A Case Approach to Perioperative Drug-Drug Interactions

<p>Part I. Introduction to Drug-Drug Interactions</p><p>1. Let’s Start at the Very Beginning: Overcoming Fear and Gaining Mastery of Drug-Drug Interactions </p><p>F. Jacob Seagull, PhD, Catherine Marcucci, MD</p><p>2. Pharmacodynamic Interactions:  Core Concepts</p><p>Erica D. Wittwer, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>3. Pharmacokinetic Interactions:  Core Concepts</p><p>Erica D. Wittwer, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc </p><p>4. A Brief Treatise On The Area Under The Curve</p><p>Michael J. Sikora, MD, Barbara Jericho, MD</p><p>Part II. Introduction to Drug-Drug Interactions:  Brief Review of CYP450 Enzymes, UGTs, and Transporters</p><p>5. CYP2D6:  Where It All Began</p><p>John C. Sanders, MBBS, FRCA, Rachel Koll, MD, Randal O. Dull, MD, PhD                                </p><p>6. CYP2E1:  The Anesthesia Enzyme</p><p>Benjamin S. Gmelch, MD, Randal O. Dull, MD, PhD</p><p>7. CYP3A4:  The Workhorse</p><p>Jennifer DeCou, MD, Nathaniel Birgenheier, MD, Randal O. Dull, MD, PhD</p><p>8. CYP1A2:  The Switch-hitter</p><p>Danielle Roussel, MD, Emily Hagn, MD, Randal O. Dull, MD, PhD</p><p>9. CYP2B:   2B or Not 2B?</p><p>Dustin Coyle, MD, Randal O. Dull, MD, PhD</p><p>10. CYP2C9:  The Support Crew I</p><p>Byron Douglas Fergerson, MD, Crystal B. Wallentine, MD, Randal O. Dull, MD, PhD</p><p>11. CYP2C19:   The Support Crew II</p><p>Barbara Jericho, MD, Alfredo Aguiar, MD, Randal O. Dull, MD, PhD</p><p>12. UGTs:  Conjugating Cousins</p><p>Neil B. Sandson, MD</p><p>13. The Cytochrome P450 System In Disease States—A Brief Review</p><p>Catherine Marcucci, MD</p><p>PART III.   Drug-Drug Interactions:  Paradigms and Core Concepts</p><p>14. P-glycoprotein and OATP Transporters</p><p>Dustin Coyle MD, Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD</p><p>15. The  “Fatal” Forty</p><p>Neil B. Sandson MD, Michael Hutchens MD, F. Jacob Seagull, PhD, Catherine Marcucci, MD</p><p>16. The Six Patterns of Pharmacokinetic Drug-Drug Interactions</p><p>Neil B. Sandson, MD, Catherine Marcucci, MD</p><p>17. The Problem with the Drug-Drug Interaction Software: A Procrustean Dilemma</p><p>Neil B. Sandson, MD, F. Jacob Seagull, PhD, Wayne T. Nicholson, MD, PharmD, MSc, Catherine Marcucci, MD  </p><p>18. Pharmacogenomics</p><p>Chad D. Moore, PhD, William Hartman, MD, PhD, Michael Hutchens, MD, Randal O. Dull, MD, PhD</p><p>19. The Pharmacoepidemiology of Drug Interactions: Why and How They Are Important</p><p>Joseph A. Lovely, PharmD, BCPS, Stephen Esper, MD, MBA, Michael Hutchens, MD, Wayne T. Nicholson, MD, PharmD, MSc, Catherine Marcucci, MD </p><p>20. The Lawyers Can Read, Too:  Case Presentations from the Courtroom</p><p>Jessica Voge, MD, David K. Miller, JD</p><p>Part IV. Drug-Drug Interactions Involving Inhalational Anesthetic Agents</p><p>21. Introduction</p><p>Catherine Marcucci, MD</p><p>22. That Sums It Up  </p><p>Volatile anesthetics, additive MACs </p><p>James A. Jernigan, MD, James W. Ibinson, MD, PhD</p><p>23. 1+1+1+1=?  </p><p>Variable effects of combined substances</p><p>Anthony T. Silipo, DO, Raymond M. Planinsic, MD, Erica D. Wittwer, MD, PhD, Juraj Sprung MD,PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>24. A Delayed Surgeon Is A “Dismayed” Surgeon? </p><p>Nitrous oxide, dexmedetomidine, somatosensory evoked potentials</p><p>Jonathan Anson, MD</p><p>25. Relax, It’s Only Gentamicin  </p><p>Volatile anesthetics, aminoglycoside antibiotics, neuromuscular junction</p><p>Brian Gierl, MD, Ferenc E. Gyulai, MD</p><p>26. Jaundice After Surgery  </p><p>Halothane hepatitis, CYP2E1</p><p>Jonathon E. Kivela, MD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD</p><p>27. Everybody Clear?  </p><p>Halothane, epinephrine arrhythmia</p><p>Nikhli Patel, MD, Barbara Jericho MD, Randal O. Dull, MD, PhD</p><p>28. The Hemodynamic Hole  </p><p>general anesthetics, ACE-I, ARBs</p><p>Arun L. Jayaraman, MD, PhD, Theresa A. Gelzinis, MD</p><p>29. Alpha-2 To The Rescue But Beware Bradycardia  </p><p>volatile anesthetics, alpha-2 agents</p><p>Phillip Adams, DO, Nashaant N. Rizk, MD</p><p>30. Hot Stuff!  </p><p>triggering drugs, ryanodine receptor, malignant hyperthermia</p><p>Cornelius B. Groenewald, MD, ChB, Juraj Sprung, MD, PhD</p><p>Part V. Drug-Drug Interactions Involving Intravenous Anesthetic Agents </p><p>31. Introduction</p><p>Catherine Marcucci, MD</p><p>32. How to Successfully Occlude an Intravenous Line  </p><p>thiopental, succinylcholine, line precipitation</p><p>Helga Komen, MD, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD       </p><p>33. A Curious Cause of Seizures  </p><p>ketamine, theophylline</p><p>Charles Galaviz, MD, Randal O. Dull, MD, PhD</p><p>34. Magnesium Mama And The Mad Dad  </p><p>magnesium sulfate, propofol, remifentanil, vecuronium</p><p>Ana Maria Manrique MD, Catherine Marcucci, MD, Kathirvel Subramaniam, MD</p><p>35. Dexy’s Midnight Spinal  </p><p>dexmedetomidine, bupivaine spinal, multiple mechanisms, CYP3A4, CYP2D6</p><p>Michael Hutchens, MD, Edward A. Kahl, MD, Matthias J. Merkel, MD, PhD</p><p>Part VI. Drug-Drug Interactions Involving Local Anesthetics  </p><p>36. Introduction</p><p>Catherine Marcucci, MD</p><p>37. Comfortably Numb  </p><p>local anesthetics</p><p>Joseph J. Yurigan, DO, Todd M. Oravitz, MD</p><p>38. Naturally Occurring And Nasty  </p><p>cocaine, propranolol</p><p>Lauren Partyka, MD, Li Meng, MD, MPH</p><p>39. LOL-LOL:  Little Old Lady—Lots of Lido  </p><p>lidocaine, bupivacaine</p><p>Kitling M. Lum, RN, BSN, CCRN-CSC, Kelly N. Stafford, BSN, CCRN, CSC</p><p>40. The Spinal Countdown  </p><p>general anesthesia after spinal anesthesia</p><p>Audra M. Webber, MD, Franklyn P. Cladis, MD, FAAP</p><p>41. Are Drug-Drug Interactions The Smoking Guns of Local Anesthetic Toxicity?  Smoking Gun I  </p><p>Fatal Forty DDI:  ropivacaine, fluoxetine, CYP1A2, CYP3A4</p><p>L. Michele Noles, MD</p><p>42. Are Drug-Drug Interactions The Smoking Guns of Local Anesthetic Toxicity?  Smoking Gun II  </p><p>Fatal Forty DDI:  bupivacaine, methocarbamol</p><p>L. Michele Noles, MD</p><p>43. A Perfect Storm?  </p><p>Fatal Forty DDI:  omeprazole, nicardipine, diltiazem, bupivacaine, CYP3A4, CYP2C19, CYP2D6</p><p>J. Andrew Dziewit, MD, Nabil M. Elkassabany, MD</p><p>44. Shake Rattle and Roll  </p><p>Fatal Forty DDI:  lidocaine, cimetidine, CYP3A4 </p><p>Hans P. Sviggum, MD, Juraj Sprung, MD, PhD</p><p>45. Hello, We Have A Patient With Acute Delirium and We Need An Urgent Psych Consult</p><p>lidocaine, metoprolol</p><p>Katarina Bojanić, MD, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD</p><p>46. Fatal Pain Relief  </p><p>local anesthetics, intrathecal morphine</p><p>Matthew M. Kumar, MD, Richard Levi Boortz-Marx, MD, MS</p><p>47. Lipid Lifesaver  </p><p>local anesthetic, lipid emulsion</p><p>Adrian Pichurko, MD, Guy Weinberg, MD</p><p>Part VII. Drug-Drug Interactions Involving Opioids  </p><p>48. Introduction</p><p>Toby N. Weingarten, MD</p><p>49. No ‘Subs’titute for Sobriety </p><p>buprenorphine, mu agonist opioids</p><p>James Hilliard, MSN, CRNA, Kirk Lalwani, MD, FRCA, MCR</p><p>50. A Needle And The Damage Done  </p><p>Fatal Forty DDI:  buprenorphine, ritonavir, CYP3A4</p><p>James Hilliard, MSN, CRNA, Kirk Lalwani, MD, FRCA, MCR</p><p>51. Dad’s Not Having Much Pain </p><p>Fatal Forty DDI:  methadone, ciprofloxacin, CYP3A4</p><p>Rani Chovatiya, MD,  Mehmet S. Ozcan, MD, FCCP, Randal O. Dull, MD, PhD</p><p>52. Royal Flush  </p><p>Fatal Forty DDI:  methadone, nortriptyline, CYP2D6, CYP3A4</p><p>Kimberly Mauer, MD, Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>53. The Worry That’s Always With Us:  Afternoon Nap  </p><p>oxycodone, diazepam</p><p>Syed M. Quadri, DO, Randal O. Dull, MD, PhD</p><p>54. The Bawling Baby </p><p>Fatal Forty DDI:  rifampin, methadone , CYP3A4, CYP2B6 </p><p>Angela Kendrick, MD</p><p>55. Sleeping Beauty  </p><p>Fatal Forty DDI:  fentanyl, ritonavir, CYP3A4</p><p>Hans P. Sviggum, MD, Juraj Sprung, MD, PhD</p><p>56. Codeine Can’t Do It  </p><p>Fatal Forty DDI:  codeine, fluoxetine, CYP2D6</p><p>Katarina Bojanić, MD, Wayne T. Nicholson MD PharmD, MSc, Erica D. Wittwer MD, PhD, Toby N. Weingarten MD, Juraj Sprung, MD, PhD </p><p>57. A Shuddering Interaction  </p><p>meperidine, phenelzine,  serotonin toxicity</p><p>Christine A. Kenyon Laundre, MD, Randall Flick, MD, Juraj Sprung, MD, PhD</p><p>58. Double Indemnity </p><p>Fatal Forty DDI:  morphine, rifampin, P-glycoprotein</p><p>Lisa Chan, MD, Catherine Marcucci, MD, Neil B. Sandson, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>59. Breaking the Codeine  </p><p>Fatal Forty DDI:  codeine, quinidine CYP2D6</p><p>Clint Christensen, MD, Nathan G. Orgain, MD, Randal O. Dull, MD, PhD</p><p>60. The Ultimate Ultram Primer I:  My Mood Is Better, But Boy Do I Hurt!