MEDICINES USED TO

TREAT MALARIA
 Learning outcomes
2

 Classify anti-malarial medicines according to

antimalarial activity and structure.

 List drugs used to treat uncomplicated and

complicated malaria.

 List drugs used for chemoprophylaxis (causal

prophylactics).

Treatment of Malaria, CMT05101, NTA Level 5

 Learning outcomes cont..
3

 Describe the mechanism of action of antimalarial

drugs.

 Describe the pharmacokinetic properties of

antimalarial drugs.

 Explain the clinical indications and contraindications

of antimalarial drugs.

Treatment of Malaria, CMT05101, NTA Level 5

 Learning outcomes cont..
4

 Explain major side effects of antimalarial drugs.

 Outline precautions to be taken when using

antimalarial drugs.

Treatment of Malaria, CMT05101, NTA Level 5

 Introduction
5

 Malaria is the most important parasitic disease of

humans and causes hundreds of millions of illnesses
per year.

 Four species of plasmodium typically cause human

malaria:-
 Plasmodium falciparum,
 Plasmodium vivax,
 Plasmodium malariae, and Plasmodium ovale.

Treatment of Malaria, CMT05101, NTA Level 5

 Introduction cont..
6

 Although all of the latter species may cause

significant illness, P falciparum is responsible for the
majority of serious complications and deaths.

 Drug resistance is an important therapeutic problem,

most notably with P falciparum.

Treatment of Malaria, CMT05101, NTA Level 5

 Introduction cont..
7

Parasite life cycle

 An anopheline mosquito inoculates plasmodium

sporozoites to initiate human infection.

 Circulating sporozoites rapidly invade liver cells, and

exoerythrocytic stage tissue schizonts mature in the
liver.

Treatment of Malaria, CMT05101, NTA Level 5

 Introduction cont..
8

 Merozoites are subsequently released from the liver

and invade erythrocytes. Only erythrocytic parasites
cause clinical illness.

 Repeated cycles of infection can lead to the infection

of many erythrocytes and serious disease.

Treatment of Malaria, CMT05101, NTA Level 5

 Introduction cont..
9

 Sexual stage gametocytes also develop in

erythrocytes before being taken up by mosquitoes,
where they develop into infective sporozoites.

Treatment of Malaria, CMT05101, NTA Level 5

 Introduction cont..
10

Treatment of Malaria, CMT05101, NTA Level 5

 Classification of Anti-malaria Drugs
11

Several classes of antimalarial drugs are available.

 According to antimalarial activity.

 According to chemical structure.

 Antibiotics.

Treatment of Malaria, CMT05101, NTA Level 5

 According to antimalarial activity.
12

 Causal prophylactic drugs (tissue schizotocides)

These drugs act on the hypnozoites of P.vivax
and P. ovale in the liver that cause relapse of
symptoms on reactivation.
Its for preventing relapses
 Primaquine is the prototype drug.
 Pyrimethamine also has such activity

Treatment of Malaria, CMT05101, NTA Level 5

 According to antimalarial activity
cont..
13

 Schizontocidal drugs (Blood schizonticides)

 These drugs act on the blood forms of the parasite
and thereby terminate clinical attacks of malaria.
 These are the most important drugs in anti malarial
chemotherapy.
 These include chloroquine, quinine, mefloquine,
halofantrine, pyrimethamine, sulphadoxine,
sulfones, and tetracyclines.

Treatment of Malaria, CMT05101, NTA Level 5

 According to antimalarial activity.
14

 Gametocytocidal drugs (gametocytocides)

 These drugs destroy the sexual forms of the
parasite in the blood and thereby prevent
transmission of the infection to the mosquito.
 Chloroquine and quinine have gametocytocidal
activity against P. vivax and P. malariae, but not
against P.falciparum.
 Primaquine has gametocytocidal activity against
all plasmodia, including P. falciparum

Treatment of Malaria, CMT05101, NTA Level 5

 Classification of Anti-malaria Drugs
cont..
15

 Sporontocidal drugs
 These drugs prevent the development of oocysts in
the mosquito and thus ablate the transmission.
 Primaquine and chloroquine have this action.

