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Pharm 2 - Exam 4 > Lecture 2 - AntiMalaria Drugs > Flashcards

Lecture 2 - AntiMalaria Drugs Flashcards

1
Q

Artemisinis

A

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

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2
Q

What is the proposed MOA of artemisinins?

A

that they are activated (something to do with Fe) and form free radicals –these bind to everything and destroy the plasmodium (endoperoxide moiety)

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3
Q

What are the SEs and CIs for artemisins?

A

artmether
artesunate

not recommended for children <5kgs or during the 1st trimester

transient heart block (rare, reversible)

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4
Q

ACTs

A

artemisin based combo therapy

artemisins fail as monotherapy

this combo increases efficacy and decreases resistance

ex. Artemether-Lumefantrine (Coartem)

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5
Q

Where is there emerging resistance with artemisins?

A

SE asia

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6
Q

What is the WHO recommended 1st line treatment for chloroquine resistant plasmodium flaciparum?

A

Artemether-Lumefantrine (Coartem)

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7
Q

How does the half life of Coartem differ from Artemether alone?

A

Coartem = artemether -lumefantrine

goes from super short to 4-5 days

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8
Q

What is a major risk of Coartem?

A

drug drug interactions with antiretrovirals/protease inhibitors

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9
Q

What are SE of coartem?

A

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

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10
Q

What are the contraindications of Coartem?

A

cardiac arrhythmia’s, cardiac disease

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11
Q

Chloroquine

A

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

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12
Q

What is the MOA of chloroquine?

A

inhibits polymerization of heme to hemozoin –> causes increase in heme to toxic levels killing both plasmodium and RBC

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13
Q

What resistance is associated with chloroquine?

A

protonated chloroquine (PfCRT) mutations associated with resistance

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14
Q

What are the indications for chloroquine?

A

chloroquine sensitive p. falciparum asexual blood stages

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15
Q

What are the contraindications of chloroquine?

A

epilepsy
myasthenia gravis
liver disease
GI/neurological or blood disorders

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16
Q

What are the adverse effects of chloroquine?

A

narrow safety margin

PO:
visual disturbances
pruritus in pts of african descent
hemolysis (increased with G6PD deficiency)
discoloration of nail beds/mucous membranes

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17
Q

Quinine

A

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

18
Q

What are the indications for quinine?

A

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)

19
Q

What are the contraindications of quinine?

A

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)

20
Q

What is the MOA of quinine?

A

interferes with heme digestion

21
Q

What resistance is seen with quinine?

A

pfmdr1 gene amplification

22
Q

What are the SE of quinine?

A

dose related toxicities
cinchonism: tinnitus, deafness, visual disturbance, HA, nausea, vomiting, dizziness, postural hypotension (reversible)
blackwater fever: severe…hemolysis; hemoglobnemia; hemoglobinuria - STOP tx

23
Q

Primaquine

A

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

24
Q

What are the indications for primaquine?

A

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

25
Q

What is the MOA of primaquine?

A

induced oxidative stress and RBC hemolysis in G6PD deficiency

something to do with NADH and glutathione

26
Q

What are the contraindications of primaquine?

A

pregnancy

r/o G6PD deficiency in breast feeding infants

27
Q

What are the contraindications of primaquine?

A

pregnancy! (fetus does not have G6PD)
r/o G6PD deficiency in breast feeding infants

RA

this means that there is really no treatment for a pregnant women infected with p. vivax

28
Q

Atovaquone

A

indication:
active against P. falciparum asexual blood stages and primary liver stages (not P. vivax)

MOA:
inhibits parasite mitochondrial electron transport by binding to cytokine specific to parasite

resistance to monotherapy
-cyt b mutations inhibit drug binding and confer resistance
combination with proguanil (Malarone)
-useful for prophylaxis

29
Q

What is the indication for atovaquone?

A

active against P. falciparum asexual blood stages and primary liver stages (not P. vivax)

30
Q

What is the MOA of atovaquone?

A

inhibits parasite mitochondrial electron transport by binding to cytokine specific to parasite

31
Q

What resistance is seen with atovaquone?

A

resistance to monotherapy
-cyt b mutations inhibit drug binding and confer resistance
combination with proguanil (Malarone)
-useful for prophylaxis

32
Q

Malarone

A

combo drug of atovaquone + proguanil

33
Q

What are the SE of atovaquone?

A

GI distress
HA
rash

risk can not be ruled out in pregnancy

34
Q

What are the contraindications of atovaquone?

A

pregnancy

35
Q

What are the drug drug reactions seen with atovaquone?

A

may compete for protein binding of other drugs

rifampin/tetracycline decrease plasma levels of atavaquone

36
Q

Proguanil

A

used with atovaquone in combo drug called malarone

active against asexual blood and primary liver stages of P. falciparum and acute P. vivax

prodrug

inhibits dihydrofolate reductase –enhances atovaquone effect

37
Q

What is the MOA of proguanil?

A

prodrug

inhibits dihydrofolate reductase –enhances atovaquone effect

38
Q

Which prophylaxis drugs are used?

A

chloroquine is ideal but there is a lot of resistance to it

atovaquone-proguanil is used
mefloquine is cheaper

39
Q

Which antimalaria drugs are used in pregnancy?

A

chloroquine

quinine + clindamycin

mefloquine

40
Q

What is the MOA of chloquine in the treatment of malaria?

A

causes an accumulation of toxic heme metabolite which poisons the parasite

41
Q

What is the BEST choice for malaria prophylaxis for a traveler?

A

atovaquone-proguanil

42
Q

Malarone

A

Malaria prophylaxis

Atovaquone - proguanil

Atovaquone: Inhibit electron transport change (decrease ATP)
-resistance cyt b mutation

Proguanil: inhibit dihydrofolate reductase
-prodrug

Pharm 2 - Exam 4 (9 decks)

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