The Brain Flashcards
What is an excitable cell?
A type of cell that is capable of generating and responding to electrical signals.
Can undergo rapid changes in their membrane potential, which allows them to transmit electrical impulses or action potentials.
What is the resting membrane potential?
~-70 mV in most neurones
Dependent on separation of charge across lipid bilayer membrane
What are action potentials?
Excitable cells can generate an action potential—a rapid, temporary reversal of the membrane potential that travels along the cell’s membrane.
An action potential is a large transient change in membrane potential and is an “all or none” response
This is what allows these cells to transmit signals over long distances (like in nerves) or trigger responses (like muscle contraction).
Action potentials are very rapid (as brief as 1–4 milliseconds) and may repeat at frequencies of several hundred per second
What is depolarisation?
Depolarization is the potential moving from RMP to less negative values
It occurs when sodium ions (Na⁺) rush into the cell, making the inside less negative (or more positive).
This is an essential process for action potentials in neurons and muscle contraction in muscle cells.
What is repolarisation?
Repolarization is the potential moving back to the RMP
It happens when potassium (K⁺) ions leave the cell, making the inside more negative again.
Repolarization is essential for resetting excitable cells (like neurons and muscle cells) so they can respond to new stimuli and transmit further electrical signals.
What is hyperpolarisation?
Hyperpolarization is the potential moving away from the RMP in a more negative direction
It usually happens after the action potential has passed through its peak and repolarization, where potassium ions continue to exit the cell.
It makes it harder for the cell to fire another action potential, contributing to the refractory period and preventing excessive or continuous firing of the cell.
Hyperpolarization helps regulate cellular activity, whether in neurons or muscles, to maintain proper function and prevent overstimulation.
How do nerve cells communicate?
Electrical signal: The neuron generates an action potential (an electrical impulse) that travels down its axon.
Chemical signal: At the axon terminal, the electrical signal triggers the release of neurotransmitters into the synapse.
Neurotransmitter action: These neurotransmitters bind to receptors on the next neuron (or muscle), either exciting or inhibiting it.
Summation: The postsynaptic neuron integrates all incoming signals to decide whether to generate its own action potential.
Neurotransmitter release by exocytosis
- Action potential arrives at the axon terminal.
- Voltage-gated calcium (Ca²⁺) channels open, allowing calcium ions to enter the presynaptic terminal.
- The rise in intracellular calcium triggers vesicle fusion with the presynaptic membrane via synaptotagmin and SNARE proteins.
- The vesicle releases its neurotransmitters into the synaptic cleft by exocytosis.
- Neurotransmitters bind to postsynaptic receptors, transmitting the signal to the next cell.
- The vesicle membrane is recycled via endocytosis
What are the two kinds of receptors?
ligand gated ion-channel
(‘ionotropic’ receptor)
G-protein coupled receptor (GPCR)
(‘metabotropic’ receptor)
What are the different types of G-coupled proteins receptors?
Gs and Gq: generally excitatory
Gi: generally inhibitory
What are the three types of synapses?
Axo-somatic
Axo-axonic
Axo-dendritic
Why are CNS disorders so hard to treat?
- Neurones are highly complex structures interconnected in complex networks
- Numerous synapses on each neurone
- Numerous neurotransmitters and receptors
- Multiple possible sites for dysfunction
- Multiple sites of possible intervention
- Even for a single neurotransmitter, numerous possible drug targets are possible
- But drugs are rarely selective
What are the sites of action of CNS drugs?
Neurotransmitter receptors (e.g., dopamine, serotonin, GABA, glutamate).
Ion channels (e.g., sodium, chloride, calcium, potassium channels).
Enzymes (e.g., acetylcholinesterase, MAO, COMT).
Reuptake transporters (e.g., serotonin, dopamine, and norepinephrine transporters).
Blood-brain barrier mechanisms that govern drug entry into the CNS.
Neuroinflammatory pathways and the immune system.
What is cerebrospinal fluid?
Cerebrospinal fluid (CSF) is a clear, colorless liquid that surrounds and cushions the brain and spinal cord, providing both mechanical and chemical protection. It compensates for changes in brain volume. It is produced by the chlorois plexus and is an aqueus solution of NaCl + glucose plus low concentrations of K+, Ca2+.
What is glutamate?
