Chapter 7 anit infective - antifungal drugs Flashcards
amphotericin B (fungizone, abelcet, ambsiome)
polyenes
- disrupts plasma membrane of fungal cells
- greater affinity for ergosterol (fungal membrane component) than for cholesterol (mammalian)
indication
* systemic fungal infections
* fungal meningitis
* fungal UTIs
effects
* toxic @ therapeutic dose
* nephrotoxicity (hydrate pt!)
* fever/chills
* hypokalemia
* thrombophlebitis (swollen or inflamed vein due to a blood clot)
* anemia
pharmcokinetics
* slow IV for systemic infections
* intrathecal for meningitis (route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space)
* bladder irrigation for cystitis
note
* check blood count, urinalysis, liver enzymes blood urea-nitrogen, creatinine and electrolytes (before and during TX)
* liposome-encased (fat capsule?) amphotericin (abelcet, ambisome) have less nephrotoxicity and infusion related toxicity
nystain (mycostatin)
polyenes
- disrupts plasma membrane of fungal cells
- greater affinity for ergosterol (fungal membrane component) than for cholesterol (mammalian)
indication
* intestinal candida (common in gut?)
* thrush (oral candida)
effects
* few when given orally
pharmacokinetics
* PO/topical
fluconazole (diflucan)
azoles
- inhibits fungal cytochrome p450 enzyme
- damages plasma membrane by inhibiting sterol demeythlation (essential step in making plasma membrane sterols)
- sterols and sterol-like compounds are ringed molecules that are found in biological membranes and help to regulate membrane fluidity, permeability, and rigidity.
indication
1) systemic histoplasmosis (Histoplasmosis is caused by a fungus that lives in soil, particularly where there’s a large amount of bird or bat poop. People can get histoplasmosis by breathing in fungal spores, and infection can be mild or life-threatening.) — fever, cough, and fatigue => or serious infection
2) blastomycosis ( fungal infection caused by Blastomyces dermatitidis. It presents as a pulmonary infection after the inhalation of spores, and it may be either asymptomatic or have severe life-threatening complications like acute respiratory distress syndrome.)
3) coccidomycosis (including meningitis) [valley fever (also called coccidioidomycosis or “cocci”) is a disease caused by a fungus that grows in the soil and dirt in some areas of California and the southwestern United States.] — Lungs => CNS + skin/bones/joints
4) sporotrichosis (infection caused by a fungus called Sporothrix. This fungus lives throughout the world in soil and on plant matter such as sphagnum moss, rose bushes, and hay. 1,2. People get sporotrichosis by coming in contact with the fungal spores in the environment.)
* infection of the joints can cause joint pain that may be confused with rheumatoid arthritis. Infections of the central nervous system can involve difficulty thinking, headache, and seizures.
* cough, shortness of breath, chest pain, and fever — pulmonary
* 1st symptom of cutaneous (skin) sporotrichosis is usually a small, painless bump that can develop any time from 1 to 12 weeks after exposure to the fungus. The bump can be red, pink, or purple, and usually appears on the finger, hand, or arm where the fungus has entered through a break in the skin.
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- opportunistic cryptococcosis ( opportunistic fungal pathogen because of its tendency to infect immunocompromised individuals, particularly those infected with HIV.)
- candidiasis (Candidiasis is a fungal infection caused by a yeast (a type of fungus) called Candida. Some species of Candida can cause infection in people; the most common is Candida albicans. Candida normally lives on skin and inside the body, such as the mouth, throat, gut, and vagina, without causing problems.)
- candidal thrush
- vaginitis
- esophagitis
effects:
* nausea/vomiting
* rash
* diarrhea
pharmaco
* CNS, eye, urine penetration
* excellent bioavailability
Fluconazole and flucytosine are only antifungal agents that reah therapeutic concentration in brain — fulconzaole is more effective against cryptococcus meningitis
PO/IV
Itraconazole (sporanex)
azole
- inhibits fungal cytochrome p450 enzyme
- damages plasma membrane by inhibiting sterol demeythlation (essential step in making plasma membrane sterols)
- sterols and sterol-like compounds are ringed molecules that are found in biological membranes and help to regulate membrane fluidity, permeability, and rigidity.
indication
1) aspergillosis (nfection caused by Aspergillus, a common mold (a type of fungus) that lives indoors and outdoors. Most people breathe in Aspergillus spores every day without getting sick.)
