BB2 Revision11 Flashcards
What are the three main molecular targets for cocaine? [3]
DA, NAd (nicotinamide adenine dinucleotide) and 5-HT uptake systems
Name 3 selected genes involved in the vulnerability to develop opiate or cocaine addiction [3]
OPRM: Mu opoid receptor
OPRK: kappa opoid receptor
OPRD: delta opoid receptor
Probably don’t need to know in loads of detail
Describe the mesolimbic pathway that controls reward circuits in the brain [2]
Which NT controls this pathway? [1]
dopaminergic projection from the ventral tegmental area
to the nucleus accumbens is essential in reward and drug dependence
State two changes to brain metabolism in cocaine addicts [2]
Reduced availability of dopamine D2 receptors
Reduced cortical metabolism in cocaine abusers
How many units a week is alcohol abuse? [1]
14 units a week
Describe the effects of acute [2] and chronic [1] alcohol abuse on the brain [1]
Acute alcohol ingestion:
* leads to depressed excitatory transmission
* potentiated inhibitory transmission
Chronic:
* Shrinkage of brain grey matter in alcoholic patients
Release of which molecule drives the physchomotor effect of MDMA use? [1]
5-HT release
Behavioural effects co-incide with time course of 5-HT release
Describe the physiological consequence of long term MDMA use [1]
Describe three effects of brain function from long term MDMA use [3]
MDMA:
- glucose metabolism reduces
- Causes decreased learning perfomance, recall, recall consistency
Describe 6 effects that occur from acute MDMA toxicity [6]
Temperature elevation
Disseminated intravascular coagulation
Rhabdomyolysis (blocked by dantrolene)
Increased renal reabsorbtion of water
Hyponatraemia
Cerebral oedema
Describe impact of long term MDMA use on axons in brain [1]
Loss of serotonin axons after long term MDMA use
Cannabinoids bind to [] and [] receptors
Main agonist present in cannabis preparations: []
Cannabinoids bind to CB1 and CB2 receptors
Main agonist present in cannabis preparations: THC
Which drug can be used for reduction of alcohol consumption? [1]
Describe MoA [1]
nalmefene: opiate antagonist
Which of the following is ketamine’s target?
NMDA glutamate receptors
CB1 receptors
GABA-A receptors
5HT3 receptors
Which of the following is ketamine’s target?
NMDA glutamate receptors: antagonist
CB1 receptors
GABA-A receptors
5HT3 receptors
Which of the following are ethanol’s targets? [2]
NMDA glutamate receptors
CB1 receptors
GABA-A receptors
5HT3 receptors
Which of the following are ethanol’s targets? [2]
NMDA glutamate receptors
CB1 receptors
GABA-A receptors - agonist
5HT3 receptors
A 32-year-old male with opioid use disorder presents to the emergency department with chest pain radiating to the left arm. Pain is rated at 5/10 and described as tightness. Currently, he is not in pain, and his vital signs are stable. For his addiction, he is currently receiving methadone prescriptions with occasional relapses for over a year. Given the chronicity of his addiction, where would changes in the patient’s brain be expected, and what neurotransmitter would be involved?
A. Occipital lobe and serotonin
B. Temporal lobe and norepinephrine
C. Prefrontal region and dopamine
D. Wernicke’s area and dopamine
C. Prefrontal region and dopamine
A 24-year-old male patient is seen in the emergency department with paranoid behavior and agitation. He attended a party an hour ago but refused to disclose any further information. His blood pressure is 160/100 mmHg, heart rate is 130 bpm, respiratory rate 20/minute, and the temperature is 38 degrees Celsius. ECG reveals wide QRS complexes suggestive of ventricular tachycardia. What drug was most likely ingested?
A. Heroin
B. Cocaine
C. Methylenedioxyamphetamine (MDMA, ecstasy)
D. Phencyclidine (PCP)
B. Cocaine
Other than dopamine, which NTs become implicated in drug addiction / drug tking behaviour? [2]
gaba; glutamate
If an addict had an impaired ability to perform the following, which part of their brain is most likely to be affected? [1]
Attention and flexibility
Working memory
Decision making
Awareness and insight
Learning and memory
Salience attribution
prefrontal cortex
Explain an example of how chronic drug abuse can alter gene expression and therefore change brain structure [1
Chronic drug use causes an increase in the expression of expression of ΔFosB gene
Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum
FosB functions as a type of sustained “molecular switch” that gradually converts acute drug responses into relatively stable adaptations that contribute to the long-term neural and behavioral plasticity that underlies addiction.
CB1 receptors are concentrated in the []
CB2 receptors are present in [] and are associated
with the [] system
CB1 receptors are concentrated in the central nervous system
CB2 receptors are present in peripheral organs and are associated
with the immune system
Which aspect of cannabis has potential to treat treatment-resistance eplepsy? [1]
Cannabidiol (CBD)
Activation of which receptor by dynorphins and GABA-A underlines the mechanism of withdrawal symptoms
NMDA receptors
Mu opoid receptors
Dopamine (D1) receptors
Kappa opoid receptors
Activation of which receptor by dynorphins and GABA-A underlines the mechanism of withdrawal symptoms
NMDA receptors
Mu opoid receptors
Dopamine (D1) receptors
Kappa opoid receptors
State the impact of spine density and dendrite branching due to cocaine [1] and morphine [1] abuse
Cocaine: increases spine density and dendrite branching
Morphine: Decreases spine density and dendrite branching
Important brain structures for arousal/sleep? [3] update !!
