L9 Introduction to Neuropharmacology Flashcards

1
Q

What are ‘psychiatric’ or ‘mental’ illnesses?

A

These disorders involve disturbances of psychological functions, such as:

  • fear or anxiety disturbance of mood, e.g. depression
  • development of abnormal, bizarre ideas
  • impairment in memory or concentration
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2
Q

How can psychiatric or mental disturbances be difficult to assess and measure?

A

–they describe their symptoms to you or

–someone else thinks their behaviour has become unusual

Both of these mechanisms are open to considerable subjectivity and do not lend themselves easily to objective measurement.

Nb these other conditions are easier

–anaemia: patient looks pale, has low RBC count, has low haemoglobin

–pneumonia: patient appears short of breath, may have ↑ temperature, shadowing on X-ray

–Parkinson’s disease: patient has slow movements and tremor, muscle tone feels increased

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3
Q

How are psyciatric disorders diagnosed?

A

Diagnosis is based on the presence of pathology -most often abnormal psychological process

Groups of signs and symptoms are brought together in psychiatric syndromes

A person may not complain (eg mania)

Be careful not to diagnose on basis of presence of “deviant” behaviour/appearance/speech

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4
Q

What is the hierarchical classification of psyciatric illness?

(in increasing severity)

A

Personality disorders

Anxiety Disorders

Mood Disorders

Psychoses

Organic Disorders

Need to work from the top of the pyramid down to rule our the most serious conditions

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5
Q

What are examples of ORGANIC DISORDERS

A

Parkinson’s

Alzheimer’s

Dementia

Symptoms resulting from many physical illnesses eg endocrine disease, brain tumour, head injury

Dementias, Delirium

Acute drug induced symptoms, e.g. Delirium Tremens from alcohol withdrawal; LSD intoxication

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6
Q

What is Parkinson’s Disease?

A

An Organic Disorder

A disorder with obvious neurological signs:

  • tremor, increased muscle tone and stiffness, dysarthria, clumsiness, shuffling gait, motor slowness

Also has psychological symptoms:

  • depression of mood
  • cognitive impairment
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7
Q

What is the cause of Parkinson’s Disease?

A

Loss of pigmented neurones in the s.nigra

Loss of dopaminergic function

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8
Q

What is Dementia?

A

Global term - a set of symptoms with evidence of decline in memory and thinking which impairs functioning in daily living and is present for 6 months or more.

Associated with changes in behaviour, motivation and personality

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9
Q

What sorts of symptoms will someone with Dementia have?

A

Obvious impairment of higher cortical function.

  • orientation
  • thinking and judgement
  • memory
  • capacity to learn new information

May also have neurological signs:

  • impairments of language
  • dysphasia, dyspraxia
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10
Q

Give examples of some types of Dementia

A
  • Alzheimer’s disease-most common
  • Vascular dementia (mini strokes in brain)
  • Lewy body dementia
  • Frontotemporal dementia
  • Dementia of Parkinson’s disease and Huntingdons disease
  • Creutzfeldt-Jacob disease (mad cow disease)
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11
Q

How does a patient with Alzheimer’s Disease present?

A
  • Early = slight changes in mood or memory
  • Short term memory becomes more affected, other features will appear
  • Loss of ability to do more complex tasks (eg finance)
  • Disorientation, concentration difficulties
  • BPSD - Behavioural and Psychological Symptoms are common later in the disease
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12
Q

What is the clinical course of Alzhiemer’s Disease?

A
  • Profound memory loss
  • Frequent BPSD symptoms
  • Loss of ability to perform basic activities of daily living
  • Mobility affected
  • Patient become dependent
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13
Q

What are the 4 domains of the caregiver burden?

A

Global Function

Cognitive Function

Activities of Daily Living

Behavioural Disturbances

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14
Q

What is Psychosis?

A
  • Loss of contact with reality- demonstrated by presence of delusions (abnormal beliefs) and hallucinations (a percept without an object)
  • Lack of insight- that is do not accept/believe they are ill/require treatment (insight is often “partial”)
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15
Q

What are delusions?

A
  • A false fixed belief which is out of keeping with ones educational, social, cultural and religious background
  • It is unshakeable by argument

(Not just one that you disagree with)

(If a belief is in keeping with a person’s social/cultural group it is unlikely to be delusional)

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16
Q

Give examples of some Psychotic Illnesses

A

Schizophrenia

Schizoaffective disorder

Persistent delusional disorders

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17
Q

What is ‘perception’?

A
  • Perceiving the outside world relates to a complex neuropsychological process
  • Sense organs collect and modulate raw data
  • Brain decodes and produces an internal neural representation of the outside world
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18
Q

What is a Hallucination?

