Antifungal Agents Flashcards
How are fungal inf. often named?
Based on where they occur
tinea pedis
…cruris=jock itch
…capitis=scalp
…unguinim=under nails (onychomycosis)
…oculus
…corporus
What is a energy source for dermatomycoses?
Keratin
Topical agents to treat skin inf
Polyene antibiotics:
- Nystatin
- Amphotericin B
- Natamycin
For ringworm:
- Tolnaftate
- Ciclopirox
- Terbinafine and other “fines”
Candida and ringworm:
- Miconazole and other conazoles
Topical agents first choice of tx for fungal skin inf.
Nystatin
Class: Antifungal
Polyene antibiotics
Mech: Binds to ergosterol in fungal CM→pores→memb. leakage
Route: Topical
Can give orally, but only for fungi in gut
Too toxic for parenteral use
Amphotericin B
Class: Antifungal
- Polyene antibiotic*
- -cidal*
DOC of systemic mycotic inf.
Mech: Binds to ergosterol in fungal CM→pores→memb. leakage
Route: Slow IV (2-4 mnths) or intrathecal
Must be given w/ detergent b/c not soluble in H2O
Topical too
SE: “amphoterrible”
- Impaired renal fxn
- Fever, chills, vomiting, convulsions, severe headache
- Anemia
Amph SE=ANF (sounds similar)
*Anemia, Nephro fxn impaired, Fever *
or
AMPHTERIC
Anemia
Muscular contractions
Pores in membrane
Headache
Temp increase
Emesis
Renal fxn impaired
IV or intrathecal
Chills
Natamycin
Class: Antifungal
Polyene antibiotics
Route: Topical
Mech: Binds to ergosterol in fungal CM→pores→memb. leakage
Only one approved for use in eye
Antifungals for ringworm
Tolfnaftate
Ciclopirox
Terbinafines and other “fines”
Route: Topical
Antifungals for candida+ ringworm
Miconazole
and other “conazoles”
Route: Topical and systemic
Griseofulvin
Class: Antifungal
Tx: Nail inf.
Nail inf. must be treated systemically to avoid painful tx
Mech: Binds to fungal microtubules→inh. fungal mitosis
Taken up by growing human skin cells and concentrated in keratin
Route: Systemic
Not well absorbed on skin
Most excreted unchanged
SE:
- Headache
- Induction of P450
- Allergies
- Derived from penicillium mold
- Eat greasy fries and you will get fat *
- Eat grise microtubules (fries) and you will get PHAT*
Griseofulvin binds microtubules. P450 induction, Headache, Allergies, t_reats _Toenail inf.
Terbinafine
Class: Antifungal
Mech: Inh. squalene epoxidase→inh. ergosterol synth
Inh. ergosterol synth→Increase in sqalene
Route: Systemic
Not well absorbed on skin
Most excreted unchanged
Metabolized and inhibits P450
SE:
- Headache
- Inhibit P450
- Allergies
- Derived from penicillium mold
- Liver damage
- SquaTer*
- inh. Squalene epoxidase TERbinfine*
Production of ergosterol
Mevalonic acid→Squalene⇒Squalene 2,3 oxide
⇒=*Squalene epoxidase *
[terbinafine]
Squalene 2,3 oxide⇒Demethyl lanosterol→→→Ergosterol
- ⇒=Lanosterol demethylase*
- [-conazole]*
Histoplasmosis
Pathogenic fungal inf.–systemic mycoses
Lung lesions (like TB)
Opportunistic fungal infections
- Who gets them?*
- What fungi?*
Immunosuppressed including cancer px
Prosthetic heart valve
IV drug use
Diabetic
Fungi:
- Candida
- Aspergillus
- Mucormycosis
Causes systemic effects
How do fungi grow in our bodies?
Gets into a cavity, like a sinus, and grows
Destroys tissues
Damage from the actual destruction of tissue as well as our inflammation response
Very hard to treat
Death is not unknown
Ketoconazole
Antifungal imidazole
Mech: Inh fungal P450, including lanosterol-14-alpha-demethylase
So inh. ergosterol synth
SE:
- Nausea
- GI upset
- Hepatic toxicity
- Inh. human P450-Strongest inh. of the conazoles
- Decrease in adrenal and gonal steroid synth
- Decrease cortisol (tx of Cushing’s)
- Decrease test. (tx of prostate cancer)
- Ket…ocon..azole*
- Ket azole=cat asshole*
- So GI, nausea, and prostate cancer tx*
- And cat’s have 9 lives so they LIVEr forever…l_iver tox_*
Fluconazole
Antifungal triazole
-static
Mech: Inh fungal P450, including lanosterol-14-alpha-demethylase
So inh. ergosterol synth
SE:
- Least effect on human P450
- Teratogenic
- Liver damage
- Hallucinations
FLUCking may lead to birth defects (teratogenic)
LUCy in the sky with diamonds=LSD=Hallucinations
Itraconazole
Antifungal triazole
-static
Mech: Inh fungal P450, including lanosterol-14-alpha-demethylase
So inh. ergosterol synth
SE:
- Strongest effect on human P450 of the triazoles
- Worsen CHF or arrythmias
_I_traconazole is the strongest _I_nhibitor of P450
ItrAConazole→Arrythmias or CHF
Posaconazole
Antifungal triazole
-static
Mech: Inh fungal P450, including lanosterol-14-alpha-demethylase
So inh. ergosterol synth
SE:
- Less effect on human P450 (triazole vs imidazole)
Posaconazole is sucha pussy, it hardly inhibits our P450
Voriconazole
Antifungal triazole
-static
Mech: Inh fungal P450, including lanosterol-14-alpha-demethylase
So inh. ergosterol synth
SE:
- Less effect on human P450 (triazole vs imidazole)
- Can cause visual disturbances
_V_oriconazole causes _V_isual disturbances
Flucytosine
Antifungal agent
Pyrimidine analog
Mech: Inh thymidine synth. in fungi
Converted to 5-fluororacil→inh. thymidilate synthatase
So inh DNA and RNA synth
Prodrug-enters fungus by specific enzymes
Does not enter human
SE:
- Bone marrow depression→anemia
- Liver toxicity
- GI upset
-fungin
Caspofungin
Micafungin
Anidulafungin
Antifungal agent
-cidal
Mech: Inh. synth of fungal CW component
Enzyme inhibitor
Route: Slow IV
Not readily absorbed
SE:
- Rash
- Fever
- Fetal Damage
Do any antifungal agents cause renal damage?
Only amphotericin B
Causes impaired renal function
Quite a few antifungal agents cause hepatotoxicity
(ketoconazole, terbinafine, fluconazole, flucytosine)
So, if in doubt antifungal causes hepatox, not nephrotox.
