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Medicine Year 2 > HNN Topic 12 - Movement, Parkinson's, CNS Pharmacology > Flashcards

HNN Topic 12 - Movement, Parkinson's, CNS Pharmacology Flashcards

1
Q

What is dopamine synthesised from?

A

Amino acid - tyrosine

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2
Q

What is the effect of psychomotor stimulants?

A

Cause wakefulness and euphoria

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3
Q

Give examples of psychomimetic drugs

A
  • LSD
  • Mescaline
  • Ketamine
  • Phenycyclidine
  • THC
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4
Q

Describe the structure of dopamine

A
  • Catecholamine (monoamine)
  • Catechol ring and amine side group
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5
Q

List the types of dopamine receptors

A
  1. D-1 like receptors
  2. D-2 like receptors
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6
Q

What is the effect of antischizophrenia drugs?

A

Effective in relieving some of the symptoms of schizophrenic illness

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7
Q

What are monoamines?

A

Neurotransmitters derived from amino acids

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8
Q

Describe the storage and exocytosis of dopamine

A
  • Stored in vescicles
  • Released in response to calcium influx caused by action potential
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9
Q

How is depressive illness categorised?

A

Affective disorder - disorder of mood rather than thought/cognition

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10
Q

What is the role of the basal ganglia in controlling voluntary movement?

A
  • Initiation of movement - putting plan into action
  • Planning complex voluntary movements
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11
Q

What are the common side effects experienced on Levodopa?

A
  • On/off episodes - freezing
  • Dyskinesia
  • Impulsive/compulsive behaviour
  • Withdrawal syndrome - depression, anxiety, pain
  • Nausea and vomiting - doperidone prescribed to prevent
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12
Q

Describe the function of the cerebellum in voluntary movement

A
  • Coordination and smooth execution of movements
  • Motor learning
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13
Q

List the dopaminergic pathways

A
  1. Nigrostriatal
  2. Mesolimbic
  3. Mesocortical
  4. Tuberoinfundibular
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14
Q

Where are noradrenergic neurons and terminals found?

A
  • Neurons
    • In pons in medualla (locus cerulus and reticular formation)
    • Sympathetic ganglia - all spinal levels
  • Terminals
    • Glands, smooth muscles (sympathetic)
    • Forebrain, cerebellum, brainstem, spinal cord
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15
Q

What is the function of the mesocortical pathway?

A
  • Mediates cognitive and emotional behaviour
    • Dopamine helps in improved working memory and attention
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16
Q

What is the goal of pharmacotherapies used to treat schizophrenia?

A

Reduce dopaminergic signalling at D2 receptors (mesolimbic/cortical pathway)

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17
Q

Describe D-2 like receptor types and their action

A
  • D2, 3, 4 receptors
  • Inhibit cAMP
  • Coupled to inhibitory G-proteins
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18
Q

Why is the therapeutic onset of antidepressant drugs potentially problematic?

A
  • Therapeutic onset = 2-4 weeks
  • Problem in acutely suicidal patients
  • Effects of ketamine (quick onset) being trialled for treating acute depression
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19
Q

Describe the mesolimbic pathway

A

Originates in ventral tegmental area, projects to amygdala, pyriform cortex, lateral septal nuclei and nucleus accumbens

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20
Q

What is the effect of general anaesthetic agents?

A
  • Used to produce surgical anaesthesia
  • Act on GABA receptors - main inhibitory neurotransmitter of brain
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21
Q

List types of drugs which act on the CNS

A
  1. General anaesthetic agents
  2. Anxiolytics and sedatives
  3. Antischizophrenia (antipsychotic) drugs
  4. Antidepressant drugs
  5. Analgesic drugs
  6. Psychomotor stimulants
  7. Pschomimetic drugs
  8. Cognition enhancers
  9. Other disease specific drugs
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22
Q

