Slide 1 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 15 Drugs Used for Parkinson’s Disease

Slide 2 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 15 Lesson 15.1

Slide 3 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Learning Objectives Prepare a list of signs and symptoms of Parkinson’s disease and accurately define the vocabulary used for the pharmacologic agents prescribed and the disease state Name the neurotransmitter that is found in excess and the neurotransmitter that is deficient in people with parkinsonism

Slide 4 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Learning Objectives (cont’d) Describe reasonable expectations of medications prescribed for treatment of Parkinson’s disease Identify the period necessary for a therapeutic response to be observable when drugs used to treat parkinsonism are initiated

Slide 5 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Learning Objectives (cont’d) Name the action of bromocriptine, carbidopa, levodopa, entacapone, and apomorphine on neurotransmitters involved in Parkinson’s disease

Slide 6 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Parkinson’s Disease Chronic progressive disorder of CNS 2 nd most common neurodegenerative disease after Alzheimers Characteristic symptoms  Muscle tremors, slowness in movement (bradykinesia), muscle weakness with rigidity, alteration in posture and equilibrium Due to dopamine deficiency in extrapyramidal system within basal ganglia of brain  Extrapyramidal system For maintaining posture and muscle tone and regulating voluntary smooth muscle activity

Slide 7 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Parkinson’s Disease Neurotransmitters  Dopamine (inhibitory)  Acetylcholine (excitatory) Deficiency of dopamine leads to ACh activity leading to symptoms of Parkinsonism Types of parkinsonism  Primary (idiopathic) Due to reduction in dopamine-producing cells in basal ganglia  Secondary (induced by head trauma, infection, tumors, or drug exposure) Due to head trauma, intracranial infections, tumors and drug exposure

Slide 8 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Therapy for Parkinson’s Disease Goal of treatment is minimization of symptoms, no cure for disease Individualized combination therapy Therapy begins when symptoms interfere with ability to function in daily life All symptoms cannot be eliminated because of side effects involved Drug therapy  Selegiline to slow deterioration of dopaminergic nerve cells  Bromocriptine, carbidopa-levodopa, entacapone in combination to enhance dopaminergic activity  Anticholinergic to inhibit excess in cholinergic activity

Slide 9 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Parkinson’s Disease Diagnosis Signs  Facial appearance  Psychological involvement Symptoms  Motor function Tremor Dyskinesia; propulsive, uncontrolled movement Bradykinesia, akinesia  Excess salivation

Slide 10 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Process for Parkinson’s Disease Therapy Assessment  Unified Parkinson’s Disease Rating Scale (UPDRS) evaluates: 1. mentation, behavior, and mood; 2. ADLs; 3. motor examination; 4. complications of therapy; 5. modified Hoehn and Yahr staging; 6. Schwab and England ADL scale Planning  Determine baselines for patent functioning Implementation  Identify patient needs  Monitor patient functioning

Slide 11 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Management of Parkinson’s Disease

Slide 12 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Amantadine hydrochloride  Originally for viral infection  Administered to Asian influenza with parkinsonism  Action Exact MOA is unknown Slows destruction of dopamine Aid in release of dopamine from its storage site Reduction in benefit after 2 to 3 months  Gradual discontinuation

Slide 13 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Amantadine hydrochloride – cont’d  Uses For relief of symptoms associated with Parkinson’s Treatment of susceptible strains of viral influenza  Therapeutic outcome Establish balance of dopamine and ACh in basal ganglia of brain by enhancing delivery of dopamine to brain cells

Slide 14 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Bromocriptine mesylate  Actions Ergot derivative the stimulates the D2 dopamine receptors in basal ganglia of brain  Uses Nearly as effective as levodopa Used alone or in treatment of mild symptoms or in combination with carbidopa-levodopa to reduce both dose of carbidopa-levodopa and parkinsonian symptoms  Therapeutic outcome To stimulate dopaminergic neurotransmission to relieve the rigidity, akinesia, and tremor associated with dopamine deficiency

Slide 15 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Carbidopa  Actions Carbidopa is an enzyme inhibitor that reduces metabolism of levodopa, allowing a greater portion of administered levodopa to reach the desired receptor sites in basal ganglia No effect when used alone Must be used in combination with levodopa  Uses To reduce dose of levodopa With levodopa, carbidopa increases both plasma levels and plasma half-life of levodopa Parcopa  Dissolves in mouth to reduce choking

Slide 16 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Carbidopa – cont’d  Therapeutic outcomes Establish balance of dopamine and ACh in basal ganglia by enhancing delivery of dopamine to brain cells

Slide 17 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Levodopa  Actions Dopamine when administered orally does not enter the brain Levodopa does cross the BBB, and metabolized into dopamine and replaces dopamine deficiency in basal ganglia Dopamine stimulates D1, D2, and D3 dopamine receptors  Uses 75% respond favorably to levodopa, but after a few years the response diminishes, becomes uneven and more side effects  Therapeutic outcomes Establish balance of dopamine and ACh in basal ganglia of brain by enhancing delivery of dopamine to brain cells

