Overview 2 Flashcards
1
Q
Loss of cells occurs where causing PD
A
Subsantia nigra pars compacta
2
Q
What forms in the brain in a patient with PD?
A
Lewy bodies
3
Q
What are Lewy bodies composed of?
A
Protein alpha-synuclein
4
Q
What cells are lost in PD?
A
Dopaminergic cells
5
Q
Where are dopaminergic cells lost in a patient with PD?
A
Substantia nigra pars compacta
6
Q
What are the three main features/presentations of PD?
A
Resting tremor
Bradykinesia
Rigidity
7
Q
Gradual development of what condition develops with PD?
A
Microphagia
8
Q
Give five non-motor presentations of PD
A
Olfactory dysfunction Depression Dementia Sleep disturbance Autonomic disturbance
9
Q
Non-motor presentations of PD can occur how much earlier than the motor symptoms?
A
Up to 12-15 years
10
Q
Loss of dopaminergic cells in PD causes an imbalance in which two pathways?
A
Direct and indirect pathways of basal ganglia
11
Q
What is meant by a score of 100% in the Schwab and England Activities of Daily living?
A
Patient is completely independent
12
Q
How can the brain be imaged for dopaminergic cells in PD?
A
Dopamine transporter imaging
13
Q
PD more common in males or females?
A
Males
14
Q
MPTP has what effect on PD?
A
Can result in very advanced PD
15
Q
Why can MPTP cause advanced PD?
A
Transformed into MPP+ which is neurotoxic to dopaminergic neurones
16
Q
MPTP causes dysfunction of which organelle?
A
Mitochondria
17
Q
What is the main enzyme causing oxidative stress in PD?
A
MAOb
18
Q
Which of the dopaminergic pathways of the CNS is involved in PD?
A
Nigrostriatal pathway
19
Q
Which of the dopaminergic pathways of the CNS is involved in PD?
A
Nigrostriatal pathway
20
Q
What are the two groups of dopamine receptors?
A
D1
D2
21
Q
D1 dopamine receptor groups consists of which dopamine receptors?
A
D1 and D5
22
Q
D2 dopamine receptor groups consists of which dopamine receptors?
A
D2, D3, D4
23
Q
Stages of metabolism of dopamine?
A
Dopamine to DOPAC to homovanillic acid
24
Q
What is the role of MAO in dopamine metabolism?
A
Dopamine to DOPAC via MAO
25
What is the role of COMT in dopamine metabolism?
DOPAC to homovanillic acid via COMT
26
What type of receptor is the dopamine receptor?
G-protein coupled receptors
27
L-dopa can be used to treat dopamine because?
Pre-cursor - will be converted into dopamine
28
L-dopa should be given to a patient along with what?
Peripherally acting DOPA decarboxylase inhibitor
29
Name two other drug groups used for the treatment of PD? x2
MAOb inhibitors
Anticholinergic compounds
COMT inhibitors
30
Why are anticholinergic compounds used to treat PD?
Dopamine loss leads to hyperactivity of cholinergic cells
31
What is the role of amantadine in PD treatment? x2
Inhibits dopamine reuptake and increases dopamine release
32
What is apomorphine?
Dopamien agonist used as infusion for major motor fluctuations
33
What is rotigotine?
Dopamine agonist - transdermal patch
34
What is carbidopa?
Peripherally acting DOPA decarboxylase inhibitor
35
What is ropinerole?
Dopaminergic agonist
36
What is rasagiline?
MAOb inhibitor
37
What is benserazide?
Peripherally acting DOPA decarboxylase inhibitor
38
What is entacapone?
COMT inhibitor
39
What is tolcapone?
COMT inhibitor
40
What is tolcapone?
COMT inhibitor
41
Give 5 non-motor effects of L-DOPA
```
Nausea/vomiting
Postural hypertension
Psychosis
Impulse-control disorders
Excessive day-time sleepiness
```
42
Give four motor complications of L-dopa therapy
On-off effect
Wearing off
Dyskinesia/dystonia
43
Three types of therapy that should be offered to patients with PD?
Physiotherapy
Speech and language therapy
Occupational therapy
44
What is Huntington's chorea?
Involuntary jerky movements
45
Cause of Huntington's chorea?
Mutation on huntington protein of chromosome 4
46
Mutation involved with Huntington's chorea is?
