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= Sección II =
== Tema 2: Farmacocinética==
 
==The Azoles==
 
These are synthetic '''fungistatic''' agents that interfere with ergosterol formation, this results in the fungal cell being uncapable to divide. It is very broad spectrum, but unfortunately the formation of ergosterol is very similar to the synthesis of mammalian sterols and hence has a very narrow therapeutic range.
 
There are two groups of azoles; imidazoles and triazoles. They differ thanks to an addition of a triazole ring, this results in the triazoles having greater half-lives, lower toxicity and potentially increased anti-fungal activities.
 
===Imidazoles===
 
'''Enilconazole'''
* It is not absorbed after oral dosing and so has a wide safety margin.
* It is only licensed for topical ringworm treatment, but has been used off-license (following the cascade) for ''Malassezia pachydermatitis'' infections and nasal aspergillosis.
 
 
'''Ketaconazole'''
* It has good oral bioavailability if given with food; it needs an acidic pH to be absorbed.
* It is metabolised by the liver into inactive compounds that are then excreted in bile.
* It has been used for deep mycoses therapy, treatment of ringworm and nasal aspergillosis.
* Toxicity is low but can result in inappetance, pruritus, alopecia and lightening of hair.
* It has been known to be tetragenic and embryotoxic and so shouldn't be used with pregnant animals.
 
===Triazoles===
 
'''Itraconazole'''
* It is more potent than ketaconazole but likewise needs an acidic environment to be absorbed, and has a wider spectrum of activity.
* It is eliminated by hepatic metabolism.
* It is used mainly to treat systemic fungal infections.
* Can cause anorexia and hepatic toxicity in dogs. If this occurs, stop therapy until appetite returns and then continue treatment at half the dose.
 
 
'''Fluconazole'''
* Can enter the CNS, unlike other azoles and so is used to treat feline cryptococcosis infections.
* It can give some mild levels of hepatotoxicity.
 
 
 
==Griseofulvin==
* This drug is a natural antifungal produced by ''Penicillium griseofulvum'', it works by interacting with fungal microtubules and halts mitosis and so is '''fungistatic'''.
* It has a narrow spectrum of activity only really inhibiting the growth of dermatophytes.
* It's oral bioavailability is variable depending on its formulation. It is deposited in new keratin in the hair, nails and skin, and moves from deep layers to superficial layers where it can then attack the ringworm.
* It is eliminated by hepatic metabolism.
* It is '''teratogenic''', so should never be given to pregnant animals. It can exacerbate liver damage and so function should be monitored. There have been reports in cats of bone marrow toxicity.
 
==Flucytosine==
* This drug is converted by fungal cells into 5-Fluorouracil, which inhibits DNA synthesis and so is fungistatic.
* It is very narrow spectrum and only works against ''Candida'' species and ''Cryptococcus neoformans'' infections.
* It has very good oral bioavailability and distrubutes widely throughout all tissue including the CSF.
 
==Links==
 
*[[Fungi|Fungal infections]]
 
[[Category:Fungi|In]]