Slide 18 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Pergolide mesylate  Actions Ergot derivative potent to D1, D2, and D3 dopamine receptor stimulant Exert its effect in patients with Parkinson’s disease by directly stimulating postsynaptic dopamine receptors in nigrostriatal system of brain  Uses Used in combination with carbidopa-levodopa Associated with development of restrictive valvular heart disease (valvular fibrosis)  Therapeutic outcome 1. improve motor and ADL scores; 2. decreased “off” time; 3. reduced dosage of levodopa

Slide 19 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Pramipexole  Action Nonergot dopamine agonist that stimulates D2 and D3 dopamine receptors  Uses Used alone to manage early S/Sx of parkinsonism by improving ADLs, tremor, rigidity, bradykinesia, postural stability Used in combination with levodopa in advanced parkinsonism to manage similar S/Sx of disease  Therapeutic outcome 1. improve motor and ADL scores; 2. decreased “off” time; 3. reduced dosage of levodopa

Slide 20 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Dopamine Agonists Ropinirole  Action Nonergot dopamine agonist that stimulates D2 and D3 dopamine receptor  Uses Used alone to manage early S/Sx of parkinsonism by improving ADLs, tremor, rigidity, bradykinesia, postural stability Used in combination with levodopa in advanced parkinsonism to manage similar S/Sx of disease and reduce degree of “on-off” symptoms associated with long-term use of levodopa  Therapeutic outcome 1. improve motor and ADL scores; 2. decreased “off” time; 3. reduced dosage of levodopa

Slide 21 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 15 Lesson 15.2

Slide 22 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Learning Objectives Develop a health teaching plan for an individual being treated with levodopa Name the action of bromocriptine, carbidopa, levodopa, entacapone, and apomorphine on neurotransmitters involved in Parkinson’s disease

Slide 23 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Learning Objectives (cont’d) List symptoms that can be attributed to the cholinergic activity of pharmacologic agents Cite the specific symptoms that should show improvement when anticholinergic agents are administered to the patient with Parkinson’s disease

Slide 24 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Levodopa Therapy Baseline assessment  UPDRS  Check for history of glaucoma Implementation  Administer with food Side effects  Report movements and nightmares Drug interactions  Numerous

Slide 25 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: COMT Inhibitor Entacapone  Actions Reduces destruction of dopamine in peripheral tissues, allows dopamine to reach brain  Uses Inhibits dopamine metabolism, resulting in a more constant dopaminergic stimulation in brain  Reduces motor fluctuations, increases on-time, reduces off- time, results in reduction in dosage of L-dopa Not effective over time Report hallucinations Monitor blood pressure Interacts with antihypertensive agents  Therapeutic outcome 1. improve motor and ADL scores; 2. decreased “off” time; 3. reduced dosage of levodopa

Slide 26 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Anticholinergic Agents Mode of action  Reduce hyperstimulation caused by excessive acetylcholine Indications  Reduce severity of tremor and drooling  More useful in patients with minimal symptoms and no cognitive impairment  Little effect on rigidity, bradykinesia, or postural abnormalities Therapeutic outcomes  Reduction in severity of tremor and drooling caused by a relative excess of ACh in basal ganglia

Slide 27 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Anticholinergic Agents Drug interactions  Amantadine, TCAs, Phenothiazines Enhance anticholinergic S/E Confusion, hallucinations are characteristic of excessive anticholinergic activity  L-dopa Large doses of anticholinergic may slow gastric emptying and inhibit absorption of L-dopa Side effects  Nightmares, depression, confusion, hallucination, orthostatic hypotension, palpitations, dysrhythmias

Slide 28 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Names of Anticholinergic Agents Benztropine mesylate (Cogentin) Biperiden hydrochloride (Akineton) Diphenhydramine hydrochloride (Benadryl) Orphenadrine citrate (Banflex, Norflex)

Slide 29 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Miscellaneous Agents Selegiline  Actions Potent monoamine oxidase type B inhibitor Reduces destruction of dopamine in brain allows dopamine to reach brain  Uses Have similar adjunctive activity to carbidopa-levodopa Combination of selegiline and carbidopa-levodopa improves memory and motor speed and may increase life expectancy Neuroprotective effect by interfering withh ongoing degeneration of striated dopaminergic neuron Used in early treatment of PD to slow progression of symptoms and delay initiation of L-dopa therapy Not effective over time

Slide 30 Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Class: Miscellaneous Agents Selegiline  Side effects and drug interactions Report hallucinations or confusion Monitor blood pressure Tell patient to avoid Chianti, fava beans, and cheese  High tyramine content  Lead to hypertensive reaction