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05.1 - FARMACOLOGIA CLÍNICA > Antiparasitic Questions > Flashcards

Antiparasitic Questions Flashcards

1
Q

What percent of the world’s population is chronically infected with parasites?

A

50%

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2
Q

How are parasites causing human disease categorized?

A

Two main categories

  • unicellular protozoa
  • multicellular helminthes
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3
Q

How are protozoa categorized?

A

Have many subgroups but can be categorized into:

  • intestinal
  • primarily extraintestinal pathogens
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4
Q

How are helminthes subdivided?

A
  • nematodes (roundworms)
  • trematodes (flukes)
  • cestodes (tapeworms)
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5
Q

What two other organisms (technically not considered parasites) are susceptible to antiparasitics?

A
  • Pneumocystis jirovecii (technically a fungus)

- Sarcoptes scabiei (scabies mite; technically an Arachnid)

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6
Q

What is plasmodium (malaria)?

A

Extraintestinal protozoa

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7
Q

What is toxoplasma?

A

Extraintestinal protozoa

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8
Q

What is trypansoma?

A

Extraintestinal protozoa

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9
Q

What is entamoeba?

A

Intestinal protozoa

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10
Q

What is giardia?

A

Intestinal protozoa

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11
Q

What is cryptosporidium?

A

Intestinal protozoa

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12
Q

What is ascaris?

A

Nematode

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13
Q

What is strongyloides?

A

Nematode

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14
Q

What is schistosoma?

A

Trematode

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15
Q

What is echinococcus?

A

Cestode

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16
Q

What is taenia?

A

Cestode

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17
Q

What is pneumocystis?

A

Fungus

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18
Q

What is scabies?

A

Ectoparasite

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19
Q

Name the quinolines?

A
  • Chloroquine
  • Mefloquine
  • Quinidine
  • Quinine
  • Primaquine
  • amodiaquine
  • hydroxychloroquine
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20
Q

From what tree are quinoline agents derived?

A

Cinchona tree bark

  • imported from Peru
  • used to treat fever in malarious areas of Europe dating back to the 17th century
  • quinine was the primary component in the bark
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21
Q

What determines differences in activity for the quinolines?

A
  • species of Plasmodium

- geographic area

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22
Q

What is the MOA of quinolines?

A

MOA on parasites are incompetent understood

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23
Q

What is the MOA of quinine, quinidine, and chloroquine?

A

Appear to interfere with the ability of the malaria parasite to detoxify hemoglobin metabolites

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24
Q

What is the MOA of primaquine?

A

Appears to affect parasitic mitochondrial function

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25
Q

What protozoa are quinolines active against?

A

Activity variable by region

  • Plasmodium falciparum
  • P. malariae
  • P. ovale
  • P. vivax
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26
Q

What fungus is primaquine active against?

A

P. jirovecii

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27
Q

Describe quinoline CV toxicity.

A

Dose related CV toxicity

  • QT interval prolongation
  • hypotension
  • potentially fatal ventricular arrhythmias
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28
Q

What class of anti-arrhythmic is quinidine?

A

Class IA

  • used therapeutically in the treatment of some arrhythmias
  • can be proarrhythmic
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29
Q

Wth which quinoline are CV effects most likely?

A

IV quinidine

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30
Q

Wth which quinolines are CV effects less common?

A
  • quinine
  • mefloquine
  • chloroquine
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31
Q

Wth which quinoline are CV effects rare?

A

Primaquine

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32
Q

Which quinoline can cause hematologic effects.

A

Primaquine

  • can cause hemolysis in patients deficient in glucose-6-phosphate dehydrogenase (G6PD)
  • testing for G6PD deficiency is required before use
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33
Q

Which quinolines can cause metabolic effects.

A

Quinidine and quinine

  • profound hypoglycemia
  • resulting from stimulated release of insulin
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34
Q

Which quinoline can cause psychiatric effects.

A

Mefloquine

  • associated with a range of psychiatric disturbances
  • well tolerated by the vast majority patients but certain patients may experience them
  • insomnia
  • vivid dreams
  • mood swings
  • depression
  • psychosis
  • suicide
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35
Q

What patients should avoid taking mefloquine?

