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, irritability, slurred speech, stupor (numbness), nephrotoxicity, arrhythmias, coma, seizures
(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?
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.
not for children with obstructive sleep apnoea after tonsilitis
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
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 sodiumSSRIsHyponatraemia 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 doseSwitching to a different SSRI or mirtazapineOther 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 inhibitorDepression particularly when sedation is required
What are SSRIs cautioned in?
Cardiac diseaseBleeding- 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?
TCAsCardiovascular 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?
HypotensionHypothermiaConvulsionsRespiratory failureDilated pupilsUrinary 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?
NAME?
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?
HaloperidolPimozide
Which antipsychotics commonly cause weight gain?
ClozapineOlanzipine
Which antipsychotics commonly cause hyperglycaemia and diabetes?
ClozapineOlanzipineRisperidoneQuetiapine
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?
AriprazoleHaloperidolAmisulpride
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 monitoringBlood lipidsWeight Fasting blood glucose and blood pressureECG if history of cardiovascular risk factors present
What is the MHRA advice regarding clozapine?
Potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileusIf constipation develops, seek immediate medical advice
What are the specific side effects with clozapine?
NAME?
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” episodesTo 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 dyskinesiasTake 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 levodopaIf 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 Drowsiness Urinary retention Resp depression Addiction/abuse
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
What is a potential side effect of IV fentanyl?
Muscle rigidity (may involve thoracic muscles)
Why should you monitor patients using fentanyl patches if they have a fever?
Increased absorption of drug
Why mustn’t you expose fentanyl patches to heat e.g. baths and saunas?
May increase absorption
True or false:Pethidine has multiple strengths in tablet form
False- only has 50mg strength so do not legally need to state the strength on the prescription
What is the difference between oxynorm and oxycontin?
Oxynorm- immediate release oxycodone
Oxycontin- modified release oxycodone
What is the difference between Shortec and Longtec
Shortec- immediate release oxycodone
Longtec- modified release oxycodone
True or false: For migraine relief, if a patient does not respond to one 5HT1-receptor agonist, an alternative 5HT1-receptor agonist should be tried.
TRUE
In what situations would you consider migraine prophylaxis?
- suffer at least two attacks a month;
- suffer an increasing frequency of headaches;-
suffer significant disability despite suitable treatment for migraine attacks;
- cannot take suitable treatment for migraine attacks
What is the most commonly used beta blocker for migraine prophylaxis?
Propranolol
A self adhesive capsaicin patch 8% is licensed in what?
Treatment of peripheral neuropathic pain in non-diabetic patients
Capsaicin cream 0.075% is licensed in what?
Post herpetic neuralgia
Painful diabetic neuropathy
Osteoarthritis
Is withdrawal is more common with the short or long acting benzodiazepines?
Short acting
Is diazepam short or long acting?
Long acting - good for if insomnia is associated with daytime anxiety
Is lorazepam short or long acting?
Short acting - little or no hangover effect
What kind of effect can happen as a result of taking benzodiazepines?
Paradoxical effects
A paradoxical increase in hostility and aggression may be reported by patients taking benzodiazepines
Why are benzodiazepines cautioned in hepatic impairment?If they are needed, are short or long acting ones recommended?
Can precipitate coma
Short acting (However, in alcohol withdrawal, a long acting e.g. chordiazepoxide or diazepam is used via fixed dosed regimen)
For patients on opioid maintenance therapy, what should happen if they miss:1) 3 or more days 2) 5 or more days
1) In community pharmacy, refer back to the prescriber. They should consider reducing the dose
2) An assessment of illicit drug use is also recommended before restarting substitution therapy
For opioid addiction, what can be used for opioid maintenance therapy?
Buprenorphine or methadone
Is buprenorphine or methadone more sedating?
Methadone
For this reason, buprenorphine may be more suitable for employed patients or those who drive, and is also safer to use if prescribed other sedating drugs
However, those who experience increased anxiety during opioid withdrawal may prefer methadone
What is first line for alcohol dependence? What would be an alternative?
