Treatment of parkinson’s disease


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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
  • Treatment of parkinson’s disease

    1. 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. 2. Disclosures • Work with various pharmaceutical companies intermittently • Honorarium will be donated Brought to you by
    3. 3. Brought to you by
    4. 4. Brought to you by
    5. 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. 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. 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. 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. 9. Parkinson’s Syndromes Metabolic causes-- • Hypothyroidism • Hypoparathyroidism • Alcohol withdrawl (pseudoparkinsonism) • Chronic liver failure • Wilson’s disease Brought to you by
    10. 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. 11. P. Syndromes Structural Causes— • Strokes • Tumors • Chronic subdurals • NPH (Normal Pressure Hydrocephalus) Brought to you by
    12. 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. 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. 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. 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. 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. 17. P. Syndromes Infections--- • encephalitis • HIV/AIDS • Neurosyphilis • Toxoplasmosis • CJD (Creuzfeld Jakob)--prion disease • Progressive multifocal leukoencephalopathy Brought to you by
    18. 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. 19. P. Disease ??DIAGNOSIS?? Brought to you by
    20. 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. 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. 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. 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. 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. 25. P. Disease INVESTIGATIONS: • TSH • Calcium, albumin • CT head Brought to you by
    26. 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. 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. 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. 29. PD-case “I don’t have Parkinson’s Disease!!” Brought to you by
    30. 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. 31. IADL Instrumental Activities of Daily Living • S shopping • H housework • A accounting • F food preparation • T transportation Brought to you by
    32. 32. ADL Activities of Daily Living • D dressing • E eating • A ambulation • T toiletting • H hygiene Brought to you by
    33. 33. PD- case 1 Brought to you by
    34. 34. PD-case 1 clock Brought to you by
    35. 35. PD –Case 1 Diagnosis: Parkinson’s disease ---Hoehn & Yahr’s** stage 2 Brought to you by
    36. 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. 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. 38. PD-case 1 clock Brought to you by
    39. 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. 40. PD-Treatment ???? Brought to you by
    41. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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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