Antiparasitics

Question 1

3 targets for antiparasitic chemotherapy

Answer 1

1. Enzyme or processes found only in the parasite - few (PFOR; folate synthesis)
2. Enzymes/processes found in both the host and parasite but indispensable only in the parasite - purine salvage pathway
3. Common biochemical functions found in both parasite and host, but with different pharmacological properties (DHFR; microtubule disrupters)

Question 2

waht parasites can metronidazole treat

Answer 2

Giardia

Entamoeba

Trichomonas

• organisms possess PFOR (we don’t have this)

Question 3

MOA of metronidazole

Answer 3

electron “sink”

inactivated under anaerobic conditions by PFOR - reactive intermediates form which bind to and disrupt protein and DNA structure/function

Question 4

SE of metronidazole

Answer 4

GI

HA, dry mouth, metallic taste

Disulfiram-like effect - avoid alcohol consumption**

safe during pregnancy

Question 5

what is the drug of choice for treating SYMPTOMATIC amebiasis

Answer 5

Metronidazole - follow with more potent luminal amebicide (idoquinol or paromycin) to eradicate non-invasive cyst forms

effective in treating invasive intestinal disease as well as extraintestinal amebiasis (liver and brain abscesses)

Question 6

what is effective at eliminating trophozoite and cyst forms of E. histolytica from the LUMEN of the intestines?

no activity against trophozoidte forms in tissues

Answer 6

Idoquinolol

Paromomycin

Question 7

what drug has been associated with optic atrophy and permanent vision loss in children who were administered high doses

Answer 7

idoquinolol

Question 8

when is idoquinolol or paromomycin used

Answer 8

treats ASYMPTOMATIC or mild cases of amebiasis

in severe cases it should be used following metronidazole

Question 9

MOA of paromomycin

Answer 9

aminoglycoside antibiotic

- inhibits protein synthesis in bacteria

Question 10

idoquinolol and paromoycin

1. oral or IV?
2. absorbed well or poorly?

Answer 10

1. oral

2. poorly

Question 11

Adverse effects of paromycin

Answer 11

Abdominal discomfort and diarrhea

less toxic than idoquinolol

Question 12

Like idoquinolol, ___ is used to treat asymptomatic or mild cases of amebiasis. Severe cases used follow mitronidazole

Answer 12

Paromomycin

Question 13

wha tis used to treat C. parvum (OI)

Answer 13

Nitazoxanide

Question 14

MOA of nitazoxamide

Answer 14

interferences with PFOR - disruption of anaerobic metabolism

Question 15

Nitazoxanide:

1 (oral/IV/parenteral) suspension approved and indicated for tx of 2 and 3 in individuals 4 years of age

Answer 15

1. oral
2. Crptosporidiosis
3. Giardiasis
4. 1+

Question 16

what folate synthesis inhibitor is used to treat Pneumocystic jirovecii (OI)

Answer 16

Trimethoprim-sulfamethoxazole

Question 17

what folate synthesis inhibitior is used to treat toxoplasma gondii?

Answer 17

Pyrimethamine-sulfadiazine

Question 18

1. MOA of sulfonamides (sulfadiazine, sulfamethoxazole)

2. diaminopyrimidines (pyrimethamine, trimethoprim)

Answer 18

folate synthesis inhibitors

1. PABA anolog; inhibits prodcution by dihydropteroate synthase
2. inhibitor of DHFR - prevent THF formation = selective toxicity

Question 19

adverse reactions for sulfonamides

Answer 19

rash

Question 20

treatment of choice for toxoplasmosis

• does not effect dormant tissue cyst

Answer 20

pyrimethamine-sulfadiazine

Question 21

antimalarial:

• oral administration
• T1/2 ~4days
• higher doses adminstered 4 times over 48 hours for clinical disease

Answer 21

chloroquine

Question 22

SE of chloroquine

Answer 22

HA
GI
Blurred vision
Dizzy
Fatigue
Confusion

Question 23

what stage will chloroquines and quinine eliminate

Answer 23

asexual erythrocytic stages of all species of plasmodium

Question 24

resistance against chloroquine

Answer 24

YES
- limited use

rapid export mechanism

Question 25

which antimalarials has the poorest therapeutic:toxic ratio and is generally not used for chemoprophylaxis due to its toxicity

Answer 25

Quinine

Question 26

SE of quinine

Answer 26

Cinchonism: tinnitus, temporary hearing loss, HA, nausea, vomiting, visual disturbance Hypoglycemia

Question 27

toxicity of mefloquine?

