Parkinson’s Disease Dr. Andrew Schmelz, PharmD Post-Doctoral Teaching Fellow Dept of Pharmacy Practice Purdue University March 4, 2009

Objectives Describe physiologic changes in patients with Parkinson’s Disease Describe physiologic changes in patients with Parkinson’s Disease List symptoms with which Parkinson’s patients typically present List symptoms with which Parkinson’s patients typically present List and define extrapyramidal symptoms List and define extrapyramidal symptoms For each drug class, state one example drug, mechanism of action, common dose, and associated side effects For each drug class, state one example drug, mechanism of action, common dose, and associated side effects

Background Parkinson’s disease: a degenerative disease of the brain that impairs motor skills, speech, and other functions Parkinson’s disease: a degenerative disease of the brain that impairs motor skills, speech, and other functions Especially prevalent in elderly white males Especially prevalent in elderly white males Characterized by specific changes in motor function Characterized by specific changes in motor function

Pathophysiology Substantia nigra Substantia nigra –Region in brain that plays a role in movement –Parkinson’s is characterized by loss of neuronal cells in this region

Pathophysiology (cont.) Neurons depleted in the substantia nigra result in imbalance of dopamine and acetylcholine Neurons depleted in the substantia nigra result in imbalance of dopamine and acetylcholine –Reduced dopamine activity –Normal acetylcholine activity DopamineAcetylcholine Dopamine Acetylcholine

Symptoms Tremor (and pill rolling) Tremor (and pill rolling) Bradykinesia Bradykinesia Rigid muscles (cogwheel rigidity) Rigid muscles (cogwheel rigidity) Impaired posture/balance Impaired posture/balance Loss of autonomic movement Loss of autonomic movement Speech changes Speech changes Dementia Dementia

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Extrapyramidal (EPS) Symptoms EPS symptoms usually occur secondary to medication EPS symptoms usually occur secondary to medication Dyskinesias (Movement disorders) Dyskinesias (Movement disorders) –Irregular body movements –Tongue movements, lip smacking –Finger movements, arm/leg movements Akathisia (Restlessness) Akathisia (Restlessness) –Extreme form of internal/external restlessness –Can be exhausting and debilitating

EPS Symptoms (cont.) Dystonia (Muscle tension disorders) Dystonia (Muscle tension disorders) –Very strong, painful muscle contractions –Unusual twisting of parts of the body “Tardive” Disorders “Tardive” Disorders –Indicates long-term observation of EPS symptoms –Can be of any classification listed above –Often indicate permanence

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Pharmacotherapy Approaches of therapy Approaches of therapy –Slow loss of dopamine in brain –Improve symptoms by other means –Prevent/delay non-muscular complications –Prevent/delay institutionalization Choice of medications used early in therapy will have a STRONG impact on long-term course of the disease Choice of medications used early in therapy will have a STRONG impact on long-term course of the disease

Levodopa/Carbidopa Example: Sinemet ® (levodopa/carbidopa) Example: Sinemet ® (levodopa/carbidopa) MOA: MOA: –L-Dopa - converted to DA in brain –Carbidopa – inc effectiveness and reduces SEs Dose: 25mg/100mg carbi/levo TID Dose: 25mg/100mg carbi/levo TID SE: EPS symptoms, orthostatic hypotension, “wearing off”, N/V SE: EPS symptoms, orthostatic hypotension, “wearing off”, N/V Most effective, used as late as possible Most effective, used as late as possible

“Wearing-Off” Phenomenon Loss of effectiveness of levodopa before next dose Loss of effectiveness of levodopa before next dose –Increased with duration of therapy –Indicates need for dosage increase –Limits duration of therapy

Dopamine Agonists Example: Mirapex ® (pramipexole) Example: Mirapex ® (pramipexole) MOA: Dopamine receptor agonist MOA: Dopamine receptor agonist Dose: 0.125mg – 1.5mg TID Dose: 0.125mg – 1.5mg TID SEs: orthostatic hypotension, impulsive behavior, hallucinations, EPS (especially when taken with levodopa) SEs: orthostatic hypotension, impulsive behavior, hallucinations, EPS (especially when taken with levodopa) Often used as initial treatment Often used as initial treatment Can be used concurrently with levodopa Can be used concurrently with levodopa

COMT Inhibitors Example: Comtan ® (entacapone) Example: Comtan ® (entacapone) MOA: inhibit COMT, responsible for breakdown of L-Dopa in periphery MOA: inhibit COMT, responsible for breakdown of L-Dopa in periphery Dose: 200mg with each levodopa/carbidopa dose Dose: 200mg with each levodopa/carbidopa dose SEs: increase in EPS symptoms, N/V, dry mouth SEs: increase in EPS symptoms, N/V, dry mouth Used in combination with levodopa/carbidopa Used in combination with levodopa/carbidopa