Explain the clinical relevance of the tuberoinfundibular pathway

A

Antipsychotic drugs may disinhibit prolactin release and cause galactorrhoea

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23
Q

Describe the symptoms of schizophrenia

A
  • Positive symptoms (additional to normal experience)
    • Hallucinations (usually auditory)
    • Dellusions of persecution/grandeur
    • Disorder of logical thought
  • Negative symptoms
    • Depression - unresponsive to typical antidepressants
    • Anhedonia
    • Avolition - lack of drive
    • Slow thought/speech/actions
    • Lack of recognition of illness
  • Cognitive deficits - difficulties in learning and planning, impaired attention
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24
Q

How is physiotherapy helpful in managing Parkinson’s disease?

A

Prevent falls, maintain/gain independence, reduce pain

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25
Q

List the common non-motor symptoms of Parkinson’s disease

A
  • Anhedonia - inability to experience pleasure
  • Sleep problems
  • Memory problems and cognitive deterioration
  • Loss of smell and taste
  • GI symptoms - constipation
  • Urinary control disturbances - incontinence
  • Depression and anxiety
  • Hallucinations
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26
Q

List the types of movement

A
  1. Ballistic movements
  2. Persuit/visual feedback movements
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27
Q

Describe the mechanism of action and effectiveness of Levodopa

A
  • Converted to dopamine by dopamine carboxylase - replaces endogenous dopamine
  • Usually effective at first, after 5 years only 20% still respond - loss of dopaminergic cells to convert to dopamine
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28
Q

What are the main inputs and outputs of the cerebellum in voluntary movements?

A
  • Input - mainly from sensory cortex
  • Output - to primary motor cortex (via thalamus)
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29
Q

What is the general function of serotonin?

A
  • Determines overall level of arousal
  • Part of descending pain control system
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30
Q

Describe classification of drugs based on their mechanism of action

A
  • Agonist - activates receptor producing functional response
  • Antagonist - binds to receptor without activating it, blocks action of agonists
  • Partial agonist - partially activates a receptor, producing a smaller functional response in the cell
  • Some don’t act on receptors e.g. enzyme inhibitor - donepezil
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31
Q

Describe the pathological changes which occur in Parkinson’s disease

A
  • Causes distinctive neuropathological brain changes
    • Formation of Lewy bodies - abnormal proteinaceous spherical bodies
    • Spindle or thread-like branching Lewy neurites in the somata of the involved nerve cells
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32
Q

What is the role of the primary somatosensory cortex in voluntary movement?

A
  • Feedback to control/adjust movements - proprioception
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33
Q

Give examples of disease specific drugs

A
  1. Anti-epilepsy e.g. gabapentin
  2. Anti-Parkinson’s e.g. L-DOPA
  3. Anti-Bipolar disorder drugs e.g. lithium
  4. To treat addiction/dependence
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34
Q

Describe the epidemiology of schizophrenia

A
  • Common psychiatric disorder - 1% of population
  • V few make long-term recovery, 10% commit suicide
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35
Q

How does the control of movements change as they are practiced?

A

Most movements are learned - complex movements initially require a lot of conscious thought, with practice they become more involuntary (subconscious)

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36
Q

What is the effect of cognition enhancers?

A
  • Improve memory and cognition
  • Mild cognition enhancing effect in early stages of Alzheimer’s - doesn’t prevent degredation of neurones causing the disease
  • Inhibit breakdown of acetyl choline in synapses - promote cholinergic function
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37
Q

How is dietary therapy helpful in management of Parkinson’s disease?

A

Adapt diet to prevent constipation

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38
Q

Describe the tuberoinfundibular pathway

A

Originates in arcuate nucleus of hypothalamus, projects to pituitary gland (median eminence)

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39
Q

Describe the mechanism of action and side effect of MAOIs

A
  • Reduce breakdown of dopamine
  • Given w/ Levodopa - worsens side effects (involuntary movements and sickness)
  • Side effects - headaches, indigestion, depression, flu-like symptoms
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40
Q

Describe the nigrostriatal pathway and its function

A
  • Originates in substantia nigra (pars compacta), projects to dorsal striatum (caudate nucleus + putamen)
  • Control of motor function and learning new motor skills
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41
Q

Why are some areas of the brain outside the BBB?