Answer 27

Severe neuropsychiatric reactions in pts receiving TREATMENT

Question 28

what is mefloquine effective against

Answer 28

all species of Plasmodium (no resistance)

Question 29

what antimalarial should people be screened for G6PD? why?

Answer 29

Primaquine RBC lysis in persons with G6PD deficiency

Question 30

Drug of choice for treating dormant liver (hypnozoite) forms of P. vivax and P. ovale or after prophylaxis with chlorquine in individuals who have substantial risk of exposure to these organisms

Answer 30

Primaquine

Question 31

which antimalarial has a longer half life (14 days), better tissue distribution than primaquine, single dose as effective as 2 weeks of primaquine, but same problem with GP6PD?

Answer 31

Tafenoquine

Question 32

Antimalarial - Malarone Combination of atovaquone (lipophilic, activity against all Plasmodium) and _1_ highly efficacious in tx of _2_ as well as prophylaxis no resistance

Answer 32

1. proguanil (inhibit DHFR - not used alone due to resistance) 2. P. flaciparum

Question 33

what protein synthesis inhibitors can also be used for the treatment and prophylaxis of malaria? (effective against all species of plasmodium)

Answer 33

Doxycycline - primarily prophylaxis

Question 34

SE of doxycycline

Answer 34

photosensitivity dermatitis staining of teeth in children ***contraindicated in children and pregnant women

Question 35

In 2009 what drug combination therapy was approved by the FDA for the treatment of P. flaciparum infection

Answer 35

Artemether:lumefantrine

Question 36

what drug can be used for all human malaria parasistes and multi-drug resistant strains of P. flaciparum

Answer 36

Artemisinin derivatives

Question 37

MOA of antihelmintics

Answer 37

inhibit mitosis in parasites (benzimidazole cmpds) cause muscle paralysis of parasite (ivermectin, pyrantel, pamoate, prazinquantel)

Question 38

of the benzimidazoles (albendazole, mebendazole, thiabendazole) whcih is more efficiently absorbed accounting for its greater toxicity

Answer 38

thiabendazole

Question 39

Benzimidazoles: generally adminitered on an _1_ when used to treat luminal nematodes may be administered after a _2_ meal to increase absorption and act on tissue dwelling helminths

Answer 39

1. empty stomach | 2. fatty

Question 40

1. toxicity of thiabendazole? | 2. albendazole and mebendazole?

Answer 40

1. GI and CNS disturbance (delirium, hallucination) | 2. GI

Question 41

when is bezimidazoles contraindicated

Answer 41

pregnancy use in children under 2

Question 42

what infections can albendazole and mebendazole treat

Answer 42

ascariasis pinworm whipworm hookworm single dose is efficient

Question 43

Thiabendazole is the second line drug used in the treatment of _1_ Topical preparation is used in the treatment of _2_ caused by the larval forms of dog and cat hookworms

Answer 43

1. strongyloidiasis (intestinal and tissue infection) | 2. cutaneous larval migrans

Question 44

MOA of ivermectin (antihelmintic)

Answer 44

hyperpolarization in muscle cells - paralysis used for intra and extraintestinal infections

Question 45

what is the drug of choice for treating strongyloidiasis (inestinal and extrainstestinal)

Answer 45

Ivermectin

Question 46

Ivermectin is used in treating ___ dwelling nematodes include what?

Answer 46

1. tissue - O. volvulus (river blindness) - L. Ioa (eye worm) - Filarial worms: W. bancrofti and B. malayi

Question 47

MOA of pyrantel pamoate

Answer 47

activates cholinergic nictonic receptors in the somatic muscles of nematodes - depolarizing neuromuscular blockade

Question 48

what does pyrantel pamoate have selective toxicity for

Answer 48

intestinal nematodes

Question 49

what is the drug of choice for treating pinworms who else needs to be treated if someone has pinworms

Answer 49

Pyrantel pamoate - **treatment of entire household

Question 50

what drug is used to treat tapeworm (cestode) and fluke (trematode) infection

Answer 50

Praziquantel

Question 51

MOA of praziquantel

Answer 51

increase Ca2+ permeability of worms tegument -- depolarization, spastic paralysis and increase immue detection

Question 52

tx of praziquantel in: 1. flukes 2. tapeworms 3. cysticercosis

Answer 52

1. 3 doses in a single day 2. single dose 3. 2 weeks