Pharmacology of Anti-Virals

Question 1

What is the fungal cell membrane made of?

Answer 1

Ergosterol

Question 2

List the 4 types of fungi

Answer 2

Yeasts (crytococcus neoformans)
Fungi resembling yeast which produce a structure resembling a mycelium (candida albicans)
Filamentous fungi with a true mycelium (aspergillus fumigatus)
‘Dimorphic’ fungi that, depending on nutritional constraints may grow as either yeast or filamentous fungi (histoplasma capsulatum)

Question 3

Why are fungal infections often more difficult to treat than bacterial?

Answer 3

They are slow growing
They often occur in tissues which are poorly penetrated by antimicrobial agents

Question 4

the 3 classes of naturally occurring anti-fungals

Answer 4

polyenes
non-polyenes
echinocandins

Question 5

3 classes of synthetic anti-fungals

Answer 5

azoles
allylamine
fluorinated pyrimidines

Question 6

General MOA and examples of polyenes

Answer 6

Reduction of cell membrane viability
Amphotericin B (fungizone), Nystatin

Question 7

General MOA and examples of echinocandins

Answer 7

Reduction of cell wall viability
Caspofungin, Micafungin, Anidulafungin

Question 8

General MOA and examples of non-polyenes

Answer 8

Disrupt microtubular function
Griseofulvin

Question 9

General MOA and examples of azoles

Answer 9

Inhibition of ergosterol synthesis in the cell membrane
Imidazoles - clotrimazole, ketoconazole, miconazole
Triazoles - fluconazole, itraconazole
Broad spectrum triazoles - voriconazole, posaconazole

Question 10

General MOA and examples of Fluorinated pyrimidines

Answer 10

block nucleic acid synthesis
- flucytosine

Question 11

General MOA and examples of allylamine

Answer 11

Inhibition of ergosterol synthesis in the cell membrane
- Terbinafine

Question 12

What organism produces Amphotericin B

Answer 12

Streptomyces nodosus

Question 13

MOA of amphotericin B

Answer 13

binds to sterols in the cell membrane
membrane deformation
pore formation/ aggregate formation
leakage of K+ and Mg2+ ions
metabolic derangement

Question 14

side effects of amphotericin b

Answer 14

fever, chills, nausea, nephrotoxicity

Question 15

ROA of amphotericin B

Answer 15

IV
topically

Question 16

Another name for amphotericin b

Answer 16

fungizone

Question 17

another name for nystatin

Answer 17

Fungicidin, Mycostatin

Question 18

what organism produces nystatin

Answer 18

streptomyces noursei

Question 19

ROA of nystatin

Answer 19

too toxic for systemic
topical applications for candida infection of the skin, mucous membranes and GI tract

Question 20

MOA of nystatin

Answer 20

binds to sterols in the cell membrane
leads to membrane deformation
pore formation/ aggregate formation
leakage of ions (K+/Mg2+)
metabolic derangement

Question 21

side effects of nystatin

Answer 21

nausea
vomiting
diarrhea

Question 22

MOA of caspofungin

Answer 22

competitive inhibitor of b glucan synthase
inhibits the synthesis of B(1,3) D glucan
leads to lysis and cell death

Question 23

clinical applications of caspofungin

Answer 23

fungicidal towards candida
fungistatic towards aspergillus

Question 24

what fungus produces griseofulvin

Answer 24

penicillum griseofulvum

Question 25

clinical applications of griseofulvin

Answer 25

severe dermatophytosis
mycotic diseases of the skin, hair and nails
oral - topical is ineffective
>1 year for toenails
6-9 months for fingernails
1 month for scalp and hair ringworm

Question 26

MOA of griseofulvin

Answer 26

Inhibits fungal mitosis
- interacts with polymerised microtubules
- inhibits microtubule function
- disrupts the assembly of mitotic spindle

new growth of hair or nails is resistant to fungi

Question 27

MOA of all azoles (imidazoles, triazoles, broad spectrum triazoles)

Answer 27

interfere with ergosterol biosynthesis
inhibit CYP450 enzyme - lanosterol 14a demethylase
accumulation of 14a demethyl lanosterol

fungistatic at low doses
fungicidal at high doses

Question 28

ketoconazole

Answer 28

imidazole
broad spectrum
topical only
liver toxicity, GI disturbances, pruritis, gynaecomastasia
requires acidity for dissolution
numerous drug drug interactions