PBL Topic 3 Case 6 Flashcards

1
Q

What is a diffusion potential?

A
  • The potential difference between the inside and outside of the membrane
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2
Q

What is the Nernst potential?

A
  • The diffusion level that exactly opposes the net diffusion of a particular ion through a memrbane
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3
Q

What is the role of the sodium potassium pump?

A
  • Moves 3Na+ to the outside of the cell
  • For every 2K+ to the inside of the cell
  • In order to restore the resting membrane potential
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4
Q

What are leak channels and how do they differ in permeability to different ions?

A
  • Channels through which ions leak

- Greater leakage of potassium because it is more permeable

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5
Q

What is the value of the resting potential in large nerve fibres?

A
  • -90 millivolts

- Meaning the potential inside is 90 millivolts more negative than the potential in the extracellular fluid

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6
Q

Explain why the Nernst potential for sodium and potassium differs

A
  • Potassium Nernst potential is -94 millivolts because there is a high ratio of potassium ions inside to outside
  • Sodium Nernst potential is +61 because there is a lower ratio of sodium ions inside to outside
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7
Q

What is the resting stage of an action potential?

A
  • Membrane is polarised due to -90 millivolts generated by sodium potassium pump
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8
Q

What is the depolarisation stage of an action potential?

A
  • Membrane becomes permeable to sodium
  • Large number of sodium ions diffuse into axon
  • Overshoot caused by excess of sodium entering
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9
Q

What is the repolarisation stage of an action potential?

A
  • Sodium channels close
  • Potassium channels open
  • Rapid diffusion of potassium out
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10
Q

Identify the two types of gating

A
  • Voltage gating involving opening of a protein channel as a result of changing potential
  • Chemical ligand gating involving opening of a protein channel due to binding of a ligand e.g. ACh
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11
Q

Describe the gates of a voltage gated sodium channels

A
  • Activation M gate opens when membrane potential becomes less negative than the resting potential
  • Inactivation H gate closes as a result of same increase in voltage but it closes slower
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12
Q

What is meant by threshold for stimulation and what is its value?

A
  • Membrane potential becomes less negative than resting potential
  • To around -65 millivolts
  • Which causes explosive development of an action potential
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13
Q

Explain the process behind the propagation of an action potential

A
  • Excited portion of nerve fibre causes local circuit of current flow to adjacent resting membrane areas
  • Positive electrical charges are carried by inward diffusion sodium ions
  • Increasing threshold in adjacent areas above threshold for stimulation
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14
Q

What is meant by the all or nothing principle?

A
  • Action potential only occurs if sufficient voltage to stimulate the next area of the membrane builds up
  • Above the threshold
  • Or it does not travel at all
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15
Q

What is the importance of ATP in nerve impulse?

A
  • Sodium potassium pump re-establishes sodium and potassium concentration differences
  • Which requires ATP
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16
Q

What is the ratio of myelinated to unmyelinated nerve fibres?

A
  • 1:2
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17
Q

What is the velocity of conduction in a small unmyelinated nerve fibre compared to a large myelinated fibre?

A
  • Small unmyelinated: 0.25m/sec

- Large myelinated: 1m/sec

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18
Q

Describe the structure of a myelinated nerve fibre

A
  • Central core is the axon filled with axoplasm

- Surrounded by a myelin sheath

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19
Q

Outline the process of myelination

A
  • Membrane of Schwann cell envelops the axon
  • Schwann cell rotates around axon many times
  • Depositing many layers of sphingomyelin
  • Which is an insulator that decreases ion flow through the membrane
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20
Q

What is saltatory conduction?

A
  • Junction between Schwann cells is known as node of Ranvier
  • Nerve impulse jumps between nodes of Ranvier
  • Increasing the velocity of transmission
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21
Q

What is primary demyelination?

A
  • Myelin sheath is destroyed

- Axons remains intact

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22
Q

What is secondary demyelination?

A
  • Damage to axon

- Resulting in breakdown of of myelin

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23
Q

What happens to the debris of myelin breakdown?