2) histoplasmosis (fungus that lives in soil, particularly where there’s a large amount of bird or bat poop. People can get histoplasmosis by breathing in fungal spores, and infection can be mild or life-threatening)
3) coccidiomycosis, not including meningitis in this case (valley fever (also called coccidioidomycosis or “cocci”) is a disease caused by a fungus that grows in the soil and dirt in some areas of California and the southwestern United States.] — Lungs => CNS + skin/bones/joints
4) sporotrichosis (This fungus lives throughout the world in soil and on plant matter such as sphagnum moss, rose bushes, and hay. 1,2. People get sporotrichosis by coming in contact with the fungal spores in the environment – skin, lung, or bump)
5) paracoccidiomycosis (systemic fungal infection caused by a dimorphic fungus endemic in Central and South America.)
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* local tinea (fungal infection of the skin. Tinea is also known as ringworm. This is because it can cause red patches on the skin in the shape of rings.) or candidal infections (Candida normally lives on skin and inside the body, such as the mouth, throat, gut, and vagina, without causing problems)
better than ketoconozole for sprothrix aspergillus
effects
* edema (rare)
* hepatitis
* nausea
glucocortioid synthesis…
PO/IV
clotrimazole (lotrimin)
azole
- unknown mechanism
indication
* candida
* dermatophyte infection of skin (fungal infections of the skin and nails caused by several different fungi and classified by the location on the body. Dermatophyte infections are also called ringworm or tinea. Symptoms of dermatophytoses include rashes, scaling, and itching)
* vaginal candidiasis
pharmaco
1) topical
2) vaginal cream and inserts
3) PO (troches — dissolves slowly)
miconazole (monistat)
azole)
- mech unknown
indication:
* vaginal candidiasis
* systemic fungal infections
effects
* phlebitis
* pruitius
* fever
* n/v (vomiting when IV)
* rash
PO/IV
posaconazole (noxafil)
azole
blocks synthesis => ergosterol (needed for fungal membrane)
indication
* prevent invasive aspergillus ( common mold (a type of fungus) that lives indoors and outdoors )
* candida as well
* oropharyngeal candidiasis RESISTANT TO itraconazole / flucnoazole
effects
* HTN
* hypotension
* hypokalemia
* diarrhea
* n/v
PO/IV
caspofungin (cancidas)
azole
inhibits synthesis of beta (1,3)-D-glucan, needed for fungal cell walls
inidcation
* aspergillosis
* candidemia
* esophageal candidiasis (fungal infection caused by a yeast (a type of fungus) called Candida.)
effects
* diarrhea
* hypotension
IV slow infusion, not bolus
micafungin (mycamine)
andiulafungin (eraxis)
azole
inhibits synthesis of beta (1,3)-D-glucan, needed for fungal cell walls
indication
* candidemia
* esophageal candidiasis
effect
hypotension, diarrhea, vomiting
IV slow infusion
Terbinafine (lamisil)
other
- inhibits squalene epoxidase
- critical enyzme that converts squalene (biochemical precursor in sterol biosynthesis, including cholesterol and steroid hormones in the human body) to ergosterol in fungi
indication
* toenail infection d/t trichphyton species
effects
* neutropenia
* skin rxn
* opthalmic toxicity
Long half life – good tissue penetration
monitor blood counts
Voriconazole isovuconazonium
other
- blocks fungal 14 alpha-lanosterol demethylation
indication
* aspergillosis
* esophageal candidiasis
* other fungal infections
effects
* visual disturbances
* hepatotoxicity
* rash
* vomiting
IV fo all cases except esophageal candidiasis
