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Drugs For Parkinson's DiseaseDrugs For Parkinson's Disease
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History of Parkinson's DiseaseHistory of Parkinson's Disease
First characterized in 1817 by James First characterized in 1817 by James Parkinson : Parkinson : An Essay On The An Essay On The Shaking PalsyShaking Palsy
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Dr. Parkinson characterized the Dr. Parkinson characterized the disease:disease:rigidityrigidity tremortremormask facemask facestooped body posturestooped body posture festinating gaitfestinating gait
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EpidemiologyEpidemiology
The Real Cause Is Under The Real Cause Is Under InvestigationInvestigationLoss of dopamine production and Loss of dopamine production and
release in the basal gangliarelease in the basal ganglia
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Presence of persistent cholinergic Presence of persistent cholinergic output in the basal ganglia in the output in the basal ganglia in the absence of dopaminergic absence of dopaminergic influences influences
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Environmental Toxins - Possible Environmental Toxins - Possible Causes?Causes?Manganese Workers In ChileManganese Workers In ChileTetrahydroisoquinoline (TIQ) - A Tetrahydroisoquinoline (TIQ) - A
Toxic Chemical Also Causes Toxic Chemical Also Causes ParkinsonismParkinsonism
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N-methyl-4-phenyl-1,2,3,6-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - A tetrahydropyridine (MPTP) - A Toxic Chemical Causing Toxic Chemical Causing Parkinsonism - Is Refractory To Parkinsonism - Is Refractory To TreatmentTreatment
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Parkinsonian DrugsParkinsonian Drugs
Anticholinergic AgentsAnticholinergic Agents Dopaminergic AgentsDopaminergic Agents Dopamine-Like AgentsDopamine-Like Agents
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Anticholinergic DrugsAnticholinergic Drugs Trihexyphenidyl HCl (Artane)Trihexyphenidyl HCl (Artane) Benztropine Mesylate (Cogentin)Benztropine Mesylate (Cogentin) Biperiden HCl (Akineton)Biperiden HCl (Akineton) Procyclidine HCl (Kemadrin)Procyclidine HCl (Kemadrin) Ethopropazine HCl (Parsidol)Ethopropazine HCl (Parsidol) Diphenhydramine HCl (Benadryl)Diphenhydramine HCl (Benadryl)
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Mainline Medications Until The Mainline Medications Until The Early 1960'sEarly 1960's
Now Are Used In A Supportive RoleNow Are Used In A Supportive RoleUseful In Patients With Minimal Useful In Patients With Minimal
SymptomsSymptoms
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Useful In Patients Who Cannot Useful In Patients Who Cannot Tolerate LevodopaTolerate Levodopa
Useful In Patients In Whom Useful In Patients In Whom Levodopa Does Not Appear Levodopa Does Not Appear EffectiveEffective
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Mechanism Of ActionMechanism Of Action Mainly Controls Salivation and Mainly Controls Salivation and
DroolingDrooling Anticholinergics Blunt Excitatory Anticholinergics Blunt Excitatory
Effects Of AcetylcholineEffects Of AcetylcholineAnticholinergics Competitively Anticholinergics Competitively
Block The Adrenergic Receptors Block The Adrenergic Receptors Thus Reduce The Effects Of Thus Reduce The Effects Of AcetylcholineAcetylcholine
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Adverse Side Effects Of Anticholinergics
Adverse Side Effects Of Anticholinergics
TachycardiaTachycardia Photosensitivity Of The SkinPhotosensitivity Of The Skin ConstipationConstipation Urinary RetentionUrinary Retention Psychiatric DisturbancesPsychiatric Disturbances
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Dry Mouth (Xerostomia)Dry Mouth (Xerostomia) Blurred VisionBlurred Vision Pupillary Dilatation (Mydriasis)Pupillary Dilatation (Mydriasis) HallucinationsHallucinations ConfusionConfusion
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Dopaminergic DrugsDopaminergic Drugs
TrueTrue Dopamine Medications Dopamine MedicationsLevodopa (Larodopa, Levodopa)Levodopa (Larodopa, Levodopa)Carbidopa-Levodopa (Sinemet)Carbidopa-Levodopa (Sinemet)
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The Problem With LevodopaThe Problem With Levodopa
When Levadopa is taken orally, When Levadopa is taken orally, it is changed in the gut into it is changed in the gut into dopaminedopamine by an enzyme called by an enzyme called dopa decarboxylase.dopa decarboxylase.