A
  • Phagocytosed by macrophages

- Transformed into droplets of neutral lipids (cholesterol esters)

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24
Q

What is an acute sub-threshold potential?

A
  • Weak negative stimulus incapable of exciting a nerve fibre
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25
What is an acute local potential?
- Excitation takes place in response to voltage increase - However it is not great enough to pass the threshold level - Therefore an action potential does not occur
26
What is an absolute refractory period and why does it occur?
- Period during a which a second action potential cannot be elicited even with a strong stimulus - Because sodium channels become inactivated
27
What is a relative refractory period?
- Period during which nerve fibre is more difficult to excite - But can be excited by a very strong signal
28
What is a membrane stabilising factor. How does lidocaine act as a stabilising factor?
- Factor that decreases excitability | - Lidocaine acts on activation gate of sodium channels making it more difficult for it to open
29
Explain how chemical synapses work
- Presynaptic cell releases neurotransmitter | - That acts on postsynaptic receptor proteins
30
Explain how electrical synapses work
- Direct open fluid channels - That conduct electricity from one cell to next - Usually through gap junctions
31
How does transmission of impulses differ between chemical and electrical synapses?
- Chemical synapses: One way transmission | - Electrical synapses: Signals are transmitted in either direction
32
What is the importance of one way transmission?
- Specific transmission of signals to discrete and highly focuses areas in the CNS and PNS - Allows the nervous system to perform its myriad functions - Including sensation, motor control, memory and many others.
33
Describe how neurotransmitters are stored and released from the presynaptic terminal
- Stored in transmitter vesicles - Mitochondria provides ATP for synthesising new transmitter substance - Action potential spreads over presynaptic terminal - Depolarisation of membrane causes release of vesicles into synaptic cleft
34
What are SNARE proteins?
- Proteins that dock vesicles in active zone of presynaptic terminal -
35
Identify two types of SNARE protein
- V-SNARES: Synaptobrevin, Synaptotagmins, found on vesicular membrane - T-SNARES: Syntax, Snap-25, found at nerve terminal membrane
36
Outline the role of calcium ions in neurotransmitter release
- Binds to another vesicle protein, synaptotagmins - Triggering conformational change in SNARE complex - Leading to membrane fusion and neurotransmitter release into the cleft
37
Identify two types of postsynaptic receptors that neurotransmitters bind to
- Ionotropic receptors: ion channels | - Metabotropic receptors: G-protein second messenger system
38
What are cation and anion channels?
- Opened as a result of activation of ionotropic / metabotropic receptors in response to neurotransmitters - Cation channels allow entry of sodium, but block entry of chloride due to lining of negative charges - Anion channels allow entry of potassium, but block entry of sodium due to small size
39
What is an excitatory postsynaptic potential (EPSP)?
- Electrical response at an excitatory cation channel
40
What is an inhibitory postsynaptic potential (IPSP)?
- Hyperpolarisation at an inhibitory anion channel
41
Outline the molecular and membrane mechanisms used at excitatory receptors
- Opening of sodium channels, influx of sodium ions - Decrease influx of chloride ions and efflux of potassium ions - Changes in internal metabolism to excite cell activity
42
Outline the molecular and membrane mechanisms used at inhibitory receptors
- Opening of chloride channels, influx of chloride ions - Increased efflux of potassium ions - Activation of receptor enzymes that inhibit metabolic functions
43
Outline the process of presynaptic inhibition
- Release of GABA by presynaptic cell - Which opens presynaptic anion channels - Allowing influx of chloride into presynaptic cell - Inhibiting synaptic transmission
44
What is spatial summation?
- Effect of triggering an action potential in a neuron from one or more presynaptic neurons. - This occurs when more than one excitatory postsynaptic potential (EPSP) originates simultaneously and a different part of the neurone
45
What is temporal summation?
