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Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Fungus is considered a ___ organisms

A

eukaryotic

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2
Q

Why are anti fungal drugs so dangerous?

A
  • the drug goes systemic - are life threatening
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3
Q

What is the cell wall of fungus made up of?

A
  • made up of chitin, which is a polymer of N-acetylglucosamine
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4
Q

What does the cell membrane of fungus contain?

A

ergosterol

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5
Q

What are 2 of the things that increases the incidence of fungal infections?

A
  • suppressed IS linked to increase in incidence

- long term antibiotic tx

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6
Q

What class of drugs does Amphotericin B fall into?

A
  • polyene macrolide

(produced by streptomycin nodosus) - used only for life threatening disease

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7
Q

How does amphotericin B work to treat a fungal infection?

A
  • binds to ergosterol (not cholesterol) in the cell membrane and forms pores
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8
Q

What fungi does amphotericin B act on?

A
  • acts on a wide range of fungi, including Candida and blastomyces, as well as aspergillus and protozoa
  • is the first line tx when substituted
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9
Q

What is the absorption of amphotericin B? How does that effect how its dosed?

A
  • poorly absorbed in the GI tract- given intravenously
  • insoluble in water
  • given intrathecally for meningitis
  • delivered now in liposomes- lowers the toxicity
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10
Q

What are the adverse effects associated with amphotericin B?

A
  • has a low TI, so it is NOT considered a safe drug
  • dose has to be under 1.5 mg/kg
  • anaphylaxis and convulsions
  • fever
  • hypotension
    If given longer term
  • renal impairment
  • anemia
  • neurological effects
  • thrombophlebitis (blood clot formation)
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11
Q

What is the action of flucytosine in the fungal cell?

A
  • synthetic pyrimidine antimetabolite
  • enters via specific cytosine permease- not in mammals
  • converted to 5’-fluorodeoxyuridine monophosphate (5-FdUMP)
  • false nucleotide inhibits thymidylate synthase
  • blocks thymidylic acid- needed for DNA
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12
Q

There is ____ when flucytosine and amphotericin B are combined

A

synergy

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13
Q

How does resistance develop when using flucytosine?

A
  • target enzyme can be down regulated- there is a need for combination therapy here
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14
Q

How does flucytosine pass into the BBB?

A

passes very well into the BBB

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15
Q

What are the adverse effects related to flucytosine?

adverse effects are related to the toxic metabolite fluorouracil

A
  • neutropenia
  • bone marrow depression
  • nausea, vomiting
  • contraindicated with renal impairment
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16
Q

What class of anti fungal does posaconazole belong to and how does it work?

A
  • synthetic azole used for a SYSTEMIC fungal infection
  • inhibits C-14 alpha-demethylase (cyt P450)
  • blocks demethylation and lanosterol to ergosterol, therefore disrupting the membrane structure and function
  • more specific than precious axle and imidazoles
17
Q

What is the range of fungi that posaconazole can treat?

A
  • species of Candida and Aspergillus
18
Q

How is posaconazole dosed and absorbed in the body?

A
  • orally dosed- gastric acid is needed for release
  • there is major binding to plasma proteins
  • drug is metabolized in the liver
  • poor CNS penetration
19
Q

What are the adverse effects associated with posaconazole?

A
  • minor GI upset
20
Q

What drug interactions are associated with posaconazole?

A
  • inhibition of cyt P450
21
Q

How does caspofungin work to treat fungal infections?

A
  • inhibits beta-(1,3)-D-glycan
  • causes cell wall disruption and death
  • treats both aspergillus and candida
  • used as second linetx
22
Q

What is terbinafine used to treat and how does it work?

A
  • terbinafine inhibits squalene epoxidase and blocks ergosterol
  • (squalene build-up can be toxic, however)
  • used to treat cutaneous dermatophyte infections
23
Q

Why is treating protozoa so difficult?

A
  • the metabolism of protozoa is very close to that of humans
  • there is a big issue with toxicity, esp against metabolically active cells such as neurons and stem cells
  • pregnant patients cannot be treated for this reason
24
Q

What is amebic dysentery caused by and what are the symptoms?

A
  • caused by entamoeba histolytica
  • anaerobic protozoa
  • causes fulminating diarrhea
  • liver abscess
  • can lie dormant
  • ultimately ulcerate the host intestine and feed off an kill the host bacteria
25
Q

What organism is metronidazole used to kill?

A
  • kills E. histolytica trophozites
26
Q

Anaerobic protozoa have ____ low redox potential electron transport proteins- nitro group of metronidazole acts as an electron acceptor. The subsequent reduced compounds are cytotoxic

A

ferridoxin like

27
Q

What are the adverse effects of metronidazole?

A

GI adverse effects

28
Q

What are luminal amebicides used for?

A
  • should apply after systemic treatment
  • asymtomatic colonization within the intestine
  • Iodoquinol is used - cyst and trophozoite forms
29
Q

What is systemic amebicides used for?

A
  • useful for liver abscess or intestinal wall infection

- chloroquine

30
Q

What parasite is malaria caused by?

A

by plasmodium protozoa parasites (plasmodium falciparum and plasmodium vivax)
- passed by the infective anopheles mosquito

31
Q

What are some of the effects of malaria?

A
  • high fever
  • orthostatic hypotension
  • erythrocytosis
  • capillary obstruction
  • anemia
  • raised intracranial pressure
32
Q

What is the life cycle of malaria?

A
  • starts off with sporozoites
  • infects the liver within 30 minutes
  • dormant hypnozoites
  • invisible to the immune system
  • form a schizont
  • merozoites infect the blood cells
33
Q

Describe the action of primaquine

A
  • primary and secondary exoerythrocytic forms - mainly found in the liver
  • kills all gametocytic forms
  • does not affect erythrocytic form - use is combined with the blood schizonticide
  • metabolites of primaquine induce oxidative stress
  • well absorbed- oral
  • drug induced hemolytic anemia in patients with low G6PDH
  • contraindicated during pregnancy
34
Q

Describe the action of chloroquine

A
  • mainstay of antimalarial therapy
  • blood schizonticide - erythrocytic form
  • effective against systemic amebiosis
35
Q

Chloroquine has ____ dosing, is ____ absorbed in only 4 days of therapy, and has a ___ volume of distribution

A
  • oral
  • rapidly
  • large
36
Q

What cells does chloroquine persist in?

A
  • erythrocytes
37
Q

Why should chloroquine not be used in pregnancy

A

cross the BBB and placenta

Pharmacology (23 decks)

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