</p><p>Fatal Forty DDI:  tramadol, paroxetine, CYP2D6</p><p>Toby N. Weingarten MD, Juraj Sprung, MD, PhD</p><p>61. The Ultimate Ultram Primer II: I “Haight” Narcotics But I Hate Seizures Worse </p><p>Fatal Forty DDI:  tramadol, buproprion, seizures, CYP2D6</p><p>Bruce T. Dumser, MD, Neil B. Sandson, MD</p><p>62. The Ultimate Ultram Primer III:  Tremor-dol Trigger in Serotonin Syndrome </p><p>Fatal Forty DDI:  tramadol, paroxetine, 2D6 inhibition, serotonin syndrome</p><p>Bryan C. Hoelzer, MD, Stephanie Neuman, MD</p><p>63. Too Much of A Good Thing  </p><p>Fatal Forty DDI:  codeine, drug-gene interaction, CYP2D6</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson MD, PharmD, MSc</p><p>Part VIII. Drug-Drug Interactions Involving Non-opioid Pain Medications</p><p>64. Introduction</p><p>Toby N. Weingarten, MD</p><p>65. Pining For Pete In The Pain Clinic  </p><p>Fatal Forty DDI:  nortriptyline, paroxetine, CYP2D6</p><p>Steven S. Liu, MD, Toby N. Weingarten MD, Catherine Marcucci, MD</p><p>66. You Do Not Look Well Today, Mon Ami  </p><p>Fatal Forty DDI:  amitriptyline, amiodarone, QRS widening</p><p>Kimberly Mauer, MD, Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>67. My Headache is Gone, But My Leg Now Hurts  </p><p>Fatal Forty DDI:  methysergide, erythromycin, CYP3A4</p><p>Jessica D. Lorenz, MD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>68. Special ‘K’ase  </p><p>Oral S-ketamine, ticlopidine</p><p>Lisa Chan, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>69. Not Manic About NSAIDs  </p><p>Fatal Forty DDI:  ketorolac, lithium, toxicity</p><p>Allen N. Gustin, MD, FCCP, Michael J. Bishop, MD</p><p>70. Keep It Capped!  </p><p>acetominophen, ethanol</p><p>Christine M. Formea, PharmD, BCPS, Wayne T. Nicholson MD, PharmD, MSc</p><p>71. The ACE Is Not Always High </p><p>Fatal Forty DDI:  ketorolac, lisinopril</p><p>Wayne T. Nicholson, MD, PharmD, MSc</p><p>72. When The Smoke Clears, Relaxation Disappears  </p><p>Fatal Forty DDI:  cyclobenzaprine, smoked tobacco, CYP1A2</p><p>Avinash Ramchandani, MD, Julio A. Gonzalez-Sotomayor, MD</p><p>73. Befuddled by Aspirin  </p><p>Fatal Forty DDI:  aspirin, valproic acid, protein binding</p><p>Melisa N. Weingarten, RN, MS, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD</p><p>74. You Can’t Trick Us!  </p><p>Fatal Forty DDI:  ibuprofen, phenytoin, CYP2C9, protein binding</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>Part IX. Drug-Drug Interactions Involving Benzodiazepines and Other Sedatives</p><p>75. Introduction</p><p>Catherine Marcucci, MD</p><p>76. The Worry That’s Always With Us:  Now I’m Depressed</p><p>benzodiazepines, opioids, propofol</p><p>Kelly T. Peretich, MD, Raymond M. Planinsic, MD</p><p>77. The Worry That’s Always With Us: Tragic But Not Rare                                             alprazolam, clonazepam, and buprenorphine</p><p>Phillip Adams, DO, Ibtesam A. Hilmi, MB, CHB, FRCA</p><p>78. Lack of Sedation</p><p>Fatal Forty DDI:  midazolam, carbamazepine interaction, CYP3A4</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>79. A Cold Isn’t Going to Slow Me Down</p><p>midazolam, goldenseal, CYP3A4, CYP3A5, CYP2D6</p><p>Leelee Thames, MD, Jessica Miller, MD, BM</p><p>80. Her Patients Never Wake Up On Time</p><p>Fatal Forty DDI:  midazolam, diltiazem, alfentanil, CYP3A4, CYP3A5, CYP3A7</p><p>Toby N. Weingarten, MD, Erica D. Wittwer, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>81. When Enough Is Now Too Much</p><p>Fatal Forty DDI:  midazolam, itraconazole, CYP3A4</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>82. The Distressed Daughter</p><p>Fatal Forty DDI:  alprazolam, carbamazepine, CYP3A4</p><p>Jennifer Egan, MD, Kirk Lalwani, MD, FRCA, MCR, Catherine Marcucci, MD</p><p>83. Check Check and Double Check</p><p>Fatal Forty DDI:  