EXAM #4: ANTI-PARASITIC DRUGS Flashcards

1
Q

What are the obstacles to treating parasitic organisms?

A

1) Eukaryotic
2) Nearly identical cellular machinery

Thus, there are limited drug targets and a high degree of toxicity.

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2
Q

What are the the three major targets for antiparasitic chemotherapy?

A

1) Enzymes only in the parasite
2) Enzymes or processes found in BOTH the host/ parasite but INDESPENSIBLE to the parasite
3) Enzymes that are the same in both host and parasite but with limited toxicity to host

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3
Q

What is an example of an enzyme found only in parasites that is targeted by antiparasitic drugs?

A

PFOR

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4
Q

List the intestinal/ luminal parasites.

A
  • Giardiasis
  • Amebiasis
  • Trichmonoiasis
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5
Q

What causes Amebiasis?

A

Entamoeba histolytica

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6
Q

What are the two forms of Entamoeba histolytica and Giardia?

A
  • Trophozite form that infects gut and disseminates to other tissue
  • Dormant cyst
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7
Q

What drug is used to treat the intestinal parasites?

A

Metronidazole

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8
Q

What is PFOR?

A

Pyruvate: ferrodoxin oxidoreductase

*Found only in parasites

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9
Q

What is the MOA of Metronidazole?

A
  • Pro-drug that enters cell and is reduced by PFOR to its active form
  • Reduced Metronidazole produces reactive intermediates that disrupt DNA/proteins
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10
Q

What adverse effects are associated with Metronidazole?

A

1) Metallic taste
2) Disulfram-like effect

Thus, patients should avoid alcohol

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11
Q

If you’re treating a patient for Trichomoniasis with Metronidazole, what do you need to remember?

A

Trichomoniasis is a STD–need to treat the partner too

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12
Q

What form of Amebiasis is Metronidazole good at treating?

A

Trophozoites that have left the gut

Does NOT do a good job treating the cyst form

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13
Q

What drugs are used to follow-up Metronidazole treatment in Amebiasis?

A

1) Iodoquinol OR
2) Paromomycin

Now Paromomycin is more commonly used–less toxicity and shorter treatment course

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14
Q

What is Halogenated hydroxyquinoline good at treating?

A

BOTH forms of Entameba histolytica in the LUMEN

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15
Q

What is Paromomycin good at treating?

A

BOTH forms of Entameba histolytica in the LUMEN

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16
Q

What are the major opportunistic parasitic infections of AIDS patients and the immunocompromised?

A

1) Cryptosporidium parvum
2) Pneumocystis jiroveci
3) Toxoplasma gondii

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17
Q

What disease is caused by Cryptosporidium parvum?

A

Cryptosporidiosis–profuse watery diarrhea

  • Self-limiting in adults
  • Can be fatal in immunosuppressed
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18
Q

How is Cryptosporidiosis treated?

A

Nitazoxanide

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19
Q

What is the MOA of Nitazoxanide?

A

Inhibition of PFOR that disrupts energy metabolism in the parasite

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20
Q

In addition to Cryptosporidiosis, what else can Nitazoxanide treat?

A

Giardiasis

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21
Q

How are Pneumocystis jirovecii and Toxoplasma gondii treated?

A

Inhibitors of folate synthesis

  • TMP-SMX
  • Pyrimethamine-Sulfadiazine
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22
Q

What is the MOA of Sulfonamides?

A

PABA analog that inhibit DIHYDROPTEROATE SYNTHASE

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23
Q

What is the MOA of Diaminopyrmidines?

A

Inhibitors of DHFR that prevent formation of tetrahydrofolate

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24
Q

What is the major adverse effect seen with Sulfonamides?

A

Rash

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25
Q

What is an adverse effects seen with Pyrimethamine-Sulfadiazine treatment?

A
  • Folic acid deficiency
  • Can cause megaloblastic anemia

Note that this is used for Toxoplasmosis

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26
Q

How can folate deficiency in Pyrimethamine-Sulfadiazine treatment be treated?

A

Leucovorin rescue

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27
Q

What is the MOA of resistance to the folate synthesis inhibitors?

A

Point mutations in the enzyme targets

28
Q

What drug is used to treat the hepatic stage of Malaria infection?

A

Primaquine

29
Q

What is the major target of most of the Malaria drugs?

