2. Plasmodium vivax (tertian)
Plasmodium ovale (tertian)
Plasmodium falciparum (tertian)
Plasmodium malariae (quartian)
Plasmodium species which infect humans
Malaria is a mosquito-borne infectious disease. It is
naturally transmitted by the bite of a female Anopheles
mosquito that is infected by Plasmodium
5. CLASSIFICATION OF ANTIMALARIAL
DRUG
i. 4-Aminoquinolines: Chloroquine,
Amodiaquine,
Piperaquine
ii. Quinoline-methanol: Mefloquine
iii. Cinchona alkaloid: Quinine, Quinidine
iv. Biguanides: Proguanil,
Cholrproguanil
v. Diaminopyrimidine Pyrimethamine
vi. 8-aminoquinoline Primaquine,
Tafenoquine
vii. Sulfonamide and sulfone Sulfadoxine, Dapsone
Sulfamethopyrazine 5
6. CLASSIFICATION OF ANTIMALARIAL
DRUG
viii. Antibiotics Tetracycline,
Doxycycline
Clindamycin
ix. Sesquiterpine lactones Artesunnate,
Artemether
Arteerther, Arterolane
x. Amino alcohols Halofantrine,
Lumefantrine
xi. Naphthyridine Pyronarindine
xii. Naphthoquinone Atovaquone
6
7. ANTIMALARIAL THERAPY
Antimalarial therapy is given in following ways
1. Causal prophylaxis:
Destroy parasite in liver cells and prevent invasion of
erythrocytes
Drug : Primaquine, proguanil
2. Suppressive Prophylaxis:
Suppress the erythrocytic phase and thus attack of
malarial fever can be used as prophylactics
Drug : Chloroquine, proguanil, mefloquine,
doxycycline
7
8. ANTIMALARIAL THERAPY
3.Clinical cure: erythrocytic schizonticides
used to terminate an episode of malarial fever
Fast acting high efficacy
Chloroquine, quinine, mefloquine, atovaquone,
artemisinin
Slow acting low efficacy drugs
Proguanil, pyrimethamine, sulfonamides, tetracyclines
8
9. ANTIMALARIAL THERAPY
4. Radical curatives:
Eradicate all forms of P.vivax & P.ovale from the body
Supressive drugs + hypnozoitocidal drugs
For vivax: primaquine 15 mg daily for 14 days
5. Gametocidal:
Destroy gametocytes and prevent transmission
Drugs :Primaquine, artemisinin – against all plasmodia
Chloroquine, quinine – P Vivax
Proguanil ,pyrimethamine – prevent development of
sporozoites
9
10. CHLOROQUINE
Synthesized by Germans in 1934 ( resochin)
d & l isomers, d isomer is less toxic
Cl at position 7 confers maximal antimalarial
efficacy
Rapidly acting erythrocytic schizontocide
against all species of plasmodia
10
11. CHLOROQUINE
MOA: Hemoglobin Globin utilized by
malarial parasite
Heme (highly toxic for malaria
parasite)
Chloroquine
Quinine, (+) Heme Polymerase
mefloquine (-)
Hemozoin (Not toxic to plasmodium) 11
12. CHLOROQUINE
Pharmacological actions:
1. Antimalarial activity:
High against erythrocytic forms of P. vivax, P. ovale, P.
malariae & sensitive strains of P. falciparum
Gametocytes of P. vivax, P. malariae, P. ovale
No activity against tissue schizonts
2. Other parasitic infections:
Giardiasis, taeniasis, hepatic amoebiasis
12
13. CHLOROQUINE
3. Other actions:
Anti-inflammatory, local irritant, , local anaesthetic ,
weak smooth muscle relaxant , antihistaminic,
antiarrhythmatic
Pharmacokinetics:
Well absorbed, peak plasma concentration in 2-5 hrs , 60
% protein bound
Concentrated in liver , spleen, kidney, lungs , leucocytes
Selective accumulation in retina: occular toxicity
T1/2 = 3-10 days increases from few days to weeks
13
14. CHLOROQUINE
Adverse effect
Well tolerated , extraordinarily safe if taken in proper
doses
Acute chloroquine toxicity is encountered most
frequently when therapeutic or high doses are
administered too rapidly by parenteral routes
Frequent side effect are nausea, vomiting ,anorexia, GI
upset, headache, visual disturbances, urticaria, Pruritus
(primarily in Africans )
14
15. CHLOROQUINE
Prolonged medication with suppressive doses
occasionally causes side effects such as headache,
blurring of vision, diplobia, confusion, convulsions,
bleaching of hair, widening of the QRS interval, and T-
wave abnormalities.
