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Treatment of parkinson’s disease

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Treatment of parkinson’s disease

Treatment of parkinson’s disease

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  • **Case of Cathy Dawson, with late stage dementiaan needed 3+hrs of care daily; my reluctance to add sin, but did very well and was able to return to ret home
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    • 1. DIAGNOSIS & TREATMENT OF PARKINSON’S DISEASE May 7, 2008 Sadhana Prasad Symposium on Changes and Challenges in Geriatric Care Brought to you by
    • 2. Disclosures • Work with various pharmaceutical companies intermittently • Honorarium will be donated Brought to you by
    • 3. Brought to you by
    • 4. Brought to you by
    • 5. OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications Brought to you by
    • 6. Parkinson’s Disease Characterized by: (Slow,Stiff,Shaky) • Bradykinesia * • Rigidity * • Rest tremor--3-6Hz pill-rolling (absent 1/3) • Postural instability Brought to you by
    • 7. Parkinson’s Disease (PD) • First description 1817 Parkinson, James An Essay on the Shaking Palsy, Sherwood, Neely, and Jones, London • Progressive neurodegenerative disease • Affects ages 40 onwards, mean age at diagnosis 70.5 • Complex disorder with motor, non-motor, neuropsychiatric features Brought to you by
    • 8. Disease vs Syndrome • Disease = a morbid process having characteristic symptoms; pathology, etiology, and prognosis may be known • Syndrome = a set of symptoms occurring together; different etiologies but similar presentation Brought to you by
    • 9. Parkinson’s Syndromes Metabolic causes-- • Hypothyroidism • Hypoparathyroidism • Alcohol withdrawl (pseudoparkinsonism) • Chronic liver failure • Wilson’s disease Brought to you by
    • 10. P. Syndromes Medications**/chemicals— • neuroleptics (typicals more than the atypicals), • SSRI (selective serotonin reuptake inhibitors), • metoclopromide/maxeran, • Reserpine, • MPTP, • in Methcathinone (ephedrone) users – high plasma Manganese levels (NEJM Mar 6, 2008) • CO, cyanide, organic solvents, carbon disulfide Brought to you by
    • 11. P. Syndromes Structural Causes— • Strokes • Tumors • Chronic subdurals • NPH (Normal Pressure Hydrocephalus) Brought to you by
    • 12. P.Syndromes Lewy Body spectrum of Diseases (DLB=Dementia with LB)--- ---early onset visual (or other) hallucinations ---fluctuating cognitive abilities ---sleep disorders ---neuroleptic sensitivity, even to atypicals Brought to you by
    • 13. P. Syndromes PSP (progressive supranuclear palsy)—or Steeles Richardson Olszewski Syndrome ---gaze abnormalities ---postural instability, early unexplained falls ---bulbar features—dysphonia, dysarthria, dysphagia ---rapidly progressive---median 6 yrs. Brought to you by
    • 14. P. Syndromes CBD (cortico basal degeneration)--- ---Asymmetric parkinsonism ---postural instability ---ideomotor apraxia ---aphasia ---alien limb phenomenon ---impaired cortical sensations Brought to you by
    • 15. P. Syndromes Multi System Atrophy-- (alpha-synuclein + glial cytoplasmic inclusions, autonomic dysfunction, pyramidal signs) • Shy Drager Syndrome, • Olivopontocerebellar atrophy, • Striatonigral degeneration Brought to you by
    • 16. P. Syndromes Other Neurodegenerative Disorders— • Alzheimer’s Disease, later stages** • Huntington’s Disease (rigid form) • Frontotemporal Dementia with Parkinsonism, Chromosome-17 linked (FTDP-17) • Spinocerebellar ataxias Brought to you by
    • 17. P. Syndromes Infections--- • encephalitis • HIV/AIDS • Neurosyphilis • Toxoplasmosis • CJD (Creuzfeld Jakob)--prion disease • Progressive multifocal leukoencephalopathy Brought to you by
    • 18. P. Syndrome Essential Tremor--- ---action tremor (not rest tremor) ---more rapid (greater than 3-6 Hz) ---usually hands, but can also affect legs, head/chin, voice, trunk ---can present with falls if legs and trunk involved Brought to you by
    • 19. P. Disease ??DIAGNOSIS?? Brought to you by
    • 20. P. Dis -- Diagnosis • A clinical diagnosis • Cardinal features: Bradykinesia, rigidity • Trial of sinemet (Levodopa/carbidopa) • Confirmatory test: neuropathologic (autopsy) Brought to you by
