Anti Malarial Drugs

Dr. Mozna Talpur

Anti Malarial Drugs
Blood schizonticides: Tissue schizonticides:
 Chloroquine  Primaquine
 Amodiaquine
 Mefloquine
 Quinine
 Artemether
Clinical Classification
Causal prophylaxis:
Chloroquine, primaquine, pyramathamine.
Clinical cure:
Chloroquine, amodaquine, mefloquine, quinine and
artemether.
Radical cure:
Primaquine (p.vivax), pyramathamine (p.ovale)
Gamatocides:
Primaquine (p.vivax, p.falciperum)
Chloroquine
Highly effective schizonticidal for all 4 types of
plasmodium
Moderately effective against gametocytes (vivax,
malarae, ovale but not falciperum)
It is not effective against pre-erythrocytic phase.
MOA
Parasite depends upon the haeme as a source of
energy.
Parasite polymerises haeme to form hemozoin.
Choloroquine inhibits the polymerases. As a result of
that haeme can not be converted to haemozoin and
accumulates inside the parasite.
Haeme is toxic for parasite.
Alkalinization of food vacuole:
The conversion of haeme to hemozoin is carried out in
acidic media.
Chloroquine converts this acidic media to basic media
so that it can not utilize haeme in alkaline media.
Decrease synthesis of DNA and RNA
Act by blocking the enzymatic synthesis of DNA and
RNA.
Resistance
Plasmodium falciperum develops resistance to
chloroquine mostly.
Chloroquine resistant parasite expel chloroquine via
p-glycoprotein pump similar to that described for
multidrug resistance cancer cells.
Clinical uses
Acute malarial attacks by,
P.M, P.F (non resistant), P.O, P.V (less effective)
Prophylaxis for all strains of malaria except for
falciperum malaria which is resistant to chloroqiune.
Amebiasis ( amebic liver abcess)
Acute immune disorder
Adverse effects
Low doses for prophylaxis (no S.E)
Slight high doses for treatment:
GIT disturbances;
 Nausea vomiting diarrhea.
Pruritis, urticaria, skin rashes(black person)
Exacerbates dermatitis produced by gold
Anorexia, malaise, headache, psychosis are rare.
Blurring of vision (mostly develop early)
Damage the retina (high doses may produce irreversible
damage)
ECG changes
Contraindication
Relative: Absolute:
 Visual disturbances. Cardiac disorder
 Hepatic dysfunction. Blood disorder
 Severe G.I.T problem. Dermatitis
 Neuralgic disorder. Psoriasis
Drug interaction
Antacids:
E.g., magnesium trisilica, antidiarrheal e.g., kaolin
interfere in absorption of chloroquine.
Chloroquine should be taken about 2 to 3 hours before
or after antacid and antidiarrheal drug use.
Mefloquine
Quinoline methanol derivative developed to deal with
chloroquine resistant malaria
Rapidly acting erythrocytic schizonticide , slower than
chloroquine & quinine
Effective against chloroquine sensitive & resistant
plasmodia
Mechanism of action similar to chloroquine.
Clinical uses
Multi drug resistant plasmodium falciperum.
Prophylaxis against P.O, P.V and plasmodium malarae.
The drug is highly effective against plasmodium
falciperum but is reserved for chloroquine resistant
areas
It can not be given in patients with cerebral malaria
par-entrally.
Side effects
At minor therapeutic dose:
GIT upset (Vomiting diarrhea gastritis) due to bitter
taste.
Transient neuro-psychiatric problem (Dizziness,
disorientation, hallucination)
Leukocytosis, thrombocytopenia.
At Higher dose:
Severe GIT upset
Severe neuro-psychiatric problem
Cardiac extra systole
Contra-indication
Psychiatric disorder
Cardiac disorders:
Cardiac arrhythmias, cardiac conduction defect
First trimester of pregnancy
Quinine
It is reserved for malaria strains resistant to other
agents.
To treat palasmodium falciperum by I/V infusion in
unconscious patient for 7 days.
Mechanism of action
Interfere with heme polymerization
Results in cell death of plasmodium falciperum
(erythrocytic phase)
Inhibits DNA synthesis
Resistance
Resistance increased if used alone.
So used in combination with pyrimethamine,
sulphadoxine, doxycycline, or clindamycin.
Clinical uses
Blood schizomticidal for all four plasmodium
Gamatocidal for P.V and P.O not for P.F
No effect on sporozoits in liver
Side effects
Gastric irritation (abdominal pain Nausea vomiting)
Cinchonism (tinnitus, Vertigo)
Visual disturbances
Hypersensitivity reaction
Cardiac depression
Curare like effects
Increase uterine contraction
Hypoglycemia (Inc insulin secretion)
Severe hypotention if used I/V
Drug interaction
N.M blocking agents aggravates curare like actions
Digoxin, warfarin inc plasma half life.
Primaquine
Weak action against erythrocytic stage of vivax
Eradicates exo-erythrocytic form of P.F and P.V.
Secondary exo-erythrocytic form of P.V and P.O
(recurring malaria)
Mechanism of action
Not well understood
They act as electron carrying redox compound which
as reactive oxygen species and cause cell injury.
Resistance
Some P.V are resistant to primaquine
Clinical uses
Prophylaxis against P. ovale and P.V
Radical cure of P.V and P.O (schizont lying in liver)
Side Effects
Epigastric pain
Nausea
Vomiting and abdominal cramps
Bone marrow supression
Leukopenia
Agranulocytosis
Hemolytic anemia in G6PD deficiency
Contra-indication
First trimester of pregnancy
G6PD deficiency
Pyrimethamine
MOA:
Inhibits plasmodial dihydrofolate reductase
Deprives tetrahydrofolate in plamodium which is a
cofactor required for biosynthesis of purines and
pyramidines and certain A.A
Clinical uses
Tasteless so suitable for children
Blood schizonticidal and sporonticidal
Strong sporonticidal for mosquitos gut. When mosquito
ingest blood of human host.
Used in combination with sulphadoxine (fansidar)
CHEMOPROPHYLAXIS:
Chloroquine resistant malaria.
Alternate to mefloquine while in endemic area of
malaria for 4 weeks after leaving the area.
CLINICAL CURE:
Chloroquine resistant P.F
Side effects
Megaloblastic anemia
Thrombocytopenia
Agranulocytosis.
Therapeutic options for treatment and
prevention of malaria
Chloroquine resistant P.F:
Quinine + Pyrimethamine-sulfadoxine
Or Doxycycline
Or Clindamycin
Alternate:
Mefloquine
Prevention of relapse:
Chloroquine
In chloroquine resistant area: Mefloquine
In pregnancy:
Amidoquine or mefloquine