Introduction
Treatment of motor symptoms
Drug | Step | Mode of action within the dopaminergic system | Tolerability | Main clinical relevant side effects | Efficacy |
---|---|---|---|---|---|
MAO-B-I | I | stabilize dopamine levels in the striatal synaptic cleft by inhibition of dopamine metabolism | +++ | risk for rise of raised blood pressure and increase of liver enzymes, contraindication for simultaneous fluoxetine and fluvoxamine use, precaution with application of SSRI in general | + |
NMDA-A | I | indirect dopaminergic modulation, reduce motor complications (?) | + | oedema, insomnia, hallucinations | + |
DA | II | stimulate directly postsynaptic striatal receptors linked to motor symptom control | + | Orthostatic syndrome, oedema, nausea, slow titriation necessary | ++ |
LD/DDI/COMT-I | III | precursor of dopamine, DDI and COMT-I reduce LD metabolism | +++ | orthostatic syndrome, homocysteine elevation (LD/DDI alone), motor complications, diarrhea (COMT-I) | +++ |
infusion systems (apomorphine, LD) | IV | See DA, respectively LD line | + | Subcutaneous local inflammatory reactions | +++ |
DBS | V | electric stimulation of the subthalamic nuclei or globus pallidus | + | Social adjustment problems, depression, cognitive dysfunction. | +++ |
Monoaminooxidase B (MAO-B) inhibition
MAO-B-I and progression of PD
Dopamine agonists (DA)
compound | dose range | administration | half life |
---|---|---|---|
bromocriptine | 10 - 50 | oral, t.i.d. | 3 – 6 |
lisurid | 0.2 - 3 | oral, 12 i.d. | 2 |
pergolid | 0.5 - 6 | oral, t.i.d. | 6-8 |
dihydro-α-ergocryptine | 20 - 120 | oral, t.i.d. | 16 |
cabergoline | 0.5 - 4 | oral, o.i.d. | 63 |
rotigotine | 2 - 16 | patch, t.i.d. | 24 |
Pramipexol [retarded release] | 0.25 - 4.5 | oral, t.i.d.[o.i.d. – b.i.d.] | 8 [24] |
Ropinirol [retarded release] | 4 - 24 | oral, o.i.d. [o.i.d. – b.i.d.] | 6 [24] |
Piribedil retarded release | 50 - 250 | oral, t.i.d. | 21 |
Why are non ergoline DA now preferred?
The advantage of slow release DA tablets
NMDA-Antagonists
Anticholinergics
Start of LD is a milestone
Basic principles of LD administration
Supplementation of LD/DDI application with inhibitors of catechol-O-methyltransferase (COMT)
Oral LD/DDI long term application and progression of PD
Clinical efficacy of COMT-inhibition in combination with LD/DDI
Safety and tolerability of COMT-inhibitors
Regulatory affairs
Oral intake of available COMT-Inhibitors
Reasons for delayed LD treatment initiation in PD patients
Causes for the onset of MC
Consequences of MC in clinical practice
LD/CD | LD/CD | LD/CD | ||
---|---|---|---|---|
150 mg | 300 mg | 600 mg | Placebo | |
dyskinesia | 3.3 | 2.3 | 16.5 | 3.3 |
wearing off | 16.3 | 18.2 | 29.7 | 13.3 |
MC: Wearing off
EN and the treatment of wearing off
LD/CD/EN | LD/CD | Total | ||
---|---|---|---|---|
dyskinesia | 2.7 | 4.2 | 3.5 | week 39 |
wearing off | 8.8 | 12.0 | 10.4 | week 39 |
dyskinesia | 5.3 | 7.4 | 6.4 | at any study visit |
wearing off | 13.9 | 20 | 17 | at any study visit |
MC: Dyskinesia
Continuous introduodenal LD/DDI treatment
Preventive treatment concepts for dyskinesia
COMT inhibition and dyskinesia onset
Failed earlier preventive strategies for MC onset by oral LD application
Current effective therapy regimen for alleviation of MC: Deep brain stimulation and infusion techniques
Deep brain stimulation
Infusion techniques
Dopamine substitution and non motor symptoms
Therapy of non motor features
Sleep disturbances
Therapy
Sleepiness
Therapy of daytime sleepiness
Depression
Therapy of depression
Cognition in PD patients
Drug therapy of cognitive problems
Psychosis
Symptomatic causes of psychosis
Drug treatment of psychosis
Cyclic mood disorder with hypomania or manic psychosis
Dopamine related impulsive-compulsive disorders
Treatment concepts
Autonomic failures
symptom | treatment options |
---|---|
salivation | belladonna compounds, anticholinergic drugs, glycopyrrolate, botulinum toxin (off label use), 1% atropine eye solution (off label use) |
seborrhea | soaps, shampoos |
hyperhidrosis | botulinum toxin |
constipation | Various kinds of laxatives, sufficient hydration, fibers, prucaloprid (Reselor®), macrogel (Movicol®) |
gastrointestinal motility | Domperidone, prucaloprid (Reselor®) (off label use !) |
bladder dysfunction | genneral approach: reduced fluid intake at night is sometimes helpful. parasympatholytics, imipramine, Fesoterodinfumarat (Toviaz®) Darifenacin (Emselex ®), botulinum toxin (off label use !) (in case of imperative urgency due to overactive bladder syndrome [detrusor hyperreflexia or overactivity]) optimum dopaminergic drug titration (in case of frequent and/or involuntary urinary incontinence due to uninhibited contractions of the detrusor muscle) distigmine bromide, reduction of anticholinergic drugs, (in case of detrusor hyporeflexia [underactivity]) |
sexual dysfunction | sildenalfil, oral apomorphine, alprostadil, psychotherapy |
orthostatic syndrome | patient education, non pharmacological interventions, midodrine, fludrocortisone, yohimbine, droxidopa |