A

History of psychiatric issues

-includes depression

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36
Q

Which quinoline can cause cinchonism?

A

Quinine

  • common in patients receiving therapeutic doses
  • tinnitus
  • headache
  • nausea
  • visual disturbances
  • can lead to discontinuation of therapy due to intolerance
  • resolves after drug discontinuation
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37
Q

Which quinoline is available as IV form in the US?

A

Quinidine

-used in combination regimens for treatment of severe malaria

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38
Q

How should IV quinidine be monitored?

A

Continuous monitoring of

  • BP
  • ECG

Serial monitoring

-blood glucose

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39
Q

How does renal failure affect IV quinidine dosing?

A

Dosing is altered

-not uncommon in severe malaria

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40
Q

What makes primaquine special compared to other antimalarials?

A

Active against the “hypnozoite” forms of P. vivax and P. ovale

  • can lay dormant in the liver and cause relapsing infections
  • 2 week course of primaquine is added when these species is documented
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41
Q

What is chloroquine good for?

A
  • treatment of uncomplicated malaria acquired in chloroquine sensitive areas (only a few regions)
  • prophylaxis against malaria in travelers to those regions
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42
Q

What is mefloquine good for?

A
  • treatment of uncomplicated malaria acquired in mefloquine sensitive areas (most of the world except Southeast Asia)
  • prophylaxis against malaria in travelers to those regions
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43
Q

What is quinine/quinidine good for?

A
  • treatment of severe malaria (quinidine) in combination with
  • doxycycline

or

-tetracycline

or

  • clindamycin
  • not used for prophylaxis
44
Q

What is primaquine good for?

A
  • treatment of uncomplicated malaria due to P. vivax or P. ovale in combination with a second agent
  • prophylaxis against malaria in travelers where P. vivax is the principal species
  • in combination with clindamycin
  • treatment of mild to moderate Pneumocystis pneumonia
45
Q

What is atovaquone?

A

Antiparasitic

-activity against several important protozoans

46
Q

What is Malarone?

A

Atovaquone in combination with proguanil

-enhanced activity against the malaria parasite

47
Q

How is atovaquone tolerability compared to other drugs?

A

Better tolerated

48
Q

What limits atovaquone use?

A
  • lack of IV formulation (for severe disease)
  • high cost
  • somewhat lower efficacy (for Pneumocystis disease)
49
Q

What is the MOA of atovaquone?

A

Appears to interfere with electron transport in the parasitic mitochondria

50
Q

What fungus is atovaquone active against?

A

P. jirovecii

51
Q

What protozoa is atovaquone active against?

A
  • Plasmodium species
  • Toxoplamsa gondii
  • Babesia species
52
Q

How is atovaquone tolerated?

A

Very well tolerated

53
Q

What are the most common adverse effects with atovaquone?

A

GI

  • nausea/vomiting
  • diarrhea
  • abdominal pain
54
Q

How is atovaquone available?

A

Suspension

55
Q

How is Malarone available?

A

Tablet

56
Q

How is atovaquone and Malarone bioavailability?

A

Low with both

-enhanced substantially when given with food (especially high fat meals)

57
Q

How active is atovaquone in treating mild to moderate Pneumocystis pneumonia in patients intolerant of TMP/SMX?

A
  • slightly less effective than comparators (dapsone or pentamidine)
  • better tolerated
  • lead to similar overall success rates
58
Q

When should atovaquone not be used against Pneumocystis?

A
  • severe Pneumocystis pneumonia

- patients whose GI absorption is thought to be poor

59
Q

Why is Malarone favorable for malaria prophylaxis for travelers?

A
  • highly effective
  • well tolerated
  • active against chloroquine resistant Plasmodium
60
Q

What is the timeframe for Malarone prophylactic use?

A
  • start 1-2 days before travel
  • take while in the malaria-endemic area
  • continue for 7 days after return
61
Q

What is the timeframe for many other antimalarials for prophylactic use?

