Infections- fungal Flashcards
1
Q
Antifungal drugs
Common indications
A
- Local fungal infections- oropharynx, vagina or skin. They may be applied topically or orally
- Systematic treatment of invasive or disseminated fungal infections
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
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
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
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
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
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
8
Q
Caspofungin
Indications
A
- Invasive candidiasis/aaspergillosis
- Empirical treatment of systemic fungal infections inpatients with neutropenia
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.
10
Q
Caspofungin
Warnings
A
- No main warnings
- NB- Dose adjustment is required when given with CYP inducers (upto 70mg daily)
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
*
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
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.
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
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
*