A

A hallucination is a perception in the absence of external stimulus that has qualities of real perception.

  • Hallucinations are vivid, substantial, and located in external objective space.
  • Hallucinations can occur in any sensory modality —visual, auditory, olfactory, gustatory, tactile, proprioceptive, equilibrioceptive, nociceptive, thermoceptive and chronoceptive.
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19
Q

What are some examples of Mood Disorders?

A

Mania

Depression

Unipolar depressive illness

Bipolar disorder: episodes of mania and depression

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20
Q

What is depression?

A

the pathological state of sadness.

A syndrome, with associated symptoms (including loss of appetite, weight loss, sleep disturbance, suicidal thoughts)

Diagnosis of depressive illness: presence of depressed mood or loss of interest, plus four other symptoms, for at least two weeks

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21
Q

What are the symptoms of Mania / Hypomania

A
  • Increased Energy
  • Over activity
  • Irritability
  • Disinhibition
  • Increased Libido
  • Grandiosity
22
Q

Give examples of Anxiety Disorders

A

Anxiety disorders, e.g. generalised anxiety disorder, panic disorder, phobias

Obsessive-compulsive disorder

Hypochondriasis

Maladaptive behaviour

Abnormal illness behaviour

23
Q

What are some SOMATIC symptoms of anxiety?

A
  • Butterflies
  • Tremor
  • Sweating
  • Dry mouth
  • Giddiness
  • Choking
  • Blushing
  • Vertigo
  • Shortness of Breath
  • Palpitations
  • Headaches
  • Chest Pains
  • Diarrhoea
  • Nausea
  • Tinnitus
  • Tingling
24
Q

What are some PSYCHIC symptoms of anxiety?

A
  • Worry
  • On edge
  • Exhaustion/Fatigue
  • Restlessness
  • Hypersensitive to noise
  • Anxious Foreboding
  • Irritable
  • Poor concentration
25
Q

What are obsessions?

A

Recurrent, persistent, forceful thoughts, impulses or images which the patient feels are senseless but recognises as his own.

They feel compelled to resist them.

26
Q

What are some themes associated with obsession?

A
  • Dirt and contamination
  • Aggression
  • Orderliness
  • Religious
  • Sexual
  • Illness

Can be accompanied by compulsive acts:

–Hand washing

–Complicated rituals

27
Q

Give examples of Personality Disorders?

A

Personality disorders, e.g. psychopathy, dependent, anankastic, borderline,

cyclothymic, narcissitic,

anxious

28
Q

What are the criteria for a neurotransmitter?

A
  • Present in nerve terminals in the area where it is thought to act.
  • Stimulation of the appropriate nerves should evoke a measurable release.
  • The proposed neurotransmitter must produce post-synaptic effects identical physiologically and pharmacologically to those produced by neuronal stimulation.
  • Enzymes present for its synthesis and a means of inactivation available.
  • Non-uniform distribution in the brain.
29
Q

What are the major CNS Transmitters?

(receptors in the picture)

A

Glutamate

GABA

Glycine

Acetylcholine (Ach)

Serotonin (5HT)

Noradrenaline

Dopamine

30
Q

Draw neurotransmitter release

A
31
Q

What are the 4 main types of neutransmitter receptors?

A

Type 1 – ligand gated ion channels (ionotropic)

Type 2 – G-protein coupled receptors (metabotropic)

[Type 3 – kinase linked receptors]

[Type 4 – nuclear receptors]

32
Q

What receptors are the main targets for current drugs targeting the CNS/

A

Type 1 – ligand gated ion channels (ionotropic)

Type 2 – G-protein coupled receptors (metabotropic)

33
Q

Describe the Neurotransmitter synthesis, metabolism, and inactivation of dopamine

A
  • CAT choline acetyl-transferase
  • Acetyl-CoA acetyl co-enzyme A
  • MAO monoamine oxidase
  • COMT catechol-O-methyltransferase
  • HVA homovanillic acid
  • DOPA dihydroxyphenylalanine
  • DOPAC dihydroxyphenylacetic acid
  • DBH dopamine beta-hydroxylase
  • MHPG 3-methoxy-4-hydroxy-phenylethyleneglycol
  • VMA vanillylmandelic acid
  • 5-HIAA 5-hydroxy-indoleacetic acid
  • PCPA para-chloro-phenylalanine
34
Q

How is dopamine locally regulated?

