MALARIA AND

ANTIMALARIALS
YABIN
Introduction
• Malaria is a febrile condition that is caused by the genus, plasmodium
and species, falciparum, malariae, ovale, and vivax. It is transmitted
by a feeding female anopheles mosquito from an infected patient.
• This condition is characterized by fever, headache, joint pains etc.
Species of plasmodium
• Plasmodium falciparum: This species causes tertian malaria that is
malignant in nature. It causes up to about 98% of malaria condition in
Africa. It is the most dangerous species and needs to be treated
vigorously to avoid mortality. Fortunately prompt therapy is usually
highly successful. Relapses are not common with this parasite.
• Plasmodium vivax: this species causes benign tertian (BT) type of
malaria, it is a less severe disease compared to that produced by
falciparum species. Relapses are very common with this species
because of exoerythrocytic schizogony process/ stage.
• Plasmodium Malariae: The species causes quartan malaria that is
benign in nature. It is named quartan because of attacks of chills and
high fever that recur every 4 days rather than every 3 days as is the
case with tertian malaria. Relapses occur but not as common as in
vivax.
• Plasmodium ovale: The species causes tertian malaria. It causes
many relapses because of the exoerythrocytic schizogony stage. The
disease is similar to that caused by vivax only that it is milder and
more readily cured.
Malaria life cycle
Classification of antimalarial
1. Antimalarial are classified broadly depending on the presence of
artemisinin base.
Artemisinin based combination therapy (ACTs) eg;
• Coartem: contains lumefantrine and artemether
• Larimal: Amodiaquine + artesunate
• Duocotexin: dihydroartemesinin + piperaquine
• Arco: Artemisinin + Napthoquine
• Artequine: Mefloquine + artesunate
Non artemisinin based drugs
• Sulphadoxine + Pyrimethamine + Chloroquine
• Sulphadoxine + Pyrimethamine = Fansider
• Sulphamethopyrazine + pyrimethamine = metekelfin
• Dapsone + pyrimethamine = Maloprim
2. Other classification

1. 4-Aminoquinolines
Examples:
• Chloroquine
• Amodiaquine
These drugs are rapid acting blood schizontocides. Amodiaquine is
more effective than chloroquine and is currently used as the first line
drug in combination with artesunate.
2. 4- methanoquinolines

Examples:
• Quinine
• Mefloquine
They are rapid acting blood schizonticides and can be used for
treatment of both uncomplicated and complicated malaria. Mefloquine
is also used for prevention of malaria in non immune patients.
3. 8- Aminoquinolines
Examples:
• Primaquine
They are tissue schizonticides and are used to prevent relapse of ovale
and vivax. Primaquine is used in radical cure (destroy) the dominant
stages in the liver.
4. Biguanides
Example: Proguanil.
They are slow acting blood schizontocides used for prophylaxis of
malaria in combination with Atovaquone.

5. Suphonamides:
Example: Sulphadoxine
Sulphonamides are slow acting blood schizontocides currently used to
prevent malaria in pregnant mothers. It is usually given in combination
with pyrimethamine (fansider).
6. Antibiotics:

Examples:
• Doxycycline
• Tetracycline
• Clindamycin
They are blood schizontocides and are usually given in combination
with quinine in the treatment of resistant malaria.
MALARIA PROPHYLAXIS
Non immune individual:
• Mefloquine 250mg weekly started 2 1/2 weeks before entering the
malaria area and 4 weeks after leaving.
• Doxycycline: 100mg once daily starting 2 days before entering the
malaria area and 4 weeks after leaving.
Intermittent treatment of malaria in pregnancy (IPT)
• Fansidar: 3 tablets single dose in the 2nd and 3rd trimester.
• Pregnant women with HIV, 3 doses of fansidar after the1st trimester
with the space of at least 1 month apart.
QUININE
Quinine is a cinchona alkaloid and 4 methanolquinoline antimalarial that is a rapid acting
blood schontocide with activity against plasmodium falciparum, p. vivax, p. ovale and p.
malariae.
Available preparation:
• Tablets 300mgs, Injections 300mg/ml, Syrup 100mg/5mls
Available brands: Quininmix, Requin, Agog quinine, Quine, Quinin-K
Pharmacokinetics:
Quinine is rapidly and almost completelt absorbed from the GIT, widely distributed
throughout the body. It is extensively metabolized in the liver and rapidly excreted in urine.
Indications: complicated and severe malaria including cerebral malaria.
Uncomplicated resistant p. falciparum malaria.
MOA: interference with the parasites ability to digest haemoglobin.
contraindications
• Known hypersensitivity to quinine
• Complete AV block
• Haemoglobinuria
• Myasthenia gravis
• Optic neuritis.
• Dose: Oral, Adults: 600mg 8 hrly for 7 days and
• Children: 10mg/kg 8 hrly for 7 days.
• By slow IV Infussion, Adults 600mg 8hrly in D5%; children 10mg/kg
8hrly in D5% for 4 hours.
Pregnancy category: Quinine stimulates the myometrium and can
cause abortion in early pregnancy.
 Definitive treatment for complicated malaria

