Pharmacology of antimalarial agents Flashcards
Symptoms of malaria
- Central : headache
- Systemic :fever
- Muscular : Fatigue and pain
- back pains
- Skin: chills and sweating
- Dry cough
- Splenomegaly
- neasea and vomitting
Patients at risk
- Pregnant woman
- children > 5 years
- Ealderly
- Immunocompromised
- Splectomised
- Non-immune patients
Prophylactic medication for malaria
> Doxycycline :1 day before / daily / 4 weeks after return - schedule
Atovaquone -proguanil : 1 day before /daily /1 weeek after return - Schedule 2
Mefloquine : 1 week before / weekly / 4 weeks after return - Schedule 4
Mefloquine C/I
- Do not drive ,climb ,fly
- T1/2= 13-33 days
- Food increase absorption
MOA: Mefloquine
- Parasite digest RBC hemoglobin to obtain aa
- The process results in a large release of hg which is toxic
- The parasite protects itself by polymerizing heme to a non-toxic hemozoin
> > Chloroquine prevents the polymerization of hemozoin. The accumulation of heme results in lysis of both the parasite and RBC
MOA of doxycycline
inhibit protein synthesis by binding to the 30S subunit of the ribosome. It is associated with apicoplast
MOA of proguanil
Proguanil is a prodrug of cycloguanil which is a dihydrofolate reductase inhibitor to disrupt malarial parasite synthesis of deoxythymidylate
MOA of atovaquone
selectively inhibits the parasite mitochondrial electron transport inhibiting parasite nucleic acid synthesis
Agents used to treat P.falciparum
- Uncomplicated : Artemether - Lumenfantrine or Quinine + Doxycycline /Clindamycin (oral / iv )
- Complicated : Artesunate -iv / Quinine -iv
Artemether Vs Lumefantrine
>Short vs long T1/2
> are blood schizoticide
>Artemether is a gametocide and Lumfanterine is not
>Fast acting Vs Slow acting to reduce parasitemia
Treatment of other plasmodium infections
- P.vivax / P.ovale / P.malariae / P.knowlesi
> Artemether-lumefantrine / quinine - clindamycine / doxycycline
The side effects of malaria in pregnant
- In severe P. falciparum: cerebral malaria, hypoglycemia, spontaneous abortion, stillbirth, premature delivery, low birth weight
Prophylaxis for pregnant women
*Avoid malaria
*Mefloquine
C/I: Doxycycline > GIt disturbance and vaginal candidiasis
Treatment of malaria in pregnant women
- 2nd/3rd trimester: Artemether / Lumefantrine > Hyperinsulinaemia, increase in hypoglycaemia
- All trimesters , severe : Quinine + clindamycine
- For first trimester : Primaquine
Treatment of malaria in lactation
- Breastfed infants > No protection from mother’s prophylaxis
- During lactation in mother > mefloquine > excereted milk >
- Doxycycline : C/I > excreted milk [ low] > effect in nursing infants ( stained deciduous teeth ,enamel hypoplasia ,bone growth inhibition in fetus )
- Atovaquone -proguanil > C/I > no safety data
Treatment of malaria in Paediatrics
*Children < 5 years of ages avoid high-risk
malaria areas
*Mefloquine > C/I > <5 kg > Kinetics ,absorption enhanced with food
*Doxycycline > C/I > < 8 years old
*Atovaquone - progusnil > >11 kg
*Primaquine > >years old
