This document discusses malaria, including its causative parasites, life cycle, symptoms, and treatment options. It describes the five Plasmodium species that cause malaria in humans. It outlines the objectives and types of antimalarial drugs, focusing on mechanisms of action and important drug classes like artemisinin derivatives. It recommends WHO-approved artemisinin-based combination therapies for treating uncomplicated malaria and identifies parenteral treatments for severe cases. It also provides guidance on treating malaria during pregnancy.

1. :By:
Ankit sharmA
M.Pharma (Pharmacology)
Bhupal Nobles University
Udaipur, Rajasthan

2. Malaria
 Malaria is an infectious disease in which intermittent and
remittent fever caused by protozoan parasites from the
Plasmodium family that can be transmitted by the bite ofth
Anopheles mosquito, which invades the RBC
 There are 5 species of the protozoal parasite Plasmodium,
found in most parts of India and other tropical countries.
 Plasmodium vivax
 Plasmodium ovale
 Plasmodium falciparum
 Plasmodium malariae
 Plasmodium knowlesi

3. Life cycle of the malarial parasite

5. Symptoms of Malaria
 Central effect: Headache
 Systemic : Fever
 Muscular : Fatigue, Pain, Back pain
 Skin: Chills, Sweating
 Respiratory : Dry cough
 Spleen: Enlargement
 Stomach: Nausea, Vomiting

6. Antimalarial Drugs

7. MOA of Various Drugs

8. Site of Action of Drugs

9. Objectives and Use
of Antimalarial Drugs
 The aims of using drugs in relation to malarial
infection are:
 To prevent clinical attack of malaria (prophylactic).
 To treat clinical attack of malaria (clinical curative).
 To completely eradicate the parasite from the patient’s
body (radical curative).
 To cutdown human-to-mosquito transmission
(gametocidal).

10. Mechanism of action

11. Artemisinin Derivatives
 Artemisinin is the active principle of the plant Artemisia
annua used in Chinese traditional medicine as ‘Quinghaosu’.
 It is a sesquiterpine lactone endoperoxide active against P.
falciparum resistant to all other antimalarial drugs as well as
sensitive strains and other malarial species.
 The duration of action is short and recrudescence rate is high
when they are used alone in short courses.

12. Mechanism of action
 These compounds have presence of endoperoxide bridge
 Endoperoxide bridge interacts with heme in parasite
 Heme iron cleaves this endoperoxide bridge
 There is generation of highly reactive free radical which
damage parasite membrane by covalently binding to
membrane proteins

13. Artemisinin Derivatives
Artesunate Artemether
 Its sodium salt is water-soluble
and is administered by oral, i.m.
or i.v. routes.
 In addition, rectal route has been
tried. After oral ingestion,
absorption is incomplete but fast,
reaching peak in <60 min.
 It is rapidly converted to the
active metabolite DHA with a t½
of 30–60 min. The t½ of DHA is
1–2 hours.
 After repeated dosing, artesunate
causes autoinduction of its own
metabolism by CYP2B6 and
CYP3A4.
 It is lipid-soluble and is
administered orally or i.m., but
not i.v.
 Absorption after oral as well as
i.m. dosing is slower taking 2–6
hours.
 It undergoes substantial first pass
metabolism and is converted to
DHA.
 Extensive metabolism by CYP3A4
yields a variable t½ of 3–10 hours.

14. Artemisinin-based
Combination Therapy (ACT)
 Artemisinin compounds fillin this requirement, as they
rapidly kill > 95% plasmodia. They leave only a small biomass
of the parasites to be eliminated by the long t½ drug,
reducing the chances of selecting resistant mutants.
 Advantages of ACT over other antimalarials are:
▪ Rapid clinical and parasitological cure.
▪ High cure rates (>95%) and low recrudescence rate.
▪ Absence of parasite resistance (the components prevent
development of resistance to each other).
▪ Good tolerability profile.
 Oral ACTs are not to be used in severe or complicated
malaria, for which parenteral drugs are needed.

15. The WHO Recommended ACT s
include
 Artemether-Lumefantrine
 Artesunate-Amodiaquine
 Artesunate-Mefloquine
 Artesunate-Sulfadoxine-Pyrimethamine
 Dihydroartemisinin-Piperaquine

16. ACT regimens for uncomplicated
falciparum malaria

17. Severe and complicated falciparum malaria
 Artesunate: 2.4 mg/kg i.v. or i.m., followed by 2.4 mg/kg after 12
and 24 hours, and then once daily for 7 days. Switchover to 3 day
oral ACT inbetween whenever the patient can take and tolerate
oral medication.
 Artemether: 3.2 mg/kg i.m. on the 1st day, followed by 1.6 mg/kg
daily for 7 days. Switchover to 3 day oral ACT inbetween whenever
the patient is able to take oral medication.
 Arteether: 3.2 mg/kg i.m. on the 1st day, followed by 1.6 mg/kg daily
for the next 4 days. Switchover to 3 day oral ACT inbetween
whenever the patient is able to take oral medication.
 Quinine diHCl: 20 mg/kg (loading dose) diluted in 10 ml/kg 5%
dextrose/dextrose-saline and infused i.v. over 4 hours, followed by
10 mg/kg (maintenance dose) i.v. infusion over 4 hours (in adults)
or 2 hours (in children) every 8 hours, untill patient can swallow.
Switchover to oral quinine 10 mg/kg 8 hourly to complete the 7
day course.

18. Falciparum Malaria during Pregnancy
 An attack of falciparum malaria occurring during pregnancy
has serious implications both for the mother as well as the
foetus. It must be treated promptly and aggressively. Drugs
recommended are:
 Quinine 600 mg TDS × 7 days + Clindamycin 300 mg
TDS/QID (20 mg/kg) for 7 days; can be used during all
trimesters, especially the 1st.
 Artemisinin-based therapy is a better tolerated 3 day
regimen, which may be used during the 2nd and 3rd
trimester as an alternative to 7 day quinine + Clindamycin
therapy.