A

RBC cycle of replication

30
Q

What the MOA of Chloroquine?

A

Unclear- maybe interferes parasite ability to detoxify metabolites

31
Q

Where is Chloroquine used today?

A

West of the panama canal?

32
Q

What is the mechanism of Chloroquine resistance?

A

Drug export pumps

33
Q

What is the MOA of quinine?

A
  • May interfere with Hb degradation and cause accumulation of toxic metabolites
  • May complex with parasite DNA to prevent replication
34
Q

What do you need to remember about Quinine?

A

Poor TI–associated with:

1) Cinchonism
2) Hypoglycemia

35
Q

How is Quinine used to treat Malaria?

A
  • NOT for prophylaxis b/c of toxicity

- Used IV if positive diagnosis

36
Q

How is Mefloquine used to treat Malaria?

A

Prophylaxis

37
Q

What adverse effects are associated with Mefloquine?

A

Severe neuropsychiatric reactions

38
Q

What is the MOA of Primaquine?

A
  • Prodrug
  • Interferes with electron transports
  • May inhibit pyrimidine synthesis
39
Q

What do you need to remember about Primaquine?

A

ONLY DRUG available for liver/hypnozoite form

40
Q

What species of malaria are associated with a liver form?

A

P. vivax

P. ovale

41
Q

What toxicity is seen with Primaquine?

A

If taken by a patient with G6PD, can lead to hemolysis

*Thus, screen for G6PD before administering

42
Q

What is Malarone good for treating?

A

P. falciparum

Good for treatment and for prophylaxis

43
Q

What is Malarone?

A

Combination of Atoaquone and Proguanil

44
Q

What is the MOA of Proguanil?

A

Inhibits DHFR

45
Q

What is the MOA of Doxycycline?

A

Inhibits plasmodium protein synthesis

46
Q

How is Doxycycline used to treat Malaria?

A

Prophylaxis

47
Q

What are the major side effects of Doxycycline?

A
  • Photosensitivity dermatitis

- Staining of teeth in kids

48
Q

What patient populations is Doxycycline contraindicated in?

A

1) Children

2) Pregnant women

49
Q

What is Artemisinin derived from?

A

Chinese wormwood

50
Q

What is the clinical utility of Artemisinin?

A

Effective treatment for multi-drug resistant strains of P. falciparum

51
Q

What is the general MOA of the antihelminthic drugs?

A

1) Inhibit mitosis of the parasite

2) Cause muscle paralysis of the parasite (allows the organism to be passed more easily)

52
Q

List the Benzimidazoles.

A

Albendazole
Mebendazole
Thiabendazole

53
Q

Which of the Benzimidazoles has the greatest toxicity? Why?

A

Thiabendazole–more easily absorbed into system circulation than the others

54
Q

How are the Benzimidazoles normally given?

A

Orally on an empty stomach

55
Q

What toxicities are associated with Thiabendazole?

A

CNS disturbances–delerium and hallucinations

56
Q

In what patient populations are the Benzimidazoles contraindicated?

A

Pregnant women

57
Q

What infections are Albendazole and Mebendazole used to treat?

A

Ascariasis
Pinworm
Hookworm
Whipworm

*Note that this is done with a SINGLE dose

58
Q

What is Thiabendazole used to treat?

A

1) Topical preparation for cutaneous larval migrans

2) Strongyloidiasis (2nd line)

59
Q

What is the MOA of Ivermectin?

A

Causes muscle paralysis in parasites BUT not in humans

60
Q

What is Ivermectin the drug of choice for?

A

1) Strongyloidiasis
2) Tissue dwelling nematodes including:
- O. volvulus (river blindness)
- Loa loa (eye worm)
- W. bancrofti (elephantiasis)

(Thiabendazole is second line for Strongyloidiasis)

61
Q

What is the MOA of Pyrantal Pamoate?

A

Depolarizing neuromuscular blockade

62
Q

What is Pyrantal Pamoate the drug of choice for?

A

Pinworm

Note that only 2 doses are needed

63
Q

What do you need to remember about Pinworm infections?

A

Treat the ENTIRE household

64
Q

What drug is used to treat Tapeworm and Fluke infections?

A

Praziquantel

65
Q

What is the MOA of Praziquantel?

A
  • Increased the Ca++ permeability of the cuticle covering these worms
  • Causes depolarizing neuromuscular blockade/ paralysis