AntiFungal Drugs Flashcards
1
Q
Systemic dimorphic fungi list
A
- Histoplasma capsulatum
- Blastomyces dermatiditis
- Coccidioides immitis
- Sporothrix schenckii (cutaneous only)
2
Q
Opportunistic fungi list
A
1) candida - esophagitus, vagina, thrush
2) aspergillus - mold - lung infections - fungus balls, burn patients
3) cryptococcus - India ink stain - CNS(fungal meningitis) and repiratory
3
Q
Cutaneous/Subcutaneous fungi list:
A
1) sporothrix schenckii
2) dermatophytes (trichophyton, epidermophyton, microsporum)
- ringworm
- athletes foot
- onychmycosis
4
Q
Sporothrix schenckii - how to get?
A
Poking yourself with rose bush thorns
5
Q
Unique targets on fungi:
A
1) fungal cell membrane - ergosterol and ergosterol synthesis (no cholesterol like us)
2) fungal cell wall - glucans
6
Q
Shared targets with fungi:
A
1) DNA/RNA synthesis
2) cell division
7
Q
Amphotericin B
-MOA?
A
attacks membrane function - BINDS to ergosterol
8
Q
Caspofugin
-MOA?
A
cell wall synthesis attacker
9
Q
5-fluorocytosine
-MOA?
A
nucleic acid synthesis attacker
10
Q
Fluconazole, itraconazole, voriconazole, naftifine, terbinafine
–>MOA for all?
A
ergosterol synthesis attacker (membrane)
11
Q
Polyene drug list:
A
amphotericin B
nystatin
12
Q
Azole drug list:
A
ketoconazole fluconazole itraconazole voriconazole posaconazole
13
Q
Nucleoside analog drug list:
A
flucytosine
14
Q
Echinocandins drug list:
A
caspofugin
micafugin
anidulafugin
15
Q
Allylamine drug list:
A
terbinafine
naftifine
16
Q
Microtubule inhibitor drug list:
A
griseofulvin
17
Q
Drugs for Systemic infections:
-Administration?
A
- polyene = amphotericin B
- Azoles= most
- flucytosine
- echinocandins
-oral or IV
18
Q
Azole used for?
A
oral or IV for systemic infections
topically for cutaneous and mucocutaneous
19
Q
- Drug with broadest spectrum of activity of all antifungals?
- Issue with drug?
A
-amphotericin B
TOxic! replaced by azole and echinocandin compounds
20
Q
Amphotericin B
MOA?
A
- binds to ergosterol in fungal cell membrane = forms Amp B containing pores = alters membrane permeability = leaky membrane
- binds more to ergosterol than cholesterol
- FUNGICIDAL
21
Q
Fungi you can use amphotericin B for?
A
- candida
- cryptococcus
- aspergillus
- histoplasma
- coccidioides
- blastomyces
- sporothrix
- mucormycoses
22
Q
Mechanism of resistance to Amphotericin B?
A
-membrane concentration decreased –> sterol target is modified
23
Q
Pharmacology of Amp B
- solubility?
- distribution?
A
- poor in water–> given IV complexed to bile
- distributed everywhere but poor CNS penetration (need intrathecal)
24
Q
Amp B
- toxicities?
- how to make less toxic?
A
- Nephrotox = Most serious long term - decreases renal perfusion
- other infusion related reactions
-liposomal packaged amp B
25
Systemic use Azoles:
TRIAZOLES:
- fluconazole
- itraconazole
- voriconazole
- posaconazole
26
Azoles used more topically/ not systemic:
IMIDAZOLES:
- ketoconazole
- miconazole (topical)
- clotrimazole (topical)
27
Azoles
| MOA?
-INH ergosterol synthesis
28
Azoles vs Amp B MOA?
- Azole = inh ergosterol synthesis
| - Amp B = binds ergosterol
29
Azoles can treat which fungi?
1) pathogenic yeast
- candida
- cryptococcus
2) systemic mycoses
- histoplasmosis
- blastomycosis
- coccidioidomycoses
3) dermatophytes
- onychomycoses
30
Resistance to azoles - mechanisms:
- efflux pumps
- mutations in target enzyme
- decreased ergosterol content in cell membrane
31
Azoles
| -Adverse reaction:
- relatively non-toxic
- minor GI
- interact with -450s
32
One of the first azoles out on market but a lot of liver inhibition (p450s) compared to newer azoles - which azole?
ketoconazole
33
Which azole has highest therapeutic index (least liver interaction) and is pretty much used all the time for fungi?
fluconazole
34
Fluconizole is agent of choice for treating which bugs?
First line:
- candida
- cryptococcus
- coccidiomycoses
Second line:
- histoplasmosis
- blastomycosis
- sporotrichosis
35
Pharmacology of fluconizole:
- solubility?
- distribution?
- absorpion?
- very water soluble
- distributes everywhere AND CNS TOO
- 90% absorbed from GI
36
Itraconazole
- why use this anti-fungal?
- why is it worse than Fluconizole?
- broader spectrum than fluconizole but poorer pharmacology and therapeutic index
- lipophillic = not water sol
- low pH needed for absorption (PPIs or H2 blockers not good = antiacid)
- no CNS penetration
37
Rifampin (anti-TB drug) interacts with which anti-fungal and lowers concentration to below therapeutic levels?
itraconazole
38
Itraconazole used for which fungal infections?