Acamprosate or naltrexone in combination with a psychological intervention
Alternative- disulfiram if the others are not suitable or if the patient wants this but understands the associated risks
What should be given to alcohol dependent patients who are at risk of Wernicke’s encephalopathy?
Thiamine
What is the patient advice regarding disulfiram?
Should be counselled on the disulfiram-alcohol reaction—reactions may occur following exposure to small amounts of alcohol found in perfume, aerosol sprays, or low alcohol and “non-alcohol” beers and wines; symptoms may be severe and life-threatening and can include nausea, flushing, palpitations, arrhythmias, hypotension, respiratory depression, and coma.
Patients and their carers should be counselled on the signs of hepatotoxicity—patients should discontinue treatment and seek immediate medical attention if they feel unwell or symptoms such as fever or jaundice develop.
What is varenicline used for?
Smoking cessation Brand name= Champix
What is the MHRA advice regarding varenicline?
Suicidal behaviour
Patients are advised to discontinue treatment and seek prompt medical advice if they develop agitation, depressed mood, or suicidal thoughts. Patients with a history of psychiatric illness should be monitored closely while taking varenicline.
What monitoring does clozapine require?
Monitor leucocyte and differential blood counts.
Clozapine requires differential white blood cell monitoring weekly for 18 weeks, then fortnightly for up to one year, and then monthly as part of the clozapine patient monitoring service
Blood lipids and weight at baseline
FASTING blood glucose baseline
Baseline prolactin
If it does need diluting, IV phenytoin should be administered in what fluid via what and why?
Sodium chloride Via large vein, in line phenytoin filter is needed as it precipitates easily
When should lithium be stopped before major surgery?
24 hours
Ethosuximide is used for what type of seizures?
Absence Myoclonic
Hair loss with regrowth of curly hair is a rare effect of which drug?ValproatePhenytoinCarbamazepineLamotrigine
Valproate
Taking trimethoprim with phenytoin primarily increases the risk of what?HyperkalaemiaMegaloblastic anaemiaBleedingLow sodium
Megaloblastic anaemia
Trimethoprim inhibits folate synthesis
Phenytoin increases folate metabolism
(Same with trimethoprim and methotrexate)
Purple glove syndrome is a rare side effect of which epilepsy drug?
Phenytoin
What is the ideal level range for lithium?For acute episodes of mania, what would the target level range be?
- 4–1 mmol/litre -lower end for elderly and for maintenance therapy
- 8–1 mmol/litre is recommended for acute episodes of mania
What is the risk of abrupt lithium withdrawal?How should it be withdrawn?
Increases the risk of relapse
The dose should be reduced gradually over a period of at least 4 weeks (preferably over a period of up to 3 months).
What is the patient advice regarding diet and fluid intake if on lithium therapy?
Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake.
How does lithium interact with ACEis?
Risk of lithium toxicity
Excretion of lithum reduced by ACEi
How does lithium interact with NSAIDs?
Risk of lithium toxicity
Excretion of lithium probably reduced by NSAIDs
How does lithium interact with loop and thiazide diuretics?
Excretion of lithium reduced by
Loop and Thiazide – Sodium depletion
How does lithium interact with amiodarone?
Risk of ventricular arrhythmias
What is the desired total serum concentration for phenytoin?What can be a disadvantage of measuring total concentration?
10-20mg/L
However, need to be careful as there are certain conditions where protein binding may be reduced e.g. elderly There is also reduced protein binding in the first 3 months of life It may be more appropriate to measure free plasma phenytoin concentration
Are preparations containing phenytoin sodium and phenytoin base bioequivalent?
No 100mg phenytoin base = 92mg phenytoin sodium
Why is it important to maintain good oral hygiene if taking phenytoin?
Can cause gingival hyperplasia
How does phenytoin interact with NSAIDs?
Effect of phenytoin enhanced by NSAIDs
How does phenytoin interact with amiodarone?
Amiodarone inhibits metabolism of phenytoin
How does phenytoin interact with warfarin?
Phenytoin accelerates metabolism of warfarin
How does phenytoin interact with cimetidine?
