Chapter 4: Nervous system Flashcards
Which of the acetylcholinesterase inhibitors is used for dementia is also licensed for mild/moderate dementia associated with Parkinsons?
Rivastigmine - This has TWICE daily dosing!
When should donepezil be given?
Once daily (Other drugs in class are BD)
Give at bedtime
What conditions are cholinergic drugs (acetylcholinerase inhibitors used in dementia) cautioned in?
Asthma
Epilepsy/history of seizures
Bradycardia
History of gastric ulcers
What are the common side effects of the Acetylcholinesterase inhibitors used in dementia?
Diarrhoea and vomiting, Dizziness, Headache, Hallucinations, Anorexia (weight loss)
Dogs Vomit Dogs Hate Hallucinating Alone
Name the 4 drugs used in dementia?
Donepezil Galantamine Rivastigmine (Acetylcholinesterase inhibitors)
Memantine (a NMDA receptor antagonist) for severe
Which acetylcholinesterase inhibitor comes as a patch?
Rivastigmine 24 hour patch
Short acting benzodiazepines?
Midazolam - Used for epileptic seizures (SE) and febrile convulsions due to its fast onset
what are the intermediate acting benzodiazepines
Clonazepam Lorazepam Oxazepam Temazepam
CLOT (Hence why some of these are used for agitation in our patients: As long-acting ones increase drowsiness)
What are the Long acting Benzodiazepines?
Chlordiazepoxide Diazepam Alprazolam
Used as sedatives (diazepam for insomnia associated with anxiety), chlordiazepoxide (alcohol withdrawal)
What is Buspirone?
A serotonin receptor agonist used for anxiety
Name some medication used in ADHD?
CNS Stimulants:
- Methylphenidate (Ritalin (IR), Concerta (SR), Medikinet, Equasym)
- Dexamfetamine Lisdexamfetamine (prodrug of dexamfetamine, Elvanse, Elvanse Adult)
Atomoxetine
Clonidine (specialist)
name 5 common side effects of CNS stimulants (lisdexamfetamine/methylphenidate)?
Aggression/Irritable: mood changes Addiction Growth deceleration - anorexia Insomnia (Take OM) Nausea/Vomiting/Diarrhoea Touretts/Tics
Tachycardia (methylphenidate)
When should antidepressants be avoided in bipolar?
In MANIC phase
Rapid cycling bipolar - recent history of hypomania (mild mania, marked by elation and hyperactivity) rapid mood fluctuations
Antidepressant exacerbates manic symptoms
What mood stabilisers do we see used in Bipolar disorder?
Carbamazepine
Valproate
Lithium
When should lithium be taken?
At night- blood test needs to be 12 hours post-dose and blood test usually in the morning
Lithium toxicity is made worse by sodium depletion, therefore what drugs should be avoided?
B2 agonists (salbutamol/terbutaline) Inhaled corticosteroids diuretic (loop - furosemide) (TLD - indapamide) NSAIDs (nephrotoxic too) PPIs Steroids SSRIs TCAs
Signs of lithium toxicity?
Within therapeutic range:
Nausea, vomiting, diarrhoea, weight gain, dehydration - polyuria, hypernatraemia
Severe:
Hand tremor, slurred speech, irritability, stupor (numbness), seizures, nephrotoxicity, arrhythmias, coma
(H I S, S N A C S)
Can lithium be used in pregnancy?
Teratogenic including cardiac abnormalities - avoid if possible
Especially in 1st trimester
In 2nd and 3rd trimester: dose may need to be increased but on delivery return abruptly to normal
What are the two different Lithium salts?
Lithium Carbonate: Camcolit, Priadel, Liskonium tablets
Lithium Citrate: Li-liquid, Priadel liquid (citrate only comes as a liquid)
Rx by brand
Why is it important to stick to the same brand of lithium?
Not all brands are bioequivalent. Brands are typically within 5% (95%-105%)
Changing the preparation would require the same precautions and monitoring as initiating treatment for the first time
In what patients are Dexamfetamine and Lisdexamfetamine cautioned
Tics & Tourettes
History of epilepsy
Mild hypertension
Susceptibility to angle closure glaucoma
May also cause growth restriction in children
Patients and carers should be advised to monitor for suicidal ideation when taking this ADHD drug
Atomoxetine
Which antipsychotic drug should be handled with care?
