Psychological Medicine Flashcards
What is consciousness?
The state of being aware of and responsive to one’s surroundings
A person’s awareness or perception of something
Involves perception, cognition, action
Ability for memory, language, emotion, abstraction, attention
What are the levels of consciousness?
Many levels
All are defined and mean different things
In an approximately descending scale
- Fully conscious
- Clouding of consciousness
- Confusional state
- Delirium
- Lethargy
- Obtundation
- Stupor
- Hypersomnia
- Minimally responsive state
- Unresponsive Wakefulness Syndrome (UWS) (formerly ‘vegetative state’)
- Akinetic mutism
- Locked-in syndrome
- Coma
- Brain death
What are some disorders of consciousness?
High to low
Locked-in syndrome - Patient has awareness, sleep-wake cycles, and meaningful behaviour (viz., eye-movement), but is isolated due to facial and body paralysis
Minimally conscious state - Patient has intermittent periods of awareness and wakefulness and displays some meaningful behaviour
Unresponsive wakefulness syndrome - Patient has sleep-wake cycles, but lacks awareness; only displays reflexive and non-purposeful behaviour
Chronic coma - Patient lacks awareness and sleep-wake cycles; only displays reflexive behaviour
Brain death - Patient lacks awareness, sleep-wake cycles, and brain-mediated reflexive behaviour
What are normal vs abnormal losses of consciousness?
Normal
- Sleep
Abnormal
- Coma
- Anaesthesia
- Unresponsive wakefulness syndrome
Vital to distinguish the properties of being conscious from levels of consciousness
How is fMRI used in the diagnosis of unresponsive wakefulness syndrome (UWS)?
Functional magnetic resonance imaging
Looks at activation in the brain
Sensitive to oxygenated blood - more activation more oxygenated blood
Ask patient to imagine playing tennis - lights up in motor cortex (motor imagery)
Ask patient to imagine walking through their house room to room - lights up in parahippocampal (spatial imagery)
Can answer yes or no by imagining these two things - yes lights up motor and no lights up spatial
What does a PET scan measure?
Positron emission tomography
Measures glucose metabolism
Involves injection of radioactive tracer
What are the causes of serious loss of consciousness?
Most common worldwide
- Malaria (cerebral)
In the UK
- Stroke (haemorrhage/thrombosis/embolus)
- Cardiovascular
- Diabetes
- Drug induced (alcohol/other poison/overdose)
- Epilepsy
- Head injury
- Raised intracranial pressure (tumour/abscess)
- Dementia
- Uraemia, liver disease (other metabolic disorders)
How do you assess an unconscious patient?
ABC - Is immediate intervention necessary?
History - What is known about why consciousness is lost?
Screening - Examinations and neurological examination, clinically assess behaviour (ACVPU)
The Glasgow Coma Scale - Reliable and objective measure of consciousness
What does ACVPU stand for?
Awake/Alert Confusion Voice Pain Unresponsive
What is the Glasgow Coma Scale?
3 categories - eye opening, verbal response, motor response
Scored for ability in each to give a number out of 15
A fully conscious patient has a GCS of 15
A person in a deep coma has a GCS of 3 (no lower score)
What are the ratings for eye response in the GCS?
4 - Spontaneous eye opening
3 - Eye opening in response to any speech (or shout, not necessarily request to open eyes)
2 - Opening to response to pain (to limbs)
1 - No response
What are the ratings for verbal response in the GCS?
5 - Oriented: patient knows who he is, where he is and why, the year, season, and month (Infant: Smiles, oriented to sounds, follows objects, interacts)
4 - Confused conversation: patient responds to questions in a conversational manner but some disorientation and confusion (Infant: Cries but consolable, inappropriate interactions)
3 - Inappropriate speech: Random or exclamatory articulated speech, but no conversational exchange (Infant: Inconsistently inconsolable, moaning)
2 - Incomprehensible speech: Moaning but no words. (Infant: Inconsolable, agitated)
1 - No verbal response
What are the ratings for motor response in GCS?
6 - Obeying command: Patient does simple things you ask (Infant: moves spontaneously or purposefully)
5 - Localising response to pain: Pinch earlobe, put pressure on the patient’s finger nail bed with a pencil, supraorbital and sternal pressure. Purposeful movements towards changing painful stimuli is a ‘localising’ response (Infant: withdraws from touch)
4 - Withdraws to pain: Pulls limb away from painful stimulus (Infant: withdraws from pain)
3 - Abnormal flexor response to pain: Painful stimulus causes abnormal flexion of limbs (decorticate)
2 - Extensor posturing to pain: Painful stimulus causes limb extension (adduction, internal rotation of shoulder, pronation of forearm) (decerebrate)
1 - No response to pain
What do results from GCS mean?