Ascending reticular activating system (ARAS): Important for alerting or arousal
Hypothalamus
Circadian clock
Suprachiasmatic nucleus (SCN) – promote arousal.
What is the prognosis of coma patients? [1]
A third of coma patients die within one month.
outcome of tbi
What are the different parameters for the Post Trauma amnesia scoring used to assess TBI? [3]
PTA:
Mild: less than 24hrs
Mild: 1-7 days
Severe: >7days
State the scores for GCS and LOC that would be classified as
Mild
Moderate
Severe
Exam qs
GCS:
* Mild: 13-15
* Moderate: 9-12
* Severe: 3-8
LOC:
* Mild: 0-30min
* Moderate: 30min - less than24hrs
* Severe: >24 hrs
Define locked-in syndrome [1]
A state of unresponsiveness in which patient lies with eyes closed and cannot be aroused to respond appropriately to any stimuli. However, patient retains eye movement and are fully conscious
Where in the brain does locked-in syndrome occur because of injury to? [1]
Which tracts are effected if this area is damaged? [2]
ventral pons
causing interruption to corticospinal and corticobulbar tracts
Define vegetative state / unresponsive wakefullness syndrome [1]
Spontaneous eye-opening signalling wakefulness, but no evidence of purposeful behaviour suggesting awareness of self or environment.
No purposeful behaviours when exposed to stimuli: visual, auditory, tactile or noxious, and no language comprehension or expression.
Where does damage occur in brain if create decoticate or decerebrate damage? [2]
Decorticate (Damage above red nucleus): arms adducted and flexed, legs internally rotated and plantar flexed
Decerebrate (Damage below red nucleus): arms adducted and extended, legs stiffly extended and plantar flexed: Between the vestibular nuclei and red nuclei
How long does a vegetative state need to persist before it is classified as permenent vegetative state after brain injury? [1]
12 months
Define minimally conscious state (MCS) [1]
Name three characteristics [3]
Condition of severely altered consciousness in which there is definite, but often subtle and inconsistent, behavioural evidence of self or environmental awareness.
E.g.
* Recognise verbal or gestural ‘yes or no’ responses.
* Follow simple commands.
* Provide purposeful movements (e.g. smile, raise a limb,
use objects (e.g. hairbrush) in a consistent manner).
State 4 characteristics of a confusional state [4]
- Interactive communication.
- Amnesia/confusion (weeks – months).
- Hypokinetic or agitated.
- Labile behaviour (e.g. rapid & exaggerated mood changes- laughing/crying).
State 4 characteristics of post-confusional state
- Resolution in amnesia/confusion (months to years).
- Cognitive impairments in higher levels of attention, memory retrieval, and executive functioning.
- Deficits in self-awareness, social awareness, behavioural and emotional regulation.
- Achieve functional independence in daily self care.
What is the percentage rate of recovery from:
<6months of persistent vegetative state? [1]
1 year of persistent vegetative state? [1]
3 years of persistent vegetative state? [1]
Exam q!
What is the percentage rate of recovery from:
<6months of persistent vegetative state: 40%
1 year of persistent vegetative state: 10%
3 years of persistent vegetative state: 5%
exam q
Describe the mechanism of assessing consciousness (Auditory stimulation) using Auditory event-related potential (AERP)
Aim to identify a mismatch negativity (MMN, a negative component appearing in the primary auditory and prefrontal cortices around 100-250 ms after an auditory change in a monotonous sequence of sounds (e.g. an oddball paradigm).
Aim to identify a P300 (a positive component appearing in the primary auditory and prefrontal cortices around 300 ms after an auditory change in a monotonous sequence of sounds (e.g. an oddball paradigm).
Which imaging modalities could you use to assess consciousness? [2]
Stimulation (e.g. auditory, tactile, visual) could carried out on the patient during imaging.
PET scan
Blood oxygenation level dependent (BOLD) fMRI
PVS treatment
Name a drug and describe MoA that may help to recover [3]
Amantadine
* NMDA receptor antagonist and block dopaminergic reuptake
* Improves functional recovery rate
PVS treatment
Name another drug and describe MoA that may help to recover [3]
What is this drug usually given for treatment for? [1]
Zolpidem
* Indirect GABAA receptor agonist
* Usually
* Causes patient to become awake, but short acting and return to vegetative state
What is the hypothesis for zolpidem treatment?
Loss of active inhibition from striatum allows GPi to tonically inhibit thalamus and pedunculopontine nucleus, so thalamocortical overactivity
Which nuclei at the hypothalamus are important with sleep / arousal? [2]
State if they promote sleep or arousal [2]
Tuberomammillary nucleus (TMN) – promote arousal.
Ventrolateral preoptic nucleus (VLPO) – promotes sleep
Which part of the ARAS influences sleep / arousal? [3]
rostral brainstem tegmentum (i.e. pontine tegmentum).
via diencephalon (i.e. thalamus).
projections to the cerebral cortex (i.e. Lateral prefrontal cortex).
Tuberomammillary nucleus increases arousal by secreting which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
Tuberomammillary nucleus increases arousal by secreting which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
Ventrolateral pre-optic nucleus in the hypothalamus increases sleep by secreting which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
Ventrolateral pre-optic nucleus in the hypothalamus increases sleep by secreting which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA & Galamin
The raphe nucleus secretes which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
The raphe nucleus secretes which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
The locus coeruleus secretes which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
The locus coeruleus secretes which of the following
5-HT
Histamines
Orexins
Noradrenaline
GABA
