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Flashcards in antifungals Deck (23):

List all antifungal agents?



What are the main modes of action of antifungals?

1) cell membrane disruption
2) inhibition of cell wall formation
3) inhibition of cell division


what are polyenes MOA?

-amphotericin, nystatin
-bind to ergosterol in membranes promoting: leakage of intracellular ions and disruption of membrane active transport mechanisms
-resistance is rare and slow to develop


Discuss the use of the polyenes: amphotericin and nystatin?

-active against almost all fungi causing systemic infection
-poorly absorbed by the gut
-IV administration
-lipid formulations (liposomal amphoteracin B: AmBisome)
-adverse effects- nephrotoxicity (monitor renal function)

-local application (not absorbed)


what are azoles MOA?

inhibit ergosterol synthesis
-inhibits key cytochrome P450 step
-Inhibits CYP P450 14-alpha-demethylase which converts lanosterol to ergosterol
-accumulation of sterol precursors, leading to a cell membrane with altered structure and function


DIscuss different imidazoles?

-active against a wide variety of fungi and yeasts
-clotrimazole, ketoconazole, miconazole: topical application for superficial infection
better absorbed by mouth than the other imidazoles
-oral preparation


Discuss different triazoles?

-similar spectrum of activity to the imidazoles
-fluconazole: well absorbed after oral admin. , penetrates well into CSF
-Itraconazole: Associated with liver damage
contraindicated in patients with history of liver disease
drug interactions
-Voriconazole: use in life-threatening infections, drug interactions
-Posaconazole: invasive fungal infections


Discuss other antifungals?

Allylamines - terbinafine
-impairs cell membrane synthesis by decreasing ergosterol synthesis
-fungal nail infections

Eichnocandins- caspofungin
-affects proteins responsible for synthesis of cell wall polysaccharides
-IV treatment of aspergillosis

-interferes with microtubule assembly
-effective for widespread dermatophyte infections
-superseeded by newer antifungals

-incorporated into RNA and inhibits protein and DNA synthesis
-resistance can develop during therapy- sensitivity testing before and after advised
-Adjunctive rather than primary therapy


Why are fungal infections increasing?

-changes in medical practice (indwelling devices, immunosuppressant therapies)
-indiscriminate use of antibacterials
-better diagnosis of fungal disease


How are fungal diseases caused?

-Mycotoxicoses: accidental or deliberate ingestion of fungi that produce mycotoxins

-hypersensitivites- e.g. pneumonitis

-colonisation and disease
1)superficial mycoses
2)cutaneous mycoses
3)subcutaneous mycoses
4)systemic mycoses


Discuss a superficial mycoses infection?

-colonise the outermost layer of the skin and hair shaft
-rarely illicits an immune response
-no physical discomfort to the host, largely cosmetic
-conditions- pityriasis veriscolar, black/white piedra
-treatment with keratolytic agents or antifungals e.g. miconazole or simply improving personal hygiene


Discuss a cutaneous mycoses infection?

-involves keratinised layer of skin- will illicit an immune response- dermatophytosis or tinea
-can affect skin (ringworm), nails, hair
-treatable- impact on patients QOL can be severe
-risk of developing into invasive disease in immunosuppressed patients
-treatment- topical: imidazoles (e.g. clotrimazole, miconazole), terbinafine, tolnaftate
oral: griseofulvin, terbinafine, itraconazole


Discuss a subcutaneous mycoses infection?

-rare e,g, chromoblastomycosis
-usually site of trauma where the organism is planted in tissue
-normally involves fungi found in soil or decaying vegetation
-infections initially involve deeper layers of skin, before eventually presenting as lesions on skin surface
-treatment depends on causative agents potassium iodide given orally, AmpB, in some cases chemo therapy.


What are the 2 categories for systemic fungal infections?

1)primary pathogens
2)opportunistic pathogens


Discuss systemic infections involving primary pathogens?

-histoplasmosis, blastomycosis
-not normally commensal fungi
-cause disease in a healthy individual
-focus of infection normally lungs, unless infection is severe
-infections tend to be short, immunity to second infection
-life threatening if immunocomprimised
- treatments= Amphoteracin B (although toxic) and ketoconazole


Discuss systemic infections involving opportunistic pathogens?

-low inherent virulence
-immune comprimised patients are susceptible and if not treated rapidly and aggressively condition may become life threatening
-incidence increasing due to: HIV/AIDS, invasive medical procedures, immunocompromised patients


Discuss candida infections?

-candida albicans, C. glabrata, C. parapsilosis
-80% people are colonised on healthy mucosal sufaces (oral cavity, vagina, GI tract) in absence of disease
-self-inoculating infection


Discuss oral infections in terms of: clinical presentation, predisposing factors and treatment?

clinical presentation
-sore mouth, especially on eating
-white patches of fungus on oral mucosa and tongue

Predisposing factors
-inhaled steroids

-topical: miconazole, amphoteracin, nystatin
-systemic: fluconazole, itraconazole


Discuss vaginal infections in terms of: clinical presentation, predisposing factors and treatment?

clinical presentation
-vaginal discharge (thick and creamy)
-Itch which may be severe

Predisposing factors
-diabetes mellitus

-topical: Imidazoles (e.g. clotrimazole, miconazole), nystatin
-systemic: fluconazole, itraconazole


Discuss candidiasis?

-life threatening and associated with high mortality
-fungemia, colonisation of IV cannula, pneumonia, meningitis, bone and joint infection, endocarditis
-high risk groups:
1)Neutropaenic patients
2)Organ transplant recipients
3)burns patients
4)High antibiotic use
5)compromised immune system


How is systemic candidiasis treated?

-IV cannulae removal
-Amphotericin: IV infusion, alone or with flucytosine by IV infusion in severe cases
-Fluconazole: alone, AIDS patient
-Voriconazole: fluconazole resistant candida spp.
-caspofungin: invasive candidiasis


Discuss aspergillosis?

-Aspergillus flavus, A. fumigatus
-not part of normal human flora
-severity depends on host immune status
-clinical presentation:
*pulmonary aspergillosis
*CNS aspergillosis
*renal abscesses


Treatment of aspergillosis?

-Amphotericin: IV infusion, drug of choice
-Itraconazole, voriconazole: Alternatives in patients in whom initial treatment has failed
-caspofungin: invasive aspergillosis unresponsive to amphotericin or itraconazole
-patients who cannot tolerate amphotericin or itraconazole