13-15 - mild head injury
9-12 - moderate head injury
3-8 - severe head injury (suggests coma with need for intubation)
> 12 minor injury 9-12 moderate severity >= 9 not in coma 90% <=8 are in coma 8 is the critical score (<=8 at 6 hours - 50% die)
What is the NHS definition of brainstem death?
A person must be unconscious and fail to respond to outside stimulation
A person’s heartbeat and breathing can only be maintained using a ventilator
There must be clear evidence that serious brain damage has occurred and it can’t be cured
What is the academy of royal colleges definition of death?
Irreversible cessation of the integrative function of the brain-stem equates with the death of the individual and allows the medical practitioner to diagnose death (keyword irreversible)
Not necessarily accompanied by cessation of all neurological activity in the brain, just conscious awareness
May be some residual reflex movement of the limbs, originating in the spinal cord
What are the criteria for diagnosis of brainstem death?
Aetiology of irreversible brain damage
Patient is deeply comatose, unresponsive, requiring artificial ventilation
Not caused by depressant drugs
Not caused by primary hypothermia
Not caused by potentially reversible circulatory, metabolic and endocrine disturbances
Not caused by potentially reversible causes of apnoea (dependence on the ventilator), such as muscle relaxants and cervical cord injury
How do you test brainstem death?
Absence of brainstem (cranial nerve) reflexes
Pupil response - shine torch in eyes (CN II and III)
Corneal reflex - gently stroke cornea (transparent part of eye) with tissue or piece of cotton wool (CN V and VI)
Vestibulo-ocular reflex (VOR) - insert ice-cold water into each ear, which would usually cause the eyes to move (CN VIII, IV, VI and III)
Cranial nerve motor response - apply to supraorbital pressure to elicit motor response (facial grimace) (CN V and VII)
Cough/gag reflex - insert catheter down trachea/stimulate posterior pharynx with spatula (CN IX and X)
Respiratory effort - when ventilator is disconnected ~5 min
What is the neurological basis of consciousness?
Brainstem areas are essential for consciousness, esp the reticular activating system (RAS)
Also called the diffuse modulatory system
No single cortical area is crucial for maintaining consciousness
Cerebral cortex is also essential for many attributes of consciousness (memory, language, abstraction, attention, etc.)
What is the reticular activating system?
Reticular formation is collection of nuclei found throughput the midbrain and extends into the hindbrain (pons and medulla) and the spinal cord
Diffuse area, no clear anatomical boundaries - not easily seen on brainstem sections
Consists of 4 principal sets of (small) nuclei
- Locus coeruleus, raphe nuclei, ventral tegmental area, cholinergic nuclei
- Send outputs to many parts of the CNS
- Belong to various diffuse neuromodulatory systems
What is the locus coeruleus?
Part of RAS
Located in pons, contain melanin so blue tinge
Sends info to nearly all the CNS
Activated by novel stimuli, and is very active during states of arousal
Hypoactivity is associated with depression
Destruction obliterates rapid eye movement (REM) sleep
Neurotransmitter - Noradrenaline (NA), aka norepinephrine (NE)
What is the raphe nuclei?
Part of RAS
Collection of nuclei in midline in midbrain, pons and medulla
Project to large areas of CNS
Cells in rostral parts active during waking state
Neurotransmitter - Serotonin (5-HT)
What is the ventral tegmental area?
Part of RAS
Ventral region of midbrain
Project mainly to frontal cortex and limbic system
Modulates frontal activity and reinforces pleasurable sensations
Implicated in drug addiction
Neurotransmitter - Dopamine (DA)
What are the cholinergic nuclei?
Part of RAS
Basal forebrain nuclei
- Major projections to all cortical areas
Dorsolateral pontine nuclei (brainstem)
- Active during states of arousal
- Contribute to synaptic plasticity and involved in learning and memory
- Damage contributes to dementia
Neurotransmitter - Acetylcholine (ACh)
What other areas are involved in consciousness and sleep?
Anterior hypothalamus
- Damage associated with insomnia (shorter sleep) (But not the major cause of insomnia)
Neurotransmitter - GABA
Posterior hypothalamus
- Encephalitic damage associated with too much sleep (longer sleep)
Neurotransmitter - Histamine
How is RAS involved in sleep?
