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Pharmacology > Antimalarial agents > Flashcards

Antimalarial agents Flashcards

1
Q

Which species of malaria is predominate in South Africa?

A

Plasmodium falciparum

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2
Q

Malaria lifecycle-human stage?

A
  1. Starts with a bit from a malaria-infected
  2. Malaria parasites leave the mosquito salivary gland and enter the human bloodstream during feeding
  3. The malaria parasities enter liver cells and multiply. The liver cells eventually rupture release more parasites into the blood
  4. The parasites invade red blood cells where they continue to multiply and rupture the cells. The blood stages cause the clinical symptoms of malaria
  5. Some parasites enter red blood cells and develop into male and female reproductive cells called gametocytes)
  6. The gametocytes are transferred to another mosquito when it feeds on the human. The phase of sexual reproduction continues in the mosquito
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3
Q

Malaria lifecycle-malaria stage?

A
  1. Begins when an insect feeds on malaria-infected blood
  2. 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.
  3. In the mosquito, the gametocytes develop further
  4. A male cell fertilizes the female cell to form a zygote.
  5. The zygote enlarges and migrates to the outer wall of the gut.
  6. The parasites multiply several times
  7. Eventually, many new parasites are released.
  8. The parasites migrate to the mosquitoes salivary gland.
  9. The parasites accumulate in the salivary glands, ready for transfer to another
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4
Q

Non-pharmacological prophylactic measures?

A

-Nets
-Permethrin (Insecticide)
-Citronella (Insect repellent)

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5
Q

Malaria Prophylaxis Meds and frequency?

A
  • 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)
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6
Q

Mefloquine MOA and elaborate?

A

Inhibit haemozin formation

  1. The malaria parasite digests the host red blood cells haemoglobin to obtain amino acids
  2. The process releases large amounts of haem that is toxic to the parasite.
  3. To protect itself, the parasite ordinarily polymerizes the haem to nontoxic haemozin, which is sequestered in the parasites food vacuole
  4. Mefloquine prevents the polymerization to haemozin. The accumulation of haem results in lysis of both the parasite & host RBC.
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7
Q

Mefloquine and BBB?

A

Readily crosses BBB and thus causes sedation

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8
Q

Mefloquine CI?

A

-Anyone needs to fine motor skills -Driving
-Diving
-Flying
-Climbing

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9
Q

Doxycycline MOA for bacteria and malaria?

A

MOA Malaria: Associated with apicoplast

MOA: Inhibit protein 30S ribosomal subunit

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10
Q

Doxycycline CI?

A

-Pregnancy
-Children <12 yrs + Bone & teeth development

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11
Q

Mefloquine admin+adjunction?

A

Taken with food(Increase absorption)

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12
Q

Atovaquone -Proguanil Dosage?

A

1 day before before/daily/a week after return(everyday)

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13
Q

Atovaquone MOA?

A

Selectively inhibits the parasitic mitochondrial electron transport
inhibiting parasite nucleic acid synthesis

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14
Q

Proguanil MOA?

A

A dihydrofolate reductase
inhibitor which disrupts
malaria parasite synthesis
of deoxythymidylate

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15
Q

Proguanil prodrug?

A

Prodrug of cycloguanil

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16
Q

Proguanil and pregnancy?

A

No safety data in pregnancy and lactation thus CI

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17
Q

Types of treatment for P.flaciparum?

A
  1. Uncomplicated-Not severe
  2. Compilcated-Severe
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18
Q

Uncomplicated treatment drugs for malaria?

A
  1. Artemether‐Lumefantrine OR
  2. Quinine + Doxycycline / Clindamycin (oral/iv
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19
Q

Which uncomplicated drug in the treatment for P.flaciparum is ideal for pregnancy

A

Quinine+ Clindamycin

20
Q

Which anti-malarial do we give to paediatrics patients?

A

-Mefloquine > 5 kg

-Atovaquone-Proguanil safe ≥ 11kg

21
Q

Paediatrics anti-malarial CI ?

A

-Doxycycline<8 yrs (12 yrs)
-Primaquine <6 months

22
Q

Elderly anti-malarial CI ?

A

Remove Mefloquine

-Patients usually has Alzheimer’s . Mefloquine crosses BBB and has CNS effects

23
Q

Primaquine MOA?

A

Free radical formation?

24
Q

Artesunate MOA

A

Formation of free radicals

25
Q

Lumfantrine MOA?

A

Inhibits haemozin formation

25
Q

Complicated treatment drugs for malaria?

A
  1. Artesunate /Quinine
  2. Artemther-Lumefantrine
  3. Primaquine
25
Q

Primaquine S/E?

A

-Headache
-Pruritus
-GIT

26
Q

Why is severe G6PD deficiency-acute contraindicated in Primaquine?

A

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

26
Q

Primaquine CI?

A
  1. Pregnancy(1st trimester)
  2. Children < 6years
  3. Severe G6PD deficiency-acute haemolytic anemia
26
Q

Quinine A/E-4?

A
  1. Cinchonism-neural, retinal and auditory toxicty
  2. Increased insulin
  3. Severe thrombocytopenia
  4. CVS-Hypotension, Ventricular arrhythmia
26
Q

Primaquine and gametes?

A

Gametocidal

26
Q

Which anti-malarial do we give to pregnant patients?

-Prophylaxis
-Uncomplicated
-Sever

A

Prophylaxis: Mefloquine

Uncomplicated: Artemether-Lumefantrine

Quinine + Clindamycin

26
Q

Artemther-Lumefantrine effectiveness?

A

Both effective against schizonites

26
Q

Malaria high risk patients?

A
  1. Pregnancy
  2. Lactation
  3. Paediatrics
  4. Elderly
  5. HIV
  6. TB
  7. Epilepsy
  8. Patients on anticoagulation therapy
  9. Acne
    10.Patients requiring fine motor skills
26
Q

Quinine and pregnancy?

A

Safe to use in pregnancy

27
Q

Artemether MOA?

A

Formation to free radicals(toxic to parasite)

27
Q

Difference between Artemether and Lumefantrine?

-Duration?
-Half life?
-Cycle?

A

Artemether
-Fast acting
-Short t1/2
-A/sexual cycle

Lumefantrine
-Slow acting
-Long 1/2
-Only asexual cycle

27
Q

Quinine MOA

A

Inhibits haemozin formation

27
Q

Which anti-malarial do we give to lactating patients?

A

-No protection from mothers prophylaxis
-Mefloquine is safe to use

28
Q

HIV anti-malarial CI ?

A

-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

29
Q

TB anti-malarial CI and safest drug ?

A

-Rifampicin→CYP450 inducer
[↓ other drugs/antimalarial
agents]

-Atovaquone→ Safest option

30
Q

Epilespsy anti-malarial CI and safest drug ?

A

All other drugs can be used except for Mefloquine

-Remove Mefloquine
-Atovaquone-Proguanil→ Recommended
-Some anticonvulsants are CYP450 inducers

31
Q

Epilespsy anti-malarial CI and safest drug ?

A

All other drugs can be used except for Mefloquine

-Remove Mefloquine
-Atovaquone-Proguanil

32
Q

Anticoagulant anti-malarial CI and safest drug ?

A

-Mefloquine best optiono
-Doxycycline & Proguanil potentiate anticoagulant effect

33
Q

Acne anti-malarial CI and safest drug?

A

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

Pharmacology (44 decks)

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