These slides explain malaria, classification of anti-malarial drugs, MOA, SAR, Uses, ADR, and management of malaria.

1. Anti-malarial
drugs
Dr. Ashwani Dhingra
Associate Professor
GGSCOP, Yamunanagar

2. • Malaria is a mosquito-borne infectious disease of
humans caused by parasitic protozoans (a group of
single-celled microorganism) belonging to the genus
Plasmodium. The disease is transmitted by biting of
infected female anopheles mosquito. About 1-3
million deaths occur world-wide and about 8 lac
deaths per year in India due to malaria.
• Malaria is diagnosed by the microscopic
examination of blood using blood films, or with
antigen-based rapid diagnostic tests. Apart from this
polymerase chain reaction method to detect the
parasite's DNA have also been developed.

4. Plasmodium species which infect
humans
• Four species of plasmodium typically cause human malaria
includes Plasmodium falciparum, P. vivax, P. malariae, and
P. ovale.
• A fifth species, P. knowlesi, is primarily a pathogen of
monkeys, but has recently been recognized to cause illness,
including severe disease, in humans in Asia.
• The risk of disease can be reduced by preventing mosquito
bites by using mosquito nets and insect repellents, or with
mosquito-control measures such as spraying insecticides and
draining standing water.

5. Sir Ronald Ross
Nobel Prize for Physiology or
Medicine in 1902 for his work on
malaria. His discovery of the
malarial parasite in
the gastrointestinal tract of
the Anopheles mosquito led to the
realization that malaria was
transmitted by Anopheles, and laid
the foundation for combating the
disease.
Charles Laveran first visualised the
malaria parasite in blood in 1880.

6. Life cycle of the malarial parasite
Sporogeny
(sexual)
Schizogony
(asexual)
Man : Intermediate host
Mosquito : Definitive host
True causal prophylactics
Causal
prophylactics
Supressives
Gametocidal
Sporonticide

7. • An anopheline mosquito/infected syringe inoculates
plasmodium sporozoites to initiate human infection.
• Circulating sporozoites rapidly invade liver cells, and
exoerythrocytic stage tissue schizonts mature in the liver
• 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.
• Sexual stage gametocytes also develop in erythrocytes
before being taken up by mosquitoes, where they develop into
infective sporozoites.

8. • In P falciparum and P malariae infection, only
one cycle of lever cell invasion and multiplication
occurs, and liver infection ceases spontaneously
in less than 4 weeks.
• Thus, treatment that eliminates erythrocytic
parasites will cure these infections.
• In P vivax and P ovale infections, a dormant
hepatic stage, the hypnozoite, is not eradicated
by most drugs, and subsequent relapses can
therefore occur after therapy directed against
erythrocytic parasites.
• Eradication of both erythrocytic and hepatic
parasites is required to cure these infections.

10. Chemical classification
Therapeutic classification
Classification of antimalarial drugs
Chemical classification:
1. Quinine derivatives:
 Cinchona Alkaloids: Quinine, Quinidine, Cinchonine,
Cinchonidine.
 4-Aminoquinolines: Chloroquine, Amodiaquine,
Hydroxychloroquine, Pyronaridine.
 8-Aminoquinolines: Primaquine, Tafenoquine, Bulaquine.
 Quinoline methanol: Mefloquine, Halofantrine.

11. 2. Bisquinoline: Piperaquine
3. Biguanides: Proguanil, Chlorproguanil.
4. Diaminopyrimidines: Pyrimethamine.
5. Sulfonamides: Sulfadoxine
6. Sulphone: Dapsone
7. Antibiotics: Doxycycline, Tetracycline,
Clindamycin.
8. Miscellaneous agents:
• Halofantrine & Lumefantrine
• Naphthoquinone: Atovaquone
• Sesquiterpene lactones: Artemisinin &
its derivatives i.e. Artemether, Artiether, Artisunate.

