ANTIMALARIAL DRUGS

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 BLOOD AND TISSUE
PROTOZOA
Blood protozoa of major clinical significance include members of
genera
– Plasmodium (P. falciparum, P. ovale, P. malariae and P.
vivax)
– Trypanosoma (T. brucei and T. cruzi)
– Leishmania (L. donovani, L. tropica and L. braziliensis)
– Others
• Toxoplasma gondii
• Babesia (B. microti).

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 Plasmodiasis
 Malaria
 World’s most devastating human infection
 300-500 million cases each year
 About 3 million death each year

 In Nigeria, More than 60% GOPD visit is due to malaria

 50% of the population have at least one episode/year

 Severe negative effects on maternal health and birth outcome

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 Etiology
 The parasite is a protozoa of the genus Plasmodium

 Caused by the presence of a unicellular parasites in the RBCs

or the in the liver cells

 Has four (4) most important species namely;

 P. vivax
 P. ovale
 P. malariae
 P. falciparum

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 Transmission
 By bite of infected female Anopheles mosquito (The Vector)

 By blood transfusion
 Congenitally
 Others

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Life Cycle

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 Clinical Features
 Incubation period
 P. vivax, ovale and falciparum =10-14 days
 P. malariae = 18 days- 6 weeks

 Clinical presentation
 Varies
 Febrile paroxysms, anaemia, splenomegaly and hepatomegaly
are usually present
 Nausea, vomiting and orthostatic hypotension are common
 Herpes labialis frequently occurs in established malaria

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 P. vivax and P. ovale
 Give rise to clinically mild infection
 Fever occurs every other day when established
 Responsible for relapse

 P. malariae
 Infection is usually mild
 Run a more chronic course
 May be complicated by nephrotic syndrome
 May be fatal between ages 4-5 yrs
 Patient may develop sallow complexion, marked muscle
wasting, mild icterus and massive splenomegaly
 Growth retardation in children

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 P. falciparum
 Potentially most severe form (pernicious malaria) with high
level of parasitaemia

 Infected RBCs develop knob-like projections, facilitate

adhesion to the endothelium of blood vessels causing
vascular occlusion leading to organ damage
 Prodrome tends to be severe

 Fever follows no specific pattern

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 Classification of Antimalarials
(1) Based on Chemical Structure
 4-aminoquinoline e.g Chloroquine, Amodiaquine
 8-aminoquinoline e.g Primaquine
 Quinoline methanol e.g Mefloquine, Quinine
 Sesquiterpene lactone e.g Arthemeter
 Hydroxynaphtoquinone e.g Atovaquone
 Phenanthrene methanol e.g Halofantrine
 Folate synthesis inhibitors and folate antagonists e.g Sulfones,
Pyrimethamine, Proguanil
 Antibiotics e.g Tetracycline and Doxycycline

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(2) Based on the Stage of Life Cycle
C.
Site of action of
drugs use in casual
prophylaxis

B.
Site of action
of drugs use in
radical cure of
vivax and ovale
malaria

E A.
Site of action of drugs which Site of
prevent transmission action of
drugs use in
clinical
attacks of
malaria

D
Site of action of
drugs which
prevent
transmission
 Blood schizonticides [A]: Act on the blood forms of the parasite
and thereby terminate clinical attacks of malaria.
 Used for clinical cure (treatment) in P. malariae and falciparum
malaria.
 In P. vivax and P. ovale, they only suppress the actual attack but
relapse may occur
 Drugs in this group include: Artemisinins, Chloroquine,
Quinine, Mefloquine, Halofantrine, Pyrimethamine,
Sulfadoxine, Sulfones, Tetracyclines etc.
 Hypnozonticides [B]: Act on the hypnozoites (tissue schizonts) of
P. vivax and P. ovale in the liver that cause relapse of symptoms on
reactivation.
 Are used in combination with blood schizontocides in effecting
a radical cure in P. vivax and P. ovale infections
 Drugs in this category include primaquine and tafenoquine,
pyrimethmine also has such activity 12
 Tissue schizonticides [C]: Act on the primary tissue forms of
the plasmodia
 They block the link between pre-erythrocytic and
erythrocytic stages
 They kill the parasites (merozoites) when they emerge from
the liver
 They prevent development of malaria attacks
 Used for chemoprophylaxis (casual prophylaxis)
 Usually given in combination
 Are usually given to individual traveling to malaria
endemic zone
 Drugs used include Chloroquine, Mefloquine, Proguanil,
Pyrimethamine, Dapsone and Doxycyline
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 Gametocytocides (Gametocides) [D]: 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.
 Other agents used include pyrimethamine and proquanil
 These are rarely used for this action alone

