CNS Flashcards
(517 cards)
1
Q
A
2
Q
What is epilepsy?
A
A disorder where spontaneous, recurrent seizures occur due to abnormal brain activity.
3
Q
What is a seizure?
A
A transient event of uncontrolled neuronal discharge starting from an epileptic focus.
4
Q
What are the two major classifications of seizures?
A
Generalised and focal (previously ‘partial’) seizures.
5
Q
Name three generalised seizure types.
A
Tonic-clonic, absence, myoclonic.
6
Q
What are tonic-clonic seizures also called?
A
Grand mal seizures.
7
Q
What is an absence seizure?
A
Brief loss of awareness, common in children; 3 Hz spike-and-wave on EEG.
8
Q
What is a simple focal seizure?
A
Localised seizure with retained awareness.
9
Q
What is a complex focal seizure?
A
Focal seizure with altered awareness or automatisms.
10
Q
What is status epilepticus?
A
A seizure lasting >5 minutes or multiple seizures without regaining consciousness.
11
Q
Which brain region is most prone to drug-refractory seizures?
A
Temporal lobe (especially hippocampus).
12
Q
What is the main excitatory neurotransmitter in the brain?
A
Glutamate.
13
Q
What is the main inhibitory neurotransmitter?
A
GABA.
14
Q
What are the goals of AED therapy?
A
Reduce seizure frequency and severity without significant side effects.
15
Q
How do sodium channel blockers work as AEDs?
A
They inhibit repetitive firing by blocking use-dependent Na⁺ channels.
16
Q
Name 3 AEDs that block voltage-gated sodium channels.
A
Phenytoin, carbamazepine, lamotrigine.
17
Q
Which drugs block voltage-gated calcium channels?
A
Ethosuximide, gabapentin, pregabalin.
18
Q
Which AED blocks glutamate release by vesicle fusion?
A
Levetiracetam.
19
Q
How do GABA-enhancing drugs work?
A
They increase GABA levels or potentiate GABA-A receptor effects.
20
Q
Which AEDs enhance GABA transmission?
A
Sodium valproate, benzodiazepines, phenobarbital.
21
Q
What is the role of topiramate in epilepsy?
A
Blocks AMPA/kainate receptors and enhances GABA.
22
Q
What is the mechanism of felbamate?
A
Blocks NMDA receptors to reduce excitatory signalling.
23
Q
Why are AEDs considered pleiotropic?
A
They act on multiple mechanisms like ion channels, neurotransmitters, and synaptic modulation.
24
Q
What is the PPP and why is it required?
A
Pregnancy Prevention Programme; mandatory for women/girls on valproate due to teratogenicity.
25
Name two non-drug treatments for epilepsy.
Surgery (e.g. temporal lobectomy), vagus nerve stimulation (VNS).
26
What is a ketogenic diet and its role in epilepsy?
High-fat, low-carb diet that alters brain metabolism; used in drug-resistant epilepsy.
27
How effective is seizure control with AEDs?
70–80% become seizure-free; ~20–30% have chronic epilepsy.
28
What is the difference between antiepileptic and antiepileptogenic drugs?
AEDs reduce symptoms (seizures); they don't prevent the underlying disease.
29
Why is epilepsy diagnosis difficult?
Seizures are unpredictable and EEG can be abnormal in people without epilepsy.
30
What imaging tools are used in epilepsy diagnosis?
EEG, MRI/fMRI, PET, MEG.
31
What are common epilepsy triggers?
Sleep deprivation, electrolyte imbalance, alcohol, infection, flashing lights.
32
Which AED requires the Pregnancy Prevention Programme (PPP)?
Sodium valproate – due to high teratogenic risk.
33
Who must initiate valproate prescribing since Nov 2023?
Specialist care only.
34
What forms of contraception are required under PPP?
At least one user-independent (e.g. IUD) or two complementary forms (e.g. pill + barrier).
35
When should vitamin D supplementation be considered with valproate?
In patients immobilised or with low sun/calcium intake.
36
What are common valproate adverse effects?
Weight gain, tremor, liver toxicity, teratogenicity.
37
What seizure types can valproate treat?
Focal, secondary generalised, and primary generalised tonic-clonic seizures.
38
What seizure types might valproate worsen?
Absence and myoclonic seizures in some patients.
39
What monitoring is required for valproate?
Liver function tests, full blood count.
40
What seizure types is carbamazepine effective for?
Focal seizures, primary/secondary generalised tonic-clonic seizures, Lennox-Gastaut.
41
What can carbamazepine exacerbate?
Absence and myoclonic seizures.
42
Which AEDs are sodium channel blockers?
Carbamazepine, lamotrigine, phenytoin.
43
What AED acts via vesicle fusion modulation?
Levetiracetam.
44
Which AED enhances GABA and blocks AMPA?
Topiramate.
45
What precautions are needed with phenytoin?
Monitor serum levels; narrow therapeutic index; gingival hyperplasia risk.
46
Which AEDs increase osteoporosis risk with long-term use?
Valproate, phenytoin, carbamazepine, phenobarbital, primidone.
47
What are common adverse effects of gabapentin?
Dizziness, somnolence, ataxia, weight gain.
48
What are gabapentin and pregabalin analogues of?
Structural analogues of GABA.
49
What pregnancy supplement is recommended for women on AEDs?
High-dose folic acid (5 mg/day).
50
Why might extended-release AEDs be considered?
To reduce peak-trough fluctuations and improve tolerability.
51
What is the goal of epilepsy treatment?
Control seizures with the lowest effective dose of a single drug, if possible.
52
When should seizure control be reviewed?
Annually, or sooner if seizures worsen or side effects occur.
53
What assessments should be made during epilepsy review?
Seizure frequency/severity, medication side effects, daily functioning.
54
What patient groups require extra monitoring on AEDs?
Women of childbearing age, elderly, patients with liver/renal issues.
55
What is an important counselling point for carers of epilepsy patients?
How to recognise and manage a seizure emergency.
56
What enzyme effects does carbamazepine have?
It is a hepatic enzyme inducer.
57
Why should branded prescribing be used for AEDs?
To avoid variability in blood levels that can trigger seizures.
58
What is the most common affective disorder?
Unipolar depression.
59
What is the difference between sadness and depression?
Sadness is a normal, transient emotion; depression is persistent, severe, and often without clear cause.
60
Name the two subtypes of unipolar depression.
Reactive (linked to stress) and endogenous (familial, recurrent).
61
List 3 emotional symptoms of depression.
Apathy, low self-esteem, suicidal thoughts.
62
List 3 biological symptoms of depression.
Sleep disturbance, appetite loss, psychomotor retardation.
63
Name 3 brain regions involved in mood regulation.
Prefrontal cortex, hippocampus, amygdala.
64
What neurotransmitters are primarily involved in depression?
Serotonin (5HT), noradrenaline (NA), dopamine (DA).
65
What is the monoamine theory of depression?
Depression is due to a functional deficit of 5HT and/or NA.
66
What is the mechanism of tricyclic antidepressants (TCAs)?
Block reuptake of 5HT and NA at synapses.
67
What are major side effects of TCAs?
Sedation, anticholinergic effects, postural hypotension, arrhythmias.
68
Why are SSRIs preferred over TCAs?
Safer in overdose, better side-effect profile, similar efficacy.
69
Give 2 examples of SSRIs.
Fluoxetine, sertraline.
70
What serious interaction can occur with SSRIs and MAOIs?
Serotonin syndrome – can be fatal.
71
What is the mechanism of MAOIs?
Inhibit breakdown of monoamines by monoamine oxidase enzymes.
72
What food interaction occurs with MAOIs?
Tyramine-containing foods can trigger hypertensive crisis ('cheese reaction').
73
What is mirtazapine's mechanism?
Alpha-2 autoreceptor antagonist; increases NA release.
74
Why are antidepressants slow to act clinically?
Adaptive changes (e.g. neuroplasticity) take weeks to develop.
75
What is ketamine’s role in depression?
A rapid-acting antidepressant; NMDA antagonist; used in treatment-resistant cases.
76
What is the neurotrophic hypothesis of depression?
Depression involves reduced BDNF and neurogenesis.
77
What drug is the gold standard for bipolar disorder?
Lithium – stabilises mood, requires plasma monitoring due to toxicity risk.
78
What are the DSM-V criteria for diagnosing major depression?
At least 5 of 9 symptoms present most of the day, nearly every day, for ≥2 weeks, including at least one core symptom.
79
What are the two core symptoms in DSM-V for depression?
Low mood and/or loss of interest or pleasure.
80
Name four additional symptoms considered in DSM-V for depression.
Fatigue, appetite/weight changes, poor concentration, suicidal thoughts.
81
What is the PHQ-9?
A 9-question depression screening tool aligned with DSM-V.
82
What is first-line management for mild depression?
Lifestyle changes and psychological therapies like CBT or guided self-help.
83
When is pharmacotherapy initiated in depression?
Moderate to severe depression or after failure of psychological therapy.
84
Name four SSRIs used in depression.
Citalopram, escitalopram, sertraline, fluoxetine.
85
Why are SSRIs preferred over TCAs?
Fewer side effects, safer in overdose, better tolerated.
86
What are common withdrawal symptoms of SSRIs?
Dizziness, nausea, electric shock sensations, insomnia, anxiety.
87
What are the risks of SSRI use around delivery?
Increased postpartum haemorrhage and bleeding risk.
88
What food interaction is critical with MAOIs?
Tyramine-rich foods can trigger hypertensive crisis.
89
What is mirtazapine’s mechanism?
Alpha-2 antagonist that increases NA and 5HT release.
90
What is the serotonin syndrome?
A potentially life-threatening reaction to serotonergic drugs; causes neuromuscular, autonomic, and mental changes.
91
How long should antidepressant treatment continue after remission?
At least 6 months at the same effective dose.
92
What is recommended if a patient does not respond to an SSRI?
Switch class or add another antidepressant or augmenting agent like lithium or quetiapine.
93
What are symptoms of antidepressant discontinuation syndrome?
Headache, fatigue, anxiety, nausea, electric shock sensations, dizziness.
94
Which TCA is considered safer in overdose?
Lofepramine.
95
Name a key counselling point when stopping a TCA.
Taper dose gradually over 4 weeks to avoid withdrawal effects.
96
What side effect is more common with antidepressants in the elderly?
Hyponatraemia.
97
What are the three most common side effects of antidepressants?
GI upset, sexual dysfunction, weight gain.
98
What are the two main mood phases in bipolar disorder?
Depressive episodes and manic episodes.
99
Name two antipsychotics used in bipolar disorder management.
Quetiapine, olanzapine.
100
What is the role of benzodiazepines in bipolar disorder?
Used short-term in early stages for agitation (e.g. lorazepam).
101
Which drug is the gold standard mood stabiliser for bipolar disorder?
Lithium.
102
What is the therapeutic range for lithium in maintenance treatment?
0.4–1 mmol/L (12 hours post-dose).
103
List three key monitoring parameters for patients on lithium.
Renal function, thyroid function, serum electrolytes.
104
What are early signs of lithium toxicity?
GI upset, visual disturbances, tremor, confusion.
105
What are serious complications of lithium toxicity?
Arrhythmias, renal failure, coma, sudden death.
106
What are major adverse effects of long-term lithium use?
Cognitive impairment, hypothyroidism, renal dysfunction, QT prolongation.
107
What should patients on lithium avoid?
NSAIDs, dehydration, major dietary sodium changes.
108
Why is valproate considered a high-risk drug?
It is highly teratogenic with risk of congenital and neurodevelopmental disorders.
109
When is valproate contraindicated?
In women of childbearing potential unless under the Pregnancy Prevention Programme (PPP).
110
What is the recent (2024) regulatory restriction on valproate use?
Cannot initiate in patients <55 years without agreement from two specialists.
111
What counselling should be provided regarding valproate side effects?
Signs of liver dysfunction, pancreatitis, blood disorders.
112
Is routine plasma-valproate monitoring recommended?
No – not a useful measure of efficacy.
113
What baseline tests are recommended before starting valproate?
Liver function and full blood count.
114
How should valproate be withdrawn?
Taper gradually over at least 4 weeks.
115
Which antiepileptic drug may be used if lithium is contraindicated?
Valproate or carbamazepine.
116
Why should valproate be prescribed by brand?
To ensure bioequivalence and avoid variability in absorption.
117
What is a key safety card patients on lithium should carry?
A lithium alert card.
118
What is the primary barrier to CNS drug delivery?
The blood-brain barrier (BBB).
119
Why is the BBB a challenge for drug delivery?
It excludes almost all high MW drugs and over 98% of low MW drugs.
120
What is the role of cerebrospinal fluid (CSF)?
Cushions the brain and spinal cord and facilitates waste removal.
121
What are the two main types of intraspinal drug delivery?
Epidural and intrathecal delivery.
122
What distinguishes epidural from intrathecal delivery?
Epidural is outside the dura mater; intrathecal is into the CSF-containing subarachnoid space.
123
What are key formulation requirements for intrathecal injections?
Sterile, pyrogen-free, isosmotic, preservative-free, ≤10 mL volume.
124
What device can be implanted for long-term intrathecal drug delivery?
SynchroMed II pump.
125
What is the nose-to-brain (N2B) delivery route?
Drug delivery via the olfactory and trigeminal nerves through the nasal cavity.
126
Why is the nasal cavity unique for CNS delivery?
It is the only site where the CNS is in direct contact with the external environment.
127
What is a limitation of nose-to-brain delivery in humans?
Positive results in animals have not consistently translated to humans.
128
What is a clinical use of intrathecal delivery?
Treatment of meningitis with antibiotics.
129
What is Gliadel® wafer?
A polyanhydride polymer implant containing carmustine for brain tumour treatment.
130
What is the key polymer used in Gliadel®?
P(CPP-SA) – poly(sebacic acid-co-carboxyphenoxy propane).
131
Why is P(CPP-SA) effective for drug delivery?
It degrades slowly, controls water ingress, and allows drug release over weeks.
132
What are the challenges of carmustine delivery?
It hydrolyses rapidly in water and has a short half-life.
133
How many Gliadel® wafers can be inserted during surgery?
Up to 8.
134
What material can secure Gliadel® wafers in place?
Surgicel® (cellulose-derived).
135
What is the main goal of polymer brain implants?
Localised drug delivery with minimal systemic side effects.
136
What property of the Gliadel® wafer protects the drug?
Hydrophobic outer monomers prevent water penetration to deeper layers.
137
Why are intraspinal routes used despite risks?
They bypass the BBB and deliver drugs directly to the CNS.
138
What is the blood-brain barrier (BBB)?
A biological barrier that separates the brain from the bloodstream, protecting it from harmful substances.
139
What are the three barriers at the brain interface?
Blood-brain barrier (BBB), blood-CSF barrier (BCB), and the arachnoid barrier.
140
What features of the BBB restrict drug entry?
Tight junctions, lack of fenestrations, active transport mechanisms, and metabolising enzymes.
141
What is passive diffusion across the BBB?
Transport without energy, favoring lipophilic, small, low-PSA molecules.
142
What are key traits for passive diffusion through the BBB?
High lipophilicity (LogD 0–3), low MW, low polar surface area, few H-bond donors/acceptors.
143
What is active efflux at the BBB?
Energy-dependent transport that removes drugs from the brain back to the blood.
144
Name one example of active efflux transporter.
P-glycoprotein (P-gp).
145
What is carrier-mediated transport (CMT)?
Selective transport of essential polar molecules (e.g., glucose, amino acids) via solute carrier proteins.
146
What is receptor-mediated transcytosis (RMT)?
Transport of large regulatory proteins via specific cell-surface receptors.
147
What is adsorptive-mediated transcytosis (AMT)?
Transport of positively charged large molecules through electrostatic interactions.
148
What is cell diapedesis?
White blood cells (e.g., neutrophils) crossing the BBB, which can be exploited for drug delivery.
149
What is Lipinski’s Rule of 5?
Guidelines for drug-likeness: ≤5 H-bond donors, ≤10 acceptors, MW <500, LogP <5.
150
What is the preferred LogD for CNS penetration?
Between 0 and 3.
151
What is the ideal topological polar surface area (TPSA) for CNS drugs?
<90 Ų.
152
What are the ideal characteristics for a CNS drug?
HBD ≤5, HBA ≤10, MW ≤450, LogD 0–3, ≤10 rotatable bonds, PSA <90 Ų.
153
How do lipophilic analogues aid BBB crossing?
Add lipid groups to drugs to increase membrane permeability (but may reduce selectivity or metabolism).
154
What is a prodrug?
An inactive compound converted into an active drug in the body to improve delivery or absorption.
155
What are Chemical Delivery Systems (CDS)?
Multistep drug modifications for site-specific or enhanced delivery to the brain.
156
What is molecular packaging?
Strategy for peptides to increase lipophilicity, reduce degradation, and enable BBB penetration.
157
Why is the BBB both protective and problematic?
It prevents harmful agents from entering the brain, but also blocks many therapeutic drugs.
158
What is drug dependence?
A compulsive desire to use a drug despite harmful consequences, involving psychological and physiological components.
159
What is tolerance?
A condition where increasing doses of a drug are needed to achieve the same effect due to repeated use.
160
What is withdrawal?
Physical symptoms that occur when drug use is reduced or stopped.
161
What is the difference between reward and reinforcement?
Reward is the subjective pleasure; reinforcement is the behavioural repetition to achieve that reward.
162
Which brain pathway is central to reward and reinforcement?
The mesolimbic dopamine pathway (VTA to nucleus accumbens).
163
Which neurotransmitters are involved in the reward system?
Dopamine, noradrenaline, and serotonin.
164
What do dopamine D1 and D2 receptors do?
D1 activates adenylyl cyclase (stimulatory); D2 inhibits adenylyl cyclase and activates K⁺ channels (inhibitory).
165
How does cocaine increase dopamine levels?
It inhibits dopamine reuptake via the dopamine transporter (DAT).
166
How does amphetamine increase dopamine levels?
It promotes dopamine release and reverses DAT function.
167
How do opiates like morphine affect dopamine release?
They inhibit GABA interneurons via μ-opioid receptors, disinhibiting dopamine neurons.
168
What receptor type does THC (from cannabis) act on?
CB1/CB2 receptors on GABAergic neurons.
169
How does alcohol affect dopamine release?
It inhibits potassium channels in VTA neurons, increasing dopamine release.
170
How does nicotine affect the reward system?
It activates nicotinic ACh receptors, increasing dopamine release both directly and via glutamate.
171
What is receptor desensitisation?
A short-term decrease in receptor response due to sustained stimulation.
172
What is receptor tolerance?
A longer-term reduction in response requiring higher doses to achieve the same effect.
173
What is the role of β-arrestin in receptor desensitisation?
It binds phosphorylated GPCRs, uncouples G-proteins, and facilitates receptor internalisation.
174
What is tachyphylaxis?
A rapid, short-term reduction in response to a drug due to continuous exposure.
175
What is a non-receptor mechanism of tolerance?
Neurotransmitter exhaustion, altered metabolism (CYP induction), or second messenger adaptation.
176
Which drugs are self-administered and increase DA in the nucleus accumbens?
Cocaine, amphetamine, nicotine, alcohol, opiates, THC, caffeine.
177
Why does repeated drug use require higher doses over time?
Due to desensitisation, downregulation of receptors, and tolerance development.
178
What are the four tiers of substance misuse treatment?
Tier 1: Non-drug services, Tier 2: Open access & harm reduction, Tier 3: Community specialist/GP services, Tier 4: Rehab.
179
What are the ICD-10 criteria for dependence syndrome?
3 or more of: strong desire, control difficulty, withdrawal, tolerance, neglect of interests, persistent use despite harm.
180
What are the three classes of illegal drugs under the Misuse of Drugs Act 1971?
Class A, B, and C based on harm and legal penalties.
181
Name an example of a stimulant, depressant, and hallucinogen.
Stimulant: cocaine, Depressant: alcohol, Hallucinogen: LSD.
182
What model describes behaviour change stages in substance misuse?
Prochaska and DiClemente's Stages of Change.
183
List three key points of assessment in substance misuse.
Type/pattern of drug use, degree of dependence, social/mental health issues.
184
What are common complications of injecting drug use?
HIV, hepatitis B/C, septicaemia, endocarditis, abscesses.
185
Name three uses of drug testing in substance misuse treatment.
Confirm drug use, monitor compliance, detect relapse.
186
What are common psychosocial interventions for substance misuse?
Motivational interviewing, harm reduction, CBT, relapse prevention.
187
What are harm minimisation strategies in drug misuse?
Safe injection education, needle exchange, BBV testing, naloxone distribution.
188
What is methadone and its pharmacological class?
Synthetic opioid; full agonist with long half-life.
189
What is buprenorphine and how does it differ from methadone?
Partial opioid agonist with longer half-life and ceiling effect on respiratory depression.
190
What is naloxone used for?
Opioid antagonist used to reverse opioid overdose.
191
What is naltrexone’s role in addiction treatment?
Opioid antagonist used in relapse prevention after detoxification.
192
What alcohol-related disorder causes facial features and CNS damage?
Fetal Alcohol Syndrome (FAS).
193
What are the three stages of Alcohol Withdrawal Syndrome (AWS)?
Stage I: mild symptoms, Stage II: seizures, Stage III: delirium tremens.
194
What is Wernicke's encephalopathy triad?
Ataxia, confusion, and eye signs (e.g., nystagmus).
195
What lab markers can indicate heavy alcohol use?
MCV, GGT, CDT, AST:ALT >2.
196
Name two relapse prevention drugs for alcohol dependence.
Acamprosate, disulfiram.
197
What is the role of chlordiazepoxide in alcohol withdrawal?
A benzodiazepine used to manage withdrawal symptoms safely.
198
What is Parkinson’s disease (PD)?
A chronic neurodegenerative condition associated with aging, primarily involving dopamine deficiency.
199
What are the 4 cardinal motor symptoms of Parkinson’s disease?
Tremor, bradykinesia, rigidity, postural instability.
200
What brain region primarily loses neurons in PD?
Substantia nigra (specifically the nigrostriatal dopamine pathway).
201
What are Lewy bodies?
Intracellular aggregates of alpha-synuclein protein found in PD patients.
202
What is the Braak hypothesis?
PD pathology spreads progressively from brainstem to cortex via Lewy body accumulation.
203
What neurotransmitter is deficient in PD?
Dopamine.
204
What is the effect of dopamine on motor pathways?
Stimulates movement by enhancing the direct pathway (via D1) and inhibiting the indirect pathway (via D2).
205
What happens to the basal ganglia in PD?
Loss of dopamine causes imbalance in motor pathways, increasing inhibition of thalamus and reducing movement.
206
What is the gold standard treatment for PD?
Levodopa combined with a peripheral AADC inhibitor.
207
What are the first-line treatments according to NICE for early PD?
Levodopa, dopamine agonists, or MAO-B inhibitors depending on symptom impact.
208
What is the role of COMT inhibitors in PD?
They prolong the effect of levodopa by inhibiting its breakdown.
209
Name a MAO-B inhibitor used in PD.
Selegiline or rasagiline.
210
What is amantadine used for in PD?
To treat L-dopa-induced dyskinesia.
211
What is an anticholinergic used for PD tremor?
Benztropine.
212
What is micrographia?
Small, cramped handwriting associated with PD.
213
What non-motor symptoms may occur in PD?
Depression, constipation, sleep disturbances, anosmia.
214
What causes rigidity in PD?
Increased muscle tone due to loss of dopaminergic control over basal ganglia.
215
How does dopamine depletion affect direct and indirect pathways?
Reduces direct (less movement), enhances indirect (more inhibition), both reducing movement.
216
Why are dopamine agonists sometimes preferred early in PD?
Delay levodopa initiation and reduce risk of motor complications.
217
How is PD diagnosed clinically?
By identifying 3 of 4 cardinal motor symptoms, typically without a definitive test.
218
What are key risk factors for Parkinson’s Disease?
Increasing age, male gender, head trauma, genetic mutations (e.g., LRRK2), environmental toxins (e.g., MPTP).
219
List three non-motor symptoms of Parkinson’s Disease.
Constipation, sleep disorders, neuropsychiatric symptoms (e.g., anxiety, depression).
220
What is the prodromal phase in PD?
A phase lasting up to 20 years before diagnosis with subtle non-motor symptoms.
221
Name two medications that can cause drug-induced Parkinsonism.
Metoclopramide and cinnarizine.
222
What is the main goal of Parkinson’s treatment?
Symptom control tailored to the individual’s presentation and progression.
223
Why must levodopa be taken on time?
To prevent ‘off-time’ symptoms and avoid complications like falls and pneumonia.
224
What is the role of carbidopa or benserazide in co-careldopa?
They inhibit peripheral decarboxylation of levodopa, allowing more to reach the brain.
225
What motor complication is associated with long-term levodopa use?
Dyskinesia and motor fluctuations.
226
What are two subclasses of dopamine agonists?
Ergoline (e.g., bromocriptine) and non-ergoline (e.g., pramipexole, ropinirole).
227
Why are ergoline DA agonists not commonly used?
They are associated with fibrotic reactions.
228
Name a dopamine agonist available as a patch.
Rotigotine.
229
What behavioural side effects can dopamine agonists cause?
Gambling, hypersexuality, binge eating, obsessive shopping.
230
What is the mechanism of COMT inhibitors?
They prevent peripheral breakdown of levodopa, extending its action.
231
What is opicapone’s advantage over entacapone?
Taken once daily, reducing pill burden.
232
What is the role of amantadine in PD?
Used as a glutamate antagonist to treat levodopa-induced dyskinesia.
233
Why are antidepressants used cautiously with MAO-B inhibitors?
Risk of serotonin syndrome.
234
What drug is preferred for hallucinations in PD?
Quetiapine.
235
Which antipsychotics should be avoided in PD?
Olanzapine, risperidone, phenothiazines, and butyrophenones.
236
What is a key counselling point for rotigotine patches?
Rotate site daily and avoid repeated use of same site for 14 days.
237
What is the salt-to-base conversion for pramipexole 2 mg salt?
Equivalent to 1400 micrograms of base.
238
What is dementia?
A chronic, progressive syndrome causing loss of mental function, interfering with daily life.
239
What is the most common type of dementia?
Alzheimer’s disease (AD).
240
What are BPSD symptoms?
Behavioural and psychological symptoms of dementia: agitation, apathy, hallucinations, delusions, etc.
241
What are two key pathological features of Alzheimer's disease?
Amyloid beta plaques and neurofibrillary tangles (NFTs).
242
What protein is found in extracellular plaques in AD?
Amyloid beta (Aβ).
243
What protein forms neurofibrillary tangles?
Tau (hyperphosphorylated).
244
Which enzymes cleave APP to produce Aβ?
Beta-secretase (BACE1) and gamma-secretase (presenilin component).
245
What is the amyloid hypothesis?
Aβ accumulation triggers the development of Alzheimer’s disease pathology.
246
What brain areas are affected early in AD?
Hippocampus and temporal lobe.
247
What is the role of acetylcholinesterase inhibitors in AD?
They prevent breakdown of acetylcholine to support cognitive function.
248
Name three AChE inhibitors used in AD.
Donepezil, galantamine, rivastigmine.
249
What is memantine and when is it used?
An NMDA antagonist used in moderate to severe AD to reduce excitotoxicity.
250
What genetic mutation is associated with early-onset familial AD?
Mutations in APP or presenilin genes.
251
What gene increases risk of late-onset AD?
Apolipoprotein E (ApoE4).
252
What are modifiable risk factors for dementia?
Smoking, hypertension, hearing loss, alcohol, inactivity, social isolation, air pollution, diabetes.
253
What are the phases of Alzheimer’s disease progression?
Early (memory loss), middle (withdrawal, aphasia), late (dependence, psychiatric symptoms).
254
What is Dementia with Lewy bodies?
A dementia with α-synuclein inclusions, hallucinations, cognitive fluctuations, and parkinsonism.
255
What is frontotemporal dementia?
Dementia affecting younger adults; impacts behaviour and language; no Aβ pathology.
256
Which new monoclonal antibodies target Aβ?
Aducanumab (Aduhelm™), Lecanemab (Leqembi™).
257
Why are AChE inhibitors less useful in FTD?
FTD spares cholinergic neurons, so AChE inhibitors show little benefit.
258
What are the core cognitive symptoms of dementia?
Memory loss, disorientation, lack of concentration, difficulty with speech.
259
What are the non-cognitive symptoms of dementia?
Agitation, aggression, distress, psychosis.
260
What is the first-line drug for mild-to-moderate Alzheimer’s disease?
Donepezil.
261
When is donepezil potentially inappropriate in elderly patients?
If they have persistent bradycardia or heart block.
262
What is the initial and maintenance dose of donepezil?
5 mg OD for 1 month, then increased to 10 mg at bedtime.
263
What is the counselling advice for donepezil orodispersible tablets?
Place on tongue, allow to disperse, then swallow.
264
What is the mechanism of action of rivastigmine?
Reversible non-competitive inhibitor of acetylcholinesterases.
265
What monitoring is required with rivastigmine?
Monitor body weight, especially in patients <50 kg.
266
How should a rivastigmine patch be applied?
Apply to clean, dry, non-hairy skin on back, upper arm or chest; rotate site every 14 days.
267
What is the mode of action of memantine?
NMDA receptor antagonist that reduces glutamate-mediated excitotoxicity.
268
How should memantine oral solution be taken?
Dose onto a spoon or into a glass of water.
269
When is galantamine contraindicated?
Avoid if creatinine clearance <9 mL/min.
270
What are common side effects of galantamine?
Appetite loss, diarrhoea, dizziness, falls, arrhythmias.
271
What approach is used to manage dementia-related agitation or psychosis?
Antipsychotics only if there is risk of harm; use lowest dose for shortest time; review every 6 weeks.
272
What is the CHM/MHRA advice on antipsychotics in dementia?
They increase risk of stroke and death; use with caution in elderly dementia patients.
273
How is depression or anxiety managed in dementia?
CBT preferred; antidepressants reserved for severe or pre-existing mental illness.
274
How is sleep disturbance managed in dementia?
Sleep hygiene, daylight exposure, and increased activity.
275
What is the VERA approach for challenging behaviours in dementia?
Validate, Emotional connection, Reassurance, Activity.
276
What is the relevance of anticholinergic burden in dementia?
High ACB increases risk of cognitive impairment; caution with drugs like amitriptyline, promethazine.
277
What are the NICE recommended therapies for cognitive symptoms in dementia?
Cognitive stimulation therapy, reminiscence therapy, occupational therapy.
278
Which drug is used for motion sickness and causes sedation?
Promethazine.
279
Name three antihistamines used for nausea.
Cinnarizine, cyclizine, promethazine.
280
Which dopamine antagonist is used for chemotherapy-induced nausea?
Prochlorperazine (buccal).
281
Which antiemetic is commonly used in palliative care?
Haloperidol or levomepromazine.
282
What combination is used post-operatively for nausea?
Ondansetron, dexamethasone, and haloperidol.
283
Which drug can cause acute dystonia, especially in young females?
Metoclopramide.
284
What is the key difference between domperidone and metoclopramide?
Domperidone acts peripherally and has fewer CNS side effects.
285
Why is domperidone preferred in Parkinson’s patients?
It does not worsen central dopamine levels or cause extrapyramidal side effects.
286
What is the role of phenothiazines in nausea?
They block dopamine receptors centrally at the chemoreceptor trigger zone.
287
Name two phenothiazine antiemetics.
Chlorpromazine and prochlorperazine.
288
What is the maximum recommended duration for metoclopramide use?
5 days.
289
What is the common adult dose of metoclopramide?
10 mg up to three times daily.
290
What is the main risk of metoclopramide in children?
Acute dystonic reactions.
291
Why is domperidone restricted in children?
Lack of efficacy and increased risk of arrhythmias.
292
What are domperidone's contraindications?
Cardiac disease, GI obstruction, GI haemorrhage.
293
What antiemetics are considered safe in pregnancy?
Chlorpromazine, cyclizine, metoclopramide, prochlorperazine, promethazine, ondansetron.
294
What condition in pregnancy may require parenteral antiemetics?
Hyperemesis gravidarum.
295
What vitamin is supplemented in hyperemesis gravidarum?
Thiamine, to reduce risk of Wernicke’s encephalopathy.
296
Why are antiemetics generally avoided unless the cause is known?
They can mask symptoms and delay diagnosis, especially in children.
297
What is a key counselling point for patients using domperidone?
Seek medical help if palpitations or fainting (syncope) occur due to arrhythmia risk.
298
Which drug is used for motion sickness and causes sedation?
Promethazine.
299
Name three antihistamines used for nausea.
Cinnarizine, cyclizine, promethazine.
300
Which dopamine antagonist is used for chemotherapy-induced nausea?
Prochlorperazine (buccal).
301
Which antiemetic is commonly used in palliative care?
Haloperidol or levomepromazine.
302
What combination is used post-operatively for nausea?
Ondansetron, dexamethasone, and haloperidol.
303
Which drug can cause acute dystonia, especially in young females?
Metoclopramide.
304
What is the key difference between domperidone and metoclopramide?
Domperidone acts peripherally and has fewer CNS side effects.
305
Why is domperidone preferred in Parkinson’s patients?
It does not worsen central dopamine levels or cause extrapyramidal side effects.
306
What is the role of phenothiazines in nausea?
They block dopamine receptors centrally at the chemoreceptor trigger zone.
307
Name two phenothiazine antiemetics.
Chlorpromazine and prochlorperazine.
308
What is the maximum recommended duration for metoclopramide use?
5 days.
309
What is the common adult dose of metoclopramide?
10 mg up to three times daily.
310
What is the main risk of metoclopramide in children?
Acute dystonic reactions.
311
Why is domperidone restricted in children?
Lack of efficacy and increased risk of arrhythmias.
312
What are domperidone's contraindications?
Cardiac disease, GI obstruction, GI haemorrhage.
313
What antiemetics are considered safe in pregnancy?
Chlorpromazine, cyclizine, metoclopramide, prochlorperazine, promethazine, ondansetron.
314
What condition in pregnancy may require parenteral antiemetics?
Hyperemesis gravidarum.
315
What vitamin is supplemented in hyperemesis gravidarum?
Thiamine, to reduce risk of Wernicke’s encephalopathy.
316
Why are antiemetics generally avoided unless the cause is known?
They can mask symptoms and delay diagnosis, especially in children.
317
What is a key counselling point for patients using domperidone?
Seek medical help if palpitations or fainting (syncope) occur due to arrhythmia risk.
318
What is ADHD according to ICD-11?
A persistent pattern of inattention and/or hyperactivity-impulsivity with early onset that interferes with functioning.
319
Which neurotransmitters are primarily involved in ADHD?
Dopamine (DA) and noradrenaline (NA).
320
What is the paradoxical effect of stimulants in ADHD?
They have a calming effect despite being stimulants.
321
What is the first-line treatment for ADHD according to NICE?
Lisdexamfetamine or methylphenidate.
322
What is the mechanism of action of atomoxetine?
Selective noradrenaline reuptake inhibitor (NARI).
323
Name two non-stimulant medications for ADHD.
Clonidine and guanfacine.
324
What are key pre-medication checks before starting ADHD medication?
Confirm diagnosis, assess comorbidities, cardiovascular history, baseline BP, pulse, weight, and height.
325
What should be monitored during ADHD medication treatment?
BP, pulse, psychiatric symptoms, weight and height (every 6 months).
326
What is the most common side effect of methylphenidate?
Appetite loss.
327
What serious cardiovascular conditions are contraindications for stimulants?
Arrhythmias, heart failure, structural abnormalities, severe hypertension.
328
Why should methylphenidate MR be prescribed by brand?
Different formulations have different release profiles and clinical effects.
329
What are the overdose symptoms of stimulants?
Paranoia, hallucinations, hypertension, hyperactivity, convulsions, coma.
330
How does dopamine dysfunction affect ADHD symptoms?
Leads to poor reward processing and impaired cognitive control.
331
What is a counselling point for lisdexamfetamine capsules?
Can be swallowed whole or dispersed in soft food or juice and consumed immediately.
332
What is the monitoring advice for lisdexamfetamine?
Monitor for aggression, BP, pulse, weight, height, and psychiatric symptoms.
333
What is the difference between tonic and phasic dopamine release?
Tonic is background activity; phasic is rapid bursts for reward/novelty.
334
What psychological interventions support ADHD treatment?
CBT, DBT, mindfulness, psychoeducation, lifestyle changes.
335
What is the benefit of stimulant therapy in ADHD?
Improves cognitive function, reduces hyperactivity and distractibility.
336
What are common adverse effects of stimulant medication?
Insomnia, nausea, tics, appetite loss, weight loss.
337
What guidance source provides current ADHD prescribing recommendations?
NICE Guideline NG87 (2018).
338
What law governs the classification and control of drugs in the UK?
Misuse of Drugs Act 1971.
339
What are the 5 drug schedules under the Misuse of Drugs Regulations 2001?
Schedule 1, 2, 3, 4 (Parts I & II), and 5.
340
What are Schedule 1 drugs used for?
They have no therapeutic use and require a Home Office licence.
341
Give an example of a Schedule 1 drug.
LSD or raw opium.
342
What is the main feature of Schedule 2 CDs?
They are subject to safe custody, prescription requirements, and CD register recording.
343
Name a few Schedule 2 drugs.
Morphine, methadone, diamorphine, oxycodone, ketamine.
344
What differentiates Schedule 3 drugs from Schedule 2?
Schedule 3 drugs have less misuse potential and do not require CD register entries.
345
What Schedule 3 CDs require safe custody?
Temazepam and buprenorphine.
346
What must be included on a valid CD prescription?
Date, prescriber signature, form, strength (if multiple), dose, total quantity in words and figures.
347
How long is a CD prescription valid?
28 days from the appropriate date.
348
What does the ‘appropriate date’ on a CD prescription mean?
Either the signature date or a specified 'not to be supplied before' date, whichever is later.
349
Can a pharmacist amend minor technical errors on a CD prescription?
Yes, but only minor typographical issues or if either words or figures are missing—not both.
350
Who can collect a dispensed CD?
Patient, representative, or authorised healthcare professional (with ID verification).
351
How should CDs be stored in pharmacies?
In a locked cabinet or room constructed to prevent unauthorised access (per Safe Custody Regulations).
352
What is required for Schedule 2 CD storage but not for some Schedule 3 drugs?
Safe custody (locked storage).
353
Name two Schedule 3 drugs exempt from safe custody.
Gabapentin and pregabalin.
354
What is a common SOP requirement for CD storage?
Handle Schedule 3–5 CDs as if they are Schedule 2 for safety.
355
How should returned or expired CDs be stored?
Under safe custody until destruction.
356
What must be recorded when supplying a Schedule 2 CD?
Date of supply on the prescription at time of dispensing.
357
What is the maximum recommended supply duration for Schedule 2–4 CDs?
30 days (not a legal limit but professional guidance).
358
What are the three main types of primary headaches?
Migraine, tension headache, and cluster headache.
359
List four red flag symptoms requiring further assessment in headache patients.
Sudden onset, neurological signs, systemic illness signs, age >50 with new onset headache.
360
What are typical migraine symptoms?
Unilateral, pulsating headache with photophobia, phonophobia, nausea, vomiting, ± aura.
361
What distinguishes episodic from chronic migraine?
Episodic: <15 days/month; Chronic: ≥15 days/month for >3 months.
362
List three common migraine triggers.
Poor sleep, missed meals, stress, menstruation.
363
What is the first-line acute treatment for migraine?
Simple analgesics (e.g. paracetamol, NSAIDs) ± antiemetics.
364
Name three triptans used for migraine.
Sumatriptan, zolmitriptan, rizatriptan.
365
When should prophylactic treatment for migraine be considered?
Frequent attacks, poor response to acute meds, risk of MOH, reduced QoL.
366
Name three prophylactic treatments for migraine.
Propranolol, topiramate, amitriptyline.
367
What is a key counselling point for triptans?
Take at symptom onset, max 2 doses/24 hours, avoid in CV disease.
368
Which migraine medications are contraindicated in pregnancy?
Aspirin, NSAIDs (in T3), ergots, most triptans unless essential.
369
What is Medication Overuse Headache (MOH)?
Headaches from frequent use of acute migraine medications.
370
What are common antiemetics used in migraines?
Metoclopramide and prochlorperazine.
371
What is the role of lifestyle in migraine management?
Sleep hygiene, hydration, meal regularity, stress management, exercise.
372
How is cluster headache treated acutely?
Subcutaneous or nasal sumatriptan, high-flow oxygen therapy.
373
What is the first-line prophylaxis for cluster headaches?
Verapamil (specialist initiation).
374
What is a common side effect of propranolol?
Fatigue, hypotension, bradycardia, sleep disturbance.
375
Why is topiramate used cautiously in women of childbearing age?
Teratogenic, requires effective contraception.
376
What is a key risk when using metoclopramide?
Extrapyramidal side effects, especially in young people.
377
How should migraine in adolescents be managed?
Lifestyle, simple analgesics, nasal triptans if needed, avoid prophylaxis in primary care.
378
What are the three main symptom categories of schizophrenia?
Positive, negative, and cognitive symptoms.
379
Give examples of positive symptoms in schizophrenia.
Hallucinations, delusions, disordered thoughts, abnormal motor behaviour.
380
Give examples of negative symptoms in schizophrenia.
Affective blunting, avolition, anhedonia, social withdrawal.
381
What are cognitive symptoms in schizophrenia?
Poor executive function, memory issues, attention deficits.
382
What is the dopamine hypothesis of schizophrenia?
Excess dopamine activity, especially in the mesolimbic pathway, contributes to positive symptoms.
383
Which brain pathway is linked to positive symptoms?
Mesolimbic dopamine pathway.
384
Which brain pathway is linked to negative symptoms?
Mesocortical dopamine pathway.
385
How does L-DOPA affect schizophrenia symptoms?
Can exacerbate positive symptoms like delusions and hallucinations.
386
What are typical antipsychotics?
First-generation D2 receptor antagonists effective against positive symptoms.
387
Name two typical antipsychotics.
Haloperidol and chlorpromazine.
388
What are key side effects of typical antipsychotics?
Extrapyramidal symptoms, increased prolactin, sedation, hypotension, anticholinergic effects.
389
What are atypical antipsychotics?
Second-generation drugs with lower D2 affinity, also block 5HT2 receptors; affect both positive and negative symptoms.
390
Name two atypical antipsychotics.
Olanzapine and risperidone.
391
What are side effects of atypical antipsychotics?
Weight gain, diabetes risk, fewer motor side effects than typical antipsychotics.
392
How does 5HT relate to schizophrenia?
5HT2 receptor activity may contribute to hallucinations; many antipsychotics block 5HT2.
393
How does glutamate dysfunction relate to schizophrenia?
NMDA receptor hypofunction may cause symptoms; ketamine induces psychosis-like effects.
394
What structural brain changes are seen in schizophrenia?
Enlarged ventricles, reduced brain volume, neuronal loss.
395
What EEG changes are seen in schizophrenia?
Reduced event-related potential amplitude in response to auditory stimuli.
396
What is the estimated prevalence of schizophrenia?
Approximately 1%.
397
What is the suicide risk among people with schizophrenia?
About 10%.
398
What is the neurodevelopmental hypothesis of schizophrenia?
Suggests increased risk with hypoxic injury at birth, viral infections in utero, epilepsy, and cannabis use.
399
What neurotransmitter changes are associated with schizophrenia?
Increased dopamine (positive symptoms), decreased mesocortical dopamine (negative symptoms), increased serotonin, decreased glutamate.
400
What is the diagnostic criteria for schizophrenia?
At least 2 symptoms for most of the time over 1 month, including one core symptom.
401
List three investigations done before schizophrenia treatment.
FBC, LFTs, fasting glucose, TFTs, urine drug screen, CT head if needed.
402
What is the care programme approach (CPA)?
Multidisciplinary plan involving assessment, care plan, key worker, and regular review.
403
What are the goals of antipsychotic treatment in schizophrenia?
Treat acute episodes, reduce positive symptoms, improve adherence, minimise side effects.
404
What is the key receptor target of antipsychotics?
Dopamine D2 receptors.
405
Name three first-generation antipsychotics.
Haloperidol, chlorpromazine, prochlorperazine.
406
Name three second-generation antipsychotics.
Olanzapine, risperidone, quetiapine.
407
What side effects are more common with first-generation antipsychotics?
Extrapyramidal symptoms (EPS), tardive dyskinesia.
408
What side effects are more common with second-generation antipsychotics?
Weight gain, glucose intolerance, lipid abnormalities.
409
What is a high-dose antipsychotic?
A dose exceeding the licensed maximum, or combination doses exceeding 100% total.
410
What monitoring is required after administering high-dose antipsychotics?
Vital signs every hour, every 15 minutes if in an emergency dose situation.
411
What is neuroleptic malignant syndrome (NMS)?
A rare reaction with hyperthermia, rigidity, altered consciousness, autonomic dysfunction.
412
What drug is least likely to cause hyperprolactinaemia?
Aripiprazole.
413
Which drug is most associated with sexual dysfunction?
Risperidone (also haloperidol, olanzapine).
414
What antipsychotic has the lowest risk of causing diabetes?
Aripiprazole or amisulpride.
415
What drug is most associated with hypotension?
Clozapine.
416
What drug is most associated with weight gain?
Clozapine and olanzapine.
417
List three major monitoring parameters for antipsychotics.
Weight, glucose/HbA1c, lipids, ECG, BP, FBC, LFTs.
418
What is Levodopa used for?
Treatment of Parkinson’s Disease as a precursor to dopamine.
419
What enzyme converts Levodopa into dopamine?
DOPA decarboxylase.
420
Why is Levodopa given with carbidopa or benserazide?
To inhibit peripheral DOPA decarboxylase and reduce side effects.
421
Why can Levodopa cross the BBB but dopamine cannot?
Levodopa uses L-amino acid transporters; dopamine is too hydrophilic.
422
What kind of inhibitor is Donepezil?
A selective and reversible acetylcholinesterase inhibitor.
423
How does Donepezil enhance cognition in Alzheimer’s Disease?
It increases cholinergic transmission by preventing ACh breakdown.
424
How does Donepezil cross the BBB?
Via carrier-mediated transport using an organic cation transporter.
425
Is Donepezil a competitive inhibitor?
Yes, it competes with acetylcholine for binding to AChE.
426
What structural property helps Levodopa cross the BBB?
It resembles amino acids and uses amino acid transporters.
427
What happens to Levodopa in the periphery if not co-administered with carbidopa?
It is converted to dopamine, causing side effects like nausea and hypertension.
428
What transporter enables Donepezil’s BBB penetration?
Organic cation transporter.
429
What does methylphenidate treat?
ADHD, formerly also depression and psychosis.
430
How does methylphenidate work?
Inhibits dopamine and noradrenaline transporters, increasing their synaptic levels.
431
How does methylphenidate enter the brain?
By passive diffusion.
432
Why does carbidopa not cross the BBB?
It is too hydrophilic.
433
What is passive diffusion dependent on?
Lipophilicity (logD), low polar surface area, and low molecular weight.
434
How many isomers does methylphenidate have?
Four, each with different diffusion and metabolism rates.
435
What SSRIs were compared for BBB crossing?
Citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, fluoxetine.
436
Which SSRI was found to have the best BBB-crossing profile?
Fluvoxamine (logP in the 0–3 range).
437
Why is escitalopram more potent than citalopram?
It is the pure S-enantiomer; the R-enantiomer in citalopram dampens activity.
438
What is anxiety?
A feeling of unease, worry or fear, ranging from mild to severe.
439
What is the role of the amygdala in anxiety?
It detects threats and triggers the 'fight-or-flight' response.
440
Which neurotransmitters are hyperactive in anxiety?
Noradrenaline and serotonin.
441
What is the role of GABA in anxiety?
It is inhibitory and reduces CNS overactivity; low GABA linked to anxiety.
442
Which brain system is most involved in emotional processing?
The limbic system.
443
What is the HPA axis?
A system involving the hypothalamus, pituitary, and adrenal glands that regulates stress.
444
What symptoms are seen in panic disorder?
Sudden fear, chest pain, palpitations, shortness of breath, feeling of doom.
445
What are the somatic symptoms of anxiety?
Tachycardia, sweating, GI disturbance, restlessness.
446
What are beta-blockers used for in anxiety?
Reduce sympathetic symptoms like tremor and tachycardia.
447
Name a beta-blocker commonly used in anxiety.
Propranolol.
448
How does buspirone work?
It is a partial agonist at 5-HT1A receptors.
449
Which drugs are first-line for GAD and panic disorder?
SSRIs and SNRIs.
450
Name two SSRIs used for anxiety.
Fluoxetine and citalopram.
451
What is the mechanism of benzodiazepines?
They enhance GABA-A receptor activity, increasing Cl⁻ influx and CNS inhibition.
452
Name a benzodiazepine used for acute anxiety.
Diazepam.
453
What are risks of long-term benzodiazepine use?
Dependence, tolerance, withdrawal symptoms.
454
What is the antidote for benzodiazepine overdose?
Flumazenil – a competitive GABA-A receptor antagonist.
455
What is a caution when using flumazenil?
May cause withdrawal or seizures in dependent individuals.
456
Which GABA receptor subtype do benzodiazepines target?
GABA-A.
457
What are the phases of CNS depression caused by benzodiazepines?
Anxiolysis → sedation → hypnosis → anaesthesia → coma → death (dose-dependent).
458
What is sleep?
A reversible state of reduced responsiveness and interaction with the environment.
459
List four functions of sleep.
Restoration, adaptation, energy conservation, memory consolidation.
460
Which brain nucleus controls circadian rhythms?
The suprachiasmatic nucleus of the anterior hypothalamus.
461
What percentage of sleep is REM and what is it associated with?
25% of sleep; associated with dreaming.
462
What is non-REM sleep and what stages does it include?
75% of sleep; includes stages 1-4 (slow wave sleep).
463
How does EEG activity differ in REM vs non-REM sleep?
REM: desynchronized (fast); non-REM: synchronized (slow waves).
464
Which brain system is central to sleep-wake control?
The Reticular Activating System (RAS).
465
What neurotransmitters stimulate arousal in the RAS?
Acetylcholine, serotonin, noradrenaline, histamine, orexin.
466
What inhibits the RAS to promote sleep?
GABAergic neurons from the hypothalamus.
467
Name three causes of transient insomnia.
Noise, jet lag, shift work.
468
Name three causes of chronic insomnia.
Depression, pain, alcohol abuse.
469
How do benzodiazepines promote sleep?
They enhance GABA-A receptor activity, increasing Cl⁻ influx and neuronal inhibition.
470
What is the role of the GABA-A receptor in sleep?
It mediates inhibitory neurotransmission via chloride channels.
471
What is a limitation of long-acting benzodiazepines?
Risk of tolerance, dependence, and rebound insomnia.
472
Give two examples of short-acting benzodiazepines.
Loprazolam and temazepam.
473
What are 'Z-drugs' and how do they work?
Non-benzodiazepine hypnotics (e.g. zolpidem) that bind to GABA-A receptors, especially α1 subunit.
474
What is a unique feature of Z-drugs vs benzodiazepines?
Z-drugs may have fewer side effects and less dependence risk.
475
Name two other classes of hypnotics besides BZDs and Z-drugs.
Orexin antagonists (e.g. suvorexant), antihistamines (e.g. diphenhydramine).
476
What is the role of melatonin in sleep?
Regulates circadian rhythms and promotes sleep initiation.
477
When is prolonged-release melatonin recommended?
For primary insomnia in adults over 55 years.
478
List four psychological symptoms of anxiety.
Irritability, restlessness, sense of dread, difficulty concentrating.
479
List four physical symptoms of anxiety.
Tiredness, fast/irregular heartbeat, muscle tension, dry mouth.
480
What is the main difference between short-acting and long-acting hypnotics?
Short-acting for sleep onset; long-acting for poor sleep maintenance and daytime anxiety.
481
Why should benzodiazepines and Z-drugs be avoided in the elderly?
Risk of confusion, ataxia, falls, and injury.
482
Name three short-acting benzodiazepines used as hypnotics.
Loprazolam, lormetazepam, temazepam.
483
What are two Z-drugs used for sleep?
Zolpidem and zopiclone.
484
What is the mechanism of benzodiazepines?
Act at benzodiazepine receptors associated with GABA receptors to enhance inhibition.
485
List four benzodiazepines used as anxiolytics.
Diazepam, alprazolam, lorazepam, chlordiazepoxide.
486
What MHRA warning applies to benzodiazepines with opioids?
Risk of potentially fatal respiratory depression.
487
What are contraindications for benzodiazepines?
Pulmonary insufficiency, psychosis, sleep apnoea, obsessional/phobic states.
488
What are signs of benzodiazepine overdose?
Drowsiness, ataxia, dysarthria, respiratory depression, coma.
489
What paradoxical effects may benzodiazepines cause?
Increased anxiety, hostility, aggression.
490
What are symptoms of benzodiazepine withdrawal?
Anxiety, insomnia, tremor, confusion, psychosis, convulsions.
491
How should long-term benzodiazepines be withdrawn?
Switch to diazepam and taper by 1–2 mg every 2–4 weeks, smaller steps toward the end.
492
What is the approximate equivalent of 250 mcg alprazolam in diazepam?
5 mg diazepam.
493
What is buspirone’s mechanism and key benefit?
5HT1A partial agonist with low dependence risk.
494
What drug is useful for palpitations and tremor in anxiety?
Beta-blockers like propranolol.
495
What hypnotic is preferred in the elderly due to low hangover effect?
Clomethiazole.
496
What are drawbacks of antihistamines for insomnia?
Headache, psychomotor impairment, antimuscarinic effects.
497
When is melatonin licensed for insomnia?
Short-term use in patients >55 years old.
498
What is the key pathological hallmark of Alzheimer’s disease?
Extracellular amyloid beta plaques and intracellular neurofibrillary tangles of tau.
499
What enzyme cleaves APP to produce Aβ?
Beta-secretase (BACE1) followed by gamma-secretase (contains presenilin).
500
Which brain regions are first affected in Alzheimer’s?
Hippocampus and temporal lobe.
501
Name two types of drugs used to treat Alzheimer’s symptoms.
AChE inhibitors (e.g. donepezil) and NMDA antagonists (e.g. memantine).
502
What do Lewy bodies contain?
Aggregated α-synuclein protein.
503
Where is dopamine loss most profound in Parkinson’s disease?
Substantia nigra pars compacta.
504
Which basal ganglia pathways are disrupted in Parkinson’s?
Direct and indirect motor pathways become imbalanced.
505
What is the primary treatment for Parkinson’s disease?
Levodopa combined with a peripheral decarboxylase inhibitor (e.g. carbidopa).
506
Why is carbidopa given with levodopa?
To inhibit peripheral conversion of levodopa to dopamine and reduce side effects.
507
What is the role of dopamine in the direct motor pathway?
It stimulates D1 receptors, promoting movement.
508
What is the role of dopamine in the indirect motor pathway?
It inhibits D2 receptors, reducing movement suppression.
509
Which dopamine pathway is linked to positive symptoms of schizophrenia?
Mesolimbic pathway.
510
Which dopamine pathway is linked to negative symptoms of schizophrenia?
Mesocortical pathway.
511
What are the 4 dopamine pathways in the brain?
Nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular.
512
How do antipsychotics work?
Primarily block D2 receptors to reduce dopamine signalling.
513
What effect does L-DOPA have on psychosis risk?
It can induce or worsen psychosis by increasing dopamine.
514
Which recreational drugs can cause psychosis via dopamine?
Cocaine and amphetamines.
515
What symptoms are linked to the tuberoinfundibular dopamine pathway?
Hyperprolactinaemia (e.g. galactorrhoea, amenorrhoea).
516
What is the mechanism of memantine?
NMDA receptor antagonist that reduces glutamate-mediated excitotoxicity.
517
What is the role of acetylcholine in Alzheimer’s disease?
Deficiency contributes to cognitive impairment; AChE inhibitors increase its availability.
