Infections- fungal Flashcards

1
Q

Antifungal drugs

Common indications

A
  1. Local fungal infections- oropharynx, vagina or skin. They may be applied topically or orally
  2. Systematic treatment of invasive or disseminated fungal infections
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2
Q

Antifungal drugs

Nystatin, fluconazole, clotrimazole

MOA

A
  • Fungal cell membranes contain ergosterol
  • Ergosterol is not seen in animal or human cells and is the target for antifungal drugs
  • Polyene antifungals bind to ergosterol in fungal cell membranes, creating a polar pore which allows intracellular ions to leak out of the cell
  • This can kill or slow growth of the fungi
  • Imidazole (e.g. clotrimazole) and triazole antifungals (fluconazole) inhibit ergosterol synthesis, impairing cell membrane synthesis, cell growth and replication
  • Resistance to antifungals is unusual but can occur during long-term treatment in immunosuppressed patients
  • Mechanisms include alteration of membrane synthesis to exclude ergosterol, changes in target enzyme =s or increased drug efflux
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3
Q

Antifungals

Adverse effects

A
  • Topical nystatin and clotrimazole have few adverse effects apart from occasional local irritation
  • Fluconazole= GI, headache, hepatitis and hypersensitivity causing skin rash
  • Rare but potentially life-threatening reactions include: Severe hepatic toxicity, prolonged QT interval predisposing to arrhythmias and severe hypersensitivity- cutaneous reaction + anaphylaxis
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4
Q

Antifungals

Warnings

A
  • Fluconazole is cautioned in liver disease because of hepatic toxicity
  • A dose reduction is required in renal impairment
  • It should be avoided in pregnancy due to the risk of fetal malformation
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5
Q

Antifungal

Interactions

A
  • Fluconazole inhibits CYP enzymes causing an increase in plasma concentrations and risk of adverse effects when prescribed with drugs that are metabolised by CYP
  • These include phenytoin, CBZ, warfarin, diazepam, simvastatin and sulphonylureas
  • It may reduce the antiplatelet effect of clopidogrel (pro-drug=reduced liver metabolism)
  • It also increases the risk of serious arrhythmias if prescribed with drugs that prolong QT interval
  • These include amiodarone, antipsychotics, quinine, quinolone, macrolides and SSRI
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6
Q

Antifungal

Prescription

A
  • Nystatin: oropharyngeal candidiasis (thrush) 1mL QDS for 7 days or until 48hrs after lesions resolved
  • Clotrimazole: is used to treat fungal infections of the skin and genital, ringworm and candida. AP BD or TDS for 1-2 weeks
  • Fluconazole: 150mg stat for vaginal candidiasis
    • For other infections 50mg daily for 1-2 weeks
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7
Q

Antifungal

Communication

A
  • Skin infection- patients should continue treatment for 1-2 weeks after symptoms resolve
  • Warn patients treated with a prolonged course of fluconazole to seek medical treatment if they experience symptoms such as nausea, loss of appetite, lethargy or dark urine which could indicate liver poisoning
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8
Q

Caspofungin

Indications

A
  • Invasive candidiasis/aaspergillosis
  • Empirical treatment of systemic fungal infections inpatients with neutropenia
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9
Q

Caspofungin

MOA

A
  • Caspofungin acetate is a semi-synthetic echinocandin
  • Caspofungin acetate inhibits the synthesis of beta-1,3-D-glucan, an essential component of the cell wall of many filamentous fungi/yeast (B-1,3-D-Glucan is not in human cells)
  • Fungicidal activity with caspofungin has been demonstrated against candida. Results in lysis and death of hyphal apicaltips and branch points where cell growth and division occur.
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10
Q

Caspofungin

Warnings

A
  • No main warnings
  • NB- Dose adjustment is required when given with CYP inducers (upto 70mg daily)
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11
Q

Caspofungin

Adverse effects

A
  • Blood-Hb decreased, WCC decreased, thrombocytopenia, leukopenia
  • Metabolism- Hypokalemia, fluid overload, electrolyte imbalances, hyperglyceamia
  • CNS- Headache, dizziness, tremor
  • Eye disorders- Visual disturbances
  • Vascular- Phlebitis
  • Resp-dyspneoa
  • Hepatic- elevated LFTs, cholestasis, hepatotoxicity
  • rash
    *
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12
Q

Amphotericin B

Indications

A
  • Severe invasive candidiasis
  • Severe systematic fungal infections
  • Severe or deep mycoses
  • Suspected or proven infection in febrile neutropenic patients unresponsive to broad spec antibiotics
  • Aspergillosis
  • Visceral leishmaniasis
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13
Q

Amphotericin B

MOA

A
  • Amphotericin B is a antifungal antibiotic
  • Amphotericin is fungistatic or fungicidal depending on the concentration attained in the body fluids and the susceptibility of the fungus
  • Molecule binds to sterols in the fungal cell membrane, with a resulting change in membrane permeability, allowing leakage of a variety of small molecules
  • Mammalian cells also contian stoles so can damage human cells
  • Lipophillic moiety allows the molecyle to be integrated into the lipid bilayer of the liposome.
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14
Q

Amphotericin

Warnings

A
  • Liposomal and lipid-complex forms- serious harm and fatal overdoses have occured following confusion of different formulation.
    • Liposomal, lipid-complex and convention forms are not interchangeable
  • Avoid rapid infusion (due to risk of arrhythmias)
  • Toxicity is common- requires a test dose and close monitoring for at least 30 minutes after
  • Anaphylaxis-
  • Manufacturer advises prophylactic antipyretics or hydrocortisone to prevent infusion related reactions
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15
Q

Amphotericin B

Adverse effects

A
  • Infusion related reactions- Fever, chills are the most common but also can get pain, dyspnoea, tachycardia, hypotension, arthalgia
  • Renal toxicity, renal tubular acidosis
  • Electrolyte imbalance
  • Abnormal hepatic function
    *
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16
Q

Amphotericin B

Interactions

A
  • Concurrent use of nephrotoxic medications (e.g. aminoglycosides, ciclosporin, tacrolimus)
  • Corticosteroids, ACTH and diureitcs- due to potentiation of hypokalaemia
  • Digoxin- Hypokalemia caused by AmB may cause dig toxicity
17
Q

Amphotericin B

Monitoring requirements

A
  • Hepatic and renal function tests
  • FBC
  • U+E