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Spring 2018 Pharm Exam 4 > #2: Malaria Drugs > Flashcards

#2: Malaria Drugs Flashcards

1
Q

Epidemiology of Malaria species

  1. which 2 MC
  2. which 2 reside in liver –> relapsing malaria
  3. which causes most deaths/severe dz
  4. where do most deaths from malaria occur
A

Epidemiology of Malaria species

  1. 2 MC = vivax, falciparum
  2. which 2 reside in liver –> relapsing malaria
    - vivax and ovale
  3. which causes most deaths/severe dz = falciparum
  4. most deaths from malaria = sub saharan africa
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2
Q

How plasmodium operates:

plasmodium breaks down Hb –> AA + heme (monomers)
- but heme is toxic to plasmodium so what do parasites do to prevent acculm of toxic heme

A

How plasmodium operates:

plasmodium breaks down Hb –> AA + heme (toxic) –> heme monomers –> heme polymers (non-toxic) by heme polymerase

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3
Q

Drugs that tx certain phases

  1. what are ONLY 2 drugs that target liver phase
    - which of those is only 1 that can target latent liver phase
A

Drugs that tx certain phases

  1. ONLY 2 drugs that target liver phase
    - Atovaquone/Proguanil
    - Primaquine = only 1 targets latent liver phase
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4
Q

Artemisinins

  1. 2 main drug prototypes
  2. acronym of combo and name of drug always given w/it
  3. MOA: all have antimalarial activity d/t what?
  4. why are they not used for ppx
A

Artemisinins

  1. 2 main drug prototypes
    - Artemether
    - Artesunate
  2. acronym of combo + drug always given w/it
    - ACT w/ Lumefantrine
  3. MOA: all have antimalarial activity d/t endoperoxide moiety
  4. not used for ppx b/c short t 1/2
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5
Q

MOA for Artemisinins

  • what does the endoperoxide moiety produce that leads to death of plasmodium
A

MOA for Artemisinins

  • endoperoxide moiety produces free radicals (toxic) –> death of plasmodium
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6
Q

Artemisinins (Artemether, Artesunate) AEs

  1. CI - what age group and what other pop
  2. what are 2 rare, dose related, reversible AEs
  3. rare AE
A

Artemisinins (Artemether, Artesunate) AEs

  1. CI
    - kids < 5
    - preg women in 1st trimester
  2. what are 2 rare, dose related, reversible AEs
    - decr RBCs/neutrophils
    - heart block
  3. rare AE= allergic rxn
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7
Q

Artemisinins: Artemether, Artesunate

  1. why considered TRUE 1st line tx
  2. targets blood stages of what 2 species
  3. why primarily used in combo
A

Artemisinins (Artemether, Artesunate)

  1. considered TRUE 1st line tx b/c Chloroquine not eff in many areas (resis)
  2. targets blood stages of 2 species
    - falciparum
    - vivax
  3. primarily used in combo b/c incr failure as monotherapy
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8
Q

Artemisinins: ACT w/Lumefantrine

  1. how does t 1/2 compare to other drugs in class
  2. 2 drug it interacts w/
  3. what must you take this drug with (2 options)
  4. 2 CIs w/ it
A

Artemisinins: ACT w/Lumefantrine

  1. longer t 1/2 vs drugs in class
  2. interacts w/ antiretrovirals/ PIs (protease inhib)
  3. must take w/ fatty food or whole milk
  4. 2 CIs
    - cardiac arrhythmias
    - CVD
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9
Q

Artemisinins: ACT w/Lumefantrine

  1. benefits of combo vs other drugs in this class (2)
  2. what is it 1st line tx for
A

Artemisinins: ACT w/Lumefantrine

  1. benefits of combo vs other drugs in class
    - incr efficacy and decr resis
  2. 1st line tx for chloroquine resistance p. falciparum
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10
Q