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Herein lies the problem ….. Herein lies the problem ….. Dopamine Dopamine cannotcannot cross the cross the blood-brain barrier. So, it is blood-brain barrier. So, it is useless to the Parkinson’s patient useless to the Parkinson’s patient if it never gets into the brain !!if it never gets into the brain !!
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So….. the key is to keep levadopa So….. the key is to keep levadopa as levadopa until it reaches the as levadopa until it reaches the blood-brain barrier.blood-brain barrier.
How do we keep levadopa from How do we keep levadopa from being converted to dopamine ?being converted to dopamine ?
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You have to combine levadopa You have to combine levadopa with a with a dopa decarboxylase dopa decarboxylase inhibitorinhibitor to insure that levadopa to insure that levadopa gets to and can cross over the gets to and can cross over the blood-brain barrier.blood-brain barrier.
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Carbidopa is the name of the Carbidopa is the name of the dopa dopa decarboxylase inhibitor decarboxylase inhibitor that is that is combined with levadopa which combined with levadopa which enables levadopa to get to and enables levadopa to get to and cross over the blood-brain barriercross over the blood-brain barrier
This medication combination is This medication combination is called called SinemetSinemet
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At the blood-brain barrier, At the blood-brain barrier, carbidopa is cleaved from carbidopa is cleaved from levadopa.levadopa.
Levadopa than easily crosses Levadopa than easily crosses over the blood-brain barrier into over the blood-brain barrier into the brain.the brain.
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In the brain, levadopa is In the brain, levadopa is converted to dopamine where it converted to dopamine where it exerts its inhibitory effects and exerts its inhibitory effects and calms the tremors, and other calms the tremors, and other symptoms of Parkinson’s Diseasesymptoms of Parkinson’s Disease
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Medical UsesMedical Uses
Treat The Symptomatology Treat The Symptomatology
To Improve Fine Motor ControlTo Improve Fine Motor ControlTo Improve Gross Motor Control To Improve Gross Motor Control
& Balance During Ambulation& Balance During Ambulation
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To Decrease Tremor, Rigidity, To Decrease Tremor, Rigidity, BradykinesiaBradykinesia
Improve SpeechImprove SpeechImprove HandwritingImprove HandwritingImprove SwallowingImprove SwallowingNormalization Of Respiratory Normalization Of Respiratory
Movement Movement
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Adverse Side EffectsAdverse Side Effects LevodopaLevodopa
TachycardiaTachycardia - Dopamine has beta- - Dopamine has beta-1 effects on the cardiovascular 1 effects on the cardiovascular systemsystem
Postural HypotensionPostural Hypotension - Is lessened - Is lessened when Levodopa is taken with when Levodopa is taken with Carbidopa (Sinemet)Carbidopa (Sinemet)
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TicsTics SpasmsSpasms Ballistic MovementsBallistic Movements
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Behavioral ChangesBehavioral ChangesDepression, Manic Behavior, Depression, Manic Behavior,
Anxiety Attacks, Confusion, Anxiety Attacks, Confusion, Hallucinatory BehaviorsHallucinatory Behaviors
May Require A Drug HolidayMay Require A Drug Holiday
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Dopamine-Like DrugsDopamine-Like Drugs
Amantadine HCl (Symmetrel)Amantadine HCl (Symmetrel)
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AmantadineMechanism Of Action
AmantadineMechanism Of Action
This Medication Is An Antiviral This Medication Is An Antiviral MedicationMedication
Its Mechanism Of Action Is Its Mechanism Of Action Is UnknownUnknownBelieved to facilitate release of Believed to facilitate release of
dopamine from storage sites in the dopamine from storage sites in the basal ganglia basal ganglia
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Adverse Side EffectsAdverse Side Effects
