PD药物治疗策略(2月28日)

1、DDC = dopa decarboxylase; COMT = catechol-O-methyltransferase; 3-OMD = 3-O-methyldopa;BBB = blood-brain barrier; MAO-B = monoamine oxidase-B; DOPAC = 3,4-dihydroxyphenylacetic acid; HVA = homovanillic acid; 3-MT = 3-methoxytyramine.-A 4-week, double-blind, crossover study (n=23).UPDRS = Unified Park

2、insons Disease Rating Scale.Adapted with permission from Ruottinen HM et al. J Neurol Neurosurg Psychiatry. 1996;60:36-40. BMJ Publishing Group.AUC 35%tmax Cmax Mean Levodopa Concentration (ng/mL)01234050010001500200025003000Time (h)BaselinePlaceboEntacaponePlasma LevodopaMean Motor Scores6055504540

3、3530012345Time (h)UPDRS Motor Scores托卡朋恩他卡朋作用位点中枢和外周外周剂量100mg bid-tid200mg with each dose L-dopa/carbidopa其他肝毒性最大剂量: 1600mg/dayC. Warren Olanow wt al An algorithm(decision tree) for the management of Parkinsons diseases 2001:Treatment Guideline 2001 Neurology 56(suppl.5):S1-88Neuropsychiatric manife

4、stationsCognitive impairmentSleep disturbancesAutonomic dysfunctionsSensory phenomena85 patients:Mean age66.2 (38-85)Mean age at onset58.9 (31-83)Mean disease duration 7.8 (0.5-33)Median H & Y 2.2 (1-5) 84.7% with motor fluctuations, all experienced one or more non-motor symptoms47.2% with neuro

5、psychiatric manifestations84.7% with autonomic disturbances69.4% with sensory phenomena Gunal DI et al. Can J Neurol Sci 2002;29:61-64.Early age of disease onsetLonger duration of diseaseHigher doses of levodopaAge of patientPresence of motor fluctuationsWitjas T et al. Neurology, 2002;59:408-413.lM

6、edication regimenlResponse to medication dosing throughout the daylSide-effects from medicationslDaily activitieslDietary habitslSleep patternslEmotional statelHistory of response to pharmacologic therapyDepressionHallucination / deliriumBehavioral fluctuation-Anxiety / panic-AgitationAffects 40-50%

7、 of patientsCharacterized by:Feeling of guiltLack of self esteemLoss of initiativeHelplessness, remorse, sadnessCauses may be endogenous, exogenous, or bothWitjas T et al. Neurology, 2002;59:408-413.Reduce / discontinue medicationsTreat underlying medical illnessAntidepressantsAtypical neurolepticsA

8、nxiolyticsKeep active / exerciseEducate caregiversPsychological counselingAffects up to 40% of patientsLate feature of PDDifferential diagnosis: PDD vs AD vs DLBFrontal-executive dysfunction, impairments of visuo-spatial abilities, temporal ordering, memory and attentionIncreases caregiver burdenNo

9、proven medical therapyCholinesterase inhibitor?Avoid offending medicationsSymptomatic behavioral treatmentCaregiver educationInsomniaREM behavior disorderNightmaresObstructive sleep apneaExcessive daytime sleepinessTreat depression / anxietyAdd controlled-release levodopa at bedtimeSleep hygiene pro

10、gramShort-acting sedative hypnoticsMinimize nocturia夜尿症Clonazepam for REM Behavior DisordersDiscontinue tricyclic drugs and MAO inhibitorsAvoid stimulants in eveningEvaluate sleep disorderJudicious use of stimulants for EDSConstipationUrinary problemsOrthostatic hypotensionSexual problemsImpaired th

11、ermoregulationDysphagiaSiarrhea/droolingDietary modificationIncrease physical activityStop anticholinergicsStool softenerBulk fibersLactulose乳果糖Mild laxativeEducationNocturia, frequency, urgencyReduce evening fluid intakeElevate head of bedMedication (oxybutynin奥昔布宁, tolterodine托特罗定)Consider urologic evaluationEliminate antihypertensives, if possibleBehavior modificationIncrease salt and fluid intakeSupport stockingsElevate head of bedMedications (fludrocortisone, midodrine)Rigidity / crampsDystonic painMusculoskeletal pain associated with immobilityHeaviness in lim