CH6 | Antifungals Flashcards
(156 cards)
1
Q
What are infectious diseases caused by fungi called?
A
Mycoses.
2
Q
What are the main types of mycotic infections?
A
- Cutaneous.
- Subcutaneous.
- Systemic.
3
Q
What type of cells do fungi have?
A
Eukaryotic cells with a rigid cell wall made of chitin.
4
Q
What is the main component of the cell membrane in fungi?
A
Ergosterol.
5
Q
What is the target of antifungal drugs?
A
Ergosterol.
6
Q
Why are antifungal drugs selective?
A
Because antibiotics are ineffective against fungi.
7
Q
What factors have contributed to the increased incidence of mycoses?
A
Cancer chemotherapy, HIV, and organ transplantation leading to immune suppression.
8
Q
What type of drug is Amphotericin B?
A
An amphoteric polyene macrolide.
9
Q
What is the source of Amphotericin B?
A
It is naturally occurring and produced by Streptomyces nodosus.
10
Q
What is the drug of choice for several life-threatening mycoses?
A
Amphotericin B.
11
Q
How is Amphotericin B administered for systemic infections?
A
It is water insoluble, so it is administered as a colloidal suspension of amphotericin B and sodium deoxycholate or liposomes via slow IV infusion.
12
Q
What is the formulation of Amphotericin B for local GI tract treatment?
A
Oral amphotericin B.
13
Q
What is the mechanism of action (MOA) of Amphotericin B?
A
It is fungicidal and binds to ergosterol, forming pores that disrupt membrane function, leading to leakage and cell death.
14
Q
What is the antifungal spectrum of Amphotericin B?
A
It has a wide antifungal spectrum including Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and many strains of Aspergillus.
15
Q
What is the resistance mechanism associated with Amphotericin B?
A
Changes in ergosterol content and structure.
16
Q
How is Amphotericin B administered?
A
As a colloidal suspension of amphotericin B and sodium deoxycholate or liposomes, parenterally via slow IV infusion.
17
Q
What is the solubility characteristic of Amphotericin B?
A
It is water insoluble.
18
Q
How extensively is Amphotericin B bound in the body?
A
It is extensively bound to plasma proteins.
19
Q
What is the distribution characteristic of Amphotericin B?
A
It has high distribution, but little of the drug is found in CSF, vitreous humor, peritoneal fluid, and synovial fluid.
20
Q
How is Amphotericin B excreted from the body?
A
It is excreted in the urine over a long period of time.
21
Q
What are the adverse effects of Amphotericin B?
A
Fever, chills, kidney failure, hypotension, anemia, thrombophlebitis.
22
Q
What are the infusion-related toxicities associated with Amphotericin B?
A
Fever, chills, muscle spasm, headache, hypotension, vomiting.
23
Q
How can infusion-related toxicities of Amphotericin B be managed?
A
By decreasing the infusion rate or daily dose, and premedication with corticosteroids and antipyretics.
24
Q
What is the most significant cumulative toxicity of Amphotericin B?
A
Renal damage.
25
What are the effects of cumulative toxicity on the kidneys when using Amphotericin B?
Decreased glomerular filtration rate and decreased renal tubular function.
26
What happens to creatinine clearance with Amphotericin B use?
It decreases.
27
What electrolytes are wasted due to Amphotericin B?
Potassium (K) and Magnesium (Mg).
28
What type of acidosis can occur with Amphotericin B?
Renal tubular acidosis.
29
Is the renal damage caused by Amphotericin B reversible?
Yes, but there can be residual damage at high doses (>4g cumulative dose; prolonged).
30
What is azotemia and how is it related to Amphotericin B?
Azotemia is a condition that may occur with Amphotericin B use, potentially requiring dialysis.
31
What can help decrease the severity of azotemia caused by Amphotericin B?
Hydration.
32
How can the risk of nephrotoxicity be minimized when using Amphotericin B?
By infusing normal saline prior to administration.
33
What type of antifungal drug is Flucytosine?
It is an antimetabolite antifungal.
34
What is the chemical classification of Flucytosine?
Synthetic pyrimidine.
35
With which antifungal agent is Flucytosine commonly combined for a synergistic effect and being overall safer?
Amphotericin B.
36
What is the mechanism of action (MOA) of Flucytosine?