Glutamate is the most abundant excitatory neurotransmitter in the brain and central nervous system (CNS). It is responsible for stimulating neurons and facilitating communication between them.
It is involved in learning, memory, synaptic plasticity, and brain development.
However, excessive glutamate activity can lead to excitotoxicity, which is harmful and has been linked to various neurological disorders.
Glutamate receptors (such as NMDA, AMPA, and kainate receptors) mediate its effects.
What is GABA?
GABA (Gamma-Aminobutyric Acid) is the primary inhibitory neurotransmitter in the brain and spinal cord, playing a key role in reducing neuronal excitability and preventing excessive neural firing.
GABA acts through two main types of receptors: GABA-A receptors (ionotropic, fast inhibition) and GABA-B receptors (metabotropic, slower inhibition).
GABA is crucial for maintaining brain balance, regulating anxiety, sleep, cognitive function, and seizure prevention.
Drugs that modulate GABAergic activity, such as benzodiazepines and barbiturates, are commonly used in the treatment of anxiety, insomnia, and epilepsy.
GABA dysfunction is implicated in several neurological and psychiatric disorders, including epilepsy, anxiety disorders, and schizophrenia.
How are amino acid transmitters distributed?
e.g. about 20% of CNS neurones are GABAergic
e.g. about 30% of all synapses are GABAergic
Glutamate mostly found in pyramidal neurones
GABA mostly found in short local interneurones
GABA also found in longer projection neurones
How is glutamate metabolised in the brain?
Glutamate in the CNS comes either from glucose (via Krebs cycle) or glutamine - synthesised by glial cells and taken up by neurones
Glutamate can be converted to GABA by the enzyme glutamic acid decarboxylase – GAD
Glutamate (Glu) is stored in synaptic vesicles and released by calcium-dependent exocytosis.
How is GABA metabolised in the brain?
GABA is released from presynaptic neurons and binds to GABA receptors on postsynaptic neurons.
After exerting its inhibitory effect, GABA is reabsorbed by neurons and glial cells.
Inside cells, GABA is primarily metabolized by GABA transaminase (GABA-T) to form succinic semialdehyde then succinate.
Succinate enters the Krebs cycle, where it is metabolized to produce energy.
In the brain, glutamate is generated as a byproduct, which is converted to glutamine and can be recycled back into the neurons, closing the glutamate-GABA-glutamine cycle.
What are ionotropic receptors?
Or ligand gated ion channels, transmembrane proteins that allow ions to pass through cell membranes.
What are metabotropic receptors?
Also G-protein-coupled receptors (GPCRs), are membrane receptors that regulate cell activity. They are involved in many neurotransmitter systems, hormone signaling, and second messenger systems
What are ionotropic gaba receptors?
Ligand-gated ion channel activated by GABA that lets through chloride
Mediates fast hyperpolarization and therefore inhibition
Multi-subunit receptors located throughout the brain
GABA a vs GABA b
GABAA: Ligand-gated ion channels that form chloride channels
GABAB: G protein-coupled receptors that modulate potassium and calcium channels
What are GABAb receptor agonists?
Spasticity can be viewed as an exaggerated activity of the stretch reflex pathways
For pain, muscle relaxation, sedation
e.g. Baclofen is used to treat spasticity
Crosses BBB so sedation is an issue
What are NMDA receptors?
ion channels in the brain essential for learning, memory, and other cognitive functions, mediate Ca2+
involved in spasticity, LTP, excitotoxicity
What are metabotropic glutamate receptors (mGluRs)?
A class of G-protein-coupled receptors that mediate slower, modulatory effects on neurons and help regulate neuronal activity
They are involved in important brain functions such as synaptic plasticity, learning, memory, and neural excitability.
mGluRs are divided into three groups (I, II, and III) based on their signaling mechanisms, and effects on the brain.
How does glutamate bind many receptors?
It is not a rigid molecule
Different constituents can rotate along two different axes
Can adopt different conformations
Rotates about bonds
Nine ‘rotamers’ are possible
What are amine neurotransmitters?
Noradrenaline (NA)
Dopamine (DA)
5-hydroxytryptamine (5HT)
Acetylcholine (ACh)
Histamine
Derived from amino acids, amine transmitters are released from one nerve to affect another nerve, gland, or muscle cell
Noradrenaline pathways in the CNS
Dorsal noradrenergic bundle (DNB)
- Originates in the locus coeruleus in the dorsal pons. It projects to the cerebral cortex, hippocampus, and cerebellum.
