Parkinson's Disease

Description

Pham1056 Mind Map on Parkinson's Disease, created by Affy MD on 30/04/2013.
Affy MD
Mind Map by Affy MD, updated more than 1 year ago
Affy MD
Created by Affy MD over 11 years ago
55
1

Resource summary

Parkinson's Disease
  1. Excitotoxicity
    1. Calcium OVERLOAD
      1. Neuronal Death: Associated with Ca++ overload of cells and membrane damage
        1. Glutamate activates: - NMDA. - AMPA, - Metabotropic receptors
      2. Epidemology
        1. More Males are affected
          1. Age of onset >50 years old
          2. Possible Trigger Factors
            1. Toxins
              1. (MPTP) •Contaminant in heroin substitute led to "frozen addict‟ syndrome •induces parkinsonism – similar to some herbicides
              2. Infection
                1. Encephalitis lethargica
                2. Genetic
                  1. Not usually familial
                  2. Enviromental
                    1. Dopamine oxidation
                      1. MPTP
                        1. Rotenone (herbicide)
                      2. Dopamine (DA) pathways
                        1. Due to: •Dopaminergic depletion in basal ganglia (nigro-striatal pathway) •Leading to a relative excess of acetylcholine in striatum
                          1. Nigrostraital – motor
                            1. Lack of DA or inhibition of dopaminergic neurones may lead to parkinsonism
                              1. Inhibits release of acetylcholine (ACh) from striatum
                            2. Mesolimbic & mesocortical – thought
                              1. Excessive DA or overactive dopaminergic neurones may lead to psychosis
                              2. Tuberohypophyseal – hypothalamus/pituitary
                                1. Prolactin release from pituitary gland - inhibited by dopamine
                                2. Chemoreceptor trigger zone - vomiting reflex
                                  1. Dopaminergic stimulation leads to vomiting
                                  2. Metabolism of dopamine
                                    1. Dopamine eventually metabolised to Homovanillic acid
                                      1. Metabolic Pathways
                                        1. Catechol-o-methyltransferase
                                          1. Monoamine oxidase
                                            1. Aldehyde dehydrogenase
                                        2. Symptoms
                                          1. TREMOR
                                            1. Rigidity
                                              1. COGWHEEL
                                              2. Bradykinesia
                                                1. Akinesia
                                                2. 'Pill rolling'
                                                3. Gait & Posture
                                                  1. Shuffling
                                                    1. Stooping
                                                    2. Speech
                                                      1. Montone
                                                    3. Early Stages: Levodopa, Dopamine Agonists, MAO-B-I
                                                      1. Treatment
                                                        1. Dopamine Precursors
                                                          1. Levodopa
                                                            1. Short Half-Life = 2 hours
                                                              1. May enhance DA in Limbic System
                                                                1. S.E. N+V, Cardiovascular - Hypotension
                                                                  1. Treat with Domperidone, does NOT cross BBB
                                                                    1. Psychological effects – delusions and hallucinations, but more commonly (20%) confusion, disorientation, insomnia or nightmares. Daytime drowsiness
                                                                      1. Dyskinesia
                                                                        1. Within 2 years of taking L-Dopa
                                                                          1. Involuntary writhing movements
                                                                          2. Motor Fluctuations ('On-off' effect)
                                                                          3. Dopa-decarboxylase inhibitor can be added
                                                                            1. Increases: Life expectancy. Improves: motor function, quality of life.
                                                                              1. Some symptoms not improved – e.g. dysphagia, cognitive decline
                                                                            2. MOA: Precursor of DA
                                                                            3. Dopa Decarboxylase Inhibitors
                                                                              1. Benserazide
                                                                                1. Can be combined with L-Dopa to make Co-beneldopa (Madopar)
                                                                                2. Carbidopa
                                                                                  1. Can be combined with L-Dopa to make Co-Careldopa (Sinemet)
                                                                                    1. Intestinal Gel - Duodopa, for late stage PD
                                                                                      1. Directly into Duodenum
                                                                                        1. Requires electronic pump device
                                                                                          1. Dose
                                                                                            1. The total morning dose is usually 5-10 ml, corresponding to 100-200 mg levodopa. (should not exceed 15 ml (300 mg levodopa)
                                                                                      2. MOA: Inhibit the breakdown of L-Dopa to DA
                                                                                      3. Monoamine Oxidase B Inhibitors
                                                                                        1. DRUGS
                                                                                          1. Selegilene
                                                                                            1. Better with Levodopa than alone
                                                                                            2. Rasagilene
                                                                                              1. Neuroprotective properties
                                                                                            3. Protect DA from intraneuronal breakdown
                                                                                            4. Catechol-O-Methyltransferase Inhibitors
                                                                                              1. DRUGS
                                                                                                1. Entacapone
