sex, drugs and rock’n’roll
TRANSCRIPT
Sex, Drugs and Rock’n’Roll
A Secret Tale of Parkinsons Disease
Objectives
• Brief overview of Parkinson’s Disease– The role of Dopamine– Clinical Features– Patho-physiology
• Treatment of PD– Psychological Side-effects
Dopamine
• Catecholamine– Neurotransmitter– Neurohormone– Precursor to noradrenaline and
adrenaline
• Synthesised by most vertebrates and invertebrates
• 5 different receptors with different responses D1 – D5
Dopamine(2)
• Made in nervous tissue and adrenal glands– Cannot cross the blood-brain barrier
• Inactivation– Broken down by Monoamine Oxidase (MAO)
and Catechol O-methyl transferase (COMT) in both brain and peripheral tissue
Dopamine pathways in human brain
Functions of Dopamine
In the Brain:Behaviour / Cognition
Voluntary movement
Motivation, punishment and reward
Inhibition of prolactin production
Sleep, mood, attention, working memory, and learning.
In peripheral tissue:Renal Blood flow / Blood Pressure / Cardiac Output
Parkinsonism
• Caused by insufficient formation or action of dopamine in the brain
• Three cardinal symptoms:– resting tremor– bradykinesia
(generalized slowness of movements)
– muscle rigidity
‘An Essay on the Shaking Palsy’
• First described by an English physician, James Parkinson, in 1817– ‘Paralysis Agitans’– 6 individuals observed on daily walks
• Parkinsons Disease is chronic progressive parkinsonism caused by loss of dopamine producing neurons in the brain
Epidemiology of PD
• The most common movement disorder affecting 1-2 % of the general population over the age of 65 years.– The second most common neurodegenerative
disorder after Alzheimer´s disease (AD).
Other Important Symptoms
Pain
Postural instability/Altered perception– Autonomic disturbances
Mental health problems– Sleep– Anxiety /Apathy / Depression– Dementia
Drug Therapy for Parkinson’s Disease
Drug therapy does not prevent disease progression, but it improves most patients' quality of life.
Strategies:1. Improve production of Dopamine2. Mimic Dopamine Effects3. Prevent Breakdown of Dopamine in the
brain
Drug Therapies
Dopamine Receptor Agonistse.g. Bromocriptine
MAO-B Inhibitorse.g. Selegiline
L-Dopa (Levodopa)– Pre-cursor of Dopamine– Crosses Blood Brain Barrier– Given with medication to inhibit peripheral
conversion of L-Dopa to Dopamine
Problems with L-Dopa Therapy
Side effects on rest of bodyMotor Complications
Fluctuating response to treatment- ‘On/Off’ Periods- ‘End-of-Dose’ deterioration
Non-Motor Complications– Vivid dreams and sleep disturbances– Psychosis / Mental Health Disturbances– Impulse Control Disorders
Impulse Control Disorders and PD
• Impulse control disorders– Repetitive, excessive and compulsive activities that
interfere with life functioning.• Compulsive eating• Pathological gambling• Compulsive shopping• Hypersexuality / Inappropriate sexualised behaviour
• ‘Punding’– Complex stereotyped behaviours characterised by
intense fascination with an excessive, repetitive activity.
Dopamine Dysregulation Syndrome
Need for increasing and excessive doses of dopamine replacement therapy DRT)
Pattern of pathological use: expressed need for increased DRT in the presence of side effects despite being ‘‘on’’, drug-hoarding or drug-seeking behaviour, unwillingness to reduce DRT
Impairment of social or occupational functioning
Development of hypomania, manic or cyclothymic affective syndrome in relation to DRT.
Development of a withdrawal state characterised by dysphoria, depression, irritability and anxiety on reducing the level of DRT
Summary
The Role of Dopamine in Parkinson’s Disease
The Importance of Dopamine Replacement Therapy– ‘Blessings and Curses’– Dopamine Dysregulation Syndrome