Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Clinical Pharmacology Final > Antifungals and Antivirals > Flashcards

Antifungals and Antivirals Flashcards

1
Q

Griseofulvin MOA***

A
  • Fungistatic***
  • This is a disadvantage from some perspective
  • Interacts with microtubules to disrupt the function of the mitotic spindle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cell membrane-directed classes of antifungals

A
  • Nystatin
  • Amphotericin B
  • Miconazole
  • Clotrimazole
  • Ketoconazole
  • Itraconazole
  • Fluconazole
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nuclear-directed antifungals

A
  • Griseofulvin

- Flucytosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Spectrum of activity of griseofulvin***

A
  • Only dermatophytes (e.g. Microsporum, Trichophyton, Epidermophyton)
  • No other group of fungi
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Toxicity of griseofulvin***

A
  • Selective toxicity based on an energy dependent uptake preference
  • Diarrhea, depression, and anorexia
  • Hepatotoxicity
  • bone marrow suppression
  • Ataxia (neurological toxicity), or skin rash or photosensitization (cats especially Persian, Siamese, and Abyssinian)
  • REPORTED TO BE TERATOGENIC AND CARCINOGENIC**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Absorption of griseofulvin***

A
  • Ultra-fine crystalline preparations are absorbed adequately from the intestinal tract
  • Absorption markedly enhanced by the presence of a high fat meal***
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Distribution of griseofulvin

A
  • Highly bound and concentrated in keratinized cells

- Likely explains narrow spectrum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Metabolism of griseofulvin***

A
  • Extensive inactivation in the liver (first-pass effect)
  • It will induce hepatic drug metabolizing enzymes***
  • Often given orally
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Clinical use of griseofulvin**

A
  • Still used for treating dermatophytosis in SA but being replaced by azoles
  • Labeled for use in horses (powdered formulation) for dermatophytosis**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How long does it take for griseofulvin to take effect?

A
  • Several weeks for full effects to be realized (total duration of therapy 1-4 months)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Use of griseofulvin in food animals

A
  • While not labeled for use in food animals, it has been reported to be effective for treatment of dermatophytes in cattle
  • DVM must determine appropriate withdrawal times (difficult)***
  • Not a good option for food animals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Flucytosine mechanism***

A
  • Fungistatic*** (disadvantage)
  • Pro-drug**; once inside the cytoplasm of the fungal organism, it is converted to 5-fluorouracil (5-FU) which is an “antimetabolite”, a drug that interferes with nucleic acid synthesis and metabolism (ultimately disrupting protein synthesis). 5-FU is actually an anti-cancer drug.
  • Know it is activated by the fungi
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Spectrum of activity of flucytosine

A
  • Cryptococcus and some Candida
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Resistance to flucytosine

A
  • Develops commonly and quickly, therefore often used in combination with amphotericin (synergism occurs with amphotericin)**
  • Systemically used
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Toxicity of flucytosine**

A
  • mammalian cells lack cytosine deaminase and, therefore, cannot convert the pro-drug FC to its active form (5-FU)
  • GI flora will convert some of the 5-FC to 5-FU; 5-FU is toxic to mammalian cells
  • Potential toxicities are bone marrow suppression** and mucous membrane ulceration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Drug class of amphotericin B

A
  • Polyenes

- Cell-membrane directed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Amphotericin B MOA***

A
  • Fungicidal**
  • Binds to ergosterol to form a transmembrane pore that disrupts membrane function by allowing small molecules to leak through the membrane**
  • Mammalian cells have cholesterol (not ergosterol) in their cell wall)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Spectrum of Amphotericin B*****

A
  • One of the most commonly used antifungals in vet med (SA)
  • Generally reserved for severe systemic fungal infections such as Histoplasma, Blastomyces, Cryptococcus, sometimes Coccidioides, and other less common infections
  • NOT DERMATOPHYTES***
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Resistance and Amphotericin B

A
  • Infrequent to develop resistance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Toxicity of Amphotericin B**

A
  • Nephrotoxicity is COMMON in treated patients*** (Vasoconstriction of renal artery for 5-6 hours after administration)
  • Potentiated by use of other nephrotoxic drugs (e.g. NSAIDs)
  • Fluid therapy may reduce occurrence or severity
  • Newer (and more $$) formulations are liposome encapsulated - greater risk of nephrotoxicity
  • Possible anaphylactic-like reactions, vomiting, and fever*** (via release of histamine; some clinicians use antihistamine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Route of Amphotericin B

A
  • Available only for IV use (diluted in 5% dextrose)

- Different protocols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Half-life of amphotericin B

A
  • Long plasma half-life (1-2 weeks)

- Given either every day or every day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the primary toxicity of amphotericin B?

