Anti-Fungal Drugs Flashcards
What is the range of fungal diseases?
commong and superficial health problem to being a rare life threatening systemic disease
What are the 2 main classes of fungi that can infext gumans?
- Yeasts
- Filamentous fungi
What are the 4 main yeast species?
- Candida spp.
- Cryptococcus neoformans
- Pityriasis versicolor
- Systemic yeasts (histoplasma)
What is the disease entity of candida spp.
Thrush
fungaemia (in immunocompromised patients)
What is the disease entity of cryptococcus neoformans?
Meningitis
Pneumonia
Fungaemia
What is the disease entity of pityriasis versicolor
chronic skin infection
What is the disease entity of systemic yeasts?
pulmonary or disseminated infections
how do yeast replicate?
by budding
Outline the predisposition and treatment of candida spp.
- predisposition
- serum
- antibiotics
- HIV
- Treatment
- imidazoles
- amphotericin
- echinocandins
Outline the predisposition, diagnosis and treatment of cryptococcus neoformane
- predisposition
- HIV
- Steroids
- Bird contact
- Diagnosis
- Culture
- Antigen detection
- Treatment
- amphotericin
- imidazole maintainence
Outline the organisms that cause systemic mycoases
- histoplasma capsulatum
- coccidiodes immitis
- paracoccidiodes brasillensis
What are the main species of filamentous fungi?
- Aspergillus spp.
- Mucor
- Rhizopius
- Absidia
- Dermatophytes
- Epifermophyton
- Microsporum
- Trichiohyton
What is the disease entity of Aspergillus spp.
- pulmonary or ocular infection
- “farmer’s lung”
- allergic bronchopulmonary aspergillosis
- aspergilloma
- invasive aspergillois
What is the disease entity of dermatophytes?
chronic infection of skin and nails, kerion
What is farmer’s lung?
- occupational health hazard
- spores inahled causing a funny immunological reaction
- acute and chronic shortness of breath
- exagerated immune response
What is bronchopulmonary aspergillosis?
- fungus = somewhere it is not supposed to be
- Inflammatory
- Aspergillomus = common in people with another lung disease
What are the 4 main tri-azole drugs?
- fluconazole
- Itraconazole
- Posaconazole
- Voriconazole
Describe the properties of fluconazole
- well absorbed orally
- achieves good penetration into the CSF to treat fungal menigitis
- can be used to treat candiduria
Describe the properties of itraconazole
- active against dermatophytes
- require acid environment of the stomach for optimal absoprtion
- associated with liver damage
Describe the properties of posaconazole
licensed for the treatment of invasive fungal infections unresponsive to conventional treatment
Describe the properties of voriconazole
- borad-spectrum
- licensed fir use in life-threatening infections
What are the main cautions and conta-indications of fluconazole?
- Cautions
- monitor liver function when used with hepatotoxic drugs
- discontinue with signs of heaptic disease
- susceptibility to prolonged OT interval
- Contra-indications
- acute porphuia
- renal impairment
- hepatic impairment
- pregnanacy
- breast feeding
What are the common side effects of fluconazole?
- nausea
- abdominal discomfort
- diarrhoea
- flatulence
- headache
- rash
What is the mechanism of tri-azole drugs?
stop the conversion of lazosterol into ergosterol which is a key component of fungal cell walls
What drugs are included in the polyenes?
amphotericin and nystatin
How are the polyenes administered?
Topical or IV
not absorbed well when given by mouth
How is nystatin used and what for?
oral, oropharyngeal and perioral infections
local application to the affected area
How is amphotericin used and what for?
used by IV infusion
treatment of systemic fungal infections and is active against most fungi and yeasts
What is amphotericin highly bound to and poor at pentrating?
Highly protein bound and penetrates poorly into body fluids and tissues
What form of amphotericin is less toxic?
lipid formualtions
What is the mechanism of action of amphotericin?
embeds itself into the cell membrane cuaisng leakage of electrolytes and the cell to die
What are the indications of flucytosine?
systemic yeast and fungal infections;
adjunct to amphotericin to cryptococcal or severe systemic candidias
What are the cautions and contraindications when prescribing flucytosine?
- Cautions
- elderly
- blood disorders
- Contraindications
- renal impairment
- pregnancy
- breast feeding
What are the main side effects of flucytosine?
- nausea
- vomitting
- diarrhoea
- rashes
- Blood disorders (bone marroe suppressor)
- thrombocytopenia
- leucopenia
- aplastic anaemia
What is 5-FC?
Flucytosine
What is the mechanism of action of flucytosine?
- Synthetic pyrimidine, used in combination with amphotericin B (increases cell permeability)
- 5-FC forms false nucleotide
- Disrupts nucleic acid and protein synthesis
- Actively stops the cell dividing
What are the main echinocandins
anidulafungin, caspofungin and micafungin
What is the mechanism of action of the echinocandins?
