half-life of about
3.5 days. It's extensively
metabolized before excretion.
Fansidar is a fixed combination
of the sulfonamide sulfadoxine
and pyrimethamine
susceptible strains of all 4
human malaria species.
 It also acts as a strong
sporontocide in the
mosquito's gut when the
mosquito ingests it with the
blood of the human host.
 Thus it's a blood
Schizonticide and
sporontocide.
plasmodial dihydrofolate chloroquine –resistant
reductase at much lower falciparum malaria.
concentrations than those 2. Fansidar is used as
needed to inhibit the presumptive therapy of
mammalian enzyme. falciparum malaria.
- The inhibition deprives the 3. Pyrimethamine, in
protozoan of tetrahydrofolate – combination with
a cofactor required in the de sulfadiazine is first line
novo synthesis of purines and therapy for
pyrimidines and in the thetreatment of
interconversion of certain amino toxoplasmosis. If
acids. megaloblastic anemia
occurs with
pyrimethamine
treatment, it may be
reversed with
Leucovorin.

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ANTI-MALARIAL DRUGS
Leon Caculitan, MD April, 2018
EXIMIUS
2021
March 2019
Drugs for treatment of Nematodes: Drugs for the treatment of trematodes:
 Mebendazole  Prazyquantel
 Pyrantel Pamoate
 Thiabendazole Drugs for the treatment of cestodes:
 Ivermectin  Niclosamide
 Diethylcabamazine  Albendazole
Mechanism of Action Pharmacokinetics Clinical use Side effect Contraindications
Diethylcarbamazine treatment of filariasis because of its ability to immobilize
microfilariae.
Pyrantel pamoate - depolarizing neuromuscular poorly absorbed orally & exerts its - effective in the treatment of infections caused by mild & include
blocking agent, causing effects in the intestinal tract roundworms, pinworms &hookworms nausea,
persistent activation of the - paralyzed worm is then expelled from the host’s vomiting &
parasites nicotinic receptors. intestinal tract. diarrhea.
Thiabendazole - targets the parasite’s Cl channel Thiabendazole is effective against: Pregnancy
receptors. (1) strongyloidiasis
- Chloride influx is enhanced & (2) cutaneous Larva migrans
hyperpolarization occurs, (3) trichinosis.
resulting in paralysis
Niclosamide - to inhibition of the parasite’s - A laxative is administered prior to The drug is lethal for the cestode’s scolex & segments of
mitochondrial anaerobic oral administration of niclosamide cestodes, but not for the ova.
phosphorylation of ADP, which to purge the bowel of all the dead 1. Diphyllobothrium latum
produces energy in the form of segments & so preclude digestion 2. T. saginata,
ATP. & liberation of the ova, which may 3. T.solium
lead to cysticercosis 4. H. nana.
Praziquantel - increase the permeability of - rapidly absorbed after oral 1. Schistosomiasis: drug of choice of all forms of include ocular
trematode & cestode cell administration & distributes into schistosomiasis (S. haematobium, S. mansoni & S. drowsiness, cysticercosis.
membrane to calcium, resulting the CSF. japonicum). dizziness & GIT
in paralysis, dislodgement & - High levels occur in the bile. The 2. Other trematodes infections e.g. clonorchiasis. upsets. not
death. drug is extensively metabolized & 3. Taeniasis & diphyllobothriasis: results in high cure rates recommended
excreted through the urine & bile. for T. saginata, T. solium & D. latum. for pregnant
4. Neurocysticercosis: albendazole is now the preferred women or nursing
drug. mothers.
5. Hymenolepis nana: drug of choice for H. nana
infections
Mebendazol - inhibits microtubule synthesis in - Little of an oral dose (that is It is the drug of choice in the treatment of infections by: abdominal pain pregnancy
nematodes thus irreversibly chewed) is absorbed by the 1. Whipworm (Trichuris trichiura). & diarrhea. &children under 2
impairing glucose uptake. body, unless it is taken with a high 2. Pinworm (Enterobius vermicularis). years.
- Affected parasites are expelled fat meal. 3. Hookworm (Ancylostoma duodenale).
with feces - It undergoes 1st pass metabolism 4. Roundworm (Ascaris lumbricoides).
to inactive compounds.
Albendazole - inhibits microtubule synthesis & - It is erratically absorbed after oral 1. Cysticercosis (caused by Taenia Solium larvae). Treatment of The drug
glucose uptake in nematodes. administration & undergoes 2. Hydatid disease ( caused by Echinococcus granulosis) hydatid disease shouldn’t be
extensive 1st pass metabolism, (3 months) has given during
including formation of sulfoxide, a risk of pregnancy or to
which is also active Albendazole hepatotoxicity children under 2
& its metabolites are primarily & rarely, years of age.
excreted in the urine. agranulocytosis
or
pancytopenia.
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 PHARMACOLOGY SPUP MEDICINE

ANTI-MALARIAL DRUGS
Leon Caculitan, MD April, 2018
EXIMIUS
2021
March 2019

TRANSCRIBERS Smile 1 of 1
 PHARMACOLOGY SPUP MEDICINE

ANTI-MALARIAL DRUGS
Leon Caculitan, MD April, 2018
EXIMIUS
2021
March 2019

TRANSCRIBERS Smile 1 of 1