anti fungals

Question 1

what are some key characteristics of fungi?

Answer 1

• cells contain nuclei like chromosomes (unlike bacteria)
• they cannot photosynthesis (they are heterotrophic, like animals)
• hyphae are key to growth (exude enzymes and absorb food)
• spores are important for reproduction (sexual and asexual)

Question 2

what type of cell are fungi?

how do they reproduce ?

Answer 2

• they are single cells/ complex filamentous networks
• ‘dimorphic’ switching between Yeats and filaments
• sexual or asexual reproduction
• highly adaptable to their new environment

Question 3

what are the key differences between fungi and bacteria?

Answer 3

• fungal walls contain polysaccharide not found in other micro-organisms
• CHITIN = this adds rigidity and support, this confers resistance to cell wall antibiotics (eg- penicillin)
• B- glucan = site of action of some anti fungals
• cell membranes consist of ergosterol rather than cholesterol (this is a good target for some anti funagls)

Question 4

why will antibiotics not work against fungus?

Answer 4

because of the chitin protein in the cell wall - adding support and rigidity.

Question 5

what type of pathogen are fungals

Answer 5

they are opportunistic pathogens - this means that they will target immunocompromised people

Question 6

what fungus is going to cause superficial mycoses?

Answer 6

malassezia furfur

Question 7

what fungus Is going to cause cutaneous mycoses?

Answer 7

• tinea capitus
• tinea cruris
• tinea pedis

Question 8

what fungal pathogens are able to induce disease of an immunocompetent host?

Answer 8

• histoplasmosis
• coccoidomycosis

Question 9

due to what, will most ‘opportunistic pathogens’ cause systemic disease in patients with compromised cell mediated immunity due to:

Answer 9

• HIV
• immunosuppressive medication
• concurrent illnesses/long term lines.

Question 10

what type of yeast will cause meningitis

Answer 10

crytococcus neoformans

Question 11

yeast?

Answer 11

single oval cells replicate by BUDDING or FISSION
(some are dimorphic, can be filamentous too)

Question 12

disease entity:
candida spp.

Answer 12

thrush, fungaemia

Question 13

disease entity:
cryptococcus neoformans

Answer 13

meningitis
pneumonia
fungaemia

Question 14

disease entity:
systemic Yeasts

Answer 14

pulmonary or disseminated infections

Question 15

disease entity:
aspergillus spp., mucor, rhizopius, absidia.

Answer 15

• allergic bronchopulmonary aspergillosis
• aspergilloma
• invasive aspergillois

Question 16

disease entity:
dermatophytes; epidermophyton, microsporum, trichophyton

Answer 16

chronic infection of skin and nails, kerion

Question 17

what are the 6 anti fungal drugs

Answer 17

• azoles
• terbinafine
• polyenes
• flucytosine
• griseofulvin

Question 18

describe the ergosterol biosynthetic pathway?

Answer 18

• selective toxicity= key principle underpinning anti-infective therapy
• ergosterol biosynthetic pathway is essential to fungal but not to eukaryotic cell membranes
• anti fungal drugs can exhibit inhibitory mechanisms on ergosterol synthesis

Question 19

what 2 drugs will act as ergosterol inhibitors?

Answer 19

azoles
terbinafine

Question 20

describe the mechanism of action of Fluconazole

Answer 20

• it will inhibit fungal cytochrome P450 enzyme 14a-demethylase
• prevents conversion of lanosterol to ergosterol
• primarily fungistatic (prevents growth)
• will need a high dose to be fungicidal

Question 21

what are 4 specific try-azole drugs ?

Answer 21

• fluconazole
• itraconazole
• voriconazole
• posaconazole

Question 22

fluconazole

Answer 22

• well absorbed after oral administration
• good penetration into the cerebrospinal fluid to treat neurological infection
• excreted largely unchanged in the urine so can be used to treat candiduria.

Question 23

itraconazole?

