Drugs For Parkinson's Disease

History of Parkinson's Disease l First characterized in 1817 by James Parkinson : An Essay On The Shaking Palsy

l Dr. Parkinson characterized the disease: l rigidity l tremor l mask face l stooped body posture l festinating gait

Epidemiology n The Real Cause Is Under Investigation l Loss of dopamine production and release in the basal ganglia

l Presence of persistent cholinergic output in the basal ganglia in the absence of dopaminergic influences

l Environmental Toxins - Possible Causes? l Manganese Workers In Chile l Tetrahydroisoquinoline (TIQ) - A Toxic Chemical Also Causes Parkinsonism

l N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) - A Toxic Chemical Causing Parkinsonism - Is Refractory To Treatment

Parkinsonian Drugs l Anticholinergic Agents l Dopaminergic Agents l Dopamine-Like Agents

Anticholinergic Drugs l Trihexyphenidyl HCl (Artane) l Benztropine Mesylate (Cogentin) l Biperiden HCl (Akineton) l Procyclidine HCl (Kemadrin) l Ethopropazine HCl (Parsidol) l Diphenhydramine HCl (Benadryl)

l Mainline Medications Until The Early 1960's l Now Are Used In A Supportive Role l Useful In Patients With Minimal Symptoms

l Useful In Patients Who Cannot Tolerate Levodopa l Useful In Patients In Whom Levodopa Does Not Appear Effective

Mechanism Of Action l Mainly Controls Salivation and Drooling l Anticholinergics Blunt Excitatory Effects Of Acetylcholine l Anticholinergics Competitively Block The Adrenergic Receptors Thus Reduce The Effects Of Acetylcholine

Adverse Side Effects Of Anticholinergics l Tachycardia l Photosensitivity Of The Skin l Constipation l Urinary Retention l Psychiatric Disturbances

l Dry Mouth (Xerostomia) l Blurred Vision l Pupillary Dilatation (Mydriasis) l Hallucinations l Confusion

Dopaminergic Drugs u True Dopamine Medications l Levodopa (Larodopa, Levodopa) l Carbidopa-Levodopa (Sinemet)

The Problem With Levodopa l When Levadopa is taken orally, it is changed in the gut into dopamine by an enzyme called dopa decarboxylase.

l Herein lies the problem ….. Dopamine cannot cross the blood-brain barrier. So, it is useless to the Parkinson’s patient if it never gets into the brain !!

l So….. the key is to keep levadopa as levadopa until it reaches the blood-brain barrier. l How do we keep levadopa from being converted to dopamine ?

l You have to combine levadopa with a dopa decarboxylase inhibitor to insure that levadopa gets to and can cross over the blood-brain barrier.

l Carbidopa is the name of the dopa decarboxylase inhibitor that is combined with levadopa which enables levadopa to get to and cross over the blood-brain barrier l This medication combination is called Sinemet

l At the blood-brain barrier, carbidopa is cleaved from levadopa. l Levadopa than easily crosses over the blood-brain barrier into the brain.

l In the brain, levadopa is converted to dopamine where it exerts its inhibitory effects and calms the tremors, and other symptoms of Parkinson’s Disease

Medical Uses Treat The Symptomatology Treat The Symptomatology l To Improve Fine Motor Control l To Improve Gross Motor Control & Balance During Ambulation

l To Decrease Tremor, Rigidity, Bradykinesia l Improve Speech l Improve Handwriting l Improve Swallowing l Normalization Of Respiratory Movement

Adverse Side Effects u Levodopa u Tachycardia - Dopamine has beta- 1 effects on the cardiovascular system u Postural Hypotension - Is lessened when Levodopa is taken with Carbidopa (Sinemet)

l Tics l Spasms l Ballistic Movements

l Behavioral Changes l Depression, Manic Behavior, Anxiety Attacks, Confusion, Hallucinatory Behaviors l May Require A Drug Holiday

Dopamine-Like Drugs l Amantadine HCl (Symmetrel)

Amantadine Mechanism Of Action u This Medication Is An Antiviral Medication u Its Mechanism Of Action Is Unknown l Believed to facilitate release of dopamine from storage sites in the basal ganglia

Adverse Side Effects l Orthostatic Hypotension l Nightmares l Confusion l Depression l Hallucinatory Behavior

Dopamine-Like Drugs l Bromocriptine Mesylate (Parlodel) l Pergolide Mesylate (Permax)

l These Medications Are Ergot Alkaloids & Belong To The Same Family As LSD

l These Medications Are Used To Decrease The Untoward Side Effects Seen In Patients Using Levodopa - i.e. Involuntary Movements

Ergolines : Adverse Side Effects l Nausea l Vomiting l Postural Hypotension l Visual and Auditory Hallucinations l Livedo Reticularis - Purple Discoloration Of The Skin

Dopamine-Like Drugs l Selegiline HCl (Eldepryl)

Selegiline Mechanism Of Action l This Medication Is A Monoamine Oxidase (MAO) Inhibitor l It inhibits MAO, the enzyme which destroys dopamine l Selegiline prolongs the biological half-life of dopamine

l This Medication Is More Effective When Given To New Parkinson's Patients

l Selegiline allows the patient to: l Take a lower dose of Levodopa l Lengthens out the dosing intervals l Side effects are insignificant

Selegiline : Adverse Reactions n Nausea & Vomiting n Orthostatic Hypotension *** n Fainting & Dizziness *** n Hallucinations *** n Loss Of Balance & Syncope *** n Depression

Dopamine-Like Drugs n Pramipexole (Mirapex) n Ropinrole (Requip)

Mechanism Of Action n Mechanism is not exactly clear u Stimulates the dopamine receptors of the Corpus Striatum

Adverse Side Effects n Drowsiness n Orthostatic Hypotension n Hallucinations n Dizziness n Syncope

Clinical Considerations l Schedule The Rehab Session One Hour After The Morning Dose l The patients will be rested from the night's sleep l The drug will be at its peak effectiveness

n Maintain Joint Range Of Motion During A Drug Holiday

l Maintain As Much Cardiovascular Fitness As Possible During The Drug Holiday l Monitor The Patient's Blood Pressure - Orthostatic Hypotension l Be Aware Of The Patient's Balance & Gross Motor Control - Protect Against Falling