The Case of Mr L: Stuck on Sinemet

1. The Case of Mr L:Stuck on Sinemet Nicole Boyko, MSPT

2. Case Overview: Mr. L • 73 y/o male with long hx of Parkinson’s disease • Retired intellectual, very respected in his day • Admitted to hospital for paranoid ideation • Believes he discovered Sinemet and that it is an absolute cure for Parkinson’s • Increased his dosage of Sinemet without physician consent • Near overdose-levels by the time family discovered what he was doing • Transferred to SNF for subacute rehab as pt required further medical mgmt and rehab prior to safe D/C home

3. Case Overview Con’t • Medications: Carbidopa/Levadopa SR • Pt previously treated with supportive measures including IV fluids and prophylactic anti-arrhythmic therapy due to near overdose • At entry to SNF, pt emerging from drug holiday with dose ½ pre-holiday MD-prescribed dose • Services Requested • Skilled Nursing • Physical Therapy • Occupational Therapy

4. Initial Rehab Evaluation Subjective: “ My Sinemet is not in effect. Therefore, I can’t walk. Please tell the doctor I need my medication.” Cognition: A + O to person, place; agitated; easily confused; suffering from ideational paranoia Memory: recalls 1/3 words in 15 min Appearance: obviously behind in grooming- hair and nails need to be cut; poor dental hygiene

5. Initial Rehab Evaluation Cont’ Objective • ROM/Tone: ROM WFLs for age; however, mild cogwheel rigidity noted in LEs > UEs (B) • Strength: Pt eliciting little effort; grossly 4- to 4/5 (B) UEs and LEs • Sensation/Proprioception: intact throughout • Fxnl Mobility • Sup>Sit: min (A) x 2 • Sit>Stand: mod (A) x 2; max (A) x 2 to maintain standing • Gait: Max (A) x 2 to take a few steps with RW; pt stating “I can’t do it without medicine;” poor trunk control

6. Problem List Impaired cognition Impaired fxnl mobility Impaired static and dynamic balance Altered muscle tone Impaired strength Impaired ability to perform basic ADLs Goals Pt initially goaled by PT/OT for min/mod (A) x 1 for all fnxl mobility and ADLs Prognosis Initial prognosis: fair- poor Pt thought to need LTC placement Initial Rehab Evaluation Cont’

7. Spotlight on Carbidopa/LevadopaBrand Name: Sinemet/Sinemet CR • Pharmacodynamics Mode of Action: • Disease due to depletion of dopamine (DA) in brain • DA itself is ineffective in Rx as unable to cross blood-brain barrier • Levadopa (L-Dopa): precursor to DA • Ability to cross blood-brain barrier and convert to DA • Rapidly decarboxylated in extracerebral tissues so large dose required for adequate amt to reach CNS • Competes with amino acids for GI absorption • impaired absorption for pts on high protein diets • Action of L-Dopa reversed in presence of Vit B6

8. Pharmacodynamics cont’ Mode of Action Cont’: • Carbidopa • Inhibits the breakdown of Levadopa in the PNS • Inhibits effect of Vit B6 on L-Dopa • Does not cross blood-brain barrier so does not affect metabolism of L-Dopa once in CNS • Decreases the amt of Levadopa required by 75% • Increases plasma levels and plasma half-life of L-Dopa • Decreases incidence of nausea/vomiting that would be associated with large doses of L-Dopa

9. Pharmacodynamics cont’ Variables • Diet: high protein interferes with body’s response to levodopa; dietary protein must be spaced throughout day • Breast-feeding: Sinemet may reduce the flow of breast milk; studies unclear on whether drug is present in breast milk • Age: not cleared for safe use on children; elderly individuals have a high sensitivity to Sinemet and may exhibit increased side effects • Comorbidities: may worsen COPD, CAD, melanoma, Sz disorder or mental illness; may alter the amt of insulin needed in diabetic pts; pts with kidney or liver disease may exhibit increased side-effects

10. Pharmocokinetics • Absorption • Administered orally • Food increases the extent of availability and peak concentration of carbidopa by 50% and levadopa by 25% • Tablets may be broken in half but not crushed or chewed • Excess stomach acidity will delay absorption of levadopa • Iron salts will  amount of levadopa and carbidopa available to body

11. Pharmacokinetics Cont’ • Absorption cont’ • Bioavailability of Sinemet • Levadopa: 71% Sinemet CR, 99% Sinemet IR* • Carbidopa: 58% Sinemet CR relative to Sinemet • Carbidopa s amt of L-Dopa needed by 75% • Sinemet CR releases medication over 4-6 hrs so blood levels maintained longer * CR= Controlled Release; IR= Immediate Release

12. Pharmacokinetics Cont’ • Elimination • Half-life • Levadopa: 50 min • Carbidopa/Levadopa IR: 1.5 hrs • Apparent half-life longer with CR • Mean time for peak concentration • IR: 30 min • CR: 2 hrs • Steady state: average trough levels of L-Dopa at steady state 2-fold higher with CR tabs vs. IR tabs

