an interesting and exhaustive presentation for medical undergraduates and postgraduates on antimalarial drugs... and also helpful to physicians for learning new concepts like ACT, for treating resistant malaria and knowing important ADR of antimalarial drugs..

7. ANTIMALARIALANTIMALARIAL
DRUGSDRUGS
Prof. Dr. V. SATHYA NARAYANAN M.D

9. MALARIAMALARIA
Caused by protozoa - plasmodium
species
Endemic in India–12-15 million cases/year
Cinchona bark – quinine – till 1942
Chloroquine – 1934 - Germans
Primaquine – 1920s
 pyrimethamine - 1951

11. ANTIMALARIAL DRUGSANTIMALARIAL DRUGS
Drugs used for
prophylaxis,
treatment and
 prevention of relapses
of malaria

15. CLASSIFICATION OFCLASSIFICATION OF
ANTIMALARIAL DRUGSANTIMALARIAL DRUGS
Cinchona alkaloid - Quinine
4 Aminoquinolines – chloroquine,
amodiaquine
8 Aminoquinolines – Primaquine,
Bulaquine
Quinoline-methanol – Mefloquine
Biguanides – proguanil
Diamino pyrimidines - pyrimethamine

16. CLASSIFICATIONCLASSIFICATION
Sulfonamides – sulfadoxine
Sulfone - dapsone
Tetracyclines – Tetracycline,doxycycline
Sesquiterpine lactones – Artesunate,
Artemether, Arteether
Amino alcohols – Halofantrine
Mannich base - pyronaridine
Naphthoquinone - Atovaquone

20. CHLOROQUINECHLOROQUINE
Rapidly acting erythrocytic schizontocide
No effect on other phases
Effective on all forms of plasmodia
Rapidly acting
M.O.A enters RBC  Concentrated inside
plasmodial acidic food vacuole  inhibit haeme
polymerase  accumulation of toxic haeme 
parasite membrane lysis  death
Also prevents digestion of hemoglobin

23. CHLOROQUINE RESISTANCECHLOROQUINE RESISTANCE
P. falciparum developed Resistance
Modulated by p-glycoprotein pumps
out chloroquine out of food vacuole
– may cause serious infection
Verapamil – restore sensitivity

25. OTHER ACTIONSOTHER ACTIONS
Active against E. histolytica,
 Giardia lamblia
Anti inflammatory

30. PKPK
Excellent oral absorption
Given parenterally attains toxic
concentration In very short time  used
only when definitely needed
Concentrated in liver, kidneys, lungs,
spleen, retina
t1/2 – 6-7 days, high Vd
Tight tissue binding – persists in the body
for months - CUMULATIVE

32. ADRADR
Poorly tolerated
Intravenous – hypotension , arrhythmias,
respiratory arrest, cardiac arrest
Nausea, vomiting quite severe in some
Pruritus, headache, visual disturbances, insomnia,
rashes, precipitates porphyria
High doses  peripheral neuropathy, hearing loss,
convulsions, mental disturbances
Long term tt  Retinal damage, corneal deposits,
Graying of hair, myopathy
NOT TERATOGENIC

41. PRECAUTIONSPRECAUTIONS
Liver damage
GI, Neurological, hematological diseases
Retinal diseases
Avoid parenteral administration ( if
required give slow infusion )

43. DRUG INTERACTIONSDRUG INTERACTIONS
Mefloquine  increased seizures,
therapeutic failure
Halofantrine  arrhythmias

44. USESUSES
Drug of choice for treatment of all 4 types of
malaria due to sensitive strains ( 1g at 0
followed by 0.5 g at 6, 24, 48 hr)
Prophylaxis – 2 tab/ week
Extra intestinal amoebiasis
Rheumatoid arthritis, DLE
Lepra reactions
Photogenic reactions
Symptomatic relief of Infectious mononucleosis

53. AMODIAQUINEAMODIAQUINE
Same as chloroquine
Less bitter = Palatable
Used in uncomplicated falciparum malaria
Not recommended for prophylaxis( fatal
toxic hepatitis)
Similar S/E, itching less common,
neutropenia in children

56. MEFLOQUINEMEFLOQUINE
Slower acting than chloroquine
Erythrocytic schizontocide
Effective against chloroquine sensitive, resistant
malaria, MDR malaria  single dose
Resistance, cross resistance seen
Relapses occur
M.O.A probably act by inhibiting haeme polymerase
 binds with heme  complex damages plasmodial
membranes