Quinolines

  1. 3 drugs in this class
  2. major AE w/ this class and what d/o is it a/w
A

Quinolines

  1. 3 drugs in this class
    - Chloroquine Phosphate
    - Quinine Sulfate/Gluconate
    - Primaquine
  2. major AE = hemolysis (a/w G6PD defic)
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11
Q

Chloroquinine (and others?) MOA

  • what does it prevent that leads to lysis of plasmodium
A

Chloroquinine (and others?) MOA

prevents conversion of heme monomers –> polymers
- toxic heme acculm –> lysis of plasmodium

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12
Q

Use of Chloroquine

  1. lst line but what is major con a/w it
  2. what species and stage is it highly eff vs
A

Use of Chloroquine

  1. lst line but con = widespread resis = limited use
  2. highly eff vs chloroquine-S P. falciparum (asexual blood stages)
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13
Q

Chloroquine: ADME

  1. what route of admin is potentially fatal
  2. what mutation incr transporter activity/drug efflux and causes resis
A

Chloroquine: ADME

  1. IV = potentially fatal
  2. pfcrt mutation–> incr transporter activity/drug efflux –> resis
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14
Q

Chloroquine: PO AEs

  1. vision SE
  2. 2 skin SEs
A

Chloroquine: PO AEs

  1. visual disturbances
  2. skin S/Es
    - pruritus on palms/soles
    - discoloration of nail beds/mucous mem
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15
Q

Chloroquine: IV AEs

  1. what IV dose a/w fatality
  2. what 2 organ systems mainly affected
A

Chloroquine: IV AEs

  1. IV dose >5 g a/w fatality
  2. 2 organ systems mainly affected
    - CV (arrthymia, arrest)
    - CNS (confusion, convulsions, PN)
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16
Q

Chloroquine: CIs

  1. what 2 neuro/ neumuscular d/o CI in
  2. what 2 AI dz CI in
A

Chloroquine: CIs

  1. 2 neuro/ neumuscular d/o CI in
    - epilepsy
    - myasthenia gravis
  2. 2 AI dz CI in
    - psoriasis
    - porphyria cutanea tarda
17
Q

Chloroquine: Drug Interactions

  1. what 2 drugs/subs can caused delayed GI abs of drug
  2. CYP2D6 inhib –> decr efficacy of
A

Chloroquine: Drug Interactions

  1. 2 drugs/subs –> delayed GI abs of chloroquine
    - Kaolin
    - antacids (Mg/Ca containing)
  2. CYP2D6 inhib –> decr efficacy of yellow fever vax
18
Q

What drug is

  1. mainstay for chloroquine-R and MDR P. falciparum asexual blood stages
  2. gametocytocidal vs P. vivax and ovale
A

Quinine Sulfate/Gluconate

  1. mainstay for chloroquine-R and MDR P. falciparum asexual blood stages
  2. gametocytocidal vs P. vivax and ovale
19
Q

Quinine Sulfate/Gluconate: ADME

  1. what route of admin is more potent/toxic
  2. what gene amplification –> resis d/t incr drug efflux
A

Quinine Sulfate/Gluconate: ADME

  1. IV = more potent/toxic
  2. Pfmdr1 amplification –> resis d/t incr drug efflux
20
Q

Quinine Sulfate/Gluconate: AEs

  1. what is the dose related toxcity
  2. what is the serious HSN rxn from it (must stop Tx)
  3. what AE can be fatal
  4. what is rare but serious AE
  5. what is the fatal PO dose range
A

Quinine Sulfate/Gluconate: AEs

  1. dose related toxcity = Cinchonism
  2. serious HSN rxn from it (must stop Tx)
    - blackwater fever
  3. Hypoglycemia (+/- fatal)
  4. HoTN = rare but serious AE
  5. Fatal PO dose = 2-8 g
21
Q

Quinine Sulfate/Gluconate: name that AE

  1. if pt on drug presents w/ hemolysis, hemoglobinemia/uria
  2. if pt on drug presents w/ pulm edema, ITP, irrev deafness, and arrhythmias
A