13. Dosing • Available forms: 1:4 or 1:10 ratio of Carbidopa/Levadopa • 25/100, 25/250 or 10/100 IR, 50/200 or 25/100 SR • Initial dose • IR: 1 tab 25/100 tid or 2 tabs 10/100 qid • SR: 1 tab 50/200 or 25/100 bid • Usual dose • IR: 30/300-150/1500 mg daily • CR: 50/200-500/2000 mg daily • When transferring from L-Dopa alone to Sinemet, L-Dopa D/C’d 8-12 hrs ahead of time

14. Nausea Vomiting Tachycardia Orthostatic hypotension Anorexia Dizziness Chorea Dystonia Depression Paranoid ideation Somnolence Asthenia On/Off syndrome Wearing Off syndrome Adverse Effects

15. Drug Interactions • Antihypertensives: can cause postural hypotension • Tricyclic antidepressants: rarely can result in HTN and dyskinesia • Non-selective MOA-inhibitors contraindicated for use with Sinemet due to extreme HTN • MOA type B inhibitors can be used with Sinemet CR • Phenothiazines, butyrophenones, phenytoin and papaverine may decrease the effect of L-Dopa

16. Suggested Rehab Considerations for patients on Sinemet • Most ideal time for treatment is early am, ½- 1hr after am dose of Sinemet • Strongly educate patient/family/staff on fall risks • Monitor BP for orthostatic hypotension • Transfer patients slowly • Monitor for dizziness/diaphoresis

17. Bringing it Back to Mr. L • Initially pt not considered a reliable source of information regarding the timing or dosingof hismeds based on past hx of medication abuse • Pt back on 50/200 dose of Sinemet CR tid to qid • PT and OT scheduled based on availability of therapist • Pt refused Rx frequently, often citing lack of meds as his reasoning • When agreeable to participation, made minimal gains in fxnl mobility, was not fully coherent and was almost (D) for ADLs • Pt appeared to be suffering from on/off syndrome, i.e. drug was either “on” or “off” with no predictable relation to timing of dose

18. Bringing it Back to Mr. L • After several days with little progress, a team meeting resulted in the following: • MD added 1 tab Parlodel 5 mg tid • Addition of Dopamine agonist helpful in smoothing out on-off syndrome • It was agreed that the team would work to coordinate meds with rehab via: • Meeting 4x/wk with nurse practitioner regarding pt’s progress • Speaking daily with medication nurse to schedule rehab visits with meds • 8AM Sinemet CR: 9 AM Physical Therapy • 12 PM Sinemet CR: 1:30 PM Occupational Therapy, 2:30 PM 2nd visit by Physical Therapy on as needed basis

19. Results of Coordinating Meds with Therapy Rehab Reassessment Revealed: Cognition: A + O x 3; pt pleasant and agreeable to therapy ROM/Tone: tone somewhat normalized Strength: 4+/5 throughout all extremities (B); good effort exhibited by patient Fxnl Mobility: • Sup > Sit: (S) • Sit > Stand: (S) • Gait: Pt amb > 500 ft with RW with (S) and occ cues for correct technique with RW. Eventually progressed to st cane.

20. Results Cont’ Impact on interventions: Pt with enhanced intellect and ability to participate in bid-tid therapy sessions for therex, gait training and ADL training Revised goals: Pt goaled for D(S) to mod (I) level for all fxnl mobility (with st cane) and ADLs Eventual outcome: Pt returned to home with private aides to assist with medicine mgmt, meal preparation and bathing

21. Take Home Message • As 1st line observers, the rehab team has the potential to provide useful insight into the effectiveness of a patient’s medication • Duty to communicate with nurse and/or MD regarding pt’s progress in relation to meds • Duty to inquire regarding timing of meds in relation to PT/OT • Duty to keep up to date on medications typically used in setting of care and potential impact on treatment • All patients (even those with mental status changes) should acknowledged when it comes to insight into their body’s response to medications

22. Resources • Bristol-Myers Squibb (2002). PDR Drug Information for Sinemet CR. Retrieved July 14, 2004 from Micromedex Physicians Desk Reference: http://www.drugs.com/PDR/Sinemet_CR_Tablets.html • Merck & Co, Inc. (1999). Sinemet CR Package Insert. Retrieved July 15, 2004 from the Federal Drug Adminstration at: http://www.fda.gov/cder/foi/label/2001/17555s55lbl.pdf • Pharmacologic management of Parkinson’s disease. In: Ciccone, C. (1996). Pharmacology in Rehabilitation (2nd ed.). Philadelphia: FA Davis Co. • RxList LLC. (2003). Carbidopa/Levadopa CR. Retrieved July 13, 2004 from RxList at: http://www.rxlist.com/cgi/generic/sinemet.htm • Yeh KC, August TF, Bush DF, Lasseter KC, Musson DG, Schwartz S, Smith ME, Titus DC. (1989). Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies.Neurology, 39 (11 Suppl 2), 25-38.

23. Questions?