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Dermatology Pharmacology > Tinea and Onchomycosis > Flashcards

Tinea and Onchomycosis Flashcards

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1
Q

Why is the use of ketoconazole extremely restricted?

A

Unique Effects:
• ADRENAL INSUFFICIENCY - affects human corticolsteriod synthesis

Not Unique:
• HEPATOTOXICY - at prolonged dose or intermittent high dose
• CYP interactions

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2
Q

What are some possible symptoms associated with Ketoconazole adrenal insufficiency?

A

• Inability to Manage Stress (surgery, intenstive care, etc.)

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3
Q

What is the MOA of all of the Azoles?

A

• Inibition of Lanosterol 14-alpha-demethylase that is necessary for conversion of lanosterol for ergosterol needed to make the cell wall

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4
Q

What side effects and contraindications that are universal across the Azoles?
• Which are unique to: Itraconazole, Posaconazole, Voriconazole, Fluconazole?

A

AZOLES: all are contraindicated with pregnancy and breastfeeding. All may cause QT prologation, CYP interactions, and Hepatoxicity.

Itraconazole:
• BBW: Negative Inotropic Effect => HF, Vent. Dysfunction
(Itraconazole has negative Inotropic effect)

Posaconazole:
• Posaconazole inhibits P-gp

Voriconazole:
• Voriconazole causes Vision changes and UV sensitivity

Fluconazole:
• Renally eliminated and may cause renal toxicity
(Fluconazole may lower your GFR)

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5
Q

What problems are there for the absorption of Posaconazole?
• what do we do to fix this?

A

Posaconazole needs to be administered with a full meal or acidic carbonated drink for adequate bioavailability

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6
Q

If you have a CNS fungal infection which Azoles should you use?

A

Use Fluconazole and Voriconazole => both can cross the BBB (F > V)

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7
Q

What effects does Griseofluvin have on CYPs?
• possible adverse drug reactions?

A

CYP3A4 Inducer

decreased activity of: Warfarin (after 12 wks), Oral contraceptives, Cyclosporine

Increased negative effects with EtOH (tachycardia, flushing)

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8
Q

What are some contraindications of Griseofluvin?

A

CONTRAINDICATIONS
Pregnancy – TERATOGENIC
Hepatotoxic
Porphyria– interferes with porphyrin metabolism
PENICILLIN Hypersensitive pts.

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9
Q

Can you give griseofulvin topically to avoid its teratogenic effects in pregnancy?

A

NO

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10
Q

What regular tests should a patient on Terbinafine get?
• Can this be given to pregnant women?

A

CBCs, this drug is knonw to cause blood dyscrasias

Terbinafine - may be your best option for a pregnant woman b/c its only category B

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11
Q

What two antifungals may be okay to give systemically in pregnancy?
• what advantage do you get from combining these with Azoles?

A

**Terbinafine and Naftifine

*these inhibit ergosterol synthesis earlier in the pathway so there is no advantage to adding topical azoles or anything like that**

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12
Q

What are the good side effects of Naftifine?

A

Several Good ones:
• High concentration can inhibit growth of Gram positive and negative bacteria
• Has anti-inflammatory properties

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13
Q

What two drugs can only be used topically to treat fungal infections?

A

• Ciclopirox
• Amorolfine

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14
Q

Itraconazole

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Itraconazole
Administration – PO? or IV or Topical

MOA
Inhibits the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is necessary for the conversion of lanosterol to ergosterol, a vital component of the cellular membrane of fungi.

INDICATION

NOT for brain infections => cannot cross BBB

SIDE EFFECTS
BBW: NEGATIVE INOTROPIC action => HF, Ventricular dysfunction, drug-drug interaction
Hepatotoxicity => liver failure => high LFTs

CONTRAINDICATIONS

  • *Pregnancy Category C**, but deformities have been reported
  • *Breastfeeding**
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15
Q

Fluconazole
Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Fluconazole, Posaconazole, Voriconazole
Administration – IV or PO? or Topical

MOA
Inhibits the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is necessary for the conversion of lanosterol to ergosterol, a vital component of the cellular membrane of fungi.