 Sporontocides [E]: These drugs render gametocytes non-

infective by inhibiting the formation of oocyst and sporozoites
in infected mosquito and thus cut-off transmission.
 Primaquine and chloroguanide have this action
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 Chloroquine
 A synthetic 4-aminoqinoline
 Its use against P. falciparum has been compromised by drug
resistance
 It is the drug of choice in the treatment of sensitive P.
falciparum and other species of human malaria parasite

 Antimalarial action
 A very potent blood schizontocidal agents against all 4
species (if sensitive to the drug)
 Possesses moderate gametocidal activity against P. vivax,
ovale and malariae but not P falciparum
 Not active against hypnozoites and sporozoites

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 Pharmacokinetics
 Chloroquine is completely almost completely absorbed
after oral administration
 May also be given I.M or I.V or SC
 Reaches peak plasma concentration in about 3h
 Is rapidly and extensively distributed to the tissues and is
concentrated in parasitized cells
 Has a very large apparent Vd (100-1000L/kg) and is slowly
released from the issues and metabolised
 Excretion is mainly in urine (70% as unchanged)
 Elimination is slow
 Initial t1/2 is 3-5 days
 Terminal elimination t1/2 is 1-2 months

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 Mechanism of action
 Acts probably by concentrating in the parasites food
vacuole and inhibiting polymerization of free (soluble)
haem into non-toxic haemozoin
 At high concentrations, it inhibits protein, RNA and DNA
synthesis

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 Resistance
 Very common to P. falciparum
 Resistance of P. vivax is also growing in many part in the world
 Appears to result from mutations in a putative transporter,
PfCRT
 Results in enhanced efflux of the drug from the parasitic
vesicles
 Clinical Uses
 Treatment – Drug of choice in the treatment of non-falciparum
and sensitive falciparum
 Chemoprophylaxis - Chloroquine is the preferred
chemoprophylactic agent in malarious region without resistant
falciparum malaria
 Amoebic liver abscess - Used for amoebic abscess refractory
to metronidazole
 Rheumatoid arthritis - Is a disease-modifying anti-
rheumatoid drugs
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 Adverse effects
 Usually well tolerated
 Nausea, vomiting, abdominal pain dizziness, blurring of
vision, headache, urticarial symptoms
 Rare reactions include haemolysis (in G6PD-deficient
persons), impaired hearing confusion, psychosis, seizure,
agranulocytosis, exfoliative dermatitis, alopecia, bleaching
of hair, hypotension, electrocardiographic changes,
retinopathies
 Large IM of rapid IV injection of Chloroquine HCl can
result in severe hypotension and respiratory and cardiac
arrest (should be avoided)
 Considered to be safe in pregnancy

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 Contraindication and Cautions
 Chloroquine is contraindicated in patients with psoriasis or
porphyria
 Also not to be used in patient with retinal or visual field
disturbances
 Should be used with caution in patients with liver disease,
neurologic or haematologic disorders (G6PD deficiency)
 Kaolin, Ca and Mg-containing antacids should not be co-
administered with chloroquine