Chlorpromazine - Causes contact sensitisation (irritates skin)
Hyponatreamia has been linked to all antidepressants, but is more likely with which class?
SSRIs
What S/E has been linked to antidepressant use
Suicidal ideation (especially if hx of this)
Hyponatraemia
Prolong QT
Bleeding risk esp with NSAIDs/ACGs/Antiplatelets
Reduced seizure threshold
Serotonin syndrome is also a risk, particularly with MAOIs
How long after discontinuation of MAOIs can interactions still occur
Up to 2 weeks. That’s why a withdrawal period is required.
Moclobemide is short acting so does not require a withdrawal/washout period
What withdrawal period is required for fluoxetine
what about other SSRIs
5 weeks
Other SSRIs: Up to 2 weeks
Which SSRIs have the greatest risk of withdrawal syndrome
Paroxetine and Venlafaxine (SNRI) due to their shorter half lives
dose to be decreased gradually over at least 4 weeks
Bromocriptine, Cabergoline, and Pergolide are all stimulants of dopamine receptors in the brain, used in Parkinson’s. What are some specific safety warnings associated with these?
Impulse control disorders - gambling, shopping
Sudden onset of sleepiness: avoid driving
Hypotensive reactions during first few days of treatment
Which antiemetic is associated with a small increased risk of cardiac effects?
Domperidone
QTc prolongation Treatment should not exceed 1 week
Do not use in <12 years/<35kg as no evidence of effectiveness
What antiemetic is associated with an increased risk of neurological effects, such as tardive dyskinesia and EPSEs?
Metoclopramide: particularly in young adults (females aged 15-19) Should not be routinely given to patients under 18 years old
Only for short term use (up to 5 days)
Drug of choice for nausea associated with myocardial infarction. Can also be used in chemo/radio/postop induced n/v + hiccups,n/v in pall care
Avoid use in Parkinson’s + Epilepsy
When used for migraine: treatment should not exceed 3 months due to risk of tardive dyskinesia
Can Fentanyl be used in opioid naive patients
NO
Manufacturer advises use only in opioid tolerant patients due to risk of respiratory depression
What schedule is tramadol?
Schedule 3 CD No Reg
Exempt from safe custody
Prescription requirements and 28 day validity still stand
Which anti epileptic should patients be warned to look out for signs of fever, rash, mouth ulcers, bruising, bleeding?
Carbamazepine
Signs of blood, hepatic or skin disorders
do not use for absence or myoclonic seizures
What has IV infusion of Fosphenytoin been associated with?
Severe cardiovascular reactions
What severe skin reaction has Lamotrigine been associated with?
Stevens Johnson syndrome
This is where cell death/ necrosis occurs causing the epidermis to separate from the dermis. Usually begins with fever, ulcers, sore throat
Which antiepileptic do we need to be careful with in liver impairment?
Sodium valproate
Monitor LFTs
Which anti-epileptic is a TDM drug? What are the signs of toxicity?
Phenytoin
Signs: Nystagmus, blurred vision, ataxia, drowsiness, ECG changes, seizures, coma
Not B A D, Ecg Solves Coma
Which antieplieptic could be a problem in patients with glaucoma?
Topiramate
Associated with acute myopia (short sightedness with secondary angle closure glaucoma
SE: kidney stones
Which antiepileptic drug is associated with visual field defects?
Vigabatrin
visual = Vi
Which drug used to aid smoking cessation should be discontinued if the person becomes agitated, depressed or suicidal?
Varenicline
This is a selective nicotine receptor partial agonist
Which is stronger, methadone oral solution or linctus?
Oral solution (1mg/1ml) is 2.5 x stronger than the linctus!
Which antidepressants are safest in overdose?
SSRI’s
These should be considered FIRST LINE in treatment of depression.
Which antidepressant is safest to use in a patient with unstable angina/ had a recent Myocardial Infarction?
Sertraline (SSRI)
Why is St Johns Wort such a problematic drug?
Its an enzyme inducer
Antidepressants can cause hyponatreamia. What are the symptoms of this?
