Parkinson's Disease treatment class ppt.pptx

Parkinson's Disease Management Dr. Md. Shamshir Alam Learning objectives Upon completion of the chapter, the reader will be able to: • For a patient initiating therapy for PD, recommend appropriate drug therapy and construct patientspecific treatment goals. • Recognize and treat various motor co...

Parkinson's Disease Management Dr. Md. Shamshir Alam Learning objectives Upon completion of the chapter, the reader will be able to: • For a patient initiating therapy for PD, recommend appropriate drug therapy and construct patientspecific treatment goals. • Recognize and treat various motor complications, nonmotor symptoms. • Formulate a plan to minimize patient “off-time” and maximize “on-time” including timing, dosage, and frequency of medications. • Construct appropriate patient counseling. • Develop a monitoring plan- effectiveness, adverse effects. Treatment: Desired Outcomes • The goals of treatment include: • Maintaining patient independence, ADL, and QOL. • Minimizing the development of response fluctuations. • Limiting medication-related adverse effects. Treatment • Initial treatment: • Age, risk of adverse effects, degree of physical impairment, and readiness to initiate therapy. • 2002 American Academy of Neurology (AAN) guidelines suggest: • Pharmacologic treatment be delayed until functional disability appears. • 2017 National Institute for Health and Care Excellence (NICE) guidelines: • Recommends (early Trt): dopamine agonists, levodopa, or MAO-B inhibitors be offered to patients even before QOL is affected. • Earlier treatment may delay the progression of • General Approach to Treatment: Treatment is categorized into 3 types: • Lifestyle changes, nutrition, and exercise; • Pharmacologic intervention; and • Surgical treatments after pharmacologic interventions fail. Nonpharmacologic Therapy • Lifestyle Modifications • Good nutrition, physical activity and social interactions. • This improves ADLs, gait, balance, and mental health. Pharmacologic Therapy of Motor Symptoms General consideration • Drug therapy aims to enhance dopaminergic activity in the substantia nigra. • Choice of pharmacologic agent: • Patient-specific parameters, and • Dose regimens to maximize “on time” and minimize “off time.” • The AAN and the MDS recommendation: • Either levodopa/carbidopa or a Dopamine agonist. • 2017 NICE recommendation: • Levodopa/carbidopa - once motor • No complete cure • Symptomatic treatment, but with no effect on progression. Treatment on three basics: • Initiate therapy with gradual dosage titration (start low and go slow). • Maintain therapy at lowest effective dosage. • In case, if needed, discontinue therapy with gradual taper. Drugs for PD I. Drugs that affect brain dopaminergic system: A. Dopaminergic agonists: Bromocriptine, Pergolide B. Dopamine precursor: Levodopa (l-dopa) C. Peripheral decarboxylase inhibitors: Carbidopa, benserazide D. MAO-B inhibitor: Selegiline, rasagiline E. COMT inhibitors: Entacapone, Tolcapone F. Dopamine facilitator: Amantadine II. Drugs that affect brain cholinergic system: A. Central anticholinergics: Procyclidine B. Antihistaminics: Orphenadrine, Promethazine Pharmacologic Therapy of Motor Symptoms • Choice of drugs is based on clinical experience and patient preference. • PD medication discontinuation is gradual and monitor worsening of motor symptoms. • Starting with a dopamine agonist may delay the onset of dyskinesias • Less motor benefit and greater risk of hallucinations or somnolence. • Levodopa: Greatest motor improvement. Ideal Initial therapy in the elderly, • ↑risk of motor fluctuations over time. • Anticholinergics, Amantadine, or MAOBIs • only for patients with mild symptoms. Levodopa (Ldopa) + Carbidopa • Carbidopa: • Dopa decarboxylase inhibitor • Clinical uses • all types but not in drug induced parkinsonism • rigidity and bradykinesia are resolved Levodopa: Adverse effects • GIT: • Anorexia, nausea, and vomiting: 80% • Tolerance develops quickly • CVS: • Orthostatic hypotension: 30-40% • Cardiac arrhythmias • Centrally mediated adverse effects • Dyskinesias: 80% • Serious mental disturbances: 10 - 15% • On-off phenomenon: Sinemet CR Pharmacologic Therapy: Anticholinergics • Decreases acetylcholine: dopamine ratio. • Minimize resting tremor and drooling • But are not as effective as other agents for rigidity, bradykinesia, and gait problems. Side effects: • Cognitive impairment (avoid in older patients), • Worsen urinary retention or constipation. With Levodopa: • erratic and decreased levodopa absorption. Pharmacologic Therapy: Amantadine • Effective as monotherapy and • adjunct therapy for off time and dyskinesia. • Extended release was approved by FDA for dyskinesias in PD. • Side effects: • Dizziness, livedo reticularis, peripheral edema, orthostatic hypotension, hallucinations, restlessness, anticholinergic effects, and • Insomnia (↓s by ER tablets at bedtime and IR tablets in the day). • Avoid in elderly who cannot tolerate Pharmacologic Therapy: Selective MAO-B Inhibitors • Safinamide, Selegiline, and Rasagiline • Less D/I with Tyramine-rich foods than nonselective MAOIs. • Selegiline and rasagiline: • Provide a mild symptomatic benefit and helps in delay dopaminergic medications • Combined with levodopa • Delay motor complications. • Reduce off time with motor fluctuations on levodopa . • Serotonin syndrome with: • Opioid analgesics, antidepressants, and • Serotonergic agents, or cold and weight loss products Pharmacologic Therapy: Selective MAO-B Inhibitors.2 • Selegiline is generally well tolerated. • Adverse effects: • Nausea, confusion, hallucinations, jitteriness • Insomnia and orthostatic hypotension. • Oral disintegrating tablet • Avoid first-pass metabolism • ↓ serum concentrations of its amphetamine-like metabolite which causes insomnia. • Daily doses: 5-10 mg • At higher doses - MAO-B selectivity may be lost. • Rasagiline has a similar adverse effects • but less insomnia. Pharmacologic Therapy: Dopamine Agonists • Advantages: • Delay levodopa therapy • Smaller risk of motor fluctuations during the first 4 to 5 years of treatment. • In late stage, added to levodopa: • • • • • Minimize response fluctuations Decrease off time, Improve wearing-off symptoms Allow a reduction in levodopa dose Improve ADLs. Pharmacologic Therapy: Dopamine Agonists .. 2 • Rotigotine patch • minimizes pulsatile stimulation of dopamine. • Common side effects: • Nausea, vomiting, • Sedation (> with apomorphine) • Orthostatic hypotension (> with pramipexole) • Uncommon ergot side effects: • Painful reddish discoloration of the skin, cardiac fibrosis. Istradefylline (1st Adenosine A2A Receptor Antagonist) • US-FDA approve for treating Off Episodes in PD. • The SD - 20 mg OD oral. May be ↑ to a Max 40 mg OD. • MOA: • Blocks adenosine A2A receptors in GABAergic neurons within the indirect pathway of the basal ganglia system. • It prolongs dopaminergic action. • The common adverse reactions: • Dyskinesia, dizziness, nausea, hallucinations, and Algorithm for diagnosis and manage ment of Parkinso n disease Specialist Care for Patients with PD • Dentist - PD medicines ↓ saliva flow and ↑ risk of dental caries • Dietician - Recommend appropriate caloric intake, meal selection, and protein consumption which may: • improve constipation and nausea • decrease weight loss and aspiration • Speech therapist - Improve swallowing, articulation, and force of speech. • Physical therapy - Improve strength, activity, sleep quality, and reduce risk of fall. May provide neuroprotection. • Occupational therapist - Educate on adaptive environment of home, specialized clothing, and personal training to evaluate and maximize: • Independence •Safety •ADLs •Handwriting •Driving ability • Social worker - Arrange for community assistance programs and family counseling. Increase engagement in family activities.