Abnormal number of repeats of glutamine (CAG)
47
Inheritance of Huntington's chorea is?
Autosomal dominant
48
Four pathological changes in the brain seen in Huntington's chorea?
Cortical atrophy
Striatal degneration
Loss of medium spiny neurones
Intranuclear inclusions of huntington
49
Main drug used to treat Huntington's chorea?
Tetrabenazine
50
Main drug used to treat Huntington's chorea?
Tetrabenazine
51
Two types of stroke are?
Ischaemic
| Haemorrhagic
52
Main cause of intercerebral bleed is?
Hypertension
53
Four secondary causes of intercerberal haemorrhages?
Trauma
Tumour
Venous thrombosis
Drug usage
54
Four complications of ICH?
Local damage
Local mass effect/herniation
Raised ICP
Hydrocephalus
55
Three medical conditions that are risk factors for stroke are?
Hypertension
Hypercholesterolaemia
Diabetes
56
Cardiac condition that is a risk factor for stroke is?
AF
57
Deficit occurring from left hemisphere stroke is?
Reading and writing deficits
58
Prognosis for stroke?
1/3 - do well
1/3 - die
1/3 - poor prognosis
59
Prognosis for stroke?
1/3 - do well
1/3 - die
1/3 - poor prognosis
60
Three common symptom of MS?
Sensory/motor problems - numbness of the limbs/tingling sensation
Vision problems - blurriness/loss/diplopia
Progressive motor deficits
61
Three uncommon symptoms of MS
Bladder dysfunction
Heat intolerance
Dementia
62
What is MS?
Demyelinating, degenerative and inflammatory condition
63
What imaging is used for MS type conditions?
MRI
64
MRI signs of MS? x2
Lesion in corpus callosum
| Areas of inflammation and brain atrophy
65
Non-imaging investigation used for MS?
Lumbar puncture
66
Three stages of MS disease progression?
Relapsing-remitting
Primary progressive
Secondary progressive
67
Lumbar puncture for MS - looking for what?
Presence of neurofilaments - oligoclonal bands
68
Four diagnostic criteria for MS?
Neurological deficits
Dissemination in space
Dissemination in time - damage occurred at two points in time
Exclusion of other causes
69
How many areas of the CNS must be damaged to diagnose MS?
At least two separate areas
70
Life expectancy of those with MS is reduced by what amount?
10-15 years
71
Loss of which cells occur in MS?
Oligodendrocytes
72
Loss of which cells occur in MS?
Oligodendrocytes
73
Oligodendrocytes produce what?
Myelin sheath
74
Four features of an MS lesion?
Astrocytic scar
Demyelination
Activated microglia
Oligodendrocyte loss
75
Cells involved in the demyelination of MS are?
Macrophages
76
Pathological hallmark of an MS lesion is?
Demyelinated axons
77
Infiltration of what cells occurs in MS?
T cells
78
T cells involved in MS are known as?
Autoreactive lymphocytes
79
T cells can enter brain in MS because?
BBB is damaged
80
Weighting of MRI for MS diagnosis?
T1
81
Differential diagnosis for MS? x4
Cerebrovascular disease
Syphilis
B12 deficiency
Lyme disease
82
Typical age of diagnosis of MS?
20s/30s
83
What comes first in MS - inflammation or degeneration?
We do not know
84
Relation of smoking to MS?
Smoking can cause MS
85
Four stages of MS treatment
Anti-inflammatory
Neuroprotection
Remyelination
Neuro-restoration
86
First line teatment for MS? x2?
IFNb
| Natalizumab
87
Second line treatment for MS? x3
Fingolimod
Natalizumab
Alemtuzumab
88
Anatomical location of lumbar puncture?
Between L3 and L4 into subarachnoid space
89
Anatomical location of lumbar puncture?
Between L3 and L4 into subarachnoid space
90
Four physiological stages in the mechanism of pain?
Transduction
Transmission
Perception
Modulation
91
Transduction of pain involves what?
Noxious stimuli into electrical activity at sensory nerve endings
92
Endings of nociceptors are free or capsulated?
Free
93
Nociceptive channel that opens in response to heat thermal stimuli is?
TRPV1
94
Nociceptive channel that opens in response to cold thermal stimuli is?
