Antifungal therapy (Marsella) Flashcards
Important drugs
1.
2.
3.
4.
5.
6.
7.
- Griseofulvin
- Amphotericin B
- Ketoconazole
- Itraconazole
- Fluconazole
- Terbinafine
- Topical therapy
Fungal infections can be
1.
2.
3.
- Superficial
- Subcutaneous
- Systemic
Ringworm
Dermatophytes
Look for drugs with affinity for the skin
Sporothricosis
(esp cats)
Zoonotic
Exudative lesions carry tons of orgs (wear gloves)
Cryptococcus
Systemic fungal infection
Griseofulvin
Only used rarely
Insoluble in water
Fungistatic
- Takes a long time to see clinical improvement
Only effective against Dermatophytes
- Microsporum
- Epidermophyton
- Trichophyton
Dermatophytosis
Very common in shelter cats (keep zes in bafroom)
Griseofulvin
MOA
Primarily active on growing cells
- Doesn’t work on quiescent organisms
Binds to intracellular microtubules and inhibits
- Mitosis
- Synthesis of nucleic acids and proteins
- Chitin synthesis
Incorporated in keratin
- but doesn’t bind tightly (gone in a couple days)
Griseofulin
Pharmacokinetics
Given orally
Absorption
- variable
- incomplete
- dependant on
- Formulation (ultramicro absorbed better)
- Food (fatty meals)
Griseofulvin
Metabolism
Oxidized by hepatic microsomal enzymes
Excreted in the urine
Metabolism 6 times faster in animals than in people
Griseofulvin
Duration of treatment
At least 4 weeks required (up to 3 months or more is normal)
Do not base conclusion of treatment based on appearance: repeat cultures
Griseofulvin
Drug interactions
Drug interactions
- lots of interactions, look up if you prescribe
- Phenobarb decreases absorption of griseofulvin
Formulations of griseofulvin
Microsize
- Capsules
- Oral suspension
- Tablets
Ultramicrosize (more absorbable, less drug required)
- Tablets
Griseofulvin
Adverse effects
GI
- Bad taste: nausea
- Vomiting
- diarrhea
Bone marrow suppression
- Cats with FIV
- Breed predilection
- persians
- Himalayans
- Siamese
- Abyssinians
- CBC every two weeks
TERATOGENIC
Amphotericin B
about
Plyene macrolide AB
Fugistatic/fungicidal
Binds to sterols
- Fungal and mammalian
Disruption of integrity of cell membrane
- leakage
- cellular death
Big gun: Systemic mycoses
Amphotericin B
Spectrum
Use for systemic infections
- Cryptococcosis
- Blastomycosis
- Histoplasmosis
- Coccidiomycosis
Amphotericin
administration
Not absorbed orally
Admin IV
- Dehydration increases toxicity
Amphotericin B
Pharmacokinetics
High protein binding
T1/2: 24 hours
Metabolism
- Tissue sites
- 10% excreted in urine (organ of toxicity think KIDNEY)
Amphotericin B
Formulations
Dose
Liposomal (newer formulations)
- Better brain penetration
- can use smaller doses
- longer half life
- decreased toxicity
Total cumulative dose
- given every other day
- up to 4-8 mg/kg
Amphotericin B
SC
Newever formulations can do SC, not idea
- cheaper
- still causes some irritation
- raises total cumulative dose
Amphotericin
Adverse effects
Thrombophlebitis
- Irritating
Nephrotoxic
- Vasoconstriction
- Direct toxicity on renal tubules
- Don’t use with other nephrotoxic drugs
- stay away from aminoglycosides
Nystatin
Yeast infections (common in dog ears)
Binds to ergosterol
Fungicidal/fungistatic
Spectrum of action
- Candida
- Malassezia
Topical use
- poor oral absorption
Azoles
Oral
Oral
- Ketaconazole
- Itraconazole
- Fluconazole
- Voriconazole
Azoles
Topical
Topical
- Ketaconazole
- Miconazole
- Clortrimazole
- Thiabendazole
- Enilconazole
Ketoconazole
Insoluble in water
Soluble in acidic solution: must give with food
Cidal/static
Inhibition of Lanosterol 14-demethylase
- Inhibits Ergosterol
- Affinity for Fungal vs. Mammalian enzyme
- Suppresses cytochrome P450 enzyme
- Must decrease doses of cyclosporin
Ketaconazole
Spectrum
Broad spectrum
- Systemic infections
- Dermatophytosis
- Malassezia
Ketaconazole
Oral admininistration
Needs acidic environment for absorption: Give with food
Lipophilic
Liver metabolism: need healthy liver
Ketaconazole
Therapeutic time frame
Delayed therapeutic effect
- 5-10 days to start seeing effect
- longer for hair to grow back
Ketoconazole
Adverse effects
DONT GIVE TO CATS
GI
Hepatotoxicity
- usually reversible in animals
- Black box warning for humans
If anorexic stop Ketoconazole
Teratogenic
Alopecia, pruritis, lightening of coat
Caution in geriatric animals
Itraconazole