Defects in the Hexomonophosphate shunt leads precipitation of hemoglobin as Heinz bodies and in lysis of the
red cell membrane. 20
 Amodiaquine
 Very similar to Chloroquine
 MOA may be similar to that Chloroquine
 Enjoys wide usage due to low cost, limited toxicity and
effectiveness in chloroquine-resistant strain of Pf (in some
areas)
 Toxicity may include agranulocytosis, aplastic anaemia and
hepatotoxicity
 Recommended as part of artemisinin-based combination
therapy by WHO
 Should be avoided in chemoprophylaxis due to increased
toxicity with long–term use
 The recommended dose is 25 – 35mg/kg po over 3 days

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 Quinine
 Quinine is the chief alkaloid of cinchona bark (known as
'Fever Bark') a tree of South American origin
 Quinine is obtained entirely from the natural sources due the
difficulties in synthesizing the complex molecule.
 Quinidine is as effective as parental quinine in the treatment of
falciparum malaria
 Antimalarial action
 Rapidly acting, highly effective blood schizontocide
against the 4 human malaria parasites
 Gametocidal for P vivax and P ovale but not P falciparum.
 Not effective against hypnozoites

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 Pharmacokinetics
 Rapid absorption after oral administration
 Peak plasma conc. achieved in 1-3 h after oral
administration
 Wide distribution in body tissue
 Pharmacokinetics varies among populations
 In acute malaria, the volume of distribution of quinine
contracts and clearance is reduced
 Toxicity is not increased because of increased protein
binding
 Elimination t1/2 increases in proportion to the severity of the
illness. (18h in severe malaria and 11h in healthy control)
 Quinidine has shorter than quinine
 Quinine is primarily metabolised in liver and excreted in
urine 23
 Mechanism of Action
 Unknown, may involve inhibition of heme polymerization
 Resistance
 is growing and common in certain areas but still provides at
least a partial therapeutic effect in most patients
 Adverse effects
 Cinchonism - a constellation of symptoms
 Hypersensitivity reactions
 Haematological abnomalities
 Hypoglycemia-due to insulin release
 Stimulation of uterine contraction especially in 3rd trimester
 Thrombophlebitis - IV infusion
 Severe hypotension - too rapid IV infusion
 ECG abnormalities (QT prolongation)
 Blackwater fever - hypersensitivity reaction to quinine
 Marked hemolysis and hemoglobinuria
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 Contraindications and Cautions
 Discontinue if signs of severe cinchonism, haemolysis and
hypersensitivity reaction occur
 Avoid (if possible) in patients with visual and auditory
problems
 Should not be given with mefloquine
 Absorption is reduced by Aluminuim-containing antacids
 Quinine can raise plasma level of warfarin and digoxin
 Dosage reduction necessary in renal insufficiency

 Clinical Uses
 Parenteral treatment of severe faciparum malaria
 Oral treatment of uncomplicated falciparum malaria
 Malarial chemoprophylaxis
 Babesiosis

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 Availability
 as tablets and capsules (containing 300 or 600 mg of the
base) and injections, containing 300mg /ml.
 Dose
 Oral- 10 mg/kg 8 hourly for 4 days and 5 mg/kg 8 hourly
for 3 days.
 Intra venous: 20 mg of salt/kg in 10 ml/kg isotonic saline
or 5% dextrose over 4 hours, then 10 mg of salt/kg in saline
or dextrose over 4 hours, every 8 hours until patient is able
to take orally or for 5-7 days.
 Intra muscular: 20 mg/kg stat, followed by 10 mg/kg 8
hourly by deep intra muscular injections for 5-7 days

 Quinidine: Dose is 10 mg of base / kg by infusion over 1-2

hours, followed by 0.02 mg/kg/min with ECG monitoring

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 Mefloquine
 A 4-quinoline methanol chemically related to quinine

 Anti malarial activity

 Has schinzontocidal activity against P falciparum
(including the chloroquine resistant types) and P vivax.
 Has no effect on gametocytes and hypnozoites