A

Postrema - responsible for vomit reflex lies outside the BBB in order to detect toxins in the blood

42
Q

What is the function of the tuberoinfundibular pathway?

A
  • Dopamine inhibits prolactin release from the anterior pituitary
  • Stimulates growth hormone release
43
Q

Give examples of antischizophrenia drugs

A
  • Typical e.g. chloromazine, haloperidol
  • Atypical e.g. clozapine, olanzapine
44
Q

List the monoamine neurotransmitters

A
  1. Dopamine
  2. Serotonin
  3. Noradrenaline
45
Q

Where is dopamine produced?

A

Several areas of the brain - substantia nigra (pars compacta) and ventral tegmental area

46
Q

What is the function of the mesolimbic pathway?

A
  • Emotions and reward system - mediates pleasure in the brain
    • Released during pleasurable situations + stimulates one to seek out pleasurable activity/occuputation
    • All drugs of abuse stimulate this pathway
47
Q

What is the role of the primary motor cortex in voluntary movement?

A
  • Origin of descending pathways - output to muscles
  • Somatotopic map shows distribution of areas of cortex which control specific muscles
48
Q

List the side effects of antischizophrenia drugs

A
  • Parkinson’s like akinesia - D2 antagonism
  • Unpleasantness - D2 antagonism
  • Prolactin hypersecretion (galactorrhoea) - D2 antagonism
  • Posterior hypotension - alpha 2 adrenoceptor antagonism
  • Sedation - histamine R antagonism
  • Dry mouth - muscarinic R antagonism
  • Weight gain - HI/5HT2C R antagonism
49
Q

What is the motor effects of damage to the cerebellum?

A

Cerebellar ataxia - poor coordination

50
Q

Which kind of receptors does dopamine act on?

A

G-protein coupled receptors

51
Q

Describe the synthesis of dopamine

A
  1. Tyrosine in blood taken up into brain by low affinity amino acid transport system
  2. Transported from extracelluar fluid of brain to dopaminergic neurons by high + low affinity amino acid transporters
  3. Tyrosine converted to L-DOPA (dopamine precursor) by tyrosine hydrogenase (TH) - rate limiting step
  4. L-DOPA converted to dopamine by 1-amino acid decarboxylase (dopa decarboxylase) in the cytoplasm
52
Q

List the predominant motor symptoms of Parkinson’s disease

A
  1. Resting tremor e.g. pill-rolling
  2. Bradykinesia/akinesia - progressive slowing/absence of voluntary movements
  3. Postural instability - shuffling gait, falls
  4. Rigidity - stooped posture, lack of arm movement when walking, axial and limb rigidity (cogwheeling/lead pipe)

Also - oral motor disorders (quiet, hurried speech and dribbling) and scrawled writing

53
Q

Describe the mesocortical pathway

A

Originates in the ventral tegmental area, projects to the frontal cortex and septohippocampal regions

54
Q

Define Parkinson’s disease

A

Progressive multisystem neurodegenerative disease affecting people mainly in the later years of life

55
Q

What is the function of the blood brain barrier?

A
  • Maintain constant environment
  • Protect brain from foreign substances
  • Protect brain from peripheral transmitters
56
Q

What are the problems with using D2 antagonists to treat schizophrenia?

A
  • D2 blockage immediate but therapeutic effect takes weeks
  • Some patients do not respond
  • Drugs effective against positive symptoms but not negative/cognitive symptoms
57
Q

Explain the clinical relevance of the mesocortical pathway

A

Antipsychotic drugs worsen negative symptoms of schizophrenia by blocking dopamine receptors in mesocortical pathway

58
Q

What is the effect of psychomimetic drugs?

