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MD3001 - Respiratory Pharmacology and Treatment > Anti-Fungal Drugs > Flashcards

Anti-Fungal Drugs Flashcards

1
Q

What is the range of fungal diseases?

A

commong and superficial health problem to being a rare life threatening systemic disease

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2
Q

What are the 2 main classes of fungi that can infext gumans?

A
  • Yeasts
  • Filamentous fungi
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3
Q

What are the 4 main yeast species?

A
  • Candida spp.
  • Cryptococcus neoformans
  • Pityriasis versicolor
  • Systemic yeasts (histoplasma)
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4
Q

What is the disease entity of candida spp.

A

Thrush

fungaemia (in immunocompromised patients)

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5
Q

What is the disease entity of cryptococcus neoformans?

A

Meningitis

Pneumonia

Fungaemia

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6
Q

What is the disease entity of pityriasis versicolor

A

chronic skin infection

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7
Q

What is the disease entity of systemic yeasts?

A

pulmonary or disseminated infections

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8
Q

how do yeast replicate?

A

by budding

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9
Q

Outline the predisposition and treatment of candida spp.

A
  • predisposition
    • serum
    • antibiotics
    • HIV
  • Treatment
    • imidazoles
    • amphotericin
    • echinocandins
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10
Q

Outline the predisposition, diagnosis and treatment of cryptococcus neoformane

A
  • predisposition
    • HIV
    • Steroids
    • Bird contact
  • Diagnosis
    • Culture
    • Antigen detection
  • Treatment
    • amphotericin
    • imidazole maintainence
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11
Q

Outline the organisms that cause systemic mycoases

A
  • histoplasma capsulatum
  • coccidiodes immitis
  • paracoccidiodes brasillensis
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12
Q

What are the main species of filamentous fungi?

A
  • Aspergillus spp.
    • Mucor
    • Rhizopius
    • Absidia
  • Dermatophytes
    • Epifermophyton
    • Microsporum
    • Trichiohyton
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13
Q

What is the disease entity of Aspergillus spp.

A
  • pulmonary or ocular infection
  • “farmer’s lung”
  • allergic bronchopulmonary aspergillosis
  • aspergilloma
  • invasive aspergillois
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14
Q

What is the disease entity of dermatophytes?

A

chronic infection of skin and nails, kerion

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15
Q

What is farmer’s lung?

A
  • occupational health hazard
  • spores inahled causing a funny immunological reaction
  • acute and chronic shortness of breath
  • exagerated immune response
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16
Q

What is bronchopulmonary aspergillosis?

A
  • fungus = somewhere it is not supposed to be
  • Inflammatory
  • Aspergillomus = common in people with another lung disease
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17
Q

What are the 4 main tri-azole drugs?

A
  • fluconazole
  • Itraconazole
  • Posaconazole
  • Voriconazole
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18
Q

Describe the properties of fluconazole

A
  • well absorbed orally
  • achieves good penetration into the CSF to treat fungal menigitis
  • can be used to treat candiduria
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19
Q

Describe the properties of itraconazole

A
  • active against dermatophytes
  • require acid environment of the stomach for optimal absoprtion
  • associated with liver damage
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20
Q

Describe the properties of posaconazole

A

licensed for the treatment of invasive fungal infections unresponsive to conventional treatment

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21
Q

Describe the properties of voriconazole

A
  • borad-spectrum
  • licensed fir use in life-threatening infections
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22
Q

What are the main cautions and conta-indications of fluconazole?

A
  • 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
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23
Q

What are the common side effects of fluconazole?

A
  • nausea
  • abdominal discomfort
  • diarrhoea
  • flatulence
  • headache
  • rash
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24
Q

What is the mechanism of tri-azole drugs?

A

stop the conversion of lazosterol into ergosterol which is a key component of fungal cell walls

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25
Q

What drugs are included in the polyenes?

A

amphotericin and nystatin

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26
Q

How are the polyenes administered?

A

Topical or IV

not absorbed well when given by mouth

27
Q

How is nystatin used and what for?

A

oral, oropharyngeal and perioral infections

local application to the affected area

28
Q

How is amphotericin used and what for?

A

used by IV infusion

treatment of systemic fungal infections and is active against most fungi and yeasts

29
Q

What is amphotericin highly bound to and poor at pentrating?

A

Highly protein bound and penetrates poorly into body fluids and tissues

30
Q

What form of amphotericin is less toxic?

A

lipid formualtions

31
Q

What is the mechanism of action of amphotericin?

