Nervous System Flashcards
Which drugs are avoided in patients with dementia?
Drugs that increase antimuscurinic burden.
- anti depressants
- anti histamines
- anti psychotics
- urinary antispasmodics
Management of Alzheimer’s disease?
Mild to moderate
1. Monotherapy with donepazil, rivastigmine, gelantamine.
2. Not tolerated or contra-indicated then memantine is an alternative
Severe
1. Memantine
If memantine is added in moderate/severe Alzheimer’s, how is it done?
Not to discontinue acetlycholinestrase inhibitor treatment. Can worsen the Alzheimer’s.
Management of dementia with Lewy bodies?
- donepazil and rivastigmine (unlicensed) are used in mild to moderate. Can also be considered in severe
- galantanine (unlicensed) if both the above the above have not been tolerated.
- memantine (unlicensed) if acetylcholinisterases are contra-indicated or not tolerated.
Which dementia can we not use medication in to treat cognitive impairment?
- frontotemporal dementia
- cognitive impairment caused by multiple sclerosis
- How to manage non-cognitive symptoms?
- What is used?
- MHRA/CHM report on the use of antipsychotics in dementia
- Reviewed every …. Weeks.
- managed with anti-psychotics but only if risks of harming themselves or others. Experiencing agitations, hallucinations and delusions causing severe distress.
- increased risk of stroke and small increase risk of death l when used in elderly patients with dementia.
- should be used at lowest effective dose for shortest time possible.
- regular review at least every 6 weeks.
Use of anti-depressants in dementia?
Reserved for patients with pre-existing severe mental health problems. Otherwise it’s non-drug treatment options.
Galantanine
Pts to be informed of the signs of serious skin reactions, advised to stop taking and seek medical advice
Rivastigmine
- if treatment is interrupted for more than several days, then re-titration is required.
- treatment should be interrupted if prolonged vomiting and diarrhoea. Withhold until resolution. Retitrate if necessary.
Anti-epileptics with long half-life.
Can be given once daily at bedtime
- lamotrigine
- perampanel
- phenobarbital
- phenytoin
How to switch between anti-epileptics?
Slowly withdraw the first drug only when the new regimen has been established
MHRA/CHM advice on anti-epileptics.
1) risk of suicidal thoughts and behaviours
(May occur as early as 1 week after starting treatment)
2) switching between different manufacturers (reports of loss of seizure control and worsening of side-effects)
Anti- epileptic hypersensitivity syndrome
Rare but potentially fatal syndrome.
- carbamazipine, oxycarbazepine
- lamotragine, lacosamide
- phenytoin, phenobarbital, primidone
- rufinamide
Symptoms usually start within 1 and 8 weeks
Symptoms - fever, rash, lymphodenopathy are most common. Other systemic signs include liver dysfunction, haematological, renal, pulmonary abnormalities, vasculitis and multi-organ failure.
Treatment - withdraw drug and not re-expose.
Withdrawl of anti-epileptics?
- how long do you have to be seizure free?
Can only do this if the patient has been seizure free for atleast 2 years.
Even if the patient has been seizure free for several years there is a significant risk of seizure recurrence on drug withdrawl.
Withdraw over atleast 3 months
If seizures do occur after discontinuation the last dose reduction should be reversed.
Driving and epilepsy
First unprovoked seizure or a single isolated seizure = can’t drive for 6 months
Established epilepsy = seizure free for 1 year (can not have a history of unprovoked seizure)
Seizure while asleep = establish that seizures only happen while asleep for a whole year (if pt has had awake seizure previously then it has to be over 3 years)
How long can you not drive if the patients epileptic medication is being changed or stopped?
Has to be seizure free for 6 months.
If the patient has a seizure during changes or withdrawl then can not drive for 1 year
Safe anti-epileptics in pregnancy
Lamotrigine and levetiracetam
Sodium valproate in pregnancy
Valproate must not be used in women of childbearing age unless the terms of pregnancy prevention programs are met.
