Anti-fungals Flashcards
(33 cards)
1
Q
fungal infections
A
can be superficial, subcutaneous, or systemic
2
Q
griseofulvin
A
- produced by Penicillium griseofulvum
- insoluble in water
- fungistatic
- spectrum of action
-
dermatophytosis
- effective against Microsporum, Epidermophyton, and Trichophyton
- no effect on other fungi and bacteria
- most common fungal disease in cats
-
dermatophytosis
3
Q
MOA of griseofulvin
A
- primarily active on growing cells
-
binds to intracellular microtubules inhibiting:
- mitosis
- synthesis of nucleic acids and proteins
- chitin synthesis
-
incorporated in keratin and excreted in sweat
- not tightly bound to keratin
- undetectable in skin after 2-3 days
- reaches skin 4-8 hrs after admin
4
Q
griseofulvin absorption
A
- variable
- incomplete
- dependent on:
-
formulation
- microsize form
- ultramicrosize particles
-
food: increase in absorption
- best with fatty meal
-
formulation
5
Q
griseofulvin metabolism
A
- oxidized by hepatic microsomal enzymes
- excreted in the urine
- metabolism 6 times faster in animals than in people
6
Q
duration of griseofulvin treatment
A
- at least 4 weeks for successful therapy of dermatophytosis
- sometimes > 3 mo of continuous therapy
7
Q
monitioring griseofulvin therapy
A
-
repeat cultures
- do not rely on physical appearance
8
Q
griseofulvin drug interactions
A
- phenobarbital decreases absorption of griseofulvin
9
Q
formulations of griseofulvin
A
-
microsize
- capsules
- oral suspension
- tablets
-
ultramicrosize
- tablets
-
smaller size -> better absorption
- less needed
10
Q
adverse effects of griseofulvin
A
- GI
- bad taste-nausea
- vomiting, diarrhea
- bone marrow suppression
- cats with FIV
- breed predilection (Persians, Himalayans, Siamese, Abyssinians)
- CBC every 2 weeks
11
Q
griseofulvin teratogenicity
A
- do not give to pregnant animals
- malformations of the brain
- skeletal malformations (spina bifida)
- eye (cyclopia and anophthalmia)
- miscellaneous
- atresia ani or coli, absence of external nares and soft palate
12
Q
additional properties of griseofulvin
A
- anti-inflammatory effects
- suppression of allergic and irritant reactions
13
Q
amphotericin B
A
- polyene macrolide AB
- fungistatic/fungicidal
- binds to sterols (fungal and mammalian)
-
disruption of integrity of membrane
- leakage and cellular death
14
Q
spectrum of action of amphotericin B
A
- Cryptococcosis
- Blastomycosis
- Histoplasmosis
- Coccidiomycosis
15
Q
administration of amphotericin B
A
- not absorbed after oral administration
-
IV
- dehydration increases toxicity
- administered diluted in 5% dextrose after saline diuresis
16
Q
pharmacokinetics of amphotericin B
A
- high protein binding
- T1/2: 24 hours
- metabolism
- tissue sites
- 10% excreted in urine
17
Q
formulations of amphotericin B
A
- amphotericin B deoxycholate
- several lipid formulations
-
colloidal disperson
- lower peak serum levels
-
lipid complex
- lower plasma and higher liver levels
-
colloidal disperson
-
liposomal
- better penetration in the brain, longer half-life
18
Q
subcutaneous admin of amphotericin B
A
- liposomal preparation
-
well tolerated
- local irritation
-
not ideal
- less expensive
19
Q
adverse effects of amphotericin B
A
- thrombophlebitis
-
nephrotoxicity
- vasoconstrition
- direct toxicity on renal tubules
- avoid concurrent use of other nephrotoxic drugs
- hypokalemia
- resistance over time
20
Q
azoles
A
-
oral
- ketoconazole
- itraconazole
- fluconazole
-
topical
- ketoconazole
21
Q
ketoconazole
A
-
insoluble in water
- needs acidic environment for absorption
- lipophilic
- fungistatic/fungicidal
22
Q
ketoconazole spectrum of action
A
-
broad spectrum
- systemic infections
- Dermatophytosis
- Malassezia
- shampoo effective against Dermatophytes and Malassezia
23
Q
ketoconazole MOA
A
-
inhibition of lanosterol to ergosterol
- affinity for fungal vs. mammalian enzyme
- cytochrome P450 enzyme depression
24
Q
ketoconazole absorption and metabolism
A
-
oral administration
- best given with food
- peak levels in 2 hours
- liver metabolism
- T1/2 2 hours
- delayed therapeutic effect (5-10 days)
- drug interactions with drugs using cytochrome P450
25
adverse effects of ketoconazole
* **common in cats**
* **GI**: nausea, V, D
* **hepatoxicity**
* usually reversible in animals
* **teratogenic**
* **alopecia**, **pruritis, lightening coat**
* caution in **geriatric** animals (liver)
26
itraconazole
* 5-100 times **more active than ketoconazole**
* increased affinity for fungal enzyme
* **fewer adverse effects**
* usually **well tolerated in cats**
* **broad spectrum**
* **lipophilic**
* **keratinophilic**
* very expensive
27
metabolism and absorption of itraconazole
* **liver metabolism: P450 suppression**
* **high concentrations reached in skin and adipose tissue**
* poor penetration in CSF, eyes
* T1/2: dogs 8-12 hrs, **cats 40-120 hrs**
* **tissue levels maintained long after stopped**
* nails- 6 months
* suitable drug for **pulse therapy** (don't have to give every day)
28
itraconazole administration
* **oral administration**
* recommended **with food**
* **avoid antacids** (needs acidity)
* **liquid** solution
* **capsules**
29
adverse effects of itraconazole
* **drug interactions**
* **GI upset**
* **liver toxicity**
* **vasculitis at high doses**
* tip of ear, nose, tail, extremities (dogs)
30
fluconazole
* **broad spectrum**
* **highly specific for fungal enzymes**
* **safest** of the azoles
* **excellent penetration** in the brain (eyes)
* **well tolerated in cats**
31
metabolism and elimination of fluconazole
* **good absorption**
* **long T1/2**
* **no liver metabolism**
* **urinary excretion**
* therapeutic levels **persist for 10 days** after discontinuation
32
terbinafine (Lamisil)
* **allylamine**
* **lipophilic**
* **keratinophilic**
* persists in nails for 2-3 mo
* spectrum: **Dermatophytosis**, **Malasseiza**
* not used for systemic infections
* available in tablets, spray and cream
* well tolerated
33
MOA of terbinafine
* inhibition of squalene epoxidase
* **inhibits ergosterol synthesis**
* **highly specific for fungal enzyme**
* **no interference with cytochrome P450**
