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36 Cards in this Set
- Front
- Back
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Fungal Infections
considerations |
Slow growing
Occur in tissues poorly penetrated by most drugs Treatment requires long-term approach Use of fungistatic agents increases risk of relapse Increase in serious systemic infections has paralleled the increase in ***immuno-compromised patient population |
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Vulvovaginal Candidiasis Treatments---types of infections
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Sporadic
Oral or topical azoles Recurrent (>4/year) Recommend daily yogurt containing Lactobacillus acidophilus Duration of therapy increased to about 10 to 14 days followed by low-dose maintenance therapy for six months Complicated(immunocomp, DM) Increase duration of therapy to about 10 – 14 days Pregnancy Preference given to topical agents |
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Vulvovaginal Candidiasis
agents named |
Topical
Clotrimazole, miconazole, ticonazole Oral Ketoconazole, itraconazole, fluconazole |
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Oropharyngeal & Esophageal Candidosis
Risk factors local and SYStem |
Risk factors - local
Use of steroids Dentures Xerostomia Smoking Trauma to mouth cavity Risk factors - Systemic Drugs that inhibit immunity Neonates or elderly HIV or AIDS Diabetes Malignancies Nutritional deficiencies |
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Oropharyngeal & Esophageal Candidiasis
Tx strategy agents |
Minimize all predisposing factors as possible
Topicals are preferred Troches, mouthwashes and rinses Require long exposure times for maximal effect Preferred agents Fluconazole and itraconazole |
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Mycotic Infections of the Skin, Hair and Nails
fungus Tx agents |
Primary infectious agents are Trichophyton, Epidermophyton, and Microsporum
Treatment Keep infected area dry and clean Topical agents preferred Oral agents often preferred for toenail and fingernail infections Preferred agents Topical – fluconazole and itraconazole Oral – terbinafine and itraconazole |
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Invasive Fungal Infections
fungus |
Histoplasmosis
Blastomycosis Coccidioidomycosis Cryptococcosis Candida Infections Aspergillosis |
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Invasive Fungal Infections
Treatment Strategies |
Typically based on severity of infection
Oral ketoconazole or itraconazole where longer treatment period is allowable Intravenous amphotericin B where infection is serious and faster treatment desired |
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Amphotericin B
moA |
(Amphocin, Fungizone)
Systemic anti-fungal for systemic infections Large ring structure with hydrophilic and hydrophobic regions. Mechanism of action Bind to fungal membrane component ergosterol(fungus only) Alters fungal cellular permeability, a “pore former” mechanism, that results in loss of intracellular constituents |
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Amphotericin B
soA |
Broad spectrum of action
Candida Cryptococcus neoformans Invasive dimorphic fungi Aspergillus, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Sporothrix schenckii an IV drug can be inhaled/oral to directly target very poor penitrat. |
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Amphotericin B
p-kin considerations |
an IV drug can be inhaled/oral to directly target
very poor penitrat. Biotransformation rate is slow Half-life of can vary considerably 24 hours with normal renal function following single dose to about 15 days with multiple dosing due to tissue storage Elimination occurs by combination of renal and biliary routes.(when saturated looks more like ZERO ORDER elimination) |
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Amphotericin B
ADV RXs common |
Nickname is Amphoterrible
Hypersensitivity Rare but serious Common – Infusion related Headache, fever, chills, hypotension, nausea/vomiting and tachypnea Manage with premedication with ibuprofen or co-infusion of hydrocortisone Chills, if severe, can be treated with meperidine (opioid anelgesic) can cause HYPERthermia so watch it |
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Amphotericin B
ADV RXs serious |
*****Nephrotoxicity and electrolyte loss, especially with long-term treatment
May be related to loss of selective toxicity to renal tubular cells Avoid other nephrotoxic agents Sodium loading and hydration may prevent or ameliorate it -Hematological problems Normochromic normocytic anemia, thrombocytopenia, leukopenia, etc. ***Black Box Warning for use in serious invasive fungal infections only |
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Amphotericin B
BBW |
***Black Box Warning for use in serious invasive fungal infections only
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Amphotericin B
Nephro scene-prevention attempt |
Amphotericin B nephrotoxicity can be reduced by saline infusion before and after the infusion
The saline infusion volume can be reduced in patients receiving intravenous extended spectrum penicillins LIPID formulations are also better |
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Amphotericin B
lipid formulations |
Infusion-related reactions are more intense with some preparations
Nephrotoxicity is lower Preferred for patients with renal impairment or intolerance to standard Amphotericin B deoxycholate preparation. Very expensive compared to standard preparation |
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Nystatin
moA soA |
(Mycostatin Pastilles Lozenges)
Mechanism of action similar to amphotericin B Oral, topical and vaginal preparations for Candida infections Lower toxicity than amphotericin B related to low systemic absorption Lipid formulation in testing for systemic infections |
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Flucytosine
moA |
(Ancobon)