A

embeds itself into the cell membrane cuaisng leakage of electrolytes and the cell to die

32
Q

What are the indications of flucytosine?

A

systemic yeast and fungal infections;

adjunct to amphotericin to cryptococcal or severe systemic candidias

33
Q

What are the cautions and contraindications when prescribing flucytosine?

A
  • Cautions
    • elderly
    • blood disorders
  • Contraindications
    • renal impairment
    • pregnancy
    • breast feeding
34
Q

What are the main side effects of flucytosine?

A
  • nausea
  • vomitting
  • diarrhoea
  • rashes
  • Blood disorders (bone marroe suppressor)
    • thrombocytopenia
    • leucopenia
    • aplastic anaemia
35
Q

What is 5-FC?

A

Flucytosine

36
Q

What is the mechanism of action of flucytosine?

A
  • 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
37
Q

What are the main echinocandins

A

anidulafungin, caspofungin and micafungin

38
Q

What is the mechanism of action of the echinocandins?

A

Act by inhibiting beta-(1-3)-D-glucan synthase

39
Q

What is the action of the echinocandins?

A
  • fungicidal (kills completely) Candidia spp.
  • fungistatic against apergillus spp.
40
Q

What is the beta-(1,3)-D-glucan chain?

A

A polysaccharide chain that forms across the top of the cell memrbane and protects it from osmotic stress - strengthening component of cell membrane

41
Q

How are the echinocandins administered?

A

IV

42
Q

What are the indications for Terbinafine?

A

Dermatophyte infection of the nails, ringworm infections (including tinea pedis, cruris, and corporis) where oral therapy appropriate (due to site, severity or extent)

43
Q

What are the cautions and contraindications of Terbinafine?

A
  • Cautions:
    • psoriasis
    • autoimmune disease (risk of SLE like effect)
  • Contraindications
    • hepatic impairment
    • renal impairment
    • pregnanacy
    • breast feeding
44
Q

What is the mechanism of action of terinafine?

A

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

45
Q

What are the indications for griesofulvin?

A

dermatophyte infections of the skin, scalp, hair and nails where topical therapy has failed or is inappropriate

46
Q

What are the cautions and contradications of griesogluvin?

A
  • Cautions
    • driving
    • hepatic impairment
    • pregnancy
    • breast feeding
  • contraindications
    • severe liver disease
    • systemic lupus-reythematosus
    • acute porphyria (linked to Hb)
47
Q

What is the mechanism of action of Griesofluvin?

A

causes disruption of miotic soindle, inhibiting mitosis

Induces hepatic CYP450 activity

48
Q

What are the unwanted effects of griesofluvin?

A
  • dysoeosia
  • fatigue
  • allergy
49
Q

Outline the mode of action of each of the antifungal drugs

A
  • 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
50
Q

What type of patients are predominatelt affected by inasvsive candidiasis?

A
  • ICU patients
  • immunocompromised
  • Very low birth weight infants
51
Q

What is the treatment of invasive candidasis?

A
  • 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
52
Q

What are the most superifical candidiasis infections of the skin treated with?

A

treated locally (e.g. miconazole)

53
Q

What is widespread or intractable infection with candidiasis treated with?

A

systemic antifungal treatment

Fluconazole

54
Q

What is vaginal candidiasis treated with?

A
  • locally acting antifungals OR;
  • fluconazole orally
  • Resistant = itraconazole
55
Q

What is oropharyngeal candidiasis usually treated with?

A

nystatin mouthwasges

56
Q

What is the main use of itraconazole?

A

treatment of infections that resisatnt to fluconazole

57
Q

Where does aspergillosis most commonly affect?

A

respiratory tract

inasvive forms = heart, brain and skin

58
Q

Treatment of choice for aspergillosis?

A

voriconazole

OR liposomal amphotericin

59
Q

Describe cryptococcus

A
  • 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
60
Q

How is cryptococcoal menigitis diagnosed?

A

Lumbar puncture or rapid diagnositc anitgen testing

61
Q

Treatment of cryptococcol meningitis?

A

amphotericin and flucytosine

62
Q

Describe histoplasmosis

A
  • 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
63
Q

Treatment of systemuc mycoses - e.g. Histoplasmosis

A
  • 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.
64
Q

Name 2 other systemuic mycoses apart from histoplasmosis?

A
  • Coccidiodes
    • can cause fever and acute respiratory illnes
  • Paracoccodioides
    • respiratory symptoms and facial leisons

MD3001 - Respiratory Pharmacology and Treatment (6 decks)

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