Parkinson's disease n management

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Information about Parkinson's disease n management

Published on June 8, 2019

Author: rupendrabharti

Source: slideshare.net

1. Parkinson’s Disease & It’s Managements Dr. Rupendra K. Bharti Assist. Professor Late. BRKM GMC Jagdalpur

2. Introduction  Parkinsonism is a generic term that is used to define a syndrome manifest as bradykinesia with rigidity and/or tremor. It has a differential diagnosis (Table 449-2) that reflects damage to different components.  Among the different forms of parkinsonism, PD is the most common (approximately 75% of cases).  Parkinsonism is a clinical syndrome characterized by motor symptoms like bradykinesia, tremor and rigidity.

3. Classification of the Parkinsonism  Primary parkinsonism (Parkinson’s disease)  Sporadic/Idiopathic  Genetic (Mutation of alpha- synuclein, parkin, LRRK2, DJ1, and PINK1gene)  Parkinsonism-plus syndromes (Atypical parkinsonism)  Progressive supranuclear palsy (PSP)  Multiple system atrophy(MSA)  Cerebellar type (MSA-c)  Parkinson's type (MSA-p)  Cortical-basal ganglionic degeneration(CBGD)  Frontotemporal dementia(FTD)

4. Secondary parkinsonism (environmental Aetiology)  Drugs induced(Antipsychotic medications,  Reserpine, Tetrabenazine)  Postencephalitic(infection)  Toxins: MPTP, cyanide,CO, Mn, hexane  Heavy metal (iron, manganese)  Vascular  Brain tumors  Head trauma  Normal-pressure hydrocephalus  Liver failure

5. OTHER NEURODEGENERATIVE DISORDER  Wilsons disease  Huntington's disease  Neurodegenaration with brain iron accumulation  SCA 3 (spinocerebellar ataxia)  Fragile x-associated ataxia- tremor parkinsonism.  Prion disease  Dystonia-parkinsonism (DYT3)  Alzheimer's disease with parkinsonism

6. Clinical differentiation

7. Neurodegenerative diseases  Parkinson’s Disease  Alzheimer’s Disease  Huntington’s Disease  Amyotrophic lateral sclerosis (ALS)  Spinocerebellar Ataxia

8. Epidemiology of Parkinson’s disease Prevalence  Crude prevalence –India - 328 per 100,00 Incidence  Crude annual incidence rates- 1.5 per 100,000 population (China) in 1986 to 14.8 (Finland) through 1968 to 1970.

9. Gender differences  Slightly more common in men than in women  Male to female ratio- 1.2:1 to 1.5:1 Geographic distribution  Crude prevalence China - 15 per 100,000 India - 328 per 100,000 Mississippi, USA - 131 per 100,000 Argentina - 657 per 100,000

10. Ethnic distribution  White people in Europe and North America have a higher prevalence, around 100 to 350 per 100,000 population.  Asians in Japan & China and Africans have lower rates, around one-fifth to one-tenth of those in whites.

11. Age Distribution  Less common before 50 years of age & increases steadily with age thereafter up to the ninth decade.  ~1 in every 200 persons aged 60–69 had PD in the United States (US) and Western Europe.  For people in their 70’s, this increased to ~1 person with PD in every 100 people.  For people in their 80’s, ~1 in every 35 had PD

12. Incidence  “Every four seconds, a new case of dementia occurs somewhere in the world.”  Cohort longitudinal studies provide rates between 10 and 15 per thousand.  Advancing age -primary risk factor  Women- higher risk of developing AD particularly in the population older than 85

13. pathophysiology

14. Clinical Presentation

15. Rest Tremor  Tremor : Rhythmical & involuntary shaking, trembling or quivering movements of the muscles.  Rest tremor ( 4 - 6 Hertz) :  Maximal when the limb is at rest  Disappears with voluntary movement and sleep  Alternating contraction of agonist and antagonist muscles at a rapid pace  Usually Unilateral at onset  Involves the hands, lips, chin, jaw and legs .  “ P i l l-rolling”

16. Rigidity  Increased muscle tone felt during examination by  passive movement  Both the agonist and antagonist muscles are involved  Rigidity :  Cogwheel rigidity  Lead-pipe rigidity

17. Postural instability  Stooped Posture  UNIVERSAL FLEXION :  Extreme neck flexion,  Extreme anterior truncal flexion (camptocormia) &  Flexion of elbows and knees.

