Académique Documents
Professionnel Documents
Culture Documents
Plasmodium falciparum.
P.vivax P.vivax & P.ovale.
P.ovale is mainly confined to
Africa.
Endemic
Endemic areas
areas of
of Malaria
Malaria
Acute falicparum
malaria is potentially
fatal.
Symptoms of malaria.
Complications:-.
Hemolytic anemia,
hepatospleenomegaly, capillary
obstruction, death
Malaria
Malaria Life
Life Cycle
Cycle Life
Life Cycle
Cycle
Sporogony
Oocyst
Sporozoite
s
Mosquito
Zygote
Salivary Gland
Sporozoites
Hypnozoites
(for P. vivax
and P. ovale)
Gametocytes
Exoerythrocytic
(hepatic) cycle
Merozoites
Erythrocytic
Cycle
Schizogony
Merozoites
Eradication of
dormant
Tissue
schizontocides:-.
1. Proguanil
(chlorguanide)
2.Pyrimethamine
Blood
schizontocides:-.
2
types
1. Chloroquine,
Mefloquine,
Halofantrine, &
Quinine.
2. Proguanil,
Pyrimethamine, &
sulfadoxine.
Gametocides:-destroy the
sexual forms of the parasite.
Primaquine, Chloroquine, & Quinie.
Primaquine the only drug that kills
P. falciparum gametocytes
Hypnozoitocides:
primaqunie
kills dormant
hypnozoites of P.vivax &
P.ovale in the liver.
Sprontocides:interrupt
development of
sporogonic
phase in
mosquitos .
Proguanil,
pyremethamine
primaquine
1.
2.
1- Prophylactic:-to prevent
clinical attack
Suppressive prophylaxis:-use
of blood schizontocides to
prevent acute attack
Causal prophylaxis:-use of
tissue schizontocides to
prevent the parasite from
establishing in the liver
2-Curative:-suppressive treatment of
the acute attack usually with blood
schizontocides.
3-Prevention of transmission:eradication of infection in mosquitos
using gametocytocides or
sporontocides.
4-Prevention of relapse:Primaquine
Mechanism of action
MOA
In the previous figure :
The parasite digests the human hemoglobin in order to get amino
acid, but the problem here is that the heme part of Hb is toxic to the
parasite.
To overcome this obstacle, the parasite has developed an enzyme
responsible for polymerization of heme. To form insoluble crystals
called hemozoin which are collected in vacuoles.
Chloroquine enters parasite cell by simple diffusion. Chloroquine then
becomes protonated as the digestive vacuole is known to be acidic
(pH 4.7), chloroquine then cannot leave by diffusion. Chloroquine
inhibits polymerization of heme accumulation of heme.
Chloroquine binds to heme (or FP) to form what is known as the
FP-Chloroquine complex, this complex is highly toxic to the cell and
disrupts membrane function. Action of the toxic compound results in
cell lysis and ultimately parasite cell autodigestion.
Contraindications:
Psoriasis or prophyria
Visual field abnormalities or myopathy
Ca and Mg containing antacid interfere with absorption
Used with caution in liver disease or neurologic or
hematologic disorders.
Other uses:
It is a disease modifying antirheumatoid drug.
(6-9 month)
SLE
In amebic liver abscess
Blood schizontocide
effective against the
erythrocytic form of all
species of malaria.
Acts by parasites heme
polymerase.
Depresses the
myocardium, why?
Because it has structural
similarity with quinidine,
an antiarrhythmic agent,
as it is its d- isomer.
Clinical uses:
Blood schizonticide against all species.
Gametocidal against P vivax and P ovale
PK:
Given orally in a7-day course or by slow IV for severe P.
falciparum infection,
bitter taste poor compliance,
metabolized in the liver, short t=10h.
ADRS:
Mild oxytoxic ( sever contraction) effects pregnant uterus, can
cause abortion
slight neuromuscular blocking action,
weak antipyretic action.
CONTRAINDICATIONS:
Prolonged QT Interval
Glucose-6-Phosphate Dehydrogenase Deficiency
Myasthenia Gravis
Hypersensitivity
Optic Neuritis, auditory problems
Dose should be reduced in renal insufficiency
Atovaquone:
Type 1 antifolates
sulphonamides &
sulphones , compete with
PABA.
Type 2 ,pyrimethamine &
proguanil
inhibition of dihydrofolate
reductase.
High resistance
Dapsone
Contraindications:
History of methemoglobinemia
Pregnancy
1.
2.
3.
4.
5.