diazepam, fluvoxamine, CYP3A4, CYP2C19</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>84. Doggone It—The Case is Cancelled </p><p>Fatal Forty DDI:  midazolam, lopinavir/ritonavir, CYP3A4</p><p>Erica D. Wittwer, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc, Corinne Wisdo, DPM, Catherine Marcucci, MD</p><p>85. Noct’ Out</p><p>Fatal Forty DDI:  chloral hydrate, phenobarbital, furosemide</p><p>Michael Wollenberg, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>86. Predisposed to Doze</p><p>promethazine, CYP2D6 poor metabolizer</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson MD PharmD, MSc</p><p>87. Synergistic Sedation</p><p>Fatal Forty DDI:  midazolam, clozapine, synergism and clozapine, sertraline, CYP2D6</p><p>Michael Hutchens, MD, Paul Schipper, MD, FACS, FACCP, Catherine Marcucci, MD</p><p>Part X. Drug-Drug Interactions Involving Neuromuscular Blockade Agents</p><p>88. Introduction</p><p>David G. Metro, MD</p><p>89. Blocked Again</p><p>succinylcholine, repeated doses</p><p>Matthew Patrick Feuer, MD, Thomas M. Chalifoux, MD</p><p>90. Irreversibility Sux</p><p>succinylcholine, neostigmine</p><p>Joseph C. Shy, MD, David G. Metro, MD</p><p>91. Keep An “Ion” The Twitches</p><p>magnesium, neuromuscular blockade</p><p>Brian Gierl, MD, Ferenc E. Gyulai, MD</p><p>92. A Reversal of Misfortune</p><p>neostigmine, glycopryrolate, </p><p>Thomas N. Talamo, MD, Richard J. Kuwik, MD</p><p>93. Stop Moving</p><p>Fatal Forty DDI:  vecuronium, phenytoin               </p><p>Michael D. Olson, PA-C, Randall Flick, MD   </p><p>94. There’s Just Not Enough Roc In The World</p><p>Fatal Forty DDI:  rocuronium, carbamazepine</p><p>Tammara S. Goldschmidt, MD, Randal O. Dull, MD, PhD</p><p>95. Slow Sux I:  A Lengthy Wake-Up Period After Electroconvulsive Therapy</p><p>succinylcholine, atypical plasma cholinesterase</p><p>Jennifer A. Rabbitts, MB, ChB, Juraj Sprung, MD, PhD</p><p>96. Slow Sux II:  I Remember Reviewing This For The Boards</p><p>succinylcholine, atypical plasma cholinesterase</p><p>Andrew Oken, MD, Scott Richins, MD</p><p>97. Slow Sux III:  Where Did the Twitches Go? </p><p>succinylcholine, donepizil, atypical pseudocholinesterase</p><p>Katarina Bojanić, MD, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD   </p><p>98. Weakened All Weekend</p><p>vecuronium, amakacin</p><p>Daniel W. Johnson, MD</p><p>99. The Patient Who Could Not Raise Her Head</p><p>vecuronium, gentamicin </p><p>Nicole L. Varela, MD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD</p><p>100. An Unexpected Wait</p><p>pancuronium,mivacurium </p><p>Michael W. Best, MD, Shawn T. Beaman, MD</p><p>101. Diabolical Cough Syrup</p><p>rocuronium, pholcodine </p><p>Melisa N. Weingarten, RN, MS, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD</p><p>Part XI. Drug-Drug Interactions Involving Antibiotics and Antifungals</p><p>102. Introduction</p><p>Catherine Marcucci, MD</p><p>103. Full Stop</p><p>ceftriaxone, calcium</p><p>Norah Janosy, MD</p><p>104. Flummoxed by the FLOX</p><p>Fatal Forty DDI:  ciprofloxacin, tizanidine, CYP1A2</p><p>Janice Kim, MD</p><p>105. Tales of Terror</p><p>Fatal Forty DDI:  ciprofloxacin, simvastatin, CYP3A4</p><p>Arun Subramanian, MBBS, Juraj Sprung, MD, PhD</p><p>106. Too Low To Go</p><p>Fatal Forty DDI:  erythromycin, nifedipine, CYP3A4</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>107. A Fungal Story</p><p>Fatal Forty DDI:  fluconazole, phenytoin, CYP2C9, CYP2C19</p><p>Jerusha Taylor, PharmD, BCPS, Ansgar M. Brambrink, MD, PhD</p><p>108. Rejection Protection Turned Kidney Killer</p><p>Fatal Forty DDI:  voriconazole, tacrolimus, CYP3A4, P-glycoprotein</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Christine M. Formea, PharmD, BCPS</p><p>109. Can’t Get Well</p><p>Fatal Forty DDI:  itraconazole, budesonide, CYP3A4</p><p>Michael J. Sikora, MD, Barbara Jericho, MD, Randal O. Dull, MD, PhD</p><p>110. Linezolid (I): Be VREy Careful</p><p>Fatal Forty DDI:  linezolid, buproprion</p><p>Bruce T. Dumser, MD</p><p>111. Linezolid (II):  Hyper and Hot</p><p>linezolid, meperidine, serotonin syndrome</p><p>Erica D. Wittwer, MD, PhD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD</p><p>112. Not Sweet At All</p><p>Fatal Forty DDI:  trimethoprim/sulfamethoxazole, glipizide, CYP2C9</p><p>Mayumi Horibe, MD, Michael J. Bishop, MD</p><p>113. Where Did All The Sugar Go?