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VETM 443 Pharmacology > Antifungals and Antiviral Pharmacology > Flashcards

Antifungals and Antiviral Pharmacology Flashcards

1
Q

What type of organism is a fungi? What is its main mechanism of damage?

A

eukaryotic
- closer to mammalian cells

most are dimorphic

mechanism of injury is cell disruption and death causing ranulomatous inflammation

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2
Q

What are the 4 different targets of antifungal medications? What are the common classes of antifungals in each?

A

Target…

cell wall = echinocandins

cell membrane = polyene/ -azoles / allyamines

nulceic acid synthesis = flucytosine

nuclear division = griseofulvin

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3
Q

What are the main features of fungal infections and their treatments?

A

fungal infections occur in immunocompromised individuals or those who have bee non antibiotics for a long time

Often antifungal treatment is for a long time
- can have adverse systemic effects = try and use topical and local treatment when possible

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4
Q

List 3 types of polyene drugs

A

amphotericin B

natamycin

nystatin

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5
Q

What kind of antifungal is amphotericin B? What is the mechanism of efficacy?

A

macrocyclic polyene

binds ergosterol in cell membranes and creates channels = leakage

auto-oxidizes and causes free radical formation in the presence of O2

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6
Q

What are the main characteristics of amphotericin B

A

concentration dependent

fungicidal

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7
Q

How is amphotericin B administered

A

IV or local administration
- poor GI absorbtion

the original formulation is given in dextrose

it is persistent in the body so intermittent treatment can be one (every other day in dogs

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8
Q

Describe the distribution ability of amphotericin B

A

poor penetration of the eye and CNS

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9
Q

What are the adverse effecs of amphotericin B

A

nephrotoxic
- toxic to the renal tubules, especially the distal tubules
- causes renal vasoconstriction and ischemia = low GFR
- worse if hyponatremic

phlebitis

fever

V+

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10
Q

What are the 4 different formulations of amphotericin B? Why are the other formulations made?

A

original formulation

liposome encapsulated

lipid complex

colloidal dispersion with cholesterol sulfate bilayer

= all formulations add lipid to increase hydrophobicity and reduce the concentration in the kidneys (reduce nephrotoxicity)

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11
Q

Describe the efficacy of amphotericin B

A

good efficacy against a range of fungi

very little resistance

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12
Q

How is natamycin administered

A

topical

it is toxic systemically

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13
Q

What is natamycin used for

A

keratomycosis

guttoral pouch mycosis
nasal aspergillosis

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14
Q

What is a main drawback of natamycin

A

expensive

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15
Q

How is nystatin adminstered

A

topical

there is no GI absorbtion so you can give PO for tx of oral and intestinal candida

toxic systemically

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16
Q

How is nystatin mainly used

A

combination with steroid or antibiotic in ointment

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17
Q

List 2 types of azoles

A

triazole

imidazole

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18
Q

What is the mechanism of action of azole antifungals

A

inhibit ergosterol synthesis via inhibiting cytochrome P450

This reduces cell membrane function

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19
Q

Are azole drugs fungicidal or fungistatic

A

fungistatic

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20
Q

How is triazole used? Give 2 examples

A

systemic with a long elimination

ex. itraconazole or fluconazole

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21
Q

How is imidazoles used? List 3 examples

A

topically

ex. ketoconazole (but can also give systemically)
- clotrimazole
- miconazole

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22
Q

What is a main adverse effect of imidazoles

A

they inhibit mammalian sterol synthesis - impact the endocrine system

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23
Q

What factors impact the pahrmacokinetics of azole drugs

A

potency and drug interactions depend on the affinity for the cytochrome P450

it is also impacted by inhibition of P glycoprotein efflux pumps
- impact the GI absorption and penetration of eye and CNS

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24
Q

How is ketoconazole administered?