Act by inhibiting beta-(1-3)-D-glucan synthase
What is the action of the echinocandins?
- fungicidal (kills completely) Candidia spp.
- fungistatic against apergillus spp.
What is the beta-(1,3)-D-glucan chain?
A polysaccharide chain that forms across the top of the cell memrbane and protects it from osmotic stress - strengthening component of cell membrane
How are the echinocandins administered?
IV
What are the indications for Terbinafine?
Dermatophyte infection of the nails, ringworm infections (including tinea pedis, cruris, and corporis) where oral therapy appropriate (due to site, severity or extent)
What are the cautions and contraindications of Terbinafine?
- Cautions:
- psoriasis
- autoimmune disease (risk of SLE like effect)
- Contraindications
- hepatic impairment
- renal impairment
- pregnanacy
- breast feeding
What is the mechanism of action of terinafine?
interfers with ergosterol biosynthetic pathways and stops the effective formation of the fungal cell membrane - more upstream of triazole drugs
Also results in a build up of toxic products that kill the cell
What are the indications for griesofulvin?
dermatophyte infections of the skin, scalp, hair and nails where topical therapy has failed or is inappropriate
What are the cautions and contradications of griesogluvin?
- Cautions
- driving
- hepatic impairment
- pregnancy
- breast feeding
- contraindications
- severe liver disease
- systemic lupus-reythematosus
- acute porphyria (linked to Hb)
What is the mechanism of action of Griesofluvin?
causes disruption of miotic soindle, inhibiting mitosis
Induces hepatic CYP450 activity
What are the unwanted effects of griesofluvin?
- dysoeosia
- fatigue
- allergy
Outline the mode of action of each of the antifungal drugs
- Triazoles: block P450 and sterol-14-alpha demethylase in the cell wall
- Polyenes inhibit form pore in funga lmembrane
- Flucytosine inhibits protein synthesis
- Echinocandins inhibit 1,3beta glucan in cell wall polysaccharide
- Terbinafine inhibits squalene epoxidase that accumulates toxic sterols in the cell wall
- Griseofulvin inhibits fungal mitosis
What type of patients are predominatelt affected by inasvsive candidiasis?
- ICU patients
- immunocompromised
- Very low birth weight infants
What is the treatment of invasive candidasis?
- An echinocandin can be used
- Fluconazole is an alternative for Candida albicans infection in clinically stable patients who have not received an “azole” “antifungal” recently.
- Amphotericin is an alternative when an echinocandin or fluconazole cannot be used, however, amphotericin should be considered for the initial treatment of CNS candidiasis.
- Voriconazole can be used for infections caused by fluconazole-resistant Candida spp. when oral therapy is required, or in patients intolerant of amphotericin or an echinocandin.
- In refractory cases, flucytosine can be used with intravenous amphotericin
What are the most superifical candidiasis infections of the skin treated with?
treated locally (e.g. miconazole)
What is widespread or intractable infection with candidiasis treated with?
systemic antifungal treatment
Fluconazole
What is vaginal candidiasis treated with?
- locally acting antifungals OR;
- fluconazole orally
- Resistant = itraconazole
What is oropharyngeal candidiasis usually treated with?
nystatin mouthwasges
What is the main use of itraconazole?
treatment of infections that resisatnt to fluconazole
Where does aspergillosis most commonly affect?
respiratory tract
inasvive forms = heart, brain and skin
Treatment of choice for aspergillosis?
voriconazole
OR liposomal amphotericin
Describe cryptococcus
- Encapsulated yeast
- 2 species (C neoformans & C gatti)
- Transmission by aerosol
- Cutaneous, pulmonary and neurological disease
- Advanced HIV infection is main risk factor
- C neoformans is the leading cause of adult meningitis in sub-Saharan Africa
How is cryptococcoal menigitis diagnosed?
Lumbar puncture or rapid diagnositc anitgen testing
Treatment of cryptococcol meningitis?
amphotericin and flucytosine
Describe histoplasmosis
- H capsulatum (worldwide), H duboisii (Africa)
- In soil contaminated with bird/bat droppings
- Transmission by inhalation
- Symptomatic illness 3-17 days post-exposure
- Often self-limiting
- May progress:
- pulmonary
- pericardial
- disseminated disease
- High mortality in HIV-infected persons
Treatment of systemuc mycoses - e.g. Histoplasmosis
- Parenteral Itraconazole may be used for the treatment of immunocompetent patients with indolent non-meningeal infection, including chronic pulmonary histoplasmosis.
- ParenteralAmphotericinispreferredin patients with fulminant or severe infections.
- Following successful treatment, itraconazole can be used for prophylaxis against relapse until immunity recovers.
Name 2 other systemuic mycoses apart from histoplasmosis?
- Coccidiodes
- can cause fever and acute respiratory illnes
- Paracoccodioides
- respiratory symptoms and facial leisons