nasty-Systemic anti-fungal Activated by fungal cytosine deaminase to 5-fluorouracil (5-FU) Incorporation into fungal RNA *****inhibits fungal protein synthesis***** Further conversion to the nucleotide form (flurodeoxyuridylic acid) inhibits thymidylate synthetase blocking synthesis of pyrimidines *Blocks DNA synthesis* |
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Flucytosine
Spectrum of action |
Rarely treatment of choice because of toxicity
Candida albicans Cryptococcus neoformans Chromomycosis |
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Flucytosine
adv RX. |
Adverse effects
Abdominal bloating Bone marrow depression Esp. Patients with renal insufficiency or receiving concurrent amphotericin B therapy Hepatotoxicity Black box warning urging caution when used in patients with renal impairment |
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Flucytosine
BBW |
Black box warning urging caution when used in patients with renal impairment
(get severe BM depR) |
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Flucytosine & Amphotericin
advantage of combo |
Synergistic mechanisms of action
Typically allows amphotericin B to be used at lower than normal doses to minimize toxicities Reduces emergence of resistant fungi |
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Azoles
named |
Miconazole (Monistat, Lotrimin, Micatin, others)
Ketoconazole (Nizoral) Itraconazole (Sporanox) Fluconazole (Diflucan) Econazole (Spectazole Cream |
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Azoles
moA |
Mechanism of Action
Inhibits cytochrome P450 enzymes thereby inhibiting fungal ergosterol synthesis (fungistatic) and increasing fungal permeability FDA pregnancy category C Broad spectrum of anti-fungal activity Resistance is emerging problem |
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Azoles
p-kinetic considerations |
Orally absorbed
Require acid environment (except fluconazole) |
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Itraconazole
Miconazole indications (not test) |
Itraconazole (Sporanox)
Long-term suppressive treatment of histoplasmosis in AIDs Oral treatment of non-life threatening blastomycosis Miconazole (Monistat) Cutaneous dermatophyte infections Mucous membrane Candida infections Local irritation may occur with topical application |
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Azoles
adv RXs |
Contraindicated in breast-feeding, pregnancy (FDA Category C) or in patients with hepatic or renal disease
-Gastrointestinal distress Reduce by taking with food Local irritation Emetic effects **********Hepatic and adrenal changes( inh steroid synth get inc infecttions) *******Endocrine, especially ketoconazole Gynecomastia, decreased libido, oligospermia (cyp450 scene--esp with oral**/LTerm Tx) |
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Azoles
DIs |
Avoid with drugs that decrease gastric acid secretion – slows absorption
Exception is fluconazole -Monitor levels and response of any drug that uses the mixed function oxidase system (esp sens drugs WARF, HIV drugs) Azoles and amphotericin B have antagonist mechanisms (azoles decr CW that ampho messes up= less available for ampho) |
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Griseofulvin
moA soA |
(Grifulvin, Gris-PEG)
Systemic anti-fungal for dermatophytic infections Mechanism of Action Inhibits tubular functions, especially mitotic spindle formation and cell wall development Disrupt synthesis and polymerization of nucleic acids Fungistatic Indications Dermatophytic infections |
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Griseofulvin
Pharmacokinetics-considerations |
Pharmacokinetics
Poor solubility limits absorption Absorption improved by Microfine preparations and by taking with a fatty meal**** Concentrated in skin, hair, nails, fat and skeletal muscles Concentrates in keratin precursor cells and binds tightly to new keratin Elimination Excreted in the urine, feces and perspiration (can wrap to conc. sweat) |
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Griseofulvin
adv. Rx |
Transient headache
********Cognitive disruptions Rashes Gastrointestinal distress *******Hepatotoxicity Esp. In patients with acute intermittent porphyria(HEME PROB) Contraindicated in pregnancy(MAKES HEPATOTOXICITY WORSE IN MOM*), patients with penicillin hypersensitivity, and patients with history of lupus or porphyria |
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Griseofulvin
DIs |
Drug-interactions
Coumarin, oral contraceptives, ethanol FDA Pregnancy category C(moms liver too) |
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Terbinafine
Naftifine moA |
Systemic or topically administered anti-fungal for dermatophytic infections
Mechanism of Action Inhibits squalene monooxygenase, a key enzyme in sterol synthesis in fungi, depleting ergosterol****** Cell membrane becomes structurally weakened Fungicidal |
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Terbinafine
Naftifine p-kinet blah |
Naftifine is topical only
Terbinafine is administered orally and topically Oral absorption is complete but first pass effect reduces blood levels by up to 60% (pre- vs. post-liver levels) 99% protein bound with wide distribution Biotransformation elimination half-life is about 36 hours, but can be found bound to nails and hair for up to 90 days after treatment*******thus good for hard to Tx nail bed inf |
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Terbinafine
ADV RXs CIs |
naftifine never oral
but terb- Oral adverse effects include Gastrointestinal upset Headache and dizziness Rash, urticaria and pruritus Impaired sense of taste(lose weight) Blood, renal and hepatic changes are rare but significant Irritation and urticaria with topical preparations Contraindicated Alcoholism Breastfeeding (?) Hepatic disorders |
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Anti fungals that mess with ergosterol
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Ampho B-pore form
Nystatin-pore also? azoles- -cyp = -ergo synthesis Terbinafine & Naftifine -Inhibits squalene monooxygenase (key ergost enz) |
