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