18. Tremor & Posture

19.  Festinating / Shuffling Gait:  i) Difficulty to initiate walking  ii) Shortened stride  iii) Reduced arm swing  iv) Rapid small steps (shuffling)  RUNNING AFTER THE CENTRE OFGRAVITY Freezing phenomenon

20. Gait & micrography

21. Non-motor symptoms  Neuropsychiatric  Depression & Anxiety disorders  Apathy  Autonomic disturbance (dysautonomia)  Urinary dysfunction  Constipation  Sensory symptoms  pain  Restless legs syndrome  Olfactory dysfunction  Sleep disturbances  REM behaviour disorder  excessive day time drowsiness  Cognitive impairment  Dementia : In >80% of patients after 20 years of disease

22. Clinical picture

23. Diagnosis of Parkinsonism  Diagnosis is primarily clinical, based on history and examination  Confirmatory diagnosis : Histological demonstration of the intraneuronal Lewy bodies on autopsy.  CT scan & MRI: to exclude other causes.

24. Examination of signs  Bradykinesia :  Ask patient to do repetitive movements as quickly and as possible Opening and closing the hand Tapping thumb and index fingers or tapping the foot on the ground  Rest tremor:  Differentiate from the intentional tremor seen in cerebellar disease  Best observed while the patient is focused on a particular mental task.

25. Rigidity:  Increased resistance to passive movements Postural stability  The “Pull test” is performed in order to assess postural stability

26. UK Parkinson’s Disease Society Brain Bank’s clinical criteria for the diagnosis of probable Parkinson’s disease  Step 1  Bradykinesia  At least one of the following criteria: Rigidity Rest tremor (4–6 Hz ) Postural instability (not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction)  Step 2  Exclude other causes of parkinsonism

27.  Step 3  At least three of the following supportive (prospective) criteria: Unilateral onset Rest tremor Progressive disorder Persistent asymmetry Severe levodopa induced chorea (dyskinesia) Clinical course of 10 years or more

28. MODIFIED HOEHN & YAHR STAGING

29. MANAGEMENT

30. Parkinson's disease No definite cure Relief of cardinal signs- rigidity, tremor , & akinesia Correction of mood changes Treatment of other symptoms such as depression, sleep disturbance . Treatment of cause when possible

31. NON-PHARMACOLOGICAL MANAGEMENTS Physiotherapy Speech therapy Dietary controls

32. Physiotherapy Helps to reduce rigidity Corrects abnormal posture Improves walking , turning & balance

33. Speech therapy Helpful in patients where dysarthria and dysphonia interferes communication

34. Dietary controls Include high-fiber diet Choose foods low in saturated fat and cholesterol. Avoid high protein diet

35. PHARMACOTHERAPY

36. ANTI-PARKINSONISM PHARMACOTHERAPY INCREASE DOPAMINE a)1. Dopamine precursors: Levodopa. b)2. Peripheral decarboxylase inhibitors: Carbidopa c)3. MAO-B Inhibitors: Selegiline, rasagiline. 4. COMT Inhibitors: Tolcapone, Entacapone. 5. Dopamine releasing drugs: Amantadine 6. Dopamine receptor agonists: Bromocriptine, pergolide, cabergoline, ropinirole, rotigotine, pramipexole. DECREASE ACETYLCHOLE NE 1. Central anticholinergic: Trihexyphenidyl, Benztropine, Biperidine, procyclidine. 2. Antihistaminics: Promethazine

37. Levodopa  ‘Gold-standard' treatment for Parkinson's..  Therapeutic benefit is nearly complete in early stages but declines as disease advances(“Wearing-off effect”) 1-2% cross BBB  Improves cardinal signs- tremor, rigidity and akinesia.

38. ACTIONS  CNS: PD  CVS: Hypotension, arrhythmia  CTZ: N/V  Endocrine: Prolactin inhibition

39. kinetics  Gastric emptying: if slow, levodopa is exposed to degrading enzymes present in gut wall and liver for a longer time—less is available to penetrate blood-brain barrier.  Amino acids present in food compete for the same carrier for absorption: blood levels are lower when taken with meals.  Levodopa undergoes high first pass metabolism in g.i. mucosa and liver.  The plasma t ½ of levodopa is 1–2 hours

40. Side Effects  At the initiation of therapy  Nausea, vomiting, hypotension, cardiac arrhythmias, angina, taste alteration.  Avoided by gradual titration  Long-term complications  Dyskinesias  Behavioural effects: hallucination, psychosis  On–off effect  Wearing-off effect (“on” episodes when the drug is working and “off” episodes when parkinsonian features return)

41. interaction Pyridoxine: Abolishes the therapeutic effect of levodopa (not combined with carbidopa) by enhancing its peripheral decarboxylation.  Phenothiazines, butyrophenones, metoclopramide reverse the therapeutic effect of levodopa by blocking DA receptors.  Antihypertensive drugs: more prominent postural hypotension.  Nonselective MAO inhibitors: may

42. LEVODOPA + Carbidopa

43. Dopamine agonist Ergot derivatives Bromocriptine, pergolide, cabergoline associated with ergot-related side effects, including cardiac valvular damage. Second generation of non ergot dopamine agonists Pramipexole, ropinirole, rotigotine, Apomorphine

44. Common Side effect cardiac valve fibrosis (Pergolide) Nausea, vomiting, and orthostatic hypotension. Hallucinations and cognitive impairment are more than levodopa so use cautiously in age more than 70 Sedation with sudden unintended episodes of falling asleep while driving a motor vehicle have been reported.