57. PKPK
Slow , good oral absorption
Highly protein bound
Enterohepatic cycling occur
t1/2 – 20 – 30 days

58. ADRADR
GI –nausea, Vomiting, dizziness
Neuropsychiatric reactions – ataxia,
hallucinations, impaired psychomotor
skills, errors in operating machinery,
ataxia, disturbed sense of balance
Rarely Hepato, hemato, cutaneus
Teratogenic in animals

65. DRUG INTERACTIONS, C/IDRUG INTERACTIONS, C/I
QTc prolongation with quinine/
halofantrine  cardiac arrest
Arrhythmias
Epileptics
Psychiatric patients

68. USESUSES
Multi drug resistant P. falciparum malaria
– 20 mg/kg single dose
Currently in ACT
Prophylaxis of malaria among travellers
to areas of multidrug resistance (250
mg/week)

74. QUININEQUININE
Alkaloid obtained from cinchona bark
Erythrocytic schizontocide for all species
Kills vivax gametes
Cause incomplete clearance
Less effective and more toxic
Exact mechanism not known, probably as
chloroquine
Non-cumulative

76. ADRADR
I.V  Cardiac depression, hypotension,
arrhythmias, cardiac arrest
 hypoglycemia
 Cinchonism – ringing in ear, nausea, vomiting,
hearing loss, visual defects, diarrhea, marked
sweating
Convulsions,
 hypersensitivity reactions
Black water fever  Hemolytic anemia,
hemoglobinuria
Fatal dose – 2-8 grams

82. USESUSES
Orally- uncomplicated falciparum malaria
i.v – complicated falciparum /cerebral
malaria ( caution – hypoglycemia )
Nocturnal muscle cramps
Babesiosis
Myotonia congenita
Spermicidal in vaginal creams

90. PROGUANILPROGUANIL
Slow acting erythrocytic schizontocide
Cyclized  cycloguanil  inhibits plasmodial DHF
reductase
Resistance develops rapidly
Non-cumulative
ADR- stomatitis, rash, N,V,D, transient loss of
hair
CAUTION – poor renal function
Prophylaxis of malaria with chloroquine
Along with atovaquone for treating MDR
falsiparum malaria
Safe in pregnancy

94. PYRIMETHAMINEPYRIMETHAMINE
Slow acting erythrocytic Schizontocide
Inhibit DHF reductase
Resistance rapidly develops
ADR- relatively safe, rash, nausea,
megaloblastic anemia in high doses
Caution –give folic acid during pregnancy
Use –only in combination for falciparum
malaria

96. PYRIMETHAMINE- SULFA/PYRIMETHAMINE- SULFA/
DAPSONEDAPSONE
Synergistic due to sequential blockade
Clinical curative for falciparum
ADR – serious cutaneous reactions
C/I –pregnancy, infants, sulfa allergy
Uses – single dose therapy in chloroquine
resistant malaria (Pyri 25 mg+ sulfa 500 mg or
dapsone 100 mg) , toxoplasmosis ( 1st
choice ),
pneumocystosis

104. PRIMAQUINEPRIMAQUINE
Highly active against gametocytes, hypnozoites
Weak activity on erythrocytic forms
Marked effect on Primary, secondary tissue
phases
Non-cumulative
Mechanism not known
ADR – GIT, uneasiness in chest, hemolysis in G-
6-PD deficiency, methemoglobinemia
C/I – pregnancy
Use –radical cure of relapsing malaria (vivax ),
pneomocystis jiroveci infection

111. BULAQUINEBULAQUINE
Congener of primaquine
Developed in india
Similar to primaquine
Better tolerated in G-6-PD deficients
Used in relapsing malaria

115. TETRACYCLINESTETRACYCLINES
Combined with other antimalarials for
chloroquine resistant falciparum malaria
 Multi Drug Resistant malaria
 2nd
line drug for prophylaxis in travelers

119. ARTEMISININ DERIVTIVESARTEMISININ DERIVTIVES
Derivative of Artemisia annua ( Quinghaosu)
Effective on falciparum resistant to all drugs
Rapidly acting schizontocide with short
duration of action
Do not kill hypnozoites
Arteether – developed in India, for institutional
use only
M.O.A – interact with heme  release free
radical species  binds to plasmodial
membrane protein  lysis

