EXAM 3- KEARNS- Antiparasitic & Antiprotozoal Meds

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What are the 2 classes of parasites?

Where are they found?

1. ectoparasites—> surface of body

2. endoparasites—> INSIDE the body

Answer the following about Giardiasis

• transmission

• acute infection vs. chronic infection

• transmission: person-person water, food, or objects

• acute infection- diarrhea

• chronic- decrease WBCs, holes in the GI tract

Describe the life cycle of Giardiasis:

• encystation vs. excystation?

• which form can survive outside the host?

• ENCYSTATION

  • when cysts are ingested

• EXCYSTATION

  • when cysts turn into trophozoites and trophozoites REPLICATE

  • replication stage!!!!!!

• only CYSTS can survive outside the host, not trophozoites

What can be used for prophylaxis against giardiasis? would it target encystation or excystation?

• bug spray!!!! would prevent ENcystation

What are the drugs and their targets used for Giardiasis?

Which is a competitive inhibitor?

1. inhibition of replication

   • metronidazole

   • tinidazole

2. inhibition of parasitic metabolism

   • nitazoxanide- competitive inhibitor

Metronidazole is only effective against ____________.

a. anaerobes

b. aerobes

a.

What is the MOA of Metronidazole?

1. diffusion into anaerobic pathogen

2. inhibits protein synthesis by

   • reduced to Tizoxanide (active form)

   • promotes free radical formation= cytotoxic

   • radicals interact with TROPHOZITE DNA= strand breaks, disrupts DNA

Would Metronidazole inhibit transcription or translation?

transcription

What is the “toxicophore” on Metronidazole?

nitro group

Boxed warnings of metronidazole?

• CNS toxicity

• C/I in pregnancy

What are the advantages of using Tinidazole over Metronidazole?

• longer t ½ , shorter course of therapy

• improved toxicity and tolerance

What is the MOA of Nitazoxamide?

• inhibits metabolism

  • inhibits PFOR enzyme= no electron transfer

What is unique about Nitazoxamide metabolism?

• 2 active metabolites!!!

  • hydrolysis and conjugation form the active metabolites

What are the 2 types of Amebicides? Drugs that belong to each?

1. luminal

   • Paromomycin

   • Idoquinol

   • Diloxanide

2. tissue

   • Metronidazole

   • Tinidazole

   • Chloroquine

Answer the following about Paromomycin:

• what type of abx?

• uses?

• MOA?

• aminoglycoside abx

• uses: giardiasis, amebiasis, tapeworms

• MOA: inhibits protein synthesis

Answer the following about Idoquinol:

• active against what?

• MOA?

• ONLY active against CYSTS (not trophs)—> for prophylaxis

• MOA: inhibits metabolism

  • chelates iron needed for metabolism

    • using e- from phenolate and pyridine groups on Idoquinol

Answer the following about Diloxanide:

• active against what?

• prodrug?

• used when?

• active against TROPHOZOITES of E. histolytica, prevents cyst formation

• prodrug

• used after met, tini or paramomycin

How is malaria transmitted?

anopheles gambiae moquito

Nonpharm prophylaxis for malaria? How does it work?

bug spray like DEET—> binds to olofactory neurons on mosquito

For Malaria, prophylaxis treatment acts on ________________, treatment acts on _________and ________.

a. sporozoites, trophozoites and schizonts

b. trophozoites, sporozoites and schizonts

c. schizonts, sporozoites and trophozoites

a

What drugs act on sporozoites?

• primaquine

• proguanil

What drugs act on trophozoites and schizonts in the intraerythrocytic stage of malaria?

• proguanil

• mefloquine

• chloroquine

• doxycycline

MOA of Quinolone antimalarials (chloroquine, quinine, mefloquine)?

• inhibits heme digestion

  • inhibits heme polymerase enzyme

  • heme builds up and is toxic

How are each of the following typically dosed?

• Chloroquine

• Mefloquine

• Primaquine

(idk how imp)

• Chloroquine- weekly

• Mefloquine- weekly

• Primaquine- daily

How are each of the following metabolized?

• Chloroquine

• Mefloquine

• Primaquine

• Chloroquine- CYP2C8, 2D6

• Mefloquine- CYP3A4

• Primaquine- CYP2D6

Which antimalarial is a racemic mixture? What is the function of each enatiomer?

• Mefloquine

  • (-) enantiomer: psychosis

  • (+) enantiomer: antimalarial

What are the mechanisms of resistance for CHLOROQUINE?

• PfCRT—> P. falciparum chloroquine resistance transporter

What are the mechanisms of resistance for MEFLOQUINE?

• pfmdr 1 and 2—> P. falciparum MDR genes

What is the MOA of Primaquine?

• inhibits metabolism

  1. converted to hydroxylated metabolites by CYP2D6

  2. metabolites oxidize

  3. oxidants target SCHIZONTICIDES

  4. H2O2 accumulates

What is the result of Doxycycline being less H2O soluble?

increased absorption, penetration, and duration of action

In addition to parasites, Doxycycline is also active against ___________.

bacteria

What are the advantages to using Atovaquone Proguanil for prophylaxis?

• gives protection in 1-2 days (usually takes 1-2 weeks)

• effective against resistant strains

Describe how Ascariasis (roundworms) mature/replicate:

1. 1st ingestion—> worm matures

2. throw up

3. 2nd ingestion—> when larvae replicate

Drugs for ascariasis target what?

metabolism via glucose depletion

Answer the following about Albendazole/Mebendazole:

• bioavailability?

• effective against?

• MOA

• low bioavailability

• effective against ascariasis and trichuriasis (round and whip worms)

• MOA: inhibits glucose

  • destabilizes microtubules

  • inhibits mitochondrial enzyme

What do Albendazole and Mebendazole NOT kill?

eggs!!!

Answer the following about pyrantel pamoate:

• absorption?

• uses?

• MOA

• poor oral absorption

• uses: enterobiasis

• MOA: paralysis

  • agonist of nematode nAChRs (nicotonic acetycholine receptors)

  • depolarizes neuromuscular pathway= paralysis

Answer the following about Ivermectin:

• MOA

• paralysis

  • increases entry of Cl ions = hyperpolarization

  • nematode paralysis

What is a topical medication that can be used for ectoparasites like mites?

crotamiton

MOA of Crotamiton?

• antipruritic

  • inhibits TRPV4

  • decreases Ca and Na influx