Confusion, Drowsiness, Convulsions
What does management (treatment) of anxiety usually involve?
A benzodiazepine (with opioids inc risk of CNS depression and with methadone risk for up to 2weeks after) or
Buspirone (if on CYP3A4 inhib reduce dose to 2.5mg BD) - contraindicated in epilepsy
Chronic anxiety
- antidepressant- usually an SSRI- usually escitalopram, paroxetine or sertraline
How do TCA’s work?
Block the reuptake of both noradrenaline and serotonin, although each to different extents.
Which TCA is frequently associated with hepatotoxicity?
Lofepramine
Which TCA should be initiated by a specialist?
Dosulepin
What are the irreversible and reversible MOAI
Phenelzine, Isocarboxazid, Tranylcypromine (irreversible inhibition)
Moclobemide (reversible inhibition)
For use on an emergency basis, the dose of an IM antipsychotic should be Lower or Higher than the corresponding oral dose?
Lower, due to absence of first pass metabolism with IM route
Are antipsychotics better at treating positive or negative symptoms?
Positive
Which antipsychotic can cause contact sensitisation so should be handled with care?
Chlorpromazine
tablets should NOT BE CRUSHED
Which antipsychotics may need their dose adjusting according to smoking status during therapy?
Clozapine, Haloperidol, Chlorpromazine and Olanzapine
What class of antipsychotics are hepatotoxic and can therefore precipitate coma?
Phenothiazines(Chlorpromazine, Promazine, Pipotiazine, Fluphenazine, Trifluoperazine, flupentixol)
What is the difference between haloperidol and haloperidol decanoate? Same with zuclopenthixol and zuclopentixol decanoate?
Decanoate is used for maintenance in schizophrenia only Should NOT be used for short term management of an acute episode e.g. zuclopentixol acetate used for this (rapid tranq.)
What side effect can antiparkinsons drugs cause in the elderly?
Confusion + drowsy (so increased risk of falls)
Which antimuscarinic, used for drug-induced parkinsons, should be taken with or after food?
Trihexyphenidyl hydrochloride
Which drug, used in parkinsons, can colour urine reddish-brown?
Entacapone
Which drug, used in parkinsons, should you avoid taking iron-containing products at the same time of day??
Entacapone, as it may form CHELATES WITH IRON, affecting its absorption
Which drug, used in parkinsons, should patients look out for signs of Hepatotoxicity (anorexia, nausea, vomiting, abdo pain, dark urine, pruritis)?
Tolcapone/entacapone (Red-brown urine)
A catechol-o-methyltransferase inhibitor (COMT-i)
What is the anti-emetic of choice in parkinsons?
Domperidone as it does not cross the BBB
Which anti-emetic is of value in the treatment of nausea and vomiting associated with cytotoxic use in cancers?
Ondansetron
What is the most effective drug used in motion sickness?
Hyoscine Hydrobromide
Promethazine also used if sedative effect needed
Domperidone, metoclopramide are ineffective! (do not give Domp to <12 years and meto <18 years)
What condition are a lot of antihistamines cautioned in?
Epilepsy, glaucoma
How should vomiting in pregnancy be managed?
Morning sickness- anti-emetic not routinely recommended- home remedies such as ginger.
1st trimester and mild - do not treat, lifestyle changes and avoid triggers/ pressure bands
If severe: short term antihistamine e.g. promethazine (metoclopramide/prochlorperazine alternative)
How is the pain from Mild Sickle-cell crisis managed? What if it is severe?
Just follow the pain ladder: Mild= paracetamol, NSAID, codeine
Severe= Morphine
A patient on warfarin requests a pack of aspirin 300mg OTC to treat a headache. What do you do?
Increased risk of bleeds when aspiring given with coumarins due to its anti-platelet effect.
What is the max strength of codeine that you can buy OTC?
12.8mg Present in Solpadeine Max and Panadol Ultra
What are the side effects of Morphine?
Constipation Nausea & Vomiting (most common) Drowsiness, Dizziness Headache Mild itching Agitation Insomnia
Morphine is the opioid of choice for severe pain in palliative care. How often is it given?
