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CMBM Exam 4 Gopi > Antifungals > Flashcards

Antifungals Flashcards

0
Q

subcutaneous fungi

A

affects muscle and conn tissue
sporothrix schenckii
Basidiobolus ranierum

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1
Q

Superficial fungi

A

dermatophytes

malassezia furfur

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2
Q

Primary systemic fungi

A 
internal organs - usually start with lungs 
Histoplasma capsulatum 
Blastomyces dermatitidis 
Coccidioides immits 
Paracoccidiodes brasiliensis
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3
Q

Primary opportunistic fungi

A 
internal organs 
candida albicans 
cryptococcus neoformans 
aspergillus fumigatus 
mucor/rhizopus 
pneumocystis jirovecii
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4
Q

Cell wall synthesis inhibitors

A

Echinocandins

inhibit Glucan synthesis

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5
Q

Cell membrane synthesis inhibitors

A

Polyene, Azoles

Ergosterol synthesis

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6
Q

DNA/RNA synthesis inhibitor

A

Flucytosinnnne

Pyrimidine analogues

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7
Q

An optimal antifungal will have

A 
Wide spectrum of activity 
favorable bioavailability 
adequate in vivo efficacy 
high therapeutic index 
low cost
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8
Q

Polyenes

A

bind ergosterol in fungal cell membrane, form pore and leads to leaky membrane
have large lactone ring with conjugated double bonds and two sides - lipophilic and hydrophilic side
unstable when taken orally

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9
Q

examples of polyenes

A

Amphotericin B

Nystatin

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10
Q

In vitro, for polyenes, antifungal activity correlates with

A

number of double bonds
at high concentration, polyenes are fungasidal
unstable orally taken

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11
Q

Resistance mechanism against Polyenes

A

If fungi lowers ergosterol in cell membrane, then polyenes can’t bind

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12
Q

Amphotericin B

A

produced by Streptomyces nodosus
‘Ampho terrible’
leakage of Na, K and Ca
not sure how differentiates between human and fungi cell
Broad spectrum - fungicidal
for severe to life threatening fungal infections
IV administration only

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13
Q

Toxicity of Amphotericin B

A

Nephrotoxic
constricts efferent arterioles
wastes Mg and bicarb
disrupts Erythropoietin and leads to anemia

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14
Q

Pharmacokinetics of Amphotericin B

A

Poorly absorbed from GI
given by IV injection with deoxycholate - bile lipid
90% bound to serum proteins
Hepatic metabolism and renal excretion - slow about 15 days

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15
Q

Acute adverse effects of Amphotericin B

A

chill, fever and vomiting
binds host cell (cholesterol) with a lesser affinity leads to toxicity
Pain at site of injection

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16
Q

chronic adverse effects of Amphotericin B

A

nephrotoxicity

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17
Q

Nystatin

A

made by streptomyces noursei
Polyene
topical for local infection
poor bioavailability

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18
Q

No’s for Nystatin?

A

No IV infusion
No drug interactions
No significant side effects

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19
Q

what would you give Nystatin for?

A

Oral thrush

Swish and swallow

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20
Q

Azoles

A 
class of drugs composed of 5 membered azole ring containing at least one non carbon atom 
classified according to number of nitrogens 
Largest group
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21
Q

Azoles activity

A

associated with broad spectrum (superifical to systemic)

can give orally, IV, IM and topically

22
Q

Mechanism of Azoles

A

inhibits ergosterl synthesis by inhibiting Lanosterol conversion to ergosterol

23
Q

What can Azoles potentiate?

A

Cyclosporin
Phynetoin
Warfarin
Isoniazide

24
Q

What are some side effects of Azoles?

A

impair drug detox (hepatic), could potentiate Diazepam

Impair steroid hormone synthesis in adrenal gland, could lead to gynocomastia in males

25
Q

Resistance to Azoles?

