Antifungal Medications Quiz

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Questions and Answers

Which type of antifungal is commonly given topically for cutaneous infections?

Allylamines

Imidazoles (correct)

Nucleosides

Triazoles

What is the primary difference between Imidazoles and Triazoles?

Imidazoles are considered fungicidal while Triazoles are fungistatic.

Triazoles have a greater degree of selectivity than Imidazoles. (correct)

Imidazoles are used systemically while Triazoles are topical.

Triazoles are exclusively for respiratory tract infections.

What contributes to the selective toxicity of Azole drugs?

Their lesser affinity for fungal cytochrome P450 enzymes.

Their greater affinity for fungal cytochrome P450 enzymes. (correct)

Their greater affinity for human cytochrome P450 enzymes.

Their ability to inhibit fungal cell wall synthesis.

Which of the following conditions increases the risk of renal toxicity with certain medications?

Patients with renal insufficiency Signup and view all the answers

Which of the following is a broad-spectrum action of Azole medications?

Effective against Candida species Signup and view all the answers

What is a common side effect of azole antifungals?

Minor gastrointestinal upset Signup and view all the answers

Which azole antifungal is reported to be fungicidal against Aspergillus?

Voriconazole Signup and view all the answers

Why should azole use be avoided during pregnancy?

They are highly teratogenic. Signup and view all the answers

What is the primary route of elimination for fluconazole?

Renal elimination Signup and view all the answers

Which organisms are usually resistant to amphotericin B?

Aspergillus terreus Signup and view all the answers

Which condition is fluconazole NOT preferred for?

Blastomycosis Signup and view all the answers

What is a primary advantage of liposomal preparations of amphotericin B?

Reduced renal toxicity Signup and view all the answers

What effect do inducers of drug metabolizing enzymes have on itraconazole?

Decrease its bioavailability Signup and view all the answers

Which statement is true regarding the administration routes of amphotericin B?

IV is the main route of administration. Signup and view all the answers

Which of the following is a co-drug of choice for invasive aspergillosis?

Voriconazole Signup and view all the answers

In patients with hepatic dysfunction, how should the dosage of amphotericin B be adjusted?

No dosage adjustment is needed Signup and view all the answers

What adverse effects are associated with high trough concentrations of voriconazole?

Visual and auditory hallucinations Signup and view all the answers

What potential immediate toxicity effects can occur after administering amphotericin B?

Fever and chills Signup and view all the answers

Itraconazole is the drug of choice for which of the following infections?

Blastomycosis Signup and view all the answers

What can lead to reversible renal impairment when using conventional amphotericin B?

High doses over extended periods Signup and view all the answers

What is a primary mechanism of action for ketoconazole in relation to other drugs?

Increases the plasma levels of certain drugs Signup and view all the answers

What is the maximum recommended total adult daily dose for the conventional formulation of amphotericin B?

1.5 mg/kg/d Signup and view all the answers

How does voriconazole differ from itraconazole in pharmacological activity?

Wider spectrum of antifungal activity Signup and view all the answers

What effect does inflammation have on the distribution of amphotericin B?

Enhances penetration into body fluids Signup and view all the answers

What is a significant side effect of voriconazole use?

Toxicity or clinical failure due to interactions Signup and view all the answers

Which drug is contraindicated when using voriconazole?

Rifampin Signup and view all the answers

Which azole was the first oral azole introduced into clinical use?

Ketoconazole Signup and view all the answers

How is posaconazole primarily administered for effective absorption?

With high-fat meals Signup and view all the answers

What is the role of posaconazole in treating invasive mucormycosis?

Licensed for salvage therapy Signup and view all the answers

Which statement about isavuconazole is correct?

It has an antifungal spectrum similar to posaconazole Signup and view all the answers

What dosage of posaconazole is recommended when taken orally?

800 mg per day Signup and view all the answers

What is the impact of ketoconazole compared to newer azoles?

Less effective in systemic use Signup and view all the answers

Which statement is true regarding nystatin?

Nystatin has no reported toxicity. Signup and view all the answers

Which condition is commonly treated with nystatin?

Oropharyngeal thrush Signup and view all the answers

What is a primary use of clotrimazole?

Management of oral thrush and vulvovaginal candidiasis. Signup and view all the answers

Which conditions can be treated with topical allylamines?

Tinea corporis and tinea cruris Signup and view all the answers

What is a common side effect of oral nystatin?

Unpleasant taste Signup and view all the answers

What is the primary mechanism of action of ibrexafungerp?

