Drugs For Parkinson's DiseaseDrugs For Parkinson's Disease

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

Dr. Parkinson characterized the Dr. Parkinson characterized the disease:disease:rigidityrigidity tremortremormask facemask facestooped body posturestooped body posture festinating gaitfestinating gait

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

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

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

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

Parkinsonian DrugsParkinsonian Drugs

Anticholinergic AgentsAnticholinergic Agents Dopaminergic AgentsDopaminergic Agents Dopamine-Like AgentsDopamine-Like Agents

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)

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

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

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

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

Dry Mouth (Xerostomia)Dry Mouth (Xerostomia) Blurred VisionBlurred Vision Pupillary Dilatation (Mydriasis)Pupillary Dilatation (Mydriasis) HallucinationsHallucinations ConfusionConfusion

Dopaminergic DrugsDopaminergic Drugs

TrueTrue Dopamine Medications Dopamine MedicationsLevodopa (Larodopa, Levodopa)Levodopa (Larodopa, Levodopa)Carbidopa-Levodopa (Sinemet)Carbidopa-Levodopa (Sinemet)

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.

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 !!

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 ?

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.

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

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.

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

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

To Decrease Tremor, Rigidity, To Decrease Tremor, Rigidity, BradykinesiaBradykinesia

Improve SpeechImprove SpeechImprove HandwritingImprove HandwritingImprove SwallowingImprove SwallowingNormalization Of Respiratory Normalization Of Respiratory

Movement Movement

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)

TicsTics SpasmsSpasms Ballistic MovementsBallistic Movements

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

Dopamine-Like DrugsDopamine-Like Drugs

Amantadine HCl (Symmetrel)Amantadine HCl (Symmetrel)

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

Adverse Side EffectsAdverse Side Effects

Orthostatic HypotensionOrthostatic HypotensionNightmaresNightmaresConfusionConfusionDepressionDepressionHallucinatory BehaviorHallucinatory Behavior

Dopamine-Like DrugsDopamine-Like Drugs

Bromocriptine Mesylate (Parlodel)Bromocriptine Mesylate (Parlodel) Pergolide Mesylate (Permax)Pergolide Mesylate (Permax)

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

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

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

Dopamine-Like DrugsDopamine-Like Drugs

Selegiline HCl (Eldepryl)Selegiline HCl (Eldepryl)

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

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

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

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

Dopamine-Like DrugsDopamine-Like Drugs

Pramipexole (Mirapex)Pramipexole (Mirapex) Ropinrole (Requip)Ropinrole (Requip)

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

Adverse Side EffectsAdverse Side Effects

DrowsinessDrowsiness Orthostatic HypotensionOrthostatic Hypotension HallucinationsHallucinations DizzinessDizziness SyncopeSyncope

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

Maintain Joint Range Of Motion Maintain Joint Range Of Motion During A Drug HolidayDuring A Drug Holiday

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