1. UMMS CRIT Module II: Pharmacist Case Review Abir O. Kanaan, PharmD Associate Professor of Pharmacy Practice Massachusetts College of Pharmacy and Health Sciences

2. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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)

3. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

4. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

5. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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?

6. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation The Framework… Ascertain all drugs –Pre and perioperatively Identify risks of experiencing adverse drug events Define and confirm indications of ongoing treatment

7. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

8. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

9. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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 T 1/2 Acute illness reduces CYP 450 enzyme activity

10. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

11. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

12. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation 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

13. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Preadmission Furosemide –Fluid and electrolyte abnormalities Naproxen –Renal dysfunction –Blood-brain barrier –Pharmacokinetics: T 1/2 : 12-15 hours 99% protein bound Metabolism: liver to inactive

14. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Preadmission Diphenhydramine (25 mg) –Muscaranic receptor antagonist –Dopamine reuptake blocker –Pharmacokinetics: T 1/2 : 13.5 hours ; duration up to 1.9 days 75-85% protein bound Metabolism: liver to inactive

15. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Preadmission Oxybutynin –Anticholinergic –Pharmacokinetics: T 1/2 : 2-3 hours; 7-8 hours for metabolite 99% protein bound Metabolism: liver to active metabolite

16. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Periop Morphine –Increase release of dopamine –Neuronal Na+/K+ ATPase inhibitor –Pharmacokinetics: T 1/2 : 1.5-4.5 hours 20-36% protein bound Metabolism: liver to inactive metabolite (minor active; codeine and normorphine)

17. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Periop Lorazepam –Stimulation of GABA receptors Increases dopamine, serotonin, and glutamate –Pharmacokinetics: T 1/2 : 12 hours 85-90% protein bound Metabolism: liver to inactive metabolite

18. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Periop Ertapenem –GABA anatgonistic properties A hyperdopaminergic state facilitates the action of glutamate at NMDA receptors –Pharmacokinetics: T 1/2 : 4-14 hours depending on kidney function 85-95% protein bound Metabolism: hydrolysis in kidneys to inactive metabolite

19. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Mrs. H’s drugs…Periop Metoprolol tartrate? –Blood pressure –Complex neurotransmitter related effects on brain adrenoceptors and serotonin receptors –Pharmacokinetics: T 1/2 : 3-7 hours 12% protein bound Metabolism: extensive in liver to inactive metabolite

20. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Lessons…

21. UMMS CRIT 2012 Module II: Pharmacist Case Review Advancing Geriatrics Education (AGE) A UMMS initiative funded by the Donald W. Reynolds Foundation Questions