1st line treatment

• IV/IM Artesunate 2.4mg/kg at stat, 12hrs, 24hrs then o.d until able to
take oral medications.
• Full oral dose of 1st line antimalarial.
• NB: 8hrs between last dose of Artesunate and 1st line antimalarial.
Alternative treatment:
• Quinine 10mg/kg IM/IV 8hrly x 7 days.
• Artemether IM 3.2mg/kg stat, 1.6mg/kg o.d x 4days.
• Change to1st line oral regimen immediately patient is able to swallow the
drug (At least 8hrs from parenteral to oral drug regimen).
Side effects
Headache, blurred vision, Abdominal pain, Diarrhea, black water fever,
Tinnitus, Hypersensitivity reaction Nausea, hot and flashed skin and
Hypoglycemia.
Drugs interactions
• Cimetidine increases the blood levels of quinine.
• Quinine increases the blood level of digoxin
• The absorption of quinine may be delayed when administered with
anti acids containing aluminium.
• Plasma level of warfarin are increased when administered with
quinine
MEFLOQUINE
• Available preparations: Tablets 250 mg
• Available brand: Mephaquine, Larium, Meflotas
• Pharmacokinetics
Mefloquine is well absorbed from the gastrointestinal tract, widely
distributed throughout the body. It has a long eliminiation half-life and
is metabolized in the liver. Mefloquine and its metabolites, are excreted
mainly in the bile and feaces.
MOA: the MOA of mefloqiune is not known, but the morphological
changes produced in the intraerythrocytic parasites resemble quinine.
Indications:
• Uncomplicated malaria due to multi resistant p. falciparum.
• Malaria prophylaxis.

