Sex, drugs and rock’n’roll

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  • The ventral tegmental area (VTA) cells project to limbic (mesolimbic projection) and cortical (mesocortical projection) areas. Neurons of the substantia nigra project to the striatum (nigrostriatal projection). In PD, dopaminergic nerve cells in the substantia nigra develop nerve cell loss, and its degeneration and the resulting striatal dopamine depletion are responsible for most of the motor abnormalities.
  • Clinically, PD is characterized by three cardinal symptoms: resting tremor, bradykinesia (generalized slowness of movements) and muscle rigidity.
  • PD is the most common movement disorder affecting 1-2 % of the general population over the age of 65 years, and it is the second most common neurodegenerative disorder after Alzheimer´s disease (AD). Tanner, CM et al. Epidemiology and genetics of Parkinson´s disease. In: Watts RL, Koller WC, ed. Movement Disorders, Neurologic principles and practice. New York: McGrawhill, pp. 137-152, 1997 .
  • Sex, drugs and rock’n’roll

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

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