Fungistatic with selective toxicity; disrupts nucleic acid and protein synthesis.
37
Why does Flucytosine have selective toxicity?
It has no effect on human cells due to the lack of necessary enzymes.
38
What is the antifungal spectrum of Flucytosine?
Restricted (narrow).
39
With which drugs is Flucytosine commonly combined for treatment?
Amphotericin B and itraconazole.
40
What conditions is Flucytosine used to treat when combined with Amphotericin B?
Systemic mycoses and meningitis caused by C. neoformans and C. albicans.
41
What is the reason Flucytosine is not used alone?
High susceptibility to resistance.
42
What is a key mechanism of resistance to Flucytosine?
Altered metabolism of 5-FC.
43
What type of infections are treated with Flucytosine?
Subcutaneous and systemic mycotic infections.
44
What type of drug is Itraconazole?
A triazole antifungal.
45
What condition is treated with Itraconazole in combination with Flucytosine?
Chromoblastomycosis.
46
How is Flucytosine absorbed?
It is well-absorbed orally.
47
Where does Flucytosine distribute in the body?
Throughout body water and penetrates into the cerebrospinal fluid (CSF).
48
What is detectable in patients due to the metabolism of Flucytosine by intestinal bacteria?
5-fluorouracil (5-FU).
49
How is Flucytosine excreted from the body?
In the urine via glomerular filtration (parent drug + metabolites).
50
What are some adverse effects of Flucytosine?
Bone marrow toxicity, nausea, vomiting, diarrhea, severe enterocolitis, and reversible hepatic dysfunction.
51
What blood disorders can result from Flucytosine's adverse effects?
Anemia, leukopenia, and thrombocytopenia.
52
What liver-related issue can arise from Flucytosine treatment?
Elevation of serum transaminases indicating reversible hepatic dysfunction.
53
What are the two main classes of azole antifungals?
Imidazoles and triazoles.
54
What is the mechanism of action (MOA) of azole antifungals?
They have similar MOA and spectra of activity.
55
How do imidazoles differ from triazoles?
They differ in pharmacokinetic (PK) properties and therapeutic use.
56
What is the primary application of imidazoles?
Applied topically for cutaneous infections.
57
What is the primary use of triazoles?
Administered systemically for the treatment or prophylaxis of cutaneous and systemic mycoses.
58
Name some examples of triazole antifungals.
Fluconazole, itraconazole, posaconazole, voriconazole, isavuconazole.
59
What is the mechanism of action (MOA) of azole antifungals?
They are fungistatic and reduce ergosterol synthesis.
60
How do azole antifungals disrupt fungal cell growth?
By inhibiting 14 α-demethylase, blocking the demethylation of lanosterol to ergosterol, disrupting fungal membrane function and structure.
61
What is one mechanism of resistance to azole antifungals?
Mutations in the 14 α-demethylase gene and efflux pumps.
62
Which hepatic isoenzyme do all azoles inhibit?
CYP450 3A4.
63
What can occur when concomitant medications are substrates for CYP450 3A4?
High concentrations and toxicity due to drug-drug interactions.
64
Which azoles are metabolized by CYP450 3A4?
Itraconazole and voriconazole.
65
What type of interactions occur with CYP450 inhibitors and inducers?
Drug-drug interactions with azoles like itraconazole and voriconazole.
66
Why do imidazoles have a higher incidence of drug interactions and adverse effects compared to triazoles?
Imidazoles exhibit a lesser degree of selectivity.
67
What is a major contraindication for azole antifungals?
They are teratogenic and should be avoided in pregnancy unless the benefit outweighs the risk to the fetus.
68
What is the first triazole antifungal?
Fluconazole.
69
How does fluconazole compare to other triazoles in terms of activity?
Fluconazole is the least active of all triazoles.
70
What is the spectrum of fluconazole?
Yeast and some dimorphic fungi.
71
What conditions does fluconazole have no role in treating?
Aspergillosis or zygomycosis.
72
Which organisms is fluconazole active against?
Cryptococcus neoformans, Candida albicans, and Candida parapsilosis.
73
What is Fluconazole used for prophylactically?
Against invasive fungal infections in recipients of bone marrow transplants.