Given every 4 hours(or 12 or 24 hours if its MR)
How often should fentanyl transdermal patches be changed?
every 72 hours
Which analgesics have been associated with psychiatric reactions/ hallucinations?
Tramadol
Pentazocine (avoid this after a myocardial infarction)
Why are opioids cautioned in respiratory disease such as COPD and acute attacks of asthma
This is because of their potential to produce respiratory depression
Long term use of opioids can result in
Hypogonadism (sexual dysfunction)
Adrenal insufficiency
Hyperalgesia: abnormal pain sensitivity (develop tolerance)
What is the dose of codeine in adults per day?
30-60mg every 4 hours PRN
MAX DOSE: 240mg per day (8 tablets- same as paracetamol)
Codeine Max dose- adults
240mg per day (8 tablets- same as paracetamol)
How old do you have to be to purchase codeine OTC? What age must children be to have codeine prescribed?
18 or over to purchase
Only for use in children over 12. 12-18 years: max dose 240mg daily (same as adults) at intervals no less than 6 hours. Treatment should be limited to 3 days
The ability to metabolise codeine into morphine can vary greatly between individuals. Ultra rapid metabolisers are more susceptible to toxicity. What enzyme is involved?
CYP2D6
Why should codeine be avoided in breast feeding mothers?
Mothers vary in their capacity to metabolise codeine to morphine, risk of morphine overdose in the infant. This does not apply to dihydrocodeine
Why aren’t fentanyl transdermal patches suitable for patients requiring rapid titration of dose/ changing doses all the time?
Due to the long time to steady state (24-72 hours)
What may increase absorption of fentanyl patches?
Fever (hot skin) Exposure to external heat
Sevredol, MST continus and Oramorph are all brands of what?
Morphine
CD schedule is Morphine sulphate solution 2mg/ml?
CD Schedule 5 Inv POM
It is only when the level of morphine exceeds 13mg/ 5ml (2.6mg/ml) that the solution becomes CD Schedule 2
What can accumulation of pethidine metabolites (norpethidine) result in?
neurotoxicity
can lead to convulsions in overdose
what is the interaction with tramadol and alcohol
Alcohol can increase the nervous system side effects of tramadol such as dizziness, drowsiness, and difficulty concentrating.
What migraine medication is not licensed for use in the elderly??
The triptans
Remember Sumitriptan only licensed for 18y-65y OTC.
What are the triptans (used for migraines) contraindicated in?
Heart problems, previous MI or TIA, moderate severe Hypertension or mild uncontrolled Hypertension.
This is because one of the side effects is an increase in blood pressure (vasoconstrict)
What can cause sensations of tingling, heat, pressure, tightness in the body?
Triptans! Discontinue if intense
What is the max daily dose of sumatriptan bought OTC dose previously diagnosed migraine?
comes as 50mg tabs OTC: Max 2 daily (100mg)
What can we use to treat cluster headache?
Sumatriptan (given by SC injection) or Zolmitriptan
How many migraines must someone be having per month to qualify for prophylactic migraine treatment?
2
Prophylaxis of migraines consists of beta blockers- usually Propranolol
Can patients with epilepsy drive a large goods or passenger carrying vehicle?
No only motor vehicles however they can if they haven’t had a seizure for 5 years
What criteria must an epileptic meet if they want to drive their car?
- Seizure free for 1 year (those that have had their first seizure must not drive for 6 months after the event)
- If they only have seizures in their sleep: 3 year past of sleep attacks with no awake attacks
- No recent medication changes or withdrawal: if so 6 months must have elapsed
What risk does Topiramate carry in terms of harm to foetus?
Risk of Cleft palate (cleft lip)
Topira - palate
Mrs M has epilepsy but she is not any medication for it at the moment as she hasn’t had a seizure for two years and is now pregnant. Does she need to sign up to the Epilepsy Register?
Yes, whether on medication or not, she still needs to
What drug should be used to manage febrile convulsions?
Brief febrile convulsions (resulting from high temp/ fever) require no specific treatment, just anti-pyretic medication- paracetamol!!
What do patients and carers need to look out for in those taking carbamazepine and phenytoin?
Signs of blood, hepatic or skin disorders:
Fever Rash Ulcers Bruising and bleeding - Known as Leucopenia (low white cell count, but this is NOT the same as agranulocytosis)
Which anti epileptics could cause agranulocytosis?