 Anti-relapse drugs (secondary tissue

schizontocides)
 Have a pronounced action on the exo-erythrocytic
phase of p.vivax and p.malariae.
 Example primaquine and pamaquine.

Treatment of Malaria, CMT05101, NTA Level 5

 According to chemical structure.
16

 4-Aminoquinoline
 Examples includes Chloroquine and Amodiaquine.

 8-aminoquinolines
 Examples includes Primaquine

 Peroxides
 Examples includes Artemisinins derivatives and
analogues artemether, artesunate,
dihydroartemisinins.
 According to chemical structure cont..
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 Bisquinoline
 Examples includes piperaquine.

 Folate antagonist combination

 Examples includes sulphadoxine-pyrimethamine

 Quinone-folate antagonist combination

 Examples includes Atovaquone-proguanil
(malarone)
Treatment of Malaria, CMT05101, NTA Level 5
 According to chemical structure cont..
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 Quinoline methanol
 Examples includes Quinine, Quinidine,
mefloquine.

 Amyl alcohol.
 Examples includes lumefantrine

 Common antibiotics having activity vs. malaria

includes Doxycycline, clindamycin.
Treatment of Malaria, CMT05101, NTA Level 5
 Classification of Anti-malaria Drugs
19

Treatment of Malaria, CMT05101, NTA Level 5

 List of drugs used to treat Malaria
20

Malaria can be classified as:-

 Uncomplicated malaria, the mild form of malaria

which usually causes a fever, with/out headache,

tiredness, muscle pains, abdominal pains, nausea, and
vomiting.

 If left untreated, uncomplicated malaria can develop

into severe malaria with kidney failure, breathing
difficulties, fitting, unconsciousness, and eventually
death.
Treatment of Malaria, CMT05101, NTA Level 5
 List of drugs used to treat Malaria
21

Drugs used to treat uncomplicated malaria includes:-

 Artemether-Lumefantrine (ALU).

 Dihydroartemisinins-piperaquine (duocotexin).

 Artesunate-mefloquine (artequin).

 Dihydroartemisinins-piperaquine-Primaquine.

 Artemisinins-piperaquine (Artequick).

 Quinine.

 Atovaquone-Proguanil (Malarone).

Treatment of Malaria, CMT05101, NTA Level 5

 List of drugs used to treat Malaria..
22

Drugs used to treat complicated malaria

includes:-
 First line is Iv Artesunate (2.4mg/kg bodyweight).
 Iv Artemether(3.2mg/kg bodyweight).
 Iv Quinine(10mg/kg bodyweight).

Treatment of Malaria, CMT05101, NTA Level 5

 List of drugs used for
chemoprophylaxis
23

The drugs used for chemoprophylaxis (causal

prophylactics) includes the following:-
 Chloroquine.

 Mefloquine.

 Doxycycline.

 Combination of atorvaquone and proguanil

 SP in IPTP

Treatment of Malaria, CMT05101, NTA Level 5

Artemether - Lumefantrine (ALu )

Description
 It is an oral fixed combination tablet of 20mg

Artemether – a derivative of artemesinin, and 120mg

Lumefantrine.
 Artemether is effective against all human malaria

parasites species.
 It has a rapid schizonticidal action against Plasmodium

falciparum.
 Recrudescence is therefore frequent when is used as

monotherapy
Artemether - Lumefantrine cont..
 An aryl amino acid
 Has a longer elimination half life of up to 10 days and
is associated with low recrudescence rate but a slower
rate of action.
 ALu contains the benefits of the fast onset of action
of Artemether with the long duration of action and
cure rate of Lumefantrine in a single oral preparation.
 It is highly efficacious even against multidrug
resistant malaria parasite with clearance of the
parasites from the blood within two days.
 Artemether - Lumefantrine cont..
26