Cimetidine inhibits the metabolism of phenytoin
How does phenytoin interact with fluoxetine?
Phenytoin concentration increased by fluoxetine
How does phenytoin interact with St John’s Wort?
St. Johns Wort (an enzyme inducer) reduces plasma conc. of phenytoin
Is lithium use associated with hyper or hypothyroidism?
Hypothyroidism
Which of these side effects is not associated with lithium? Hyperthyroidism Tremors Increased urination/thirst Leukocytosis
Hyperthyroidism - Associated with hypothyroidism
Which of these side effects is not associated with phenytoin? Skin coarsening Gum hypertrophy Hair loss Osteomalacia
Hair lossAssociated with substantial hair growth (hypertrichosis)
Has diazepam got a short or long half life?
Long half life
Sinemet absorption is reduced when taken with foods high in what nutrient?
Protein
Fat
Carbohydrates
Protein as it competes with levodopa for absorption
Are typical antipsychotics first or second generation antipsychotics?
First generation
Are atypical antipsychotics first or second generation antipsychotics?
Second generation
What antibiotic class can result in carbamazepine toxicity?
Macrolides
What antidepressant can be used for smoking cessation?
Bupropion - can cause seizures
Carbamazepine commonly causes what electrolyte imbalance?
Hyponatraemia
True or false:Phenytoin is not known to cause skin pigmentation
False
Causes yellow-brown pigmentation
What is the advice surrounding antipsychotics and sunlight?
As photosensitisation may occur with higher dosages, patients should avoid direct sunlight.
What is the general advice regarding monitoring patients on antipsychotics?
ECG may be required before treatment
Monitor prolactin concentration at the start of therapy, at 6 months, and then yearly.
Patients with schizophrenia should have physical health monitoring (including cardiovascular disease risk assessment) at least once per year.
What is the advice regarding treatment cessation of antipsychotic drugs?
There is a high risk of relapse if medication is stopped after 1–2 years.
Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
Patients should be monitored for 2 years after withdrawal of antipsychotic medication for signs and symptoms of relapse.
What is the NICE 2017 guidance surrounding choice of Donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease?
The three acetylcholinesterase (AChE) inhibitors donepezil, galantamine, and rivastigmine as monotherapies are recommended as options for managing mild to moderate Alzheimer’s diseaseIf prescribing an AChE inhibitor (donepezil, galantamine, or rivastigmine), treatment should normally be started with the drug with the lowest acquisition cost (taking into account required daily dose and the price per dose once shared care has started). However, an alternative AChE inhibitor could be prescribed if it is considered appropriate
What is ergotamine used for?In what patient groups would this not be appropriate for?
Cluster headaches - unlincensedcoronary heart disease; hyperthyroidism; inadequately controlled hypertension; obliterative vascular disease; peripheral vascular disease; Raynaud’s syndrome; sepsis; severe hypertension; temporal arteritis
What are the contraindications for benzodiazepines?
Acute pulmonary insufficiency; marked neuromuscular respiratory weakness; sleep apnoea syndrome; unstable myasthenia gravis
Selegiline is what type of drug?
Monoamine oxidase B inhibitor
What is used as adjunct to co-beneldopa or co-careldopa to reduce ‘end of dose’ deterioration?
Selegiline - can be used alone
Enatcapone - colours urine red brown
Tolcapone - hepatotoxic
What parkinsons disease drug colours your urine reddish brown?
Entacapone
What Parkinson’s Disease medicine can exacerbate oedema and cautioned in congestive heart failure?,
Amantadine
Hair loss is a common side effect of what Parkinsons Medicine?
Selegiline
How do you manage status epilepticus?
- IV lorazepam if seizure has lasted more than 5 minutes - Must have resuscitation facilities available (if not, use rectal diazepam or buccal midazolam although absorption is slower)
- Can administer lorazepam again after 10 mins if no response
- If after 25 minutes after onset and no response, give phenytoin (slow IV)/fosphenytoin (can be given more rapidly) /phenobarbital
- If after 45 minutes after onset and no response, sedate patient
Treatment with domperidone should not exceed how many days?
