Lecture 2 - AntiMalaria Drugs Flashcards
Artemisinis
Artemether (PO/IM)
Artesunate (IV/rectal)
blood stages of P. falciparum and asexual blood stages of P. vivax
anti-malarial activity has been attributed to endoperoxide moiety - free radical production
rapid absorption and metabolism (CYP) -biliary excretion
short t1/2 - not useful for prophylaxis
artemisin-based combination therapies (ACTs) increase their efficacy and decrease resistance
What is the proposed MOA of artemisinins?
that they are activated (something to do with Fe) and form free radicals –these bind to everything and destroy the plasmodium (endoperoxide moiety)
What are the SEs and CIs for artemisins?
artmether
artesunate
not recommended for children <5kgs or during the 1st trimester
transient heart block (rare, reversible)
ACTs
artemisin based combo therapy
artemisins fail as monotherapy
this combo increases efficacy and decreases resistance
ex. Artemether-Lumefantrine (Coartem)
Where is there emerging resistance with artemisins?
SE asia
What is the WHO recommended 1st line treatment for chloroquine resistant plasmodium flaciparum?
Artemether-Lumefantrine (Coartem)
How does the half life of Coartem differ from Artemether alone?
Coartem = artemether -lumefantrine
goes from super short to 4-5 days
What is a major risk of Coartem?
drug drug interactions with antiretrovirals/protease inhibitors
What are SE of coartem?
adverse effects of ACTs:
GI distress, HA
take with fatty food or whole milk. If pt throws up within 30 minutes of taking dose, take another
What are the contraindications of Coartem?
cardiac arrhythmia’s, cardiac disease
Chloroquine
drug of choice
highly effective against chloroquine sensitive plasmodium flaciparum asexual blood stages
loading dose is required
parenteral routes can be fatal (esp if >5g)
MOA: interferes with heme digestion
inhibits polymerization of heme to hemozoin –> causes toxic levels of heme that destroy plasmodium and the RBC
What is the MOA of chloroquine?
inhibits polymerization of heme to hemozoin –> causes increase in heme to toxic levels killing both plasmodium and RBC
What resistance is associated with chloroquine?
protonated chloroquine (PfCRT) mutations associated with resistance
What are the indications for chloroquine?
chloroquine sensitive p. falciparum asexual blood stages
What are the contraindications of chloroquine?
epilepsy
myasthenia gravis
liver disease
GI/neurological or blood disorders
What are the adverse effects of chloroquine?
narrow safety margin
PO:
visual disturbances
pruritus in pts of african descent
hemolysis (increased with G6PD deficiency)
discoloration of nail beds/mucous membranes
Quinine
Indications:
mainstay for chloroquine resistant and MDR P. falciparum asexual blood stages; gametocyticdal against P. vivax and P. ovale
MOA:
interferes with heme digestion
ADME:
good tissue distribution (CNS and placenta)
Resistance:
pfmdr1 gene amplification
Adverse effects:
dose related toxicities
cinchonism: tinnitus, deafness, visual disturbance, HA, nausea, vomiting, dizziness, postural hypotension (reversible)
blackwater fever: severe…hemolysis; hemoglobnemia; hemoglobinuria - STOP tx
CI:
caution in pts with hyersensitivity - d/c if hemolysis
tinnitus/optic neuritis
decrease dose with renal insufficiency
*potentially safe in pregnancy (monitor glucose)
commonly used in adjunctive therapies to decrease duration/toxicity
-doxycycline, clindamycin
What are the indications for quinine?
mainstay for chloroquine resistant and MDR P. falciparum asexual blood stages; gametocyticdal against P. vivax and P. ovale
*potentially safe in pregnancy (monitor glucose)
commonly used in adjunctive therapies to decrease duration/toxicity
-doxycycline, clindamycin
good tissue distribution (CNS and placenta)
What are the contraindications of quinine?
caution in pts with hyersensitivity - d/c if hemolysis
tinnitus/optic neuritis
decrease dose with renal insufficiency
potentially safe in pregnancy (blood glucose needs to be monitored)
What is the MOA of quinine?
interferes with heme digestion
What resistance is seen with quinine?
pfmdr1 gene amplification
What are the SE of quinine?
dose related toxicities
cinchonism: tinnitus, deafness, visual disturbance, HA, nausea, vomiting, dizziness, postural hypotension (reversible)
blackwater fever: severe…hemolysis; hemoglobnemia; hemoglobinuria - STOP tx
Primaquine
indications:
acts on primary and latent hepatic stages of plasmodia; effective against replast in P. vivax and P. ovale; gametocytocidal against P. falciparum
(inactive against asexual blood stages)
ONLY agent that can eradicate liver stages of P. vivax and P. ovale
YOU MUST SCREEN for G6PD deficiency FIRST –hemolysis risk
SE:
mild GI distress
methemoglobinemia
hemolytic anemia in G6PD deficiency (X-linked)
CI:
pregnancy
r/o G6PD deficiency in breast feeding infants
What are the indications for primaquine?
acts on primary and latent hepatic stages of plasmodia; effective against replast in P. vivax and P. ovale; gametocytocidal against P. falciparum
(inactive against asexual blood stages)
ONLY agent that can eradicate liver stages of P. vivax and P. ovale
YOU MUST SCREEN for G6PD deficiency FIRST –hemolysis risk