12. • 8. Combinations:
• Pyrimethamine & Sulfadoxine ( Fansidar)
• Mefloquin , Pyrimethamine & Sulfadoxine
(Fansimef)
• Atovaquone & Proguanil (Malarone)
• Amodiaquine & Artisunate (Coarsucam)
• Amodiaquine , Sulfadoxine -Pyrimethamine
• Piperaquine & Dihydroartemisinins (Artikin)
• Pyrimethamine & Dapsone (Maloprim)

13. Therapeutic classification
• Causal prophylaxis: (Primary tissue
schizonticides)
– Destroy parasite in liver cells and prevent
invasion of erythrocytes
– Primaquine, proguanil
• Supressives Prophylaxis:
– Supress the erythrocytic phase and thus
attack of malarial fever can be used as
prophylactics
– Chloroquine, proguanil, mefloquine,
doxycycline.

14. •used to terminate an episode of malarial fever
Clinical cure: erythrocytic schizonticides
•Chloroquine, quinine, mefloquine, atovaquone,
artemisinin
Fast acting high efficacy
•Proguanil, pyrimethamine, sulfonamides,
tetracyclines
Slow acting low efficacy drugs

15. •Eradicate all forms of P.vivax & P.ovale
from the body
•Supressive drugs + hypnozoitocidal
drugs
•For vivax: primaquine 15 mg daily for 14
days
Radical curatives:
•Destroy gametocytes and prevent
transmission
•Primaquine, artemisinin – against all
plasmodia
•Chloroquine, quinine – Pl Vivax
•Proguanil ,pyrimethamine – prevent
development of sporozoites.
Gametocidal:

17. 1. Quinine & its derivatives
In 1820 Pelletier & caventou isolated quinine from
cinchona bark. It is a stereoisomer of quinidine,
which, unlike quinine, is an antiarrhythmic.
Quinine Quinidine
N
H3CO
HO
N
N
H3CO
HO
N

18. These alkaloids have quinoline heterocycle attached
through a 2° alcohol linkage to quinuclidine moiety.
There are four chiral centres at C-3, C-4, C-8 and C-9.
Quinine and cinchonidine have 8S,9R configuration
whereas Quinidine and cinchonine have 8R,9S
configuration.
Neither methoxy nor vinyl group is required for activity.
Any changes in 2° alcohol by oxidation or esterification
diminishes the activity.
The quinuclidine part in quinine is not necessary for
activity.
An alkyl 3° amine linked to C-9 is necessary, which leds
to study of different amino alcohols derivatives of
quinoline.

19. Cinchonine Cinchonidine

20. Hemoglobin Globin utilized by
malarial parasite
Heme (highly toxic for malaria parasite)
Chloroquine
Quinine, (+) Heme Polymerase
Mefloquine (-)
Hemozoin (Not toxic to plasmodium)
Mechanism of action

21. 1. Antimalarial action:
– Erythrocytic forms of all malarial parasites
including resistant falciparum strains .
– Gametocidal for vivax & malariae
2. Local irritant effect:
– Local pain sterile abcess.
3. Cardiovascular:
– depresses myocardium, ↓ excitability, ↓ conductivity,
↑ refractory period, profound hypotension IV.
4. Miscellaneous actions:
– Mild analgesic, antipyretic activity , stimulation of
uterine smooth muscle, curaremimitic effect
Pharmacological actions

22. Adverse drug reactions
• Cinchonism:
• Tinnitus, nausea & vomiting
• Headache mental confusion, vertigo, difficulty in hearing & visual disturbances
• Diarrhoea , flushing & marked perspiration
• Exagerated symptoms with delirium , fever, tachypnoea, respiratory depression,
cyanosis.
• Cardiovascular toxicity:
• Cardiac arrest, hypotension ,fatal arrhytmias
• Hypoglycemia

23. Uses
• Malaria:
• uncomplicated resistant falciparum
malaria
• Cerebral malarial
• Myotonia congenita: 300 to 600 mg BD/ TDS
• Nocturnal muscle cramps: 200 – 300 mg
before sleeping
• Spermicidal in vaginal creams
• Varicose veins: along with urethane causes
thrombosis & fibrosis of varicose vein mass

24. 4-Aminoquinolines
Chloroquine Amodiaquine
Pyronaridine
Hydroxychloroquine

25. Chloroquine
• Synthesized by Germans in 1934
(Resochin)
• Most widely used anti-malarial,
blood schizonticide
• d & l isomers, d isomer is less
toxic
• Cl at position 7 confers maximal
antimalarial efficacy.