TRPM8
95
Noxious fibres lost in diabetic neuropathy are?
C fibres
96
C fibres/a-delta fibres - which are myelinated?
A-delta
97
C fibres/a-delta fibres - which are fast conducting?
A-delta
98
C fibres/a-delta fibres - which is first and which is second pain?
A-delta - first, immediate pain
| C - second, emotional pain
99
Resulting action from activation of a-delta fibres is?
Reflex withdrawal
100
Two classes of C fibres are?
Peptidergic c-fibres
| Peptide-poor c fibres
101
Peptidergic C fibres release what? x2
Substance P
| CGRP
102
Receptor of peptide poor c fibres is?
P2X3 - peptide poor C fibres
103
C fibre classes - which involves ATP receptors?
Peptide poor
104
A delta fibres project to which laminae?
I and V
105
C fibres project to which laminae?
I and II
106
What projects to lamina I?
All nociceptors
107
Gene responsible for the development of nociceptors is?
trkA
108
A-beta fibres enter/innervate which lamina?
V
109
What are projection neurones?
Second order neurones
110
What are VPL and VPM?
Nuclei:
Ventral posterior lateral
Ventral posterior medial
111
VPL and VPM project to where?
Primary somatosensory cortex
112
A-delta fibres mainly run into which spinal tract?
Anterior spinothalamic
113
Function of anterior spinothalamic tract is?
Regulates immediate need to withdraw arm from pain
114
A-delta fibres innervate which nuclei? x4
VPL
VPM
VPI (inferior)
CL (central lateral)
115
C-fibres mainly run into which spinal tract?
Lateral spinothalamic tract
116
C-fibres innervate which nucleus? x2
Posterior thalamus
| Mediodorsal nucleus
117
Function of the lateral spinothalamic tract?
Regulation of punishing aspects of pain - prevent repetition
118
Lateral spinothalamic tract projects to where?
Anterior cingulate cortex (limbic system)
| Rostral insular cortex
119
Anterior spinothalamic tract projects to where?
Primary and secondary somatosensory cortex
120
Lateral spinothalamic associated with which pain pathway?
Periaqueductal grey PAG
121
PAG pathway located where?
Midbrain
122
Lateral spinothalamic projects to which three specific areas?
PAG
Reticular formation
Parabrachial nucleus
123
Four signs of inflammation?
Calor - heat
Rubor - redness
Dolor - pain
Tumor - swelling
124
Inflammation results in what type of sensitisation?
Peripheral sensitiation
125
Three hallmarks of sensitisation?
Hyperalgesia
Allodynia
Spontaneous pain
126
Hyperalgesia is?
Abnormally heightened sensitivity to pain
127
Allodynia is?
Sensation of pain from non-noxious stimuli
128
Two features of peripheral sensitisation?
Reduced activation threshold
| Increased responsiveness
129
NaV1.8 is?
Sodium channel
130
NaV1.9 is?
Sodium channel
131
Arachidonic acid released via what enzyme?
Phospholipase A2
132
Arachidonic acid converted to what?
Prostaglandins
133
Arachidonic acid converted to prostaglandins via what enzymes?
COX1
| COX2
134
COX1 present what?
Normally present in all tissues at low levels
135
COX2 present when?
COX-2 induced during inflammation
136
Prostaglandins sensitise which pain fibres?
C-fibres
137
Prostaglandins are targeted by which pain relieving drug specifically?
NSAIDs
138
Central sensitisation caused by?
Prolonged nociceptive input
139
Central sensitisation results in what?
Modified response - low level inputs produce repsonse
140
Neurotransmitter involved in central sensitisation development?
Glutamate
141
Neuropathic pain is?
Pain due to injury/dysfunction in the PNS or CNS
142
Gate control theory of pain is?
Endogenous modulation e.g. acupuncture e.g. DNIC
143
Neurones responsible for pain modulation are?
Interneurones in lamina II
144
DNIC works how? - which fibres and pain pathway are activated?
Diffuse noxious inhibitory control
Activation of a-delta fibres
Stimulation of PAG pathway
145
PAG pathway involves which two neurotransmitters?
Serotonin
| Noradrenaline
146
PAG pathway involves which other mediator, other than the neurotransmitters?
Opioids
147
MS lesions are located where?
Periventricular
148
Three types of pain are?