Approximately 10% risk of congenital malformation and 30-40% neurodevelopmental disorders.
Using anti-epileptics in pregnancy?
- those planning pregnancy should receive folic acid throughout the first trimester to prevent neural tube defects.
- treat monotherpay with lowest effective dose.
- plasma concentration will be affected by the physiological changes of pregnancy and post-partum. Especially with phenytoin and lamotrigine.
- if a female patient has seizures in the second half of pregnancy then assess for eclampsia before making changes to treatment.
- routine injection of vitamin K at birth can minimise neonatal haemorrhage associated with anti-epileptic.
- withdrawl effect can happen in newborns.
What is given at birth to prevent neonatal haemorrhage?
Vitamin K injection
Breastfeeding in epileptic mothers
- encouraged to breastfeed
- monitor the baby for symptoms like sedation, feeding difficulties, inadequate weight gain, and developmental milestones.
Some anti-epileptics are readily transferred into breast milk
- ethosuximide
- lamotrigine
- primidone
- zonisamide
Drugs can accumulate in the babies due to slower metabolism
- phenobarbital
- lamotrigine
Established risk of drowsiness in breast fed babies.
- primidone
- phenobarbital
- benzodiazepines
Withdrawl effects can happen if mother suddenly stops breastfeeding.
Focal seizures with or without secondary generalisation - Treatment options?
Lamotrigine
Levetiracetam
Generalised - Tonic-clonic seizures - treatment options
Sodium valproate
Lamotrigine or levetiracetam (women of child bearing potential)
Absence seizures - treatment options
Ethosuximide
Sodium valproate
Lamotrigine or levetiracetam (for women of childbearing potential)
Myoclonic seizures - Treatment options
Sodium valproate
Levetiracetam (for women of childbearing potential)
Atonic or tonic seizures - treatment options
Usually seen in childhood and associated with cerebral damage or learning disabilities.
Offer -
Sodium valproate
Lamotrigine (for women of childbearing age)
What is epilepsy syndrome
Specific types of epilepsy characterised according to the seizure types, age of onset and EEG.
Most of the time patients with these have drug resistance (when two or more drugs have failed)
Referred to tertiary epilepsy service.
Repeated or cluster seizures and prolonged seizures
Repeated or cluster seizures - typically 3 or more self terminating seizures in 24 hours
Prolonged seizures - seizure that is 2 minutes longer than normal seizures.
Treatment options - benzodiazepines (clobazam and midazolam)
If seizure lasts longer than 5 minutes then treat as convulsive status epilepticus.
Convulsive status epilepticus
This is a seizure that lasts longer than 5 minutes or more.
Management
- positioning the patient to avoid injury
- supporting respiration including oxygen, maintaining BP, correction of hypoglycaemia.
- parenteral thiamine if alcohol abuse is suspected
- pyridoxine if Status epilepticus is caused by pyridoxine deficiency.
Drugs -
Buccal midazolam
Rectal diazepam
IV lorazepam
Second dose is given after 5-10 minutes if not responded.
No responses to 2 doses of benzodiazepines. Second line treatment options = levetricticam, phenytoin or sodium valproate.
Febrile convulsions
Antipyretics - paracetamol
Carbamazipine
1) vitamin D supplementation in patients who are immobile for long periods
2) blood, hepatic or skin disorders - withdraw immediately in cases of aggravated liver dysfunction and leucopenia.
3) presence of HLAB1502 allele - increased risk of Steven’s- Johnson syndrome.
4) anti-epileptic hypersensitivity syndrome
5) blood concentration for optimum level should be between 4-12mg/Liter
6) monitoring of FBC, hepatic and renal function.
7) patients should be told how to recognise signs of blood, liver and skin disorders. To seek attention if fever, rash, mouth ulcers, bruising or bleeding develops.
8) carbamazipine is an enzyme inducer so interacts with certain medications and reduces the efficacy of them.
Like
- warfarin, contraceptives
- drugs that lower seizure threshold; tramadol
- enzyme inhibitors like macrolids
Ethosuximide
Blood counts are required if features of blood disorders occur. To seek immediate medical attention.
