Fungal Derm Pharm

Question 1

How is widespread tinea treated?

Answer 1

terbinafine, itraconazole, fluconazole, griseofulvin

Question 2

How is localized tinea treated?

Answer 2

topical:

-azoles, terbinafine, naftifine, ciclopirox

Question 3

What are the treatment options for onychomycosis?

Answer 3

PO: terbinafine, griseofulvin, itra, fluconazole

Topical: Ciclopirox, amorolfine

Question 4

T or F. Topical drug therapy is largely devoid of significant systemic toxicity

Answer 4

T. if used as indicated.

Question 5

Recent FDA ruling on ketoconazole

Answer 5

The FDA is moving to restrict further use of this agent only to topical use, because of issues of toxicity including:

-adrenal dysfunction, via this azole’s ability to interupt intermediary synthetic pathways of steroid synthesis, leading to an inability to synthesize adequate cortisol.

Whereas the remaining azoles do not have this aspect to their pharmacology, you will notice a recurring theme in regards to the other 2 issues listed here. The first is hepatoxicity/dysfunction, and the second is inhibition of CYP activity, potentially leading to elevated serum levels of concurrent drugs.

Question 6

AEs of Itraconazole?

Answer 6

• negative inotropic effect (heart failure, ventricular dysfunction)-BBW
• hepatotoxicity
• Category C teratogen (can be present in breast milk as well)

Question 7

Common toxicities of fluconazole, posaconazole, and voriconazole?

Answer 7

• QT prolongation
• hepatotoxicity
• contraindicated in pregnancy

Question 8

Unique AEs of voriconazole?

Answer 8

• visual disturbances (optic neuritis-photophobia, color changes)
• photosensitizes skin (SCC and melanoma reported)

Question 9

______ must be administered with a full meal or acidic carbonated drunk for adequate bioavailability

Answer 9

Posaconazole

Question 10

How are the azoles metabolized?

Answer 10

Most undergo hepatic metabolism but Fluconazole is eliminated renally (dose adjustment necessary)

Question 11

Which AZOLEs have good CNS penetration?

Answer 11

-**Fluconazole** and Voriconazole (via P-gp interactions)

Question 12

T or F. Griseofluvin can be given topically

Answer 12

F. It is unable to penetrate skin

Question 13

How is Griseo metabolized and eliminated?

Answer 13

It undergoes hepatic metabolism and is eliminated in a mixture of renalhepatic/perspiration

Question 14

AEs of Griseo?

Answer 14

• rash
• disulfram-like effect (like metronidazole and cefotetan and some PO anti-diabetic agents)
• teratogenic
• Hepatotoxic
• Interferes with porphyrin metabolism

Question 15

Griseofluvin is a CYP inducer. What are some drugs affected by this?

Answer 15

• coumarin and warfarin are less effective
• oral contraceptives are less effective
• cyclosporine is less effective
• ethanol effects are increased (tachycardia, diaphoresis, flushing)

Question 16

Common AE of Griseo?

Answer 16

Photosensitiver

Question 17

Note: There is an issue of cross-sensitivity of griseofluvin with penicillin, cephalosporin, or carbapenem hypersensitivity.

Question 18

How does Griseofluvin work?

Answer 18

.Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.

Question 19

How does Terbinafine work?

Answer 19

terbinafine inhibits ergosterol synthesis by inhibiting the fungal squalene monooxygenase (squalene 2,3-epoxidase), an enzyme that is part of the fungal cell wall synthesis pathway

Question 20

Metabolism of Terbinafine?

Answer 20

Hepatic metabolism with renal elimination

Question 21

AEs of Terbinafine?

Answer 21

• transient lymphopenia and neutropenia with oral drug (avoid in immunosuppressed)
• rare hepatotoxicity
• category B preg

monitor CBC and LFTs

Question 22

How does Naftifine work?

Answer 22

selectively inhibits enzyme squalene 2,3-epoxidase

At higher doses, this drug is also locally bactericidal and has anti-inflammatory properties via inhibition of prostaglandins, leukotrienes, and histamine

Question 23

Notes about Naftifine

Answer 23

topical agent (no significant systemic drug interactions)

hepatic metab/renal elim

-cat B drug

Question 24

How does Ciclopirox work?

Answer 24

Unlike antifungals such as itraconazole and terbinafine, which affect sterol synthesis, ciclopirox is thought to act through the chelation of polyvalent metal cations, such as Fe3+ and Al3+. These cations inhibit many enzymes, including cytochromes, thus disrupting cellular activities such as mitochondrial electron transport processes and energy production.

Ciclopirox also appears to modify the plasma membrane of fungi, resulting in the disorganization of internal structures. The anti-inflammatory action of ciclopirox is most likely due to inhibition of 5-lipoxygenase and cyclooxygenase. Ciclopirox may exert its effect by disrupting DNA repair, cell division signals and structures (mitotic spindles) as well as some elements of intracellular transport.

Question 25

Notes about Ciclopirox (Penlac) and Amorolfine (Loceryl)

Answer 25

Topical only; limited absorption

Hypersensitivity/allergy possible

Question 26

How does Amorolfine work?

Answer 26

Inhibits ergosterol synthesis