Intimately involved in regulation of sleep-wake cycle, arousal and attention
Damage can lead to loss of consciousness and coma
Interaction between 3 areas: cerebral cortex, reticular nucleus and thalamus
Awake - cholinergic fibres increase firing
Asleep - cholinergic fibres decrease firing
What systems are active in the sleep/wake cycle?
Awake
- ACh system active
- Sensory thalamus facilitated
- Reticular nucleus inhibited
- Thalamocortical neurons active
- EEG desynchronous
Asleep
- ACh system inactive
- Sensory thalamus inhibited
- Reticular nucleus active
- Thalamocortical neurons in slow rhythm
- EEG synchronous
What generates oscillations on an EEG?
Generated by the interaction between 3 types of neurones
Thalamocortical (in thalamus)
Reticular (in reticular nucleus)
Corticothalamic (in cerebral cortex)
What are the two main types of sleep?
Synchronised or NREM (Non-REM) sleep
- EEG waves are slow and synchronised
- Dominated by low frequency activity (e.g. delta waves <4Hz)
Desynchronised or REM sleep
- REM = ‘Rapid Eye Movements’
- High frequency activity in EEG (like waking state)
- Also called paradoxical sleep
- Abolition of muscle tone
- Associated with dreams
What are the stages of sleep?
Sleep is cyclical - each cycle lasts about 90 minutes, and involves multiple stages
- Awake
- REM sleep
- Stage 1 non-REM sleep
- Stage 2 non-REM sleep
- Stage 3 non-REM sleep
- Stage 4 non-REM sleep
What are some disorders of sleep?
Common disorders
- Psychiatric conditions including anxiety
- Indicators of other conditions:
Obstructive sleep apnoea (temporary cessation of breathing)
Enuresis (bladder control)
Epilepsy (neuronal seizures)
Rare disorders
- Narcolepsy - spontaneous transition from wakefulness to REM sleep (can be caused by alterations in levels of orexin)
What are the consequences of sleep deprivation?
Short Term
- Slower reflexes
- Memory disorders
- Muscle fatigue
- Mood swings
- Aggressive behaviour
- Disorientation
- Hallucinations
Long Term (chronic)
- Obesity
- Diabetes
- High blood pressure
- Cardiovascular disease
Insomnia can be insidious, and self-perpetuated by bad sleep habits
What is the circadian rhythm?
An internal clock, which may be demonstrated using light deprivation
Body clock ‘day’ = 24.5 to 25.5 hrs
What regulates the circadian rhythm?
Neurones in the retina project to the Suprachiasmatic Nucleus (SCN) of the hypothalamus
SCN innervates multiple nearby structures setting up a ‘biological clock’
SCN secretes neuropeptide vasopressin (to local brain areas only)
Indirectly modulates the pineal gland, which releases melatonin, a sleep promoting neurohormone
Why is memory important?
Allows us to produce adaptive behaviour
Supports sense of self and our culture
Practical importance of memory failures
Autobiographical memory gives rise to our self-identity, eroded in Alzheimer’s disease
What is a simple model of memory?
Sensory stores (<500ms) with attention goes to short-term store (a few seconds, longer with rehearsal) Short-term store can go to response (capacity limited by attentional bottleneck) Short-term store can go to long-term store (minutes to a lifetime) which has a huge capacity Memories can be retrieved to the short-term store
How can you show rapid loss from STM?
Participants look at letters to remember then asked to count backwards to prevent rehearsal
Leads to forgetting the letters
What is retrieval failure in the long term memory?
Information is still held in LTM but can’t be retrieved
Retrieving the particular memory you want is hard given other similar memories - interference
How does encoding matter in LTM?
Ability to recall information later depends on how it was processed
Three orienting tasks:
Physical - is word in capitals?
Acoustic - rhyme with pain?
Semantic - does it fit sentence?
Semantic encoding reduces interference
- memories are more distinctive
Processing meaning of the words helps memory
What is context dependency in LTM?
Match between environment (or state) between encoding and retrieval is crucial
Divers learn list of words on land or under water, and then recall on land or under water
- Memory better when same context of encoding and retrieval
What is mood-dependency in LTM?
Continuous cycle of sad thoughts -> depressed mood -> recall upsetting events -> sad thoughts
And so on
- Easier to recall unhappy events when sad which makes more sad
Why do we forget?
STM
- Information is rapidly lost when we are distracted
LTM
- Cues are ineffective - can’t access the memory
- Many similar memories that cues don’t separate - interference
- But also involuntary retrieval when encoding and retrieval states match
What can cause amnesia?