</p><p>Fatal Forty DDI:  levofloxacine, glyburide, complex interaction</p><p>Nicole L. Varela, MD, Federica Scavonetto, MD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD</p><p>114. Exposed! (Part 1)</p><p>Fatal Forty DDI: rifampin, buspirone, CYP3A4 </p><p>L. Michele Noles, MD, Catherine Marcucci, MD</p><p>115. Exposed! (Part 2)</p><p>Fatal Forty DDI: rifampin, ondansetron, CYP3A4</p><p>L. Michele Noles, MD, Catherine Marcucci, MD</p><p>116. Seizures on 5 West</p><p>carbapenem, valproic acid, P-glycoprotein, UGT</p><p>Elizabeth Duggan, MD, Nabil M. Elkassabany, MD</p><p>Part XII. Drug-Drug Interactions Involving Cardiovascular Medications</p><p>117. Introduction</p><p>Michael Hutchens, MD</p><p>118. Riding The Rollercoaster</p><p>nitroglycerine, sodium nitroprusside, propofol, </p><p>Catherine Marcucci, MD, Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD</p><p>119. A Pressing Need For Vasopressin!</p><p>ACE-Is, general anesthesia</p><p>Erin B. Payne, MD, Anna Dubovoy, MD</p><p>120. Too Young To Die</p><p>Fatal Forty DDI: bupropion, pseudoephedrine, pharmacodynamic interaction</p><p>Catherine Marcucci, MD</p><p>121. A Widening Gyre</p><p>epinephrine, phosphorus, insulin</p><p>Edward A. Kahl, MD, Michael Hutchens, MD</p><p>122. Misusing Mom’s Meds</p><p>chronic amphetamine, indirect acting sympathomimetics</p><p>Pulsar Li, DO, Steven L. Orebaugh, MD</p><p>123. If the Patient Has No Renal Failure, Why is Her Potassium So High?</p><p>candesartan,  spironolactone, </p><p>Jennifer A. Rabbitts, MB, ChB, Wayne T. Nicholson, MD, PharmD, MSc, Juraj Sprung, MD, PhD</p><p>124. Prazosin and the PTSD Paratrooper</p><p>prazosin, tadalafil, </p><p>Allen N. Gustin, MD, FCCP, Michael J. Bishop, MD</p><p>125. Nicardipine Notes</p><p>Fatal Forty DDI: nicardipine, tacrolimus, CYP3A4</p><p>Nenna Nwazota, MD, Randal O. Dull, MD, PhD</p><p>126. Hypotension Harry</p><p>Fatal Forty DDI: nicardipine, clarithromycin, CYP3A4</p><p>Matthew Hart, MSN, CRNA, Bryan J. Read, MSN,CRNA, Wayne T. Nicholson, MD, PharmD, MSc, Toby N. Weingarten, MD</p><p>127. Too Slow to Flow </p><p>Fatal Forty DDI: CYP2D6 ultraslow metabolism of metoprolol</p><p>Scott W. Cantwell, MD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD</p><p>128. Better Sleep But Slower Heart</p><p>metoprolol, diphenhydramine, CYP2D6</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD</p><p>129. Extreme Blood Pressure After Ephedrine:  Should We Rule Out Pheochromocytoma?</p><p>ephedrine, selegiline</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>130. Heart-Stopping Treatment</p><p>Fatal Forty DDI: verapamil, erythromycin, CYP3A4</p><p>Erica D. Wittwer, MD, PhD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD</p><p>131. Induction Crashes:  Are There Clues In the Ashes?</p><p>Fatal Forty DDI: theophylline, smoked tobacco, CYP1A2</p><p>Dawn L. Baker, MD, MS, L. Lazarre Ogden, MD</p><p>132. The Wakeup Call: 2AM Trauma</p><p>beta blockers, cocaine</p><p>Devin C. Tang, MD, Nabil M. Elkassabany, MD</p><p>133.  Falling Down</p><p>Fatal Forty DDI: nifedipine, fluoxetine, CYP3A4</p><p>Scott Kennedy, MD, Norman A. Cohen, MD</p><p>134. A Hidden Drug</p><p>Fatal Forty DDI: diltiazem, sildenafil, CYP3A4 and sildenafil, nitroglycerin</p><p>Helga Komen, MD, Toby N. Weingarten, MD, Juraj Sprung, MD, PhD       </p><p>135. I’m Listening, I’m Listening</p><p>Fatal Forty DDI: diltiazem, carbamazepine, CYP3A4 </p><p>Catherine Marcucci, MD, Jerusha Taylor, PharmD, BCPS, Ansgar M. Brambrink, MD, PhD, Neil B. Sandson, MD</p><p>136. Jump Start My Heart</p><p>metoprolol, amiodarone              , CYP2D6, CYP1A2</p><p>Katarina Bojanić, MD, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD</p><p>137. The Statin Trilogy (I): ‘Statin’ From The Beginning</p><p>Fatal Forty DDI: simvastatin, cimetidine, diltiazem, CYP3A4</p><p>Brian Mitchell, MD</p><p>138. The Statin Trilogy (II): Tripped And Fell At The Train ‘Statin’</p><p>Fatal Forty DDI: simavastatin, itraconazole, CYP3A4</p><p>Brian Mitchell, MD</p><p>139. The Statin Trilogy (III): Welcome To The United ‘Statins’ Of America</p><p>Fatal Forty DDI:  atorvastatin, phenytoin, CYP3A4</p><p>Brian Mitchell, MD</p><p>140. Be Still, My Beating Heart</p><p>Fatal Forty DDI: amiodarone, digoxin, P-glycoprotein </p><p>Branka Polić, MD, MSc, Julije Meštrović, MD, PhD, Toby N. Weingarten,                MD, Juraj Sprung, MD, PhD</p><p>141. The Nice Niece</p><p>digoxin, St. John’s wort, CYP3A4, P-glycoprotein</p><p>Michael Hutchens, MD, Catherine Marcucci, MD</p><p>142. Cyclo Killer: Qu’est-ce que c’est?