45. Apomorphine  Apomorphine is a dopaminergic agonist that can be administered by subcutaneous injection.  It has high affinity for D4 receptors; moderate affinity for D2, D3, D5, and adrenergic α1D,α2B, and α2C receptors; and low affinity for D1 receptors.  Apomorphine has been used as a “rescue therapy” for the acute intermittent treatment of “off” episodes in patients with a fluctuating response to dopaminergic therapy  Dose: 2-6mg (depends upon tolerability of pts)

46. S/E  Apomorphine is highly emetogenic and requires pre- and post-treatment anti-emetic therapy.  Oral trimethobenzamide, 300 mg three times daily, should be started 3 days prior to the initial dose of apomorphine and continued at least during the first 2 months of therapy.  Profound hypotension and loss of consciousness have occurred when apomorphine was administered with ondansetron; hence, the concomitant use of apomorphine with antiemetic drugs of the 5-HT3 antagonist class is contraindicated.  Other potentially serious side effects:  QT prolongation,  injection-site reactions, and  the development of a pattern of abuse characterized by increasingly frequent dosing leading to hallucinations, dyskinesia, and abnormal behaviour.

47. MAO-B INHIBITORS Selegiline, Rasagiline  Monotherapy in early disease.  These agents selectively inactivate MAO-B through irreversible inhibition of the enzyme  They inhibit the breakdown of DA in the striatum.  Reduced “off” time when used as an adjunct to levodopa in patients with motor fluctuations.

48. Selegiline  Used for symptomatic treatment for early or mild PD.  Well tolerated in younger patients with PD.  Also having antioxidant property.  Selegiline reduces motor & cognitive effects of levodopa therapy in advance PD.  S/e: anxiety, insomnia is more common selegiline therapy due to production of its active metabolites such as Amphetamine and methamphetamine.

49. Rasagiline No undesirable amphetamine effects. Rasagiline monotherapy was effective in early PD. Also significantly reduced levodopa- related “wearing off” symptoms in advanced PD.

50. Interactions Selegiline & Rasagiline can lead to the development of stupor, rigidity, agitation, and hyperthermia when administered with the analgesic meperidine. Concomitant therapy of MAO-B inhibitors with tricyclic antidepressants or with serotonin- reuptake inhibitors

51. COMT INHIBITORS Tolcapone Entacapone The principal therapeutic action of the COMT inhibitors is to block this peripheral peripheral conversion of levodopa to 3-O- methyl DOPA, increasing both the plasma t t ½ of levodopa as well as the fraction of each dose that reaches the CNS. Levodopa with a COMT inhibitor reduces “off” time and prolongs “on” time. Two COMT inhibitors have been approved, approved, tolcapone and entacapone.

52. Tolcapone has a relatively long duration of action, allowing for administration two to three times a day, and appears to act by both central and peripheral inhibition of COMT. Entacapone has a short duration of action (2 hours) and usually is administered simultaneously with each dose of levodopa/carbidopa. The action of entacapone is attributable principally to peripheral inhibition of COMT.

53. S/E Nausea, orthostatic hypotension, vivid dreams, confusion, and hallucinations An important adverse effect associated with tolcapone is hepatotoxicity, requires special monitoring. Entacapone has not been associated with hepatotoxicity and requires no special monitoring.

54. Anticholinergic drugs These agents helpful in patients with severe tremor. Anticholinergic drugs currently used in the treatment of PD include Trihexyphenidyl (2-4 mg three times per day), Benztropine Mesylate (1-4 mg two times per day), and Diphenhydramine hydrochloride (25-50 mg three or four times per day). Diphenhydramine also is a histamine H1 antagonist

55.  These drugs have relatively modest antiparkinsonian activity and are only used in the treatment of early PD or as an adjunct to dopamimetic therapy.  Adverse effects result from their anticholinergic properties.  Most troublesome are sedation and mental confusion.  Other side effects are  constipation,  urinary retention, and  blurred vision through cycloplegia.  All anticholinergic drugs must be used with caution in patients with narrow-angle glaucoma.

56. Amantadine  Amantadine, an antiviral agent used for the prophylaxis and treatment of influenza A , has antiparkinsonian activity.  Amantadine appears to alter DA release in the striatum, has anticholinergic properties, and blocks NMDA glutamate receptors.  Its used in mild PD & L-Dopa induced motor fluctuations and abnormal movements.  Fixed dose of 100 mg BD is used.  S/E: Dizziness, lethargy, anticholinergic effects, and sleep disturbance

57. Treatment approaches to newly diagnosed PD

58. Surgery  Deep Brain Stimulation  Thalamotomy  Pallidotomy  Neural Transplantation

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