 Pharmacokinetics
 Mefloquine is available for oral administration
 It is absorbed rapidly and reaches peak plasma
concentration in about 18h
 It is extensively bound to plasma proteins.
 Elimination half-life is about 2-3 weeks-weekly dosing
 It is mainly excreted in the faeces. 27
 Resistance
 Has been reported for many areas
 Associated with resistance to quinine and halofantrine but
not with resistance to chloroquine

 Clinical Uses
 Chemoprophylaxis
 Treatment of uncomplicated malaria

 Mechanism of Action
 Mefloquine has been found to produce swelling of the P.
falciparum food vacuoles.
 It may act by forming toxic complexes with free heme that
damage membranes and interact with other plasmodial
components.
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 Adverse Effects
 GI disturbance
 Transient CNS toxicity - giddiness, confusion, dysphoria and
insomnia
 Alteration of cardiac conduction, arrhythmia and bradycardia
 Contraindications and Cautions
 Prophylaxis in pregnancy, particularly during the first
trimester.
 Patients with history of seizures, severe neuropsychiatric
disturbances, or adverse reactions to chloroquine and quinine.
 Mefloquine is reported to increase the risk of seizures in
patients taking valproate.
 May compromise adequate immunisation by live typhoid
vaccine.
 Patients taking mefloquine should refrain from driving or
operating machinery.
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 Availability
 It is available as 250 mg tablets.
 Dose
 15 mg/kg in a single dose.
 If the dose exceeds 1000 mg, the second dose can be given
after 4-8 hours to minimize gastric irritation.
 Total dose should not exceed 1500 mg.

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 Primaquine
 Other slowly metabolised analogues are etaquine and
tafenoquine
 Primaquine is the drug of choice for the eradication of
dormant liver forms of P vivax and P ovale

 Mechanism of action
 Not well understood.
 It may be acting by generating reactive oxygen species
or by interfering with the electron transport in the
parasite

 Resistance
 Some resistance strains of P vivax have been found
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 Pharmacokinetics
 Well absorbed after oral administration and rapidly
metabolised.
 Peak plasma level is reached in 1-2h
 Widely distributed in the body but only small amount is
bound
 Its elimination half-life is about 6 hours.

 Antimalarial activity
 Active against hepatic stage of all human malarial parasites
 Only available agent active against the hypnozoites of P
vivax and P ovale
 Gametocidal against the four malarial specie
 Weakly blood schizontocidal

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 Clinical Uses
 Radical cure of acute vivax and ovale malaria
 Terminal prophylaxis of vivax and ovale malaria
 Chemoprophylaxis of malaria
 Pneumocystis jiroveci infection
 Adverse Effects
 Well tolerated in therapeutic doses
 Occasional epigastric distress and abdominal cramps - in
large doses
 Hemolysis and methemoglobinemia (manifested as
cyanosis) in patient with G6PD deficiency or other
hereditory metabolic disorders.
 Severe methemoglobinemia rarely in patients with
deficiency of NADH methemoglobin reductase.
 Granulocytopenia and agranulocytosis are rare
complications
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 Contraindications and Cautions
 In patients with severe systemic illness that is likely to
cause leukopenia
 Not to be used with other myelosuppressive drugs
 Concurrent administration of primaquine can increase
blood concentrations of mefloquine
 Patients should be tested for G6PD deficiency before
primaquine is prescribed.
 Simultaneous use of quinine or mefloquine is
contraindicated
 Avoid in pregnancy-fetus is relatively G6PD-deficient
 Availability
 Primaquine is available as tablets containing 2.5, 7.5 and
15 mg of the salt

