This document provides information on antimalarial pharmacology. It discusses the different Plasmodium species that cause malaria, the life cycle of the malaria parasite, and classification of antimalarial drugs. It provides treatment guidelines for both uncomplicated and severe malaria caused by P. vivax, P. ovale, P. malariae, and P. falciparum. First-line treatments include chloroquine, primaquine, quinine, and various artemisinin-based combination therapies. Adverse effects and contraindications of the different antimalarial drugs are also summarized.

1. Antimalarials Pharmacology
Dr.Himanshu Agrawal ,DCH.M.D

2. competency

3. INTRODUCTION
mala (bad)aria(air)
• These are drugs used for prophylaxis , treatment
and prevention of relapses of malaria.
• Malaria, caused by 4 species of the protozoa
parasite Plasmodium, is endemic in most parts of
India and other tropical countries.
• The NMEP was renamed National Antimalaria
Programme (NAMP), which now is :
National vector borne diseases control programme
(NVBDCP) with a wider disease coverage.

4. Malaria occurs throughout most of the tropical regions of the
world, with Plasmodium falciparum causing the largest burden
of disease, followed by Plasmodium vivax .
P. falciparum predominates in sub-Saharan Africa, New Guinea, and
Hispaniola (Haiti and the Dominican Republic)
P. vivax is much more common in the Americas and the western Pacific.
The prevalence of these two species was approximately equal in the Indian
subcontinent, eastern Asia, and Oceania in the late 1900s but P.
falciparum is now responsible for two-thirds of cases.
Plasmodium malariae is uncommon and is found in most endemic
areas, especially in sub-Saharan Africa.
Plasmodium ovale, less common, is relatively unusual outside of Africa
and comprises <1 percent of isolates.
Plasmodium knowlesi, similar morphologically to P. malariae, has been
identified by molecular methods in patients in Malaysia, the Philippines,
Thailand, and Myanmar, this species has not yet been proven to be
transmitted from humans to mosquitoes (ie, a monkey reservoir may be
required to infect mosquitoes).
Plasmodium simium is a malaria species resembling P. vivax that occurs in
primates; it has been isolated from humans in Brazil

5. SPECIES Cycle Relapse MISC.
P.FACIPARUM
(Malignant
tertian)
48hrs NO CEREBRAL MALARIA/COULD
BE FATAL
P.VIVAX
(Bening tertian)
48hrs YES LOWER MORTALITY RATE
P.OVALE
Tertian
48hrs YES -
P.MALARIE
Bening quartan
72hrs YES -
P.KNOWLESI 24hrs - -

7. Phases of malarial life cycle

8. • Tissue schizontocides
• Blood schizontocides
• Gametocides

9. LIFE CYCLE

11. OBJECTIVES

12. Classification of drugs

14. Treatment of uncomplicated malaria

15. Vivax (also ovale, malariae) malaria
Chloroquine 600 mg (10 mg/kg) stat
Chloroquine 300 mg (5 mg/kg) after 8 hours
Chloroquine 300 mg (5 mg/kg) for next 2 days
(total 25 mg/kg over 3 days)
+
Primaquine 15 mg (0.25 mg/kg) daily x 14
days

16. Other regimen
Chloroquine 600 mg (10 mg/kg) stat
Chloroquine 300 mg ( 5 mg/kg ) after 6 hours
Chloroquine 300 mg ( 5 mg/kg ) for next 2
days (total 25 mg/kg over 3 days)
+
Primaquine 15 mg (0.25 mg/kg) daily x 14
days

18. In occasional case of chloroquine resistance
Quinine 600 mg (10 mg/kg) 8 hourly x
7days+Doxycycline 100 mg daily x 7 days
or
Clindamycin 600 mg 12 hourly x 7 days +
Primaquine 15 mg (0.25 mg/kg) daily x 14 days
or
Artemisinin-based combination therapy (except
sulfa-pyrimethamine based ACT) + Primaquine 15
mg (0.25 mg/kg) daily x 14 days

21. Chloroquine-sensitive falciparum malaria
Chloroquine 600 mg (10mg/kg)
Chloroquine 300 mg (5 mg/kg) after 8 hours
Chloroquine 300 mg (5 mg/kg) for next 2 days
(total 25 mg/kg over 3 days)
+
Primaquine 45 mg (0.75 mg/kg) single dose
(as gametocidal) on day 2.