A

Hallucinogens - drugs that cause disturbances of perception and behaviour

59
Q

List the causes of Parkinson’s disease

A
  1. Aging
  2. Genetic factors - synuclein, Parkin and other genes
  3. Environmental factors - toxins (e.g. MPTP), herbicides, pesticides
60
Q

List the potential routes of administration of drugs which act on the CNS

A
  1. Enteral - lipophilic drugs (absorbed by GI tract)
  2. Parenteral - IM, SC
  3. Invasive routes (intrathecal)
61
Q

List the treatment/management options for Parkinson’s disease

A
  1. Occupational therapy
  2. Physiotherapy
  3. Speech and language therapy
  4. Dietary therapy
  5. Pharmacotherapies
62
Q

List diseases affecting movement caused by damage to the basal ganglia

A
  • Parkinson’s disease - difficulty initiating movement
  • Huntington’s disease - random involuntary movements
63
Q

What are the main inputs and outputs of the basal ganglia in controlling voluntary movement?

A
  • Input - mainly prefrontal cortex
  • Output -
    • Pre-motor area (via thalamus)
    • Supplementary motor area
64
Q

Describe the types of D-1 like receptors and their action

A
  • D1, D5
  • Cause activation of cAMP
  • Coupled to stimulatory G-proteins
65
Q

What are anxiolytics/sedatives used to treat?

A

Anxiety, epilepsy, anaesthesia, panic disorder, alcohol withdrawal, muscle relaxation

66
Q

What is the role of the supplementary and premotor areas?

A
  • Planning of movement
  • SMA = upper body, PMA = lower body
67
Q

What are the benefits of invasive routes of administration of CNS drugs, give examples of drugs which would be administered in this way?

A

V quick action

E.g.:

  • Meningitis antibiotics
  • Opiate analgesics
  • Regional anaesthesia (epidural)
68
Q

What is the general function of noradrenaline?

A

Maintaining attention and vigilance

69
Q

Give examples of psychomotor stimulants

A
  • Cocaine
  • Amphetemines e.g. Vyvanse for ADHD
  • Methylphenidate (Ritalin)
  • Caffeine
70
Q

Give examples of analgesic drugs

A
  • Opiates e.g. morphine
  • Baclofen
  • NSAIDs - ibuprofen, aspirin
71
Q

Give examples of cognition enhancers

A

Galantamine, donepezil

72
Q

List the types of Parkinson’s pharmacotherapies

A
  1. Drugs that replace dopamine e.g. Levodopa
  2. D2/3 agonists e.g. Bromocriptine
  3. Monoamine oxidase inhibitors e.g. Selegiline
73
Q

Where are D-1 like receptors found?

A

Throughout the brain, blood vessels and smooth muscle

74
Q

What is the chemoreceptor trigger zone?

A

Postrema of brainstem - outside BBB, vomiting reflex

75
Q

How is dopamine inactivated?

A
  • Reuptake into presynaptic terminal by dopamine transporter
  • Metabolism - monoamine oxidase or catechol-O-methyl transferase
76
Q

Describe persuit/visual feedback movements

A
  • Motor command continually updated according to sensory feedback
  • Accurate (modified while in progress) but slow
77
Q

Where are monoamine containing neurons found?

A

Mainly in the brainstem

78
Q

What is the role of the prefrontal cortex in voluntary movement?

A

Decision to make movement - analyses environment

79
Q

How can it be proven that the effectiveness of antischizophrenia drugs is due to their action on D2 receptors?

A
  • Not selective - efficacy is due to action on D2 receptors as drugs with high affinity for D2 receptors require a lower dose for clinical efficacy than other similar drugs
80
Q

Describe the structure of the BBB

A
  • Astrocytes, pericytes, microglia
  • Basement membrane
  • Endothelial cells - tight junctions between
  • Blood - lymphocytes, monocytes, neutrophils
81
Q

Describe the mechanism of action and side effects of D2/3 agonists

A
  • Mimics action of dopamine
  • Side effects
    • Drowsiness, fainting, nausea, constipation
    • Impulsive/compulsive behaviour
    • Hypotension
    • Headaches
    • Psychological problems e.g. hallucinations
82
Q

What is the effect of antidepressant drugs?