Answer 23

• capsules require an acid environment in the stomach for optimal absorption
• hepatotoxic
• issues with drug to drug interaction

Question 24

voriconazole

Answer 24

complex issues with drug to drug interaction

Question 25

posaconazole

Answer 25

lisensed for the treatment of invasive fungal infections unresponsive to conventional treatment

Question 26

what enzyme will terbinafine

Answer 26

squalene epoxidase

Question 27

terbinafine: indications?

Answer 27

dermatophyte infections of the nails, ringworm infections, where oral therapy is appropriate.

Question 28

terbinfine: cautions?

Answer 28

psoriasis, autoimmune disease

Question 29

terbinafine: hepatic/renal impairment?

Answer 29

manufacturer advises avoid in liver disease - elimination reduced. - use half the normal dose if eGFR is less than 50mL/minute/1.73m2 and no suitable alternative is available.

Question 30

terbinafine: pregnancy and breast feeding?

Answer 30

- only use in pregnancy if potential benefit outweighs the risk - avoid in breast feeding as present in milk

Question 31

Polyenes: mechanism of action?

Answer 31

amphotercin B binds with ergosterol in fungal cell membranes, pores form which cause rapid leakage of monovalent ions and fungal cell death.

Question 32

describe the use/action of polyenes?

Answer 32

- not absorbed well when given by mouth - nystatin is applied locally for oral, oropharyngeal and peri oral infections. - amphotercin B by intravenous fusion is used to treat systemic fungal infections and is active against most fungi - it is highly protein bound and penetrates poorly into tissues - amphotercin B is toxic and side effects are common - less toxic than Ampotericin B liposomal formulations are increasingly used

Question 33

Flucytosine indications

Answer 33

systemic yeast and fungal infections, often as an adjunct to amphotericin B

Question 34

how does flucytosine work?

Answer 34

it disrupts the replication of dna by interfering with the nucleic acid chain as a false nuceltide. but it is non selective so it will also do this to the host cells.

Question 35

renal impairment for flucytosine

Answer 35

reduce the dose in case of renal impairment and measure the drug concentration.

Question 36

pregnancy and breast feeding indications for flucytosine?

Answer 36

avoid in breast feeding teratogenic in animal studies, only use if potential benefits outweigh the risks.

Question 37

what are the side effects for flucytosine?

Answer 37

hepatoxicity blood disorders

Question 38

mechanism of echinocandins? examples?

Answer 38

examples = andifulafungin, caspofungin, micafungin - they act by inhibiting beta -(1,3)-D-glucan synthase. - fungicidal against candida spp. - fungistatic against aspergillum spp. but are not used for the treatment of aspergillosis - not effective against fungal infections of the CNS - CAN ONLY BE GIVEN INTRAVENOUSLY

Question 39

griseofulvin indications

Answer 39

dermatophyte infections of the skin, scalp, hair and nails where topical therapy has failed

Question 40

griseofulvin cautions

Answer 40

may pair perofmrnace of skilled tasks, the effects of alcohol will be enhanced.

Question 41

griseofulvin contra indications

Answer 41

avoid in severe liver disease

Question 42

griseofulvin pregnancy and breast feeding

Answer 42

avoid!!!!!

Question 43

side effects of griseofulvin

Answer 43

nausea, vomitting, diarrhoea, headache, glossitis

Question 44

summary: mode of action tri-azoles

Answer 44

blocks P450 and sterol 14 alpha demthylase in the cell wall

Question 45

summary: mode of action terbinafine

Answer 45

inhibits squalene epoxidase that accumulates toxic steroid in the cell wall

Question 46

summary: mode of action polyenes

Answer 46

inhibits form pores in funga membrane

Question 47

summary: mode of action flucytosine

Answer 47

inhibits protein synthesis

Question 48

summary: mode of action echinocandins

Answer 48

inhibits 1,3 beta glucan in cell wall polysaccharide

Question 49

summary: mode of action griseofulvin

Answer 49

inhibits fungal mitosis (induces hepatic CYP450)