                                                                                                  1. Combo: Levodopa, Carbidopa & Entacopone - STALEVO
                                                                                                  2. Tolcapone
                                                                                                  3. MOA: Inhibits breakdown of peripheral l-dopa by COMT to increase levodopa level and enhance effect. May be able to reduce levodopa dose by 10-30%
                                                                                                  4. Amantadine
                                                                                                    1. MOA: Increase DA release inhibit amine uptake, direct action on DA receptors
                                                                                                      1. Limited by SE & worsening on withdrawal
                                                                                                        1. Anti-viral drug
                                                                                                        2. Dopamine Receptor Agonists
                                                                                                          1. Ergot-Derived (Fibrotic Reactions)
                                                                                                            1. Drugs
                                                                                                              1. Bromocriptine
                                                                                                                1. Cabergoline
                                                                                                                  1. Lisuride
                                                                                                                    1. Pergolide
                                                                                                                    2. Increase risk of pulmonary, retroperitoneal and cardiac fibrosis
                                                                                                                    3. Non-Ergot Derived
                                                                                                                      1. Pramipexole
                                                                                                                        1. Ropinirole
                                                                                                                          1. Apomorphine
                                                                                                                            1. D1 & D2 Agonist
                                                                                                                              1. SC or Infusion
                                                                                                                                1. Initiation - Hospital
                                                                                                                                  1. Discharge: Monitor, adjust dose
                                                                                                                              2. Side Effects
                                                                                                                                1. Nausea, vomiting, drowsiness, hallucinations, injection site nodules, < commonly postural hypotension, breathing difficulties, dyskinesias, anaemia
                                                                                                                                2. Expensive
                                                                                                                              3. Increase sleepiness
                                                                                                                                1. Side Effects
                                                                                                                                  1. Nausea/vomiting
                                                                                                                                    1. Postural hypotension
                                                                                                                                      1. Hallucinations
                                                                                                                                        1. Confusion
                                                                                                                                          1. Dyskinesias
                                                                                                                                            1. Reckless Behaviour /Gambling
                                                                                                                                          2. Antimuscarinic Drugs
                                                                                                                                            1. DRUGS
                                                                                                                                              1. Procyclidine
                                                                                                                                                1. Orphenadrine
                                                                                                                                                  1. Artane
                                                                                                                                                    1. Benzatropine
                                                                                                                                                    2. Ach: excitatory effect on striatal neurones. Also exerts presynaptic inhibitory effect on dopaminergic nerve terminals
                                                                                                                                                      1. Treat tremor effectively
                                                                                                                                                        1. SIDE EFFECTS
                                                                                                                                                          1. dry mouth, urinary retention, visual disturbances, constipation - euphoria, drowsiness, confusion, hallucinations, cognitive impairment
                                                                                                                                                      2. Later Stages: Dopamine Agonists, COMT-I, MAO-B-I
                                                                                                                                                        1. 2nd Choice: Amantadine, Apomorphine
                                                                                                                                                          1. All must be used as adjunctive therapy
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