74
What is the drug of choice for Cryptococcus neoformans after induction therapy with amphotericin B and flucytosine?
Fluconazole.
75
For which infections is Fluconazole used?
Candidemia and coccidiomycosis.
76
Is Fluconazole active against mucocutaneous candidiasis?
Yes, it is active against vulvovaginal candidiasis.
77
What are the routes of administration for Fluconazole?
Oral and intravenous (IV).
78
How is Fluconazole excreted from the body?
It is excreted in the urine.
79
What are some common adverse effects of Fluconazole?
Nausea, vomiting, headache, and skin rashes.
80
What is the broader spectrum antifungal compared to fluconazole?
Itraconazole.
81
What is the drug of choice for treating blastomycosis?
Itraconazole.
82
What conditions is itraconazole used to treat?
Blastomycosis, sporotrichosis, paracoccidioidomycosis, and histoplasmosis.
83
How should itraconazole capsules and tablets be taken?
With food and an acidic beverage.
84
How should itraconazole solution be taken?
On an empty stomach.
85
What is the distribution characteristic of itraconazole in the body?
It has high distribution in the body.
86
Where is itraconazole metabolized?
In the liver.
87
What happens to itraconazole after metabolism?
It is excreted as drug and inactive metabolites in urine and feces.
88
What are some adverse effects of itraconazole?
Nausea, vomiting, rash, hypokalemia, hypertension, edema, headache.
89
Why should itraconazole be avoided in patients with heart failure?
Because it has a negative inotropic effect.
90
What is Voriconazole used for?
It is the drug of choice for invasive aspergillosis and is used for invasive candidiasis and infections caused by Scedosporium and Fusarium species.
91
What forms is Voriconazole available in?
Oral and intravenous (IV).
92
What type of drug interactions does Voriconazole have?
It metabolizes and inhibits various CYP450 isoenzymes.
93
What is a significant side effect of high doses of Voriconazole?
Visual and auditory hallucinations, and hepatotoxicity.
94
What is the spectrum of activity of Voriconazole?
It has a broad spectrum of activity.
95
What are Echinocandins?
The newest class of antifungal agents.
96
What is the mechanism of action of Echinocandins?
Inhibiting the synthesis of β(1,3)-D-glucan, leading to cell lysis and death.
97
What is the formulation for Echinocandins?
They are administered intravenously (IV).
98
Which Echinocandins require a loading dose?
Caspofungin and anidulafungin.
99
What type of activity do Echinocandins have against Aspergillus and Candida species?
Potent activity, including against those resistant to azoles.
100
What are the structural components of Echinocandins?
Large cyclic peptides linked to a long-chain fatty acid, so they're given IV.
101
What is the effect of Echinocandins on the fungal cell wall?
They act on the cell wall, leading to cell death.
102
What are the three main Echinocandins used for antifungal treatment?
Caspofungin, micafungin, and anidulafungin.
103
What are the common adverse effects of Echinocandins?
Fever, rash, nausea, and phlebitis at the infusion site.
104
How should Echinocandins be administered to prevent adverse reactions?
Via a slow IV infusion to prevent histamine-like reactions (flushing).
105
What is the first-line treatment option for patients with invasive candidiasis?
Caspofungin.
106
What is the second-line treatment option for invasive aspergillosis?
Caspofungin in patients who have failed or cannot tolerate amphotericin B or an azole.
107
How is Caspofungin metabolized?
Via CYP450 enzymes, which can lead to drug-drug interactions.
108
Which Echinocandins are first-line options for the treatment of invasive candidiasis?
Micafungin and anidulafungin.
109
What condition do micafungin and anidulafungin treat?
Invasive candidiasis, including candidemia.
110
Do micafungin and anidulafungin interact with CYP450 enzymes?
No, they are not substrates for CYP450 enzymes.
111
What is a significant advantage of Echinocandins regarding drug interactions?
They have no drug-drug interactions.
112
What type of fungi primarily cause cutaneous infections?
Mold-like fungi known as dermatophytes.
113
What is the term for infections caused by dermatophytes?
Dermatophytosis.
114
What are some examples of dermatophytosis?
Tinea pedis, tinea corporis (ringworm), tinea capitis, tinea cruris, tinea versicolor, and onychomycoses.
115
Which fungi are the majority causes of dermatophytosis?