Quinine Sulfate/Gluconate: name that AE

  1. if pt on drug presents w/ hemolysis, hemoglobinemia/uria = Blackwater fever
  2. if pt on drug presents w/ pulm edema, ITP, irrev deafness, and arrhythmias = fatal PO dose
22
Q

Quinine Sulfate/Gluconate CIs/drug interactions

  1. 2 CIs
  2. what pts must you decr dose in
  3. what can delay GI abs
  4. what type of inhib –> incr levels of warfarin/digoxin
A

Quinine Sulfate/Gluconate CIs/drug interactions

  1. 2 CIs = tinnitus, optic neuritis
  2. decr dose in pts w/ renal insuffic
  3. antacids (Mg/Al containing) delay GI abs
  4. CYP34A inhib –> incr levels of warfarin/digoxin
23
Q

Uses of Primaquine

  1. what 2 species is eff vs
  2. what is unique about what phase this drug works vs
  3. gametocytocidal vs which species
A

Uses of Primaquine

  1. eff vs p vivax and ovale
  2. unique = ONLY drug works vs latent liver phase of plasmodium (also works vs primary liver phase)
  3. gametocytocidal vs P. falciparum
24
Q

Primaquine: ADME

  1. why given PO (what is risk given IV)
A

Primaquine: ADME

  1. given PO b/c given IV –> risk of HoTN
25
Q

Primaquine: CIs

  1. pts w/ what d/o is it CI in
  2. what pt pop group is it also CI in
  3. what 2 AI dzs is it CI in
  4. what other drugs cant it be given w/
A

Primaquine: CIs

  1. G6PD defic
  2. Pregnancy
  3. 2 AI dzs –> RA and Lupus
  4. cant be given w/ myelosuppressive drugs
26
Q

Name of the 2 ABX given as adjuncts w/Quinolone class

ineffective as monotherapy

A

2 ABX given as adjuncts w/Quinolone class

  1. Doxycycline
  2. Clindamycin
27
Q

Adjuncts w/Quinolone class

  1. what do they inhibit in the protoza and what does this cause in their progeny
  2. what species are they used to tx (in combo)
A

Adjuncts w/Quinolone class

  1. inhibit protein translation –> death of protoza progeny
  2. tx P. falciparum (in combo)
28
Q

What drug inhibits the parasite mitochondrial ETC by binding to cytochrome b (unique to plasmodium) –> cant generate ATP

A

Atovaquone

-inhibits parasite’s mitochondrial ETC by binding to cytochrome b (unique to plasmodium) –> cant generate ATP

29
Q

Atovaquone

  1. what mutations –> resis by inhibiting drug binding
  2. what other 2 drugs –> decr plasma levels of drug
  3. what is unique about phase its eff vs in plasmodium
A

Atovaquone

  1. cyt b mutations –> resis by inhibiting drug binding
  2. 2 drugs –> decr plasma levels of drug
    - rifampin
    - tetracycline
  3. eff vs primary liver stages of plasmodium
30
Q

Atovaquone: Use

  1. which species is it NOT eff for primary liver stage
  2. why is it used in combo, what used in combo w/
A

Atovaquone: Use

  1. NOT eff for primary liver stage in vivax
  2. used in combo b/c resis to monotherapy and synergy w/combo
    - combo w/ Proguanil
31
Q

Proguanil

  1. MOA: what enzyme does it inhibit
  2. what type of CYP polymorphism may affect drug’s hepatic metab
  3. what phase eff vs for p. falciparum (2)
  4. what species also eff vs
A

Proguanil

  1. MOA: inhibit DHFR
  2. CYP2C19 polymorphism may affect drug’s hepatic metab
  3. what phase eff vs for p. falciparum
    - asexual blood stage and primary liver stage
  4. also eff vs vivax
32
Q

Atovaquone/Proguanil

  1. AE common to both
  2. both are useful for what
A

Atovaquone/Proguanil

  1. AE common to both = risk cant be r/o in preg
  2. both are useful for ppx

Spring 2018 Pharm Exam 4 (7 decks)

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