WBR0881

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A new drug is being developed for the treatment of intermittent claudication. One of the main studied mechanisms of action of this drug is the inhibition of phosphodiesterase III leading to arterial vasodilation to improve blood flow to ischemic areas and decrease the symptoms of claudication. What would you expect drugs with a similar mechanism of action to have as added benefit?]]
Answer A	AnswerA::Slowing of atherosclerotic vessel changes
Answer A Explanation	AnswerAExp::Although cilostazol was shown to decrease smooth muscle migration in a few studies this was not considered a class effect of PDE3 inhibitors.
Answer B	AnswerB::Inhibition of platelet aggregation
Answer B Explanation	AnswerBExp::PDE3 inhibitors lead to cAMP accumulation that inhibits platelet aggregation.
Answer C	AnswerC::Conversion of plasminogen to plasmin
Answer C Explanation	AnswerCExp::Thrombolytics such as alteplase and reteplase break down formed fibrin clots by activating plasminogen into plasmin.
Answer D	AnswerD::Dulling of inflammatory response
Answer D Explanation	AnswerDExp::PDE3 inhibitos have not been involved in the diminution of the inflammatory response. Drugs such as aspirin, ibuprofen, and celecoxib are used as anti-inflammatory drugs.
Answer E	AnswerE::Curing erectile dysfunction
Answer E Explanation	AnswerEExp::PDE5 inhibitors cause accumulation of cGMP helping cure erectile dysfunction. PDE3 inhibitors are not used in patients with ED.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Phosphodiesterase III (PDE3) inhibitors such as cilostazol and dipyridamole are potent vasodilators that can be used in the treatment on intermittent claudication. By inhibiting PDE3, cAMP accumulates leading to the activation of protein kinase A (PKA). PKA in turn leads to the inhibition of myosin light-chain kinase (MLCK) causing the vascular smooth muscle to relax. Another important effect of PDE3 inhibition and cAMP accumulation is the inhibition of platelet aggregation. PDE3 inhibitors have also been used clinically for TIA and stroke prevention and have been shown to be a potent antithrombotic agent when compared with aspirin or ADP receptor blockers. Educational Objective: PDE3 inhibitors cause cAMP accumulation leading to vasodilation as well as a decrease in platelet aggregation. References: Schror K. The pharmacology of cilostazol. Diabetes Obes Metab. 2002;4(s2):S14-S19.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Dipyridamole, WBRKeyword::Cilostazol, WBRKeyword::PDE3 inhibitors, WBRKeyword::Vasodilation, WBRKeyword::cAMP, WBRKeyword::Platelet aggregation
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