Common causes
- Viral infection (especially herpes simplex encephalitis)
- Long-term alcoholism - Korsakoff’s syndrome
- Anoxia (cardiac arrest, carbon monoxide poisoning)
- Head injury
- Alzheimer’s disease
All associated with damage to medial temporal lobes
Amnesia from damage to hippocampus and associated structures (fornix, cortex surrounding hippocampus, etc)
E.g. conductor Clive Wearing who developed dense amnesia following herpes simplex infection (encephalitis)
Herpes simples virus spreads from face along cranial or olfactory nerves to brain
What is the temporal gradient in amnesia?
Childhood memories are fine
Events shortly before brain damage are not remembered
Events since brain damage are not remembered
- Birth to date of brain injury - retrograde period
- Date of brain injury to present day - anterograde period
Memories become less dependent on hippocampus following consolidation
What is semantic information?
Preserved in amnesia
Normal retention of factual knowledge - semantic memory
Normal on tests such as providing definitions, naming pictures, understanding sentences
Conclusion - hippocampus is not final store of knowledge
What is non-declarative memory?
Preserved in amnesia
Mirror drawing - procedural memory
Conclusion - hippocampus not required for some types of non-conscious long-term learning
What are the memory systems?
STM
Goes to LTM
LTM splits into declarative/explicit and non-declarative/implicit
Declarative/explicit splits in to episodic (events) and semantic (factual knowledge)
Non-declarative/implicit splits into procedural (skills and habits), perceptual priming and classical conditioning (not dependent on the hippocampus)
Role of hippocampus in episodic memory
What are the roles of the different parts of the hippocampus?
Place - e.g. parahippocampal place area
Object - e.g. inferior temporal cortex
People - e.g. anterior temporal lobes
All of these aspects bind together when forming the memory
In retrieval one thing may trigger the retrieval of the others e.g. you go to the place remember the people and object
This binding process is disrupted in amnesia
How does retrieval occur from the hippocampus?
One element (cue) brings back whole experience - mental time-travel
Why are childhood memories spared in amnesia?
Childhood memories and facts are stored in neocortex around hippocampus
Through a process of consolidation, memories lose their reliance on the hippocampus - forming links in the neocortex
What is semantic dementia?
Damage to the neocortical store
Subtype of frontotemporal dementia (FTD)
Progressive loss of conceptual knowledge across modalities
Other aspects of cognition are largely intact
- Phonology/syntax
- Visual-spatial skills
- Non-verbal reasoning
- Memory for recent events
Can be tested using Ravens progressive matrices (test of non-verbal reasoning)
How is semantic dementia different to amnesia?
SD has a reverse temporal gradient - impaired repository of distant events as well as facts
What are the two LTM stores?
Hippocampus
- Episodic memory
- Unique episodes involving people/places/objects
- Damaged in amnesia
Anterior temporal lobes
- Semantic memory
- Similarities between experiences to form concepts
- Damaged in semantic dementia
What is antisocial behaviour?
Generally defined as behaviour that transgresses a society’s rules, norms and laws and likely to cause harm to others
Legally defined in the 2003 ASB Act as behaviour by a person which causes, or is likely to cause, harassment, alarm or distress to persons not of the same household as the person
Thus ‘domestic’ aggression and abuse is not covered in this aspect of law, though is considered ASB more generally
What is the prevalence of antisocial behaviour?
About one in twenty (4.6%) 5-19 year olds meet the criteria for a ‘behavioural disorder’
Rates higher in boys (5.8%) than girls (3.4%)
NHS digital survey (2017)
Rates seem fairly similar across cultures
What is the cost of antisocial behaviour?
Behaviours that challenge is associated with an exceptionally high societal and economic burden
Accounts for ~1% of all years lived with disability
Exceeds autism and ADHD in this respect
Mean cost per each young person with ‘conduct disorder’ estimated to be around £70k in 2001 (£103k today)
Costs in terms of policing, social work, educational provision, impact of crime, criminal justice processes
What age is the level of delinquency highest?
13-17
What are some psychiatric syndromes associated with antisocial behaviour?
Oppositional defiant disorder (ODD)
- Younger children (<10)
- Challenge adult authority
Conduct disorder (conduct-dissocial disorder)
- Tends to be adolescents
- Repeated rule/law breaking
- Disregarding the rights/wellbeing of others
- Lacking empathy - can now be specified with or without low prosocial emotions
Antisocial personality disorder (dissocial personality disorder)
- Generally adults
- Lacking empathy
- Repeated flouting social morals and/or laws
- Failure to respond to punishment
- Risk taking, superficial charm, manipulative
What are the limited prosocial emotions?