Ethosuximide Look out for fever, mouth ulcers, bruising, bleeding Phenobarbital possibly?
Which antieplieptic has been associated with the serious skin rash, Steven Johnsons syndrome?
LamotrigineUsually in first 8 weeks of treatment
Which antieplieptic do you need to look out for symptoms of anaemia, bruising and infection?
Lamotrigine Suggestive of BONE MARROW failure/ blood disorder
Which anti-epileptic requires monitoring of ECG and BLOOD PRESSURE with intravenous use?
Phenytoin
What is the target plasma concentration of the TDM drug phenytoin?
10-20mg/L
What are the signs of phenytoin toxicity?
Nystagmus (uncontrolled eye movement) Diplopia (double vision) Slurred speech Ataxia (uncontrolled body movement) Confusion HYPERglyceamia
No Dude Seizures Are Crazy Hhigh
In what 3 circumstances should phenytoin treatment be discontinued?
Signs of toxicity (NDSACH - Nystagmus, dipolopia, slurred speech, ataxia, confusion, hypreglycaemia)
Rash
Hepatoxicity
Coarsened facial appearance, acne, weight loss, constipation, dizziness, mouth tenderness, headache, nausea All side effects of?
Phenytoin
What antieplieptic requires opthalmological monitoring/ discolouration of ocular tissue/ blue- grey discolouration of nails lips and skin?
Retigabine
Which anti-epileptic is particularly associated with hepatic dysfunction and what are the symptoms?
Sodium valproate
- Persistent vomiting, abdominal pain Anorexia, jaundice, oedema, malaise
Monitor liver function before therapy and during first 6 months of treatment!
- always check alcohol usage in patients as this increases the risk further
Which antieplieptic has been associated with pancreatitis?
Sodium valproate
Should we routinely monitor plasma valproate levels?
No Not a useful index of efficacy
- Should monitor liver function, before and first 6 months
Also measure FBC as blood disorders noted with valproate and check if patient is of child-bearing age
Which anti-epileptics can cause problems with vision??
Vigabatrin
Topiramate
Vision Topi!!
In terms of anxiety, what are benzodiazepines indicated for?
Short term relief of severe anxiety (2-4 weeks) - Not for mild anxiety!
Hypnotics should not be used for more than _____ for short term insomnia?
3 weeks
What hypnotics should be avoided in the elderly?
Benzodiazepines and Z drugs - the elderly are more at risk of becoming confused and falling and also becoming dependant
Which parkinsons medication may exacerbate oedema and therefore should be avoided in those with HEART FAILURE?
Amantadine
Which parkinsons medication may cause hair loss (alopecia) and hypersexuality as a side effect?
Selegiline (MAO-Bi) - Also gets converted to amphetamines so DRUGS AND DRIVING
What is the deal with migraine medication and hypertension?
Ergotamine and triptans (5HT1 agonists) cause vasoconstriction: contraindicated in severe/ uncontrolled hypertension = blood vessel damage/bleeding
When should SSRI’s be taken? What about TCA’s? What about Mirtazepine?
SSRI’s- take in the morning as they are mildly stimulating
TCA’s- take at night as can cause drowsiness
Mirtazepine (tetracyclic)- take at night as can cause drowsiness
At what strength does Oramorph solution turn from a Schedule 5 CD to a schedule 2?
Strengths exceeding 13mg/ 5ml
Zonisamide is an anti-epileptic drug. What should patients be told to avoid when on this medication?
Avoid OVERHEATING (hyperthermia) and ensure they are adequately hydrated during exercise, especially in children, as fatal cases of HEAT STROKE have been reported in children on this medication.
Which anti-epileptic is cautioned in patients with a LOW BODY WEIGHT?
Zonisamide - Monitor weight throughout treatment as fatal cases of weight loss reported in children.
Which anti-epileptic do we need to monitor plasma bicarbonate levels due to risk of metabolic acidosis?
Zonisamide Metabolic acidosis is an increase in plasma acidity
What should patients on Bromocriptine for parkinsons be advised with regards to OTC drugs?
