Drug Benztropine Cogentin MOA Anticholinergic agent cholinergic activity in PD pts worsening symptoms Block this Trihexylphenidyl Artane Anticholinergic Amantadine Symmetrel Unclear DA anticholinergic Carbidopa Levodopa Sinemet Oral disintegrating tabs Parcopa intrajejunal infusion enteral suspension Duopa Sinemet L Dopa gets broken down into DA in periph before gets to CNS DA does NOT cross BBB ADE when DA in periph Carbidopa blocks breakdown of LD in periph cross BBB Dose 0 5 1mg PO qHS titrate to 3 6 mg day 2 4 divided doses know normal range and titration is necessary 1 mg PO TID with meals titrate to 6 10 mg d in 3 4 divided doses 100 mg PO qAM with breakfast titrate to 200 400 mg PO QD divided BID tachyphylaxis may develop 1 2m acute response to drug VERY pt specific 25 100 mg PO daily titrate to TID max 800 1000 LD daily CR unpredictable kinetics mimic natural DA release like CIV Place in Therapy ADE First widely accepted tx of PD efficacious for minor symptomatic control mostly tremor current use limited early in disease more efficacious agents ADE ANTI SPLUD limits use drowsiness confusion memory impairment dry eyes dry mouth blurred vision constipation urinary retention Same as Above Elderly esp sensitive Same as Above Modest efficacy in control of PD symptoms tremor bradykinesia rigidity shown to improve dyskinesia involuntary muscle movement i e Tics from Levodopa treated Pts CNS confusion insomnia dizziness dry skin Peripheral nausea dry mouth Livedo reticularis reversible fishnet like skin discoloration Most effective drug to treat PD improves bradykinesia rigidity less effective against speech gaint Timing early vs late controversy Early s sx but with faster onset of ADE efficacy over time GI N V anorexia 50 avoid tx w compazine reglan droperidol blocks DA CV orthostatic hypotension Neuropsych Agitation confusion hallucinations psychosis worsening dementia motor complications Carbdopa Levodopa Motor complication ADE 20 75 of pts after 3 5 years 1 Motor fluctuations a Wearing off gradual symptom 1 L dopa metabolic pathway control toward end of dosing interval strategy dosing frequency CR tx or adjunct therapy COMTI agonist MAOBI b On Off symptoms controlled uncontrolled strategy adjunct therapy drug holiday 2 Peak Dose Dyskinesias associated with peak levels of DA admin DA cells buffer capacity non continuous erratic release of DA strategy dose while frequency DA agonist MAOB I or COMT I Motor fluctuations 1 Dyskinesia abnormal involuntary excessive movements a orofacial lip smacking tongue thrusting blinking grimacing speech can be affected b extremity involvement spasmodic twisting of limbs c Posture Rocking swaying Use of amantadine may help Clozapine Olanzapine effective 2 Dystonia sustained painful muscle contractions distal lower extremities feet toes usually seen in AM improvement with first levodopa dose cervical dystonia responds to botulinum toxin Tx 3 Myoclonus bursts of muscle activity during sleep can affect toes ankle knee hip bedtime levodopa dose 4 Akathisia feeling of inner restlessness pt can t sit still pacing shifting tapping feet tx with benzos ativan CAUTION IN ELDERLY Recent Cochrane review DA agonists MOST effective adjunct tx vs COMTI and MAOBI better s sx control odd time and reducing levodopa dose BUT incidence of dyskinesia ADE compared to placebo Drug Entacapone Comtan MOA COMT inhibitors prevents breakdown of L Dopa in periph and CNS 200 mg with each sinemet dose up to 8x day shorter half Dose life Tolcapone tasmar off market in Europe COMT inhibitor 100 mg PO TID w sinemet Monitor AST ALT at baseline bi weekly in first year then monthly x 6m then every 2 months D C if ASL ALT exceed upper limit Place in Therapy Longer clinical levodopa response penetration Adjuct tx with levodopa levodopa metab BBB to motor fluctuations NOT monotx improves symptomatic control motor fluctuations in levodopa tx patients Improves symptomatic control with Levodopa efficacious for motor fluctuations off on time 1 2 hrs day Drug Stalevo levodopa carbidopa entacapone MOA Combo sinemet and COMT inhibitor Dose N A Place in Therapy pill burden Same as Sinemet and Entacapone Selegiline Eldepryl Deprenyl Irreversible MAO B inhibitor DA 5 mg PO qAM w breakfast Titrate to Effective as monotherapy levodopa sparing NOT FDA approved Well tolerated similar to placebo dopaminergic effects when added ADE DA Nausea dyskinesia transient Liver enzymes few cases of elevations NO hepatotoxicity no monitoring required Dopaminergic N dyskinesias hallucinations anorexia insomnia orthostatic hypotension Non DA diarrhea tolerance HEPATOTOXICITY why not commonly used LFT elevations and reported cases of liver failure NOT 1st line agent unless beneft risk ADE above 2 breakdown into inactive components 5mg PO BID Zydis Selegiline Irreversible MAO B Rasagiline Azilect 1 25 mg PO QD AM for 6 weeks 2 5 0 5 1 mg PO QD inhibitor Potent irreversible MAO B inhibitor Safinamide Phase III studies investigaitional MAO B inhibitor Rotigotine Neupro DA agonist 2 4 6mg patches questionable efficacy as adjunct tx LD dose not associated with improved symptomatic control Neuroprotective oxidative stress Oral disintegrating tablet Direct absorption no first pass effect dose plasma concentration Indicated for PD motor symptoms monotherapy in early disease adjunct tx with levodopa in late disease significant improvements in off time off time vs levodopa alone equivalent in on time though more dyskinesias in rasagiline levodopa Transdermal delivery system off time levodopa dose fluctuations Modest improvements in UPDRS scores as monotherapy in pts with early stage disease to levodopa psychosis N dyskinesias orthostatic hypotension insomnia metabolized to amphetamine derivatives may have effects on cognition confusion insomnia consistent w levodopa treated pts in studies dopaminergic similar to ADE if levodopa levels dyskinesias psychosis insomnia orthostatic hypotension hallucinations D D interactions Metabolized by CYP1A2 Ciprofloxacin plasma levels of rasagiline Patches contain metabisulfite DO NOT USE IN SULFA ALLERGIC PATIENTS May cause significant N V Apomorphine Apokyn DA agonist inhaled formulation investigational better tolerated SC formulation indicated for acute unpredictable off episodes better response in pts with early disese Drug Pergolide permax Bromocryptine Parlodel MOA Ergot derivative DA agonist older Ergot derivative DA agonist older D1 D2 and 5HT effects on striatal DA receptors