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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor=[[User:Gonzalo Romero|Gonzalo A. Romero, M.D.]] [mailto:gromero@wikidoc.org]
|QuestionAuthor=[[User:Gonzalo Romero|Gonzalo A. Romero, M.D.]] (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
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|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|SubCategory=Cardiology, Endocrine
|SubCategory=Cardiology, Endocrine
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
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|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|MainCategory=Pathology, Pathophysiology, Pharmacology, Physiology
|SubCategory=Cardiology, Endocrine
|SubCategory=Cardiology, Endocrine
|Prompt=A 56-year-old male is treated chronically with an antiarrhythmic drug.  After several months the patient comes to the clinic complaining of difficulty with concentration, constipation, decreased libido and hair loss. On physical exam the doctor notices a bluish coloration of the skin that catches the physician attention, as it is the first time seeing this unique physical sign. Which of the following changes in the cardiac cell action potential mostly correlates to the drug being used?
|Prompt=A 66-year-old man presents to the cardiology clinic with complaints of constipation, decreased libido and excessive hair loss. He has a three year history of atrial fibrillation that is well controlled on medical therapy. Physical examination demonstrates dry, coarse skin with a distinct bluish-grey discoloration of the nose, cheeks, and lips. Which of the following electrophysiological changes is characteristic of the drug most likely to be used in this case?
|Explanation='''Overall explanation:''' This patient is receiving an anti-arrhythmic which is causing hypothyroidism represented by: difficulty concentrating, constipation, decreased libido and hair loss. Amiodarone typically causes thyroid problems and bluish discolorations of the skin.
|Explanation=Amiodarone is a class III antiarrhythmic drug that has effects of class Ia, II, III, and IV antiarrhythmics. Electrophysiological effects of amiodarone include prolongation of phase 3 of the action potential (repolarization) leading to an increase in AP duration, and increase of the refractory period causing a decrease in the heart rate. Amiodarone also increases the QT interval, however, it is not associated with an increase risk of torsade de pointes. Amiodarone has a chemical structure that closely resembles thyroxine, which replaces thyroxine at its receptor. The molecule also inhibits the action of type 1 5'-deiodinase that is responsible for the peripheral conversion of T4 to T3. Several other pathological effects on the thyroid gland and its hormones have been described including cytotoxic effects, and inhibition of feedback regulation. Clinically, these effects may manifest as either hypo- or hyperthyroidism, which is the main reason for the close follow-up of thyroid function among patients receiving amiodarone. Amiodarone also has several other side-effects including interstitial fibrosis, corneal deposits, peripheral neuropathy, and skin discoloration. The bluish skin discoloration (ceruloderma) associated with skin deposits of amiodarone is also known as "blue-man syndrome". It most commonly involves the face and is also associated with severe corneal deposits. It resolves within weeks to months of amiodarone discontinuation.  
<br>
|AnswerA=Decreased conduction velocity, increased ERP and PR interval
<font color="MediumBlue"><font size="4">'''Educational Objective:'''</font></font>
|AnswerAExp=These electrophysiological changes are observed with calcium channel blockers.
Amiodarone causes hypothyroidism and bluish skin discoloration if used long term.
|AnswerB=Decreased AP duration with activity more significant in ischemic and depolarized ventricular tissue
[[File:Anti-arrhytmic.png|center|600px]]
|AnswerBExp=These electrophysiological changes are observed with class IB antiarrhythmics.
<br>'''References:'''First Aid for STEP 1 2013, endocrinology chapter
|AnswerC=Increased repolarization phase, AP duration, ERP, and QT interval
|AnswerA=Decreases conduction velocity, increases the ERP and PR interval.
|AnswerCExp=This mechanism of action corresponds to amiodarone, the drug most likely to be causing this patient's symptoms.
|AnswerAExp=<font color="red">'''Incorrect.'''</font> This mechanism corresponds to calcium channel blockers.
|AnswerD=Decreases slope of phase 0, Minimal effect on AP duration
|AnswerB=Decreases the AP duration, acts preferably on ischemic and depolarized ventricular tissue.
|AnswerDExp=These electrophysiological changes are observed with class IC antiarrhythmics
|AnswerBExp=<font color="red">'''Incorrect.'''</font> This mechanism corresponds to class IB sodium channel blockers.
|AnswerE=Decreased SA and AV nodal activity, Increased PR interval, Decreased slope of phase 4
|AnswerC=Increases the AP duration & ERP. Increases the QT interval. Increases the Phase III.
|AnswerEExp=These electrophysiological changes are observed with beta blockers.
|AnswerCExp=<font color="Green">'''Correct.'''</font> This mechanism of action corresponds to Amiodarone
|EducationalObjectives=Amiodarone is a class III antiarrhythmic associated with hypo or hyperthyroidism and bluish-grey discoloration with prolonged use.
|AnswerD=Increases AP duration, increases ERP, increases QT interval. Acts on both atria and ventricle.
|References=Zimetbaum P. Amiodarone for atrial fibrillation. N Engl J Med. 2007;356(9):935-41.<br>
|AnswerDExp=<font color="red">'''Incorrect.'''</font>  This mechanism corresponds to class IA sodium channel blockers.
Enseleit F, Wyss CA, Duru F, Noll G, Ruschitzka F. Images in cardiovascular medicine. The blue man: amiodarone-induced skin discoloration. Circulation. 2006;113(5):e63.<br>
|AnswerE=Decreases SA and AV nodal activity. Increases the PR interval. Decreases the slope of phase 4.
First Aid 2013 page 303
|AnswerEExp=<font color="red">'''Incorrect.'''</font>   This corresponds to the mechanism of action of the beta blockers.
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=Amiodarone
|WBRKeyword=Amiodarone, Blue man syndrome, Hypothyroidism, Hyperthyroidism, Antiarrhythmics, Class III, Side effects
|Approved=Yes
|Approved=Yes
}}
}}