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 Halofantrine
 Halofantrine is related to the quinine and lumefantrine
 The mechanism of action of halofantrine is unknown.
 Pharmacokinetics
 The absorption of halofantrine is erratic, but is increased
when taken with fatty food. Because of fears of toxicity due
to increased halofantrine blood levels, halofantrine should
be taken on an empty stomach.
 Plasma levels peak at 16 hours and the half-life of the drug
is about 4 days.
 Uses
 Halofantrine is only used to treat malaria. It is not used to
prevent malaria (prophylaxis) because of the risk of
toxicity and unreliable absorption.
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 Adverse effects
 Halofantrine can cause abdominal pain, diarrhoea,
vomiting, rash, headache, itching and elevated liver
enzymes.
 It can be associated with cardiotoxiciy; the most dangerous
side effect is cardiac arrhythmias by causing significant QT
prolongation and this effect is seen even at standard doses.
 The drug should therefore not be given to patients with
cardiac conduction defects and should not be combined
with mefloquine
 Dosing
 Adult dose: Three doses of 500 mg six hours apart.
 Halofantrine should be taken on an empty stomach

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 Lumefantrine
 Structurally related to quinine.
 Effective against the erythrocytic stage of all four human
malarial parasites
 Its mechanism of action may involve forming toxic
complexes with ferritoporphyrin IX that damage the
membrane of the parasite.
 Lumefantrine is an aryl alcohol related to halofantrine
 Available in a fixed combination with arthemeter as
arthemeter-lumefantrine (coartemTM)
 Available only as a tablet

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 Pharmacokinetics
 Oral absorption is variable and enhanced with food
 The peak plasma concentration is achieved in 4-16 h after
the oral dose.
 The elimination half-life is 1-3 days for the parent drug
and 3-7 days for the active metabolite.
 Elimination is mainly in feaces

 Clinical Uses
 Treatment of chloroquine resistant and multi-drug resistant,
uncomplicated P. falciparum malaria.
 The clinical response to treatment may be unpredictable
due to the variable drug absorption.
 Not to be used in chemoprophylaxis

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 Adverse effects
 GI disturbance (abdominal pain, vomiting, diarrhoea)
 Prolongation of QT interval and arrhythmias that could be
fatal.
 Contraindication and caution
 In patients with prolonged QT interval (congenital,
electrolyte disorders, myocardial disease).
 In pregnancy and lactation, infants, and patients who have
received mefloquine in the preceding 3 weeks
 Dose
 For adults, three tablets of 500 mg each at 6 h interval
 Children, three doses of 8 mg/kg of the salt at 6h interval
 Treatment should be repeated after 7 days.

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 Atovaquone
 A synthetic hydroxynaphthoquinone

 It has a highly lipophilic molecule that supposedly

interferes with the mitochondrial electron transport
(thereby ATP and pyrimidine biosynthesis)

 it is found to target cytochrome bc1 complex and

disrupt the membrane potential in plasmodia

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 Pharmacokinetics
 Bio-availability is poor and may be increased by a fatty
meal
 Heavily bound to plasma protein
 it undergoes entero-hepatic circulation.
 It has a long half-life of 2-3 days
 Elimination (unchanged) in feaces

 Clinical Uses
 Treatment and prophylaxis of malaria-In combination with
proguanil (as malarone)
 P jiroveci pneumonia

 Adverse effects
 May cause rash, fever, vomiting, diarrhoea and headache.
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 Antifolate drugs
 Classified into type 1 and 2
 Type 1: folate synthesis inhibitors e.g sulphonamides and the
sulphones
 Type 2: folate antagonists e.g pyrimethamine and proguanil
 Combination of types 1 and 2 drugs results in sequential
blockade affecting the same pathways at different points
 The biosynthesis of purine and pyrimidine, which are so
essential for DNA synthesis and cell multiplication is inhibited

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 P-Aminobenzoic acid

Dihydopteroate Sulphonamides and

synthase sulphones
(competes with
PABA)
Dihydrofolate
Dihydofolate Trimethoprim,
reductase pyrimethamine
and proguanil

Tetrahydrofolate

Purines

DNA

Actions of sulfonamides, sulfones, pyrimethamine and proguanil 43

 Pyrimethamine
 A 2,4, diaminopyrimidine structurally similar to trimethoprim
 Inhibits nuclear division at the time of schizont formation in
erythrocytes and liver.
 Pharmacokinetics
 Slow but complete absorption after oral administration
 Elimination is slow with a plasma half-life of about 80-95
hours.
 Suppressive drug levels may be found in the plasma for up
to 2 weeks.
 The drug is excreted in breast milk.
 Toxicity:
 Occasional skin rashes and depression of hematopoiesis.
 Excessive doses can produce megaloblastic anemia.