- High frequency of action potentials in the presynaptic neuron elicits postsynaptic potentials that summate with each other
46
What is the role of small molecular neurotransmitters?
- Acute responses of nervous system e.g. sensory signals to brain and motor signals to muscle
47
What is the role of neuropeptide transmitters?
- More prolonged actions such as long-term changes in numbers of neuronal receptors, long term opening and closure of certain ion channels
48
How are small molecular neurotransmitters synthesised?
- In cytosol of presynaptic terminal by active transport into transmitter vesicles in the terminal
49
How are neuropeptides produced?
- Ribosomes as integral parts of large protein molecules - Which is then enzymatically split from the protein by the Golgi apparatus - Transported to tips of nerve fibres by axonal steaming
50
What is Multiple Sclerosis?
- Autoimmune T-cell mediated inflammatory disorder - Formation of plaques of demyelination throughout the brain and spinal cord - Occurring sporadically over years (dissemination in time and space)
51
Outline the epidemiology of MS
- Prevalence of 1.2/1000 - Women outnumber men 2:1 - Typically affects people between 20 and 40 years - More common in white populations with increasing distance from the equator
52
Outline 4 environmental causes of MS
- Epstein-Barr Virus (EBV) - Human Herpes Virus 6 (HHV-6) - Low levels of vitamin D - Lack of sunlight
53
Outline the pathology of MS
- T-cells cross the BBB - They recognised myelin derived antigens on microglia and undergo clonal proliferation - Resulting in inflammatory cascade and cytokine release initiating destruction of oligodendrocyte-myelin unit - Impaired impulse propagation - Progressive axonal loss
54
Outline the three types of MS
- Relapsing-remitting, symptoms occurring in attacks over days, and then recovery over weeks - Secondary progressive, late stage symptoms with gradually worsening disability caused by axonal loss - Primary progressive, late stage symptoms with gradually worsening disability without relapses or remissions
55
Outline 3 clinical features of multiple sclerosis
- Optic neuritis caused by demyelination of optic nerve - Diplopia, vertigo, facial numbness, weakness caused by brainstem demyelination - Paraparesis with possible Lhermitte's sign caused by spinal cord lesions in cervical or thoracic cord
56
Outline the investigations and diagnosis of MS
- Clinical history of neurological symptoms - MRI demonstrates demyelination - CSF examination shows lymphocytic pleocytosis and oligoclonal bands of IgG
57
What is the Clinically Isolated Syndrome?
- Diagnosis of MS cannot be made on first episode of neurological symptoms - Though an abnormal brain MRI confers a high chance of developing MS
58
What is treatment for acute relapses of MS?
- Methylprednisolone
59
How does B-interferon work?
- Inhibits T cell activation - Preventing T cell proliferation - Blocks T-cell migration across the BBB
60
How does glatiramer acetate work?
- Competitive inhibitor of MHC-II | - Since it has a similar structure to myelin basic protein
61
How does oral fingolimod work?
- Sphingosine-1-phosphate receptor | - That prevents T cells leaving lymph nodes
62
How does natalizumab work?
- Alpha-4 integrin vascular adhesion molecule | - Preventing lymphocytes entering the CNS
63
How does alemtuzumab work?
- Anti-CD52 molecule | - Responsible for lymphocyte depletion
64
What is the prognosis of MS?
- Life expectancy reduced by 7 years on average
65
Outline the mechanism of action of methylprednisolone
- Binds to intracellular glucocorticoid receptors - Which dimerises then enters the nucleus - Which binds to glucocorticoid response element and upregulates transcription
66
Outline the immunosuppressive and anti-inflammatory properties of glucocorticoids such as methylprednisolone
- Reduced activation of neutrophils, macrophages, mast cells - Reduced activation of T-helper cells, reduced clonal proliferation of T-cells - Decreased production of prostanoids owing to decreased COX-2 expression - Decreased generation of cytokines - Increased synthesis of inflammatory factors such as IL-2 and annexin 1
67
Outline 4 adverse effects of glucocorticoids
- Poor response to infection or injury, poor wound healing - Oral candidiasis - Peptic ulceration
68
Describe the biosynthesis of serotonin