Nociceptive - acute
Inflammatory - chronic
Neuropathic - chronic maladaptive
149
What are enkephalines?
Endogenous opioids used in the PAG pathway
150
Transmitters from NRM to dorsal horn in the PAG pathway are? x2
5-HT
| Enkephalines
151
Transmitter from LC to Dorsal horn in PAG pathway is?
Noradrenaline
152
Opioids have action at which sites of the PAG pathway? X3
PAG
NRPG
Dorsal horn
153
Six factors that influence pain perception are?
```
Cognition
Mood
Chemicals and structure
Context
Genetics
Injury
```
154
Enkepahline are short or long peptides?
Short
155
Enkephalines are derived from?
Proenkephalin
156
Opioid receptors are what type of receptor?
G protein coupled receptor
157
Three opioid/opiate receptors are?
Mu 1, 2, 3
Delta 1, 2
Kappa 1, 2, 3
158
Mu opioid receptors are located where?
All over the body
159
Morphine works on what channels? x2
Increased at K+ channel
| Decreased at Ca2+ channel
160
Overall effect of morphine is?
Decreased excitability
| Increased release of neurotransmitters
161
What is naloxone?
Opiate antagonist
162
Half life of naloxone is long or short?
Short
163
What is opioid switch?
Patient becomes tolerant to one particular opioid drug - switch them to another
164
Strongest side effect associated with kappa opioid receptors is?
Dysphoria
165
Three side effects associated with opioid medication?
Respiratory depression
Sedation
Reduced GI motility - constipation
166
Three stages of analgesic ladder?
Non-opioids and adjuvant drugs
Moderate efficacy opioids
High efficacy opioids
167
Function of paracetamol in pain management?
Reduces Cox-2 levels
| Analgesic and antipyretic
168
Function of NSAIDs in pain management?
Cox 1 and Cox 2 inhibitors
169
Two side effects of NSAIDs?
Nausea
| GI bleeding
170
Amitriptyline is?
Tricyclic antidepressant
171
Indication for amitriptyline in pain management is? x2
Neuropathic pain
| Cancer
172
Indication for anticonvulsant drugs in pain management is? x2
Neuropathic pain
| Trigeminal neuralgia
173
Carbamazepine is?
Anticonvulsant - sodium channel
174
Sodium valproate is?
Anticonvulsant - sodium channel
175
Pregabalin is?
Anticonvulsant - calcium channel
176
Pregabalin works on which part of the calcium channel?
alpha 2 delta
177
Anaesthetics work via what mechanism?
Blockage of sodium channels
178
Cause of trigeminal neuralgia?
Compression/stretching of trigeminal nerve root
179
Artery that tends to compress trigeminal nerve in trigeminal neuralgia is? x2
AICA or PICA
180
Treatment for trigeminal neuralgia? x3
Carbamazepine
Baclofen
Phenytoin
181
The most common site of chronic pain in the UK is?
Back pain
182
CBT programme for management for pain lasts how long?
12 weeks
183
Four types of pain behaviours are?
```
Negative affect
Facial/audible expression
of distress
Distorted posture
Avoidance of activity e.g. work
```
184
Seizures in epilepsy are described as? x2
Recurrent and unprovoked
185
Seizures are?
Abnormal paroxysmal changes in electrical activity of the brain
186
Epileptogenesis is?
Development of epilepsy in a normal brain
187
Prevalence of epilepsy in the UK?
1%
188
Status epilepticus is?
Form of epilepsy where seizures last more than 5 minutes/more than one seizure in the space of 5 minutes
189
Is status epilepticus a medical emergency?
Yes
190
Five stages of tonic-clonic seizure?
```
Premonition
Pre-tonic-clonic phase
Tonic phase
Clonic phase
Postictal period
```
191
What happens in the premonition stage?
Vague sense that seizure is immunent
192
What happens in the pre-tonic-clonic phase?
Few myoclonic jerks/brief clonic seizures
193
What happens in the tonic phase?
Contraction of axial muscles
Upward eye deviation
Epileptic cry
Respiratory muscle contraction
194
What happens in the clonic phase?
Jerks of increasing amplitude
| May have sphincter opening
195
What happens in the postictal period?
Generalised lethargy
Decreased muscle tone
Headaches
Sore
196
A person may wet themselves in which stage of a tonic clonic seizure?
