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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor= {{SSK}} (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|Prompt=A 72 year old patient presents to the emergency department for high grade fever and altered mental status. His past medical history is significant for a radical prostatectomy several days before presentation. Following appropriate work-up, he is diagnosed with urosepsis. Blood cultures grow ESBL-producing E. coli. Based on image shown below, at which site on penicillin G does the organism's beta-lactamase act?
|SubCategory=Infectious Disease
 
|Prompt=To study the effects of a newly developed drug, a researcher uses polarized microscopy to monitor the changes in living Pectinaria oocytes exposed to intermittent doses of this agent. Although most oocytes are not directly affected, those in active replication seem to arrest at a certain point during mitosis with a significant reduction in the size of meiotic spindles, as measured by loss of birefringence under polarized light. The researcher also notices that shortly after the drug is washed, mitosis would resume and the spindles would regain birefringence. Which of the following drugs most likely has the same mechanism of action?
[[Image:WBR0529.png|500px]]
|Explanation=Griseofulvin is a fungistatic antifungal drug used mostly in the treatment of fungal skin infections. It is deposited in keratin precursor cells and tightly bound to keratin, which explains its efficacy in dermatologic infections. It acts by inhibiting mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule function. It binds to microtubules and inhibits their ability to polymerize leading a decrease in the effective mitotic spindles. It is among the fastest reversible drugs acting on microtubules. Common side effects include urticaria and drug induced rashes. A more severe but rare adverse effect is severe liver toxicity. Treatment is indicated for resistant infections affecting skin, body, hair, or nails, including tinea capitis, tinea corporis, and tinea pedis.
|Explanation=Extended spectrum beta-lactamase (ESBL) producing bacteria, such as E.coli or Klebsiella species, acquire resistance to penicillin and its derivatives by the action of beta-lactamase enzyme which hydrolyzes the beta-lactam ring of the antibiotic and prevents its action. The penicillin G structure is shown in the image above. Beta-lactam is the ring structure that is hydrolyzed by beta-lactamase enzyme
|AnswerA=Carboplatin
 
|AnswerAExp=Carboplatin is a chemotherapeutic agent that cross-links DNA.
Educational Objective: Beta-lactam ring on penicillin G is an important site for resistance by ESBL-producing bacteria.
|AnswerB=Amantadine
|AnswerA=A
|AnswerBExp=Amantadine is an antiviral drug that inhibits influenza uncoating by binding to the M2 protein.
|AnswerAExp=This is not the site of beta-lactamase action.
|AnswerC=Griseofulvin
|AnswerB=B
|AnswerCExp=Griseofulvin is a fungistatic agent that inhibits microtubule polymerization and inhibits mitosis.
|AnswerBExp=This is not the site of beta-lactamase action.
|AnswerD=Etoposide
|AnswerC=C
|AnswerDExp=Etoposide is an antineoplastic agent that acts as a topoisomerase inhibitor.
|AnswerCExp=This site on the beta-lactam ring is the site that beta-lactamases use to break down penicillin and thus acquire resistance.
|AnswerE=Caspofungin
|AnswerD=D
|AnswerEExp=Caspofungin is an antifungal drug that inhibits the enzyme β-glucan synthase and disturbs the integrity of the fungal cell wall.
|AnswerDExp=This is not the site of beta-lactamase action.
|EducationalObjectives=Griseofulvin is a fungistatic agent that inhibits microtubule polymerization halting mitotic divison.
|AnswerE=E
|References=Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends in Microbiology. 2003;11(6):272-279.
|AnswerEExp=This is not the site of beta-lactamase action.
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=ESBL, producing, bacteria, E. coli, Klebsiella, urosepsis, extended, spectrum, beta-lactamase, penicillin
|WBRKeyword=Griseofulvin, Microtubule, Mitosis, Antifungal, Fungistatic, Fungal infection,
|Approved=No
|Approved=Yes
}}
}}

Latest revision as of 00:52, 28 October 2020

 
Author [[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Infectious Disease
Prompt [[Prompt::To study the effects of a newly developed drug, a researcher uses polarized microscopy to monitor the changes in living Pectinaria oocytes exposed to intermittent doses of this agent. Although most oocytes are not directly affected, those in active replication seem to arrest at a certain point during mitosis with a significant reduction in the size of meiotic spindles, as measured by loss of birefringence under polarized light. The researcher also notices that shortly after the drug is washed, mitosis would resume and the spindles would regain birefringence. Which of the following drugs most likely has the same mechanism of action?]]
Answer A AnswerA::Carboplatin
Answer A Explanation AnswerAExp::Carboplatin is a chemotherapeutic agent that cross-links DNA.
Answer B AnswerB::Amantadine
Answer B Explanation AnswerBExp::Amantadine is an antiviral drug that inhibits influenza uncoating by binding to the M2 protein.
Answer C AnswerC::Griseofulvin
Answer C Explanation AnswerCExp::Griseofulvin is a fungistatic agent that inhibits microtubule polymerization and inhibits mitosis.
Answer D AnswerD::Etoposide
Answer D Explanation AnswerDExp::Etoposide is an antineoplastic agent that acts as a topoisomerase inhibitor.
Answer E AnswerE::Caspofungin
Answer E Explanation AnswerEExp::Caspofungin is an antifungal drug that inhibits the enzyme β-glucan synthase and disturbs the integrity of the fungal cell wall.
Right Answer RightAnswer::C
Explanation [[Explanation::Griseofulvin is a fungistatic antifungal drug used mostly in the treatment of fungal skin infections. It is deposited in keratin precursor cells and tightly bound to keratin, which explains its efficacy in dermatologic infections. It acts by inhibiting mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule function. It binds to microtubules and inhibits their ability to polymerize leading a decrease in the effective mitotic spindles. It is among the fastest reversible drugs acting on microtubules. Common side effects include urticaria and drug induced rashes. A more severe but rare adverse effect is severe liver toxicity. Treatment is indicated for resistant infections affecting skin, body, hair, or nails, including tinea capitis, tinea corporis, and tinea pedis.

Educational Objective: Griseofulvin is a fungistatic agent that inhibits microtubule polymerization halting mitotic divison.
References: Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends in Microbiology. 2003;11(6):272-279.]]

Approved Approved::Yes
Keyword WBRKeyword::Griseofulvin, WBRKeyword::Microtubule, WBRKeyword::Mitosis, WBRKeyword::Antifungal, WBRKeyword::Fungistatic, WBRKeyword::Fungal infection
Linked Question Linked::
Order in Linked Questions LinkedOrder::