- Tryptophan is converted into 5-hydroxytryptophan by tryptophan hydroxylase - 5-hydroxytryptophan is converted to 5-hydroxytryptamine by an amino acid decarboxylase
69
How is serotonin degraded?
- Monoamine oxidase - Which converts it to 5-hydroxindole acetaldehyde - Which is then dehydrogenated and excreted in the urine
70
Where in the body are the highest concentrations of serotonin found?
- Enterochromaffin cells of the gut regulating peristalsis and motility - Platelets, causing platelet aggregation - CNS where it excites and inhibits neurons - In sensory nerve endings to stimulate nociceptive nerve endings
71
Where are serotonergic cell bodies found and how do the nuclei project to other regions of the brain?
- Raphe nuclei of the pons and upper medulla | - Via the median forebrain bundle
72
What type of receptors are serotonin receptors? What is the exception?
- All are G-protein coupled | - Except for 5-HT3 which is a ligand gated cationic channel
73
What are 5-HT1 receptors?
- Somatodendritic autoreceptors in the raphe nuclei | - Major target for drugs used to treat anxiety and depression
74
Outline the four physiological functions that relate to 5-HT pathways
- Hallucinatory effects - Sleep, wakefulness and mood - Feeding behaviour - Pain pathways
75
Describe the biosynthesis of noradrenaline
- L-tyrosine is converted to dopa by tyrosine hydroxylase - Dopa is converted to dopamine by dopa decarboxylase - Dopamine is converted to noradrenaline by dopamine beta-hydroxylase
76
Which protein is involved with transport of noradrenaline into vesicles. What is stored in vesicles containing noradrenaline?
- Reserpine-sensitive Vesicular Monoamine Transporter (VMAT) - ATP - Chromogranin - DBH
77
Which receptor is responsible for noradrenaline reuptake?
- Noradrenaline (NET) transporter
78
Where are noradrenergic cell bodies found and how do the nuclei project to other regions of the brain?
- Locus coeruleus located in the pons | - Via the median forebrain bundle
79
What type of receptors are adrenoreceptors?
- G-protein coupled receptors
80
Identify 3 functions of alpha-1 receptors
- Motor control - Condition - Fear
81
Identify 3 functions of alpha-2 receptors
- Blood pressure control - Sedation - Analgesia
82
What are beta-1 receptors?
- Found in cortex, striatum and hippocampus | - Involved in long-term effects of antidepressant
83
What are beta-2 receptors?
- Found in cerebellum | - Involved in long-term effects of antidepressant drugs
84
Outline the physical features of depression
- Insomnia or hypersomnia - Poor appetite and weight loss - Increased appetite and weight gain - Loss of libido and erectile dysfunction
85
Outline the emotional features of depression
- Feelings of unworthiness - Worrying - Suicidal thoughts - Delusions of guilt - Feelings of futility - Hypochondriacal preoccupations
86
Outline the epidemiology of depression
- 5% prevalence - More common in women - No increase with age, difference by ethnic group of socio-economic class
87
What is dysthymia?
- Mild or moderate depressive illness - Intermittently over 2 years - Characterised by tiredness and low mood
88
What is seasonal affective disorder?
- Recurrent episodes of depressive illness - Occurring in the winter months in the northern hemisphere - Can be treated with bright light therapy
89
Identify three types of puerperal affective disorder
- Maternity blues, brief episode of tearfulness that occurs in the majority of women and resolves spontaneously - Postnatal depressive disorders, lack of emotional bonding and poor relationship with partner - Postpartum psychosis, attempts to kill the child or suicide
90
Outline two differential diagnoses for depression?
- Alcohol misuse | - Thyroid disease
91
Outline two investigations for depression
- Clinical history to rule out alcohol misuse | - Less commonly used T4 or TSH measurements
92
Outline the pathogenesis of depression
- Deficit of noradrenaline and 5-HT and BDNF - Elevated levels of glutamate and action of NMDA receptors - Stress leads to increased cortisol release - All of which result in a detrimental gene transcription response and neural apoptosis
93
Outline the genetic component of depression
- Polygenic - Polymorphisms include serotonin transport genes - Short/short allele implicated in greatest risk. long/long allele implicated in lowest risk
94
Outline environmental factors that predispose a person to depression