Clonic
197
You may hear a person cry out in which stage of a tonic-clonic seizure?
Tonic
198
Someone may smell a burning smell that is not apparent to anyone else around them in which stage of a tonic-clonic seizure?
Premonition - this may be their aura
199
Diagnostic criteria for epilepsy diagnosis?
Occurence of two or more seizures
| Witness account essential
200
Reorganisation of what particular region occurs in temporal lobe epilepsy?
Hippocampus
201
What happens to the hippocampus in temporal lobe epilepsy?
Becomes sclerotic
202
What may happen to fibres in the temporal lobe in temporal lobe epilepsy?
May have a sprouting of new fibres
203
Why is a sprouting of new fibres problematic?
Can lead to development of aberrant circuits
204
Sprouting of new fibres in temporal lobe epilepsy typically occurs from which cells?
Granule cells
205
What cells are typically lost in epilepsy?
Chandelier cells
206
What are chandelier cells?
Inhibitory GABAeric interneurones
207
Chandelier cells synapse where?
On axon initial segment of pyramidal cells
208
Chandelier cells control activity of what?
Cortical pyramidal cells
209
Loss of chandelier cells results in what?
Increased risk of abnormal excitatory activity
210
Three causes of secondary epilepsy?
Stroke
Brain tumour
CNS infection
211
Three cellular mechanisms resulting in the development of epilepsy are?
Increased excitation - glutamate dependent
Decreased inhibition - GABA dependent
Abnormal neuronal excitability - ion channels
212
What are the receptors involved in the paroxysmal depolarising shift of a seizure?
NMDA glutamate receptor
213
Abnormalities/mutations of what cell may be involved in development of epilepsy?
Glial cells
214
Role of glial cells with glutamate neurotransmitter?
Glial cells - glutamate transport and clearance
215
Two pathways that may be involved in the development of epilepsy?
mTOR
| REST
216
Phenytoin has an effect on what channel?
Sodium
217
Phenytoin should not be used in what type of seizure?
Absence
218
Carbamazepine works on what channel?
Sodium
219
Phenytoin has what order kinetics?
Zero
220
Carbamazepine should not be used in what type of seizure?
Absence seizure
221
Lamotrogine works at what two channels?
Sodium
| Calcium
222
Lamotrogine has what effect?
Presynaptic inhibition of glutamate release
223
What drug should be used in absence seizures?
Ethosuxomide
224
Ethosuxomide targets what channels?
T-type calcium channels
225
Gapapentin/pregabalin targets what channels?
Alpha2delta subunit of calcium channels
226
Tiagabine has what effect and what target?
Inhibits GABA uptake
GAT-1 transporter
227
Vigabatrin has what effect?
Inhibits GABA metabolism
228
Which two anti-epileptic drugs increases hepatic levels of their own enzymes?
Phenytoin
| Carbamazepine
229
Treatment for status epilepticus?
IV diazepam
230
Three potential treatments for epilepsy? (non pharmacological)
DBS
Vagal nerve stimulation
Ketogenic diet
231
Three types of primary headaches?
Tension-type
Migraine
Cluster headache
232
Treatment of cluster headache?
Provision of 100% O2
233
Pathophysiology of migraine revolves around what?
Cortical spreading depression
234
What types of brains are subject to migraines?
Excitable brains
235
What is heightened during a migraine?
Senses - smell, light, sounds, touch
236
Four factors that could result in the onset of a migraine?
Hormones
Lack of food
Dehydration
Lack of sleep
237
Migraine with/without aura - which is more common?
Without aura
238
What part of the brain plays a major role in the onset of a migraine?
Hypothalamus
239
A migraine aura comes from what part of the brain?
Visual cortex - occipital lobe
240
Cortical spreading depression occurs in which region of the brain?
Visual cortex - occipital lobe
241
Effect of cortical spreading depression on arteries?
Swelling of arteries - increased inflammation
242
What type of inflammation occurs from cortical spreading depression?
Neurogenic inflammation
243
Via what activation does cortical spreading depression result in the onset of pain?
Trigeminal ganglion activation leads to peripheral sensitisation
244
Swelling of what arteries occurs during a migraine?
Meningeal arteres
245
Trigeminal nerve conveys pain impulses to where in a migraine?