Latest revision as of 00:46, 28 October 2020

 
Author [[PageAuthor::Gonzalo A. Romero, M.D. (Reviewed by Serge Korjian)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pathology, MainCategory::Pathophysiology, MainCategory::Pharmacology, MainCategory::Physiology
Sub Category SubCategory::Cardiology, SubCategory::Endocrine
Prompt [[Prompt::A 66-year-old man presents to the cardiology clinic with complaints of constipation, decreased libido and excessive hair loss. He has a three year history of atrial fibrillation that is well controlled on medical therapy. Physical examination demonstrates dry, coarse skin with a distinct bluish-grey discoloration of the nose, cheeks, and lips. Which of the following electrophysiological changes is characteristic of the drug most likely to be used in this case?]]
Answer A AnswerA::Decreased conduction velocity, increased ERP and PR interval
Answer A Explanation AnswerAExp::These electrophysiological changes are observed with calcium channel blockers.
Answer B AnswerB::Decreased AP duration with activity more significant in ischemic and depolarized ventricular tissue
Answer B Explanation AnswerBExp::These electrophysiological changes are observed with class IB antiarrhythmics.
Answer C AnswerC::Increased repolarization phase, AP duration, ERP, and QT interval
Answer C Explanation AnswerCExp::This mechanism of action corresponds to amiodarone, the drug most likely to be causing this patient's symptoms.
Answer D AnswerD::Decreases slope of phase 0, Minimal effect on AP duration
Answer D Explanation AnswerDExp::These electrophysiological changes are observed with class IC antiarrhythmics
Answer E AnswerE::Decreased SA and AV nodal activity, Increased PR interval, Decreased slope of phase 4
Answer E Explanation AnswerEExp::These electrophysiological changes are observed with beta blockers.
Right Answer RightAnswer::C
Explanation [[Explanation::Amiodarone is a class III antiarrhythmic drug that has effects of class Ia, II, III, and IV antiarrhythmics. Electrophysiological effects of amiodarone include prolongation of phase 3 of the action potential (repolarization) leading to an increase in AP duration, and increase of the refractory period causing a decrease in the heart rate. Amiodarone also increases the QT interval, however, it is not associated with an increase risk of torsade de pointes. Amiodarone has a chemical structure that closely resembles thyroxine, which replaces thyroxine at its receptor. The molecule also inhibits the action of type 1 5'-deiodinase that is responsible for the peripheral conversion of T4 to T3. Several other pathological effects on the thyroid gland and its hormones have been described including cytotoxic effects, and inhibition of feedback regulation. Clinically, these effects may manifest as either hypo- or hyperthyroidism, which is the main reason for the close follow-up of thyroid function among patients receiving amiodarone. Amiodarone also has several other side-effects including interstitial fibrosis, corneal deposits, peripheral neuropathy, and skin discoloration. The bluish skin discoloration (ceruloderma) associated with skin deposits of amiodarone is also known as "blue-man syndrome". It most commonly involves the face and is also associated with severe corneal deposits. It resolves within weeks to months of amiodarone discontinuation.

Educational Objective: Amiodarone is a class III antiarrhythmic associated with hypo or hyperthyroidism and bluish-grey discoloration with prolonged use.
References: Zimetbaum P. Amiodarone for atrial fibrillation. N Engl J Med. 2007;356(9):935-41.
Enseleit F, Wyss CA, Duru F, Noll G, Ruschitzka F. Images in cardiovascular medicine. The blue man: amiodarone-induced skin discoloration. Circulation. 2006;113(5):e63.
First Aid 2013 page 303]]

Approved Approved::Yes
Keyword WBRKeyword::Amiodarone, WBRKeyword::Blue man syndrome, WBRKeyword::Hypothyroidism, WBRKeyword::Hyperthyroidism, WBRKeyword::Antiarrhythmics, WBRKeyword::Class III, WBRKeyword::Side effects
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