- Physical, sexual and emotional abuse or neglect in childhood - Serious life events, including divorce in women and unemployment in men
95
Outline two examples of SSRI
- Fluoxetine, sertraline
96
Outline two examples of TCAs
- Amitriptyline, nortriptyline
97
Outline an example of an SNRI
- Venlafaxine
98
Outline an example of an NRI
- Bupropion
99
Outline two examples irreversible, non-selective MAOIs
- Phenelzine, tranylcypromine
100
Outline three examples example of MRA
- Mirtazapine, trazodone, mainserin
101
Outline the effects of acute administration of SSRIs
- Increased levels of 5-HT results in increased activation of 5-HT1a receptors - Which reduce 5-HT release
102
Outline the effects of prologued administration of SSRIs
- Elevated levels of 5-HT desensitise 5-HT1a receptors | - Which increases 5-HT release
103
How can alpha-2 adrenoreceptor antagonism enhance 5-HT release?
- Block of a2 autoreceptors on noradrenergic nerve terminals innervating cell bodies of 5-HT containing neurons in dorsal raphe - Enhanced noradrenaline release will activate excitatory postsynaptic a1 receptors on 5-HT neurons - Increasing firing and thus release of 5-HT
104
How is sertraline administered and what is the dosage?
- Taken orally 50mg daily - Increased in steps of 50mg weekly - To a maximum of 200mg
105
Outline three common side effects of sertraline
- Nausea - Anorexia - Insomnia - Loss of libido and anorgasmia
106
Outline three uncommon side effects of sertraline
- Serotonin syndrome when combined with MOI characterised by tremor, hyperthermia, and cardiovascular collapse - Risk of bleeding associated with inhibition of 5-HT reuptake by platelets - Discontinuity syndrome marked by shivering, anxiety and dizziness
107
How is venlafaxine administered and what is the dosage?
- Orally - Taken 75mg daily in 2 divided doses - To a maximum of 375mg daily
108
Outline 4 side effects of venlafaxine
- Antimuscarinic effects such as dry mouth, blurred vision, constipation and urinary retention - Cardiovascular effects such as postural hypotension - Weight gain - Sedation
109
Outline two roles of monoamine oxidase
- Within nerve terminals it regulates intraneuronal concentration of NA and 5-HT - Inactivation of endogenous amines such as tyramine
110
What is the cheese reaction?
- Tyramine is normally metabolised by NAO so little reaches circulation - MAO inhibition results in acute hypertension, severe throbbing headache and rarely intracranial haemorrhage
111
What is ECT?
- Used in severe life-threatening depression - Performed under general anaesthetic, involves passage of current over scalp to induce epileptic fit - Given twice a week for 3-6 weeks - Free of serious side effects
112
What is CBT?
- Identification of automatic thoughts about self, situation and future - Including catastrophising, overgeneralising, categorical thinking - Identifying links between thoughts, behaviour and mood - Testing logic of said thoughts e.g. Socratic questioning
113
Outline the mechanism of action of nortriptyline and amitriptyline
- Inhibition of noradrenaline (physical symptoms), 5-HT (emotional symptoms) and dopamine uptake (less so) - By competition for the binding site of the nerve terminal
114
Identify 3 side effects of nortriptyline and amitriptyline
- Antimuscarinic effects e.g. dry mouth, blurred vision, constipation and urinary retention - Cardiovascular effects e.g. postural hypotension and QT prolongation - Weight gain - Sedation
115
Identify another use of TCAs aside from antidepressants and outline how they work
- Neuropathic pain - Preventing noradrenaline reuptake - Which inhibits transmission of nociception
116
Outline the mechanism of action of mirtazapine
- Blocks a2 adrenoceptors - Blocks 5-HT2C receptors - Enhancing noradrenaline and 5-HT release
117
Outline the mechanism of action of trazodone
- Blocks 5-HT2A and 5-HT2C receptors | - Enhancing 5-HT release
118
Outline the mechanism of action of mainserin and explain why it is no longer used
- Blocks a1 adrenoreceptors - Blocks 5-HT2a receptors - Blocks H1 receptors - Causes bone marrow depression
119
Give an example of a selective, MAO-A specific inhibitor and an advantage of this type of drug over phenelzine and tranylcypromine
- Moclobemide | - Cheese reaction and drug reactions are much less severe
120
What is meant by coping?
- The process of managing stressors | - That have been appraised as taxing or exceeding a person's resources
121
What is meant by primary appraisal?