Trigeminal nucleus caudalis in the brainstem
246
What must you never give to a patient suffering from a migraine?
Codeine
247
Function of vestibular system? x3
Maintenance of balance, posture and spatial orientation
248
Three receptors systems to the vestibular system are?
Eyes
General proprioception - muscles, joints, tendonds
Vestibular apparatus in inner ear
249
Three components of the inner ear are?
Labyrinth
Vestibular apparatus
Cochlea
250
Two parts of the vestibular apparatus?
Vestibular part
| Auditory part
251
What are the two solutions in the labyrinth?
Endolymph
| Perilymph
252
Which part of the vestibular system is the membranous part?
Labyrinth
253
Where is the endolymph located?
Inner solution
254
Endolymph electrolyte balance?
High K+ and low Na+
255
Perilymph electrolyte balance
Low K+ and High Na+ (CSF)
256
Where is the perilymph located?
Surrounds the labyrinth
257
Components of the labyrinth are known as what?
Semicircular ducts
258
What moves around in the semicircular ducts?
Endolymph
259
What is on the surface of vestibular cells?
Cilia - hair cells
260
Function of the cilia on vestibular cells?
These are mechanoreceptors
261
Activation of cilia results in what in vestibular cells?
Depolarisation of the cell
262
Cilia on the vestibular cells are known as what?
Stereocilia
263
Function of the semi-circular ducts? x2
Provides kinetic sensitivity i.e. awareness of movement of the head
Provides information about angular acceleration
264
What are utricles?
Cilia on hair cells are angled towards the striola
265
What are saccules?
Cilia on hair cells are angled away from striola
266
What is Meniere's disease?
Mixing of the endolymph and the perilymph
267
Cause of Meniere's disease?
Overproduction of endolymph
268
Most common symptom of Meniere's disease?
Tinnitis
269
What is Kinnetosis?
Motion sickness
270
Hallpike maneuver tests for what?
Benign paroxysmal positional vertigo
271
Mental state examination tests what?
Someone's mindset
272
Mini mental state examination tests what?
Someone's cognition
273
What is psychopathology?
The study of all abnormal experiences, cognition and behaviour
274
What is penomenology?
The study of subjective psychological evetns
275
Six components of the mental state examination?
```
Appearance and behaviour
Speech and form of thought
Mood
Perceptions
Cognition
Insight
```
276
What is classical conditioning?
Paring of two stimuli
Neutral stimulus elicits biological response e.g. dogs and bell
277
What is operant conditioning?
Association between a behaviour and its consequence
278
One main region of the brain where operant conditioning occurs?
Nucleus accumbens
279
Role of nucleus accumbens in operant conditioning?
Release of dopamine after e.g. sex, exercise
280
What is social learning?
People do what other people do - see them as role models
281
MS is a disease of which cells in the CNS?
Oligodendrocytes
282
Neurodegeneration of MS is most visible where?
Ventricles
283
Three core symptoms of MS?
Pain
Tremor
Spasms
284
Two cannabinoid receptors found in the body?
CB1 and CB2
285
CB1 found where?
Abundant in adult CNS:
```
Brain
Adipose tissue
Muscle
Liver
GI tract
Pancreas
```
286
CB2 found where?
Restricted to the immune system
287
CB1 is what type of receptor?
G-protein coupled receptor
288
Function of cannabinoids in the body?
Regulation of synaptic neurotransmission
289
Define addiction?
Chronic disease characterised by drug seeking use that is compulsive/difficult to control DESPITE harmful consequences
290
What is drug abuse?
Drug use in amounts/methods that is directly or indirectly harmful to themselves or others
291
What is drug dependence?
Adaptive state developing after repeated drug use - results in withdrawal symptoms upon cessation
292
What is drug tolerance?
Diminishing effect of a drug following repeated admission at a set dose
293
What is psychological dependence?
Dependence involving emotional-motivational symptoms e.g. depression, restlessness, anhedonia
294
What is physical dependence?
Dependence resulting in significant physical-somatic withdrawal symptoms e.g. fatigue, nausea
295
Ethanol has an action at which receptors? x2
GABAa
| NMDA
296
Hallucinogens has action at which receptor?
5-HT2
297
Three factors that determine the development of addiction?
