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62944
Parkinson's Disease
Description
Pham1056 Mind Map on Parkinson's Disease, created by Affy MD on 30/04/2013.
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pham1056
Mind Map by
Affy MD
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Created by
Affy MD
over 11 years ago
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Resource summary
Parkinson's Disease
Excitotoxicity
Calcium OVERLOAD
Neuronal Death: Associated with Ca++ overload of cells and membrane damage
Glutamate activates: - NMDA. - AMPA, - Metabotropic receptors
Epidemology
More Males are affected
Age of onset >50 years old
Possible Trigger Factors
Toxins
(MPTP) •Contaminant in heroin substitute led to "frozen addict‟ syndrome •induces parkinsonism – similar to some herbicides
Infection
Encephalitis lethargica
Genetic
Not usually familial
Enviromental
Dopamine oxidation
MPTP
Rotenone (herbicide)
Dopamine (DA) pathways
Due to: •Dopaminergic depletion in basal ganglia (nigro-striatal pathway) •Leading to a relative excess of acetylcholine in striatum
Nigrostraital – motor
Lack of DA or inhibition of dopaminergic neurones may lead to parkinsonism
Inhibits release of acetylcholine (ACh) from striatum
Mesolimbic & mesocortical – thought
Excessive DA or overactive dopaminergic neurones may lead to psychosis
Tuberohypophyseal – hypothalamus/pituitary
Prolactin release from pituitary gland - inhibited by dopamine
Chemoreceptor trigger zone - vomiting reflex
Dopaminergic stimulation leads to vomiting
Metabolism of dopamine
Dopamine eventually metabolised to Homovanillic acid
Metabolic Pathways
Catechol-o-methyltransferase
Monoamine oxidase
Aldehyde dehydrogenase
Symptoms
TREMOR
Rigidity
COGWHEEL
Bradykinesia
Akinesia
'Pill rolling'
Gait & Posture
Shuffling
Stooping
Speech
Montone
Early Stages: Levodopa, Dopamine Agonists, MAO-B-I
Treatment
Dopamine Precursors
Levodopa
Short Half-Life = 2 hours
May enhance DA in Limbic System
S.E. N+V, Cardiovascular - Hypotension
Treat with Domperidone, does NOT cross BBB
Psychological effects – delusions and hallucinations, but more commonly (20%) confusion, disorientation, insomnia or nightmares. Daytime drowsiness
Dyskinesia
Within 2 years of taking L-Dopa
Involuntary writhing movements
Motor Fluctuations ('On-off' effect)
Dopa-decarboxylase inhibitor can be added
Increases: Life expectancy. Improves: motor function, quality of life.
Some symptoms not improved – e.g. dysphagia, cognitive decline
MOA: Precursor of DA
Dopa Decarboxylase Inhibitors
Benserazide
Can be combined with L-Dopa to make Co-beneldopa (Madopar)
Carbidopa
Can be combined with L-Dopa to make Co-Careldopa (Sinemet)
Intestinal Gel - Duodopa, for late stage PD
Directly into Duodenum
Requires electronic pump device
Dose
The total morning dose is usually 5-10 ml, corresponding to 100-200 mg levodopa. (should not exceed 15 ml (300 mg levodopa)
MOA: Inhibit the breakdown of L-Dopa to DA
Monoamine Oxidase B Inhibitors
DRUGS
Selegilene
Better with Levodopa than alone
Rasagilene
Neuroprotective properties
Protect DA from intraneuronal breakdown
Catechol-O-Methyltransferase Inhibitors
DRUGS
Entacapone
Combo: Levodopa, Carbidopa & Entacopone - STALEVO
Tolcapone
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%
Amantadine
MOA: Increase DA release inhibit amine uptake, direct action on DA receptors
Limited by SE & worsening on withdrawal
Anti-viral drug
Dopamine Receptor Agonists
Ergot-Derived (Fibrotic Reactions)
Drugs
Bromocriptine
Cabergoline
Lisuride
Pergolide
Increase risk of pulmonary, retroperitoneal and cardiac fibrosis
Non-Ergot Derived
Pramipexole
Ropinirole
Apomorphine
D1 & D2 Agonist
SC or Infusion
Initiation - Hospital
Discharge: Monitor, adjust dose
Side Effects
Nausea, vomiting, drowsiness, hallucinations, injection site nodules, < commonly postural hypotension, breathing difficulties, dyskinesias, anaemia
Expensive
Increase sleepiness
Side Effects
Nausea/vomiting
Postural hypotension
Hallucinations
Confusion
Dyskinesias
Reckless Behaviour /Gambling
Antimuscarinic Drugs
DRUGS
Procyclidine
Orphenadrine
Artane
Benzatropine
Ach: excitatory effect on striatal neurones. Also exerts presynaptic inhibitory effect on dopaminergic nerve terminals
Treat tremor effectively
SIDE EFFECTS
dry mouth, urinary retention, visual disturbances, constipation - euphoria, drowsiness, confusion, hallucinations, cognitive impairment
Later Stages: Dopamine Agonists, COMT-I, MAO-B-I
2nd Choice: Amantadine, Apomorphine
All must be used as adjunctive therapy
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