Antimalarial agents Flashcards
Which species of malaria is predominate in South Africa?
Plasmodium falciparum
Malaria lifecycle-human stage?
- Starts with a bit from a malaria-infected
- Malaria parasites leave the mosquito salivary gland and enter the human bloodstream during feeding
- The malaria parasities enter liver cells and multiply. The liver cells eventually rupture release more parasites into the blood
- The parasites invade red blood cells where they continue to multiply and rupture the cells. The blood stages cause the clinical symptoms of malaria
- Some parasites enter red blood cells and develop into male and female reproductive cells called gametocytes)
- The gametocytes are transferred to another mosquito when it feeds on the human. The phase of sexual reproduction continues in the mosquito
Malaria lifecycle-malaria stage?
- Begins when an insect feeds on malaria-infected blood
- In blood, the parasites exist as mature male and female reproductive cells (termed gametocytes). The gametocytes are taken up in the mosquito gut when it feeds.
- In the mosquito, the gametocytes develop further
- A male cell fertilizes the female cell to form a zygote.
- The zygote enlarges and migrates to the outer wall of the gut.
- The parasites multiply several times
- Eventually, many new parasites are released.
- The parasites migrate to the mosquitoes salivary gland.
- The parasites accumulate in the salivary glands, ready for transfer to another
Non-pharmacological prophylactic measures?
-Nets
-Permethrin (Insecticide)
-Citronella (Insect repellent)
Malaria Prophylaxis Meds and frequency?
- Doxycycline – 1d before/daily/4wks after return(daily)
- Atovaquone‐proguanil – 1d before/daily/1wk after return
- Mefloquine – 1wk before/wkly(once)/4wks after return(once a week)
Mefloquine MOA and elaborate?
Inhibit haemozin formation
- The malaria parasite digests the host red blood cells haemoglobin to obtain amino acids
- The process releases large amounts of haem that is toxic to the parasite.
- To protect itself, the parasite ordinarily polymerizes the haem to nontoxic haemozin, which is sequestered in the parasites food vacuole
- Mefloquine prevents the polymerization to haemozin. The accumulation of haem results in lysis of both the parasite & host RBC.
Mefloquine and BBB?
Readily crosses BBB and thus causes sedation
Mefloquine CI?
-Anyone needs to fine motor skills -Driving
-Diving
-Flying
-Climbing
Doxycycline MOA for bacteria and malaria?
MOA Malaria: Associated with apicoplast
MOA: Inhibit protein 30S ribosomal subunit
Doxycycline CI?
-Pregnancy
-Children <12 yrs + Bone & teeth development
Mefloquine admin+adjunction?
Taken with food(Increase absorption)
Atovaquone -Proguanil Dosage?
1 day before before/daily/a week after return(everyday)
Atovaquone MOA?
Selectively inhibits the parasitic mitochondrial electron transport
inhibiting parasite nucleic acid synthesis
Proguanil MOA?
A dihydrofolate reductase
inhibitor which disrupts
malaria parasite synthesis
of deoxythymidylate
Proguanil prodrug?
Prodrug of cycloguanil
Proguanil and pregnancy?
No safety data in pregnancy and lactation thus CI
Types of treatment for P.flaciparum?
- Uncomplicated-Not severe
- Compilcated-Severe
Uncomplicated treatment drugs for malaria?
- Artemether‐Lumefantrine OR
- Quinine + Doxycycline / Clindamycin (oral/iv
Which uncomplicated drug in the treatment for P.flaciparum is ideal for pregnancy
Quinine+ Clindamycin
Which anti-malarial do we give to paediatrics patients?
-Mefloquine > 5 kg
-Atovaquone-Proguanil safe ≥ 11kg
Paediatrics anti-malarial CI ?
-Doxycycline<8 yrs (12 yrs)
-Primaquine <6 months
Elderly anti-malarial CI ?
Remove Mefloquine
-Patients usually has Alzheimer’s . Mefloquine crosses BBB and has CNS effects
Primaquine MOA?
Free radical formation?
Artesunate MOA
Formation of free radicals
Lumfantrine MOA?
Inhibits haemozin formation
Complicated treatment drugs for malaria?
- Artesunate /Quinine
- Artemther-Lumefantrine
- Primaquine
Primaquine S/E?
-Headache
-Pruritus
-GIT
Why is severe G6PD deficiency-acute contraindicated in Primaquine?
G6PD binds to neutralise naturally forming free radicals.
Primaquine forms increased free radicals and without G6PD then there would be an accumulation of the radicals and make it toxic for the cells
Primaquine CI?
- Pregnancy(1st trimester)
- Children < 6years
- Severe G6PD deficiency-acute haemolytic anemia
Quinine A/E-4?
- Cinchonism-neural, retinal and auditory toxicty
- Increased insulin
- Severe thrombocytopenia
- CVS-Hypotension, Ventricular arrhythmia
Primaquine and gametes?
Gametocidal
Which anti-malarial do we give to pregnant patients?
-Prophylaxis
-Uncomplicated
-Sever
Prophylaxis: Mefloquine
Uncomplicated: Artemether-Lumefantrine
Quinine + Clindamycin
Artemther-Lumefantrine effectiveness?
Both effective against schizonites
Malaria high risk patients?
- Pregnancy
- Lactation
- Paediatrics
- Elderly
- HIV
- TB
- Epilepsy
- Patients on anticoagulation therapy
- Acne
10.Patients requiring fine motor skills
Quinine and pregnancy?
Safe to use in pregnancy
Artemether MOA?
Formation to free radicals(toxic to parasite)
Difference between Artemether and Lumefantrine?
-Duration?
-Half life?
-Cycle?
Artemether
-Fast acting
-Short t1/2
-A/sexual cycle
Lumefantrine
-Slow acting
-Long 1/2
-Only asexual cycle
Quinine MOA
Inhibits haemozin formation
Which anti-malarial do we give to lactating patients?
-No protection from mothers prophylaxis
-Mefloquine is safe to use
HIV anti-malarial CI ?
-No safety data for Atovoquone-Proguanil for HIV thus CI
-Plasma concentrations of other agents will decrease due to drug-interactions with ARVS
i.e: Efavirenz→ CYP450 inducer
TB anti-malarial CI and safest drug ?
-Rifampicin→CYP450 inducer
[↓ other drugs/antimalarial
agents]
-Atovaquone→ Safest option
Epilespsy anti-malarial CI and safest drug ?
All other drugs can be used except for Mefloquine
-Remove Mefloquine
-Atovaquone-Proguanil→ Recommended
-Some anticonvulsants are CYP450 inducers
Epilespsy anti-malarial CI and safest drug ?
All other drugs can be used except for Mefloquine
-Remove Mefloquine
-Atovaquone-Proguanil
Anticoagulant anti-malarial CI and safest drug ?
-Mefloquine best optiono
-Doxycycline & Proguanil potentiate anticoagulant effect
Acne anti-malarial CI and safest drug?
Replace Minocycline with Doxycycline.
Doxycycline will be able to treat both acne and malaria while Minocycline only treats acne and would need another tetracycline drugs and would resultantly potentiate the S/E of tetracyclines