</p><p>carvedilol, cyclosporine, P-glycoprotein</p><p>Jeff Chen, MD, Michael Hutchens, MD, Wayne T. Nicholson MD, PharmD, MSc</p><p>143. Blurry-Eyed With Rapid Heart Beats</p><p>Fatal Forty DDI: digoxin, hydrochlorothiazide, </p><p>William A. Shakespeare, MD, Juraj Sprung, MD, PhD</p><p>Part XIII. Drug-Drug Interactions Involving Coagulation Modifiers</p><p>144. Introduction</p><p>Catherine Marcucci, MD</p><p>145. Seize the Day</p><p>Fatal Forty DDI: tranexamic acid, furosemide, ibuprofen   </p><p>Roman M. Sniecinski, MD, Erica D. Wittwer, MD, PhD, Kenichi Tanaka, MD, MSc, James Zaidan, MD</p><p>146. The Third and Final Complication</p><p>Fatal Forty DDI: warfarin, nafcillin   </p><p>Daniel W. Johnson, MD</p><p>147. An Interaction With the Furniture</p><p>Fatal Forty DDI: warfarin, metronidazole, ciprofloxacin, CYP2C9, CYP1A2</p><p>Heather Norvelle, PharmD, BCPS, Ines P. Koerner, MD, PhD</p><p>148. Macrolide Mishap for Little Miss Muffett</p><p>Fatal Forty DDI: warfarin, clarithromycin, CYP2C9</p><p>Elizabeth Pedigo, MD</p><p>149. From Asymptomatic to Symptomatic:  a Cause of Nosebleed</p><p>Fatal Forty DDI: warfarin, amiodarone, CYP2C9</p><p>Joško Markić, MD, MSc, Julije Meštrović, MD, PhD, Juraj Sprung, MD, PhD</p><p>150. The Consequences of Not Following A Cardiac Diet</p><p>Fatal Forty DDI: clopidogrel, omeprazole, CYP2C19</p><p>Kristen B. McCullough, PharmD, BCPS, BCOP, Wayne T. Nicholson, MD, PharmD, MSc</p><p>151. Clopidogrel (I):  Bagel Brunch</p><p>Fatal Forty DDI: clopidogrel, omeprazole, CYP2C19</p><p>Ann Marie Canelas, MD, Randal O. Dull, MD, PhD</p><p>152. Clopidogrel (II):  Conferring Over The Kung Pao</p><p>clopidogrel, proton pump inhibitors, calcium channel blockers, CYP2C19, CYP3A4</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>Part XIV. Drug-Drug Interactions Involving Immunosuppressants, Antiemetics, and Chemotherapy</p><p>153. Introduction</p><p>Catherine Marcucci, MD</p><p>154. Beaned</p><p>Fatal Forty DDI:  diltiazem, tacrolimus, CYP3A4, P-glycoprotein</p><p>Matthew Hart, MSN, CRNA, Michael Hutchens, MD                                                                                         </p><p>155. Addisonian Adjustment</p><p>Fatal Forty DDI: prednisone, fluconazole, CYP3A4</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>156. Tea Time</p><p>Fatal Forty DDI: St. John’s Wort, tacrolimus, cyclosporine, CYP3A4, P-glycoprotein</p><p>Nikki Jaworski, MD</p><p>157.  No Fits at Uffizi</p><p>Fatal Forty DDI: phenytoin, cyclosporine, CYP3A4</p><p>Michael Hutchens, MD, Christine M. Formea, PharmD, BCPS</p><p>158. Quit Steroids Quit Kidneys</p><p>steroid, tacrolimus, CYP3A, P-glycoprotein</p><p>Toby N. Weingarten, MD, Wayne T. Nicholson, MD, PharmD, MSc, Christine M. Formea, PharmD, BCPS</p><p>159. The Fall Guy (I)</p><p>Fatal Forty DDI: tamoxifen, metoclopramide, CYP2D6</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>160. The Fall Guy (2)</p><p>Fatal Forty DDI: tamoxifen, diphenhydramine, CYP2D6</p><p>Catherine Marcucci, MD, Neil B. Sandson, MD</p><p>161. The Topic of the Day</p><p>Fatal Forty DDI: cimetidine, lidocaine, CYP1A2, CYP3A4</p><p>Catherine Marcucci, MD</p><p>162. Bounce Back</p><p>ondansetron, CYP2D6 ultrarapid metabolism</p><p>Erica D. Wittwer, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc, Juraj Sprung, MD, PhD</p><p>163. Call The Cath Lab! </p><p>Fatal Forty DDI: omeprazole, clopidogrel, CYP2C19</p><p>Anna Dubovoy, MD, Erin B. Payne, MD</p><p>164. The Imatinib Inquiry:  A Theoretical Case (For Now)</p><p>imatinib, metoprolol, midazolam, fentanyl, CYP3A4</p><p>Stephen J. Gleich, MD, Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Nicole Henwood, MD</p><p>165. A HAART-Breaking Tale</p><p>metformin, tenofovir</p><p>Dean Laochamroonvorapongse, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>Part XV. Drug-Drug Interactions Involving Neuropsychiatric Drugs </p><p>166. Introduction</p><p>Neil B. Sandson, MD</p><p>167. Phenytoin (I): Going Crazy!