A
  • CAT choline acetyl-transferase
  • Acetyl-CoA acetyl co-enzyme A
  • MAO monoamine oxidase
  • COMT catechol-O-methyltransferase
  • HVA homovanillic acid
  • DOPA dihydroxyphenylalanine
  • DOPAC dihydroxyphenylacetic acid
  • DBH dopamine beta-hydroxylase
  • MHPG 3-methoxy-4-hydroxy-phenylethyleneglycol
  • VMA vanillylmandelic acid
  • 5-HIAA 5-hydroxy-indoleacetic acid
  • PCPA para-chloro-phenylalanine
35
Q

How is neurotransmitter release dampened?

A

The long-loop feedback process

(autoreceptors create this process)

  • CAT choline acetyl-transferase
  • Acetyl-CoA acetyl co-enzyme A
  • MAO monoamine oxidase
  • COMT catechol-O-methyltransferase
  • HVA homovanillic acid
  • DOPA dihydroxyphenylalanine
  • DOPAC dihydroxyphenylacetic acid
  • DBH dopamine beta-hydroxylase
  • MHPG 3-methoxy-4-hydroxy-phenylethyleneglycol
  • VMA vanillylmandelic acid
  • 5-HIAA 5-hydroxy-indoleacetic acid
  • PCPA para-chloro-phenylalanine
36
Q

What are the EXITATORY Amino Acid Neurotransmitters?

A

–glutamate

–aspartate

–(NMDA, AMPA, kainate)

37
Q

What are the INHIBITORY Amino Acid Neurotransmitters?

A

–GABA (gamma amino butyric acid)

–glycine (spinal cord grey matter; blocked by strychnine; no therapeutically useful drugs)

38
Q

Where is glutamate stored?

Do any drugs interfere with its metabolism?

What happens after release?

When is there excessive release?

A
  • Glutamate is stored in vesicles
  • No clinically useful drugs interfere with its metabolism
  • Following release, there is re-uptake into terminals and astrocytes (like GABA)
  • Excessive release in ischaemia causes neuronal damage and death.
39
Q

What is used to treat dementia?

A

Nootropic drugs

40
Q

What is used to treat Parkinson’s Disease?

A

Anti-parkisonian drugs

41
Q

What is used to treat epilepsy?

A

Anti-convulsant drugs

42
Q

What is used to treat psyciatric disorders?

  • Psychosis
  • Depression and mania
  • Anxiety
  • OCD
A

Treatment of psychiatric disorders – psychotropic drugs:

  • Psychosis - antipsychotics
  • Depression and Mania – antidepressants and mood stabilisers
  • Anxiety - antidepressants
  • Obsessive-compulsive disorder - antidepressants
43
Q

What are the Potential mechanisms for drug action

  1. Stimulate synthesis
  2. Stimulate release
  3. Receptor agonist
  4. Receptor antagonist
  5. Re-uptake blocker
  6. Enzyme inhibitor
A
  1. L-dopa in Parkinson’s
  2. Stimulate release amphetamine
  3. bromocriptine
  4. antipsychotic drugs
  5. SSRI antidepressants
  6. MAOI antidepressants
44
Q

Discuss the Dopamine NT function

and pathway

A

Control of movement

Cognition/Emotional Expression

Hormone Secretion

Nigrostriatal

Mesolimbic

1.Hypothalamic-pituitary

45
Q

Treatment of clearly definable ‘organic’ brain disorders, such as Parkinson’s disease or Alzheimer’s disease, involves what?

Treatment of epilepsy involves what?

A

‘replacement’ in some way of the neurochemical deficit.

drugs designed to control the electrical hyper-excitability.

46
Q

What is the noradrenaline pathway involved in?

A

limbic system

REM sleep

reward mechanisms

hypothalamic fn

autonomic functions

47
Q

What is the Serotonin Pathway involved in?

A

sleep

pain & temp control

aggression

sexual behaviour

hormone control

punishment

48
Q

Discuss the acetylcholine neuronal pathways

and their function

A
  1. septo-hippocampal
  2. nucleus basalis
  3. s.nigra – thalamus
  4. striatal interneurons

memory arousal

learning movement

49
Q

What are the general principles for medication in

  1. Depression
  2. Psychosis
  3. Dementia
A

For most psychiatric meds the aim is to increase levels of whatever brain chemical (or neurotransmitter) is thought to be low or lacking

  1. serotonin and adrenaline
  2. dopamine
  3. acetylcholine

Often symptons are treated by meds instead

50
Q

What can antidepressants be used to treat?

What can mood stabilisers also be used to treat?

A

anti-anxiety and anti-pain

epilepsy

51
Q

What are the difficulities with under and over prescribing?

A

What is the correct balance between psychological therapies, medication and doing nothing?