Contraindications:
• Known hypersensitivity to mefloquine
• Prophylaxis in the 1st trimester of pregnancy.
• History of convulsion
• Patients with acute depression.
Dose
• For treatment of malaria: 20-25mg/kg as a single dose or in two divided
doses 6-8 hours apart.
• For prophylaxis: Adults and children over 45kg: 250mg (1 tablet) once
weekly.
Note: Prophylaxis should start at 21/2 weeks before entering endemic area
and continue for 4 weeks after last exposure.
Side effects:
1. Nausea 5. Visual disturbance 9. Skin Rash
2. Insomnia 6. Confussion 8. Vomiting
3. Abdominal pain 7. Loss of balance 10. Convulsion
4. Loss of appetite 8. Anxiety 11. Muscle weakness
Drug interaction
• Mefloquine may antagonize the effect of anti epileptics such as
carbamezapine, Sodium Valporate.
• Mefloquine may increase the risk of adverse effects when taken with
other antimalarials.
• Mefloquine may increase the risk of bradycardia when given together
with beta blocker, calcium channel blockers and digitalis.
Key Issues to note:
• Advise the patient to take mefloquine after a meal.
• Pregnant mothers should not use mefloquine for prevention of
malaria.
SULFADOXINE WITH PYRAMETHAMINE
• Pyramethamine and sulfadoxine act synergistically in the inhibition of folic acid
synthesis in the parasites.
• Available preparations: Tablet 500/25mg
• Available brands: Fansidar, Falcistat, Malarest, Malaren, Kamsidar.
Pharmacokinetics:
Pyramethamine with sulfadoxine is well absorbed when taken orally, widely
distributed and metabolized in the liver and slowly excreted in urine.
Contraindication:
• Known hypersensitivity to any of the ingredients.
• Severe renal failure.
• Infants less than two months old.
• Blood dyscrasias.
Dose
Treatment of uncomplicated malaria.
Adults and children
• 30-45kg (10-14 yrs): 2 tablets single dose
• 20-30kg (5-10 yrs) 1.5 tablet single dose
• 10-20kg (2-5 yrs) 1 tablet single dose.
• Less than 10 kg (upto 2 yrs) 0.5 tablet single dose.
Prophylaxis:
Adults and children over 45kg. 1 tablet once weekly.
30-45kg 1.5 tablets every 2 weeks
10- 30kg 1 tablet every 2 weeks
Less than 10kg 0.5 tablet every 2 weeks
Indications
• Treatment of malaria.
• Prophylaxis of malaria.
MOA: Sulphadoxine and pyramethamine are folic acid antagonists.
Sulphadoxine inhibits the activity of dihydropteroate synthase whereas
pyramethamine inhibits dihydrofolate reductase.
Side effects
Urticaria, Vomiting, Diarrhoea, Vertigo, Serum sickness, Nausea,
Abdominal pain, Headache, Arthralgia, Tinnitus.
Drug interactions:
• Sulfadoxine+ pyramethamine may increase the anti folate effects of
methotrexate
• There is an increased anti folate effect when SP is given with
cotrimoxazole.
• Sulfadoxine+pyramethamine may increase the plasma concentrations
of phenytoin.
Primaquine
• Available preparations: Tablets 15mg
Pharmcokinetics.
Primaquine is readily absorbed from the gastrointestinal tract, rapidly
metabolized in the liver to carboxy primaquine and a small amount is
excreated unchanged in urine.
Indications:
Radical cure of P. vivax and p. ovale (eradicates dormant parasites from the
liver)
Pneumocystis carinii pneumonia.
Contraindications:
Pregnancy, Lactating mothers, Children less than 1 yr, known hypersensitivity
to primaquine, active rheumatoid arthritis.
Dose
• Malaria: 15mg once daily for 14 days.
• Pneumocystis carinii pneumonia: 30 mg once daily plus clindamycin 300-
450mg 4 times daily for 3 weeks.
Side effects
Abdominal pain, Nausea and vomiting, Leucocytosis, acute haemolytic
anaemia, epigastric distress, Anorexia, agranulocytosis.
Drugs interactions:
• Primaquine should not be used with drugs liable to induce haemolysis or
bone marrow depression eg methotrexate
• Chloramphenicol should not be administered with primaquine.
• Primaquine should be taken after a meal to avoid stomach upset.
• MOA:
Primaquine is active against hepatic stages of all human malaria
parasites. It is the only available agent active against the dormant
hypnozoite stages of P vivax and P ovale. Primaquine is also
gametocidal against the four human malaria species. Primaquine acts
against erythrocytic stage parasites, but this activity is too weak to play
an important role. The mechanism of antimalarial action is unknown.
Doxycycline
• Available preparations: Capsules 100mg, tablets 100mg.
• Available brands: Remycin
• Pharmacokinetics:
• Doxy is readily and almost completely absorbed from the GIT and
absorption is not significantly affected by the presence of food. It is widely
distributed in body tissues and fluids and is slowly excreted in urine.
Indications:
• Supplement to quinine in the treatment of multidrug resistant p.
falciparum malaria.
• Short term prophylaxis of malaria.
contraindications
• Pregnancy, Children under 12 years, known hypersensitivity to
doxycycline.
 Dose
• Treatment: 100mg twice daily for 7 days following quinine
treatment.
• Prophylaxis: 100mg daily starting 1-2 days before entering
malaria endemic area.
Side effect:
Nausea and vomiting, staining of growing teeth, headache,
vaginal candidiasis, diarrhoea, mouth ulcers, photosensitivity
and skin rash.
 Drug interactions

• Doxycycline may increase the blood levels of drugs like digoxin

and lithium
• Antacids and preparations containing iron, calcium and
magnesium may reduce the absorption of doxycycline
• There is decrease in the therapeutic effects of doxycycline
when it is given with barbiturates, phenytion and
carbamazepine.
Artemisinin Derivatives