Mechanism of action
 Lumefantrine binds to hemin produced during

hemoglobin breakdown, preventing detoxification to

crystalline malaria pigment (hemozoin). During the
same process, the peroxide group in artemether binds
to heme and releases toxic free-radicals
 The artemesinin radical binds subsequently to

membrane proteins, and alkylation reactions

eventually cause destruction of the parasite

Treatment of Malaria, CMT05101, NTA Level 5 12/21/2023

 Artemether - Lumefantrine cont..
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Pharmacokinetics properties
 Orally absorbed.

 Peak plasma time artemether 2hrs, lumefantrine 3-6

days
 Metabolized in liver by CYP3A4 to produce

metabolites DHA and desbutyl-lumefantrine.

Excreted in urine

Treatment of Malaria, CMT05101, NTA Level 5

 Artemether - Lumefantrine cont..
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Indications
 First line tx of uncomplicated malaria.

Contraindications
 1st trimester pregnancy .

 Hypersensitivity to Artemisinins derivatives.

 Co administration with strong CYP3A4 inducers e.g.

rifampicin, carbamazepine and phenytoin.

Treatment of Malaria, CMT05101, NTA Level 5

 Artemether - Lumefantrine cont..
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Precautions
 Not approved for severe/complicated of p falciparum

infections.
 Not approved for prevention.

 May render hormonal contraceptives ineffective.

 If pts vomits out drug repeatedly use alternative tx.

 Concurrent CYP3A4 or CYP2D6.

Treatment of Malaria, CMT05101, NTA Level 5

 Artemether - Lumefantrine cont..
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Side effects
 Artemisinins derivatives are generally very well

torlalated, the most commonly reported side effects

of ALU are:-
 Abdominal pain, anorexia, arthralgia.
 Asthenia, chills, dizziness, fatigue.
 Headache, myalgia, palpitation, pyrexia, sleep
disorder, nausea and vomiting.

Treatment of Malaria, CMT05101, NTA Level 5

 Artesunate
31

Mechanism of action
 Unclear, may inhibit DNA replication and

transcription.

Pharmacokinetics properties
 Peak plasma time within 1 hr., Half life elimination

40-50min
 Metabolized in liver DHA active.

 Excreted in urine and feces.

Treatment of Malaria, CMT05101, NTA Level 5

 Artesunate cont..
32

Indications
 IV artesunate is indicated for severe form of malaria.

 Oral combination therapy for uncomplicated malaria.

Contraindications
 Hypersensitivity reaction

Treatment of Malaria, CMT05101, NTA Level 5

 Artesunate cont..
33

Side effects
 Generally well tolerated.

 Cardio toxicity under high dose, Drug inducer fever,

Skin rashes.

 Lower reticulocyte count, Post artesunate delayed

hemolysis.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine
34

Mechanism of action.
 Unknown, may disrupt plasmodium DNA

transcription/replication.

Pharmacokinetics properties
 Absorption readily mainly from upper small

intestine, Metabolized primarily hepatic, Peak

plasma 1-3 hrs., Excreted in feces, saliva and urine.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
35

Indications
 Tx of malaria with concomitant tetracycline,

doxycycline, or clindamycin.

 Iv quinine used in severe falciparum malaria

 Babesiosis with clindamycin.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
36

Contraindications
 Hypersensitivity.

 G6PD deficiency.

 Optic neuritis, tinnitus, hx of quinine associated

black water fever and thrombocytopenic purpura.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
37

Precautions
 Quinine should be discontinued if signs of severe

cinchonism, hemolysis, or hypersensitivity occur.

 It should be avoided if possible in patients with

underlying visual or auditory problems.

 Reduced in renal insufficiency.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
38

 It must be used with great caution in those with

underlying cardiac abnormalities.

