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Drugs For Parkinson's Disease History of Parkinson's Disease First characterized in 1817 by James Parkinson : An Essay On The Shaking Palsy Dr. Parkinson characterized the disease: rigidity tremor mask face stooped body posture festinating gait Epidemiology The Real Cause Is Under Investigation Loss of dopamine production and release in the basal ganglia Presence of persistent cholinergic output in the basal ganglia in the absence of dopaminergic influences Environmental Toxins - Possible Causes? Manganese Workers In Chile Tetrahydroisoquinoline (TIQ) - A Toxic Chemical Also Causes Parkinsonism N-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) - A Toxic Chemical Causing Parkinsonism - Is Refractory To Treatment Parkinsonian Drugs Anticholinergic Agents Dopaminergic Agents Dopamine-Like Agents Anticholinergic Drugs Trihexyphenidyl HCl (Artane) Benztropine Mesylate (Cogentin) Biperiden HCl (Akineton) Procyclidine HCl (Kemadrin) Ethopropazine HCl (Parsidol) Diphenhydramine HCl (Benadryl) Mainline Medications Until The Early 1960's Now Are Used In A Supportive Role Useful In Patients With Minimal Symptoms Useful In Patients Who Cannot Tolerate Levodopa Useful In Patients In Whom Levodopa Does Not Appear Effective Mechanism Of Action Mainly Controls Salivation and Drooling Anticholinergics Blunt Excitatory Effects Of Acetylcholine Anticholinergics Competitively Block The Adrenergic Receptors Thus Reduce The Effects Of Acetylcholine Adverse Side Effects Of Anticholinergics Tachycardia Photosensitivity Of The Skin Constipation Urinary Retention Psychiatric Disturbances Dry Mouth (Xerostomia) Blurred Vision Pupillary Dilatation (Mydriasis) Hallucinations Confusion Dopaminergic Drugs True Dopamine Medications Levodopa (Larodopa, Levodopa) Carbidopa-Levodopa (Sinemet) The Problem With Levodopa When Levadopa is taken orally, it is changed in the gut into dopamine by an enzyme called dopa decarboxylase. 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 !! So….. the key is to keep levadopa as levadopa until it reaches the blood-brain barrier. How do we keep levadopa from being converted to dopamine ? You have to combine levadopa with a dopa decarboxylase inhibitor to insure that levadopa gets to and can cross over the blood-brain barrier. 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 This medication combination is called Sinemet At the blood-brain barrier, carbidopa is cleaved from levadopa. Levadopa than easily crosses over the blood-brain barrier into the brain. 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 To Improve Fine Motor Control To Improve Gross Motor Control & Balance During Ambulation To Decrease Tremor, Rigidity, Bradykinesia Improve Speech Improve Handwriting Improve Swallowing Normalization Of Respiratory Movement Adverse Side Effects Levodopa Tachycardia - Dopamine has beta1 effects on the cardiovascular system Postural Hypotension - Is lessened when Levodopa is taken with Carbidopa (Sinemet) Tics Spasms Ballistic Movements Behavioral Changes Depression, Manic Behavior, Anxiety Attacks, Confusion, Hallucinatory Behaviors May Require A Drug Holiday Dopamine-Like Drugs Amantadine HCl (Symmetrel) Amantadine Mechanism Of Action This Medication Is An Antiviral Medication Its Mechanism Of Action Is Unknown Believed to facilitate release of dopamine from storage sites in the basal ganglia Adverse Side Effects Orthostatic Hypotension Nightmares Confusion Depression Hallucinatory Behavior Dopamine-Like Drugs Bromocriptine Mesylate (Parlodel) Pergolide Mesylate (Permax) These Medications Are Ergot Alkaloids & Belong To The Same Family As LSD These Medications Are Used To Decrease The Untoward Side Effects Seen In Patients Using Levodopa - i.e. Involuntary Movements Ergolines : Adverse Side Effects Nausea Vomiting Postural Hypotension Visual and Auditory Hallucinations Livedo Reticularis - Purple Discoloration Of The Skin Dopamine-Like Drugs Selegiline HCl (Eldepryl) Selegiline Mechanism Of Action This Medication Is A Monoamine Oxidase (MAO) Inhibitor It inhibits MAO, the enzyme which destroys dopamine Selegiline prolongs the biological half-life of dopamine This Medication Is More Effective When Given To New Parkinson's Patients Selegiline allows the patient to: Take a lower dose of Levodopa Lengthens out the dosing intervals Side effects are insignificant Selegiline : Adverse Reactions Nausea & Vomiting Orthostatic Hypotension *** Fainting & Dizziness *** Hallucinations *** Loss Of Balance & Syncope *** Depression Dopamine-Like Drugs Pramipexole (Mirapex) Ropinrole (Requip) Mechanism Of Action Mechanism is not exactly clear Stimulates the dopamine receptors of the Corpus Striatum Adverse Side Effects Drowsiness Orthostatic Hypotension Hallucinations Dizziness Syncope Clinical Considerations Schedule The Rehab Session One Hour After The Morning Dose The patients will be rested from the night's sleep The drug will be at its peak effectiveness Maintain Joint Range Of Motion During A Drug Holiday Maintain As Much Cardiovascular Fitness As Possible During The Drug Holiday Monitor The Patient's Blood Pressure - Orthostatic Hypotension Be Aware Of The Patient's Balance & Gross Motor Control - Protect Against Falling