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233 FINAL > Antimicrobial 5: Other Antiprotozoals > Flashcards

Antimicrobial 5: Other Antiprotozoals Flashcards

1
Q

Protozoa

What are the 4 major groupings (Phylums)?

A

i. Flagellates
ii. Amoebas
iii. Sporozoans
iv. Ciliates

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2
Q

Protozoa

• ____: any stage in a protozoan’s life cycle which can
ingest food. In practice also refers to the motile
form

• ____: the non motile form which is protected by a
distinct membrane or cyst wall. This is an
infective stage of the parasite

• ____: the process of emergence of the trophozoite
from the cyst (vs. encystation)

A

TROPHOZOITE

CYST

EXCYSTATION

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3
Q

Protozoa

Name 8 infections:

A
  1. Amoebiasis: organisms Infection caused by
    Entamoeba
    – Entamoeba hystolytica is the main organism of
    concern
  2. Trypanosomiasis: Trypanosomes belong to
    pathogenic flagellate protozoa
    – Trypanosoma brucei infection causes African
    sleeping sickness
    – Trypanosoma cruzi infection causes Chagas
    disease
  3. Leishmaniasis : Leishmania are protozoa spread by
    the sandfly
  4. Trichomoniasis: The principle organism infecting
    humans is Trichomonas vaginalis
  5. Giardiasis: Ingestion of food/water contaminated with
    fecal matter containing cysts from Giardia
    lamblia
    – Giardia lamblia colonizes the upper GI tract
    (trophozoite)
  6. Cryptosporidiosis: Caused by the coccidian protozoal
    species Cryptosporidium parvum
    and Cryptosporidium hominis
  7. Toxoplasmosis: Cat is the definitive host and its
    infective cysts are found in the feces
    – Toxoplasma gondii is a pathogenic member that can
    infect humans (disease is usually self-limiting)
  8. Pneumocystis: Caused by Pneumocystis jirovecii
    (previously known as P. carinii ) and
    causes pneumonia
    – Shares structural features with both protozoa and
    fungi
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4
Q

Protozoa

Drugs

A

See slide 8 picture

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5
Q

Metronidazole

Characteristics

A

• Clinically effective in trichomoniasis, amebiasis and
giardiasis

• Nitroimidazole antibiotic

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6
Q

Metronidazole

MOA

A

• Metronidazole is a prodrug: it requires reductive
activation of the nitro group to a reactive radical anion
by susceptible anaerobic organisms.

• The radical anion and other generated radicals target
DNA and other biomolecules of the parasite.

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7
Q

Metronidazole

AE

A

• * Rare neurotoxicity (encephalopathy, ataxia)

  • Headache
  • Nausea & vomiting
  • Diarrhea
  • Urticaria, flushing & pruritus
  • Stevenson-Johnson syndrome
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8
Q

Metronidazole

Contraindications & Precautions

A

• Can interact with alcohol and disulfiram, resulting in
side effects such as headache, confusion, psychotic
states

• Not indicated in patients with active disease of the
CNS

• Not indicated in the first trimester of pregnancy
(teratogenic)

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9
Q

Tinidazole

Characteristics

MOA

A
  • can be used during pregnancy

- same MOA as Metronidazole

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10
Q

Iodoquinol

Characteristics

MOA

A

• Orally administered to eliminate intestinal E.
histolytica
• Not effective on tissue trophozoites
• Halogenated 8-hydroxyquinoline

• Potent metal-binding agent. MOA unknown

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11
Q

Iodoquinol

AE

A
    • Optic atrophy
    • Permanent loss of vision

• Neuropathy

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12
Q

Iodoquinol

Contraindications & Precautions

A

• Use with caution in patients with neuropathies or

thyroid diseases

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13
Q

Paromomycin

Characteristics

A

• Aminoglycoside of the neomycin/kanamycin family

• Used to treat cryptosporidiosis, giardiasis and
trichomoniasis. It is also the drug of choice (in
combination with metronidazole) for treating intestinal
colonization with E. histolytica

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14
Q

Paromomycin

MOA

A

• Bind irreversibly to the 30S ribosomal subunit and
inhibit protein synthesis (trap ribosomes at the AUG
start codon)

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15
Q

Paromomycin

AE

A
    • Nephrotoxicity
    • Ototoxicity
  • Abdominal pain
  • Nausea & vomiting
  • Diarrhea
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16
Q

Nitazoxanide

Characteristics

A

• Nitazoxanide is an oral antiparasitic and antiviral gent,
its metabolite tizoxanide is active and this agent is
approved for the treatment of giardiasis and
cryptosporidiosis

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17
Q

Nitazoxanide

MOA

A

• Proposed mechanism of action is due to inhibiting
pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-
dependent electron transfer, which is important for
parasite anaerobic energy metabolism

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18
Q

Nitazoxanide

AE

A
  • Headache
  • GI upset (abdominal pain, vomiting, diarrhea)
  • Teratogenic in animal studies
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19
Q

Co-Trimoxazole

Characteristics

A

• Combination therapy of sulfamethoxazole (sulfa
antibiotics) and trimethoprim (folic acid antagonist)
that is the treatment of choice for toxoplasmosis and
pneumocystis pneumonia

20
Q

Co-Trimoxazole

MOA

A
  • Sulfamethoxazole inhibits dihydropteroate synthetase

* Trimethoprim inhibits dihydrofolate reductase

21
Q

Co-Trimoxazole

AE

A

• Similar to those discussed sulfadoxine + pyrimethamine

22
Q

African Sleeping Sickness

What are 2 subtypes of Trypanosoma brucei that
can cause African sleeping sickness?