Features are fever, sore throat, mouth ulcers, bruising or bleeding
Lamotrigine
1) serious hypersensitivity syndrome
2) Steven Johnson syndrome and toxic epidermal necrolysis. Factors that increase risks are combined use with valproate, higher doses of lamotrigine and a more rapid escalation.
3) plasma-drug concentration monitored before, during, and after birth.
4) avoid immediate withdrawl. Taper off over 2 weeks or longer unless serious skin reactions occur.
5) advise patients about skin reactions and blood disorders.
Phenytoin
1) theraputic range = 10-20mg/L
2) vitamin D supplementation is required in pts who are immobilised for long periods
3) IM phenytoin should not be used
4) patients with HLAB1502 allele are at greater risk of developing Steven Johnson syndrome.
5) side effects with oral use - electrolyte imbalances, vit D deficiency, pneumonitis.
6) rash - withdraw, re-introduce if mild.
7) bradycardia and hypotension with IV use - reduce the rate of administration if this occurs
8) overdose - symptoms of toxicity = nystagmus, diplopia, slurred speech, ataxia, confusion and hyperglycaemia.
9) antiepileptic hypersensitivity syndrome
10) increase risk of major congenital malformation and possible adverse effects on neurodevelopment
11) monitoring of blood counts
12) advise patients to report blood and skin disorders and how to recognise symptoms.
Sodium valproate
- Risk of suicidal thoughts
- Women of child-bearing age need to be on pregnancy prevention programme.
- Use of valproate in migraine and bipolar is contra-indicated in pregnant women.
- Consider Vitamin D supplements in long term immobilised patients, inadequate sun exposure or dietary calcium intake.
- Liver toxicity can occur. Patients told to monitor for signs and seek immediate medical attention. Withdrawl may be required.
- Pancreatitis - seek medical attention if symptoms develop. Discontinuation of treatment maybe required.
- In pregnancy dose should be divided or modified release preparation to be used to avoid peak plasma valproate. Dose should be below 1g, greater dose is increased risk of teratogenicity.
- Monitoring of FBC and LFT (Before and during the first 6 months).
Topiramate
- Risk of suicidal thoughts
- Dose dependent association between prenatal exposure and an increase risk of autism spectrum disorders, intellectual disability, and neurodevelopment disorders in children. - counsel on avoiding pregnancy.
- Contraception - Highly effective contraception is required.
- Perform pregnancy test before initiating
- Pregnancy - If used in pregnancy - major congenital abnormalities and intrauterine growth restrictions.
- Side effects - use associated with acute myopia with secondary angle close glaucoma. Choroidal effusion resulting in anterior displacement of lens and iris. To stop topiramate and treat. Refer to ophthalmologist.
Vigabatran
1) Visual field defects
2) encephalopathic symptoms - symptoms include marked sedation, stupor, confusion
Zonisamide
Avoid overheating and ensure adequate hydration especially in children, during strenuous activity or if in warm environment.
Children should be made aware of how to prevent and recognise overheating and dehydration
Phenobarbital
- Risk of suicidal thought and behaviour
- Brand specific
- Vitamin D supplementation
- Anti-epileptic hypersensitivity syndrome
- Pregnancy - increased risk of major congenital abnormalities and intrauterine growth restriction and possibility of adverse effect on neurodevelopment.
- Monitoring plasma concentration - therapeutic range for optimum response is 15-40mg/L
- To avoid abrupt withdrawl.
Benzodiazepines
Long acting
- nitrazepam
- flurazepam
- diazepam
Short acting
- Loprazolam
- Lormetazepam
- Temazepam
Withdrawl from benzodiazepines can occur so need to gradually withdraw
MHRA - risk of respiratory depression when co-prescribed with opioids. Risk of sedation, respiratory depression, coma and death.
Paradoxical effect. - increase in hostility and aggression may be reported. Opposite effect to what the benzo’s are supposed to do.