22. Chloroquine-resistant falciparum malaria
1. Artesunate 100 mg BD (4 mg/kg/day) x 3 days
+
Mefloquine 750 mg (15 mg/kg) on 2nd day
and 500 mg (10 mg/kg) on 3rd day.
or
2. Artemether 80 mg + Lumefantrine 480 mg
twice daily x 3 days
child 25-35 kg BW ¾ dose;
15-25 kg BW ½ dose;
5-15 kg BW ¼ dose)

23. 3.* Artesunate 100 mg BD (4 mg/kg/day) x 3 days
+
Sulfadoxine 1500 mg (25 mg/kg) + Pyrimethamine
75 mg (1.25 mg/kg) single dose
or
4. Arterolane (as maleate) 150 mg+ Piperaquine 750
mg once daily x 3 days
or
5.sQuinine 600 mg (10 mg/kg) 8 hourly x 7 days
+ Doxycycline 100 mg daily x 7 days / Clindamycin
600 12 hourly x 7 days

24. *First line ACT under NVBDCP, except in
Northeastern states where FDC of artemether-
lumefantrine is used.
' In India (including under NVBOCP) all P.f. cases,
irrespective of CQ-resistance status, are treated
with artemisinin based combination therapy (ACT)
+ Primaquine (0.75 mg/kg) single dose on the 2nd
day (as gametocidal).
s Falciparum malaria during 1st trimester of
pregnancy should be treated with a 7 day course
of quinine+ clindamycin.

25. Treatment of severe and complicated
falciparum malaria

26. Artesunate: 2.4 mg/kg
i.v. or i.m.
2.4 mg/kg after 12 and
24 hours,
once daily for 7 days.
Switchover to 3 day oral
ACT in between
whenever the patient
can take and tolerate
oral medication.

27. • 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 in between whenever
the patient is able to take
oral medication.
• C/I in G6PD defeciency
• Adult dose 80mgq12hrly IM
D1 f/b 80mg OD for 4 days

28. Quinine diHCl. 20 mg/kg
(loading dose) diluted in 10
ml/kg 5% dextrose or
dextrose-saline and infused
i.v. over 4 hours
10 mg/kg (maintenance
dose) i.v. infusion over 4
hours (in adul1s) or 2 hours
(in children) every 8 hours,
until patient can swallow.
Switchover to oral quinine
10 mg/kg 8 hourly to
complete the 7 day course.

29. CHLOROQUINE
It is a rapidly acting erythrocytic schizontocide
against all species of plasmodia (except CQ
resistant P falciparum).
It Controls most clinical attacks in 1- 2 days
with disappearance of parasites from
peripheral blood in 1- 3 days.

30. 1. Therapeutic plasma concentrations are in the
range of 15- 30 ng/ml.
2. It has no effect on primary and secondary
hepatic stages of the parasite
3. It does not prevent relapses in vivax and
ovale malaria.
4. CQ has no clinically useful gametocidal
activity.

31. MECHANISM OF ACTION
• The mechanism of action of CQ is not exactly
known.
• Plasmodia derive nutrition by digesting
haemoglo bin in their acidic vacuoles.
• CQ is actively concentrated by sensitive
intraerythrocytic plasmodia.
• Higher concentraation is found in infected RBCs
than in noninfected ones.

32. • By accumulating in the acidic vacuoles of the parasite
and because of its weakly basic nature, it raises the
vacuolar pH and thereby interferes with degradation
of haemoglobin by parasitic lysosomes.
• Polymerization of toxic haeme generated from
digestion of haemoglobin to nontoxic parasite
pigment haemozoin is inhibited by the formation of
CQ-haeme complex.
• Haeme itself or its complex with CQ then damages
the plasmodial membranes.
• Clumping of pigment and changes in parasite
membranes follow.
• Other related antimalarials like quinine,mefloquine,
lumefantrine, pyronaridine appear to act in an
analogous manner.

34. Other actions of CQ
Chloroquine is active against E.histolytica and
Giardia lamblia as well.
lt has :
1. Anti inflammatory
2. Local irritant
3. Local anaesthetic (on injection),
4. Weak smooth muscle relaxant,
5. Antihistaminic
6. Antiarrhythmic properties.