Examples:
• Artemether, Artesunate, Dihydroartemisinin.
They are rapid acting schizontocides used in the treatment of
complicated malaria and uncomplicated malaria when combined with
other drugs.
MOA: The MOA of artemisinin is not definitely known however,
endoperoxide bridge in its molecule appears to interact with heame in
the parasite. Iron mediated cleavage in the bridge releases a highly
reactive free radicals species that binds to membrane proteins and
causes lipid peroxidation, damages endoplasmic reticulum, inhibits
protein synthesis and ultimately results in lysis of the parasites.
Artemether
Artemether is a semi-synthetic artemisinin derivative with schizontocidal and
gametocidal activity against multidrug resistant strains of plasmodium falciparum.
Available preparation:
• Inj. 20mg/ml, 40mg/ml, 80mg/ml, 100mg/ml.
Available brands: Artenum, Artesiane, Larither.
Pharmacokinetics: Artemether is rapidly hydrolyzed to the active metabolize
dihydroartemisinin.
Contra indications:
• Known hypersensitivity to artemether
• 1st trimester of pregnancy
Indications: Uncomplicated malaria.
• Severe malaria.
Dose
• IM injection, adults: 300mg as a loading dose on day 1, then 100mg once a day
for 4 days. Children: 3.2mg/kg on day 1, followed by 1.6mg/kg once daily for 4
days.
Side effects:
Nausea, diarrhea, vomiting, headache, dizziness, Tinnitus.
Drug interactions:
Manufacturers advise to avoid concurrent use of artemether with the following
drugs:
• Erythromycin
• Amiodarone
• Tricyclic antidepressants
• Phenothiazine
 Lumefantrine
Lumefantrine is an antimalarial agent used in combination with
artemether for the treatment of acute uncomplicated malaria caused
by Plasmodium falciparum.
It is administered in combination with artemether for improved
efficacy. This combination therapy exerts its effects against the
erythrocytic stages of Plasmodium spp. and may be used to treat
infections caused by P. falciparum and unidentified Plasmodium
species, including infections acquired in chloroquine-resistant areas.
Pharmacodynamics
Lumefantrine is a blood schizonticide active against erythrocytic
stages of Plasmodium falciparum.
It is thought that administration of lumefantrine with artemether
results in cooperate antimalarial clearing effects.
Artemether has a rapid onset of action and is rapidly cleared from
the body.
It is thus thought to provide rapid symptomatic relief by reducing the
number of malarial parasites.
Lumefantrine has a much longer half life and is believed to clear
residual parasites.
Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is

unknown.
However, available data suggest that lumefantrine inhibits the formation of β-
hematin by forming a complex with hemin and inhibits nucleic acid and protein
synthesis.
 COMBINATION PREPARATION
Artemether + lumefantrine
• Available preparation: tablets 20mg/120mg, 40mg/240mg,
80/480mg
Suspension 15mg/ 90mg/5mls
Available brand: Coartem, Lonart, Artefan, Co-Artesiane, Lumartem,
Co-Malartem
Indication: First line treatment of uncomplicated malaria
Contraindications: hypersensitivity to artemether or lumefantrine,
patients with severe malaria, breast feeding, history of
arrhythmias.
Suspension: each 5ml artemether + 90mg lumefatrine
 Toxicity
Common side effects of combination artemether/lumefantrine
therapy in adults include headache, anorexia, dizziness, and
asthenia.
Common side effects in children include pyrexia, cough,
vomiting, anorexia, and headache.
Possible serious adverse effects include QT prolongation, bullous
eruption, urticaria, splenomegaly (9%), hepatomegaly (adults,
9%; children, 6%), hypersensitivty reaction, and angioedema.
 TREATMENT
UNCOMPLICATED MALARIA:

DEFINITIVE
1st line treatment:
Artemether/Lumefantrine 20/120mg

Weight Age Day one Day 2 Day three

(Kgs)
5-14 4months- 1 tablet b.d 1 tablet b.d 1 tablet b.d
3years
15-24 3-7years 2 tablets b.d 2 tablets b.d 2 tablets b.d
25-34 7-12years 3 tablets b.d 3 tablets b.d 3 tablets b.d
35+ 12years+ 4 tablets b.d 4 tablets b.d 4 tablets b.d
 Side effects
• Abdominal pain, diarrhoea, skin rash, dizziness, fatigue, anorexia,nausea
and vomiting, headache, pruritis, tinnitus
• Pregnancy category: Pregnant mothers in the first trimester and children
less than 4 months should not be given ACT combinations because of
limited information about their safety in this category of patients.
Drug interactions
Manufacturer advises avoid concurrent use with the following drugs:
Amitriptiline, Quinine, Azithromycin, Ciprofloxacin, Fluconazole,
Mefloquine
Food: Should be given with afatty meal such as milk fried sauce to improve
on its absorption.
 Artesunate/mefloquine
• Available preparations: tablets 600/750mg,stick packs 50/125
• Available brands: artequin
Indications
• Un complicated malaria due to resistant p.falciparum
Contraindications
• Known hypersensitivity to either artesunate or mefloquine
• Prophylaxis against malaria
Dose: adult; 2 tablets (1 tab of artesunate 600mg and 1 tab of mefloquine
750mg) once daily for 3 consecutive days.
children: 10-20mg 1 sticks pack once a day for three days
Side effects: Abdominal pain, insomnia, fatigue, dizziness, headache, nausea
and vomiting, asthenia, diarrhoea, anorexia
 ARTESUNATE/AMODIAQUINE

Available preparations: tablets 50mg/200mg

Available brands: amonate, Coarsucam
Contraindications
• Known hypersensitivity to either artesunate or amodiaquine
• History of liver disease
• Children below 2 months of age
Side effect: abdominal cramps, drowsiness, skin itching,
diarrhoea, skin rashes, severe disturbance of liver function.
Cont’n

1st line alternative: Artesunate/Amodiaquine 50/153mg. (4mg/kg of artesunate

+10mg/kg of amodiaquine) once daily for 3 days

Dose in mg (no. of tablets)

Age
Artesunate (50mg) Amodiaquine (153mg)
Day 1 Day 2 Day 3 Day 1 Day 2 Day 3
5-11 ½ tablet ½ tablet ½ tablet ½ tablet ½ tablet ½ tablet
months
1-6 years 1 tablet 1 tablet 1 tablet 1 tablet 1 tablet 1tablet
7-13 2 tablets 2 tablet 2 tablets 2 tablets 2 tablets 2 tablets
years
>13 years 4 tablets 4 tablet 4 tablets 4 tablets 4 tablets 4 tablets
DIHYDROARTEMISININ/PIPERAQUINE (2nd line treatment)

Available preparation: tablets 40mg/320mg

Available brands: Duo-cotexin, P-Alaxin
Indication: Uncomplicated malaria
Contraindications
• Known hypersensitivity to any of the ingredients
• Pregnancy (first trimester)
Dose adults and children above 40kg
3 tablets once on day 1
3 tablets once on day 2
3 tablets once on day 3
Side effects: nausea and vomiting, pruritus, skin rash, loss of appetite, diarrhoea
Dosage
Dihydroartemesinin plus piperaquine (Duo-Cotexin) 30/320mg

Day Age (years)

6-11 years 11-16 years Adults

1 ½ tablet 2tablets 3tablets

2 ½ tablet 2tablets 3tablets

3 ½ tablet 2 tablets 3 tablets

Artemisinin/Naphthoquine
Available preparations: Tablets 125mg/50mg.
Available brand: arco
Indications
Uncomplicated malaria due to p. falciparum and p. vivax
Contraindications:
• Known hypersensitivity to any of the ingredients
• Liver impairments
• Kidney impairment
• Pregnancy
Dose
• Adults: 8 tablets single dose (equivalent to 1000mg of artemisinin+ 400mg
of Naphthoquine)
• Children:
• 7-10kg 1 tablet
• 10-15kg 2 tablets
• 15-25kg 4 tablets
• 25-35kg 6 tablets.
Side effects:
Nausea
Abdominal discomfort.
References
• Katzung,G.B (201). Basic and Clinical pharmacology 10th Ed. San
Francisco: Mc Graw hill Lange
• Muyinda.N (2011) Precise pharmacology 2nd ed. Kampala: ISBN.
9789970186006.
• Tripathi, N.D (2008). Essentials of Medical Pharmacology 6th. Ed. New
Delhi: Jaypee Brothers medical publishers (Ltd).