MAO-B Inhibitors Example: Deprenyl ® (selegiline) Example: Deprenyl ® (selegiline) MOA: inhibit MAO-B, responsible for breakdown of DA in brain MOA: inhibit MAO-B, responsible for breakdown of DA in brain Dose: 5mg BID Dose: 5mg BID SEs: dizziness, N/V, EPS symptoms SEs: dizziness, N/V, EPS symptoms Use with low-tyramine diet may be required Use with low-tyramine diet may be required Potential for drug interactions Potential for drug interactions

Anti-cholinergic Drugs Example: Cogentin® (benztropine) Example: Cogentin® (benztropine) MOA: inhibit ACh; restore balance to DA- ACh relationship MOA: inhibit ACh; restore balance to DA- ACh relationship Dose: 0.5-6mg daily Dose: 0.5-6mg daily SEs: anti-ACh effects (see prev lecture!) SEs: anti-ACh effects (see prev lecture!) Can impair cognitive function which limits use Can impair cognitive function which limits use

Amantadine Example: Symmetrel ® (amantadine) Example: Symmetrel ® (amantadine) MOA: enhance dopamine release, anti- ACh properties, NMDA antagonist MOA: enhance dopamine release, anti- ACh properties, NMDA antagonist Dose: mg/day (daily to BID) Dose: mg/day (daily to BID) SEs: dizziness, anxiety, N/V/D, anti-ACh effects SEs: dizziness, anxiety, N/V/D, anti-ACh effects Most commonly used later in therapy as adjunct Most commonly used later in therapy as adjunct

PT Considerations Coordinate therapy session with peak effects of drugs Coordinate therapy session with peak effects of drugs –After breakfast dose of levodopa Need to monitor BP while receiving antiparkinsons meds Need to monitor BP while receiving antiparkinsons meds –Concern for orthostatic hypotension PT can reduce need for Parkinson’s drugs PT can reduce need for Parkinson’s drugs

Features of PT Program Regular exercise Regular exercise –Walking (1+ miles/day), swimming, golf, etc Stretching and strengthening Stretching and strengthening Exaggerated or patterned movements Exaggerated or patterned movements Mobility aids, orthotics Mobility aids, orthotics Training in transfer techniques Training in transfer techniques Training in techniques to improve posture and walking Training in techniques to improve posture and walking

Questions?

Alzheimer’s Disease

Objectives Describe physiologic changes in patients with Alzheimer’s Disease Describe physiologic changes in patients with Alzheimer’s Disease For each drug class, state one example drug, mechanism of action, common dose, and associated side effects For each drug class, state one example drug, mechanism of action, common dose, and associated side effects

Background Alzheimer’s Disease is an age-related, non-reversible brain disorder Alzheimer’s Disease is an age-related, non-reversible brain disorder –Characterized by memory loss and confusion –Gradually leads to personality and behavioral changes Most common cause of dementia in patients age 65 and older Most common cause of dementia in patients age 65 and older

Pathophysiology Etiology of Alzheimer’s disease is unknown Etiology of Alzheimer’s disease is unknown Disease is characterized by: Disease is characterized by: –Amyloid plaques –Neurofibrillary tangles –Loss of connection of neurons responsible for memory and learning

Pharmacotherapy Currently, no FDA-approved treatment for slowing progression of disease Currently, no FDA-approved treatment for slowing progression of disease Pharmacotherapy aimed at treating symptoms and improving cognitive function Pharmacotherapy aimed at treating symptoms and improving cognitive function

Cholinesterase Inhibitors Example: Aricept ® (donepazil) Example: Aricept ® (donepazil) MOA: Increase ACh, increasing cholinergic function MOA: Increase ACh, increasing cholinergic function Dose: 5 – 10mg daily at bedtime Dose: 5 – 10mg daily at bedtime SEs: SLUD, N/V, bradycardia, hypotension, GI bleeding (rare) SEs: SLUD, N/V, bradycardia, hypotension, GI bleeding (rare)

Cholinesterase Inhibitors (cont.) Other examples: Other examples: –Exelon ® (rivastigmine) –Reminyl ® (galantamine) Appear to help patients for months to a few years Appear to help patients for months to a few years Indicated for mild to moderate Alzheimer’s symptoms Indicated for mild to moderate Alzheimer’s symptoms

NMDA Antagonist Example: Namenda ® (memantine) Example: Namenda ® (memantine) MOA: inhibit NMDA receptor, which plays a role in transmission of excitatory neurotransmission MOA: inhibit NMDA receptor, which plays a role in transmission of excitatory neurotransmission Dose: 5mg daily to 10mg BID Dose: 5mg daily to 10mg BID SEs: Drowsiness/dizziness SEs: Drowsiness/dizziness

PT Considerations Cognitive impairment will have negative effect on ability to follow instruction Cognitive impairment will have negative effect on ability to follow instruction

Questions?