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Pharmacology Test 3 > Antifungal therapy (Marsella) > Flashcards

Antifungal therapy (Marsella) Flashcards

(55 cards)

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1
Q

Important drugs

1.

2.

3.

4.

5.

6.

7.

A
  1. Griseofulvin
  2. Amphotericin B
  3. Ketoconazole
  4. Itraconazole
  5. Fluconazole
  6. Terbinafine
  7. Topical therapy
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2
Q

Fungal infections can be

1.

2.

3.

A
  1. Superficial
  2. Subcutaneous
  3. Systemic
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3
Q

Ringworm

A

Dermatophytes

Look for drugs with affinity for the skin

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4
Q

Sporothricosis

(esp cats)

A

Zoonotic

Exudative lesions carry tons of orgs (wear gloves)

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5
Q

Cryptococcus

A

Systemic fungal infection

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6
Q

Griseofulvin

A

Only used rarely

Insoluble in water

Fungistatic

  • Takes a long time to see clinical improvement

Only effective against Dermatophytes

  • Microsporum
  • Epidermophyton
  • Trichophyton
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7
Q

Dermatophytosis

A

Very common in shelter cats (keep zes in bafroom)

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8
Q

Griseofulvin

MOA

A

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)

​

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9
Q

Griseofulin

Pharmacokinetics

A

Given orally

Absorption

  • variable
  • incomplete
  • dependant on
    • Formulation (ultramicro absorbed better)
    • Food (fatty meals)
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10
Q

Griseofulvin

Metabolism

A

Oxidized by hepatic microsomal enzymes

Excreted in the urine

Metabolism 6 times faster in animals than in people

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11
Q

Griseofulvin

Duration of treatment

A

At least 4 weeks required (up to 3 months or more is normal)

Do not base conclusion of treatment based on appearance: repeat cultures

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12
Q

Griseofulvin

Drug interactions

A

Drug interactions

  • lots of interactions, look up if you prescribe
  • Phenobarb decreases absorption of griseofulvin
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13
Q

Formulations of griseofulvin

A

Microsize

  • Capsules
  • Oral suspension
  • Tablets

Ultramicrosize (more absorbable, less drug required)

  • Tablets
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14
Q

Griseofulvin

Adverse effects

A

GI

  • Bad taste: nausea
  • Vomiting
  • diarrhea

Bone marrow suppression

  • Cats with FIV
  • Breed predilection
    • persians
    • Himalayans
    • Siamese
    • Abyssinians
  • CBC every two weeks

TERATOGENIC

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15
Q

Amphotericin B

about

A

Plyene macrolide AB

Fugistatic/fungicidal

Binds to sterols

  • Fungal and mammalian

Disruption of integrity of cell membrane

  • leakage
  • cellular death

Big gun: Systemic mycoses

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16
Q

Amphotericin B

Spectrum

A

Use for systemic infections

  • Cryptococcosis
  • Blastomycosis
  • Histoplasmosis
  • Coccidiomycosis
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17
Q

Amphotericin

administration

A

Not absorbed orally

Admin IV

  • Dehydration increases toxicity
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18
Q

Amphotericin B

Pharmacokinetics

A

High protein binding

T1/2: 24 hours

Metabolism

  • Tissue sites
  • 10% excreted in urine (organ of toxicity think KIDNEY)
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19
Q

Amphotericin B

Formulations

Dose

A

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
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20
Q

Amphotericin B

SC

A

Newever formulations can do SC, not idea

  • cheaper
  • still causes some irritation
  • raises total cumulative dose
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21
Q

Amphotericin

Adverse effects

A

Thrombophlebitis

  • Irritating

Nephrotoxic

  • Vasoconstriction
  • Direct toxicity on renal tubules
  • Don’t use with other nephrotoxic drugs
    • stay away from aminoglycosides
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22
Q

Nystatin

A

Yeast infections (common in dog ears)

Binds to ergosterol

Fungicidal/fungistatic

Spectrum of action

  • Candida
  • Malassezia

Topical use

  • poor oral absorption
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23
Q

Azoles

Oral

Study These Flashcards
A

Oral

  • Ketaconazole
  • Itraconazole
  • Fluconazole
  • Voriconazole
24
Q

Azoles

Topical

Study These Flashcards
A

Topical

  • Ketaconazole
  • Miconazole
  • Clortrimazole
  • Thiabendazole
  • Enilconazole
25
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**
26
Ketaconazole Spectrum
Broad spectrum * Systemic infections * Dermatophytosis * Malassezia
27
Ketaconazole
Oral admininistration Needs acidic environment for absorption: **Give with food** Lipophilic Liver metabolism: **need healthy liver**
28
Ketaconazole Therapeutic time frame
Delayed therapeutic effect * 5-10 days to start seeing effect * longer for hair to grow back
29
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
30
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
31
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
32
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
33
Itraconazole Adverse effects
Drug interactions GI upset Liver toxicity **Vasculitis at high doses** * vessel injury and necrosis at extremities
34
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
35
Fluconazole administration
**Well tolerated in cats** Prices fluctuate Now available in generic form Therapeutic levels persist for 10 days after discontinuation
36
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
37
Voriconazole Administration
Better tolerated than ketaconazole but more expensive Adverse effects in humans * photophobia * blurred vision Give at same dose in dogs as humans
38
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)**
39
Terbinafine Spectrum
Spectrum: only skin infections * Dermatophytosis * Malassezia * Yeast
40
Terbinafine Administration
Available in tablets, spray, cream * animals have too much hair for creams Well tolerated Very cheap
41
Iodides
Used for **Sporotrichosis** * **drug of choice in horses** * **hunting dogs** **​**Unknown MOA Cheap
42
Iodides Adverse effects
GI * nausea, vomiting, diarrhea * give with food Twitching, hypothermia Scaling, alopecia
43
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
44
Ketoconazole shampoo
Nizoral, Ketochlor (over the counter) Expensive Effective against * Dermatophytes * Malassezia
45
Chlorhexidine topical
Limited antifungal efficacy Concentration * 2-4% Frequent treatments Irritating in some animals
46
Miconazole Onlyl given topically
Leave on conditioner * used for Malassezia dermatitis Available as liquid * Conofite * Treatment for yeast otitis * May cause contact allergy
47
Clotrimazole (lotrimin) | (Only topical)
OTC Spectrum * Yeasts and dermatophytes * Treatment in ears * Don't do body spot treatments (systemic instead)
48
Enilconazole
Can use in environment * Dermatophytes survive in environment for up to 2 years Spectrum * Dermatophytes * Malassezia * Aspergillus Fungicidal
49
Selenium Disulfide Selsun blue
Kills yeast Effective against Malassezia No effect on dermatophytes **Toxic for Cats** Can dry out the skin
50
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
51
Thiabendazole Tresaderm
Antihelpmintic imidazole Combo product Malassezia otitis Ear mites * life cycle is three weeks (longer therapy) Length of therapy
52
Tresaderm
Steroid antibiotic thiabendazole * yeast and mites
53
Clinical case 1 Sam * 5 yo, MC, healthy labrador * Diagnosed with dermatophytosis * Microsporum gypseum in the nail bed
Options: 1. Itraconizole * expensive....hundreds of dollars 2. Terbinafine * generic option (cheap) * also likes nails
54
Clinical Case Isabelle * 14 yo, FS * On cyclosporine therapy for IMHA * Diagnosed with generalized Malassezia
1. 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
55
Cyclosporins
Cause colitis...? Maybe overdose...

Pharmacology Test 3 (12 decks)

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