Anti-malarial drugs

 Caused by the plasmodium protozoa species:

1-p.falceprum
2-p.vivax
3-p.ovale
4-p.malarae
 Sites of Action for Anti-malarial Drugs:-
1. EXO- erythrocyte (hepatic
stage)

2. Erythrocytic stage

3. Gametocyte stage
 Aims Of Treatment:
1.To remove symptoms
2.To prevent relapses
3.To prevent spread
 Antimalarial agents according to phases:

 Erythrocytic phase drugs:

chloroquine, hydroxychloroquine, quinine,mefloquine
 Exoerythrocytic phase drug:
primaquine
 Gametocytic phase drug:
primaquine

 May be used together for synergistic or additive

killing power.
 Blood schizonticides
Drugs that act on erythrocytic parasites stages.
This drugs is used for:-
Treatment of acute attacks of malaria

1. Suppressive prophylaxis:-
Prevention of attacks by early destruction of the erythrocytic forms.
Includes :

 Chloroquine
 Mefloquine.
 Quinine.
 Artemisinine
 Chloroquine :-

Chemistry:

4-amino quinoline
 Highly effective blood schizonticide.
 It is also moderately effective against gametocytes of P vivax, P
ovale, and P malariae but not against those of P falciparum.
 Chloroquine is not active against liver stage parasites.

Pharmacokinetics:

It is rapidly and almost completely absorbed from the
gastrointestinal tract, reaches maximum plasma concentrations
in about 3 hours, and is rapidly distributed to the tissues.

Large volume of distribution.

Other therapeutic use of choloroquine:
1. Rheumatoid arthritis.
2. Lupus erythematosus.
3. Second line for amebic liver abcess.

Advere effects:
1. GIT disturbance: Nausea, vomiting,

abdominal pain,, anorexia.

2. Blurred vision.

3. Headache.

4. Pruritic.
 Mechanism of resistance:

 Resistance appears to result from enhanced

efflux of the drug from parasitic vesicles as a
result of mutations in plasmodia transporter
genes.
 Chloroquine combined with primaquine is the treatment of choice
for chloroquine-sensitive infections.
􀁺
 In areas with chloroquine resistant P. vivax, ACTs (with partner
medicines with long-half lives) is recommended for the treatment
of P. vivaxmalaria
 􀁺I in mild -moderate G6PD deficiency, primaquine 0.75mg
base/kg bwgiven once a week for 8 weeks. In severe cases,
primaquine is contraindicated.
 Quinine:-
 Spectrum of activity:
1. Highly effective blood schizonticide against the four
species of human malaria parasites.
2. Gametocidal against P vivax and P ovale but not P
falciparum.
3. It is not active against liver stage parasites.
 Quinine is not generally used in chemoprophylaxis .
 Adveres effects:
1. Cinchonism: tinnitus, headache, nausea, dizziness, flushing, and
visual disturbances.
2. Hypoglycemia.
3. Hypotension.
4. Hypersensitivity reactions include skin rashes, urticaria,
angioedema, and bronchospasm.
5. Hematologic abnormalities include hemolysis (especially with
G6PD deficiency), leukopenia, agranulocytosis, and
thrombocytopenia.
6. Black water fever.
 Artemisinin:-
 Chemistry: Artemisinin is the extraction product from the herb Artemisia annua.
 Mechanism of anti-malarial action:
Artemisinin are concentrated in parasitised red cells.
 It exerts antimalarial activity by interaction with haem in the parsite.asite
 Artemisinin is insoluble and can only be used orally.
 Analogs have been synthesized to increase solubility and improve antimalarial efficacy.
 They include:

1. Artesunate:-
 Water-soluble.
 Useful for oral, intravenous, intramuscular, and rectal administration.
2. Artemether:-
 Lipid-soluble.
 Useful for oral, intramuscular, and rectal administration.
 Artemisinins appear to be better tolerated than most
antimalarials.
 The most commonly reported adverse effects have been
nausea, vomiting, and diarrhea
 Guidelines for the Treatment of Malaria
1-For uncomplicated p.falciparum:-
Artemisinin-based combination therapies (ACTs) are the recommended treatments for uncomplicated
falciparum malaria.

2-for severe malaria :-

For adults(, artesunate i.v. or i.m)
For child;-
artesunate i.v. or i.m.
–quinine (i.v. infusion or divided i.m. injection)
–artemether i.m.
Pregnancy:- Quinine
–An ACT is indicated only if this is the only treatment immediately available, or if
treatment with quinine + clindamycin fails or compliance issues with a 7-day
treatment.
 Halofantrine and lumefantrine:-
 Halofantrine:
is a blood schizonticidal drug.
 Pharmacokinetic:
Halofantrine is given orally.
 Halofantrine is rapidly effective against most chloroquine-
resistant strains of P falciparum, but its use is limited by
irregular absorption and cardiac toxicity.
 Should not be used for chemoprophylaxis.
 Adverse effects:
 Abdominal pain, diarrhea, vomiting, cough, rash,
headache, pruritus, and elevated liver enzymes.
 It alters cardiac conduction, with dose-related
prolongation of QT and PR intervals
 Lumefantrine:
 Is available as a fixed-dose combination with artemether
known as Coartem.
 Tissue schizonticides
 Drugs that eliminate developing or dormant liver forms
 Primaquine:
Chemistry: Primaquine phosphate is a synthetic 8-aminoquinoline.
 Spectrum of anti-malarial activity:
Primaquine is active against hepatic stages of all human malaria
parasites.
 Gametocidal against the four human malaria species.
 Acts against erythrocytic stage parasites, but this activity is too weak
to play an important role.
 Drugs that Inhibitors of folate synthesis:-

1. Pyrimethamine.
2. Proguanil.
3. Fansidar: a fixed combination of the sulfonamide
sulfadoxine (500 mg per tablet) and pyrimethamine
(25 mg per tablet).
 Other antibiotics effect:-
1. Tetracycline and doxacycline.
2. Clindamycin.
3. Azithromycine.
 ‫اعداد الطالب‬
‫‪-1‬معتز هاشم حسين كنة‬
‫‪2‬مثقال علي حسن عيايدة‬
‫‪-3‬خالد تاج السر النور‬
‫‪-4‬محمد ابوبكر احمد‬

‫اشراف ‪ -:‬د‪.‬محمد البكري‬