A
  • start 2 weeks before travel

- continue for 4 weeks afterward

62
Q

What is atovaquone good for?

A
  • treatment of mild to moderate Pneumocystis pneumonia

- prophylaxis against Pneumocystis in patients intolerant of first line therapy

63
Q

What is Malarone good for?

A
  • treatment of uncomplicated malaria

- prophylaxis against malaria

64
Q

How should patients take atovaquone?

A
  • with food (or at least a glass of milk)

- bioavailability is increased 5x when administered with food

65
Q

Name the benzimidazoles.

A
  • albendazole
  • mebendazole (no longer available in US)
  • thiabendazole (no longer available in US)
66
Q

What are benzimidazoles used for?

A

Primarily for helminthes (worms)

  • range from common pinworms to pathogens causing massive cystic lesions in the brain
  • most intestinal worm infections can be cured with a single dose
  • tissue invasive diseases require prolonged courses
67
Q

What is the MOA of benzimidazoles?

A

Interfere with elongation of the microtubules responsible for parasitic cellular structure

-leads to disruption of growth and division

68
Q

What nematodes (roundworms) are benzimidazoles active against?

A
  • Ascaris lumbricoides (roundworm)
  • Enterobius vermicularis (pinworm)
  • Necator americanus (hookworm)
  • Strongyloides stercoralis (threadworm)
69
Q

What cestodes (tapeworms) are benzimidazoles active against?

A
  • Echinococcus (liver abscess)

- Taenia solium (neurocysticercosis)

70
Q

How is single dose therapy of albendazole for intestinal worm infections tolerated?

A

Very well tolerated

71
Q

What adverse effects do multi dose regimens of albendazole have?

A
  • primarily GI
  • hepatotoxicity (rare)
  • neutropenia (rare)
72
Q

Which benzimidazole is most toxic?

A

Thiabendazole

-can cause CNS adverse effects

73
Q

Can benzimidazoles be used in pregnancy?

A

Should generally be avoided

-some data suggest may be safe after first trimester

74
Q

Are benzimidazoles affected by drug interactions?

A
  • appear to be substrates of the P450 system

- strong inducers (rifampin, phenytoin) may lower serum levels

75
Q

How is oral absorption of albendazole?

A

Limited

  • generally does not pose a problem for treatment of intestinal nematode infections (drug interactions not a concern)
  • for systemic infections, be aware of interactions
76
Q

What are benzimidazoles good for?

A
  • single dose therapy of most intestinal nematode infections
  • alternative for treatment of Strongyloides infection
  • treatment for tissue invasive Echinococcus or Taenia infection
77
Q

What can drug induced killing of some parasitic infections cause?

A

Releases antigens that can cause allergic reactions

-corticosteroids are sometimes administered to mitigate these effects

78
Q

What is the primary alternative to TMP/SMX for patients with Pneumocystis pneumonia?

A

Pentamidine

-Pneumocystis was once an extremely common cause of severe pneumonia in HIV patients before effective antiretrovirals

79
Q

How can pentamidine be administered?

A

IV or inhalation

-proper route depends on indication

80
Q

What is the MOA of pentamidine?

A

Appears to bind to and disrupt function of tRNA

-results in inhibition of protein synthesis

81
Q

What fungus is pentamidine active against?

A

P. jirovecii

82
Q

What protozoa is pentamidine active against?

A
  • Trypanosoma

- Leishmania

83
Q

What are the categories of adverse effects of IV pentamidine?

A
  • CV
  • metabolic
  • renal
  • respiratory
84
Q

Describe the CV effects of IV pentamidine.

A
  • hypotension with rapid infusion (infuse over at least an hour)
  • cases of QT prolongation with ventricular arrhythmia have been reported
85
Q

Describe the metabolic effects of IV pentamidine.

A

Toxic to the pancreas

  • dysglycemias in up to 25% of patients
  • other manifestations of pancreatitis may occur
86
Q

Describe pentamidine induced dysglycemia?