</p><p>Fatal Forty DDI: phenytoin, quetiapine, CYP3A4</p><p>Sara M. Skrlin, MD, Ansgar M. Brambrink, MD, PhD</p><p>168. Phenytoin (II):  The Wrong Drug for the Schizophrenic</p><p>Fatal Forty DDI: phenytoin, quetiapine, CYP3A4</p><p>Melisa N. Weingarten, RN, MS, Juraj Sprung, MD, PhD, Toby N. Weingarten, MD</p><p>169. Dizzy and Depressed</p><p>Fatal Forty DDI: nefazodone, carbamazepine, CYP3A4</p><p>William A. Shakespeare, MD, Juraj Sprung, MD, PhD</p><p>170. The Funeral Is On Monday</p><p>Fatal Forty DDI: phenytoin, valproic acid, CYP2C9</p><p>Elizabeth Macri, MD, Ansgar M. Brambrink, MD, PhD, Neil B. Sandson, MD</p><p>171. This Antacid Is Making Me Sick!</p><p>Fatal Forty DDI: phenytoin, cimetidine, CYP2C9, CYP2C19</p><p>Arun Subramanian, MBBS, Toby N. Weingarten MD, Juraj Sprung, MD, PhD</p><p>172. Young at Heart</p><p>Fatal Forty DDI: pimozide, nefazodone, CYP3A4</p><p>Catherine Marcucci, MD</p><p>173. Shiver Yes, Die No –</p><p>selegiline patch, meperidine, serotonin syndrome</p><p>Ahmed F. Zaky, MD, MPH, Michael J. Bishop, MD</p><p>174. Clip and Dip</p><p>Fatal Forty DDI: carbamazepine, felodipine, CYP3A4</p><p>David W. Barbara, MD, Randall Flick, MD, Juraj Sprung, MD, PhD</p><p>175. Blue Fog</p><p>citalopram, methylene blue, serotonin syndrome</p><p>Toby N. Weingarten, MD, Wayne T. Nicholson, MD, PharmD, MSc, Juraj Sprung, MD, PhD</p><p>176. Confiscated Contraceptives</p><p>Fatal Forty DDI: lamotrigene, ethinylestradiol, UGT1A4</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD PharmD, MSc</p><p>177. Gotta Love Derm</p><p>Fatal Forty DDI: lamotrigine, valproic acid, UGT1A4</p><p>Jonathan Anson, MD, Richard C. Month, MD</p><p>178. Desperate for A Drink</p><p>Fatal Forty DDI: amitriptyline, CYP2D6 poor metabolizer</p><p>Erica D. Wittwer, MD, PhD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>Part XVI. Drug-Drug Interactions Involving QT Prolonging DDIs</p><p>179. Introduction</p><p>Matthew DeCaro, MD, FACC, FACP</p><p>180. Delusion At Heart</p><p>Fatal Forty DDI: thioridazine, ondanestron, QT-prolongation</p><p>Arun Subramanian, MBBS, Toby N. Weingarten, MD, Juraj           Sprung, MD, PhD</p><p>181. At Long Last</p><p>Fatal Forty DDI: ziprasidone, moxifloxacin, CYP3A4, CYP2D6, QT-prolongation,</p><p>Kristen B. McCullough, PharmD, BCPS, BCOP, Wayne T. Nicholson, MD, PharmD, MSc</p><p>182. Metha-don’t!</p><p>Fatal Forty DDI: methadone, amitriptyline, levofloxacin,  CYP2D6 , QT-prolongation</p><p>Bryan C. Hoelzer, MD, Juraj Sprung, MD, PhD, Wayne T. Nicholson, MD, PharmD, MSc</p><p>183. Flash Fire</p><p>amiodarone, haloperidol, CYP1A2, CYP3A4, CYP2D6, QT-prolongation,</p><p>Michael Hutchens, MD, Catherine Marcucci, MD, Neil B. Sandson, MD </p><p>184. I Am Dizzy When I Stand Up</p><p>Fatal Forty DDI: thioridazine, propranolol, CYP2D6,  QT-prolongation,</p><p>Tasha L. Welch, MD, Toby N. Weingarten, MD, Juraj Sprung MD, PhD</p><p>Part XVII. Drug-Drug Interactions Involving Foods and Nutrition</p><p>185. Introduction</p><p>Kevin W. Cleveland, PharmD, David G. Metro, MD</p><p>186. High Fat Diet (I): No Juice For The Ketotic Kid</p><p>ketosis, carbohydrates, seizures</p><p>Denise M. Hall Burton, MD, Miya Asato, MD, Charles Boucek, MD</p><p>187. Protein Huffing and Puffing</p><p>theophylline, dietary protein, CYP1A2</p><p>Brian C. Bane, MD, James Gordon Cain, MD, MBA, FAAP</p><p>188. Salty Sam</p><p>high salt diet, nitroprusside</p><p>Robert Scott Lang, MD, Li Meng, MD, MPH</p><p>189. A Peak Potassium Problem</p><p>salt substitute, spironolactone, lisinopril</p><p>Justin McCray, MD, Steven L. Orebaugh, MD</p><p>190. Awake?