WBR0478

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pharmacology
Sub Category	SubCategory::Dermatology
Prompt	[[Prompt::A 72-year-old diabetic woman presents to the dermatology clinic with complaints of a nail lesion. Following history-taking and physical examination, the patient is diagnosed with onychomycosis. She is then prescribed an oral antimicrobial medication and is instructed to follow-up routinely. One month later, the patient reports she is experiencing an unusual taste disturbance; and she is found to have markedly elevated liver function tests. Which of the following best describes the mechanism of action of the prescribed antimicrobial agent?]]
Answer A	AnswerA::Inhibits squalene epoxidase
Answer A Explanation	[[AnswerAExp::Terbinafine is now considered a first line treatment for onychomycosis. It is an anti-fungal medication that selectively inhibits fungal squalene epoxidase.]]
Answer B	AnswerB::Inhibits DNA polymerase
Answer B Explanation	AnswerBExp::Several antiviral medications, which are not used to treat onychomycosis, inhibit DNA polymerase.
Answer C	AnswerC::Inhibits aminoacyl-tRNA attachment
Answer C Explanation	AnswerCExp::Tetracyclines, which are not used to treat onychomycosis, inhibit aminoacyl-tRNA attachment.
Answer D	AnswerD::Inhibits synthesis of beta-glucan
Answer D Explanation	AnswerDExp::Caspofungin, which is not used to treat onychomycosis, inhibits synthesis of beta-glucan.
Answer E	AnswerE::Inhibits ergosterol synthesis
Answer E Explanation	AnswerEExp::Azoles inhibit ergosterol synthesis and may be administered to treat onychomycosis; but the patient's symptoms and history are more consistent with terbinafine adverse reactions.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Onychomycosis is a common fungal infection of the nail apparatus. Although it is usually only a cosmetic concern, treatment of onychomyocis is very difficult and often necessitates systemic antifungal therapy. Onychomycosis typically affects older patients with co-morbidities, such as diabetes mellitus, HIV, trauma, and peripheral vascular disease. If left untreated, onychomycosis results in toe pain, spreads to other adjacent toe nails, and may be complicated by superimposed bacterial infections (erysipelas and cellulitis) and ingrown nails. The most common cause of onychomycosis is Trichophyton rubrum. Treatment options classically included griseofulvin and ketoconazole; but newer antifungals, such as fluconazole, itraconazole, and terbinafine, are currently available and more efficacious. Terbinafine is now considered a first line treatment for onychomycosis. It is an anti-fungal medication that selectively inhibits fungal squalene epoxidase. It is present in both topical and oral forms. Classical adverse drug reactions associated with oral terbinafine are altered liver function tests (LFTs), GI upset, and taste disturbances. During treatment with terbinafine, patients are instructed to routinely perform LFT testing to monitor to drug-induced liver injury (DILI) that usually occurs within the first 6 months of terbinafine therapy and generally resolves within 3-6 months of drug discontinuation. Educational Objective: Terbinafine is now considered a first line treatment for onychomycosis. It is an anti-fungal medication that selectively inhibits fungal squalene epoxidase. Classical adverse drug reactions to oral terbinafine are altered liver function tests (LFTs), GI upset, and taste disturbances. References: de Sa DC, Lamas AP, Tosti A. Oral therapy for onychomycosis: an evidence-based review. Am J Clin Dermatol. 2014;15(1):17-36. First Aid 2014 page 190]]
Approved	Approved::Yes
Keyword	WBRKeyword::Terbinafine, WBRKeyword::Drug induced liver injury, WBRKeyword::Hepatotoxicity, WBRKeyword::Adverse drug reaction, WBRKeyword::Adverse drug event, WBRKeyword::Side effect, WBRKeyword::Squalene epoxidase, WBRKeyword::Onychomycosis, WBRKeyword::Antifungals
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::