A
  • Nephrotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Elimination of Amphotericin B

A
  • 60% of the drug is eliminated by urine (causes nephrotoxicity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Labeled use of Amphotericin B

A
  • Not labeled for veterinary use
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Species for Amphotericin B

A
  • Sporadically in horses; no reports in food animals
  • Used in small animals for treating systemic fungal infections (Blastomycosis, Histoplasmosis, Cryptococcus most commonly)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Drug interactions with Amphotericin B**

A
  • Do NOT combine amphotericin with azoles since there will be less ergosterol in the cell membrane available for the drug. Amphotericin can interfere with the influx of triazoles
  • Ketoconazole is a fungistatic which blocks cytochrome p450 which will decrease ergosterol production
  • In Amphotericin B, it decreases the amount of ergosterol
  • NSAIDs too
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Ketaconazole mechanism**

A

***Fungistatic (azole class)

  • Inhibits ergosterol synthesis (ergosterol is the primary sterol of fungal cell membranes vs cholesterol in mammalian cell membranes) by inhibiting a CYP450 enzyme (CYP51A)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Spectrum of ketoconazole

A
  • Usually susceptible - Candida, Malassezia, dermatophytes

- Sometimes Coccidioides, Histplasma, and Blastomycoses

30
Q

Toxicity of ketoconazole***

A
  • Much safer than amphotericin B
  • Most common = GI upset and hepatotoxicity (especially in cats)***
  • Will inhibit mammalian steroid biosynthesis by inhibiting mammalian CYP enzymes
  • Avoid use in pregnant animals (interferes with progesterone)***
  • May result in infertility in males (interference with testosterone)***
  • Has been used to treat adrenal hyperplasia (interference with cortisol)
31
Q

Drug interactions of ketoconazole***

A
  • Due to inhibition of mammalian CYP450 and inhibition of P-glycoprotein
  • Probably contributes to more serious drug interactions than any other drug in dogs*****
32
Q

Protein binding of ketoconazole

A
  • Highly protein bound (>98%) therefore doesn’t distribute well to CNS, prostate, eye
  • Disadvantage
33
Q

Ketoconazole and absorption with pH***

A
  • requires acid pH for oral absorption

- Be careful; do not give with antacids***

34
Q

Clinical use of ketoconazole**

A
  • Most common use in vet med is for Malassezia dermatitis in dogs (topical formulations and systemic administration)**
  • Used for dermatophytosis in dogs and cats and sometimes as an adjunct treatment for systemic mycotic infections**
  • Poor oral absorption in horses and not recommended. Not approved for food animals
35
Q

Itraconazole efficacy compared to ketoconazole

A
  • better against Candida, Aspergillus, dermatophytes, and most systemic fungi than ketoconazole
36
Q

How long do you have to give azole antifungals?

A
  • At least 6 months to 1 year
37
Q

Itraconazole adverse effects compared to ketoconazole

A
  • Fewer adverse effects and more expensive than ketoconazole
38
Q

Clinical use of itraconazole

A
  • Used to treat mycotic rhinitis in horses
39
Q

Compounded itraconazole

A
  • had essentially ~5% oral bioavailability compared to commercial preparation
40
Q

Fluconazole metabolism

A
  • Not metabolism

- Makes it different than Itraconazole and ketaconazole

41
Q

Fluconazole excretion

A
  • Excreted by urine

- Makes it different than Itraconazole and ketaconazole

42
Q

Fluconazole distribution**

A
  • Penetrates into CNS and urinary tract ***

- Makes it different than Itraconazole and ketaconazole

43
Q

Absorption of fluconazole**

A
  • Better oral absorption than ketoconazole or itraconazole (bioavailability in horses approximately 100%)
  • Makes it different than Itraconazole and ketaconazole
  • Oral absorption is independent of gastric pH (vs ketoconazole and itraconazole)**
44
Q

Clotrimazole route

A
  • Not orally bioavailable

- Used topically as a cream

45
Q

Clotrimazole indication**

A
  • Used topically for treating nasal aspergillosis in dogs
  • Infused into bladder of dogs and cats with fungal candiduria
  • For treating otitis externa caused by Malassezia pachydermatitis**
46
Q

Miconazole indication***

A
  • Undergoes rapid metabolism therefore would require frequent systemic use
  • Available as a cream, spray, lotion, and in a combination shampoo for treatment of dermatophytosis in dogs and cats***
47
Q

Why is it unlikely that miconazole and clotrimazole would cause adverse effects?