Ventral noradrenergic bundle (VNB)
- Originates in nuclei in the pons and medulla. It projects to the amygdala, hypothalamus, and areas of the midbrain and medulla.
Noradrenaline functions in the CNS
Arousal: Noradrenaline is released during stressful events and plays a role in the body’s stress response.
Attention: Noradrenaline helps maintain attentional homeostasis.
Memory: Noradrenaline enhances the formation and retrieval of memory.
Mood disorders: Noradrenaline is involved in mood disorders.
Overactivity in mania
Noradrenaline synthesis?
Tyrosine → L-DOPA (via tyrosine hydroxylase),
L-DOPA → dopamine (via aromatic L-amino acid decarboxylase),
Dopamine → noradrenaline (via dopamine β-hydroxylase). Stored in synaptic vesicles for release into the synapse or, in the case of the adrenal medulla, into the bloodstream.
Noradrenaline action and inactivation
Reuptake by NAT (noadrenaline transporter)
Degradation by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT)
Noradrenaline inactivation – important therapeutic points
MAO inhibitors - antidepressant
COMT overexpression - schizophrenic phenotype
Cocaine blockade of uptake - reward
Amphetamine - NA displacement - stimulatory effects
Dopamine pathways in the CNS
Mesolimbic pathway
Originates in the VTA of the midbrain. Involved in motivation, reward, and emotions, and is linked to positive symptoms of schizophrenia.
Mesocortical pathway
Originates in the VTA and innervates the frontal cortex. This pathway is involved in cognition, executive function, and emotions.
Nigrostriatal pathway
Involved in motor planning and purposeful movement. Associated with parkinsons
Tuberoinfundibular pathway
Originates in the hypothalamus and projects to the anterior pituitary.
Dopamine function in the CNS
Dopamine is essential for normal movement, motivation, reward processing, cognition, and emotional regulation.
motor control via the nigrostriatal pathway,
brain’s reward system via the mesolimbic pathway
cognitive functions via the mesocortical pathway
hormonal regulation via the tuberoinfundibular pathway.
Dopamine dysfunction is implicated in a wide range of neurological and psychiatric disorders, including Parkinson’s disease, schizophrenia, addiction, and depression.
Serotonin pathways in the CNS
Dorsal Raphe Nucleus (DRN) Pathway:
Origin: Dorsal raphe nucleus in the brainstem.
Functions: Regulates mood, emotion, cognition, and arousal.
Important for sleep-wake cycles, particularly wakefulness and REM sleep.
Linked to depression and anxiety.
Median Raphe Nucleus Pathway:
Origin: Median raphe nucleus, near the dorsal raphe.
Functions: Involved in memory, learning, and mood regulation.
Plays a role in sleep and REM sleep.
Linked to depression and anxiety.
Serotonergic Pathways to the Cortex:
Functions: Regulate attention, decision-making, and working memory.
Implicated in psychiatric conditions like schizophrenia and ADHD.
Serotonergic Pathways to the Limbic System:
Functions: Regulates emotion, behavior, and stress response.
Dysfunction can contribute to mood disorders
Serotonin uses in the CNS
Mood and emotion: Regulates mood and is involved in depression and anxiety.
Sleep: Influences sleep-wake cycles and sleep quality (thalamus)
Pain: Modulates pain perception and pain responses.
Cognition: Affects learning, memory, and attention.
Appetite: Regulates appetite and satiety signals.
Motor control: Supports motor coordination and fine motor control.
Social behavior: Modulates social behavior, impulsivity, and aggression.
Serotonin synthesis
Tryptophan → 5-Hydroxytryptophan (5-HTP)
(via Tryptophan Hydroxylase)
5-Hydroxytryptophan (5-HTP) → Serotonin (5-HT)
(via Aromatic L-Amino Acid Decarboxylase)
5HT synthesis and inactivation - important therapeutic points
Tryptophan hydroxylase not saturated
Tryptophan availability is rate limiting
Tryptophan or 5HTP - increase 5HT synthesis – antidepressant?
Vesicular uptake blocked by reserpine
5HT depletion - depression
Inactivation by re-uptake
Blocked by antidepressants - SSRIs
Acetylcholine pathways in the CNS
The basal forebrain pathway (important for cognition and memory).
The pontine pathway (involved in REM sleep and arousal).
The striatum (important for motor control, especially in Parkinson’s disease).
The medial septal nucleus pathway (critical for memory formation in the hippocampus).
ACh uses in the CNS
Cognition and Memory: Critical for learning, memory, and synaptic plasticity.
Attention and Arousal: Regulates focus, attention, and wakefulness by modulating the prefrontal cortex and arousal systems.
Sleep: Important for the regulation of REM sleep and the sleep-wake cycle.
Motor Control: Involved in movement initiation, coordination, and motor function through its role in the basal ganglia.
Autonomic Functions: Modulates autonomic reflexes and influences functions like heart rate and digestion.
Sensory Processing: Plays a role in sensory gating and filtering stimuli, influencing attention and perception.
Mood Regulation: Implicated in mood disorders such as depression and anxiety (though less central than other neurotransmitters).
Brain Plasticity: Supports neuroplasticity, particularly in areas involved in learning and memory (e.g., hippocampus).
ACh synthesis
Choline uptake into the presynaptic neuron via the choline transporter.
Choline acetyltransferase catalyzes the synthesis of acetylcholine from choline and acetyl-CoA.
Acetylcholine is stored in synaptic vesicles by the vesicular acetylcholine transporter (VAChT).
Upon neuron activation, acetylcholine is released into the synapse to bind to muscarinic or nicotinic receptors, exerting its physiological effects.
Histamine as a neurotransmitter
Histamine produced from amino acid histidine
Synthesized and localized to the tuberomammillary nucleus within the hypothalamus
Histamine H1, H2, H3 and H4 receptors are GPCRs
Diphenhydramine (Benadryl) is a CNS penetrant H1 antagonist that is sedating (also muscarinic AChR antagonist)
Newer allergy antihistamines (e.g. loratadine) don’t cross the BBB
Histamine H2 antagonists (e.g. cimetidine) don’t cross the BBB
Histamine uses in the CNS
Histamine neurons project to monoamine and cholinergic neurons involved in arousal, attention, learning and memory
Histamine plays a role in sleep, feeding and energy balance
Stroke prevalence
~100,000 strokes in UK each year
~1 in 8 strokes are fatal within the first 30 days (4th biggest cause of death in UK)
1.2 million stroke survivors in UK
Transient or permanent interruption in cerebral blood supply - ischaemia - lack of O2/glucose
What is an ischaemic stroke?
Blood clot in the brain
What is the haemorrhagic stroke?
Bleed in the brain
What is the main cause of cell death in stroke?
Excitotoxicty
Excessive release of glutamate
Neurones “excited to death”
Ca2+ overload
How does excitotoxicity occur?
Excessive glutamate release into the synapse (trauma or injury)
Prolonged activation of NMDA receptors, leading to excessive calcium influx.
Intracellular calcium overload triggers:
- Activation of destructive enzymes (phospholipases, proteases, endonucleases).
- Mitochondrial dysfunction and ROS production.
- Oxidative stress and damage to cell components.
Activation of microglia and astrocytes, leading to neuroinflammation.
Neuronal injury and death, which can occur through necrosis or apoptosis.
Peri-infarct depolarisation
PID occurs in the penumbra (surrounding tissue) during ischemic stroke and refers to a wave of neuronal depolarization that spreads outward from the infarcted area.
This depolarization leads to ion imbalance, calcium influx, and glutamate release, which in turn causes excitotoxicity and neuroinflammation, further damaging the surrounding neurons.
How are future strokes prevented?
Antihypertensives (eg. ACE inhibitors) – ischaemic and haemorrhagic
Statins - cholesterol reduction – ischaemic only?
Antiplatelet drugs (eg. aspirin, clopidogrel) – ischaemic only
Anticoagulants (eg. warfarin) – ischaemic only
How are strokes treated?
Tissue plasminogen activator (tPA) only licensed treatment
restores blood flow - disperses thrombus within 3 hours only for ischaemic stroke
What are TIAs?
Transient ischaemic attacks (TIAs) -short-lived neurological signs (aka ‘ministroke’). Initial symptoms identical to stroke
>25% of people who have had a stroke have previously had a TIA
Other examples of excitotoxicity
Other disease states (eg. Alzheimer’s, Parkinson’s, motor neurone disease)
Food-induced excitotoxicity
Glutamate receptor agonist
Causes confusion + disorientation, memory loss, seizures
Eventually death
Neurolathyrism
Glutamate receptor agonist
From Grass Pea (Lathyrus Sativus) – famine food
Guam disease
Glutamate receptor agonist
Symptoms of Motor neurone disease, Alzheimer’s and Parkinson’s
From cycad seeds to humans via bats
What are the three basic mechanisms for crossing the BBB?
Passive, transcellular diffusion: more lipophilic molecules can move through the cell membrane (most CNS active drugs use this process).
Active transport: substances that the brain needs such as glucose and amino acids are carried across by transport proteins.
Receptor-mediated transport: e.g., insulin
What is lipinskis rule of 5?
The number of H-bonds (donor under 5 and acceptor under 10)
Lipophilicity logP under 5
Polar surface area under 140
Molecular weight under 500Da
pKa (in particular, the acidity)
Best chance of good BBB penetration when…
Molecular weight is reduced
Lipophilicity is ‘high’ (within limits)
Low number of polar atoms (N and O) (particularly H-bond donors)
No carboxylic acids
What is the definition of learning disability?
Significantly reduced ability to understand new or complex information and to learn new skills (impaired intelligence).
with a reduced ability to cope independently (impaired social functioning).
which started before adulthood, with a lasting effect on development.
How is intellectual functioning measured?
Weschler Adult Intelligence Scale (WAIS-IV)
Subtests grouped together to form ‘Indexes’:
Verbal Comprehension (VCI)
Perceptual Reasoning (PRI)
Working Memory (WMI)
Processing Speed (PSI)
All 10 subtests grouped together to form ‘Full Scale IQ’
FSIQ < 70 = learning disability
How do you know if someone has a learning disability?
Communication difficulties
Limited understanding
Limited reading, writing and numeracy skills
No academic qualifications (or below GCSE level)
Needing support with daily living activities or managing household
Unable to maintain employment without support
Likely unable to drive (esp theory test)
Pointers in history: Delayed developmental milestones, special schooling (esp if statemented for learning difficulty)
Which physical health conditions are likely to be co-morbid with a LD?
Dementia – higher risk of early onset dementia (in Downs Syndrome)
Epilepsy
Dental hygiene issues
Sensory impairments – both sight and hearing problems affect 40% of the population with learning disabilities.
Heart disease – Increased risk of heart disease, high blood pressure and obesity. reduced access to health promotion campaigns and poorer diet and exercise
Gastro-intestinal problems – including ulcers, gastro-oesophageal reflux disease and dysphagia.
Cancer – increased risk of gastro-intestinal cancers
Health Needs of People with Learning Disability
Some health problems relate to the underlying cause of learning disability including physical phenotypes of genetic conditions:
Eg people with Down syndrome have ↑risk of congenital heart disease, thyroid disease, blood dyscrasias, coeliac disease, diabetes
Many relate to difficulty accessing healthcare and lifestyle factors
Eg Dental disease and obesity-related illness
Epilepsy in LD
Approx 40% of people with LD have epilepsy
Often multiple seizure types which are refractory to treatment
Rescue medication in community (Buccal Midazolam)
High co-morbidity with mental illness/challenging behaviour
SUDEP (Sudden Unexpected Death in Epilepsy) rates are higher in LD population
Dementia in Learning Disability
↑ Risk overall - approx 2.5 X higher in 70-74 age group
Specific ↑ in risk of Alzheimer’s dementia in Down syndrome
earlier age of onset
Neuropathological changes in almost all by age 40
Clinical diagnosis in up to 50% of people in their 50s
May be as young as 30/40 decade
Management of Alzheimer’s Dementia in Down’s syndrome
Evidence base for use of anti-dementia drugs in PLD is relatively poor
Few studies and no RCTs
May improve QOL for person and carers
Donepezil only Ach-I systematically evaluated in Down syndrome
Two drugs with regulators (Lecanumab and Decanumab) – UK approval yet TBC
Major tolerability problems for service users with LD
Mental illness in learning disability
Mental illness – 2 X ↑ rates in people with LD
Specialist service only when needs cannot be met by primary care or mainstream MH services eg due to:
Co-morbidity (eg with epilepsy or autism)
Diagnostic uncertainty (+/- communication difficulties)
Treatment resistance
Complex risks
Autism and challenging behaviour
20-30% people with LD have ASD
Difficulties with social communication, repetitive and restrictive interests
Sensory differences
Autistic needs important in understanding behaviours that challenge
Self-injury/aggression to others
High rates of comorbid mental illness (anxiety +++) and epilepsy
Challenges to meeting physical health needs
Mortality in LD Population
Learning from lives and deaths - People with a learning disability and autistic people
6/10 people with LD die < 65 years (compared with 1/10 of general population)
Top 5 groupings for causes of death:
1. Covid-19
2. Diseases of circulatory system
3. Diseases of respiratory system
4. Cancer
5. Diseases of the nervous system
49% deaths in LD were ‘avoidable’ compared with 22% of general population
Causes of premature mortality in LD population
Challenges to accessing healthcare:
Communication
Estimated that 50% of people with learning disabilities have communication difficulties.
Behaviours
ASD/anxiety/dementia
Capacity
Lack of understanding of specialist needs
Perceptions/quality of life judgements (DNARs)
LD should not be considered a ‘life-limiting’ condition
What are the 6 reasonanble adjustments?
- reduced waiting time
- quiet environment (side room)
- longer appointments
- accessible information
- understanding how the person communicates
- family/carer input
Communication in LD
Strategies to check understanding
Ask the person to summarise what you have said
Ask them to repeat the key information… e.g ‘so how often should you take this medication?’
Use visual aids to supplement verbal information were possible – (e.g. easy read leaflet)
Don’t assume the individual does not understand.
Don’t assume they do.
Learning Disabilities Annual Health Checks
Everyone >14 on GP LD Register
RCGP Health Checks for People with Learning Disability Toolkit
Syndrome specific guidance eg for Down syndrome, Cerebral palsy, Foetal alcohol syn and Fragile X syn
Important opportunity to review medication and polypharmacy!!
STOPP-START guidelines – Comprehensive Geriatric Assessment Toolkit
Mental Capacity Act 2005
The 2-stage test
-Is there an impairment of or disturbance in the functioning of the person’s mind or brain?
-Is the impairment or disturbance sufficient that the person lacks the capacity to make that particular decision?
Must be able to:
1. Understand information relevant to the decision
2. Retain the information
3. Use or weigh-up the information as part of the decision process
4. Communicate their decision
What are the 5 key principles of capacity?
- Presumption of capacity
Every adult has the right to make their own decisions & must be assumed capable of doing so until proved otherwise - Support to make decisions
Everyone should be given all the support they need to make their own decisions before conclusions are made that they cannot - Unwise decision accepted
People should be able to make unwise or eccentric decisions – it is capacity to make decisions that is the issue. - Best interests
Any decisions or anything done for or on behalf of a person who lacks capacity must be made or done in their best interests and in consultation with the people close to them - Least restrictive option
Anything done for or on behalf of people without capacity should restrict their rights & freedoms as little as possible
General principles of prescribing in LD
Increased contraindications and susceptibility to side effects due to:
- Physical health co-morbidities
- Epilepsy- impact on seizure threshold and drug interactions
- Blood-brain barrier dysfunction
- Genetic conditions (CHD, metabolic differences
Difficulty communicating side effects
Diagnostic overshadowing (adverse effects ‘hidden’)
Challenges with monitoring
Start low- go slow (similar to older adult population)
Monitor closely for side effects especially:
Deterioration in seizure control
Mood and behaviour side effects on antiepileptics
Cognitive side effects on antimuscarinics
Mobility impairment/falls
Weight gain (esp in Down syndrome)
Swallowing problems (guidelines for enteral feeding tubes or swallowing difficulties)
Use of psychotropic medication for people with learning disability
Mental illness vs challenging behaviour
Early intervention in psychosis
Medication ‘last resort’ for challenging behaviours
Concerns that psychotropic drugs are overprescribed with poor review and assessment of their benefit
Indications often unclear (eg mood stabilisers)
Historical perspective and controversy
Monitoring and review of psychotropic meds in people with LD
Plan for discontinuation if for challenging behaviour
Weight monitoring and healthy lifestyles input important with antipsychotics
Blood test monitoring
Restrictive practices may or may not be appropriate
Hyponatraemia and hyperprolactinaemia relatively common
Sodium valproate annual risk acknowledgement form
Need for clarity around requirements for women lacking capacity
