antifungals Flashcards Preview

Infectious disease > antifungals > Flashcards

Flashcards in antifungals Deck (23):
1

List all antifungal agents?

-polyenes
-Azoles
*imidazoles
*triazoles
-others
*terbinafine
*caspofungin
*Griseofulvin
*flucytosine

2

What are the main modes of action of antifungals?

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

3

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

4

Discuss the use of the polyenes: amphotericin and nystatin?

amphoteracin:
-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)

Nystatin
-local application (not absorbed)

5

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

6

DIscuss different imidazoles?

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

7

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

8

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

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

Flucytosine
-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

9

Why are fungal infections increasing?

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

10

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

11

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

12

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

13

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.

14

What are the 2 categories for systemic fungal infections?

1)primary pathogens
2)opportunistic pathogens

15

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

16

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

17

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

18

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
-dentures
-inhaled steroids
-AIDS

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

19

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
-Antibiotics
-diabetes mellitus
-pregnancy

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

20

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

21

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

22

Discuss aspergillosis?

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

23

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