- Assessing the potential threat of the external stressor
122
What is meant by secondary appraisal?
- Assessing the effectiveness of options to manage the situation and the person's internal responses
123
Identify 5 goals of coping
- Reduce stressful conditions - Adjust or tolerate negative effects - Positive self image - Emotional equilibrium - Maintain relationships
124
What is meant by approach coping and what type of stressor is it more suitable for?
- Confronting problem and taking direct action | - Long-term stressor
125
What is meant by avoidance coping?
- Minimising the importance of the event | - Short term stressor
126
Identify two types of approach coping
- Problem focused | - Emotional focused
127
Identify two examples of emotional-focused coping
- Behavioural strategies e.g. talking to friends about the emotions - Cognitive strategies e.g. thinking about a problem in a positive way
128
Which type of problem evokes problem focused coping?
- Work related
129
Which type of problem evokes emotional focused coping?
- Health | - Relationships
130
How does coping strategy differ between ages?
- Children and middle-aged people use problem focused coping | - Teens and elderly people use emotional focused coping
131
How does coping strategies differ between men and women?
- Men tend to use problem focused | - Women tend to use emotional focused
132
How does controllability affect coping strategies?
- If the individual believes the condition is controllable they are more likely to use problem-focused coping - If the individual does not believe the condition is controllable they are more likely to use emotion-focused coping
133
What does the 'ways of coping' checklist measure?
- Different coping styles
134
Identify two effects coping should have
- Reduce intensity and duration of stressor | - Reduce likelihood that stress will lead to illness
135
Which type of coping is associated with better outcomes?
- Approach, problem-solving coping
136
Outline Leventhal's self regulatory model
- Illness is dealt with in the same way as any other problem - Individuals try to maintain status quo in three stages - Interpretation of problem - Coping strategy - Appraisal
137
Identify four causes of help-seeking behaviour
- Interpersonal crisis - Interference with social and work life - Sanctioning (family and friends encouraging help-seeking) - Temporising (putting a time limit on symptoms)
138
Identify two reasons for not demonstrating help-seeking behaviour
- Fear of embarrassment | - Fear of the condition
139
What is the purpose of the Mental Capacity Act?
- Protect people who cannot make decisions for themselves or lack the capacity to do so
140
Who does the Mental Capacity Act apply to?
- Severe mental health condition - Severe learning disability - Brian injury - Stroke - State of unconsciousness
141
Identify five key principles of the Mental Capacity Act
- Person assumed to have capacity unless established otherwise - Person not to be treated as unable to make a decision unless all steps to help them do so are unsuccessful - Person not to be treated as unable to make a decision because they make an unwise decision - Act or decision must be in their best interests. - Regard must be had to whether the outcome can be as effectively achieved in a way that is less restrictive of the person’s rights and freedom of action
142
What is meant by advanced decision?
- A decision made by a person - After they have reached the age of 18 and have the capacity to do so - Regarding specified treatment (or lack of) when they eventually lack capacity
143
When does an advanced decision have full legal force?
- In writing - Signed by patient or by a person in patient's presence - With a signature fo a witness
144
When is an advanced decision invalid?
- If patient does something inconsistent with advanced decision
145
What is Lasting Power of Attorney?
- Legal document allowing a person who is at least 21 - To appoint a person to make decisions on their behalf should they lose capacity one day - Personal welfare or property and affairs matters
146
Outline the NICE guidelines for depression
- Mild depression: Psychological intervention e.g. CBT - Moderate - severe depression: Stepwise treatment: - (1) SSRI (sertraline) - (2) SNRI (venlafaxine) / MRA (mirtazapine) > - (3) Antipsychotic (quetiapine) / lithium - (4) TCA (nortriptyline) - (5) MAOI (phenelzine)