Important to warn patients not to take OTC sympathomimetics when taking bromocriptine, such as pseudoephedrine, as this could lead to severe peripheral vasoconstriction, ventricular tachycardia and seizures and therefore may be fatal.
Why do parkinsons drugs come as combination preparations e.g. Co-careldopa, Co-benedlopa
PD= decrease in dopamine in the brain so the brain cannot control movement
Dopamine itself is not lipophilic enough to cross the BBB. So we give a dopamine pre-cursor: Levodopa. This is very lipophilic which helps DA cross the BBB. But the problem is it also gets everywhere in the periphery and causes EPSE’s.
So we give it in combo with a periphery-specific dopamine decarboxylase inhibitor in these combo preps, so that it doesn’t get converted to its active form in the periphery.
What are the common SEs of pregabalin (used for neuropathic pain)?
Appetite changes
Blurred vision
Disturbance in muscle control/ movement
Early treatment with____ can delay the need for levodopa therapy in Parkinsons
Selegiline
Which parkinsons drug is used at a dose of 1mg daily?
Rasagaline
Prochlorperazine belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. What is their M of A?
Act centrally by blocking the chemoreceptor trigger zone
phenothiazine are a class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo and also migraines. Can you name any drugs in this class?
Piperazines, Prochlorpromazine, Fluphenazine, Trifluoperazine, chlorpromazine, promazine, triflupromazine
Which antidepressant drug is associated with weight gain?!
MIRTAZEPINE(Tetracyclic)
Which opioid can cause convulsions in overdose?
Pethidine due to accumulation of its metabolite norpethidine
and tramadol
What is methylphenidates mechanism of action?
N-Methyl-D-Aspartate (NMDA) antagonist (hence the methyl!) it has a neuro-protective effect
Which Benzo is indicated before dental surgery?
TemazepamTake 30-60 mins beforeAlso indicated for insomnia- take 30-60 mins before bed time Has a medium duration of action so good for these two things
Which antidepressant class do we need to do LFT’s before starting?
TCAsThis is because you need to avoid them in severe liver disease as they can cause increased sedative effects (they cause drowsiness as it is)
Surely CNS stimulants Indicated for ADHD would make it worse?
Stimulants increase dopamine and norepinephrine in the brain, and increase blood flow to the brain. This stimulates the child… A child with ADHD has something called “self-stimulation” where they are constantly stimulated and never switch off. Giving drugs that cause stimulation kind of distracts them from this self-stimulation, so it actually calms them down and they just have a normal level of stimulation, as soon as their mind focuses on something else their self-stimulation goes away
What conditions are stimulants (methylphenidate, lisdexamfetamine, atomoxetine etc) used in ADHD cautioned in?
Heart conditions This is because they can cause tachycardia (fast heart beat)
Which CNS stimulant is licensed for use in Narcolepsy?
DexamfetamineCan also use methylphenidate but this is unlicensed use
When starting carbamazepine, what ethnicity of people require testing for the HLA-B*1502 allele and therefore may be more at risk of Stevens Johnson Syndrome?
Thaiand Han Chinesepeople of chinese ethnicity are most at risk of genetic polymorphisms of the CYP2D6 enzyme
What kind of drugs should be minimised in patients with cognitive impairment, such as dementia?
Antimuscarinicse.g. amitriptyline, paroxetine, solifenacin, antipsychoticsCan 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:
Donepezil
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-JohnsonStop 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 drugsThe symptoms usually start between 1 and 8 weeks of exposure; fever, rash, and lymphadenopathy (enlarged lymph nodes) 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 or 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)?
ClobazamClonazepam
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/fosphenytoinIf 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 - folic acid 5mg OD
Pregnant patients who are taking what antiepileptics should have fetal growth monitoring?
Topiramate or levetiracetam
What conditions can lamotrigine exacerbate?
Parkinson’s DiseaseMyoclonic 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 syndromeSeek medical help if fever, rash, mouth ulcers etc occurALSO 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 (short 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)
Renal - Polyuria - increased urination + thirst, AKI, renal failure (esp due to dehydration - ensure fluid intake)
CNS disturbances- confusion, drowsiness, lack of coordination, memory imp, restless, tremor
Hypernatraemia
Cardiac arrhythmias
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