7 days
Treatment with metoclopramide should not exceed how many days?
5 days
A withdrawal regimen after stabilisation with methadone hydrochloride or buprenorphine should be attempted only after careful consideration. How long does complete opioid withdrawal usually take in:i) an inpatient settingii) community setting
Inpatient setting is usually 4 weeks
Community setting is usually 12 weeks
If a patient is on an opioid withdrawal regime but starts to use illicit drugs again, what should happen?
The withdrawal regimen should be stopped and maintenance therapy should be resumed at the optimal dose.
Following successful opioid withdrawal treatment in the management of addiction, how long should the patient be followed up for?
6 months at least
True or false:For opioid addiction replacement therapy, buprenorphine has to be given every day
False
Can be given on alternate days in higher doses
Does buprenorphine or methadone require a shorter drug-free period (before naltrexone is needed for relapse prevention)?
Buprenorphine
Which carries a higher risk of overdose during opioid replacement therapy:MethadoneBuprenoprhine
Methadone Has more severe withdrawal symptoms
Which of the following can you titrate faster:MethadoneBuprenoprhine
Buprenoprhine - can titrate within 1 week
Methadone can take several weeks
After how many hours of heroin use can you administer: Methadone Buprenoprhine
Why does there need to be a gap?
At least 8 hours after for methadone
6-12 hours after for Buprenoprhine
This is to reduce the risk of precipitated withdrawal
What is the recommendation of opioid withdrawal in pregnancy during:i) 1st trimesterii) 2nd trimesteriii) 3rd trimester
1st trimester- avoid as increased risk of spontaneous miscarriage
2nd trimester - can do withdrawal however needs to be slow (dose reduction every 3-5 days)
3rd trimester - avoid as increased risk of stillbirth and foetal distress
What is the only trimester that you can do opioid withdrawal therapy?
2nd
If a patient on methadone becomes pregnant, should they stop the methadone?
No
Therapy should be continued
Drug metabolism can be increased in the third trimester; it may be necessary to either increase the dose of methadone hydrochloride or change to twice-daily consumption (or a combination of both strategies) to prevent withdrawal symptoms from developing.
What do you need to consider in the third trimester in terms of methadone and drug metabolism?
Drug metabolism can be increased in the third trimester; it may be necessary to either increase the dose of methadone hydrochloride or change to twice-daily consumption (or a combination of both strategies) to prevent withdrawal symptoms from developing.
What is the advice regarding opioid substitution during breastfeeding?What red flag symptoms should you look out for?
Doses of methadone and buprenorphine should be kept as low as possible in breast-feeding mothers.
Increased sleepiness, breathing difficulties, or limpness in breast-fed babies of mothers taking opioid substitutes should be reported urgently to a healthcare professional
What is lofexidine used for?
Management of symptoms of opioid withdrawal
Can be prescribed as an adjuvant to opioid substitution therapy
Smokers who wish to stop smoking should be referred to where?
Their local NHS Stop smoking services
What are the most effective drug treatments for smoking cessation?
Varenicline
or
Combination of long acting NRT (patch 16/24h) - give 24hrs if gets craving in the am AND short acting NRT (gum, lozenge etc)
How long are nicotine patches generally applied for?In what group of patients would this be longer?
16 hours a day, patch removed overnight
24 hours a day if the patient experiences strong nicotine cravings upon waking
Can varenicline be used alongside NRT?
No
Can varenicline be used alongside bupropion for smoking cessation?
No
For smoking cessation, how much treatment should be prescribed for the patient?
2 weeks with an assessment just before their supply finishes
Can e-cigarettes be supplied by smoking cessation services?
No
When should NRT be used in smoking pregnant patients?
Only if non-drug treatment options have failed
What drugs do cigarettes interact with and require higher doses as metabolism is increased?
Theophylline
ClozapineOlanzapine - 2nd gen antipsychotics
HaloperidolChlorpromazine - 1st gen antipsychotics
Ropinirole
Cinacalcet - used in hyperparathyroidism
What are the side effects of nicotine containing preparations?