A

Trypanosoma brucei gambiense

Trypanosoma brucei rhodesiense

23
Q

African Sleeping Sickness

Transmission?

A

When bitten by an infected tsetse fly, the protozoa is injected into the human skin. From there, it then move into the lymphatic system and bloodstream, where it is
able to travel throughout the body and reach the brain.

24
Q

African Sleeping Sickness

Symptoms

A

Skin:
A bump on the skin within a few days from
tsetse fly bite

Blood/lymph nodes:
fevers, chills, headache, muscle/joint pain

Brain/cerebrospinal fluid:
persistent headaches, drowsiness that worsens,
loss of concentration, troubles with
balance/walking

See slide 18 for more details :-)

25
Q

Chagas Disease

Also called the Kissing Bug Disease.

What infection causes Chagas disease?

A

Trypanosoma cruzi infection

26
Q

Chagas Disease

Transmission

A

• When a kissing bug (Triatromine) bites a human or
animal, the infected bug deposits feces that contains
the protozoa. The protozoa then enters the body
through the bite wound.

• The protozoan can also enter through tissues around
the eye

27
Q

Chagas Disease

Symptoms

A

1st stage:
- swollen red bump at bite wound or swelling at area
around the eye

2nd stage:
- Latent period. No symptoms. ECG and imaging tests
are normal, despite protozoa still present in body
- Many people remain in this stage for the rest of their
lives

3rd stage:
- Mainly affects heart and digestive system

28
Q

African Sleeping Sickness

Drugs (4)

A
  • Suramin
  • Pentamidine
  • Melarsoprol
  • Eflornithine
29
Q

Chagas Disease

Drugs (2)

A
  • Nifurtimox

- Benznidazole

30
Q

Suramin

MOA

A

Binds to plasma proteins and enters the parasite via endocytosis, where it inhibits key enzymes (e.g. glycolysis enzymes, thymidine kinase, dihydrofolate reductase) inducing gradual destruction of organelles

31
Q

Suramin

AE

A
    • Renal toxicity
    • Leukopenia (in people with AIDS)
  • Optical atrophy
  • Adrenal insufficiency
  • Skin rashes
  • Hemolytic anemia
32
Q

Pentamidine

MOA

A

Taken up into parasite via an energy-dependent carrier and thought to interact with DNA (may inhibit both DNA and protein synthesis)

33
Q

Pentamidine

AE

A
    • Hypoglycemia
  • Decreased blood pressure
  • Tachycardia
  • Headache
  • Breathlessness
  • Vomiting
  • Kidney damage
  • Hepatic impairment
  • Blood dyscrasias
34
Q

Melarsoprol

MOA

A

• Organic arsenic compound used when CNS infection
at play as it enters the CNS in high concentrations
(prodrug that gets converted to melarsen oxide)

• Interacts with protein sulfhydryl groups (enzyme
inactivation)

35
Q

Melarsoprol

AE

A 
Highly toxic, can cause encephalopathy and sometimes
immediate fatality (administered only under strict supervision)
36
Q

Eflornithine

MOA

A

Inhibits parasite ornithine decarboxylase (ODC) enzyme

irreversibly (decreases formation of polyamines needed for cell replication)

37
Q

Eflornithine

AE

A
  • Abdominal pain
  • Headache
  • Fever
  • Seizures
  • Hearing loss
38
Q

Nifurtimox/Benznidazole

MOA

A

• Nifurtimox is a nitrofuran analog and benznidazole a
nitroimidazole analog

• Both are activated by NADH dependent
nitroreductases in mitochondria, leading to
generation of nitro free radicals that are believed to
kill the parasite

39
Q

Nifurtimox/Benznidazole

AE

A
  • Hypersensitivity (dermatitis, fever, anaphylaxis)
  • GI upset (nausea, vomiting)
  • Peripheral neuropathy
  • Neurotoxicities (less frequent)
  • Leukopenia
40
Q

Summary

____ which is a prodrug that is converted into a free radical that can interact with DNA, and is used for the treatment of trichomoniasis, amebiasis and giardiasis

A

Metronidazole

41
Q

Summary

____ and ____ (aminoglycoside antibiotic) are used to treat intestinal colonization with E. histolytica as they are not absorbed by the GI tract

A

Iodoquinol

paromomycin

42
Q

Summary

____ is a prodrug metabolized to tizoxanide, which
inhibits pyruvate:ferredoxin oxidoreductase and thereby
impairs anaerobic energy metabolism

A

Nitazoxanide

43
Q

Summary

____ or ____ are used for early stage infection
Sleeping Sickness

A

Suramin

pentamidine

44
Q

Summary

____ or ____ are used for late stage infection
Sleeping Sickness

A

Melarsolprol

eflornithine

45
Q

Summary

____ and ____ are used for Chagas disease

A

Nifurtimox

benznidazole

233 FINAL (15 decks)

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