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Anti fungal Pharmacology
Vet Med - Module 7
List some of the reasons why fungal infections may be on the increase
Use of agents that disrupt normal host microflora
Failure to develop a strong immune system
Patient management that suppresses the immune system
Chemotherapy, HIV/AIDs, transplants, steroid treatments
Antibiotic use - disrupts communities of microbes and allows fungal populations to increase
Invasive surgical procedures that introduce fungi
What are fungal infections called?
Give examples of systemic and superficial fungal infections
Systemic - aspergillus, candida, cyrptococcus
Superficial - dermatophytes, candida, malessezia
Fungi are prokaryotes/eukaryotes?
What are some of the sites of action of common anti-fungal drugs?
What steoid are fungal cell membranes rich in?
Which three classes of anti fungal drugs target ergosterol?
mphotericin B (polyenes)
What is the mechanism of action of Allyamines?
Inhibits ergosterol biosynthesis via inhibition of squalene epoxidase
What is the spectrum of activity of Allyamines?
What are routes of administration for Allyamines?
Oral and topical
Describe the pharmacokinetics of allyamines
Highly lipophilic, hepatic metabolism, faecal and renal elimination
Are allyamines fungicidal or fungistatic?
What is the mechanism of action of azoles?
Inhibition of cytP450-dependent 14-sterol de-methylase
What are the side effects of azoles?
GIT, anorexia, hepatotoxicity, suppression of steroid production, teratogenic
What are the routes of administration for azoles?
Oral and topical
Describe the pharmacokinetics of azoles
Depends on the agent:
Ketoconazole and Itraconazole - weak bases, lipophilic, highly plasma protein bound, hepatic metabolism and excretion in faeces
Fluconazole - not affected by gastric pH, water soluble and can be given IV, minimally plasma protein bound, minimally metabolised, 80% excreted by kidney unchanged
What is the mechanism of action of polyenes?
Binds to ergosterol and disrupts osmotic integrity of the membrane
What are the side effects of polyenes?
Nephrotoxicity, hypokalaemia, thrombophlebitis
What are the routes of administration of polyenes?
Some are now encapsulated in liposomes/lipid complexes to increase uptake in certain areas of the body
Describe the pharmacokinetics of polyenes
Poorly water soluble, little absorption from GIT
What is the cell wall of fungal cells composed of?
Chitin is on the inside and mannoproteins & b-glucans on the outside
What is the mechanism of action of drugs that target the cell wall?
Block the synthesis of b(1,3)glucan
What is the spectrum of activity of cell wall antifungals?
Candida and aspergillus species
What is the route of administration of cell wall antifungals?
Describe the pharmacokinetics of cell wall antifungals
Water soluble, highly plasma protein bound, eliminated in urine and faeces as metabolites
What type of anti fungal drug targets protein synthesis?
What is the mechanism of action of antimetabolites?
Disrupts protein synthesis
What is the spectrum of activity of antimetabolites?
Cryptococcus and Candida species
What is the route of administration of antimetabolites?
Describe the pharmacokinetics of antimetabolites
Excreted unchanged by the kidney
What other anti fungal drug are antimetabolites combined with to give better anti fungal action?
What type of anti fungal drug targets microtubules?
What is the mechanism of action of griseofulvin?
Selectively deposited in newly formed keratin, inhibits mitosis, disorganises the spindle microtubules
What are the side effects of griseofulvin?
Idiosyncratic reaction in cats, teratogenic
What is the route of administration of griseofulvin?
Oral (with high fat diet)
Describe the pharmacokinetics of grisefulvin
Poorly water soluble, hepatic metabolism and faecal elimination
What is griseofulvin licenced for in the UK?
Treating ringworm in horses