</p><p>vitamin C, general anesthetics</p><p>Nicole Scouras, MD, David G. Metro, MD</p><p>191. Tropical Punch Packing a Real Knockout</p><p>Fatal Forty DDI: grapefruit juice, midazolam, CYP3A4</p><p>Brian Blasiole, MD, PhD, Shawn T. Beaman, MD</p><p>192. When The Fire Won’t Go Out</p><p>pomegranate juice, sildenafil, CYP3A4</p><p>Thomas P. Pontinen, MD, Randal O. Dull, MD, PhD</p><p>193. Peppermint Patty</p><p>Fatal Forty DDI: peppermint, felodipine, CYP3A4</p><p>Ryan D. Ball, MD, Karen Boretsky, MD</p><p>194. From Bleeding Gums to Green Thumbs- A True Story</p><p>Fatal Forty DDI: warfarin, green vegetables  </p><p>Audra M. Webber, MD, Patricia L. Dalby, MD</p><p>195. Delicious but Malicious</p><p>licorice, spironolactone, hypokalemia</p><p>Eric Fox, BA, Kirk Lalwani, MD, FRCA, MCR</p><p>196. I Just Can’t Lick This Problem</p><p>Fatal Forty DDI: licorice, electrolytes, digoxin  </p><p>Koshy M. Mathai, MD, Michael Hutchens, MD, Robert G. Krohner, MD</p><p>197. Sommelier’s Surprise</p><p>tyramine rich foods, MAO-i drugs, monoamine oxidase</p><p>Charles Lin, MD, Joseph F. Talarico, DO</p><p>198. Dairy Carefully</p><p>Fatal Forty DDI: dairy, fluoroquinolone  </p><p>Kristin Ondecko Ligda, MD, Erin A. Sullivan, MD</p><p>199. Cold And Sick, Sick And Cold</p><p>fiber, thyroxine replacement, malabsorption</p><p>A. Murat Kaynar, MD, MPH, Nikhil K. Bhatnagar, MD</p><p>200. TPN (I):  A Review and Two Interactions</p><p>TPN basics and complications</p><p>Lavinia Kolarcyzk, MD, Patrick J. Forte, MD</p><p>201. TPN (II):  A Traumatic Case of Increased Metabolism</p><p>TPN, valproic acid</p><p>Erica D. Wittwer, MD, PhD, Wayne T. Nicholson, MD, Pharm D, MSc, Juraj Sprung, MD, PhD</p><p>202. Skin and Bones</p><p>starvation, perioperative drugs</p><p>Mariam M. El-Baghdadi, MD, Ibtesam A. Hilmi, MB, CHB, FRCA</p><p>203. Enough to Make You Sick</p><p>syrup of ipecac, general anesthesia</p><p>John Hache, MD, Thomas M. Chalifoux, MD</p><p>204. Determined and Desperate to Diet</p><p>Fatal Forty DDI: Orlistat, warfarin</p><p>Lisa Chan, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>Part XVIII. Drug-Drug Interactions Involving Spices and Supplements </p><p>205. Introduction</p><p>Kirk Lalwani, MD, FRCA, MCR</p><p>206. Caffeine Crash</p><p>Fatal Forty DDI: caffeine, ethinylestradiol, ciprofloxacin, CYP1A2 </p><p>Brian Gierl, MD, Ryan Romeo, MD  </p><p>207. Sad Sequelae</p><p>Fatal Forty DDI: Dong quai, warfarin</p><p>Stacy L. Fairbanks, MD</p><p>208. The Scary Side of Ginkgo Biloba Is No Match For An Anesthesia Superstar: Seizures</p><p>Ginkgo biloba, phenytoin, CYP2C19</p><p>Shreya Patel, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>209. The Scary Side of Ginkgo Biloba Is No Match For An Anesthesia Superstar:  Sugar</p><p>Ginkgo biloba, tolbutamide, CYP2C9</p><p>Shreya Patel, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>210. The Scary Side of Ginkgo Biloba Is No Match For An Anesthesia Superstar: Subdural</p><p>Ginkgo biloba</p><p>Shreya Patel, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>211. “Khat” Unawares</p><p>depletion of central and peripheral endogenous catecholamines</p><p>Brian D. Tompkins, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>212. Pain on the Plane</p><p>Fatal Forty DDI: ginseng, warfarin, CYP2C9 </p><p>Lei Wu, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>213. Ca va, c’est Kava</p><p>kava,carbidopa-levodopa, dopamine receptors</p><p>Solina Tith, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>214. Summertime and the Herbals are Hot</p><p>Fatal Forty DDI: goldenseal, amitriptyline CYP2D6, CYP3A4</p><p>Jessica Miller, MD, BM, Leelee Thames, MD</p><p>215. Garlic I:  More Than Just Bad Breath</p><p>Fatal Forty DDI: garlic, ritonavir, CYP3A4, P-glycoprotein</p><p>Vincent Lew, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>216. Garlic II:  A Girl Named Allicin</p><p>garlic, inhibition of clotting cascade</p><p>Vincent Lew, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>217. “Danshen” the Night Away</p><p>Fatal Forty DDI: Salvia miltiorrhiza, warfarin, CYP2C9, CYP1A2</p><p>Tara C. Carey, BA, MD, Kirk Lalwani, MD, FRCA, MCR</p><p>218. Caught Yellow-Handed</p><p>Fatal Forty DDI: tumeric, warfarin, CYP1A2, CYP2C9</p><p>Giorgio Veneziano, MD, Michael Mangione, MD</p><p>219. St. John:  Not Such A Saint</p><p>Fatal Forty DDI: St. John’s Wort, cyclosporine, CYP3A4, P-glycoprotein</p><p>Heather Norvelle, PharmD, BCPS, Ines P. Koerner, MD, PhD</p><p>220. Hearing the News</p><p>Fatal Forty DDI: St. John’s Wort, oral contraceptives, CYP3A4, P-glycoprotein</p><p>Nikki Jaworski, MD</p>