Local irritation GI disturbances Dry mouth if spray, lozenge Palpitations - rarely with patches and oral spray Hot flushes
Abnormal dreams can occur with which NRT preparation?
Patch- this is reduced if removed before bed
Where should you apply an NRT patch?Do you have to rotate sites of application?
Trunk, upper arm, hip
Yes- Avoid using the same site for several days
How long before the target smoking quit date should varenicline and bupropion be started?
7-14 days before
Are e-cigs licensed is smoking cessation?
No - aways recommend a licensed treatment if asked e.g. NRT patch
A CO level of what suggests the person has stopped smoking or is a non-smoker?
10 ppm or less
How long after starting varenicline or bupropion should the person be followed up?How does this compare with NRT?
3-4 weeks
2 weeks for NRT
How many weeks is a course of varenicline?
12 weeks
Capsaicin 0.025% cream is licensed for what?
Symptomatic relief in osteoarthritis
Using antipsychotics and what drug for dementia can increase the risk of neuroleptic malignant syndrome?
Donepezil
What Acetylcholinerase inhibitor is licensed for dementia in Parkinson’s Disease (Lewy body)?
Rivastigmine
For rivastigmine patches, you should avoid using the same area on the body for how many days?
14 days
What are the side effects of cholinergic drugs? (DUMB BELS)
Diarrhoea Urination Muscle weakness/cramps Bronchospasm Bradycardia Emesis Lacrimation (teary eyes) Salivation/sweating
Does lamotrigine have a short or long half life?
Long, allows for OD dosing
Does phenytoin have a short or long half life?
Long, allows for OD dosing
Does phenobarbital have a short or long half life?
Long, allows for OD dosing
Does levetiracetam need to be prescribed by brand?
No - Category 3
Does lamotrigine need to be prescribed by brand?
Based on clinical judgement - Category 2
Does valproate need to be prescribed by brand?
Based on clinical judgement - Category 2
Does ethosuximide need to be prescribed by brand?
No- Category 3
Does topimarate need to be prescribed by brand?
Based on clinical judgement - Category 2
With antiepileptic carries the risk of cleft palate following exposure in the first trimester?
Topiramate
What antiepileptics are present in high amounts in breast milk? (ZELP)
ZonisamideEthosuximideLamotriginePrimidone
What antiepileptics accumulate in breast feeding children due to a slower metabolism?
Phenobarbital Lamotrigine
What antiepileptics inhibit sucking reflex in breast feeding?
Phenobarbital Primidone
What antiepileptics have an established risk of drowsiness in babies?
BenzodiazepinesPhenobarbital Primidone
What antiepileptics carry a high risk of withdrawal symptoms?
Phenobarbital Primidone
What antiepileptics are mainly associated with antiepileptic hypersensivitiy syndrome?(CP3L)
Carbamazepine Phenytoin Phenobarbital Primidone Lamotrigine
In first 8 weeks of starting discontinue immediately
What antiepileptics can cause blood dyscrasias?
Carbamazepine Valproate Ethosuximide Topiramate Phenytoin LamotrigineZ onisamide
What are the signs of phenytoin toxicity? (SNACHD)
Slurredspeech Nystagmus Ataxia Confusion Hyperglycaemia Diplopia
What pre-treatment screening is needed in Chinese and Thai patients when starting phenytoin and carbamazepine- why?
HLB-B*1502 allele - have an increased risk of Steven-Johnson syndrome
True or false:Phenytoin inhibits Vitamin D metabolism
False
It induces Vitamin D metabolism- consider supplementation in immobilised patients/inadequate sun exposure or dietary intake of calcium
Why is phenytoin cautioned in hepatic impairment?
Decreased protein binding so increased risk of toxicity
How does phenytoin and levothyroxine interact?
Phenytoin= enzyme inducer so reduces drug concentration
Increased risk of hypothyroidism
What are the symptoms of carbamazepine toxicity (I HANDBAG)?