35. Pharmacokinetics
• Oral absorption of CQ is excellent. About 50% gets
bound in the plasma.
• It has high affinity for melanin and nuclear chromatin
• Gets tightly bound to these tissue constituents and is
concentrated in liver, spleen, kidney, lungs (several
hundred-fold), skin, leucocytes and some other tissues.
• Its selective accumulation in retina is responsible for
the ocular toxicity seen with prolonged use.
• Chloroquine is partly metabolized by liver and slowly
excreted in urine.
• The early plasma t½ varies from 3- 10 days.
• Because of tight tissue binding, small amounts persist in
the body with a terminal t½ of 1- 2 months.

36. Adverse effects
Toxicity of CQ is low,
Side effects like :
• Nausea,vomiting,anorexia,
• Uncontrollable itching,
• Epigastric pain, uneasiness,
• Difficulty in accommodation
• Headache are frequent and quite unpleasant.
Weekly suppressive doses have been safely given for 3 years.
• Prolonged use of high doses (as needed for rheumatoid
arthritis, DLE, etc.) may cause loss of vision due to retinal
damage.
• Corneal deposits may also occur andaffect vision, but arc
reversible on discontinuation.

37. Onlong-term use:
1. Loss of hearing,
2. rashes,
3. photoallergy,
4. mental disturbances,
5. myopathy and
6. graying of hair can occur
• CQ can be used for treatment of malaria during pregnancy,
no abortifacient or teratogenic effects have been reported.
Caution is to be exercised in the presence of liver damage,
severe g.i.t,neurological, retinal and haematological diseases.
Attacks of seizures,porphyria and psoriasis may be precipitated.
CQ should not be coadministered with mefloquine,amiodarone
and other antiarrhythmics.

38. USES
• Malaria
• Extraintestinal amoebiasis
• Rheumatoid arthritis
• DLE
• Lepra reaction
• Photogenic reaction
• Infectious mononucleosis

39. ACT(artemisin combination therapy)
• ACT is WHO recommended treatment for all
confirmed cases of falciparum malaria.
• They act quickly to produce better clinical
response and parasitic clearance
• They have short half life which is compensated
by adding other drug
• For uncomplcated oral drugs are used while
for complicated parentral drugs are used

40. ARTEMISIN COMBINATION THERAPY

41. ACT
1. Artemether +lumefantrine
2. Artesunate+mefloquine
3. Artesunate+amodiaquine
4. Artesunate+sulfadoxine+pyramethamine
5. Dihydroartemisin+piperaquine
6. Arteriolane+piperaquine

42. 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
componentsprevent development of
resistance to each other).
• Good tolerability profile.

43. PRIMAQUINE

44. PRIMAQUINE & HEMOLYSIS
• Dose related
hemolysis,methhaemoglob
inemia,tachypnoea,cyanosi
s.
• Oxidant property
• G6PD def are highly
suspectible
• Should not be given during
pregnancy (fetus is G-6PD)

45. • Radical cure of relapsing
malaria(vivax,ovale)

46. Salient points
• Single dose antirelapse
drug for vivax malaria.
• Tafenoquine t1/2-14-19
days,PQ-6-8hrs
• Side effect profile
similar to PQ

47. Salient points
• Oldest antimalarial still in
use
• D isomer QUINIDINE is
used as antiarrythmic
• Erythrocytic schizonticidal
• Quinine may not prevent
recrudescence.

48. No effect on preerythrocytic
stage.
Other actions:
1. Local irritant and
anaesthetic
2. Weak analgesic &
antipyretic
3. Rapid injection may cause
fall in BP and CVS collapse
4. Stimulate myometrium and
can cause abortion in early
pregnancy.
5. Rapid i.v injection causes
HYPOGLYCEMIA due to
release of insulin from
pancreas.

49. CINCHONISM

50. CINCHONISM
A large single dose or higher therapeutic doses taken
for a few days produce a syndrome called
'cinchonism'.
It consists of:
1. Ringing in ears,
2. Nausea,
3. Vomiting (due to both gastric irritation and CTZ stimulation),
4. Headache,
5. Mental confusion,
6. Vertigo,
7. Difficulty in hearing and visual defects {due to direct neurotoxicity as
well as constriction of retinal and auditory vessels).
8. Diarrhoea,
9. flushing and marked perspiration may also appear.
The syndrome subsides completely if the drug is stopped.

51. Malaria in pregnancy

54. • P.vivax malaria: chloroquine
• P.falciparum malaria
– UNCOMPLICATED
• 1ST TRIMESTER: QUNINE+CLINDAMYCIN
• 2nd & 3rd trimester-ACT(artemether+lumifantrine
COMPLICATED: ACT

56. THANKS