WBR0507

Author	[[PageAuthor::Serge Korjian M.D., Gonzalo A. Romero, M.D. (Reviewed by Alison Leibowitz)(Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Embryology, MainCategory::Microbiology, MainCategory::Pharmacology
Sub Category	SubCategory::Infectious Disease
Prompt	[[Prompt::A 2-year-old girl is brought to the pediatrician because her mother is concerned that her teeth have turned a dark shade of gray since her last check-up. The mother explains that her daughter has been developing normally, but she recently started refusing formula. She also reports that approximately 2 months ago, the child had an episode of cough and sore throat for which she gave her some left-over antibiotics she had at home. Physical exam is unremarkable except for annular gray-brown stains apparent mostly across the front teeth. Which of the following was most likely mechanism of action of the drug used in this patient?]]
Answer A	AnswerA::Prevents attachment of aminoacyl-tRNA to the 30S ribosomal subunit
Answer A Explanation	AnswerAExp::The main mechanism of action of tetracycline antibiotics is the inhibition of protein synthesis by preventing the attachment of aminoacyl-tRNA to the 30S ribosomal subunit.
Answer B	AnswerB::Inhibits the formation of initiation complex
Answer B Explanation	AnswerBExp::Aminoglycosides act mainly on the 30S ribosomal subunit inhibiting the formation of the initiation complex, essential for protein synthesis. Although tetracyclines also bind to the 30S subunit, they do not affect the initiation complex.
Answer C	AnswerC::Inhibits protein synthesis by binding to the 50S ribosomal subunit
Answer C Explanation	AnswerCExp::Clindamycin and macrolides both inhibit protein synthesis by binding to the 50S ribosomal subunit. Tetracyclines do not bind to the 50S subunit.
Answer D	AnswerD::Inhibits the translocation by binding to the 23S rRNA
Answer D Explanation	AnswerDExp::Macrolides act on the 50S ribosomal subunit (particularly the 23S rRNA) to inhibit protein synthesis. They act by preventing the translocation step. Tetracyclines have no action on the 23S rRNA.
Answer E	AnswerE::Inhibits protein elongation by blocking peptidyl-transferase
Answer E Explanation	AnswerEExp::Chloramphenicol inhibits elongation by blocking the peptidyl-transferase halting protein synthesis. Tetracyclines do not affect the peptidyl-transferase enzyme.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Tetracycline antibiotics are a group of bacteriostatic agents whose name is derived from their main structure comprising four hydrocarbon rings. Tetracycline antibiotics inhibit protein synthesis by preventing the binding of aminoacyl-tRNA to the mRNA-ribosome complex. The main site of action of these agents is the 30S ribosomal subunit. Tetracyclines have a broad spectrum of activity against both gram-positive and gram-negative organisms. Despite growing resistance, tetracyclines still have several indications including atypical (Chlamydia, Legionella), rickettsial (typhus, ehrlichiosis, anaplasmosis, rocky mountain spotted fever), and spirochetal (lyme disease, leptospirosis, syphylis) infections. Administration of these agents should be separated from calcium or iron containing preparations as well as dairy products because cations bind to tetracycline molecules and inhibit proper absorption in the gut. The main mechanism of resistance to tetracyclines is the acquisition of an efflux protein transporter through a resistance plasmid. Another mechanism is through acquiring a protein that blocks the binding of the tetracycline to the ribosomal subunit. Major side effects of tetracyclines include photo-sensitivity, discoloration of the teeth, and rarely pseudotumor cerebri with chronic administration. Tetracycline administration is contraindicated in pregnant and lactating women, and in children <8 years of age because use is associated with abnormal teeth and bone development as well as permanent staining of the teeth. Teeth stains are typically annular, gray-brown, and more pronounced at the crown fading as they move towards the root of the tooth. Educational Objective: Tetracycline antibiotics are a group of agents that inhibit protein synthesis by binding the 30S ribosomal subunit and preventing the binding of aminoacyl-tRNA to the mRNA-ribosome complex. Their use in pregnant and lactating women or children younger than 8 years of age is associated with gray-brown discoloration of the teeth References: Klein NC, Cunha BA. Tetracyclines. Med Clin North Am. 1995;79(4):789-801. Sánchez AR, Rogers RS, Sheridan PJ. Tetracycline and other tetracycline-derivative staining of the teeth and oral cavity. Int J Dermatol. 2004;43(10):709-15.]]
Approved	Approved::Yes
Keyword	WBRKeyword::tetracycline, WBRKeyword::side effects, WBRKeyword::teeth, WBRKeyword::discoloration, WBRKeyword::mechanism of action, WBRKeyword::antibiotics, WBRKeyword::tRNA, WBRKeyword::pregnancy, WBRKeyword::lactation
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