5-100 times more active than ketaconazole
Increased affinity for fungal enzyme
- fewer adverse effects
- usually well tolerated in cats
Broad spectrum
Lipophilic
Keratinophilic
Itraconazole
Liver metabolism
High concentrations reached in skin, adipose tissue
- poor penetration in CSF, eyes
Longer half life in cats
Tissue levels maintained for a long time
- suitable for pulse therapy
Itraconazole
Administration
Oral administration
- recommended with food
- avoid antacids
- liquid solution (10mg/mL)
- capsules (100mg)
Lower doses for skin problems
Higher doses for systemic infections
Itraconazole
Adverse effects
Drug interactions
GI upset
Liver toxicity
Vasculitis at high doses
- vessel injury and necrosis at extremities
Fluconazole
Newest, most specific, safest
Broad spectrum
Highly specific for fungal enzymes
Good absorption, long half-life
Excellent penetration in the brain
No liver metabolism
Urinary excretion
Fluconazole
administration
Well tolerated in cats
Prices fluctuate
Now available in generic form
Therapeutic levels persist for 10 days after discontinuation
Voriconazole (Vfend)
Not used frequently in Vet med
Used in infections in immune compromised patients: Aspergillus
Excellent oral absorption
Liver metabolism
- P450 suppression: drug interactions
Voriconazole
Administration
Better tolerated than ketaconazole but more expensive
Adverse effects in humans
- photophobia
- blurred vision
Give at same dose in dogs as humans
Allylamines
Terbinafine (Lamisil)
About
MOA
Primarily
Lipophilic
Keratinophilic
- persistence in nails for 2-3 months after discontinuation
Mechanism
- Inhibition of squalene epoxidase
- inhibition of ergosterol synthesis: highly spec for fungal enzymes
- No suppression of cytochrome P450 (can give with phenobarb)
Terbinafine
Spectrum
Spectrum: only skin infections
- Dermatophytosis
- Malassezia
- Yeast
Terbinafine
Administration
Available in tablets, spray, cream
- animals have too much hair for creams
Well tolerated
Very cheap
Iodides
Used for Sporotrichosis
- drug of choice in horses
- hunting dogs
Unknown MOA
Cheap
Iodides
Adverse effects
GI
- nausea, vomiting, diarrhea
- give with food
Twitching, hypothermia
Scaling, alopecia
Caspofungin (Cancidas)
Echinocandin
Pythium: doesn’t have ergostral but has glucan
Glucan synthesis inhibitor
- specific for fungal walls
Effective against
- Aspergillus
- Candida
- Oomyces: Pythium
IV use
No adverse effects in dogs
Ketoconazole shampoo
Nizoral, Ketochlor (over the counter)
Expensive
Effective against
- Dermatophytes
- Malassezia
Chlorhexidine
topical
Limited antifungal efficacy
Concentration
- 2-4%
Frequent treatments
Irritating in some animals
Miconazole
Onlyl given topically
Leave on conditioner
- used for Malassezia dermatitis
Available as liquid
- Conofite
- Treatment for yeast otitis
- May cause contact allergy
Clotrimazole (lotrimin)
(Only topical)
OTC
Spectrum
- Yeasts and dermatophytes
- Treatment in ears
- Don’t do body spot treatments (systemic instead)
Enilconazole
Can use in environment
- Dermatophytes survive in environment for up to 2 years
Spectrum
- Dermatophytes
- Malassezia
- Aspergillus
Fungicidal
Selenium Disulfide
Selsun blue
Kills yeast
Effective against Malassezia
No effect on dermatophytes
Toxic for Cats
Can dry out the skin
Lime Sulfur
Extremely effective against dermatophytosis
Will stain skin yellow
Will stain tub
Will ruin jewelry
Drying
Sulfur smell
Don’t rinse, must dry on patients
Thiabendazole
Tresaderm
Antihelpmintic imidazole
Combo product
Malassezia otitis
Ear mites
- life cycle is three weeks (longer therapy)
Length of therapy
Tresaderm
Steroid
antibiotic
thiabendazole
- yeast and mites
Clinical case 1
Sam
- 5 yo, MC, healthy labrador
- Diagnosed with dermatophytosis
- Microsporum gypseum in the nail bed
Options:
- Itraconizole
* expensive….hundreds of dollars - Terbinafine
- generic option (cheap)
- also likes nails
Clinical Case
Isabelle
- 14 yo, FS
- On cyclosporine therapy for IMHA
- Diagnosed with generalized Malassezia
- Ketoconazole
- old
- on cyclosporin
- NOT A GOOD CHOICE
2. Fluconazole
- would have to decrease the cyclosporin
3. Terbinafine - Not best choice for yeast
- Wont have to mess with cyclosporin dose
Also use with a topical shampoo
Cyclosporins
Cause colitis…? Maybe overdose…