 Quinine should not be given concurrently with

mefloquine and should be used with caution in a
patient with malaria who has previously received
mefloquine.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
39

Side effects
 Cinchonism(tinnitus, headache, nausea, dizziness,

flushing, and visual disturbances)

 More marked visual and auditory abnormalities,

vomiting, diarrhea, and abdominal pain. Often after
prolonged therapy.

 IV of quinine may cause thrombophlebitis.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
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 Hypersensitivity rxn ( skin rashes, urticaria,

angioedema, and bronchospasm)

 Hematologic abnormalities include hemolysis

(especially with G6PD deficiency), leukopenia,
agranulocytosis, and thrombocytopenia.

 Severe hypotension can follow too-rapid iv infusions

of quinine.

Treatment of Malaria, CMT05101, NTA Level 5

 Quinine cont..
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 Hypoglycemia through stimulation of insulin release.

 Stimulation uterine contractions, especially in 3 rd

trimester. However, this effect is mild, and quinine
remain drug of choice for severe falciparum malaria
even during pregnancy.

Treatment of Malaria, CMT05101, NTA Level 5

 Dihydroartemisinins-Piperaquine
(DHA-P)
42

Description
 DHA-P is one Artemisinins-based combination

therapies recommended to treat malaria.

 These combinations contain an Artemisinins

component (dihydroartemisinin) which works very

quickly to clear the malaria parasite from the person's
blood, and a longer acting drug (piperaquine) which
clears the remaining parasites from the blood and
may prevent new infections with malaria for several
weeks.
Treatment of Malaria, CMT05101, NTA Level 5
 Dihydroartemisinins-Piperaquine
cont..
43

Mechanism of action of DHA

 Its endoperoxide bridge is thought to be essential for

its antimalarial activity, causing free radical damage

to parasite membrane system.

Mechanism of action of piperaquine

 Thought to bind to haeme within malaria parasite

preventing its detoxification via polymerization step.

Treatment of Malaria, CMT05101, NTA Level 5

 Dihydroartemisinins-Piperaquine
cont..
44

DHA Piperaquine
 Very rapidly absorbed.  Lipophilic compound
 Highly protein bound is slowly absorbed.
to human plasma  Highly protein bound
 Metabolized in liver to human plasma
 t0.5 is 1hr  Metabolized in liver
 t0.5 is 22days

Treatment of Malaria, CMT05101, NTA Level 5

 Dihydroartemisinins-Piperaquine
cont..
45

Indications
 Tx of acute uncomplicated malaria , its particularly

recommended in the case of mult resistant

plasmodium falciparum malaria.

Contraindications
 Hypersensitivity

 Children <6 months or weight below 5 kg

 Salt imbalance

Treatment of Malaria, CMT05101, NTA Level 5

 Dihydroartemisinins-Piperaquine
cont..
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Precautions
 Avoid if patient is suffering from severe malaria

affecting brain, lungs or kidneys, heart condition,

such as changes to the rhythm or rate of heartbeat, or
any heart disease or any of family members having
heart complaints.

 Pregnant or planning to become pregnant or are

breastfeeding.

Treatment of Malaria, CMT05101, NTA Level 5

 Dihydroartemisinins-Piperaquine
cont..
47

Side effects
 Fever, Loss of appetite, Cough, Vomiting, General

weakness, Abnormal heartbeat.

 Shortness of breath, Heart palpitation, Feeling of

sickness.

 Anorexia, nausea, abdominal pain, diarrhea,

dizziness, and itching.
Treatment of Malaria, CMT05101, NTA Level 5
 References
48

 B. G. Katzungu et al (2009), Basic & clinical

pharmacology (11th ed), Norwalk, USA: Appleton &
Lange.

 Foster, R.W. (1996). Basic Pharmacology. (4th ed.).

Oxford: Butterworth-Heinemann.

 Laurence, D. R. et al. (1997): Clinical Pharmacology

(8th ed.). Edinburgh: Churchill Livingstone.

Treatment of Malaria, CMT05101, NTA Level 5