Chapter 4: Nervous System Flashcards
What kind of drugs should be minimised in patients with cognitive impairment, such as dementia?
Antimuscarinics
e.g. amitriptyline, paroxetine, solifenacin, antipsychotics
Can result in cognitive impariment
What is first line treatment options for patients with mild to moderate Alzheimer’s?
Monotherapy with one of the following Ach inhibitors:
Donezipil
Rivastigmine
Galantamine
Drug treatment should only be initiated under a specialist (however can then be managed in primary care)
What is first line for patients with severe Alzheimer’s in someone who is not on any medication for the condition?
Memantine
If a patient is on an Ach inhibitor for their mild/moderate Alzheimer’s, however their condition gets more severe, what should be done?
Consider adding memantine. In this case, it can be initiated in primary care without the advice from a specialist
In patients with moderate Alzheimer’s, what is the risk of stopping Ach inhibitor treatment?
Can cause a substantial worsening in cognitive function
What is the MHRA warning regarding prescribing antipsychotics in elderly patients with dementia?
Increased risk of stroke and a small increased risk of death
If needed, use the lowest effective dose and for the shortest time
Review every 6 weeks
What is the risk of prescribing antipsychotics in patients with Lewy body/Parkinson’s Disease dementia?
Antipsychotic drugs can worsen the motor features of the condition, and in some cases cause severe antipsychotic sensitivity reactions
What patient advice is needed for galantamine?
Risk of serious skin reaction including Stevens-Johnson
Stop taking if reaction occurs
What is the MHRA advice surrounding switching between different manufacturers’ products in epilepsy?
Antiepileptic drugs have been divided into three risk-based categories to help healthcare professionals decide whether it is necessary to maintain continuity of supply of a specific manufacturer’s product.
Category 1:
Carbamazepine, phenobarbital, phenytoin, primidone. For these drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer’s product.
Category 2
Clobazam, clonazepam, eslicarbazepine acetate, lamotrigine, oxcarbazepine, perampanel, rufinamide, topiramate, valproate, zonisamide. For these drugs, the need for continued supply of a particular manufacturer’s product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure control
Category 3
Brivaracetam, ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin, tiagabine, vigabatrin. For these drugs, it is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product as therapeutic equivalence can be assumed
What is antiepileptic hypersensitivity syndrome?
Rare but potentially fatal syndrome associated with some antiepileptic drugs
The symptoms usually start between 1 and 8 weeks of exposure; fever, rash, and lymphadenopathy are most commonly seen.
What is the MHRA advice regarding antiepileptic drugs and psychological side effects?
Associated with a small increased risk of suicidal thoughts and behaviour (can occur as early as one week after starting treatment)
Seek medical advice if they develop mood changes
True or false:
Routine injection of vitamin K at birth minimises the risk of neonatal haemorrhage associated with antiepileptics.
True
What is 1st line for newly diagnosed focal seizures?
Carbamazepine or Lamotrigine
What is 1st line for tonic-clonic seizures?
What would be an alternative if this is unsuitable? What is the problem with this?
Sodium valproate
Lamotrigine, carbamazepine is an alternative however may exacerbate myoclonic seizures
What is 1st line for absence seizures?
What would be an alternative?
Ethosuximide or sodium valproate
Lamtorogine is an alternative
What is 1st line for myoclonic seizures?
What would be alternative options?
Sodium valproate
Topiramate or levetiracetam
Atonic and clonic seizures are usually seen in which patient group?
What is the drug of choice for this?
Childhood or associated with cerebral damage or mental retardation
Sodium valproate
Lamotrigine can be added
Which benzodiazepines can be used in epilepsy management (not status epilepticus)?
Clobazam
Clonazepam
Seizures lasting longer than 5 minutes should be treated with what benzodiazepine?
What should you monitor?
IV lorazepam - can repeat once after 10 minutes if response fails
Monitor for hypotension and respiratory depression
IV diazepam is effective in seizures but carries a high risk of what?
Thrombophlebitis
True or false:
Diazepam IM or suppositories should be used for status epilepticus
False- absorption is too slow
If after initial treatment of IV lorazepam and there is no response after 25 mins, what should be used?
Phenytoin/phenobarbital/fosphenytoin
If this does not work- anaesthesia
Do brief febrile convulsions need any treatment?
No, may give paracetamol to reduce fever
However, if prolonged (>5 mins) or recurrent, treat as epileptic seizure.
Is long term anticonvulsant prophylaxis recommended?
Rarely indicated
If an epileptic patient becomes pregnant, what supplement is recommended alongside their pregnancy, especially in the first trimester?
Folate supplementation to prevent neural tube defects
High dose 5mg OD
Pregnant patients who are taking what antiepileptics should have fetal growth monitoring?
Topiramate or levetiracetam
What conditions can lamotrigine exacerbate?
Parkinson’s Disease
Myoclonic seizures
What is a main side effect of lamotrigine?
What are the risk factors of this?
Hypersensitivity syndrome.Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have developed (especially in children); most rashes occur in the first 8 weeks.
Risk factors include concomitant use of valproate, too high dose or too rapid dose increase
What is the patient advice surrounding lamotrigine?
- Don’t suddenly stop treatment as needs to be tapered off gradually
- Contact doctor immediately if any rash or signs of hypersensitivity
- Rare - be alert for symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, or infection.
What vitamin supplementation should you consider if a patient is on carbamazepine?
Vitamin D
Especially if immobilised for long periods, or who have inadequate sun exposure/dietary intake of calcium
What are the main side effects to look out for if a patient is on carbamazepine?
Blood or skin disorders
Antiepileptic hypersensitivity syndrome
Seek medical help if fever, rash, mouth ulcers etc occur
ALSO can cause hepatotoxicity so report signs of dark urine, nausea, vomiting
What is an important side effect to look out for with ethosuximide?
Blood disorders (fever, mouth ulcers, or bleeding develops)
What severe side effect is associated with fosphenytoin (used for status epilepticus)?
Associated with severe cardiovascular reactions- asystole, ventricular fibrillation. Observe patient for at least 30 minutes after infusion
What is the MHRA advice regarding gabapentin?
Risk of severe respiratory depression
What are the serious side effects of lamotrigine?
Skin reactions: these develop within 1-8 weeks. They include serious skin reactions i.e. Steven-
Johnson syndrome and toxic epidermal necrolysis
Blood disorders - Patients and their carers should be alert for symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, or infection
What antiepileptic is licensed for migraine prophylaxis?
Topiramate
What vitamin supplementation should you consider if a patient is on sodium valproate?
Consider vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
What types of toxicity is associated with sodium valproate?
Blood disorders
Hepatic failure
Pancreatitis
What is the safety alert associated with injectable phenytoin?
Risk of death and severe harm from error with the prescribing/preparation/administration
What vitamin supplementation should you consider if a patient is on phenytoin?
Consider vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
What are the symptoms of phenytoin toxicity?
Nystagmus (involuntary eye movement), diplopia (double vision), slurred speech, ataxia, confusion, and hyperglycaemia
What is nystagmus?
Involuntary eye movement
What is diplopia?
Double vision
What is the patient advice surrounding phenytoin?
Can cause agranulocytosis- Recognise signs of blood or skin disorders- report if mouth ulcer, bruising, bleeding develops
Antiepileptic sensitivity syndrome
What are specific side effects with topiramate? Hint - eyes
Acute myopia (near sightedness) with secondary angle-closure glaucoma Encephalopathic symptoms - sedation, confusion
Patients should report signs of raised intra-ocular pressure
What is primidone used for?
Essential tremor
Epilepsy
What are specific side effects of IV phenytoin?
Bradycardia
Hypotension
What is buspirone used for?
Acute anxiety
What is a risk with IV diazepam?
Venous thrombophlebitis
What is methylphenidate used for?
ADHD
How long should bipolar therapy be for?
For at least two years from the last manic episode and up to five years if the patient has risk factors for relapse.
Can lithium lower seizure threshold?
Yes
Long term use of lithium has been associated with what?
Thyroid disorders
Mild cognitive and memory impairment
What are the signs of lithium toxicity?
GI disturbances- vomiting and diarrhoea Visual disturbances, nystagmus (involuntary movement of the eyes) Polyuria - increased urination Tremor Restlessness CNS disturbances- confusion, drowsiness, lack of coordination Hypernatraemia Cardiac arrhythmias Renal failure Circulatory failure Increased thirst Memory impairment Coma
When should lithium samples be taken?
12 hours post dose
How often should serum lithium monitoring take place in the initial and continuous treatment phase?
Weekly initially
Weekly after every dose change
3 months thereafter
What should you test/measure before starting lithium treatment?
Cardiac- ECG - can prolong QT Renal function Thyroid function Blood count - can cause leukocytosis Body weight - dosing for Priadel is based on weight
Once initiated on lithium therapy, how often should you measure BMI, electrolytes, eGFR and thyroid function?
Every 6 months
What is lithium used for?
Treatment and prophylaxis of: Mania Bipolar disorder Recurrent depression Aggressive/self harming behaviour
What class of drug is first line in depression?
SSRI
In patients with a history of unstable angina or recent MI, what is the most appropriate antidepressant?
Sertraline
Are SSRIs or TCAs more sedating?
TCAs are more sedating
Also have more antimuscarinic and cardiotoxic side effects
How often should patients be reviewed at the start of antidepressant treatment?
Every 1-2 weeks
Antidepressant treatment should be continued for at least how many weeks before you consider switching?
How many weeks is this in the elderly?
4 weeks
6 weeks in the elderly as they may take longer to respond
Following first remission, how long should antidepressant treatment be continued for?
How long in the elderly?
At least 6 months
12 months in the elderly
Patients with recurrent depression should receive maintenance treatment for how long?
At least 2 years
How long should antidepressant treatment be continued for in generalised anxiety disorder?
At least 12 months as risk of relapse is high
What electrolyte imbalance is associated with antidepressants?
Which class of antidepressant is this the most common in?
Low sodium
SSRIs
Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.
True or false:
The use of antidepressants has been linked with suicidal thoughts and behaviour
True
What are the symptoms of serotonin syndrome?
Neuromuscular hyperactivity (such as tremor, hyperreflexia, clonus, myoclonus, rigidity), autonomic dysfunction (tachycardia, blood pressure changes, hyperthermia, diaphoresis, shivering, diarrhoea), and altered mental state (agitation, confusion, mania).
If a patient fails to respond to their first line SSRI treatment for depression, what would be the options?
Increasing the dose
Switching to a different SSRI or mirtazapine
Other 2nd line options:
Lofepramine (TCA), moclobemide (reversible MAOI), and reboxetine (NRI)
Management of acute anxiety involves the use of what drug class options?
Benzodiazepine or buspirone
For chronic anxiety, what is used?
Antidepressant - SSRI
If patient cannot tolerate SSRI, pregabalin can be considered
Benzodiazepine may be needed until the antidepressant starts to work
After how many weeks is anxiety classed as chronic?
4 weeks
Panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and phobic states such as social anxiety disorder are treated with what drug class?
SSRIs
What are the less sedating TCAs?
Imipramine hydrochloride, lofepramine, and nortriptyline.
If a patient is on an antidepressant and is going to be changed to an MAOI, what time period should they have stopped the previous antidepressant?
2 weeks
3 weeks if starting clomipramine or imipramine
What is the patient advice surrounding MAOIs?
Advised to only eat fresh foods and avoid “going off” or stale food (meat, fish)
Avoid alcohol
Avoid large amounts of tyramine-rich foods e.g. mature cheese - hypertensive reaction
MAOI interactions can persist for how long after discontinuing MAOI?
2 weeks
Can SSRIs cause QT prolongation?
Yes
What type of drug is duloxetine?
SNRI
What type of drug is venlafaxine?
SNRI
What type of drug is trazadone and what is it used for?
Serotonin uptake inhibitor
Depression particularly when sedation is required
What are SSRIs cautioned in?
Cardiac disease
Bleeding- especially GI
Epilepsy as they can cause seizures
Can mirtazapine cause QT prolongation?
Yes
What is the patient advice regarding mirtazapine?
Blood disorders- report fever, sore throat etc
Can TCAs cause QT prolongation?
Yes
Which antidepressant class is associated with a high rate of fatality?
TCAs
Cardiovascular and epileptogenic effects
Cautioned in those with a high risk of suicide- consider reduced supply on prescription so there are more regular reviews
What class of drug is dosulepin?
TCA
What are the symptoms of TCA overdose?
Hypotension Hypothermia Convulsions Respiratory failure Dilated pupils Urinary retention
What do you need to consider in terms of the dose in patients on oral antipsychotics that require a change to IM?
IM bypasses first pass metabolism so consider a lower dose than that of the oral
In schizophrenia, are antipsychotics more effective on the negative or positive symptoms?
More effective on the positive symptoms
What are the main side effects of antipsychotics?
- Extrapyramidal side effects - parkinsonism, dystonia, tardive dyskinesia
- Hyperprolactinaemia
- Sexual dysfunction
- Cardiovascular - QT prolongation, hypotension, arrhythmias
- Hyperglycaemia, diabetes
- Weight gain
- Hypo/hyperthermia
- Neuroleptic malignant syndrome
- Blood dyscrasias
- Photosensitisation
What is dystonia?
Abnormal face/body movements
Which antipsychotic is least likely to cause hyperprolactinaemia?
Ariprazole
Which antipsychotics are most likely to cause hyperprolactinaemia?
Risperidone, amisulpride, first generation antipsychotics
Which antipsychotics carry the highest risk of QT prolongation?
Haloperidol
Pimozide
Which antipsychotics commonly cause weight gain?
Clozapine
Olanzipine
Which antipsychotics commonly cause hyperglycaemia and diabetes?
Clozapine
Olanzipine
Risperidone
Quetiapine
Are first or second generation antipsychotics better at treating negative symptoms of schizophrenia?
Second generation
If extra-pyramidal side effects are a concern, should first or second generation antipsychotics be prescribed?
Second generation
Which antipsychotic is least likely to cause QT prolongation?
Aripriprazole
Are first or second generation antipsychotics more likely to cause insulin resistance and diabetes?
Second generation is more likely
Which antipsychotics are least likely to cause weight gain?
Ariprazole
Haloperidol
Amisulpride
Patients should receive an antipsychotic for how many weeks before it is deemed ineffective?
4-6 weeks
When should clozapine be used in schizophrenia?
When 2 or more antipsychotics have not worked
One of the antipsychotics tried must have been a second generation
All the tried antipsychotics must have been tried each for at least 6-8 weeks
True or false:
Clozapine patients must be registered with a clozapine patient monitoring service
True
What monitoring is required at the start of antipsychotic treatment?
Full blood count, urea and electrolytes, and liver function test monitoring
Blood lipids
Weight
Fasting blood glucose and blood pressure
ECG if history of cardiovascular risk factors present
What is the MHRA advice regarding clozapine?
Potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus
If constipation develops, seek immediate medical advice
What are the specific side effects with clozapine?
- Agranulocytosis
- Cardiomyopathy
- Intestinal obstruction
- Hypersalivation
How does clozapine interact with smoking?
Smoking breaks down clozapine so a higher dose may be needed
Is haloperidol a first or second generation antipsychotic?
First
Is olanzapine a first or second generation antipsychotic?
Second
Is clozapine a first or second generation antipsychotic?
Second
What is the important safety information associated with dopamine-receptor antagonists e.g. levodopa?
Impulse control disorders e.g. gambling, binge eating
What is the patient advice regarding co-benelodopa?
Sudden onset of sleep
Caution when driving/operating machinery
Madopar contains which drug?
Co-beneldopa
Sinemet contains which drug?
Co-careldopa
Stalevo contains which drug combination?
Levodopa, carbidopa, entacapone
What neurological condition is amantadine used in?
Parkinson’s Disease
What is apomorphine used for?
How do you manage the associated nausea and vomiting side effect?
Advanced Parkinson’s Disease - “off” episodes
To combat the associated nausea and vomiting side effects, you can use domperidone but only short term (due to QT prolongation risk with domperidone and apomorphine used together)
What is the important safety information regarding bromocriptine and cabergoline?
Associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions.
Impulse control disorders
What would be first line in the following condition:
A patient with Parkinson’s whose motor symptoms are decreasing their quality of life
Co-carelopda or co-benelopda
What would be first line in the following condition:
A patient with Parkinson’s whose motor symptoms are NOT affecting their quality of life
Could be prescribed a choice of levodopa, non-ergot-derived dopamine-receptor agonists (pramipexole, ropinirole or rotigotine) or monoamine-oxidase-B inhibitors (rasagiline or selegiline hydrochloride).
Levodopa is associated with what side effect?
Motor complications, including response fluctuations (on and off periods) and dyskinesias
Take at specific times of the day to avoid “off” periods
However, the overall motor improvement is more noticeable with levodopa
Patients who develop dyskinesia or motor fluctuations despite optimal levodopa therapy should be offered what?
A choice of non-ergotic dopamine-receptor agonists (pramipexole, ropinirole, rotigotine), monoamine oxidase B inhibitors (rasagiline or selegiline hydrochloride) or COMT inhibitors (entacapone or tolcapone) as an adjunct to levodopa
If these do not work, then bromocriptine/cabergoline/pergolide could be considered
If drug therapy is required for a Parkinson’s Disease patient who develops postural hypotension, what is considered as first line?
Midodrine
What is an advantage of domperidone over metoclopramide?
Less readily crosses the BBB so less likely to cause sedation and dystonic reactions
What is aprepitant used for?
Nausea and vomiting in chemotherapy
If vomiting during the first trimester of pregnancy is severe and requires drug therapy, what is used?
Short term antihistamine e.g. promethazine
What is Hyperemesis gravidarum?
Severe vomiting in pregnancy
In Hyperemesis gravidarum what vitamin supplementation should be considered?
Thiamine to reduce the risk of Wernicke’s
What is the MHRA warning associated with domperidone?
Risk of cardiac side effects
QT prolongation
Max treatment duration should not normally exceed 1 week
What is the MHRA warning associated with metoclopramide?
Risk of neurological side effects
Extrapyramidal disorders and tardive dyskinesia
Recommended that it should only be prescribed for up to 5 days
Especially in young adults <20 years
Can ondansetron cause QT prolongation?
Yes
What is the problem with enteric coated aspirin in acute pain?
Slow onset of action
What are the weak opioids?
Codeine
Dihydrocodeine
Meptazinol
At what body weight should IV paracetamol be adjusted and what dose should you use?
<50kg
15mg/kg
What are the side effects of opioid analgesics?
- Constipation
- Nausea
- Respiratory depression
- Drowsiness
- Dependence and withdrawal
- Overdose - pinpoint pupils, coma
What is the MHRA warning regarding codeine?
Restricted use in children due to reports of morphine toxicity
Codeine should only be used to relieve acute moderate pain in children older than 12 years and only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen alone.
A significant risk of serious and life-threatening adverse reactions has been identified in children with obstructive sleep apnoea who received codeine after tonsillectomy or adenoidectomy