The effects range from - talkativeness and excitement to aggressive and antisocial acts. Increased anxiety and perceptual disorders can also occur.
Overdose symptoms - if taken alone can cause dowsniess, ataxia, dysarthria, nystagmus and occasional respiratory depression and coma.
Pregnancy - risk of neonatal withdrawl. High dose administration during late pregnancy or labour can cause neonatal hypothermia, hypotonia, and respiratory depression.
Side-effects also cause drowsiness impair judgement and increase reaction time. Can affect the ability to perform skilled tasks. Effects of alcohol maybe enhanced.
Primidone
This is partially converted to phenobarbital. Also has some anti-epileptic properties of its own.
Withdrawl of benzodiazepine- suggested protocol.
How is withdrawl of benzodiazepines carried out?
- Transfer the patient stepwise. A dose at a time over a week. To equivalent dose of diazepam taken at night time
- Reduce dose of diazepam 1-2mg every 2-4 weeks (if withdrawl symptoms occur, maintain this dose until symptoms lesson)
- Withdraw in slower steps towards the end. Doses of 500mcg. Then stop
Avoid beta-blockers, antidepressants and antipsychotics.
For long terms uses, withdrawl can take 6-18months after the last dose.
Short acting hypnotics/anxiolytic
Who are they preferred in?
Examples?
Preferable -
1. Pts have sleep onset insomnia but don’t struggle to stay asleep and also don’t need daytime sedation
2. Prescribing in elderly patients
Examples
- Loprazolam
- Lormetazepam
- Temazepam
Long acting hypnotic/anxiolytic
Who are they preferred in?
Examples?
Preferable -
1. Pts with poor sleep maintenance (early waking)
2. When anxiolytic is needed during the day or when sedation the following day is acceptable.
Examples
- nitrazepam
- flurazepam
- diazepam
Zolpidem and zopiclone
- act at the benzodiazepine receptors.
- not licensed for long-term use
- short duration of action
Clomethiazole
- useful hypnotic in elderly due to no hangover symptoms
- long term use is not desirable
- dependance can occur
Promethazine
- sedating anti-histamine
- prolonged duration of action and can cause drowsiness the following day.
- associated side-effects - headache, pychomotor impairment and antimuscurinic effects.
Melatonin
- pineal hormone
- licensed for short-term treatment of insomnia in adults over 55 years.
- avoid melatonin in patients with auto-immune disease.
- modified-release tablets should be taken with or after food
- immediate-release preparation should be taken on an empty stomach. 2 hours before or 2 hours after.
Buspirone
- Act at the specific serotonin 5HT1a receptor.
- response can take upto 2 weeks to develop
- to discontinue any benzodiazepines before starting buspirone
- licensed for short-term use only
If given with potent CYP3A4 inhibitor dose should be 2.5mg BD.
Modafinil
- CNS stimulant - centrally acting sympathomimetic. Used in excessive sleepiness.
- increased risk of congenital malformations if used during pregnancy. Use effective contraception during and for 2 months afterwards.
- side-effects - discontinue treatment if rash develops, or psychiatric symptoms.
- monitor blood pressure and heart rate in hypertensive patients.
How long does it take for withdrawal symptoms to occur when taking heroin?
Peak symptoms?
How long do the withdrawal symptoms last?
8 hours.
36-72 hours
Symptoms subside after 5 days
What drugs are used for opioid substitution therapy?
Methadone
Buprenorphine
Duration of opioid substitution in in-patient/ residential setting/community setting?
Inpatient/residential = 4 weeks
Community setting = 12 weeks
After successful opioid withdrawal, how long do you monitor the patients?
At least 6 months.
Number of days missed.
3 days
5 days
3 days = reduce dose - risk of overdose due to loss of tolerance
5 days = check for illicit drug use. Especially with buprenorphine, risk of precipitated withdrawal
What is precipitated withdrawal?
When does it start?
When does it peak?
What drug can you use for severe symptoms of precipitated withdrawal?