In co-cordinationHyponatraemiaAtaxiaNystagmusDrowsinessBlurred vision, diplopiaArrhythmiasGI disturbances
If a whole pack of sodium valproate cannot be dispensed, what must be put on the part pack?
Warning sticker
If a patient on sodium valproate is experiencing nausea, vomiting, abo pain, what should you do?
Refer Could be hepatotoxicity or pancreatitis
What groups of patients are short acting benzodiazepines more suitable for?
Short acting
What is a disadvantage of short acting benzodiazepines?
ElderlyHepatic impairment (however in acute alcoholic withdrawal a longer benzodiazepine is used)
Withdrawal symptoms can occur without how much time of stopping a short acting benzodiazepine?
Carries greater risk of withdrawal symptoms
Withdrawal symptoms can occur without how much time of stopping a long acting benzodiazepine?
Within 1 day
How would you reduce someone’s diazepam dose if on long term therapy to prevent withdrawal?If on high doses, how is this done?
Within 3 weeks
What schedule is methylphenidate (Concerta)?
Reduce diazepam dose, usually by 1–2 mg every 2– 4 weeksFor high doses- reduce by up to one tenth every 1-2 weeks
What are the side effects of methylphenidate and dexamfetamine?
CD2
What is dexamfetamine used for?
- Appetite loss, insomnia, weight loss- Increased HR and BP - Tics, Tourette’s- Growth restriction in children- monitor height and weight, allow drug free periods to grow - Psychiatric disordersMonitor the above after a dose change and then every 6 months
How would you treat an acute episode of mania?
Narcolepsy Refractory ADHD
What can you use for prophylaxis of bipolar disorder?
BenzodiazepinesAntipsychotics- quetiapine, olanzapine, risperidone Lithium or valproic acid can be added if inadequate response
What should you not give in patients with bipolar?
Lithium salts Sodium valproate / valproic acid Olanzapine
What are the signs of lithium toxicity? (REVNG)
Antidepressants
If a patient has persistent headaches and on lithium, what should you do?
Renal disturbancesExtrapyramidal symptomsVisual disturbancesNervous system disturbancesGI side effects
A deficiency in what electrolyte can lead to lithium toxicity?
ReferLithium can cause benign intracranial hypertension
What is the only antidepressant licensed in children?
Fluoxetine
Can SSRIs lower seizure threshold?
Fluoxetine
Can TCAs cause seizures?
Yes
What is the interaction between TCAs and antihypertensives?
Yes
Is moclobemide a reversible or irreversible MAOI?
Increased risk of hypotension
With what MAOIs are hepatotoxicty more likely?
Reversible - no washout period needed as it is short acting
What is the advice surrounding clozapine and missed doses?
Phenelzine Isocarboxazid
Sexual dysfunction is most common with what antipsychotics?
If 2 or more doses missed, then need to re-titrate dose
Can antipsychotics interfere with your temperature regulation?
Haloperidol and risperidone
Can antipsychotics cause neuroleptic malignant syndrome?
Yes
What are the advantages of using peripheral dopa-decarboxylase inhibitors for Parkinson’s?
Yes
What class of drug is pramipexole?
Lower dose needed for therapeutic effectFewer side effects - nausea, vomiting, cardiovascular events
What class of drug is ropinerole?
Non ergot derived dopamine agonist
What class of drug is rotigotine?
Non ergot derived dopamine agonist
What are the side effects of ergot derived dopamine agonists?
Non ergot derived dopamine agonist
Is COMT inhibitor monotherapy licensed in Parkinson’s?
Fibrotic reactionsPulmonary- look out for SOB, coughRetroperitoneal - look out for abdominal pain and tendernessPericardial- look out for cardiac failure
What kind of toxicity is caused by tolcapone?
No Used as an adjunct to levodopa
What is the antisickness choice of drug in Parkinson’s?
Hepatotoxicty Look out for vomiting, dark urine, abdominal pain
What two electrolyte imbalances should be corrected before using 5HT3 antagonists e.g. ondansetron?