26. Pharmacological
actions
Antimalarial activity:
• High against erythrocytic forms of vivax,
ovale, malariae & sensitive strains of
falciparum
• Gametocytes of vivax
• No activity against tissue schizonts
• Resistance develops due to efflux mechanism
Other parasitic infections:
• Giardiasis, taeniasis, extrainstestinal
amoebiasis
Other actions:
• Depressant action on myocardium, direct
relaxant effect on vascular smooth muscles,
antiinflammatory, antihistaminic , local
anaesthetic

27. 4. Rheumatoid diseases:
Systemic lupus erythematosis, Sjogren syndrome
Rheumatoid Arthritis
MOA not clear, proposed mechanism are:
• Suppression of T lymphocyte responses to
mitogens.
• Decreased leukocyte chemotaxis
• Stabilization of lysosomal enzymes.
• Inhibition of DNA & RNA synthesis.
• Trapping of free radicals.
5. Hepatic amoebiasis / abscess not responding to
Metronidazole
• Concentrated in liver kills trophozoits of E.
histolytica
• Not effective for amoebic colitis or luminal
amoebae because absorbed in upper intestine.

28. Pharmacokinetics
• Orally Chloroquine phosphate & I/M / I/V
injection Chloroquine sulphate
• Well & almost complete absorbed from GIT. ↓ by
Kaolin & antacids containing Calcium &
Magnesium.
• tmax 2-3 hrs, 60 % protein bound specially to
melanin containing tissues.
• Concentrated in RBCs, liver, spleen, kidney, lungs,
leucocytes, melanin containing tissues. It also
penetrates into the CNS & traversesplacenta.
• Partly metabolized by liver and slowly excreted in
urine.
• Selective accumulation in retina: occular toxicity

29. MOA of Chloroquine as Antimalarial
• It is highly effective blood schizonticide .
• Moderate gametocide for P vivax, P ovale & P malariea.
• No effect on liver stages of malarial parasites
• Chloroquine is a weak base, it is concentrated in parasite’ s food
vacuoles by ion trapping.
• Malarial Parasites utilize hemoglobin as food, it is broken down
into heme which is toxic but it is polymerized into harmlessm
hemozoin by enzyme heam polymerase.
• Chloroquine prevents biocrystallization of heme in to Hemozoin,
by inhibiting HAEM POLYMERASE.
• Increased pH & accumulation of toxic heme, produces oxidative
damage to the membranes, leading to lysis of both the Malarial
Parasites & RBCs.

31. Resistance to chloroquine
• V. common in P falciparum
• Uncommon but ↑ for P vivax.
• In P falciparum, it has been correlated with mutations in a
transporter, PfCRT.
• There is decreased accumulation of drug in MP.
• It can be reversed by verapamil, desipramine and
chlorpheniramine, clinical value not established.

32. Adverse drug reactions
A/E are minimal with low doses for
chemoprophylaxis.
1. Intolerance:-
 Pruritis (primarily in Africans)sometimes with
Urticaria.
 Nausea, vomiting , Abdominal Pain, Anorexia.
 skin rashes, angioneurotic edema, photosensitivity,
pigmentation, exfoliative dermatititis.
 Long term therapy may cause bleaching of hair,
Rarely thrombocytopenia, agranulocytosis,
pancytopenia
 Headache.
 Blurring of vision.