Orthostatic HypotensionOrthostatic HypotensionNightmaresNightmaresConfusionConfusionDepressionDepressionHallucinatory BehaviorHallucinatory Behavior
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Dopamine-Like DrugsDopamine-Like Drugs
Bromocriptine Mesylate (Parlodel)Bromocriptine Mesylate (Parlodel) Pergolide Mesylate (Permax)Pergolide Mesylate (Permax)
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These Medications Are Ergot These Medications Are Ergot Alkaloids & Belong To The Same Alkaloids & Belong To The Same Family As LSDFamily As LSD
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These Medications Are Used To These Medications Are Used To Decrease The Untoward Side Decrease The Untoward Side Effects Seen In Patients Using Effects Seen In Patients Using Levodopa - i.e. Involuntary Levodopa - i.e. Involuntary MovementsMovements
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Ergolines : Adverse Side EffectsErgolines : Adverse Side Effects
NauseaNausea VomitingVomiting Postural HypotensionPostural Hypotension Visual and Auditory HallucinationsVisual and Auditory Hallucinations Livedo Reticularis - Purple Livedo Reticularis - Purple
Discoloration Of The SkinDiscoloration Of The Skin
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Dopamine-Like DrugsDopamine-Like Drugs
Selegiline HCl (Eldepryl)Selegiline HCl (Eldepryl)
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Selegiline Mechanism Of Action
Selegiline Mechanism Of Action
This Medication Is A Monoamine This Medication Is A Monoamine Oxidase (MAO) InhibitorOxidase (MAO) InhibitorIt inhibits MAO, the enzyme which It inhibits MAO, the enzyme which
destroys dopaminedestroys dopamineSelegiline prolongs the biological Selegiline prolongs the biological
half-life of dopaminehalf-life of dopamine
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This Medication Is More Effective This Medication Is More Effective When Given To New Parkinson's When Given To New Parkinson's PatientsPatients
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Selegiline allows the patient to:Selegiline allows the patient to:Take a lower dose of LevodopaTake a lower dose of LevodopaLengthens out the dosing intervalsLengthens out the dosing intervalsSide effects are insignificantSide effects are insignificant
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Selegiline : Adverse ReactionsSelegiline : Adverse Reactions
Nausea & VomitingNausea & Vomiting Orthostatic Hypotension ***Orthostatic Hypotension *** Fainting & Dizziness ***Fainting & Dizziness *** Hallucinations ***Hallucinations *** Loss Of Balance & Syncope ***Loss Of Balance & Syncope *** DepressionDepression
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Dopamine-Like DrugsDopamine-Like Drugs
Pramipexole (Mirapex)Pramipexole (Mirapex) Ropinrole (Requip)Ropinrole (Requip)
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Mechanism Of ActionMechanism Of Action
Mechanism is not exactly clearMechanism is not exactly clear Stimulates the dopamine receptors Stimulates the dopamine receptors
of the Corpus Striatumof the Corpus Striatum
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Adverse Side EffectsAdverse Side Effects
DrowsinessDrowsiness Orthostatic HypotensionOrthostatic Hypotension HallucinationsHallucinations DizzinessDizziness SyncopeSyncope
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Clinical ConsiderationsClinical Considerations
Schedule The Rehab Session One Hour Schedule The Rehab Session One Hour After The Morning DoseAfter The Morning DoseThe patients will be rested from the The patients will be rested from the
night's sleepnight's sleepThe drug will be at its peak The drug will be at its peak
effectivenesseffectiveness
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Maintain Joint Range Of Motion Maintain Joint Range Of Motion During A Drug HolidayDuring A Drug Holiday
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Maintain As Much Cardiovascular Maintain As Much Cardiovascular Fitness As Possible During The Drug Fitness As Possible During The Drug HolidayHoliday
Monitor The Patient's Blood Monitor The Patient's Blood Pressure - Pressure - Orthostatic HypotensionOrthostatic Hypotension
Be Aware Of The Patient's Balance Be Aware Of The Patient's Balance & Gross Motor Control - & Gross Motor Control - Protect Protect Against FallingAgainst Falling