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Pit Vipers, Fat Lips and Personalized Medicine

Pit Vipers, Fat Lips and Personalized Medicine. Nancy J. Brown, MD. Funding: HL079184, HL065193 Consulting: Merck, Novartis, Forest, Via Investigation drug: icatibant . Drugs that interrupt the renin-angiotensin-aldosterone system save lives. DRI X. X. X MR antag.

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Pit Vipers, Fat Lips and Personalized Medicine

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  1. Pit Vipers, Fat Lips and Personalized Medicine Nancy J. Brown, MD Funding: HL079184, HL065193 Consulting: Merck, Novartis, Forest, Via Investigation drug: icatibant

  2. Drugs that interrupt the renin-angiotensin-aldosterone system save lives DRI X X X MR antag ARB X

  3. Risk of ACE inhibitor-associated angioedema is increased in black Americans Utilized Tennessee Medicaid database Confirmed cases by chart review Compared rates of angioedema blacks and whites taking ACE inhibitors Normalized to rates in patients taking a calcium channel blocker Brown Clin Pharmacol Ther 1996

  4. Mechanism(s) of ACE inhibitor-associated angioedema

  5. KHPM KHPM pKK FXI Leu10 Met11 C Arg1 Pro2 Lys3 Pro4 Gln5 Gln6 Phe7 Phe8 Gly9 C Arg1 Pro2 Pro3 Gly4 Phe5 Ser6 Pro7 Phe8 Arg9 Arg1 Pro2 Pro3 Gly4 Phe5 Ser6 Pro7 Phe8 C Negative surface - - - FXII Substance P FXIIa FXIa KK C1INH KHPM APP ACE CPN DPPIV NEP Activation of the intrinsic coagulation pathway KK Bradykinin Des Arg9-BK

  6. DPPIV deficiency increases susceptibility to ACE inhibitor-induced peritracheal edema Byrd et al J Allergy ClinImmunol 2008

  7. DPPIV inhibitor use is associated with increased risk of ACEi angioedema Brown et al Hypertension 2009

  8. A Healthy Tension “Personalized Medicine” “Evidenced-based Medicine” “Comparative Efficacy” “Blockbuster Drugs” from Monty Python

  9. Thank you Alencia Woodard-Grice, PhD Libby Stone, RN Brian Byrd, MD Annis Marney, MD Marie Griffin, MD Wayne Ray, PhD Division of Pharmacoepidemiology Albert Adam, PhD University of Montreal

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