122. ARTEMISININ DERIVTIVESARTEMISININ DERIVTIVES
PK – artesunate (oral, IM, IV, rectal ), artemether
( oral, IM, rectal )  prodrugs
Arteether – longer acting, IM
ADR – GI effects, itching, fever, ST changes, Q-T
prolongation arrhythmias  close monitoring
required
Bone marrow toxicity – rare, reversible
D/I – with astemizole, terfenadine, TCAs  risk of
arrhythmias
Use cautiously in pregnancy
Use – restricted use in severe forms of malaria,
Chloroquine/MDR falciparum malaria

129. ADVANTAGES OF I.VADVANTAGES OF I.V
ARTESUNATEARTESUNATE
Faster parasite clearance
Safer
Better tolerated
Simpler dosing shedule
Higher efficacy
Lower mortality

134. HALOFANTRINEHALOFANTRINE
Activity comparable to mefloquine
t1/2 – 1 day
ADR – GI effects, itching, rash, elevated
liver enzymes, prolongation of QTc
interval
C/I - pregnancy
Not approved in India
Use –alternative in MR falciparum
malaria ( 1500 mg in 3 divided doses )

141. ATOVAQUONEATOVAQUONE
Rapidly acting schizontocide
M.O.A – collapses mitochondrial
membranes, interferes with ATP
production
Uses- chloroquine resistant malaria, 2nd
line drug in toxoplasmosis, Pneumocystis
carinii in AIDS
ADR – headache , rash, fever, vomiting,
diarrhoea
C/I - pregnancy

150. OBJECTIVES OF USEOBJECTIVES OF USE
Prevent, treat clinical attack
Complete eradication of the parasite
from the patient
Reduce human reservoir of infection

154. ANTIMALARIALSANTIMALARIALS
Erythrocytic schizontocides
Tissue schizontocides
gametocides

157. TREATMENT OF MALARIATREATMENT OF MALARIA
CAUSAL PROPHYLAXIS – pre
erythrocytic phase in liver is the target –
PROGUANIL, PRIMAQUINE
SUPPRESSIVE PROPHYLAXIS – Suppress
erythrocytic phase- CHLOROQUINE,
PROGUANIL, MEFLOQUINE,
DOXYCYCLINE

158. TREATMENT OF MALARIATREATMENT OF MALARIA
CLINICAL CURE –erythrocytic schizontocide –
Fast acting -CHLOROQUINE, MEFLOQUINE,
QUININE, HALOFANTRINE, ARTEMISININ-
given or combinations of slow acting drugs like
proguanil,pyrimethamine, sulfonamides
CHL .RES.MALARIA, MR FALCIPARUM –
MEFLOQUINE, QUININE, ARTESUNATE
Severe falciparum – PARENTERAL QUININE/
ARTESUNATE/ARTEMETHER/ARTEETHER

160. TREATMENT OF MALARIATREATMENT OF MALARIA
RADICAL CURE – hypnozoites/
exoerythrocytic phase – PRIMAQUINE
+CLINICAL CURATIVE
GAMETOCIDAL – elimination of
gametes – PRIMAQUINE,ARTEMISININ
– all species,
 CHLOROQUINE, QUININE - vivax

162. ARTEMISININ-BASEDARTEMISININ-BASED
COMBINATION THERAPY-ACTCOMBINATION THERAPY-ACT
Combining one of the artemisinin
compounds with another effective
erythrocytic schizontocide for
uncomplicated resistant falciparum
malaria – AS/S/P, AS/MQ, A/L
Rapid clinical, parasitological cure
Absence of resistance
Good tolerability

164. LUMEFANTRINELUMEFANTRINE
Orally active, high efficacy, long acting
erythrocytic schizontocide
Acts in the food vacuole of plasmodia to
inhibit haeme polymerization
Only ACT available as fixed dose combination
Used in multi drug resistant, mefloquine
resistant malaria
Given with food
C/I – PREGNANCY, Prolonged QTc interval

171. PREVENTION OF MALARIAPREVENTION OF MALARIA
Chloroquine, Proguanil and Maloprim
Malarone (atovaquone/proguanil )
Doxycycline

180. Prevention is better than cure

183. If you have built castles in the air, yourIf you have built castles in the air, your
work need not be lost; that is where theywork need not be lost; that is where they
should be. Now put foundations undershould be. Now put foundations under
them.them.
Henry David ThoreauHenry David Thoreau

184. THANK YOU…THANK YOU…