A
  • Alleviate the symptoms of depressive illness
  • Bind to selective serotonin reuptake receptor - block reuptake of serotonin, prolonging its action
83
Q

List the areas of the cortex involved in planning/instruction of voluntary movement

A
  1. M1 - primary motor cortex (area 4)
  2. S1 - primary somatosensory cortex
  3. Supplementary + pre-motor areas (area 6)
  4. Prefrontal cortex
  5. Area 5
  6. Area 7
84
Q

Describe the symptoms of Huntington’s disease

A
  • Choreas - involuntary movements
  • Difficulty speaking and swallowing
  • Progressive cognitive decline
85
Q

List other sensory areas involved in voluntary movement

A
  • Visual to visual cortex
  • Vestibular - feedback from organs of balance to subcortical areas
86
Q

How is speech and language therapy helpful in managing Parkinson’s disease?

A
  • Maintain communication ability
  • Help with problems with eating/drinking - swallowing, dribbling etc.
87
Q

What is the aim of pharmacotherapies used to treat Parkinson’s disease?

A

Enhance dopaminergic signallnig in nigrostriatal pathway

88
Q

Describe the progression of the pathological changes which occur in Parkinson’s disease

A
  • Lewy bodies confined to medulla, pontine tegmentum and olfactory bulb in early pre-symptomatic stages - loss of sense of smell
  • Progression - substantia nigra etc. affected = clinical symptoms
89
Q

What causes Huntington’s disease?

A

Inherited triple repeat base disorder

90
Q

Describe ballistic movements

A
  • Based on a pre-programmed set of instructions
  • Rapid but innaccurate - no time for compensation
91
Q

How are general anaesthetic agents administered?

A
  • Inhalation (short action) or intravenous (rapid acting)
  • Often IV induction then maintenance with inhalation
92
Q

Give examples of antidepressant drugs?

A
  • Monoamine oxidase inhibitors e.g. phenelzine
  • Tricyclic antidepressants e.g. imipramine
  • SSRIs e.g. fluoxetine
93
Q

Why is drug entry to the CNS restricted?

A

Blood brain barrier

94
Q

What is the effect of analgesic drugs?

A
  • Painkillers - used clinically for blocking nociceptive pain
95
Q

Describe the synthesis of monoamines

A
  • Dopamine and noradrenaline derived from tyrosine
  • Serotonin derived from tryptophan
96
Q

Give examples of anxiolytics/sedatives

A
  • Barbiturates e.g. phenobarbital
  • Benzodiazepines e.g. diazepam
97
Q

Explain the clinical relevance of the mesolimbic pathway

A

Antipsychotic drugs decrease positive symptoms of schizophrenia by blocking dopamine receptors in the mesolimbic pathway

98
Q

How is entry of drugs to the CNS aided?

A
  • Prodrugs e.g. L-DOPA
  • Carrier molecules
  • Transient BBB disruption e.g. mannitol
99
Q

When do motor symptoms of Parkinson’s appear?

A

After 95% of nigrostriatal dopaminergic neurons are lost

100
Q

Where are serotonergic neurons and terminals found?

A
  • Neurons - most levels of brainstem, concentrated in raphe nucleus
  • Terminals - widespread in forebrain, cerebellum, brainstem and spinal cord
101
Q

What is the effect of anxiolytics and sedatives?

A
  • Cause sleep and reduce anxiety
  • Act on GABA A receptor
102
Q

How are most movements performed?

A
  • Mixture of ballistic and persuit
  • Mixture of voluntary and involuntary
  • Most are learned

Medicine Year 2 (41 decks)

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