Daring impulsive
Callous unemotional
Grandiose manipulative
What is conduct disorder?
Persistent behaviour problems
Defiant, disobedient, provocative or spiteful behaviours
Violate the basic rights of others or age-appropriate societal norms
Now can be specified with or without Limited Prosocial Emotions (LPE) - daring impulsive, callous unemotional, grandiose manipulative
Lacking these results in worse traits and less likely to respond well to treatment
What are co-morbidities with conduct disorder?
Developmental issues
- Specific and generalised learning problems
- Literacy issues (‘dyslexia’ etc)
- Speech and language problems
- (Global) learning disability
- Autism spectrum conditions (ASCs)
- Attention deficit hyperactivity disorder (ADHD)
Mental health issues
- Depression (‘depressive CD’)
- Anxiety
- Substance misuse/dependency
- Post-traumatic stress disorder (PTSD)
- Attachment disorder/problems
- (Emerging) personality disorder
- Psychosis-spectrum illness (e.g. ‘schizophrenia’)
How can you assess young people with conduct issues?
NICE guidelines (CG158)
Holistic and multidisciplinary/agency
Information from multiple sources/settings
Developmental history and assessment
Cognitive assessment often useful
Mental health assessment (incl. screening)
Early life history/care and trauma
Think ACEs (Adverse Childhood Experiences)
What are some adverse childhood experiences (ACEs)?
Physical abuse
Verbal abuse
Sexual abuse
Physical neglect
Emotional neglect
An alcoholic parent
A family member in jail
The disappearance of a parent through divorce, death or abandonment
A family member diagnosed with a mental illness
A mother who’s a victim of domestic violence
What are some counter-ACEs?
Liking school Teachers who care Opportunities to have fun A predictable home routine Feeling comfortable with yourself Having a caregiver whom you feel safe with Beliefs that provide comfort Having good friends and neighbours
What is nature vs nurture in the cause of anti-social behaviour?
Adversity is associated with ASB
Hereditary component to criminal behaviour (CB)
Scandinavian adoption studies
- Risk for all CB was significantly elevated in the adopted-away offspring of biological parents with CB (odds ratio (OR) 1.5, 1.4-1.6)
- Risk also elevated if environmental risk factors in adoptive home
- Genetic risk factors for violent and non-violent offending may be partially distinct
What are ‘envirome’/genome interactions in the cause of anti-social behaviours?
‘Warrior gene’/s
Monoamine oxidase A gene (MAOA)
Breaks down MA neurotransmitters (e.g. dopamine, noradrenaline and serotonin etc) in synaptic cleft
Low activity allele -> aggression in observational studies
Risk of CD/ASPD much lower in absence of early childhood adversity
Cadherin-13 (CDH13)
Risk for ADHD and CD
Impacts GABAergic function in hippocampus and cognition
What does ASB have to do with doctors?
Young people with CD often have other developmental or mental health issues
Psychiatrists can help other professional and the CJS to understand if these play a role in offending
ASB can be viewed as a public health problem
Medical staff have a key role to play in the multi-agency response to ASB
Feeding into child protection arrangements
Leading teams that can deliver evidence-based management
How can CD be managed using medication?
Medication may have a role in treating comorbidity
- ADHD
- Depression
- Anxiety
The evidence for medication reducing aggression long-term is weak
Low doses of the antipsychotic risperidone licensed for short-term use (<6 wks), including in autism
Other medications have been trialled but little evidence of consistent benefit
What is some psychosocial management for CD?
Parent-management training (PMT)
- More effective in under 11s
- Supports carers in delivering consistent, effective parenting
Cognitive-behavioural therapy (CBT) based approaches
- May be used to improve ‘anger management’
- Useful in older children (>12 years)
Multi-systemic therapy
- Based on family therapy
- Involves people and organisations involved with the young person
- Good evidence, if young people and family engage
What are some examples of neurotoxins?
Snake venom - α-bungarotoxin
Botulinum toxin
Atropa belladonna - atropine
What are neurotransmitters?
