Fungi

Question 1

What is a fungal cell wall made up of?

Answer 1

Cross linked glycoprotein, glucan and chitin form the structural basis of the cell wall

Question 2

What is the main sterol in a mammal cell wall and fungal cell wall?

Answer 2

Mammals- cholesterol

Fungal- ergosterol

Question 3

What are cytochrome P450 enzymes, what are their major functions and what interactions do they have with drugs?

Answer 3

Membrane-associated protein present in most body tissues (hormone metabolism and synthesis)
Major function is drug metabolism in liver
Drug interactions- some drugs induce enzymes, some inhibit enzymes

Question 4

What are the 6 classes of antifungals and which are only used in humans?

Answer 4

Azoles
Allylamines
Polyenes
Mitotic inhibitors
DNA/RNA inhibitors 
Glucan-synthase inhibitors- human only

Question 5

What is the mode of action of azoles?

Answer 5

Azoles block cytochrome P450 14-DM which blocks the production of ergosterol

Question 6

Do azoles have a narrow or broad spectrum of activity, how protein bound are they?

Answer 6

Broad spectrum of activity

95% albumin bound

Question 7

What are the two groups of Azoles?

Answer 7

Triazoles - itraconazole
Imidazoles - ketaconazole

Suffix- ‘azole’

Question 8

What addition does the azole triazole have?

Answer 8

Higher specificity for cytochrome p450 14-dm than mammalian co-enzyme
Increased affinity for fungal cell membrane so effective at low concentrations
Lipophilic and karatinophillic, so increases affinity for keratin and residual concs in hair

Question 9

Where are azoles metabolised and excreted?

Answer 9

Metabolised- hepatic metabolism

Excretion mainly billiary, some in urine

Question 10

What are the adverse effects of azoles?

Answer 10

GI- diarrhoea and vomiting
Hepatotoxicity 
Thrombocytopenia 
Teratogenic
Supression of hormones 
Vasculitis with intraconzole

Question 11

What contraindications do Azoles have?

Answer 11

Weak base- avoid H2 blockers, antacids, anticholinergics

Inhibits cytochrome P450- may cause higher conc of other substrates

Question 12

What is the mode of action of allyamines?

Answer 12

Allyamines act of squalene epoxidase and block the production of ergosterol

Question 13

What allyamine is licensed in dogs, where is it metabolised and excreted?

Answer 13

Terbinafine in veterinary ear drops- authorised to treat malassezia otitis externa in dogs
Systemic unauthorised
Hepatic metabolism and urinart excretion

Question 14

What are the side effects of allyamine?

Answer 14

Side effects uncommon- GI, hepatotoxicity, skin

Question 15

What is the mode of action of polyene antibiotics?

Answer 15

Has a high affinity for ergosterol and therefore binds

Question 16

What is the action of amphotericin B (AMB) and when is it used and what can it be synergised with?

Answer 16

Action- fungicidal
Used- for severe life threatening, deep, systematic
Synergistic- azoles

Question 17

Where is AMB not well distributed and what are the adverse effects?

Answer 17

Poor distribution- CSF, pancreas, bone, pericardial

Adverse effects- Nephrotoxicity, monitor creatinine

Question 18

What is the mode of action of Griseofulvin, where is is metabolised and excreted?

Answer 18

MOA- binds to tubular, interferes with microtubule formation and disrupts mitosis 
Only treats dermatophytes 
Metabolised- hepatic 
Excreted- faecal 
Binds to keratin

Question 19

What are the side effects of griseofulvin?

Answer 19

Teratogenic- not for pregnant animals
GI disorders
Decreased RBCs and WBCs
Potent cytochrome P450 inducer

Question 20

What other topical drugs can be administered?

Answer 20

Lime sulfur dips- dermatophytosis

Stains yellow