Trichophyton, Microsporum, and Epidermophyton.
116
What class of antifungal drugs includes terbinafine, naftifine, and butenafine?
Squalene epoxidase inhibitors.
117
What is the mechanism of action of squalene epoxidase inhibitors?
They inhibit squalene epoxidase, blocking the synthesis of ergosterol.
118
What happens as a result of squalene accumulation in fungal cells?
Increased membrane permeability leading to cell death.
119
What class of antifungal drugs does Terbinafine belong to?
Squalene epoxidase inhibitors.
120
What is the mechanism of action of Terbinafine?
Fungicidal.
121
What is the drug of choice for onychomycosis?
Terbinafine (orally).
122
How does Terbinafine compare to itraconazole and griseofulvin in terms of tolerance and effectiveness?
Better tolerated, shorter duration of therapy, and more effective.
123
What is the typical duration of therapy with Terbinafine for onychomycosis?
3 months (shorter than griseofulvin).
124
What condition requires an oral formulation of Terbinafine?
Tinea capitis.
125
What are the topical formulations of Terbinafine available?
1% cream, gel, or solution.
126
What is the treatment duration for tinea pedis, tinea corporis, tinea cruris, and tinea versicolor when using Terbinafine topically?
1 week.
127
What are the routes of administration for Terbinafine?
Oral and topical administration.
128
What is the bioavailability percentage of Terbinafine?
40% due to first-pass metabolism.
129
What is the half-life range of Terbinafine?
200 to 400 hours.
130
How is oral Terbinafine metabolized and excreted?
Metabolized in the liver and excreted in the urine.
131
In which patients should Terbinafine be avoided?
Patients with moderate to severe renal impairment or hepatic dysfunction.
132
What is the protein binding characteristic of Terbinafine?
Highly protein-bound and deposited in skin, nails, and adipose tissue.
133
Which CYP450 isoenzyme does Terbinafine inhibit?
CYP450 2D6 isoenzyme.
134
What type of drug interactions can occur with Terbinafine?
Drug-drug interactions due to CYP450 2D6 inhibition.
135
What are some adverse effects of Terbinafine?
Diarrhea, dyspepsia, nausea, headache, rash.
136
What visual disturbances have been reported with Terbinafine use?
Taste and visual disturbances.
137
What laboratory abnormality can occur with Terbinafine?
Elevations in serum hepatic transaminases.
138
What type of action does Griseofulvin exhibit?
Fungistatic and keratophilic.
139
How does Griseofulvin affect fungal cells?
It causes disruption of the mitotic spindle, inhibiting fungal mitosis.
140
Where is Griseofulvin deposited in the body?
In newly forming skin where it binds to keratin.
141
For what condition was Griseofulvin previously used?
Onychomycosis, requiring 6 - 12 months of treatment.
142
What current conditions is Griseofulvin still used for?
Dermatophytosis of the scalp and hair.
143
How should Griseofulvin be taken for optimal absorption?
With high-fat meals.
144
What effect does Griseofulvin have on the liver?
It induces hepatic CYP450, leading to drug-drug interactions.
145
In which patients is Griseofulvin contraindicated?
In pregnancy and patients with porphyria.
146
What does Nystatin resemble?
Amphotericin B.
147
What infections is Nystatin used to treat?
Cutaneous and oral Candida infections.
148
How is Nystatin absorbed in the body?
Not absorbed from the gastrointestinal tract; systemic toxicity can occur if given parenterally.
149
What is the method of administration for oral Nystatin?
Swish and swallow or swish and spit.
150
What condition is treated with oral Nystatin?
Oropharyngeal candidiasis (thrush).
151
How is Nystatin administered for vulvovaginal candidiasis?
Intravaginally.
152
What is the topical use of Nystatin?
To treat cutaneous candidiasis.
153
What class of antifungal drugs includes butoconazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sertaconazole, sulconazole, terconazole, and tioconazole?
Imidazoles.
154
What are some common uses of imidazoles?
Tinea corporis, tinea cruris, tinea pedis, oropharyngeal and vulvovaginal candidiasis.
155
What systemic fungal infection treatment has historically used oral ketoconazole?
Systemic fungal infections.
156
Why is oral ketoconazole rarely used today?
Due to the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions.