Concentration dependent fungicidal activity Signup and view all the answers

What is the recommended dosage of griseofulvin for systemic treatment of dermatophytosis?

1 g/d Signup and view all the answers

Which population should avoid taking griseofulvin?

Patients with hepatic failure Signup and view all the answers

What is an important characteristic of nystatin in terms of administration?

It is used only in topical formulations Signup and view all the answers

How does terbenafine achieve a high cure rate for onychomycosis?

One tablet daily for 12 weeks Signup and view all the answers

Which of the following statements about ibrexafungerp is correct?

It is effective against azole-resistant Candida species Signup and view all the answers

What are the primary methods of metabolism for ibrexafungerp?

Hydroxylation followed by glucuronidation and sulfation Signup and view all the answers

What kind of drug interaction does griseofulvin have?

It decreases the serum concentration of warfarin Signup and view all the answers

Study Notes

Antifungal Drugs

Antifungal drugs are used to treat infections caused by fungi.
Increased use of broad-spectrum antimicrobial therapy in critically ill patients, along with advances in surgery, cancer treatment, and solid organ/bone marrow transplantation, have led to an increase in fungal infections.
Fungal infections can manifest as skin rashes, skin lesions, nail bed infections, and oral thrush.

Classification of Antifungals

Systemic drugs: Used for systemic infections (oral or parenteral).
Oral systemic drugs: Used for mucocutaneous infections (affecting mucosal surfaces, skin, and nails).
Topical drugs: Used for mucocutaneous infections.

Antifungal Drugs Classification Chart

Antibiotics: Flucytosine
Antimetabolites: Flucytosine, Heterocyclic benzofuran (e.g., Griseofulvin)
Azoles: Imidazoles (e.g., Clotrimazole, Miconazole, Ketoconazole, Oxiconazole) and Triazoles (e.g., Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole, Oteseconazole)
Allylamine: Terbinafine
Polyenes: Amphotericin B, Nystatin, Hamycin
Echinocandins: Caspofungin, Micafungin, Anidulafungin
Topical Agents: Tolnaftate, Undecylenic acid, Benzoic acid, Ciclopirox olamine, Butenafine, Quiniodochlor, Sod. thiosulfate

Mechanism of Action of Amphotericin B

Amphotericin B binds to ergosterol in fungal cell membranes.
It forms pores in the membrane, leading to leakage of electrolytes and small molecules.
This disruption leads to cell death.

Amphotericin B: Properties and Spectrum

Amphotericin B is the only effective antifungal drug for systemic use, but it's highly toxic.
Newer agents offer more targeted therapy, with less toxicity.
The spectrum of activity is wide, encompassing Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and strains of Aspergillus. It is also used for leishmaniasis (protozoan infection).
Resistance is infrequent but may be associated with a decreased ergosterol content in the fungal membrane. Some organisms, including those causing chromoblastomycosis, Aspergillus terreus, Candida lusitaniae, Scedosporium spp., and some Fusarium spp. are usually resistant.

Amphotericin B: Pharmacokinetics

Amphotericin B is administered by slow intravenous infusion.
It's insoluble in water and requires co-formulation with sodium deoxycholate or artificial lipids (liposomes).
Liposomal preparations have a reduced toxicity profile, particularly concerning renal toxicity and infusion toxicity, but at a higher cost.
The drug and its metabolites are present in low concentrations in the urine for an extended period. Some are also eliminated via the bile.

Amphotericin B: Dosage Adjustment

Dosage is not adjusted for hepatic dysfunction.
If renal dysfunction occurs, the daily dose is lessened by 50%.

Amphotericin B: Adverse Effects

Amphotericin B has a narrow therapeutic index.
The traditional formulation dose should not exceed 1.5 mg/kg/day. Lipid formulations allow for a higher dose (up to 10 mg/kg/day)
Immediate toxicities (fever, chills, muscle spasms, vomiting, headache, phlebitis) often occur 1-3 hours post-administration. Preventative premedication with corticosteroids, heparin, and antipyretics can help.
Cumulative toxicity can lead to renal impairment, exacerbation by other drugs, and a need for adequate hydration.
Hypotension, anemia, seizures, and arachnoiditis are also possible side effects.

Flucytosine: Characteristics and Mechanism of Action

Flucytosine is a pyrimidine analog related to 5-fluorouracil.
Discovered in 1957 as an antineoplastic agent.
It works by being converted into a toxic metabolite that interferes with fungal DNA and RNA synthesis.
It has synergy with amphotericin B.
The spectrum of activity is limited to C. neoformans, some Candida species, and dematiaceous molds.
The drug is not used alone but as part of a combination therapy.