A
  • They are topical

- Likely to decrease the number of adverse effects

48
Q

Terbinafine mechanism**

A
  • Inhibits the enzyme squalene epoxidase which results in decreased ergosterol synthesis
49
Q

Distribution of terbinafine

A
  • High concentratiosn are reached in nailbeds; although it takes several months of therapy to achieve results for onychomycosis
50
Q

Indication of terbinafine**

A
  • Used topically and systemically for dermatophytosis in dogs and cats
  • No reports of use in large animals
51
Q

What factors are involved in therapeutic failure or relapse after antifungal therapy?

A
  • Most of the antifungals are fungistatics, therefore clearance of the infection relies mainly on host response*** (most animals are immune-compromised)
  • Poor penetration into the foci of infection
  • Intrinsic and acquired resistance to antifungal
  • Toxicity
  • Inappropriate dosage regimens (e.g. discontinuation of the treatment after resolution of the clinical signs but not eradication of the infection)
  • Not well developed antifungal C&S testing methods
52
Q

MOA of Oseltamivir**

A
  • Inhibitor of Neuraminidase**
  • Neuraminidase is an enzyme required by the virus in order to release newly formed virus particles

Virus can’t affect other cells

53
Q

Spectrum of activity of oseltamivir***

A
  • According to human pharmacology reviews, oseltamivir (Tamaflu) is a potent and selective inhibitor of influenza A and B neuraminidase***
54
Q

Oseltamivir and parvovirus***

A
  • Unsubstantiated lcaims have been made about the efficacy of oseltamivir for reducing severity of parvovirus einfection in dogs***
55
Q

Oseltamivir use in birds

A
  • FDA has banned the use of this drug in birds (chickens)

- Unsure of its benefit to treat dogs or other veterinary patients is debatable***

56
Q

Mechanism of idoxuridine and trifluridine

A
  • Thymidine analogs
  • Phosphorylated once inside mammalian cells and then are able to enter thymidine synthetic pathway
  • Resulting DNA more susceptible to breakage and synthesis of faulty proteins**
57
Q

**Spectrum of activity of idoxuridine and trifluridine

A
  • Only DNA viruses (primarily Herpes and Pox viruses)***
58
Q

Most common use of idoxuridine and trifluridine

A
  • Most common use in topical corneal therapy of susceptible viral keratitis (e.g. herpetic keratopathies)***
59
Q

Trifluridine relation to idoxuridine

A
  • Fluorinated analog of idoxuridine; more potent and selective for viral DNA; also more expensive*
60
Q

MOA of acyclovir, ganciclovir, famciclovir, and penciclovir

A
  • Analogs of deoxyguanosine

- Compete with GTP for binding to DNA polymerase leading to premature termination of DNA synthesis**

61
Q

Spectrum of acyclovir, ganciclovir, famciclovir, and penciclovir

A
  • Only susceptible for herpes viruses
62
Q

Famclovir use

A
  • Prodrug converted to penciclovir

- Poor oral bioavailability

63
Q

Clinical use of famciclovir

A
  • Oral famciclovir has shown benefit in treating feline herpes virus cats (ocular and respiratory manifestations)
64
Q

Evidence of safety and efficacy for famciclovir

A
  • Limited safety and efficacy
65
Q

Zidovudine (Azidothymidine or AXT) Mechanism

A
  • Thymidine analog

- Once phosphorylated in mammalian cells, it inhibits viral reverse transcriptase (RNA-dependent DNA polymerase**)

66
Q

Spectrum of activity of Zidovudine (Azidothymidine or AXT)

A
  • Some evidence for activity against reverse transcriptase enzymes of FIP and FeLV
  • NOT CURATIVE
67
Q

Amantadine MOA**

A
  • Not well understood, but probably interferes with late-stage assembly of the virus
68
Q

Spectrum of activity of amantadine

A
  • Influenza type-A viruses in horses*
69
Q

Interferon classes

A
  • Class 1 (Interferona, interferon w, and interferon b)

- Class 2 (interferon gamma)

70
Q

MOA of interferon

A
  • All are cytokines produced by virus-infected cells and which stimulate the transcription of interferon-stimulated genes (ISGs) by other cells. Many of the ISG proteins have antiviral (and frequently other anti-pathogen or anti-tumor) effects, primarily interfering with viral RNA and protein synthesis.***
  • Induces the immune system to release proteins that will have an anti-viral effect
71
Q

Spectrum of activity of interferon**

A
  • Rather viral non-specific, but growing clinical interest for treating FIP, FeLV, and canine parvovirus**

Clinical Pharmacology Final (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions