The Brain

Question 1

What is an excitable cell?

Answer 1

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.

Has a resting membrane potential (an electrical potential difference between inside and outside) of roughly -70mV

Question 2

What is the resting membrane potential?

Answer 2

~-70 mV in most neurones

Dependent on separation of charge across lipid bilayer membrane

Question 3

What are action potentials?

Answer 3

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

The generation of action potentials relies on ion channels in the cell membrane.
These channels can be voltage-gated or ligand-gated

Threshold: There is a minimum level of depolarization (called the threshold) that must be reached for an action potential to be generated. If the depolarization does not reach this threshold, no action potential will occur.

Question 4

What is depolarisation?

Answer 4

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.

Question 5

What is repolarisation?

Answer 5

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.

Question 6

What is hyperpolarisation?

Answer 6

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.

Question 7

How do nerve cells communicate?

Answer 7

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.

Refractory period: After firing an action potential, the neuron enters a refractory period where it cannot fire again immediately.

Summation: The postsynaptic neuron integrates all incoming signals to decide whether to generate its own action potential.

Question 8

Neurotransmitter release by exocytosis

Answer 8

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

Question 9

What are the two kinds of receptors?

Answer 9

ligand gated ion-channel
(‘ionotropic’ receptor)
G-protein coupled receptor (GPCR)
(‘metabotropic’ receptor)

Question 10

What are the characteristics of graded (local) potentials?

Answer 10

• Can be a depolarization or a hyperpolarization
• Graded – size/duration
• Decay rapidly
• Travel small distances
• Show summation

Question 11

Neurotransmitter receptors

Answer 11

Slower, more diffuse and modulatory effect

Affect multiple intracellular messengers - e.g. ion channels, cAMP, IP3, Ca2+

Gs and Gq: generally excitatory

Gi: generally inhibitory

Question 12

What are the three types of synapses?

Answer 12

Axo-somatic
Axo-axonic
Axo-dendritic

Question 13

Why are CNS disorders so hard to treat?

Answer 13

• 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

Question 14

What are the sites of action of CNS drugs?

Answer 14

Neurotransmitter receptors (e.g., dopamine, serotonin, GABA, glutamate).
Ion channels (e.g., sodium, 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.

Question 15

What is cerebrospinal fluid?

Answer 15

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+.

It is essential for maintaining the proper environment for the brain and spinal cord, supporting their function and health.

Abnormalities in CSF production or flow can lead to serious neurological conditions such as hydrocephalus, meningitis, and CSF leaks.

Question 16

What is glutamate?

Answer 16

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, while the glutamate-glutamine cycle regulates its synthesis, release, and recycling in the brain.

Question 17

What is GABA?

Answer 17

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.

Question 18

How are amino acid transmitters distributed?

Answer 18

Not localized to discrete brain regions, ubiquitous compared to amine neurotransmitters (e.g.5-HT)
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

Question 19

How is glutamate metabolised in the brain?

Answer 19

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.

Released Glu is taken up into nerve cells and glial cells (astrocytes) by excitatory amino acid transporter (EAAT) proteins.

In astrocytes Glu is converted to glutamine (Gln) and recycled via transporters (GlnT) back to neurones.

Glu is taken up into synaptic vesicles by vesicular glutamate transporters (VGluT).

Question 20

How is GABA metabolised in the brain?

Answer 20

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.

Succinic semialdehyde is further converted to succinate via succinic semialdehyde dehydrogenase (SSADH).

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.

Question 21

What are ionotropic receptors?

Answer 21

Multisubunit receptors
Heterogeneous receptors
Affects physiological function and pharmacology
Rapid cellular effects

Question 22

What are metabotropic receptors?

Answer 22

Hetero- and homodimers
Activate second messenger systems
Slower effects on synaptic transmission
May be “autoreceptors” located presynaptically on nerve terminals

Question 23

What are ionotropic gaba receptors?

Answer 23

Ligand-gated chloride ion channel
Mediates fast hyperpolarization and therefore inhibition
Multi-subunit receptors located throughout the brain
Complex pharmacology

Question 24

What are the main sites of drug action on GABAA receptors

Answer 24

GABAA Rs have multiple modulatory or allosteric sites
Highly permeable to Cl- ions
Drug actions at allosteric sites “turn up” or “turn down” gating of Cl- ions in the presence of GABA bound to the orthosteric sites
Many therapeutic agents target the GABAA R

Question 25

What are GABAb receptor agonists?

Answer 25

Spasticity can be viewed as an exaggerated activity of the stretch reflex pathways
In spinal cord injuries, descending inhibition of these pathways is removed
Baclofen is a GABAB R agonist used to treat spasticity associated with e.g. some motor disorders, multiple sclerosis
Crosses BBB so sedation is an issue

Question 26

What are the main sites of drug action on NMDA receptors?

Answer 26

Most widely studied of ionotropic GluRs – multiple modulatory or allosteric sites
Highly permeable to Ca2+ (excitotoxicity)
Readily blocked by Mg2+ but is voltage sensitive and disappears when cell is depolarized
Activation requires glycine as well as glutamate
Ketamine and memantine are clinically useful selective antagonists of NMDARs

Question 27

What are metabotropic glutamate receptors (mGluRs)?

Answer 27

Metabotropic glutamate receptors (mGluRs) are a class of G-protein-coupled receptors that mediate slower, modulatory effects on neurons, as opposed to the rapid effects of ionotropic glutamate receptors.

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 each group has different effects on the brain.

Dysregulation of mGluRs is linked to a range of neurological and psychiatric disorders, making them important targets for therapeutic research. No drugs on the market; clinical potential in pain, Parkinson’s disease, epilepsy and drug abuse

Question 28

How does glutamate bind many receptors?

Answer 28

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

Question 29

What are the 5 amine neruotransmitters?

Answer 29

Noradrenaline (NA)
Dopamine (DA)
5-hydroxytryptamine (5HT)
Acetylcholine (ACh)
Histamine

Question 30

Amine transmitters = diffuse, modulatory systems

Answer 30

Cell bodies are restricted to a small number of brainstem nuclei
Axons project widely throughout the nervous system
Modulate (+ or -) fast excitation or inhibition via multiple receptors
Lack specialised synaptic contacts (cf. glutamate and GABA)
Key roles in arousal, attention, sleep and survival

Question 31

Noradrenaline pathways in the CNS

Answer 31

Origin in Locus Coeruleus
C1 group may use adrenaline
Diffuse innervation of forebrain, particularly cerebral cortex and hippocampus
Also descending pathways
“Arousal chemical”

Question 32

Noradrenaline functions in the CNS

Answer 32

Acts at 1, 2, 1 and 2 receptors - (GPCRs)
Brainstem - blood pressure control - baroreceptor reflex
Descending - movement and pain
Ascending - arousal and mood
Cognitive processes, learning and memory, movement, attention
Depletion in forebrain (cortex, hippocampus) - involved in depression
Overactivity in mania

Question 33

Noradrenaline synthesis?

Answer 33

Tyrosine → L-DOPA (via tyrosine hydroxylase),
L-DOPA → dopamine (via aromatic L-amino acid decarboxylase),
Dopamine → noradrenaline (via dopamine β-hydroxylase). Once synthesized, it is stored in synaptic vesicles for release into the synapse or, in the case of the adrenal medulla, into the bloodstream.

Question 34

Noradrenaline action and inactivation

Answer 34

Reuptake by NET (norepinephrine transporter)

Degradation by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT)

Question 35

Noradrenaline inactivation – important therapeutic points

Answer 35

MAO inhibitors - antidepressant
COMT overexpression - schizophrenic phenotype
Uptake 1 most important
Uptake blockers - antidepressant
Cocaine blockade of uptake - reward
Amphetamine - NA displacement - stimulatory effects

Question 36

Dopamine pathways in the CNS

Answer 36

midbrain origin - SN and VTA
Nigro-striatal most important pathway
VTA to cortex and hippocampus - mesolimbic/mesocortical pathways
TI system from hypothalamus to pituitary
“Reward chemical”

Question 37

Dopamine in the CNS

Answer 37

Dopamine is essential for normal movement, motivation, reward processing, cognition, and emotional regulation.

It plays a central role in motor control (via the nigrostriatal pathway), the brain’s reward system (via the mesolimbic pathway), cognitive functions (via the mesocortical pathway), and 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.

Acts at D1-5 dopamine receptors - all GPCRs
Control of movement
Nigro-striatal – Parkinson’s disease
Control of attention, emotion and reward
VTA to cortex/limbic system – “mesocorticolimbic system”
Schizophrenia
Involved in action of drugs of abuse (cocaine, heroin, amphetamine)
Control of endocrine function
TI system controls pituitary hormone output
Brainstem - vomiting

Question 38

Serotonin pathways in the CNS

Answer 38

Dorsal Raphe Nucleus (DRN) Pathway:
Origin: Dorsal raphe nucleus in the brainstem.
Targets: Cortex, hippocampus, amygdala, striatum, thalamus, spinal cord.
Functions: Regulates mood, emotion, cognition, and arousal.
Important for sleep-wake cycles, particularly wakefulness and REM sleep.
Dysfunction linked to depression, anxiety, and bipolar disorder.

Median Raphe Nucleus Pathway:
Origin: Median raphe nucleus, near the dorsal raphe.
Targets: Hippocampus, cortex, limbic regions.
Functions: Involved in memory, learning, and mood regulation.
Plays a role in sleep and REM sleep.
Linked to depression and anxiety.

Rostral and Caudal Raphe Nuclei:
Functions: The rostral raphe affects cognition and emotion, while the caudal raphe plays a key role in pain modulation and motor control through projections to the spinal cord.

Serotonergic Pathways to the Cortex:
Target Areas: Prefrontal cortex, parietal cortex, occipital cortex.
Functions: Regulate attention, decision-making, and working memory.
Implicated in psychiatric conditions like schizophrenia and ADHD.

Serotonergic Pathways to the Limbic System:
Target Areas: Amygdala, hippocampus, cingulate gyrus.
Functions: Regulates emotion, behavior, and stress response.
Dysfunction can contribute to mood disorders (e.g., depression, anxiety).

Question 39

5HT in the CNS

Answer 39

Receptors - 5HT1-7 mostly GPCRs(5HT3 ionotropic)

Cortical inputs dampen sensory overload

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.

Question 40

5HT synthesis

Answer 40

Tryptophan → 5-Hydroxytryptophan (5-HTP)
(via Tryptophan Hydroxylase)
5-Hydroxytryptophan (5-HTP) → Serotonin (5-HT)
(via Aromatic L-Amino Acid Decarboxylase)

Question 41

5HT synthesis and inactivation - important therapeutic points

Answer 41

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

Question 42

Acetylcholine (ACh) pathways in the CNS

Answer 42

Acetylcholine in the CNS is involved in cognition, memory, learning, sleep, arousal, and motor control. Major cholinergic pathways include:

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).

Question 43

ACh in the CNS

Answer 43

Cognition and Memory: Critical for learning, memory, and synaptic plasticity. Loss of cholinergic function is a hallmark of Alzheimer’s disease.

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).

Question 44

ACh synthesis

Answer 44

Choline uptake into the presynaptic neuron via the choline transporter.

Choline acetyltransferase (ChAT) 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.

Question 45

Histamine

Answer 45

Histamine produced from the amino acid histidine

Synthesized and localized to the tuberomammillary nucleus within the hypothalamus

Storage, release and reuptake mechanisms not well defined

Histamine H1, H2, H3 and H4 receptors are GPCRs

Histamine neurons project to monoamine and cholinergic neurons involved in arousal, attention, learning and memory ?H3 antagonists neuroprotective?

Histamine plays a role in sleep, feeding and energy balance

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

Question 46

Stroke prevalence

Answer 46

~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

Question 47

What is an ischaemic stroke?

Answer 47

Blood clot in the brain

Question 48

What is the haemorrhagic stroke?

Answer 48

Bleed in the brain

Question 49

What is the main cause of cell death in stroke?

Answer 49

Excitotoxicty
Excessive release of glutamate
Neurones “excited to death”
Ca2+ overload
Also, Alzheimer’s, Parkinson’s, Huntington’s, motor neurone disease

Question 50

How does excitotoxicity occur?

Answer 50

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.

Question 51

Peri-infarct depolarisation

Answer 51

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.

Recurrent depolarization waves can exacerbate neuronal damage and increase the extent of infarction.

Targeting PID mechanisms offers potential therapeutic strategies to improve stroke outcomes by protecting penumbral tissue and limiting neurodegeneration.

Question 52

AS FAR AS I GOTT :)

Question 53

How are future strokes prevented?

Answer 53

Reduce risk of future strokes
Antihypertensives (eg. ACE inhibitors) – ischaemic and haemorrhagic
Statins - cholesterol reduction – ischaemic [possible contraindication in haemorrhagic though evidence is scant]
Antiplatelet drugs (eg. aspirin, clopidogrel) – ischaemic only
Anticoagulants (eg. warfarin) – ischaemic only

Obesity, Lack of exercise, Smoking, Alcohol

Question 53

How are stroke treated?

Answer 53

Tissue plasminogen activator (tPA) only licensed treatment
restores blood flow - disperses thrombus
within 3 hours
only for ischaemic (thrombotic) stroke

Neuroprotective agents?
AMPA/NMDA receptor blockers
glutamate release blockers
Na+/Ca2+ blockers
free radical scavengers
protease inhibitors
caspase inhibitors

Neuroregeneration? Eg. stem cells

Question 53

What are TIAs

Answer 53

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

Question 53

Other examples of excitotoxicity

Answer 53

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

Causes motorneuron degeneration leading to paralysis

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

Question 54

What are the three basic mechanisms for crossing the BBB?

Answer 54

(A) Passive, transcellular diffusion: more lipophilic molecules can move through the cell membrane (most CNS active drugs use this process).

(B)Active transport (facilitated diffusion): substances that the brain needs such as glucose and amino acids are carried across by transport proteins.

(C)Receptor-mediated transport (receptor mediated endocytosis): (e.g., insulin).

Question 55

What is lipinskis rule of 5

Answer 55

The number of H-bonds (donor and acceptor)
Lipophilicity
Polar surface area (PSA)
Molecular weight
pKa (in particular, the acidity)

Question 56

best chance of good BBB penetration when

Answer 56

Molecular weight is reduced
Lipophilicity is ‘high’ (within limits)
Low number of polar atoms (N and O) (particularly H-bond donors)
No carboxylic acids

Question 57

What is the definition of learning disability?

Answer 57

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.

Question 58

How is intellectual functioning measured?

Answer 58

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

Question 59

How do you know if someone has a learning disability?

Answer 59

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)

Question 60

What is the multidisciplinary team for LD?

Answer 60

Psychiatry
LD Nursing (Health facilitation and behaviour nurses)
Psychology
Physiotherapy
Occupational Therapy
Speech and Language Therapy
(Dietetics)
(Pharmacy)

Question 61

Which physical health conditions are likely to be co-morbid?

Answer 61

Dementia – higher risk of early onset dementia (in Downs Syndrome)
Epilepsy – higher prevalence within LD
Dental hygiene – Less likely to visit the dentist; difficulties with dental hygiene.
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

Question 62

Health Needs of People with Learning Disability

Answer 62

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

Often combination of both factors

Question 63

Epilepsy in LD

Answer 63

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

Question 64

Dementia in Learning Disability

Answer 64

↑ Risk overall - approx 2.5 X higher in 70-74 age group
Aetiology - ↓ cognitive reserve, ↑health inequalities

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 4th/5th decade

Question 65

Management of Alzheimer’s Dementia in Down’s syndrome

Answer 65

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

? Potential for use of new Disease Modifying Treatments (monoclonal antibody therapies)
Two drugs with regulators (Lecanumab and Decanumab) – UK approval yet TBC
Major tolerability problems for service users with LD

Question 66

Mental illness in learning disability

Answer 66

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

Question 67

Autism and challenging behaviour

Answer 67

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

Question 68

Mortality in LD Population

Answer 68

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

Question 69

Causes of premature mortality in LD population

Answer 69

Challenges to accessing healthcare:

Communication
Estimated that 50% of people with learning disabilities have communication difficulties.
(RCN, 2010; Holt, Hardy and Bouras, 2011)
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

Question 70

What are reasonanble adjustments?

Answer 70

reduced waiting time
quiet environment (side room)
longer appointments
accessible information
understanding how the person communicates
family/carer input
thinking outside the box/’detective work’
Objective measures eg NEWS-2 score

Question 71

Communication in LD

Answer 71

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.

Question 72

Learning Disabilities Annual Health Checks

Answer 72

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 	(cgakit.com)

Question 73

LD Liaison Nurses in general hospitals

Answer 73

Working with people with LD should be everyone’s business!

Support understanding of reasonable adjustments and use of Mental Capacity Act

Example – person with learning disability declining treatment

Question 74

Mental Capacity Act 2005

Answer 74

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

5 Key Principles:

Presumption of capacity
Every adult has the right to make their own decisions & must be assumed capable of doing so until proved otherwise

2. 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
3. Unwise decision accepted
   people should be able to make unwise or eccentric decisions – it is capacity to make decisions that is the issue.
4. 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
5. Least restrictive option
   Anything done for or on behalf of people without capacity should restrict their rights & freedoms as little as possible

REMEMBER – be clear about who is the decision-maker

Question 75

General principles of prescribing in LD

Answer 75

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
eg Down syndrome – CHD, metabolic differences (see next slide)

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 (↑ dysphagia in LD) NEWT guidelines for enteral feeding tubes or swallowing difficulties

Question 76

Use of psychotropic medication for people with learning disability

Answer 76

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

Question 77

Monitoring and review of psychotropic meds in people with LD

Answer 77

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