A
  • initially may manifest as hypoglycemia (pentamidine induced pancreatic injury causes release of insulin from islet cells)
  • continuing injury can cause decrease in pancreatic function (hypoinsulinemia and hyperglycemia)
  • continued use may lead to irreversible damage (leaving patients with DM)
87
Q

Describe IV pentamidine renal effects.

A

Nephrotoxicity is common

-generally reversible upon drug discontinuation

88
Q

What electrolyte disturbances can IV pentamidine cause?

A
  • hypokalemia

- hypocalcemia

89
Q

Describe IV pentamidine respiratory effects.

A

Inhalation administration may induce bronchoconstriction (especially in asthma patients)

-pretreatment with an inhaled bronchodilator may lessen these effects

90
Q

How does pentamidine compare to SMX/TMP for Pneumocystis pneumonia?

A

About equal in efficacy

-only half could tolerate a full course of IV pentamidine without stopping or decreasing the dose

91
Q

What are considerations when giving IV pentamidine?

A

Careful monitoring

  • ECG
  • metabolic panel

Supportive care interventions

  • electrolyte replacement
  • glucose
  • insulin
92
Q

Is dosage adjustment for pentamidine in renal sufficiency required?

A

Recommended

93
Q

How often is inhaled pentamidine given for prophylaxis against Pneumocystis pneumonia?

A
  • once monthly

- reasonable efficacy as 2nd line agent

94
Q

What are the downsides to giving inhaled pentamidine for prophylaxis?

A
  • cases of extrapulmonary Pneumocystis infections have been reported
  • does not protect against Toxoplasma disease or bacterial pneumonia like TMP/SMX
95
Q

What is IV pentamidine used for?

A
  • alternative for treatment of severe Pneumocystis pneumonia
  • alternative for treatment of leishmaniasis and trypanosomiasis
96
Q

What is inhaled pentamidine used for?

A

-alternative for prophylaxis against Pneumocystis pneumonia

97
Q

What drugs may a patient on pentamidine also be in on that could exacerbate its toxicities?

A
  • insulin
  • furosemide
  • aminoglycosides
  • antiarrhymthics
98
Q

What is ivermectin active against?

A
  • scabies
  • Norwegian scabies (highly contagious)
  • Strongyloides hyperinfection syndrome (increasingly recognized cause of life threatening illness in immunocompromised patients)
  • several diseases endemic in tropical settings
99
Q

Which tropical diseases is ivermectin active against?

A
  • river blindness
  • strongylodiasis (infrequent in US)
  • cutaneous larva migrans (infrequent in US)
100
Q

What is the MOA of ivermectin?

A

Binds to the parasitic neuromuscular junction

  • causes muscular paralysis of the parasite
  • parasite dies directly from the effects or starvation
101
Q

What ectoparasites is ivermectin active against?

A
  • Sarcoptes scabiei (scabies mite)

- Pediculus humanus (lice)

102
Q

What nematodes (roundworms) is ivermectin active against?

A
  • Onchocerca volvulus (river blindness)
  • Strongyloides stercoralis (strongylodiasis)
  • Ancylostoma braziliense (cutaneous larva migrans)
  • other nematodes
103
Q

How is ivermectin tolerated when used for treatment of scabies?

A

Very well tolerated

104
Q

How is ivermectin tolerated when used for management of nematode infections in endemic settings?

A

Severe adverse reactions

  • fever
  • myalgia
  • hypotension
  • thought to be a result of the host’s immune response to antigens released from killed parasites
  • more severe in patients with higher worm burdens
  • resolve soon after drug administration
105
Q

What is ivermectin used as an alternative for?

A
  • alternative to topical permethrin for scabies
  • to topicals for treatment of head or body louse infestation
  • treatment of Ancylostoma infections
106
Q

What is ivermectin a drug of choice for?

A
  • Strongyloides

- Onchocerca

107
Q

How is ivermectin dosed for ectoparasitic (scabies or lice) infestation?

A

Administer as 2 doses

  • 1 week apart
  • only giving a single dose increases the risk of relapse

05.1 - FARMACOLOGIA CLÍNICA (50 decks)

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