- blastomycosis
- coccidiomycoses
- histoplasmosis
- sporotrichosis
- dermatophyte (onychomycosis)
39
*Old and new tx of choice for aspergillus? Why?
- was fluconazole
| - now is voriconazole --> **much lower toxicity**
40
Voriconazole
- liver complications?
- adverse effects?
- like other azoles it reacts with p450s = drug interactions are a concern
- visual disturbances
- blurred vision
- photophobia
- hallucinations
- liver enzyme abormalities*
- rash*
41
**Which azole can be used to treat cryptococcus, candida, **mucormycoses** and *aspergillus*?
posaconazole
42
Newest antifungal on market with good results- low tox, broad spectrum, distribution good...:
posaconazole
43
Flucytosine can be used to treat in combo therapy?
cryptococcus* (meningitis)*
| some candida
44
Flucytosine
- MOA?
- pharm stuff:
- Active form 5-FU and derivatives are incorporated into RNA or DNA disrupting protein/DNA synthesis
- oral
- water sol
- rapid and well distributed+CNS!
45
Key drug for tx of cryptococcal infections?
-flucytosine
46
How is resistance to flucytosine developed?
altered metabolismof flucytosine
47
Flucytosine adverse reactions:
-bone marrow suppression = anemia, leukopenia, thrombocytopenia
48
Echinocandins
- molecular level-type of drug?
- MOA?
- 3 main drugs in this category?
- lipopeptide
- Inh synthesis of Beta-glucan (fungal cell wall)
- caspofungin
- micafungin
- anidulafungin
49
Drug name ends in fungin - what class of drug?
echinocandins - beta-glucan synthesis inh = no cell wall
50
Echinocandins good for what kind of fungi?
only those that have a lot of beta glucan in cell wall = membrane instability with drug
51
- Primary use for echinocandins?
| - why not used often?
- invasive infections -candida and aspergillus
| - so effin expensive $$$
52
Echinocandins
- route?
- distribution? CNS?
- IV
| - wide distribution but not CNS
53
echinocandins
| -Adverse stuff?
-we dont have cell walls so not many side effects but YES drug interactions
54
Griseofulvin
- MOA?
- where does it concentrate?
- dosing?
- Microtubule inhibitor drug (mitosis inh)
- concentrates in keratin precursor cells = bound to keratin
- daily for weeks=skin and hair inf
- daily for months for nail inf
55
Which drug is a microcrystaline drug = susspension of drug that patient takes with fatty meal?
griseofulvin
56
scalp or hair fungal infection give which drug?
griseofulvin
57
Which drug interacts with warfarin and also dec effectivenes of oral contraceptives
-griseofulvin
58
Allylamines
| -MOA?
- inhibitors of ergosterol synthesis (like azoles)
| - inh squalene epoxidase enzyme = damaged cell membrane
59
First line drug for onychomycosis?
| -MOA?
- terbinafine - concentrates in keratin cells
| - -ergosterol synthesis -inh squalene epoxidase enzyme = damaged cell membrane
60
Topical antifungals
- polyenes?
- MOA?
nysatin
- binds to ergosterol in membrane (like AmpB) and forms pores
- ONLY TOPICAL - toxic otherwise
61
Topical antifungals
- azoles?
- used for?
clotrimazole
miconazole
-give for tinea corporis, pedis and cruri
-also good for candida
62
Topical antifungals
| -allylamines?
- terbinafine
| - naftifine
63
- some pateint has oral candidasis
- some patient has vaginal candidiasis?
WHAT drug to give?
nystatin!!!
64
Which drug to give for tinea corporis, pedis and cruris?
clotrimazole or miconazole (azoles)
-can do terbinafine and naftifine for cruris (jock itch) and corposris (ringworm)
65
patient has oral THRUSH - which drug?***
lozenges - azoles - clotrimazole or miconazole
66
Aspergillosis
| -drug of choice?
voriconazole
67
Mild to moderate blastomycosis
| -drug of choice?
itraconazole
68
moderate to severe blastomycoses
| -drug of choice?
-amphotericin B followed by itraconazole
69
Vaginal candidiasis
| -drug of choice?
- intravag azole (clotrimazole or miconazole)
- intravag nystatin
- oral floconazole
70
Oral candidiasis
| -drug of choice?
- clotrimazole or miconazole lozenge
- nystatin oral suspension
- fluconazole
71
esophageal candidiasis
| -drug of choice?
-fluconazole
72
invasive blood stream candidiasis?
- fluconazole
| - echinocandin
73
Coccidioidomycoses
| -drug of choice?
- fluconazole
| - itraconazole
74
cyroptococcosis - normal pt?
-drug of choice?
cryptoccoccosis - HIV patients
-drug of choice?
- amphotericin B +flucytosine followed by fluconazole
| - fluconazole
75
Histoplasmosis - normal pt
-drug of choice?
Histoplasmosis - HIV+
-drug of choice?
- amphotericin B and then itraconazole
| - itraconazole
76
Mucomycosis
| -drug of choice?
-amphotericin B
77
Sporotrichosis - cutaneous
--drug of choice?
Sporotrichosis - extracutaneous
-drug of choice?
- itraconazole
| - amphotericin then itraconazole
78
Dermatomycosis
| -drug of choice?
- topical azole (clotrimazole or miconazole)
| - topical terbinafine
79
Onchymycosis
| -drug of choice?
- terbinafine (oral)
| - itraconizole (oraL)