A

pump

26
Q

Imidazole

A

two nitrogens
Ketoconazole
Miconazole

27
Q

Triazole

A

Itraconazole
Fluconazole
these are new and less toxic

28
Q

What is contraindicated to take with azoles?

A

Antiacids

29
Q

Fluconazole issue

A

resistance is emerging

30
Q

Voriconazole

A

newer drug

been shown to be fungicidal against Candida

31
Q

Ketoconazole

A

broad spectrum
PO administration
replaced by Fluconazole
S/e Gynecomastia, hepatic failure

32
Q

Miconazole

A

topical and vaginal suppositories

Dermatophytes

33
Q

Clotrimazole

A

topical and vaginal suppositories

34
Q

Fluconazole

A

oral, esophageal and vaginal candidias
Used for Cryptococcal meningitis
oral and IV
better tolerated by KCZ
Post initial treatment with Amp B and Flucytosine
Excellent bioavailability out of all the other azoles

35
Q

Itraconazole

A

broad spectrum including - tinea unguium
indicated for systemic fungal infections
also for oral and esophageal candidiasis

36
Q

Voriconazole

A

oral and IV
high bioavailability
indicated for invasive Aspergillosis

37
Q

Adverse effects of Voriconaole

A

Visual changes
Hepatotoxicity
Rash, Pruritus - hypersensitivity reaction
Hallucinations

38
Q

Allylamines mechanism

A

inhibits squalene epoxidase which downstream decreases the synthesis of Erogsterol

39
Q

Allylamines

A

used for superficial fungal infections and some systemic
available for oral and topical
very little side effects - N&V, upset stomach, loss of taste

40
Q

Flucytosine

A

deaminated to 5-fluorocytosine which blocks DNA and RNA synthesis
blocks Thymidine
Oral administration - 75% CSF penetration

41
Q

What is Flucytosine given for?

A

candida species and Cryptococcus neoformans
Not effective against Aspergillus
usually in conjunction with Amp-B for Crytococcal meningitis

42
Q

Adverse effects of Flucytosine

A

dose dependent bone marrow suppression
decreased WBCs and platelets
leukopenia
Thrombocytopenia

43
Q

What is Flucytosine not effective against?

A

Aspergillus

44
Q

Mechanism of Flucytosine?

A

cyotsine specific permease
Converted to 5FdUMP which disrupts DNA
Converted to 5FUMP which disrupts RNA

45
Q

Echinocandins (Caspofungin)

A

Semisynthetic lipid - bearing polypeptide
Large molecular weight
low oral bioavailability so IV administered

46
Q

Mechanism of Caspofungin

A

Inhibits 1,3 b-glucan synthase

cell wall synthesis inhibitor

47
Q

Prescribe Caspofungin for

A

Invasive Amp-B resistant Aspergillosis
Esophageal Candidasis
Pneumocystitis pneumonia
use when Amp B is not working

48
Q

Griseofulvin mechanism

A

binds fungal tubulin which interferes with microtubule function
-disrupts cell division and inhibits mitosis

49
Q

What is Griseofulvin prescribed for?

A

Taenia infections

Highly effective against Athlete’s foot

50
Q

Side effects of Griseofulvin?

A

Teratogenic
Increased CYP450 metabolism
distributes in skin

51
Q

29 yo pt with white marks on tongue and buccal mucosa which leave red mark upon scraping. Over past 4 months, experienced repeated hospital admissions with respiratory symptoms and marked weight loss. Dx? and management?

A

Pt should get an HIV test
should give an oral azole or fluo
Most likely oral candiasis
give the swish and spit drug - Nystatin

52
Q

34 yo pt lower abdominal pain, discomfort and painful urination. Mild vaginal bleeding. Ultrasound shows tubal-ectopic pregnancy. After surgery, developed high fever. Sputum and urine culture were positive for Candida albicans. Tx?

A

Clotrimazole - best for yeast infections

Amp B too strong for this purpose

CMBM Exam 4 Gopi (10 decks)

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