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 Chloroguanide (proguanil)
 It is a biguanide derivative
 Uses
 It has causal prophylactic and suppressive activity against
P. falciparum and cures the acute infection.
 It is also effective in suppressing the clinical attacks of
vivax malaria.
 Chloroguanide along with chloroquine is used as
prophylaxis effective against P. falciparum malaria.=
 Pharmacokinetics
 Chloroguanide is slowly but adequately absorbed from the
gastrointestinal tract.
 Peak plasma levels are attained within 5 hours and
elimination half-time is about 16-20 hours.
 Chloroguanide is available as tablets, each containing 100
mg of the drug. The dose for prophylaxis is 100-200 mg
daily.
 At the prophylactic doses, it produces occasional nausea and
diarrhoea. 45
 Sulphonamides
 Absorption from the gut is rapid
 Are bound to plasma proteins.
 Metabolism is in the liver and excretion in the urine.
 They pass through the placenta freely.
 Sulfadoxine is a long acting sulfonamide with a half-life of 7-9
days.
 Sulfonamides can cause numerous adverse effects.

 Contraindications and caution

 The drug is contraindicated in patients with known
hypersensitivity to sulfa drugs
 Infants below 2 months of age
 Patients with advanced renal disease
 First and last trimesters of pregnancy.

46
 IPT in pregnancy
 Intermittent preventive therapy (IPT) is recommended
 Sulphadoxime-pyrimethamine (SP) is used
 All pregnant women should receive 2 doses of IPT
 HIV positive pregnant women should receive at least 3 doses
of IPT
 Best given when the fetal growth velocity is at its highest.
 Contraindications of IPT
 Before 16 weeks of pregnancy
 SP doses in the last 4 weeks
 Allergies to sulfa drugs
 Currently on sulfa drugs.

47
 Artemisia annua
 Also known as sweet wormwood “take a handful of
sweet wormwood,
 Artemisia means bitter soak it in a sheng
(liter) of water, and
 Origin from northern parts of China squeeze out the juice
and drink it all”
 Artemisinin present in leaves and
flower of the plant in 0.01-0.08% dry
weight
 Used in Traditional Chinese Medicine
for more than 2000 years
 Earliest record found in the “Fifty Two Li Shizhen, a great
Chinese herbalist
Prescription”
 First antimalarial application described
in “The Handbook of Prescriptions for
Emergencies” in the 4th century by a
Chinese alchemist 48
 Artemisinin
 Qinghaosu ("ching-how-soo")
 One of the most novel discoveries in recent medicinal plant
research
 Orally administered
 Not very soluble either in water or oil.
 Has short elimination half life
 These led to the search for the derivatives that had
improved pharmacological properties as well as better
antimalarial activity
 Converted to dihydroartemisinin, which is a potent
antimalarial compound
 Available for oral and rectal use in several countries.

49
 Artemether
 Methyl ether of dihydroartemisinin
 Superior to intravenous quinine
 Survival and parasite clearance
 Available as tablets, capsules and as IM injectable form
 Available as 40mg capsules and 80mg/ml ampoule
 Arteether
 Ethyl ether of dihydroartemisinin
 Therapeutically equivalent to quinine in cerebral malaria
 Available as  arteether and / arteether
 A longer t1/2 and more lipophilic properties than artemether
favouring accumulation in brain tissue and thus the
treatment of cerebral malaria were regarded as advantages
over the other compounds.
 Available as 150mg per 2ml ampoule
50
 Artesunate
 Water soluble hemisuccinate derivative
 Used for oral, rectal, intravenous and intramuscular
administration.
 Available as 50mg tablets and 60mg/ml injection

