W2 LECT 10: Pharm of drugs used in the management of malaria Flashcards
what are the characteristics of malaria?
- Infection of RBC
- Plasmodium
. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi - Transmission - bite of a vector
who are the pts. at greater risk of contracting malaria?
- Pregnant
- Children < 5years
- Elderly
- Immunocompromised
- Splenectomised
- Non-immune patients
what are the symptoms of malaria?
- headache
- fever
- fatigue, pain
- back pain
- nausea, vomiting
- enlarged spleen
- dry cough
- chills and sweating
what do antimalarial drugs target?
- hepatic stage
- gametocytes
- intra erythrocytic stage
what are the prophylatic agents?
- Mefloquine: 1wk before/wkly/4wks after return
- Doxycycline: 1d before/daily/4wks after return
- 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)
what is the action of mefloquine?
inhibits haemozoin formation
what is the PK of mefloquine?
PK: 98% protein bound, T1/2: 13 – 33 days (absorption
increased food)
what are the adverse effects of mefloquine?
- Neuropsychiatric disturbances (tremor, anxiety, mood
changes, seizures, anxiety attacks) - GIT disturbances
- Visual disturbances (visual impairment, retinal
disorders, optic neuropathy) - CVS effects (chest pains, oedema, sinus bradycardia
what are the contraindications of mefloquine?
-hypersensitivity,
-depression or
-psychosis
what is the MOA of doxycycline?
inhibit protein synthesis, assoc with apicoplast
*apicoplast found in the plasmodium species
what is proguanil?
-is a prodrug of
cycloguanil,
-dihydrofolate reductase
inhibitor which disrupts
malaria parasite
synthesis of
deoxythymidylate
what is atovaquone?
-selectively inhibits the parasitic mitochondrial electron
transport inhibiting parasite nucleic acid synthesis
* Ubiquinol cytochrome c oxidoreductase bc1 complex
what are the agents used to treat p. falciparum?
-UNCOMPLICATED: Artemether-Lumefantrine or Quinine +
Doxycycline / Clindamycin (oral/iv)
- COMPLICATED: Artesunate (iv) / Quinine (iv)
compare artemether and lumefantrine?
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
treatment of other plasmodium infections
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
CI of other plasmodium treatment
pregnancy [Tx after delivery]
: children <6 months
A/E of primaquine
GIT, headache, pruritus
MOA of other plasmo. infection treatment
Free radical formation lipid peroxidation
- cell membrane damage RBC lysis
- parasite death
caution of treatment of plasm. infections
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)
