Anti-Malarials

Question 1

what is the first-line anti-malarial?

Answer 1

chloroquine, but resistance is widespread

Question 2

What is WHO’s first-line treatment for malaria if chlorquine resistant P. falciparum?

Answer 2

artemether-lumefantrine (Coartem)

target blood stages

Question 3

which species of malaria cause a relapsing form (live in liver)

Answer 3

ovale - least common (Africa)

vivax - most common

Question 4

P. vivax and falciparum make up what percentage of malaria infections?

Answer 4

95%

Question 5

Where do the various agents act?

Answer 5

Question 6

what is the only agent that acts at the hypnozoite stage?

Answer 6

primiquine

Question 7

what are the only agents that acts at the hepatic schizont stages

Answer 7

primiquine

atovoquone-proguanil

(this occurs within 30 minutes of bite)

Question 8

what agents only act at the blood schizont stage (not the gametocyte stage)

Answer 8

mefloquine

doxycycline

clindamycin

Question 9

what agents act at the gametocyte stage (blood)

Answer 9

ACT

quinine

chloroquine

primaquine

atoquavone-proguanil

Question 10

where do the artemesinins act?

Answer 10

blood stages of falciparum

some gametocyte of falciparum

asexual blood stages of vivax

Question 11

what are the artemisinins?

Answer 11

artemether (PO/IM)

artesunate (rectal/IV)

Question 12

what is the ADME of the artemesinins?

Answer 12

1-2 hr 1/2 life - not useful for prophylaxis

biliary excretion

Question 13

what is the mechanim of action of the artemisinins?

Answer 13

peroxide bridge reduced by heme results in free radical production

Question 14

What are the contraindications of the artemesinins?

Answer 14

1st trimester of pregnancy

children < 5kg

Question 15

what are the S/E of the artemesinins?

Answer 15

decrease in RBC and neutrophils

transient heart block

*rare, dose, related; reversible

Question 16

What is the ADME of Coartem?

Answer 16

Large Vd

t1/2= 4-5 days

absorption increased with high fat meal

drug-drug with antiretroviral/protease inhibitors

Question 17

What are contraindications to ACT?

Answer 17

cardiac arrhythmias

cardiac disease

(kids and pregos)

Question 18

what are the adverse effects of ACT?

Answer 18

Adults: GI distress, headache

Kids: fever, cough, vomiting, headache, anorexia

cardiac arrhythmias/neurologic symptoms with high doses

TAKE with fatty food or whole milk

Question 19

what is the MOA of chloroquine?

Answer 19

inteferes with heme digestion

Question 20

what is the ADME of chloroquine?

Answer 20

CYP3A4 metabolism

renal excretion

loading does required - high doses usually fatal

Question 21

what’s the greatest thing about chloroquine?

Answer 21

It is safe in pregnancy!

Question 22

What are the AEs of chloroquine?

Answer 22

GI distress

headache

visual disturbances

urticaria

rare hemolysis (increased with G6PD deficiency)

Question 23

What are the contraindications of chlorquinolone?

Answer 23

epilepsy/myasthenia gravis

psoriasis/poryphia cutanea

advanced liver disease, blood disorders, severe GI or neurological disorders

can prolong QT

antacids delay absorption

decreases efficacy of yellow fever vaccine

Question 24

quinine acts on what stages?

Answer 24

falciparum asexual blood stages

gemetocyticidal against vivax and ovale

Question 25

What is the ADME of quinine?

Answer 25

oral, IM, IV (more toxicity) readily absorbed, extensive tissue distribution t1/2=11 hours

Question 26

what are the AEs of quinine?

Answer 26

Cinchonism: tinnitus, hearing loss, visual disturbance, headache, nausea, vomiting, dizziness, postural hypotension rash, angiodema, bronchospasm blackwater fever: severe hemolysis (STOP) IV - hypoglycemia, hypotension fatal arrythmia and ITP at 2-8 g

Question 27

what are the contraindications/cautions with quinine?

Answer 27

D/c if evidence of hemolysis tinnitus/optic neuritis caution: cardiac dysrhythmias decrease dose in renal insufficiency potentially safe in pregnancy (monitor glucose) inhibits CYP3A4 (digoxin and warfarin)

Question 28

what are doxycycline, clindamycin and tetracycline good for?

Answer 28

adjunct therapy with quinine/quinidine they act slowly in killing blood schizonts by inihibiting protein translation in protozoa

Question 29

when is primaquine active?

Answer 29

only agent that can eradicate liver stages of vivax and ovale gametocytocial against falciparum

Question 30

what must you do before giving primiquine?

Answer 30

screen for G6PD deficiency

Question 31

What's the MOA of primiquine?

Answer 31

interferes with mitochondrial ETC in parasite

Question 32

what is the ADME of primiquine?

Answer 32

large Vd t1/2=3-8 h rapid hepatic metabolism and renal excretion

Question 33

what are the contraindications of primiquine?

Answer 33

* pregnant women * lupus and rheumatoid arth (if active) * hemolytic anemia in G6PD deficiency (x-linked) * 11% of AA males * Sardinians, Sephardic Jews, Greeks, Iranians

Question 34

what is the MOA of atovaquone?

Answer 34

inhibits mitochondrial ETC

Question 35

what is atovoquone active against?

Answer 35

asexual blood stages and primary liver stages in falciparum (ONLY)

Question 36

what is the ADME of atovoquone?

Answer 36

oral, lipophilic slow absorption (increased with fatty meal) t 1/2 2-3 days no sig. metab, bilary excretion

Question 37

what is the mechanism of resistance to atovoquone?

Answer 37

cytochrome b mutations inhibit drug binding

Question 38

what are the AEs of atovoquone?

Answer 38

GI distress headache rash risk can not be ruled out for pregos rifampin/tetracycline reduce plasma levels

Question 39

what is proguanil active against?

Answer 39

asexual blood and primary liver stages of falciparum and vivax

Question 40

what is the MoA of proguanil?

Answer 40

inhbits dihydrofolate reductase (enhances atovaquone effect)

Question 41

what is the ADME of proguanil?

Answer 41

slow absorption t1/2=18-20 hours hepatic metabolism (CYP2C19) renal excretion

Question 42

is proguanil safe in pregnancy?

Answer 42

risk cannot be ruled out

Question 43

where does mefloquine act?

Answer 43

against asexual blood stages

Question 44

what is mefloquine used for?

Answer 44

prophylaxis and treatment of drug-resistant falciparum (best for prophylaxis) MOA Unknown

Question 45

what is the ADME of mefloquine?

Answer 45

rapidly absorbed (variable) extensive Vd t/12-13-24 days (extensive protein binding( CYP3A4 metabolism mainly biliary excretion

Question 46

what are the AE's and contraindications of mefloquine?

Answer 46

GI distress and dizziness (short-term) vivid dreams black box: severe and permanent neuro and psych effects (10%) 2011: pregnant women, all trimesters CDC recommended NO in seizures, depression bipolar