Environment
Drug-induced effects
Genes
298
Where is the projection of dopamine in the brain that is most important for drug dependence? (x2 regions)
From ventral tegmental area to the
| Nucleus accumbens
299
Three stages of the addiction cycle?
Binge/intoxication
Withdrawal/negative affect
Preoccupation/anticipation
300
What is released upon multiple uses of drug consumption?
GABA
301
What is the effect of GABA release upon multiple drug use?
Attempts to dampen down the dopamine release from the drug - drug tolerance
302
Drug tolerance is mediated via which neurotransmitter?
GABA
303
Drug addicts have reduced numbers of which receptors in the brain?
D2 dopamine
304
Lack of self-control, emotional regulation, motivation, attention, decision making, working memory etc in drug addicts is due to damage in which region of the brain?
Pre-frontal cortex
305
Where is the ventral tegmental area/ventral tegmentum located?
Floor of the midbrain - near the midline
306
Alcohol has an effect on which receptors?
NMDA - excitatory
| GABAa - inhibitory
307
Alcohol abuse involves drinking over how many units per day - men?
5
308
Alcohol abuse involves drinking over how many units per day - women?
3
309
General effect of alcohol abuse on the brain?
Shrinking of grey matter
310
Loss of what percentage of grey matter occurs in alcohol abuse?
12%
311
Ecstasy is also known as?
NMDA
312
Five receptors of MDMA are?
```
5-HT
5-HT2
Dopamine
Histamine H2
Alpha-2 adrenergic
```
313
Loss of what innervation pathways occurs when you take NMDA?
5-HT
314
Cannabis acts on what receptor? x2
CB1
| CB2
315
CB1 receptors are located where?
CNS
316
CB2 receptors are located where? x2
Peripheral organs
| Immune system
317
Cannabinoids are inhibitory or excitatory?
Inhibitory
318
What type of receptor are CB1 and CB2?
G protein coupled receptor
319
Five methods for drug addiction management
```
Detoxification - eliminate from the body
Psychological support - counselling
Medication
Treatment for mental health
Long term follow up
```
320
What is nalmefene?
Opioid antagonist
321
Function of nalmefene in treatment drug addiction?
Reduction of alcohol consumption
322
Use of antibiotic ceftriaxone in treatment of drug addiction?
Attenuate cocaine relapse after cessation
323
Treatment for rhabdomyelosis?
Dantrolene
324
Monoaminergic theory for depressions states that?
Reduced levels of monoamines is responsible for the development of depression
325
Two monoamines outlined in the monoaminergic theory of depression?
Serotonin
| Noradrenaline
326
Patients with depression have decreased rates of metabolism where in the brain?
Subgenual prefrontal cortex
327
Sign of depression in grey matter is?
Decreased cortical thickness
328
What is meant by 'default mode network' in teh brain?
Network of brain regions that are active whilst the brain is at wakeful rest
329
Pathway for rumination?
Negative stimulus activates amygdala and hippocampus
Activates subgenual cingulate cortex
Prefrontal cortex normally stops pathway here
330
Effect of depression on rumination?
Prefrontal cortex does not have the desired effect to stop the rumination pathway
331
Function of tricyclic antidepressants?
Inhibition of monoamine reuptake - increase levels of monomines
332
SO three theories to explain development of depression?
Monoamine theory
Reduced dopamine level theory
Reduced grey matter theory
333
Adverse effects of tricyclic antidepressants? x3
Dry mouth
Blurred vision
Loss of libido
334
Main adverse effect of MAOb inhibitors?
Cheese effect
335
Cheese effect involves foods containing what compound?
Tyramine
336
Main disadvantage of TCAs?
Have widespread selectivity at different receptors e.g. histamine receptor
337
The most selective SSRI is?
Citalopram
338
Advantages of using SSRIs? x2
Similar efficacy to tricyclic antidepressants
| No selectivity for other receptors
339
What is moclobemide?
Reversible monoamine oxidase inhibitor
340
Advantage of moclobemide? x3
Increased selectivity of MAOa
Not irreversible
No cheese effect
341
Why is there a delay of action of antidepressant drugs?
Action of autoreceptors - these then become desensitised
342
What is antidepressant drug discontinuation syndrome?
Symptoms occurring following sudden cessation of antidepressant medication
343
Gradual decrease in antidepressant medication over how long to avoid the onset of antidepressant drug discontinuation syndrome?