Domperidone
True or false:Naloxone only partially reverses the effects of buprenorphine
Hypokalaemia and hypomagnesaemia
In what situations is it advised for patients to immediately remove a fentanyl patch?
TRUE
Can tramadol lower the seizure threshold?
Breathing difficultiesDrowsiness, impaired speechSigns of opioid toxicity
True or false:You can take two doses of sumatriptan for the same attack 2 hours later?
Yes
How would you treat trigeminal neuralgia (facial pain with electric shocks in the jaw)?
True but symptoms must have been improved after taking the first tablet
Transient insomnia is caused by what?
Carbamazepine or phenytoin
Is zopiclone a long or short acting hypnotic?
Shift workJet lag
For short term insomnia, hypnotics should not be used for longer than what?
Short acting
Can methadone cause QT prolongation?
3 weeks maxIdeally 1 week
For short term relief of anxiety, hypnotics should not be used for longer than what?
Yes
What are the signs of benzodiazepine withdrawal?
2-4 weeks
During benzodiazepine withdrawal, what 3 classes of drugs should be avoided if possible (in the case of additional therapy to help with withdrawal symptoms)?
It is characterised by insomnia, anxiety, loss of appetite and of body-weight, tremor, perspiration, tinnitus, and perceptual disturbances
In terms of insomnia, in what cases are short acting hypnotics preferred?
Beta blockersAntidepressantsAntipsychotics
In terms of insomnia, in what cases are long acting hypnotics preferred?
Sleep onset insomniaWhere sedation the following day is not desirableElderly Short term insomnia
How should transient insomnia be managed?
Poor sleep maintenance e.g. early morning awakening that causes daytime effectsIf an anxiolytic effect is needed during the day Diazepam
How can chronic insomnia be managed?What are the common causes of chronic insomnia?
Usually self-limiting and short term e.g. jet lagIf a hypnotic is indicated one that is rapidly eliminated should be chosen, and only one or two doses should be given
What is the risk of long term benziodiazepine therapy in the management of insomnia?
Rarely benefited by hypnotics and is sometimes due to mild dependence caused by injudicious prescribing of hypnoticsThe underlying psychiatric complaint should be treated, adapting the drug regimen to alleviate insomnia.Anxiety, depression, and abuse of drugs and alcohol are common causes
Is withdrawal more common with short or long acting benzodiazepines?
Can cause rebound insomnia and a withdrawal syndrome.
Is temazepam long or short acting?
Short acting
What would be an appropriate benzodiazepine for someone suffering from insomnia with daytime anxiety?
Short acting
What role do beta blockers play in anxiety?
Diazepam - long actingSingle dose at night
True or false:A benzodiazepine may be used as short-term adjunctive therapy at the start of antidepressant treatment to prevent the initial worsening of symptoms.
Can help with the autonomic physical symptoms e.g. tremor and palpitationsThey do not reduce non-autonomic symptoms, such as muscle tensionThey do not help with psychological symptoms
What is 1st line for mild depression if a patient is presenting for the first time?
TRUE
What class of drug is mirtazapine?
Psychological therapy should be considered initiallyIf history of moderate or severe depression, consider antidepressant therapy
Venlafaxine is generally reserved for what type of depression?
TETRAcycline antidepressant
What is classed as chronic anxiety?
More severe
Is generalised anxiety disorder a form of acute or chronic anxiety?
> 4 weeks duration
What class of drug is duloxetine?
Chronic
If changing from fluoxetine to MAOI, what is the period of time you can start this after fluoxetine has been stopped?What about starting an MAOI from other SSRIs?
SNRI
How long should a patient not drive through after an unprovoked seizure?
At least 5 weeksWith other SSRIs, it is only 1 week
How long should a patient not drive through after a seizure in established epilepsy?How about if the seizure was whilst the patient was asleep?
6 months
If an epileptic patient has had a seizure whilst asleep, the patient should not drive for 12 months. What are the exceptions?
12 months even if the patient was asleep unless:- Established pattern of only having seizures when the patient is asleep over one year- If had seizures in the past awake, need to have 3 years of only having seizures asleep
Should an epileptic person drive during medication changes?