It’s what happens when buprenorphine is administered when other opioid agonists are in the patients system.
Starts within 1-3 hours
Peaks at 6 hours
Lofexidine can be used to help with severe symptoms.
How do you reduce the risk of precipitated withdrawal in patients who want to start buprenorphine or methadone?
Buprenorphine- give when pt is exhibiting signs of withdrawal or 6-12 hours after the heroin dose.
Methadone - 24-48 hours after the last heroin dose.
Lofexidine
Alpha 2 adrenergic agonist
- Used to help with severe symptoms of precipitated withdrawal or opioid withdrawal.
- Can also be used in young patients or those of short-term illicit drug use
Monitor - BP and pulse rate on initiation, for atleast 72 hours or until stable dose is achieved. Also on discontinuation.
Withdrawal - gradually over 2-4 days or longer to reduce the risk of rebound hypertension
Take dose at bedtime to help with insomnia associated with opioid withdrawal.
Can be used in children over 12 years for opioid withdrawal.
Buprenorphine with naloxone - suboxone
Given to patients who are at high risk of dose diversion - when they may take the buprenorphine parenterally.
Buprenorphine - who/why it may be better
- Less sedating
- Suitable for employed patients or skilled tasks like driving
- Safer than methadone
- Can be used with other sedating drugs
- Less drug interactions
- Dose reductions may be easier than with methadone
- Withdrawal symptoms are milder
- Lower risk of overdose
- Shorter drug free period is required than with methadone before giving the patient naltrexone for prevention of relapse.
- With patches, hear can increase the rate of absorption.
Naltrexone
Opioid receptor antagonist
Works by precipitating withdrawal in opioid dependant patients.
Used for the prevention of relapse after opioid dependency or in alcohol dependant patients.
Given when the patient has remained opioid free for atleast 7-10 days.
Caution further info - concomitant use of opioid should be avoided but increased dose of opioid analgesic may be required for pain.
An attempt to overcome the blockade of opioid receptors by overdosing could result in acute opioid intoxication
Pre-treatment screening - Test for opioid dependance with naloxone before treatment
Monitor - liver function
Methadone - who/why it may be preferable?
- Long-acting opioid agonist
- Preferred in pt who require a sedative effect like those who use other sedating drugs, become anxious at wothdrawl.
- Initiate at 8 hours after last heroin dose but patient should be experiencing symptoms of withdrawl.
- Due to the long half-life, plasma concentration rise rapidly. So a dose tolerated on day 1 can become toxic on day 3.
- Takes several weeks to reach maintenance treatment dose
Caution - QT interval prolongation
Overdose - long duration of action so monitor patients with overdose for longer periods
Avoid abrupt withdrawal.
Opioid substitution during pregnancy
Avoid acute withdrawal in pregnancy - can cause fetal death
Buprenorphine not licensed in pregnancy
Trimesters
1st = avoid - increased risk of spontaneous miscarriage
2nd = ok - gradually. Dose reduction every 3-5 days.
3rd = avoid/ not recommended - associated with fetal distress, still birth, and risk of neonatal mortality.
Drug metabolism - increases in 3rd trimester therefore may need to increase the dose or give dose twice daily.
Neonatal withdrawal - monitoring required.
Neonatal withdrawal
Develops within 24-72 hours. Symptoms may be delayed upto 14 days
Symptoms
- High pitched crying
- rapid breathing
- hungry but ineffective suckling
- excessive wakefullness
- hypertonicity and convulsion (severe)
Opioid substitution in breastfeeding
Keep dose as low as possible in breastfeeding mothers
Signs to look out for and report urgently to a HCP.
- increased sleepiness
- breathing difficulties
- limpness
Adjunctive therapy for opioid withdrawal symptoms
Diarrhoea - loperamide
Stomach cramps - mebevarine
Muscular aches and headaches - NSAIDs / paracetamol / topical rubefacients
Nausea and vomiting - metoclopromide / prochlorperazine
Insomnia - short-acting benzos/zopiclone