33. 2.Chronic use of high daily doses in Rheumatoid
diseases:-
• Discoloration of nail beds and mucus membranes
• Bleaching of hair & Alopecia
• Irreversible Ototoxicity , Retinopathy, myopathy &
Peripheral Neuropathy.
• It can exacerbate dermatitis produced by gold /
phenylbutazone therapy.
3. Large I/M or Rapid I/V administration:-
• Excessive hypotension.
• Respiratory & cardiac arrest.

34. 4. Occular toxicity:-
• High dose prolonged therapy.
• Temporary loss of accommodation.
• Lenticular opacities, subcapsular cataract.
• Retinopathy: constriction of arteries, edema, blue
black pigmentation , constricted field of vision.
5. CNS:-
• Insomnia, transient depression seizures, rarely
neuromyopathy & ototoxicity.
6. CVS:-
• ST & T wave abnormalities, abrupt fall in BP &
cardiac arrest in children reported

35. Therapeutic
uses
1. Hepatic amoebiasis:
2. Giardiasis
3. Clonorchis sinensis
4. Rheumatoid arthritis
5. Discoid Lupus
Erythematosus
6. Control manifestation of
lepra reaction
7. Infectious mononucleosis

36. • Hydroxy chloroquine:
– Less toxic, properties & uses similar
• Amodiaquine:
– As effective as chloroquine
– Pharmacological actions similar
– Chloroquine resistant strains may be
effective
– Adverse events: GIT, headache ,
photosensitivity, rarely agranulocytosis
– Not recommended for prophylaxis
• Pyronaridine: effective in resistant cases

37. 8-Aminoquinolines
Primaquine
Bulaquine
Tafenoquine

38. Primaquine
Liver hypnozoites
Weak action against erythrocytic stage of
vivax, so used with supressives in radical
cure
No action against erythrocytic stage of
falciparum
Has gametocidal action and is most
effective antimalarial to prevent
transmission disease against all 4 species

39. Mechanism of action:
– Interferes with oxygen transport system
Primaquine
Converted to
electrophiles
Generates reactive
oxygen species

40. Adverse effects
• Gastrointestinal:
– epigastric distress,
abdominal cramps ,
• Hemopoetic:
– mild anemia,
methaemoglobinemi
a, cyanosis,
hemolytic anemia in
G6PD deficiency
• Avoided during
pregnancy, G6PD
deficient

41. • More active slowly metabolized
analog of primaquine, has
advantage that it can be given on
weekly basis.
Tafenoquine:
• Congener of primaquine
developed in india
• Comparable antirelapse activity
when used for 5 days
• Partly metabolized to primaquine
• Better tolerated in G6PD deficiency
Bulaquine:

42. Quinoline methanol derivatives
Halofantrine
• developed to deal with chloroquine resistant malaria
• Rapidly acting erythrocytic schizonticide , slower than
chloroquine & quinine
• Effective against both chloroquine sensitive & resistant
plasmodia.

43. • Mefloquine is exits as racemic mixture, the
respective S,S and R,R isomer is more active. It is
reserved for the treatment caused by
chloroquine resistant P. falciparum. The
mechanism of action is not clear but in certain
respects, it behaves like quinine, but it dos’t
intercalate with DNA.
• Halofantrine is used as an alternative to
quinine and mefloquinine to treat acute maleria
attacks caused by chloroquine resistant and
multidrug resistant strains of P. falciparum.

44. Adverse events
• GIT:
– bitter in taste, nausea, vomiting , abdominal pain , diarrhoea
• Neuropsychiatric disturbances:
– anxiety, hallucinations, sleep disturbances, psychosis, errors in
operating machinery, convulsions
• CVS:
– Bradycardia, sinus arhythmia, & QT prolongation
• Teratogenicity:
– Avoided in first trimester
• Miscellaneous:
– allergic skin reactions, hepatitis & blood dyscrasias

45. Uses
• Effective drug for MDR falciparum
1. T/t of uncomplicated falciparum in MDR malaria should be used along with
artesunate (ACT)
2. Prophylaxis in MDR areas 250 mg per week started 2- 3 weeks before to asses
side effects
• Due to fear of development of drug resistance mefloquine should not be used as
drug for prophylaxis in residents of endemic area

46. 2. Bisquinoline:
Piperaquine
• Piperaquine, a bisquinoline first synthesised in 1960s,
and was used for treatment of malaria from 1970s-
1980s in China, the use waned due to resistance.
• Piperaquine & Dihydroartemisinins (Artikin)– first line
therapy for falciparum malaria , without apparent
resistance.
• Now it is combined with Dihydroartemisinins

47. 3.Biguanides: Dihydrofolate reductase inhibitors
Proguanil
Chlorproguanil.

48. • Proguanil :
– Biguanide converted to cycloguanil active compound
– Act slowly on erythrocytic stage of vivax & falciparum
– Prevents development of gametes
– Chlorproguanil was found to be more active than
proguanil and has longer duration of action.
 Adverse effects:
 Stomatitis, mouth ulcers, larger doses depression of
myocardium , megaloblastic anemia

49. 4. Diaminopyrimidines:
Pyrimethamine
• Diaminopyrimidine more
potent than proguanil &
effective against
erythrocytic forms of all
species.
• Tasteless so suitable for
children
 Adverse events:
megaloblastic anemia,
thrombocytopenia,
agranulocytosis.

50. 5. Sulfonamides:
Sulfadoxine
• Sequential blockade not
recommended for
prophylaxis
• sulfadoxine 500 mg +
pyrimethamine 25 mg, 3
tablets once for acute
attack
• Use:
– single dose
treatment of
uncomplicated
chloroquine resistant
falciparum malaria
– patients intolerant to
chloroquine
– First choice
treatment for
toxoplasmosis

51. 6. Sulphone: Dapsone
• Combination with pyrimethamine is useful in the
prevention of malaria.
• Dapsone, also known as diaminodiphenyl sulfone
(DDS), is an antibiotic commonly used in combination
with rifampicin and clofazimine for the treatment of
leprosy.
• It is used to both treat and prevent Pneumocystis
pneumonia (PCP) and prevent toxoplasmosis in people
unable to tolerate trimethoprim with
sulfamethoxazole.
• Severe side effects may include: a decrease in blood
cells, red blood cell breakdown, or hypersensitivity.

52. 7. Antibiotics
• Doxycycline:
• For chemoprophylaxis of chloroquine / Mefloquine resistant
malaria
• For treatment of P falciparum malaria with
quinine/quinidine.
• Clindamycin: slow blood schizonticide used with
quinine/quinidine if doxycycline is contraindicated.
• Azithromycin: under study for chemoprophylaxis.

53. • Tetracycline:
• Slow but potent action on erythrocytic stage
of all MP & Pre-erythrocytic stage of
falciparum
• Always used in combination with quinine or
S-P for treatment of chloroquine resistant
malaria

54. 8. Miscellaneous agents:
• Halofantrine
• Used in chloroquine resistant malaria since 1980
• Erratic bioavailabilty, lethal cardiotoxicity & cross resistance to
mefloquine limited its use
• Now a days used only when no other alternative available
• Adverse events; Nausea, vomiting, QT prolongation, diarrhoea,
itching , rashes
• C/I: along with quinine, chloroquine, antidepressants,
antipsychotics.

55. • Lumefantrine
• related to halofantrine.
• Used in combination with artemether -
Coartem as first line drug for resistant P.
falciparum malaria.
• Not cardiotoxic.

56. Atovaquone
• Synthetic napthoquinone
• Rapidly acting erythrocytic
schizonticide for plasmodium
falciparum & other plasmodia
• MOA: Collapses
mitochondrial membrane &
interferes ATP production
• Proguanil potentiates action
of atovaquone and prevents
development of resistance
• Also used in P. Jivoreci &
Toxoplasma gondii infections

57. Sesquiterpene lactones: Artemisinin & its derivatives
Artimisia annua

58. • Artemisinin is the active constituent of the
plant Artimisia annua.
• Sesquiterpine lactone endoperoxide.
• Most potent and rapid acting blood
schizonticides.
• Active against P. Vivax and both
chloroquine sensitive and resistant strain
of P. flaciparum.
• Poorly soluble in water & oil, whereas
other derivatives i.e. artemether and
arteether are more lipid soluble and Sodiu
artesunate is more water soluble.
• These drugs are usually given in
combination of other anti-malarial agents.

59. Mechanism of action
• These compounds
contains an
endoperoxide bridge
which interacts with
heme in parasite
• Heme iron cleaves this
endoperoxide bridge
• There is generation of
highly reactive free
radicals which damage
parasite membrane by
covalently binding to
membrane proteins

60. Antimalarial
action
Artemisinin
Artemisinin
Conventional
Treatment

61. Artemether: Methyl ether of dihydroartemisinin
• Used orally or intramuscularly.
Arteether: Ethyl ether of dihydroartemisinin
• Therapeutically equivalent to quinine in cerebral
malaria
• A longer t1/2 & more lipophilic than artemether
favoring accumulation in brain
Artesunate: Used Orally, intramuscularly, intravenously
or rectally
Dihydroartemisinin: only used Orally.

62. Adverse events
• Leucopenia
• Hypersensitivity: Drug fever, itching
• GIT: nausea, vomiting, abdominal pain (common)
• ECG changes: ST-T changes, QT prolongation
• Abnormal bleeding, dark urine
• Reticulocytopenia

63. • Rapid clinical & parasitological cure
• High cure rates and low relapse rates
• Absence of resistance
• Good tolerability profile
Why combination therapy?
Combination therapy

64. Artemisinin
based
combination
therapy
(ACT)
Artemisinin compunds are shorter acting drugs
Monotherapy needs to be extended beyond
disappearance of parasite to prevent
recrudescence
This can be prevented by combining 3-5 day
regimen of artemisin compounds with one long
acting drug like mefloquine 15 mg/kg single
dose
Indicated by WHO in acute uncomplicated
resistant falciparum malaria

65. ACT
Regimens in
use
Artesunate – Sulfadoxine,
pyrimethamine:
• Adopted as first line in india under NMP
• ARTESUNATE 100 mg BD for 3 days with
S-P, 3 tablets
Artesunate Mefloquine:
• By combining artesunate further spread
of mefloquine resistance can be
prevented
• Artesunate 100 mg BD for 3 days, +
mefloquine 750 mg on second day & 500
mg on third day

66. Artemether & lumefantrine
• Lumefantrine is highly effective , long acting
oral erythrocytic schizonticide related to
mefloquine
• Highly lipophilic onset delayed , peak 6 hrs
• Available as fixed dose combination
• 80 mg artemether BD WITH 480 mg
lumefantrine BD for 3 days
Other ACTs:
– DHA – Piperaquine, Artesunate-
pyronaridine

67. Combination therapy for
Chloroquine Resistant Malaria
1. Artemether in combination with lumefantrine. (Coartem)
2. Artesunate in combination with Mefloquine /
Amodiaquine(Coarsucam) / Sulfadoxime & Pyrimethamine.
3. Dihydroartemisinins with Piperaquine (Artikin)
4. Pyrimethamine & Sulfadoxine ( Fansidar)
5. Pyrimethamine & Dapsone ( Maloprim)
6. Mefloquine, Pyrimethamine & Sulfadoxine (Fansimef)
7. Amodiaquine with Sulfadoxine –Pyrimethamine
8. Atovaquone & Proguanil ( Malarone)
9. Quinine & Doxycycline
10. Quinine & Clindamycin
Treatment of complicated P falciparum malaria.
I/V Artemether & Artesunate

