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:
 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