Can be excitatory or inhibitory
Released at the synapse
Currently there are >100 neurotransmitters
Can be subdivided into two main types
- Small molecule neurotransmitters (generally mediate fast synaptic signalling
- Neuropeptides (composed of 3-36 amino acids, mediate slower synaptic signalling, modify ongoing synaptic function)
Abnormalities of neurotransmitter function underlies a wide range of neurological and psychiatric disorders e.g. Alzheimer’s, Parkinson’s, Schizophrenia, Depression etc
What are the different types of neurotransmitters?
Small neurotransmitters
- Enzymes that are required to metabolise these compounds are produced by the nucleus and trafficked to the axon terminal
- Enzymes metabolise neurotransmitter precursors and neurotransmitters are packaged into vesicles
- Vesicles can release contents if neurone activated
- Precursors taken back up into the neurone and process started again
Peptide transmitters
- Neuropeptide precursor and enzymes produced by the nucleus and transported together down the axon
- Enzymes modify the neuropeptides
- After release neuropeptides diffuse away and is degraded
What are the major classes of neurotransmitters?
Acetylcholine (ACh) (small)
Biogenic amines (small)
- Noradrenaline (NA)
- Adrenaline
- Dopamine (DA)
- Serotonin (5-HT)
- Histamine
- Catecholamines
Amino acids (small)
- Glutamate (Glu)
- Gamma-amino butyric acid (GABA)
- Glycine (Gly)
Gases (small)
- NO (Nitric oxide)
- CO (carbon monoxide)
Neuropeptides (larger)
- Substance P
- Enkephalins/endorphins
- Vasopressin
- Oxytocin
- Somatostatin
- Thyrotropin releasing hormone (TRH)
What is co-transmission?
Neurone can release more than one neurotransmitter (co-transmission)
Synaptic vesicles can contain different transmitters
Low frequency stimulation: release of small vesicles
High frequency stimulation: release of small and large vesicles (neuropeptides)
Co-transmitters give versatility to neurotransmission
What is the criteria for a chemical messenger to be a neurotransmitter?
1 - Chemical must be synthesised or present in the neurone
2 - When released the chemical must produce a response in the target cell
3 - Specific receptors are present on the post synaptic cell to continue the signal
4 - A chemical can induce the same response when placed on target
5 - The chemical must be removed from the synaptic cleft
How are neurones classified?
According to the main neurotransmitter present using the ‘ergic’ suffix
Although neurones can contain more than one type of neurotransmitter
Cholinergic neurones (contain acetylcholine) Glutamatergic neurones (contain glutamate) GABAergic neurones (contain GABA) Catecholaminergic neurones (contain noradrenaline/adrenaline/dopamine) Serotonergic neurones (contain serotonin/5-HT) Peptidergic neurones (contain peptides)
What are some types of receptors?
Ionotropic receptors
- Movement of ions across the membrane
- Open and close when ligand binds
Metabotropic receptors
- G protein coupled
- Then activate ion channel or stimulates second messenger
What is the sympathetic vs parasympathetic nervous system?
Sympathetic - fight or flight
- nicotinic linked ACh nerves link to muscarinic linked ACh nerves
Parasympathetic - rest and digest
- nicotinic linked ACh nerves link onto the epinephrine nerves
What is the most common neurotransmitter in the PNS?
Acetylcholine
The neurotransmitter at the neuromuscular junction
Autonomic nervous system
What is the role of acetylcholine in the CNS and autonomic nervous system?
In the CNS acetylcholine plays a role in:
- Learning and memory
- Sleep
- Arousal
- Biorhythms
- Thermoregulation
- Sexual behaviour
Acetylcholine is found in neurones of hippocampus and cerebral cortex, regions devastated by Alzheimer’s
How can AChE inhibitors be used to treat Alzheimer’s disease?
Raise ACh levels using AChE inhibitors e.g. donepezil
Neostigmine and physiostigmine used to treat
- glaucoma
- myasthenia gravis
- smooth muscle dysfunction
What is the neuropharmacology of cholinergic synaptic transmission?
Cholinergic receptor subtypes (ionotropic)
- Nicotinic receptors found in NMJs, autonomic ganglia, adrenal medulla and CNS
- Two types
Nicotinic Nₙ postganglionic neurones and some presynaptic cholinergic terminals
Nicotinic Nₘ skeletal motor endplates
Muscarinic receptors (G-protein coupled)
- Found in peripheral tissues, ANS and CNS
5 subtypes:
M₁, M₂, M₃, M₄ and M₅
- M₁, and M₃, M₅ coupled to G-protein/PLC
- M₂, M₄ coupled to Gᵢ/open K+ ion channels
What amino acids are neurotransmitters?
Glutamate
GABA
Glycine
