EXAM #4: ANTI-PARASITIC DRUGS

Question 1

What are the obstacles to treating parasitic organisms?

Answer 1

1) Eukaryotic
2) Nearly identical cellular machinery

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

Question 2

What are the the three major targets for antiparasitic chemotherapy?

Answer 2

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

Question 3

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

Answer 3

PFOR

Question 4

List the intestinal/ luminal parasites.

Answer 4

• Giardiasis
• Amebiasis
• Trichmonoiasis

Question 5

What causes Amebiasis?

Answer 5

Entamoeba histolytica

Question 6

What are the two forms of Entamoeba histolytica and Giardia?

Answer 6

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

Question 7

What drug is used to treat the intestinal parasites?

Answer 7

Metronidazole

Question 8

What is PFOR?

Answer 8

Pyruvate: ferrodoxin oxidoreductase

*Found only in parasites

Question 9

What is the MOA of Metronidazole?

Answer 9

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

Question 10

What adverse effects are associated with Metronidazole?

Answer 10

1) Metallic taste
2) Disulfram-like effect

Thus, patients should avoid alcohol

Question 11

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

Answer 11

Trichomoniasis is a STD–need to treat the partner too

Question 12

What form of Amebiasis is Metronidazole good at treating?

Answer 12

Trophozoites that have left the gut

Does NOT do a good job treating the cyst form

Question 13

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

Answer 13

1) Iodoquinol OR
2) Paromomycin

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

Question 14

What is Halogenated hydroxyquinoline good at treating?

Answer 14

BOTH forms of Entameba histolytica in the LUMEN

Question 15

What is Paromomycin good at treating?

Answer 15

BOTH forms of Entameba histolytica in the LUMEN

Question 16

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

Answer 16

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

Question 17

What disease is caused by Cryptosporidium parvum?

Answer 17

Cryptosporidiosis–profuse watery diarrhea

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

Question 18

How is Cryptosporidiosis treated?

Answer 18

Nitazoxanide

Question 19

What is the MOA of Nitazoxanide?

Answer 19

Inhibition of PFOR that disrupts energy metabolism in the parasite

Question 20

In addition to Cryptosporidiosis, what else can Nitazoxanide treat?

Answer 20

Giardiasis

Question 21

How are Pneumocystis jirovecii and Toxoplasma gondii treated?

Answer 21

Inhibitors of folate synthesis

• TMP-SMX
• Pyrimethamine-Sulfadiazine

Question 22

What is the MOA of Sulfonamides?

Answer 22

PABA analog that inhibit DIHYDROPTEROATE SYNTHASE

Question 23

What is the MOA of Diaminopyrmidines?

Answer 23

Inhibitors of DHFR that prevent formation of tetrahydrofolate

Question 24

What is the major adverse effect seen with Sulfonamides?

Answer 24

Rash

Question 25

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

Answer 25

- Folic acid deficiency - Can cause megaloblastic anemia *Note that this is used for Toxoplasmosis*

Question 26

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

Answer 26

Leucovorin rescue

Question 27

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

Answer 27

Point mutations in the enzyme targets

Question 28

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

Answer 28

Primaquine

Question 29

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

Answer 29

RBC cycle of replication

Question 30

What the MOA of Chloroquine?

Answer 30

Unclear- maybe interferes parasite ability to detoxify metabolites

Question 31

Where is Chloroquine used today?

Answer 31

West of the panama canal?

Question 32

What is the mechanism of Chloroquine resistance?

Answer 32

Drug export pumps

Question 33

What is the MOA of quinine?

Answer 33

- May interfere with Hb degradation and cause accumulation of toxic metabolites - May complex with parasite DNA to prevent replication

Question 34

What do you need to remember about Quinine?

Answer 34

Poor TI--associated with: 1) Cinchonism 2) Hypoglycemia

Question 35

How is Quinine used to treat Malaria?

Answer 35

- NOT for prophylaxis b/c of toxicity | - Used IV if positive diagnosis

Question 36

How is Mefloquine used to treat Malaria?

Answer 36

Prophylaxis

Question 37

What adverse effects are associated with Mefloquine?

Answer 37

Severe neuropsychiatric reactions

Question 38

What is the MOA of Primaquine?

Answer 38

- Prodrug - Interferes with electron transports - May inhibit pyrimidine synthesis

Question 39

What do you need to remember about Primaquine?

Answer 39

ONLY DRUG available for liver/hypnozoite form

Question 40

What species of malaria are associated with a liver form?

Answer 40

P. vivax | P. ovale

Question 41

What toxicity is seen with Primaquine?

Answer 41

If taken by a patient with G6PD, can lead to hemolysis *Thus, screen for G6PD before administering

Question 42

What is Malarone good for treating?

Answer 42

P. falciparum *Good for treatment and for prophylaxis*

Question 43

What is Malarone?

Answer 43

Combination of Atoaquone and Proguanil

Question 44

What is the MOA of Proguanil?

Answer 44

Inhibits DHFR

Question 45

What is the MOA of Doxycycline?

Answer 45

Inhibits plasmodium protein synthesis

Question 46

How is Doxycycline used to treat Malaria?

Answer 46

Prophylaxis

Question 47

What are the major side effects of Doxycycline?

Answer 47

- Photosensitivity dermatitis | - Staining of teeth in kids

Question 48

What patient populations is Doxycycline contraindicated in?

Answer 48

1) Children | 2) Pregnant women

Question 49

What is Artemisinin derived from?

Answer 49

Chinese wormwood

Question 50

What is the clinical utility of Artemisinin?

Answer 50

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

Question 51

What is the general MOA of the antihelminthic drugs?

Answer 51

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

Question 52

List the Benzimidazoles.

Answer 52

Albendazole Mebendazole Thiabendazole

Question 53

Which of the Benzimidazoles has the greatest toxicity? Why?

Answer 53

Thiabendazole--more easily absorbed into system circulation than the others

Question 54

How are the Benzimidazoles normally given?

Answer 54

Orally on an empty stomach

Question 55

What toxicities are associated with Thiabendazole?

Answer 55

CNS disturbances--delerium and hallucinations

Question 56

In what patient populations are the Benzimidazoles contraindicated?

Answer 56

Pregnant women

Question 57

What infections are Albendazole and Mebendazole used to treat?

Answer 57

Ascariasis Pinworm Hookworm Whipworm *Note that this is done with a SINGLE dose

Question 58

What is Thiabendazole used to treat?

Answer 58

1) Topical preparation for cutaneous larval migrans | 2) Strongyloidiasis (2nd line)

Question 59

What is the MOA of Ivermectin?

Answer 59

Causes muscle paralysis in parasites BUT not in humans

Question 60

What is Ivermectin the drug of choice for?

Answer 60

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

Question 61

What is the MOA of Pyrantal Pamoate?

Answer 61

Depolarizing neuromuscular blockade

Question 62

What is Pyrantal Pamoate the drug of choice for?

Answer 62

Pinworm *Note that only 2 doses are needed*

Question 63

What do you need to remember about Pinworm infections?

Answer 63

Treat the ENTIRE household

Question 64

What drug is used to treat Tapeworm and Fluke infections?

Answer 64

Praziquantel

Question 65

What is the MOA of Praziquantel?

Answer 65

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