Antifungal Agents

Question 1

Classification by Mechanism of Action

Answer 1

1. Polyenes (Amphotericin B, Nystatin)
2. Antimetabolite (5 Flucytosine, Terbinafine)
3. Echinocandins
4. Azoles (Triazoles, Imidazoles)

Question 2

Classification by Site of Infection

Answer 2

1. Subcutaneous and Systemic Mycotic Infections (Amphotericin B, 5 Flucytosine, Echinocandins, Triazoles)
2. Cutaneous Mycotic Infections (Nystatin, Imidazoles, Terbinafine)

Question 3

Parenteral Antifungals

Answer 3

1. Amphotericin B
2. Echinocandins

Question 4

Oral antifungals

Answer 4

1. 5 Flucytosine
2. Itraconazole

Question 5

Oral and parenteral antifungals

Answer 5

Triazoles

Question 6

Topical and Vaginal Suppositories

Answer 6

1. Imidazole
2. Nystatin (Oral also)
3. Terbinafine (Oral also)

Question 7

Terbinafine MOA as Squalene epoxidase inhibitor and Administration?

Answer 7

Inhibit squalene conversion to lanosterol and thus biosynthesis of ergosterol, reducing cell membrane function. Toxic accumulation of squalene increases membrane permeability and fungal cell death

Oral and Topical (Cream, gel)

Question 8

Terbinafine antifungal activity against _______ and is indicated in treatment of ___________________

Answer 8

Trichophyton - Cause tinea

Onychomycosis, Tinea capitis (Scalp) - Oral

Tinea corporis (Ringworm), Tinea cruris (Groin), Tinea pedis (Foot) - Topical

Question 9

Why are onychomycosis and tinea capitis treated by terbinafine orally?

Answer 9

Accumulation in the keratin is necessary

Question 10

Can terbinafine be used in renal and hepatic impairment?

Answer 10

To be avoided

Question 11

Why is terbinafine bioavailability 40%?

Answer 11

Extensive CYP450 metabolism and excretion by urine

Question 12

Terbinafine ADR?

Answer 12

1. GI disturbance
2. Headache, rash
3. Elevated LFTs

Question 13

Terbinafine is contraindicated in ________ but is it safe in pregnancy?

Answer 13

Breastfeeding (Accumulation in milk)

Safe in pregnancy

Question 14

Nystatin oral administration instructions

Answer 14

Swish and swallow or Swish and spit

Question 15

Nystatin is indicated for use in …

Answer 15

1. Oropharyngeal candidiasis (Thrush)
2. Vulvulovaginal candidiasis
3. Cutaneous candidiasis

Question 16

Why is nystatin not given parenterally?

Answer 16

Acute infusion-related adverse effects and nephrotoxicity can occur (Systemic toxicity)

Question 17

Nystatin ADR

Answer 17

Well tolerated. Some skin irritation for topical and vaginal formulations

Question 18

How long does miconazole stay on the skin and how deep it penetrates?

Answer 18

Stratum corneum for more than 4 days

Question 19

Miconazole is indicated in …

Answer 19

1. Tinea pedis (Foot)
2. Tinea cruris (Groin)
3. Tinea versicolor
4. Vulvulovaginal candidiasis

Question 20

Clotrimazole is used for …

Answer 20

1. Dermatophyte infections (Cutaneous candidiasis)
2. Vulvulovaginal candidiasis
3. Oropharyngeal candidiasis

Question 21

Imidazole ADRs

Answer 21

Contact dermatitis, vulvulovaginal irritation, edema

GI disturbance

Elevated liver enzymes (Clotrimazole oral)

Question 22

Which triazole requires dose adjustment in renal impairment?

Answer 22

Fluconazole

Question 23

How are each triazole cleared?

Answer 23

1. Fluconazole - Renally excreted unchanged
2. Posaconazole - Fecal excretion
3. Itraconazole - Hepatic metabolism and renally excreted
4. Voriconazole - Hepatic metabolism and renally excreted

Question 24

Which triazole is taken orally only?

Answer 24

Itraconazole

Question 25

Oral administration counselling points for posaconazole, itraconazole and voriconazole?

Answer 25

Take with high fat meal (Dairy product) - Posaconazole Avoid antacids, PPI, H2RAs Best taken on empty stomach - Itraconazole, Voriconazole

Question 26

Azole inhibit hepatic CYP450 3A4 and enhance the activity of which drugs?

Answer 26

Warfarin, cyclosporine, oral hypoglycemic agents

Question 27

Can azoles be used in pregnancy?

Answer 27

Teratogenic - Avoid in pregnancy

Question 28

How are echinocandins cleared?

Answer 28

Hepatic metabolism by hydrolysis and N-acetylation and excreted in urine and feces

Question 29

Echinocandin ADR

Answer 29

Well tolerated, sometimes GIT, fevers, chills, rashes, skin flushing, thrombocytopenia

Question 30

Mycotic Drugs with good CSF penetration

Answer 30

Fluconazole, Voriconazole, 5 Flucytosine

Question 31

How does conventional amphotericin B cause nephrotoxicity?

Answer 31

Despite low drug levels excreted in the urine, conventional amphotericin B causes renal vasoconstriction and reduces GFR by more than half

Question 32

Amphotericin B ADRs

Answer 32

Fever and chills, Nephrotoxicity, Electrolyte imbalances (Hypotension), Thrombophlebitis, Bone Marrow Suppression (Anemia)