Flucytosine: Pharmacokinetics and Adverse Effects

Well absorbed orally (over 90%) with peak concentrations within 1-2 hours.
Poorly protein-bound.
Penetrates well into body fluids, including the cerebrospinal fluid (CSF).
Half-life is about 3-4 hours
Toxicity is often a result of metabolism to a toxic compound, fluorouracil
Common adverse effects include bone marrow toxicity (anemia, leukopenia, thrombocytopenia), liver enzyme abnormalities, and toxic enterocolitis.
Toxic levels can increase rapidly with renal dysfunction, often needing to be managed in AIDS patients with renal issues.

Azoles Characteristics

Azoles are divided into Imidazoles and Triazoles.
They are notable for their broad spectrum of activity, while also exhibiting varying degrees of selectivity.
Usually, Imidazoles are used topically for cutaneous infections, whilst Triazoles are used systemically for cutaneous and systemic infections.
The mechanism of action involves the reduction of ergosterol synthesis through the inhibition of cytochrome P450 enzymes.
A higher affinity for fungal cytochrome P450 enzymes compared to human enzymes explains their selective toxicity.

Azoles: Spectrum, Effects, and Practical Uses

Azoles are generally fungistatic against Candida species.
They're effective against various infections, including dermatophytes, Aspergillus infections, blastomycosis, sporotrichosis, paracoccidioidomycosis, and histoplasmosis.
Side effects are usually minor gastrointestinal upset; liver enzyme abnormalities; and ketoconazole-associated, drug-induced infertility or gynecomastia are possible.
Azole use during pregnancy should be avoided.
The drugs may interact with other medications, mainly because they affect human cytochrome P450 enzymes.

Azoles: Pharmacokinetics

Water solubility, absorption, CSF-serum concentration ratios, half-lives, and routes of elimination vary between the different azole drugs.
The elimination often takes place via hepatic metabolism, but fluconazole is primarily excreted unchanged from the kidneys.

Echinocandins Summary

Echinocandins are the first systemic, selective antifungal that destroys fungal cell walls.
They work by inhibiting the synthesis of β(1-3)-glucan.
Semisynthetic derivatives (e.g., Caspofungin, Micafungin, Anidulafungin) are available for intravenous (IV) administration, with dosages generally adjusted only for moderate hepatic dysfunction rather than renal issues.
Adverse effects are typically mild, but can include fever, rash, nausea, and phlebitis.
They're primarily used to treat candidiasis and invasive aspergillosis.

Griseofulvin

A very insoluble, fungistatic drug derived from a species of Penicillium.
The drug inhibits keratin production.
Primarily used for systemic treatment of dermatophytosis and administered at a dosage of 1 g daily.
Absorption is best when ingested with fatty foods.

Terbinafine

A topical allylamine
Used in the treatment of dermatophytoses, especially onychomycosis.
It's administered orally at 250 mg/day for 12 weeks
Oral administration has approximately a 90% cure rate for onychomycosis
Effective compared to Griseofulvin and Itraconazole.
Adverse effects are mainly gastrointestinal disturbance and headache,
It doesn't appear to inhibit the P450 system significantly.

Topical Antifungal Therapy

Nystatin is a polyene macrolide, too toxic for IV administration so it is topical.
It is not absorbed significantly and has minimal toxicity.
Commonly used for suppressing local Candidal infections, such as oral thrush, vaginal candidiasis and intertriginous candidal infections (areas where skin surfaces rub).
Available as creams, ointments, suppositories, and other forms for application to skin and mucous membranes, is used for treatment of infections such as seborrheic dermatitis, tinea capitis, and pityriasis versicolor
Clotrimazole and miconazole both are OTC and used frequently for vulvovaginal candidiasis, oral thrush as well as vaginal candidiasis.

Antifungal Drugs in Pregnancy

The risk categories of different antifungal drugs during pregnancy vary.
Some, such as amphotericin B and nystatin, are in Category B or A, indicating relative safety.

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Description

This quiz tests your knowledge on antifungal medications, specifically focusing on azole drugs and their mechanisms, uses, and side effects. Answer questions about different types of antifungals, their effectiveness, and considerations in special populations. Challenge your understanding of these critical pharmaceuticals in dermatology and infectious diseases.