    • 21. P. Disease-Diagnosis • 1/3 will not respond to levodopa therapy • 1/5 with P. Syndrome will respond to levodopa ---Follow- up with time needed to clarify diagnosis Brought to you by
    • 22. P. Disease---Diagnosis Minimum therapeutic dose: ---300mg levodopa per day in divided doses ---can be lower in biologically old old ---vast majority will need 400-600mg levodopa daily to achieve significant benefit Brought to you by
    • 23. P. Disease- Diagnosis Consider alternative diagnosis if: • Early falls (postural instability) • Poor response to levodopa • Dysautonomia (urinary retention/atonic bladder, incontinence, orthostatic hypotension, impotence) • No rest tremor (in 1/3) Brought to you by
    • 24. P. Disease-Diagnosis Alternative Diagnosis cont’d… • Cerebellar signs • Positive Babinski • Apraxia • Gaze abnormailities • Dementia concurrently with Parkinsonism • Strokes Brought to you by
    • 25. P. Disease INVESTIGATIONS: • TSH • Calcium, albumin • CT head Brought to you by
    • 26. OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications Brought to you by
    • 27. PD- CASE • Mr AB, married, active farmer, stressed care-giver • Drove his wife to the clinic, wife to see me re agitated dementia • One son also attended • Mr AB –stressed care-giver, on paxil (SSRI) Brought to you by
    • 28. PD- case Mr. AB--- stressed caregiver • Slightly flexed posture • Slightly bradykinetic • Slightly diminished facial expression • No difficulty turning, getting in/out of armless chair Brought to you by
    • 29. PD-case “I don’t have Parkinson’s Disease!!” Brought to you by
    • 30. PD- case Mr. AB--- • 1 month later, referred re ? PD?? • CT head, TSH, Ca normal • Slowing down x 1 yr, hypophonia, denied trouble turning in bed but took 5 tries in clinic, trouble getting out of soft chair, stopped taking baths x 3 years, mild rest tremor R hand, trouble doing up buttons and laces Brought to you by
    • 31. IADL Instrumental Activities of Daily Living • S shopping • H housework • A accounting • F food preparation • T transportation Brought to you by
    • 32. ADL Activities of Daily Living • D dressing • E eating • A ambulation • T toiletting • H hygiene Brought to you by
    • 33. PD- case 1 Brought to you by
    • 34. PD-case 1 clock Brought to you by
    • 35. PD –Case 1 Diagnosis: Parkinson’s disease ---Hoehn & Yahr’s** stage 2 Brought to you by
    • 36. Hoehn and Yahr scale • 1. Unilateral involvement only, usually with minimal or no functional disability • 2. Bilateral or midline involvement without impairment of balance • 3. Bilateral disease; mild to moderate disability with impaired postural reflexes; physically independent • 4. Severely disabling disease; still able to walk or stand unassisted • 5. Confinement to bed or wheelchair unless aided Hoehn, MM, Yahr, MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17:427. Brought to you by
    • 37. PD- case 1 • MTO notified, “not to cancel license” • Paxil * • Sinemet regular 100/25 mg ½ tid, increase by ½ weekly till 1 tid • Calcium and vitamin D3 • 2 months later, smiling, clock better, moving better, still flexed, no fallsBrought to you by
    • 38. PD-case 1 clock Brought to you by
    • 39. PD—other issues • Depression • Dementia • Driving • Falls • Neuropsychiatric features • “slowing down of thought processes” (the clock in Mr AB) • Constipation Brought to you by
    • 40. PD-Treatment ???? Brought to you by
    • 41. OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications Brought to you by
    • 42. PD--Treatment • Geared towards mobility—levodopa, dopamine agonists, MAO B inhibitors • Rest tremor, cosmetic—anticholinergics (may worsen cognition) • Postural imbalance—no pharmacological treatment; exercise, gait aids, prevent fractures (Ca, Vit D3, +/- bisphosphonates) • Dyskinesias-- ?amantadine (no clear evidence) Almeida,QJ, Recent Patents on CNS Drug Discovery, 2008:3, 5--54 Brought to you by
    • 43. PD--Which pharmaceutical? In Elderly-- • Levodopa/ carbidopa (sinemet) – regular vs CR (controlled release) or Levodopa/ benserazide (prolopa) – regular vs HBS • COMT- inhibitor– entacapone (comtan)Brought to you by