Contraindication
Psoriasis ,porphyria
Retinal and visual field abnormalities or myopathy
Calcium , magnesium containing antacids
15
17. AMODIAQUINE(AQ)
Almost identical to CQ
Low cost , limited toxicity
May effectiveness against CQ resistant of P. falciparum .
Imp. Toxicities : agranulocytes, aplastic anemia,
hepatotoxicity
Not recommended for Chemoprophylaxis
17
18. MEFLOQUINE(MQ) `
Effective against CQ resistant P. falciparum
Exact Mechanism of action is unknown but may similar
to that of chloroquine
Pharmacokinetics
Oral absorption is good and peak plasma concentration
are reached in about 18 hours.
Highly protein bound, extensively distributed in tissues
18
19. MEFLOQUINE(MQ) `
Extensive metabolism occurs in liver, primarily secreted
in bile, under goes enterohepatic circulation
Elimination half life : about 20 days
Antimalarial action:
Has strong blood schizonticidal activity against P.
falciparum, P. vivax
has no activity against early hepatic stages and mature
gametocytes of P. falciparum or latent tissue forms of P.
vivax
19
20. MEFLOQUINE(MQ)
Adverse effects
Mainly dose related (more common with higher dose )
Common reaction are nausea, vomiting , abdominal pain
, diarrhoea, headache, sinus bradycardia, Q-T
prolongation
Neuropsychiatric disturbances( anxiety, hallucinations,
sleep disturbances, psychosis, ataxia )
20
21. MEFLOQUINE(MQ)
Uses
Effective against DR P. falciparum and P. vivax
As prophylactic
Contraindication and cautions
Contraindicated if there is history of epilepsy ,
psychiatric disorder, arrhythmias .
Should not co administered with quinine/quinidine,
halofantrine
21
22. QUININE
Derived from bark of Cinchona tree.
Moa is similar to chloroquine
Erythrocytic schizontocide for all species
22
23. QUININE
PHARMACOLOGICAL ACTIONS
1. Antimalarial action :
acts primarily against asexual erythrocytic forms
The alkaloid also is gametocidal for P. vivax and P.
malariae but not for P. falciparum.
Quinine is more toxic and less effective than
chloroquine against malarial parasites susceptible to
both drugs.
23
24. QUININE
2. Local irritant
Intensely bitter and irritant . Orally it causes nausea,
vomiting, epigastric discomfort
Injections can cause pain and local necrosis in the
muscle and thrombosis in vein.
3. Cardiovascular:
depresses myocardium, ↓ excitability, ↓
conductivity, ↑ refractory period, profound
hypotension IV.
4. Miscellaneous actions:
Mild analgesic, antipyretic activity , stimulation of
uterine smooth muscle, curare mimitic effect
24
25. QUININE
Pharmacokinetics
Administered orally , completely absorbed
PPB: 70% ( mainly binds to alpha acid glycoprotein)
Peak plasma level reaches in 1-3 hours
Metabolized in liver degradation products excreted in
urine
t ½ = 10-12 hrs
25
26. QUININE
Adverse drug effect
1.Cinchonism:
Ringing in ears , nausea & vomiting
Headache mental confusion, vertigo, difficulty in
hearing & visual disturbances
Diarrhoea , flushing & marked perspiration
Still higher doses , exaggerated symptoms with
delirium , fever, tachypnoea, respiratory depression ,
cyanosis.
26
27. QUININE
2. Idiosyncrasy/hypersensitivity
3. Cardiovascular toxicity: cardiac arrest, hypotension
,fatal arrhythmias
“Blackwater fever”~the triad of massive hemolysis,
hemoglobinemia, and hemoglobinuria leading to anuria,
renal failure, and even death¾is a rare type of
hypersensitivity reaction to quinine therapy .
27
28. QUININE
USES
1. Malaria:
uncomplicated resistant falciparum malaria
Complicated and severe malaria including cerebral
malarial
2. Treatment of Nocturnal Leg Cramps
28
29. PROGUANIL
proguanil in body is cyclized to cycloguanil, a cyclic
triazine metabolite
In sensitive P. falciparum malaria, it exerts activity
against both the primary liver stages and erythrocytic
stage.
