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Antifungals Flashcards

1
Q

What types of treatment are used for viral infections in veterinary practice?

A
  • Antiviral chemotherapy
  • Immunomodulation - IFN/IL
  • Passive immunity
  • Therapeutic vaccination
  • Chemovaccination
  • Supportive and symptomatic
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2
Q

Why are antivirals not commonly used in vet med?

A
  • Expensive
  • Little development of drugs for animals
  • Niche market - SA/equine
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3
Q

When are antivirals used in viral infection?

A

In chronic viral infection/ early caught acute infection since clinical signs often persist beyond elimination of viral load (no need for antivirals)

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4
Q

Outline the potential mechanisms of action for antiviral drugs.

(x7)

A

They act upon a viral lifecycle stage which is unique to the viral, not the host cell.

  • Attachment
  • Penetration
  • Uncoating
  • Transcription & replication - most drugs act here
  • Translation
  • Virus assembly
  • Release
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5
Q

This antiviral drug has been used to treat FHV but has been seen to have no in vitro effect.

A

Famciclovir

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6
Q

These antiviral drugs, used to treat FHV, are effective against the virus but are toxic at high doses.

A

Idoxuridine, trifluridine

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7
Q

Ribavirin has been used to treat which feline viral disease. What effect does it have on the disease process?

A

FIP

Has a synergistic effect when given with IFNalpha. It doesn’t prevent death but delays time until death.

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8
Q

This antiviral drug has been used to treat FIV. Strangely it reduces clinical signs in cats but does not reduce viral load.

A

AZT

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9
Q

Which sterol makes up the fungal cell membrane? Is this different to mammals?

A

Fungi cell membranes are 1/4 ergosterol, in mammals this fraction is made up of glycerol.

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10
Q

How is ergosterol produced in the fungal cell?

A

Acetyl CoA > Lanosterol >> Lanosterol 14 a-demethylase>> Ergosterol

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11
Q

This class of antifungals targets and inhibits Lanosterol 14 a-demethylase.

What effect does this have on the fungal cell?

A

Azoles

Causes increased cell permeability and cell death

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12
Q

There are two classes of Azole antifungals, name them and specific drugs from each class.

(HINT: TIFV, IKMEC)

A
  • Triazoles:
    • Itraconazole
    • Fluconazole
    • Voriconazole
  • Imidazoles:
    • Ketoconazole
    • Micoazole
    • Enilconazole
    • Clotrimazole
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13
Q

What side effects can be caused by Azole use? (x6)

Which species is more sensitive?

A
  • Gastrointestinal
  • Hepatotoxicity
  • Thrombocytopenia
  • Teratogenic
  • Hormone suppression
  • Vasculitis with itraconazole at higher doses

Cats appear more sensitive.

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14
Q

Teratogenic

A

An agent which can disturb the normal development of the embryo or foetus

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15
Q

What ratio of excretion from biliary and renal system is seen with Azoles?

A

biliary : renal

80:20

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16
Q

Describe the PK data for Azoles.

What are the contraindications for this drug and why?

A
  • Mainly hepatic metabolism (some excreted unchanged)
  • Biliary:renal excretion = 80:20
  • Broad spectrum
  • Highly protein bound
  • Widely distributed – particularly liver, kidney, adrenal glands

Contraindicated in pregnancy and hepatic disease

17
Q

Azoles can interact with many different drug types, give three examples and explain the effect drugs have on one another.

A
  • H2 blockers, antacids and anticholinergics < absorption
  • Inhibits cytochrome P450 & P-glycoprotein
  • Ciclosporin, digoxin, cisapride, midazolam, vincristine, anti-histamines, anti-coagulants, ivermectin **doses need decreasing **- < metabolism
  • Rifampin decreases azole concentrations
18
Q

What types of pathologies can be treated using Fluconazole?

A

Cryptocococcis infection of:

  • CNS
  • Urinary
  • Ocular
  • Lung
19
Q

What is the mechanism of action for Allylamines?

A

Non-competitive inhibitor of squalene epoxidase, an enzyme in the ergosterol synthesis pathway.

20
Q

This antifungal drug persists in the body for up to 2-3 months and has been used to treat Dermatophytosis, Malassezia and other yeasts in animals, although it is used off liscence.

Which structures does the drug persist in?

A

Terbinafine

  • Skin
  • Hair
  • Sebum
  • Fat
  • Nails
21
Q

How can GI side effects of Terbinafine be reduced?

A

If given with food GI side effects are reduced.

22
Q

Outline the mechanism of action of Polyene antifungals.

A

Binds to sterols (particularly ergosterol) in cell membranes creating pores and increasing cell permeabilities

23
Q

Name a Polyene and the other antifungal class which acts as its synergist.

A

Amphotericin B

Azoles act as synergists for this class

24
Q

AMB is generally used for what type of fungal infection?

A

Deep, systemic, multifocal, severe mycosis

eg Crytococcosis

25
Q

Describe the Biphasic elimination of AMB from the body.

A
  1. Initial phase - Lasts 24hrs with a rapid decrease (70% for plasma and 50% for urine)
  2. Secondary phase - has a t1/2 of 15 days
    1. 5% excreted unchanged in urine
    2. 10-30% excreted via hepatobiliary system
    3. Remainder unknown
26
Q

What side effects can be caused by AMB?

How can side effects be minimised?

A
  • Nephrotoxicity common – monitor.
  • Renal arterial vasoconstriction - <gfr.>
    </gfr.><li>Binds cholesterol in DCT, PU/PD, distal renal tubular acidosis syndrome, nephrocalcinosis</li>

</gfr.>

LOWER DOSE/ new formulations are better

27
Q

Describe the mechanism of action of Griseofulvin.

What class does this drug belong to?

A

Binds tubulin and interrupts microtubule formation – disrupts mitosis.

Mitotic inhibitor

28
Q

What side effects are caused by Griseofulvin?

A
  • Teratogenic
  • GI
  • Hepatotoxicity
  • <rbc.wbc>
    <li>Ataxia, hypersensitivity, vasodilation, proteinuria, nephrosis</li>
    <li>Cytochrome P450 inducer</li>
    </rbc.wbc>
29
Q

What is the PK data for Griseofulvin?

A
  • Irregular GI absorption unless taken with high fat food
  • Binds keratin
  • Hepatic metabolism to 6-demethylgriseofulvin
  • Renal excretion
  • Unchanged in biliary excretion
30
Q

What is the mechanism of action of DNA/RNA inhibitors?

Name a drug from this class and side effects it may cause.

A

Converted by fungal cells (containing cytosine permease) to 5-Fluorouracil – inhibits thymidylate synthase – interferes with pyramidine metabolism.

Flucytosine

  • GI
  • Reversible hepatic damage
31
Q

This antifungal is often used with Amphotericin B since resistance to it develops quickly.

A

Flucytosine

32
Q

Describe the mechanism of action for Glucan-synthase inhibitors and name three drugs from this class.

A

Blocks synthesis of 1,3 –D glucan of the fungal cell wall.

  • Caspofungin
  • Micafungin
  • Anidulafungin
33
Q

How do interferons work?

A

Enhance antiviral immune response. They effect a stage of the viral lifecycle such as:

  • Attachment
  • Penetration
  • Uncoating
  • Translation/ transcription & replication
  • Virus assembly
  • Release

ID (13 decks)

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