UNLESS:- Established pattern of only having seizures when the patient is asleep over one year- If had seizures in the past awake, need to have 3 years of only having seizures asleep
If withdrawn from an epilepsy med, how long should a patient not drive for?
No
What is the MHRA warning associated with the sedating antihistamine hydroxyzine?
6 months
What is the therapeutic range for carbamazepine?
QT prolongation
Has pregabalin got an MHRA warning on the risk of severe respiratory depression?
4-12 mg/L
What is amitriptyline used for?
No - Gabapentin does
What would be the starting dose of amitriptyline for neuropathic pain?
Major depressive disorder- not recommendedMigraine prophyaxisNeuropathic pain
What is pregabalin used for in terms of pain?
10-25mg ON Max of 75mg
What is the max dose of pregabalin a day?
Peripheral AND central neuropathic pain
What would be the starting dose of pregabalin for neuropathic pain?
600mg
What is the max dose of gabapentin a day?
150mg daily in divided doses
What is gabapentin used for in terms of pain?
3.6g
What would be the dosing regimen of gabapentin in neuropathic pain?
Only peripheral neuropathic pain
Examples of antimuscarinic drugs
Day 1 - 300mg ODDay 2 - 300mg BDDay 3 -300mg TDS
Effects of Atropine as antimuscarinic drug
AtropineScopolamineIpratropiumTiotropiumToleterodine SolifenacinBenztropineTrihexyphenidyl
3 types oc holinergic antagonists
Eye - relaxation ciliary muscle = dilation of pupil, not responsive to light, can be used prior to eye surgery but due to long duration of action (lasting days) cyclopentolate or tropicamide is preferred (lasting hours)GI - blocks M3 Rec reducing gut motility, prolonging transit time and gastric emptyingHeart - blocks M2 receptors on SA/AV => tachycardia (^30-40bpm)Salivary/sweat/lacrimal glands = dry mouth, dry skin and ultimately increase in body temperature
Scopolamine
1 antimuscarinics2 Ganglionic blockers3 Neuromuscular blockers
Ipratropium and TiotropiumMOAIndicationDifference?
unlike atropine has greater CNS effect and longer duration of action- prevent motion sickness- post op n+vpatch formulation effect lasting up to 3 days
Antimuscarinics USE
Block muscarinic Acetylcholine receptors without specificity for subtypes M3 block results in decreased contractility of smooth muscle in lungs = bronchodilation =& reduction of mucus secretionBoth administered as inhalation treatment for maintenance bronchospasms for pt in COPDIpratropium <= nasal spray = rhinorrea = runny noseTiotropium long acting agent dosed once dailyIpratropium short acting dosed up to qdstiotropium bromide is electrically charged, not absorbed by the GI tract and does not pass the BBB
Antimuscarinics for bladder conditions
Prior to eye operation = atropine Motion sickness = scopolamineCOPD maintenance of bronchospasms = ipratropium/tiotropiumBladder problems = Tolterodine / solifenacin/ oxybutynin/ fesoterodineParkinson like disorders = Benztropine / Trihexyphenidyl
Trihexyphenydil
TolterodineSolifenacinOxybutyninFesoterodine M3 receptor. overall efficacy similar.
Anticholinergic adverse effects
Trihexyphenidyl exerts its effects by reducing the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.
Ganglionic blockers’ main agent?
ABCDsA - agitationB - blurred visionC - constipation/ confusionD - dry mouthS - stasis of urine and sweating
Neurotransmitters and effectson Mood and Cognitive function
main agent is nicotine - cig smoke; stimulates and later represses autonomic ganglia. Cholinergic agonist but also functional antagonist as it can stimulate and block cholinergic function. Acts on nicotinic rec or parasympathetic and sympathetic autonomic ganglion, ^release of neurotransmitters such as dopamine, norepinehprine and serotonin.
What antidepressant is the safest in those at a risk of bleeding e.g. haemorrhagic stroke patients
Mirtazapine
What antidepressant is the safest in those with parkinsons?
Quetiapine
