2. Phenanthrene
⢠It is a polycyclic aromatic system comprising
three fused benzene rings
⢠The name phenanthrene is a composite
of phenyl and anthracene
5. ⢠This compound was synthesized in World War-II
⢠Developed into a drug in 1960s
⢠It contains one chiral center;
â Two enantiomers
â Which are active equally
â Hence, the drug is a racemic mixture
6. ⢠It is an alternative drug for both chloroquine sensitive
and chloroquine resistant falciparum
⢠The drug is metabolized via N-dealkylation by CYP 3A4
to desbutylhalofentrine;
â Which is many fold more sensitive than the parent drug
7. ⢠Only available in oral dosage forms
⢠Main problems associated are low bioavailability
(Excretion in feces)-treatment failure and resistance
⢠Prolong half-life of the drug and its metabolite is
responsible for resistance
⢠Fatty meal may enhance bioavailability
8. ⢠Halofantrine has caused serious, even fatal,
heart problems (ventricular arrhythmias), even
at the recommended dose.
⢠Halofantrine is not recommended for use while
other medicines known to cause heart
problems (prolonged QT interval)
9. Mode of action
⢠The mode of action is unknown, although
⢠Crystallographic study showed that it binds
to hematin in vitro, suggesting a possible
mechanism of action
⢠Halofantrine has also been shown to bind
to plasmpesin, a hemoglobin degrading
enzyme
10. ⢠In addition there is evidence to suggest that
halofantrine may inhibit the energy-dependent
proton pump on the external surface of the
plasmodia in erythrocytes, thereby destroying
the membrane integrity of the parasite
12. 2-Artemisnin
⢠Is a natural compound separated from a
herb named Artemisia annua, which has
been used by Chinese for thousands years
for treating malaria
⢠Nowadays, a derivative of artemisnin
(artemether) is being used for treating
malaria
- Is active against erythrocytic stage
- In body converted to free radicals
which cause oxidative decomposition of
plasmodium cell membrane
Artemether
Artemisnin
13. ⢠Chemically, artemisinin is a sesquiterpene
lactone containing an unusual peroxide
bridge. It is believed that this peroxide is
responsible for the drug's mechanism of
action.