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What we know about the case…

What we know about the case…. 84 year old woman Estimated CrCl upon arrival: 36 mL /min BUN/ SCr : 35 Medications: Prior to admission Furosemide ( Lasix ) Rosuvastatin ( Crestor ) Oxybutynin ( Ditropan ) APAP/ Diphenhydramine (Tylenol PM) Naproxen (Aleve). What we know about the case….

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What we know about the case…

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  1. What we know about the case… • 84 year old woman • Estimated CrCl upon arrival: 36 mL/min • BUN/SCr: 35 • Medications: • Prior to admission • Furosemide (Lasix) • Rosuvastatin (Crestor) • Oxybutynin (Ditropan) • APAP/Diphenhydramine (Tylenol PM) • Naproxen (Aleve)

  2. What we know about the case… • Medications: • Hospital • Furosemide (Lasix)- D/C • Rosuvastatin (Crestor)- ∆Simvastatin • Oxybutynin (Ditropan)- D/C • APAP/Diphenhydramine (Tylenol PM)- D/C • Naproxen (Aleve)-D/C • Oral antidiabetic regimen- ∆ to insulin • Valsartan (Diovan)- dose reduced

  3. What we know about the case… • Medications: • Hospital • New medications • Ertapenem • Metoprolol tartrate • Morphine sulfate • Lorazepam • UFH 2 mg IV every 2 hours as needed for pain (Total dose on post-op day #1: 10 mg) 1 mg po q 12 hours prn

  4. What we are missing… • Last doses of home medications • Adherence an issue….but to all medications? • Alcohol and illicit substance use • Withdrawal? • Medications during surgery • Anesthetics, sedatives… • Differential diagnosis • Emergence delirium?

  5. The Framework… • Ascertain all drugs • Pre and perioperatively • Identify risks of experiencing adverse drug events • Define and confirm indications of ongoing treatment

  6. The Framework... • Review the utility of individual drugs • Class A: a very effective drug with minimal toxicity • Identify drugs that can be discontinued or have dosing modifications • Implement and monitor a pharmacotherapeutic plan • Continued reappraisal of drug utility

  7. More considerations… • Drug related problems • Interactions: drug/drug, drug/disease • Pharmacokinetic parameters • Reduced metabolic capacity • Reduced renal elimination • Reduced blood flow, renal mass, glomerular filtration rate • Altered protein binding

  8. More Considerations... • Pharmacokinetic parameters (cont) • Altered volume of distribution (Vd) • Expands for lipid soluble drugs • Decreases for water soluble drugs • Decreased muscle mass • Affects Vd • Altered metabolism • Phase I declines leading to extended T1/2 • Acute illness reduces CYP 450 enzyme activity

  9. More Considerations... • Pharmacodynamic parameters • Total anticholinergic or dopaminergic burden • Changes in receptor function • Cholinergic receptors become more sensitive • Drug and disease state interaction • Alzheimer’s disease and decrease in cholinergic reserve

  10. How this relates to Mrs. H... • Drugs are one of the common risk factors for delirium • Account for 12%-39% of all cases • Preoperative triggers: • Use of narcotics or benzodiazepines • Perioperative triggers: • Addition of three or more new medications in 24-48 hours

  11. How this relates to Mrs. H... • Drugs are one of the common risk factors for delirium • Various mechanisms are involved • Increased brain dopaminergic activity • Decreased brain cholinergic activity • Muscaranic receptor blockade • Stimulation of central GABA receptors • Crossing of blood-brain barrier

  12. Mrs. H’s drugs…Preadmission • Furosemide • Fluid and electrolyte abnormalities • Naproxen • Renal dysfunction • Blood-brain barrier • Pharmacokinetics: • T1/2: 12-15 hours • 99% protein bound • Metabolism: liver to inactive

  13. Mrs. H’s drugs…Preadmission • Diphenhydramine (25 mg) • Muscaranic receptor antagonist • Dopamine reuptake blocker • Pharmacokinetics: • T1/2: 13.5 hours ; duration up to 1.9 days • 75-85% protein bound • Metabolism: liver to inactive

  14. Mrs. H’s drugs…Preadmission • Oxybutynin • Anticholinergic • Pharmacokinetics: • T1/2: 2-3 hours; 7-8 hours for metabolite • 99% protein bound • Metabolism: liver to active metabolite

  15. Mrs. H’s drugs…Periop • Morphine • Increase release of dopamine • Neuronal Na+/K+ ATPase inhibitor • Pharmacokinetics: • T1/2: 1.5-4.5 hours • 20-36% protein bound • Metabolism: liver to inactive metabolite (minor active; codeine and normorphine)

  16. Mrs. H’s drugs…Periop • Lorazepam • Stimulation of GABA receptors • Increases dopamine, serotonin, and glutamate • Pharmacokinetics: • T1/2: 12 hours • 85-90% protein bound • Metabolism: liver to inactive metabolite

  17. Mrs. H’s drugs…Periop • Ertapenem • GABA anatgonistic properties • A hyperdopaminergic state facilitates the action of glutamate at NMDA receptors • Pharmacokinetics: • T1/2: 4-14 hours depending on kidney function • 85-95% protein bound • Metabolism: hydrolysis in kidneys to inactive metabolite

  18. Mrs. H’s drugs…Periop • Metoprololtartrate? • Blood pressure • Complex neurotransmitter related effects on brain adrenoceptors and serotonin receptors • Pharmacokinetics: • T1/2: 3-7 hours • 12% protein bound • Metabolism: extensive in liver to inactive metabolite

  19. Lessons…

  20. Questions

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