Inhibitor of fungal mitosis

Question 1

Griseofulvin

Microtubule formation inhibitors

Answer 1

Mechanism of effect: inhibition of microtubule formation → mitotic spindle is disrupted → fungistatic activity
active transport uptake into dermatophytes

Spectrum: narrow, dermatophytes
Kinetics: po. administration → good absorption (fatty meal, margarine enhances) → good distribution → accumulation in str. corneum and nails
Toxicity: cat is more sensitive!
liver, GI, teratogenic!

PO, SPOT ON

Question 2

INHIBITORS OF FUNGAL MEMBRANE STABILITY- Poliene antibiotics

Answer 2

Mechanism of effect: membrane disruption → bind to ergosterol-binding site → complex-formation → permeability-changes
→ K+ efflux, H+ influx → acidic pH
→ amino acids and sugars leave the cell

fungistatic → fungicidal effect

Spectrum: yeasts, decreased against dermatophytes
some protozoa ( Leishmania
spp.)
Pharmacokinetics: bad PO. Absorption (except amphotericin – see at systemic antifungals)
Resistance: rare! develops slowly (ergosterol)
Toxicity: very toxic!
Locally: natamycin, nystatin
Systemically: amphotericin-B

Question 3

Poliene antibiotics Substances

Answer 3

-Natamycin ( Pimafucort ® )
spectrum: dermatophytes, yeasts not irritant
local treatment of eye and skin

-Nystatin
treatment of oral cavity, GI tract candidiasis (mucomycosis)
+ ear drop ( Malassezia pachydermatis

-Amphotericin-B (colloidal<=>lipid form)
Spectrum: broad, systemic mycoses!! ( Cryptococcus
spp., Histoplasma spp., Aspergillus spp.)
Kinetics: IV application → good distribution (BBB?)
Toxicity: highly toxic (but: lipid form!)
1. nephrotoxicity
2. systemic reactions („citokine storm”)
3. haematological changes (EPO decreases)
Indication: life threatening systemic mycoses!

Lufenuron ( Program A.U.V .)
chitin-inhibitor; orally every 14 days

Flucytosine
mainly yeasts ( Cryptococcus neoformans )
can be given po.
severe systemic cryptococcosis (combined with amphotericin-B)

Echinocandins
cell wall synthesis inhibitors (β-(1,3)-D glucan)
Caspofungin , Micafungin , Anidulafungin
only parenteral!
Candida spp.

Question 4

INHIBITOR OF FUNGAL NUCLEIC ACID SYNTHESIS: FLUCYTOSINE

Answer 4

Th: candidiasis, cryptococcosis
Target: it inhibits thymidylate synthase
Advantage: good distribution
Side effects- dose dep:
bone marrow suppression
cardiotoxicity
GI symptoms (nausea, vomiting, diarrhoea)
hepatic dysfunction
CI: for dogs more than 10-14 days and pregnancy kidney tox