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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}, {{AJL}} {{Alison}}
|QuestionAuthor={{YD}} (Reviewed by {{YD}} and {{AJL}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Microbiology, Pharmacology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|SubCategory=Dermatology
|Prompt=A 42-year-old female presents to the dermatology clinic with complaints of a nail lesion. Upon diagnosis of onychomycosis she is prescribed an antimicrobial medication that is then promptly stopped due to alteration of liver function tests and taste disturbance. Which of the following is the mechanism of action that best describes the medication prescribed?
|MainCategory=Microbiology, Pharmacology
|Explanation=[[Terbinafine]], considered a first line treatment for [[onychomycosis]], is an anti-fungal medication that inhibits squalene epoxidase. The most frequently occurring side effects of [[Terbinafine]]] are altered liver function tests (LFTs), GI upset, and taste disturbances. During treatment with [[terbinafine]], patients are requested to routinely perform LFT testing to monitor to drug-induced liver injury (DILI).
|SubCategory=Dermatology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|MainCategory=Microbiology, Pharmacology
|MainCategory=Microbiology, Pharmacology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|MainCategory=Microbiology, Pharmacology
|MainCategory=Microbiology, Pharmacology
|SubCategory=Dermatology
|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 elevated liver function tests. Which of the following best describes the mechanism of action of the prescribed antimicrobial agent?  
|Explanation=Onychomycosis is a common fungal infection of the nail apparatus. Although it is usually only a cosmetic concern, treatmnet of onychomyocis is very difficult, resistant, and often necessitates systemic antifungal therapy. Onychomycosis typically affects older patients with co-morbidities, such as diabetes mellitus, HIV, trauma, and peripheral vascular disease. Treatment of onychomycosis is important because if left untreated, the infection results in toe pain, spreads to other adjacent toe nails, and may be complicated by super-imposed 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 to 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.  
|AnswerA=Inhibits squalene epoxidase
|AnswerA=Inhibits squalene epoxidase
|AnswerAExp=See explanation.
|AnswerAExp=[[Terbinafine]] is now considered a first line treatment for [[onychomycosis]]. It is an anti-fungal medication that selectively inhibits fungal squalene epoxidase.
|AnswerB=Inhibits DNA polymerase
|AnswerB=Inhibits DNA polymerase
|AnswerBExp=Several antiviral medications, which are not used to treat onychomycosis, inhibit DNA polymerase.
|AnswerBExp=Several antiviral medications, which are not used to treat onychomycosis, inhibit DNA polymerase.
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|AnswerE=Inhibits ergosterol synthesis
|AnswerE=Inhibits ergosterol synthesis
|AnswerEExp=Azoles, which are not used to treat onychomycosis, inhibit ergosterol synthesis.
|AnswerEExp=Azoles, which are not used to treat onychomycosis, inhibit ergosterol synthesis.
|EducationalObjectives=[[Terbinafine]], considered a first line treatment for [[onychomycosis]], is an anti-fungal medication that inhibits squalene epoxidase.  
|EducationalObjectives=[[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.  
The most frequently occurring side effects of [[Terbinafine]] are altered liver function tests (LFTs), gastrointestinal disturbances, 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.<br>
|References=First Aid 2014 page 190
First Aid 2014 page 190
|RightAnswer=A
|RightAnswer=A
|WBRKeyword=terbinafine, drug induced liver injury, DILI, adverse reaction, side effect, adverse drug reaction, antifungal, onychomycosis, liver function test, LFT, dermatology, digestive system, fungus
|WBRKeyword=terbinafine, drug induced liver injury, DILI, adverse reaction, side effect, adverse drug reaction, antifungal, onychomycosis, liver function test, LFT, dermatology, digestive system, fungus
|Approved=Yes
|Approved=Yes
}}
}}

Revision as of 19:39, 29 October 2014

 
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 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, which are not used to treat onychomycosis, inhibit ergosterol synthesis.
Right Answer RightAnswer::A
Explanation [[Explanation::Onychomycosis is a common fungal infection of the nail apparatus. Although it is usually only a cosmetic concern, treatmnet of onychomyocis is very difficult, resistant, and often necessitates systemic antifungal therapy. Onychomycosis typically affects older patients with co-morbidities, such as diabetes mellitus, HIV, trauma, and peripheral vascular disease. Treatment of onychomycosis is important because if left untreated, the infection results in toe pain, spreads to other adjacent toe nails, and may be complicated by super-imposed 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 to 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::DILI, WBRKeyword::adverse reaction, WBRKeyword::side effect, WBRKeyword::adverse drug reaction, WBRKeyword::antifungal, WBRKeyword::onychomycosis, WBRKeyword::liver function test, WBRKeyword::LFT, WBRKeyword::dermatology, WBRKeyword::digestive system, WBRKeyword::fungus
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