INDICATION
Fluconazole and Voriconazole can cross the BBB (Flu > Vori)

SIDE EFFECTS
CYP interactions (ALL)
• Posaconazole also affects P-gp activity
Hepatoxicity – high LFTs
Voriconazole causesVisual disturbances and may make you sensitive to UV light (photosensitivity)

QT prolongation + Arrythmias

CONTRAINDICATIONS

  • *Pregnancy** => All are contraindicated
  • *Fluconazole** => Renal Insufficiency (dose adjust)
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16
Q

Posaconazole

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Fluconazole, Posaconazole, Voriconazole
Administration – IV or PO? or Topical

MOA
Inhibits the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is necessary for the conversion of lanosterol to ergosterol, a vital component of the cellular membrane of fungi.

INDICATION
Fluconazole and Voriconazole can cross the BBB (Flu > Vori)

SIDE EFFECTS
CYP interactions (ALL)
• Posaconazole also affects P-gp activity
Hepatoxicity – high LFTs
Voriconazole causesVisual disturbances and may make you sensitive to UV light (photosensitivity)

QT prolongation + Arrythmias

CONTRAINDICATIONS

  • *Pregnancy** => All are contraindicated
  • *Fluconazole** => Renal Insufficiency (dose adjust)
17
Q

Voriconazole

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Fluconazole, Posaconazole, Voriconazole
Administration – IV or PO? or Topical

MOA
Inhibits the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is necessary for the conversion of lanosterol to ergosterol, a vital component of the cellular membrane of fungi.

INDICATION
Fluconazole and Voriconazole can cross the BBB (Flu > Vori)

SIDE EFFECTS
CYP interactions (ALL)
• Posaconazole also affects P-gp activity
Hepatoxicity – high LFTs
Voriconazole causesVisual disturbances and may make you sensitive to UV light (photosensitivity)

QT prolongation + Arrythmias

CONTRAINDICATIONS

  • *Pregnancy** => All are contraindicated
  • *Fluconazole** => Renal Insufficiency (dose adjust)
18
Q

Griseofluvin

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Griseofluvin
Administration – PO, never topical

MOA
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

INDICATION

SIDE EFFECTS
CYP3A4 Inducer => decreased activity of: Warfarin (after 12 wks), Oral contraceptives, Cyclosporine; Increased negative effects with EtOH (tachycardia, flushing)

PHOTOSENSITIVIY

CONTRAINDICATIONS
Pregnancy – TERATOGENIC
Hepatotoxic
Porphyria– interferes with porphyrin metabolism
PENICILLIN Hypersensitive pts.

19
Q

Terbinafine

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Terbinafine
Administration – Topical or PO

MOA
Inhibits squalene monooxygenase, thus blocking the biosynthesis of ergosterol,

INDICATION
Pregnancy Cat. B

SIDE EFFECTS
Lymphopenia, Neutropenia => GET REGULAR CBCs.
Rare hepatotoxicity

CONTRAINDICATIONS
Avoid in immunosuppressed b/c of opportunists

20
Q

Naftifine

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Naftifine
Administration – PO

MOA
Inhibits squalene 2,3 epoxidase blocking ergosterol synthesis

INDICATION

Would be acceptable for use in pregnancy (Cat. B), low risk of Drug-Drug interaction

SIDE EFFECTS

Several Good ones:
• High concentration can inhibit growth of Gram positive and negative bacteria
• Has anti-inflammatory properties

CONTRAINDICATIONS – none listed

21
Q

Ciclopirox

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Ciclopirox
Administration – TOPICAL ONLY

MOA
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.

SIDE EFFECTS
Skin rash due to reaction with formulation

22
Q

Amorolfine

Administration

MOA

INDICATION

SIDE EFFECTS

CONTRAINDICATIONS

A

Amorolfine
Administration – TOPICAL ONLY

MOA
Inhibits Ergosterol Synthesis

SIDE EFFECTS
Skin rash due to reaction with formulation

Dermatology Pharmacology (11 decks)

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