6 months
344
Drug used in treatment of bipolar disorder?
Lithium
345
What is bipolar disorder?
Cycles of depression and mania
346
Function of which two organs should be checked prior to lithium treatment?
Thyroid
| Renal
347
Four non-pharmacological treatments for depression?
Electrocompulsive therapy
CBT
Vagal nerve stimulation
DBS
348
Disadvantage of ECT?
Long lasting cognitive effects
349
Advantage of CBT in treatment of depression?
Can augment pharmacological effects
350
Indication for use of vagal nerve stimulation for treatment fo depression?
Chronic depresson
351
DBS in which area for treatment of depression?
Area 25 - subcallosal cingulate cortex
352
Indication for use of ECT for treatment of depression?
Severe and treatment resistant depression
353
Neuronal loss occurs specifically where in the brain with depression?
Hippocampus
354
Depression - increase in levels of what in the brain? x2
Cortisol
| IL6
355
Three symptom types in schizophrenia are?
Positive
Negative
Cognitive
356
Positive symptoms of schizophrenia are?
Hallucinations, delusions - things people would not normally experience
357
Negative symptoms of schizophrenia are?
Introversion, apathy, low self-esteem - things mentally stable may experience
358
Cognitive symptoms of schizophrenia are?
Poor memory, attention deficit
359
Diagnostic criteria for schizophrenia?
Two or more of the outlines symptoms each present for a significant portion of time during a one month period
360
Four genes associated with the development of schizophrenia?
BDNF
COMT
DAOA
Neuregulin 1
361
Function of BDNF?
Neurotrophic factor that has an effect on long term memory
362
Function of COMT?
Dopaminergic transmission
363
Function of DAOA?
Glutaminergic transmission
364
Function of neuregulin 1?
Neuroplasticity
365
Treatment for schizophrenia are generally used for the management of which symptoms?
Positive symptoms
366
Normally - what is seen in MRI of schizophrenia patient?
Normally see no change
367
What might be seen in MRI of schizophrenia patient? x2
Larger ventricles
| Smaller mesial temporal lobe structures
368
Changes in cerebral perfusion in schizophrena? x3
Decreased perfusion in the prefrontal cortex
| Increased perfusion in the thalamus and cerebellum
369
Kraepelinian definition of a poor outcome for schizophrenia is?
Progressive deteriorating course
370
Involvement of which dopaminergic pathways in schizophrenia? x2
Mesolimbic pathway
| Mesocortical pathway
371
Changes in the dopaminergic pathways in schizophrenia are?
Hyperactivity in the mesolimbic pathway
| Hypoactivity in the mesocortical pathway
372
Nigrostriatal dopaminergic pathway is involved in what condition?
PD
373
D1 type receptors are?
D1, D2
374
D2 type receptors are?
D2, D3, D4
375
First medication available for treatment of schizophrenia was?
Chlorpromazine
376
What is chlorpromazine?
Typical antipsychotic
377
Typical vs. atypical antipsychotics?
Atypicals also have an effect at 5-HT receptors SO on cognitive and negative symptoms
378
Typicals vs. atypicals - which is the first line treatment for schiz?
Atypicals
379
Clozapine is?
Atypical antipsychotic
380
Clozapine has significant action at which receptor?
D4
381
Use of antipsychotic drugs (typicals and atypicals) restuls in an increase in which hormone?
Prolactin
382
Usage of atypicals results in which metabolic adverse effects? x3
Weight gain
Dyslipidaemia
Type 2 diabetes
383
Extrapyramidal effects of antypsychotic drug use? x3
Dystonia
Parkinsonism
Tardive dyskinesia
384
Two antipsychotics that can be used as depot IM injections for slow release are?
Fluphenazine
| Haloperidol
385
Why might depot IM injection be used for treatment of schiz?
High levels of non-compliance
386
Antipsychotic drug used in drug resistance in treatment of schiz?
Clozapine
387
Percentage of schiz patients that do not respond to treatment is?
30%
388
Adverse effect of clozapine?
Agranulocytosis
389
Two non-phamacological treatments for schiz?
CBT
| Family therapy
390
Can non-pharmacological treatments replace the pharmacological treatments in schiz?
No
391
Schiz associated with decreased levels of which neurotransmitter and receptor?
Glutamate NMDA
