WBR0481

Author	[[PageAuthor::Ayokunle Olubaniyi, M.B,B.S [1]]]
Exam Type	ExamType::USMLE Step 2 CK
Main Category	MainCategory::Internal medicine
Sub Category
Prompt	[[Prompt::In a quest to find the ultimate low density liproprotein cholesterol (LDL-C) lowering drug for the treatment of heterozygous familial hypercholesterolemia, researchers have discovered an endogenous substance, Proprotein convertase subtilisin/kexin type 9 (PCSK9), which acts by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the low-density lipoprotein receptor (LDLR). It was also postulated that developing monoclonal antibodies against this compound will have a tremendous effect in lowering the level of LDL-cholesterol in this group of patients. Which of the following mechanisms of action best describes this experimental drug?]]
Answer A	AnswerA::Prevention of LDL receptor degradation in the lysosomes
Answer A Explanation	AnswerAExp::Correct – LDL receptors function in the removal of cholesterol from the plasma. Agents that can preserve these receptors will indirectly increase the removal of LDL cholesterol from the plasma
Answer B	AnswerB::Promotes the activity of HMG-CoA reductase
Answer B Explanation	[[AnswerBExp::Incorrect – Medications that inhibits (not promote) the activity of HMG-CoA reductase help lower the serum level of cholesterol e.g., statins.]]
Answer C	AnswerC::Inhibits cholesterol ester transfer protein
Answer C Explanation	[[AnswerCExp::Incorrect - An example of a cholesterol ester transfer protein inhibitor is anacetrapid which is still an experimental drug that prevents the transfer of cholesterol esters from HDL molecules to either VLDL or IDL molecules in the reverse cholesterol transport pathway]]
Answer D	AnswerD::Blocks cholesterol absorption at the brush border of small intestine
Answer D Explanation	[[AnswerDExp::Incorrect – Ezetimibe is an example of a drug that works by preventing cholesterol absorption in the brush border of small intestines.]]
Answer E	AnswerE::Promotes the degradation of LDL receptors
Answer E Explanation	AnswerEExp::Incorrect – Any drug which promotes the degradation of LDL receptors indirectly prevents the removal of cholesterol from the plasma, thereby leading to hypercholesterolemia
Right Answer	RightAnswer::A
Explanation	[[Explanation::Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protein encoded by the PCSK9 gene, mainly expressed in the liver, intestine and the kidneys. It has been found to promote the degradation of LDL receptors, thereby causing an increase in the serum levels of LDL cholesterol leading to poor cardiovascular outcomes. There are on-going clinical trials involving the use of monoclonal antibodies directed against this compound. Results have shown that these agents when given either subcutaneously or intravenously in combination with statins, have a synergistic effect in lowering serum LDL-cholesterol in the plasma. Source – PCSK9 Inhibition http://www.wikidoc.org/index.php/PCSK9_Inhibition Educational Objective: References: ]]
Approved	Approved::Yes
Keyword	WBRKeyword::LDL receptors, WBRKeyword::PCSK9 inhibition
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::