    • 44. PD- medications LevodopaLevodopa • Well-established, for bradykinesia and rigidity • SE: nausea, orthostatic hypotension • Combined with peripheral decarboxylase inhibitor (carbidopa, benserazide) to prevent conversion to dopamine in the periphery before it crosses blood brain barrier Brought to you by
    • 45. PD- medications Levodopa (l-dopa) -- l-dopa / carbidopa = sinemet reg. or CR -- l-dopa / benserazide = prolopa, medopar or medopar HBS • Competes with amino acids from protein for GI absorption • Regular-- before meals, quick in quick out, T1/2 = 90 min • CR--- With meals,Controlled Release, slow in slow out, need 30% more to achieve same effect as reg. dose, erratic absorption in elderly Brought to you by
    • 46. PD-medications L-dopa cont’d • SE- Nausea (Rx Domperidone) -Hallucinations (Rx lower dose, atypical n neuroleptics) -somnolence, confusion, agitation -motor fluctuations- after sev yrs of Rx Brought to you by
    • 47. PD- medications L-dopa cont’d • Motor fluctuations (in 50%, after 5-10yrs) -wearing-off– Rx COMT – inhibitor*, ?CR -dyskinesias –(??Rx amantadine??) -dystonias -variety of complex fluctuations in motor function Brought to you by
    • 48. PD- medications L-dopa cont’d • Discontinuation— - gradually –over weeks, - to prevent malignant neuroleptic like syndrome or akinetic crisis Brought to you by
    • 49. PD-medications L-dopa cont’d • Dopaminergic dysregulation syndrome (DDS)— tolerance to mood elevating effects - Compulsive use of dopaminergic drugs - Early onset males - Cyclical mood disorder - Impulse control disorder (hypersexuality, pathologic gambling) Giovannoni, G, Hedonistic homeostatic dysregulation…J. Neurol Neurosurg Psychiatry 2000; 68:243 Brought to you by
    • 50. PD- medications COMT – inhibitorCOMT – inhibitor -Catechol-O-Methyl Transferase Inhibitor -((eg Tolcapone (Tasmar)---off market due to fulminant hepatitis causing 3 deaths)) -eg Entacapone (Comtan) -for wearing-off at end-of-dose of L-dopa -dose 200mg-1600mg, divided, daily, with L-dopa -SE-diarrhea in 5%, due to increased dopaminergic stimulation from L-dopa availability Brought to you by
    • 51. PD-medications Dopamine Agonists: adjunct Rx to L-dopa. -Ergotamines—bromocriptine, ((pergolide)), ((cabergoline)) SE-same as L-dopa, uncommon Raynaud’s, erythromelalgia, retroperitoneal/pulmonary fibrosis -Non-Ergot—pramipexole, ropinirole, ((transdermal rotigotine)) SE—same as L-dopa, Sudden somnolence – caution with driving Brought to you by
    • 52. PD-medications MAO-B inhibitors-MAO-B inhibitors--adjunct Rx to L-dopa -eg selegiline (eldepryl), rasagiline -somewhat helpful in young, early in disease -neuroprotective properties in animal models only Arch Neurology. 2002; 59:1937 Brought to you by
    • 53. PD-medications AnticholinergicsAnticholinergics—adjunct Rx to L-dopa, best avoided in elderly -acetylcholine (ACh) and dopamine in balance in basal ganglia -decrease Ach to balance decrease in L-dopa -eg trihexyphenidyl (artane), benztropine (cogentin), orphenadrine, procyclidine (kemadrin) -SE-confusion, hallucinations, dry mouth, blurred vision, constipation, nausea, u. retention, glaucoma Brought to you by
    • 54. PD-medications Amantadine-adjunct to L-dopa, best avoided in elderly -for dyskinesias -Antiviral agent—mechanism unknown -NMDA-receptor antagonist properties- interferes with excessive glutamate -SE-livedo reticularis, ankle edema, hallucinations Brought to you by
    • 55. PD- Medications When do you stop the medications? --ALWAYS taper gradually over days to weeks to avoid NM-like syndrome --unable to take meds (dysphagia) --significant, intolerable SE impairing QOL --end-stage--- “infection comes as a friend” Brought to you by
    • 56. OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications Brought to you by
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    • 58. Our views have increased the mark of the 20,000  Thank you viewers  Looking forward for franchise, collaboration, partners. Brought to you by
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