A

topical and PO

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25
What is ketoconazole used for in small animals and horses
SA - malassezia - candida - not great for aspergillus or sporothrix horse - fungal keratitis
26
What are the adverse effects of ketoconazole? List 2 contraindications
inhibit cytochrome P450 = lots of drug interaction inhibit testosterone and cortisol synthesis hepatotoxic v+ anorexia worse in cats not for pregnant or if they have liver disease
27
Describe the pharmacokinetics of ketoconazole
absorb - soluble in acid (= give with food) - poor GI absorption in horses Distribute - in skin and SC Metabolized - liver Excrete - bile for long term tx - 4-6wk
28
What is the first line treatment for systemic mycoses that are non life-threatening and non CNS related
itraconazole
29
What is itraconazole used for?
dermatophytes all fungi except fusarium
30
What is the pharmacokinetics of itraconazole
absorb - if given fed = higher AUC - if given fasted = higher C max (recommended) Distribute - accumulate in skin and har because it is lipophilic
31
How is itraconazole administered
pulse treatment - given periodically because it can persist for weeks or months give 2 consecutive days per week - this is for skin treatment only
32
What are the adverse effects related to itraconazole
GI upset hepatocellular toxicity +/- teratogen BUT it doesn't inhibit testosterone or cortisol synthesis (more specific for fungal CYP450) drug interactions
33
What are the pharmacokinetics of fluconazole
Absorb - good PO Distribute - water soluble - cross into eye and CNS - not very protein bound Excrete - urine (reduce the dose in patients with renal failure)
34
What is fluconazole used for mainly
candida cryptococcus not aspergillus
35
What are the adverse effects of fluconazole
few
36
How is miconazole administered? What is it used for?
topical - can be IV but must monitor keratomycoses dermatophytoses malassezia
37
How is clotimazole administered? How is it usually used?
topical only combination with steroid or antibiotic for otitis treatment
38
How is enilconazole administered? What is it used for?
topical dermatophyte fungal sinusitis
39
How is the 1 main allyamine? What is its main mechanism of action?
terbinafine fungicidal inhibit ergosterol synthesis by inhibiting fungal CYP450 - specific for the fungal CYP
40
What is terbinafine used for
malassezia systemic fungal infection of the skin/nail
41
What are the adverse effects of terbinafine
GI upset hepatotoxic
42
What is the mechanism of action of flucytosine drugs
uptaken into fungal cells via cytosine permease converted to 5-fluorouracil by cytosine deaminase - chemotherapy agent - incorporated into RNA = disrupt protein synthesis - incorporated into DNA = disrupt DNA synthesis
43
What is flucytosine used for?
Adjunct treatment with amphotericin B for candida/cryptococcus It is synergistic with amphotericin B and so you can lower the dose of amphotericin B when giving together
44
What is one drawback of using flucytosine
resistance is common
45
How does sodium iodide/potassium iodide work as an antifungal
mechanism is unknown it is a systemic tx
46
What is Na/K iodide mainly used for
actinomycosis (lumpy jaw)
47
What are the adverse effects of Na/K iodide
lacrimation hypersalivation cough dry scaly skin tachycardia thyroid dysfunction abortion infertility careful when using in breeding/pregnant animals
48
How is lime sulfur administered? What type of antifungal is it? What is its mechanism of action?
topical fungicide unknown mechanism
49
What is lime sulfer used for? What is an adverse effect? What is another name for lime sulfur?
dermatophytoses stinky calcium polysulfide
50
How is chlorine used as an antifungal? What is it mainly used for
effective but irritates tissue can use chlorine dioxide gas for white line disease - ex. white lightning
51
What is the mechanism of efficacy of antivirals?
it targets steps in the replication cycle of the virus they are all virostatic timing of administration is important
52
What 4 conditions are antivirals used for?
herpes keratitis equine herpes virus 1 herpes in psittiscine birds FIP (remdesivir)
53
What additional type of drug can be used as an adjunct treatment with antivirals? Give an example
immunomodulators ex. imiquimod
54
List 3 classes of antivirals and give examples of drugs within each class
nucleoside analogs - acyclovir - famcicylovir - remdesivir idoxuridane/trifluridine L-lysine
55
What species is acyclovir mainly used in?
birds (mainly) also horse/dog
56
How is acyclovir administered and absorbed?
PO - dog = good - cat/horse = poor topical = cat eye
57
What is the mechanism of action of nucleoside analogs
similar structure to guanosine phosphorylated by tyrosine kinase and DNA replication is prevented it is fairly selective for virus
58
What is famciclovir used for?
feline herpes virus (systemic use in cats)
59
What are the pharmacokinetics of famciclovir
it is a prodrug and is converted to penciclovir - complicated process in cats must monitor renal function and adjust the dose for renal failure patients
60
How is idoxuridine and trifluridine administered? What is it used for
topical herpes keratitis (ulcers iin young cats)
61
What is the mechanism of action of idoxuridine and trifluridine?
thymidine analog is incorporated into DNA synthesis and makes the DNA more breakable good against DNA viruses
62
What are the adverse effects of idoxuridine and trifluridine
non specific for virus-infected cells = lots of adverse effects topical use can cause conjunctival irritation - trifluridine is more effective but can be more irritating
63
What is the mechanism of action of L-lysine? How is it administered
it blocks the availability of arginine - it is controversial and may or may not reduce viral shedding and it may improve herpes conjunctivitis PO
64
What is imiquimod? What is it used for?
immunomodulator human genital warts superficial basal cell carcinoma equine aural plaques equine sarcoids
65
What are the pharmacokinetics of remdesivir? What is its mechanism of action?
It is a prodrug and is converted to GS441524 It's mechanism is that it is an adenosine analog
66
What is remdesivir used for? How is it administered?
FIP tx remdesivir is given parenterally GS441524 is given PO
67
What are the adverse effects of remdesivir and GS441524
remdesivir - it is acidic (1.5 pH) and can cause vx site reaction - it increases liver enzymes - eosinophilia - pruritus - uroliths (rarely) GS441524 - pruritus or urotliths (rare)
68
What should you expect when treating a cat with FIP with remdesivir?
get remdesivir with emergency drug release expect improvement within 24-48hrs monitor body weight

VETM 443 Pharmacology (23 decks)

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