Also active against erythrocytic stage of P. vivax.
Half life : 16 hrs
29
30. PROGUANIL
MOA
proguanil selectively inhibits the bifunctional
dihydrofolate reductase-thymidylate synthetase of
sensitive plasmodia, causing inhibition of DNA synthesis
and depletion of folate cofactors
Toxicity and side effect
In prophylactic doses occasional nausea and diarrhea
30
31. PROGUANIL
High dose may cause vomiting, abdominal pain,
diarrhea, hematouria, and the transient
appearance of epithelial cells and casts in the
urine
USES
For causal prophylaxis
MALARONE- proguanil +atovaquone, used for
multi drug resistance malaria.
31
32. PYRIMETHAMINE
Diaminopyrimidine more potent than proguanil &
effective against erythrocytic forms of all species.
Tasteless so suitable for children
Longer half life than cycloguanil (t1/2: 4 days)
Used only in combination with sulfonamide or dapsone
Adverse events: relatively safe
megaloblastic anemia, thrombocytopenia,
agranulocytosis( may occur with higher doses)
32
33. SULFADOXINE-
PYRIMETHAMINE(S/P)
Form supra-additive synergistic combination with
pyrimethamine sequential block
Not recommended for prophylaxis
Use:
single dose treatment of uncomplicated chloroquine
resistant falciparum malaria
patients intolerant to chloroquine
First line therapy for treatment of toxoplasmosis
33
34. PRIMAQUINE
Inactive against asexual blood stages parasites
Drug of choice for the eradication of dormant liver forms
of P. vivax and P. ovale
exert a marked gametocidal effect against all four species
of plasmodia that infect humans
Plasma half life : 6-8 hrs
Excreted in urine
34
35. PRIMAQUINE
MOA:
Has not been elucidated
May converted into electrophilic intermediates that act as
oxidation-reduction mediators . This could contribute to
antimalarial effect by generative reactive oxygen species
or by interfering with mitochondrial electron transport in
the parasite
Toxicity and Side Effects
Nausea, vomiting, epigastric distress(can be minimized
by taking with food)
Methaemoglobinemia 35
36. PRIMAQUINE
Therapeutic or higher doses of primaquine may cause acute
hemolysis and hemolytic anemia in humans with G6PD
deficiency
USES
Radical cure of acute vivax and ovale infection
Terminal prophylaxis of vivax and ovale infection
Chemoprophylaxis of malaria
Gametocidal action
Pneumocystis jiroveci infection
36
37. ARTEMISININ AND DERIVATIVE
It is a Sesquiterpine lactone extracted from Artemisia sp.
More rapid parasite clearance and fever resolution than
any other currently licensed Antimalarial drug.
Suited for severe treatment of severe malarial infection
caused by P. falciparum
Important Derivatives are Artesunate
Artemether
Dihydroartemisinin
37
38. ARTEMISININ AND DERIVATIVE
MOA:
Contentious
heme iron within the parasite catalyzes cleavage
of the endoperoxide bridge. This releases highly
active carbon centered free radical species that
bind to membrane protein , causes lipid
peroxidation, damages endoplasmic reticulum
Results lysis of the parasite
38
39. ARTEMISININ AND DERIVATIVE
Artesunate
Sodium salt is water soluble and administered by oral,
i.m. or i.v. routes
peak plasma > 60 min
Artemether
Lipid soluble and administered by oral , im
Peak plasma : 2-6 hrs
Both artesunate and artemether are converted extensively
to dihydroartemisinin,
39
40. ARTEMISININ AND DERIVATIVE
Adverse effect
Very few adverse effect: most are mild
Nausea, vomiting, abdominal pain, itching, drug
fever, dizziness,
Safe in pregnancy
Uses
Uncomplicated falciparum malaria
Severe and complicated falciparum malaria
40
41. ATOVAQUONE(MEPRON)
hydroxynapthoquinone
Rapidly acting erythrocytic schizonticide for plasmodium
falciparum & other plasmodia
MOA: Collapses mitochondrial membrane ; interferes ATP
production and pyrimidine biosynthesis
Proguanil potentiates action of atovaquone and prevents
development of resistance
Also used in Pneumocystis Jivoreci & Toxoplasma gondii
infections
Contraindicated in pregnancy
41