69. Management of Malaria

70. Prophylaxis of malaria
• Indication:
• Duration :1-2 weeks before to 4 weeks after returning from
endemic area
• Drug regimens:
– Chloroquine sensitive malaria: 300 mg / week
– Chloroquine resistant malaria:
• Mefloquine 250 mg once a week ,
• Doxycycline 100 mg daily ,
• Atovaquone + proguanil daily

71. Drugs not allowed for prophylaxis
• Quinine , artemisinin compounds
– Shorter acting, higher toxicity
• Pyrimethamine sulfadoxine
• Amodiaquine

72. Acute attack of
chloroquine
sensitive
malaria:
• Tab. Chloroquine phosphate 250
mg
– Contains 150 mg of base
– Give 4 tablets stat , 2 tablets
after 8 hours and , 1 tablet BD
for 2 days
• Patients who cannot take orally
– 3.5 mg/kg IM every 6 hrs for 3
days
• Tab primaquine 15 mg OD for 14
days in Plasmodium vivax, ovale
• Primaqine 45 mg single dose for
falciparum after chloroquine
(gametocidal)

73. Acute attack of
chloroquine
resistant
malaria
A. Pts who can take orally:
– 3 tablets of (Pyrimethamine +
sulfadoxine) single dose
followed by quinine 600 mg
TDS for 2 days or
– Tab Quinine 600 mg TDS X 3
days with Cap doxycycline 100
mg BD for 7 days or
– Quinine 3 days with
mefloquine or
– (Atovaquone 250 mg +
proguanil 100 mg) 4 tab(Single
dose ) for 3 days or
– artesunate 100 mg BD x 3 days
with Sulfadoxine-
pyrimethamine or mefloquine

74. • Pts who cannot take orally
– Inj Quinine Hcl 20 mg/kg in 500 ml
dextrose saline over 4 hrs then
– 10 mg/kg in dextrose saline over 2 hrs
every 8 hrly till patient is able to swallow
– Then quinine 600 mg TDS for 7 days &
tetracycline/ doxycycline
Or
– artemether / arteether injection

75. When
should
resistance
be
suspected
All pts with complication
Any pt who has already received
chloroquine last 1 month
Hb continues to fall in absence of
bleeding & asexual forms persist
along with symptoms after 48 hrs
of treatment

76. Severe and
complicated
falciparum
malaria
Hyperparasitaemia
Hyperpyrexia
Fluid electrolyte disturbances, acidosis
Hypoglycemia
Cardiovascular collapse
Jaundice, severe anaemia
Spontaneous bleeding
Pulmonary edema
Renal failure
Hemoglobinuria, black water fever
Cerebral malaria

77. Treatment of severe and complicated
falciparum malaria
• Artesunate 2.4 mg/kg IV/IM, BD on day1 then 2.4 mg/kg
daily for 7 days OR
• Artemether 3.2 mg/kg IM on day 1 then 1.6 mg/kg daily
for 7 days OR
• Arteether 3.2 mg/kg IM on day1, followed by 1.6 mg/kg daily
for next 4 days
– Switchover to 3 Day oral ACT in between whenever
patient can take oral medication

78. • Quinine: 20 mg quinine salt/kg on admission
(i.v. infusion in 5% dextrose/dextrose saline
over a period of 4 hours) followed by
maintenance dose of 10 mg/kg body weight 8
hourly.
– When ever patient can swallow orally
switch over to oral quinine 10 mg/kg 8
hrly and complete 7 days course

79. • Malaria in children:
– Quinine parenteral high toxicity / oral well tolerated
– Primaquine avoided in neonates
– Mefloquine not used in children below 15 kg weight
• Acute malaria in pregnant women
– Chloroqune in usual doses
– Mefloquine C/I in first trimester
– Primaquine/ tetracycline avoided
– Anemia: folic acid & iron

80. Practice
points
Most antimalarials are bitter in
taste give along with milk or fruit
juice
If vomiting occurs within hour of
drug repeat full dose, in case of
mefloquine repeat half dose
If vomiting after 1 hour no need to
repeat
Postural hypotension : quinine,
chloroquine

81. Thank you