 Antimalarial activity of Artemisinins, (Artemisinin,

Artemether, Arteether and Atesunate)
 Rapidly acting blood schizontocides against 4 human
plasmodial species
 Act also on the gametocytes
 No effect on hepatic stage

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 Mechanism of Action
 Heme/iron mediates
breakage of endoperoxide
bridge
 Artemisinin-derived free
radicals bind to protein Artemisinin

through alkylation
 May inhibit P falciparum
encoded sarcoplasmic
endoplasmic reticulum Conventional
Treatment
calcium ATPase

Artemisinin
52
 Pharmacokinetics
 Rapid absorption after oral administration
 Peak plasma conc. Reached in 1-2h
 T1/2 is short (45 min for artesunate, 4h for artemisinin and
4-11h for artemether
 Rapidly metabolised to active metabolite,
dihydroartemisinin
 Rapidly cleared, predominiantly through the bile

53
 Adverse Effects
 Very few adverse reactions
 Common side effects include - Nausea ;Vomiting;
diarrhoea; Anorexia; dizziness
 Irreversible neurotoxicity observed in animals (at high
doses)
 Very limited data on the use of artemisinin group in
pregnant women.
 Artemisinin and derivatives should be avoided during first
trimester of pregnancy, but in case of severe malaria the
risks have to be balanced against the benefits.

54
 Clinical Uses
 Treatment of uncomplicated P falciparum malaria -
Combination is preferred as standard treatment : Artemether
in combination with lumefantrine, Artesunate in combination
with Mefloquine / Amodiaquine / Sulfadoxime &
Pyrimethamine, Dihydroartemisinins with Piperaquine
 Treatment of complicated/multidrug resistant P falciparum
malaria - I/V Artemether or I/V Artesunate; Artemether has
efficacy like Quinine & I/V Artisunate is even superior
 Not used for chemoprophylaxis due to short T1/2

 Availability
 Artemether (injection 80 mg/1 ml; capsules 40mg)
 Arteether (injection 150 mg/2 ml)
 Artesunate (powder for injection; tablets 50 mg)

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 Doses
 Artemether: 3.2 mg/kg intra muscularly as a loading dose,
followed by 1.6 mg/kg daily until oral therapy or a
maximum of 7 days.

 Arteether: 3 mg/kg once a day for 3 days, as deep intra

muscular injection.

 Artesunate: Oral- 5 mg/kg on the first day followed by 2.5

mg/kg on the second and third days with mefloquine 15
mg/kg in a single dose on the second day. Oral artesunate is
not recommended in pregnancy.

 Parenteral- Loading dose of 2.4 mg/kg followed by 1mg/kg

after 4 hours and 24 hours; thereafter, 1.2 mg/kg daily for
maximum of 7 days. For children, the recommended dose
is 1.2 mg/kg/day for 5-7 days.

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 Combination Therapy
 Use of artemisinin-based combined therapies would help
delay antimalarial drug resistance

 Some recommended artemisinin combination therapy

 Artesunate-amodiaquine
 Artesunate-mefloquine
 Artesunate-sulfadoxine/pyrimethamine
 Artemether-lumefantrine

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58
 Tetracyclines
 Use in malaria: These anti microbials are useful in the
treatment of drug resistant P. falciparum malaria.

 They act relatively slowly and hence should always be

combined with a faster acting drug like quinine.

 They are contraindicated in children below the age of 8 years

and in pregnant women because of their adverse effects on
bones and teeth.

 Both tetracycline and doxycycline are equally effective.

 Tetracycline is given at a dose of 250 mg every 6 hours for 7-
10 days.

 Dose of doxycycline is 100 mg twice daily for 7-10 days.

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 Other antimalarials
 Clindamycin
 Azithromycin
 Fluoroquinolones (norfloxacin, ciprofloxacin)
 Pyronaridine
 Piperaquine

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