W2 LECT 10: Pharm of drugs used in the management of malaria

Question 1

what are the characteristics of malaria?

Answer 1

• Infection of RBC
• Plasmodium
  . falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi
• Transmission - bite of a vector

Question 2

who are the pts. at greater risk of contracting malaria?

Answer 2

• Pregnant
• Children < 5years
• Elderly
• Immunocompromised
• Splenectomised
• Non-immune patients

Question 3

what are the symptoms of malaria?

Answer 3

• headache
• fever
• fatigue, pain
• back pain
• nausea, vomiting
• enlarged spleen
• dry cough
• chills and sweating

Question 4

what do antimalarial drugs target?

Answer 4

• hepatic stage
• gametocytes
• intra erythrocytic stage

Question 5

what are the prophylatic agents?

Answer 5

1. Mefloquine: 1wk before/wkly/4wks after return
2. Doxycycline: 1d before/daily/4wks after return
3. Atovaquone – Proguanil: 1d before/daily/1wk after return

*stand by medication
Artemether-Lumefantrine (used as an emergency treatment option for individuals who develop malaria symptoms while traveling in areas where the disease is prevalent)

Question 6

what is the action of mefloquine?

Answer 6

inhibits haemozoin formation

Question 7

what is the PK of mefloquine?

Answer 7

PK: 98% protein bound, T1/2: 13 – 33 days (absorption
increased food)

Question 8

what are the adverse effects of mefloquine?

Answer 8

1. Neuropsychiatric disturbances (tremor, anxiety, mood
   changes, seizures, anxiety attacks)
2. GIT disturbances
3. Visual disturbances (visual impairment, retinal
   disorders, optic neuropathy)
4. CVS effects (chest pains, oedema, sinus bradycardia

Question 9

what are the contraindications of mefloquine?

Answer 9

-hypersensitivity,
-depression or
-psychosis

Question 10

what is the MOA of doxycycline?

Answer 10

inhibit protein synthesis, assoc with apicoplast
*apicoplast found in the plasmodium species

Question 11

what is proguanil?

Answer 11

-is a prodrug of
cycloguanil,
-dihydrofolate reductase
inhibitor which disrupts
malaria parasite
synthesis of
deoxythymidylate

Question 12

what is atovaquone?

Answer 12

-selectively inhibits the parasitic mitochondrial electron
transport inhibiting parasite nucleic acid synthesis
* Ubiquinol cytochrome c oxidoreductase bc1 complex

Question 13

what are the agents used to treat p. falciparum?

Answer 13

-UNCOMPLICATED: Artemether-Lumefantrine or Quinine +
Doxycycline / Clindamycin (oral/iv)
- COMPLICATED: Artesunate (iv) / Quinine (iv)

Question 14

compare artemether and lumefantrine?

Answer 14

Artemether:
-2hr T1/2
-blood schizonticide present
- gametocide present
-Reduction in parasitaemia: fast acting
- recrudescence rate: high

Lumefantrine:
- long 4-6 days
-blood schizonticide present
- gametocide absent
-Reduction in parasitaemia: slow acting
- recrudescence rate: low

Question 15

treatment of other plasmodium infections

Answer 15

P. vivax / P. ovale / P. malariae / P. knowlesi:
- Artemether-lumefantrine / quinine-clindamycin/ doxycycline
- Primaquine (15mg daily (50-100kg adult) / 14 days) radical
cure of P. vivax/ P. ovale

Question 16

CI of other plasmodium treatment

Answer 16

pregnancy [Tx after delivery]
: children <6 months

Question 17

A/E of primaquine

Answer 17

GIT, headache, pruritus

Question 18

MOA of other plasmo. infection treatment

Answer 18

Free radical formation  lipid peroxidation
- cell membrane damage  RBC lysis
- parasite death

Question 19

caution of treatment of plasm. infections

Answer 19

G6PD-Deficiency:
 acute haemolytic anaemia
Mild – moderate (10-60% residual
G6PD activity)  45mg (0.5-0.8mg/kg)
/weekly for 8wks
Test for Anaemia, Haemoglobinuria – 3,7,10d
after start PQ Tx
C/I: Severe G6PD-deficiency (<10%)  CQ
(3yrs)