Nervous System Flashcards
1
Q
Which drugs are avoided in patients with dementia?
A
Drugs that increase antimuscurinic burden.
- anti depressants
- anti histamines
- anti psychotics
- urinary antispasmodics
2
Q
Management of Alzheimer’s disease?
A
Mild to moderate
1. Monotherapy with donepazil, rivastigmine, gelantamine.
2. Not tolerated or contra-indicated then memantine is an alternative
Severe
1. Memantine
3
Q
If memantine is added in moderate/severe Alzheimer’s, how is it done?
A
Not to discontinue acetlycholinestrase inhibitor treatment. Can worsen the Alzheimer’s.
4
Q
Management of dementia with Lewy bodies?
A
- 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.
5
Q
Which dementia can we not use medication in to treat cognitive impairment?
A
- frontotemporal dementia
- cognitive impairment caused by multiple sclerosis
6
Q
- How to manage non-cognitive symptoms?
- What is used?
- MHRA/CHM report on the use of antipsychotics in dementia
- Reviewed every …. Weeks.
A
- 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.
7
Q
Use of anti-depressants in dementia?
A
Reserved for patients with pre-existing severe mental health problems. Otherwise it’s non-drug treatment options.
8
Q
Galantanine
A
Pts to be informed of the signs of serious skin reactions, advised to stop taking and seek medical advice
9
Q
Rivastigmine
A
- 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.
10
Q
Anti-epileptics with long half-life.
A
Can be given once daily at bedtime
- lamotrigine
- perampanel
- phenobarbital
- phenytoin
11
Q
How to switch between anti-epileptics?
A
Slowly withdraw the first drug only when the new regimen has been established
12
Q
MHRA/CHM advice on anti-epileptics.
A
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)
13
Q
Anti- epileptic hypersensitivity syndrome
A
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.
14
Q
Withdrawl of anti-epileptics?
- how long do you have to be seizure free?
A
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.
15
Q
Driving and epilepsy
A
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)
16
Q
How long can you not drive if the patients epileptic medication is being changed or stopped?
A
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
17
Q
Safe anti-epileptics in pregnancy
A
Lamotrigine and levetiracetam
18
Q
Sodium valproate in pregnancy
A
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.
19
Q
Using anti-epileptics in pregnancy?
A
- 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.
20
Q
What is given at birth to prevent neonatal haemorrhage?
A
Vitamin K injection
21
Q
Breastfeeding in epileptic mothers
A
- 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.
22
Q
Focal seizures with or without secondary generalisation - Treatment options?
A
Lamotrigine
Levetiracetam
23
Q
Generalised - Tonic-clonic seizures - treatment options
A
Sodium valproate
Lamotrigine or levetiracetam (women of child bearing potential)
24
Q
Absence seizures - treatment options
A
Ethosuximide
Sodium valproate
Lamotrigine or levetiracetam (for women of childbearing potential)
25
Myoclonic seizures - Treatment options
Sodium valproate
Levetiracetam (for women of childbearing potential)
26
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)
27
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.
28
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.
29
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.
30
Febrile convulsions
Antipyretics - paracetamol
31
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
32
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
33
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.
34
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.
35
Sodium valproate
1. Risk of suicidal thoughts
2. Women of child-bearing age need to be on pregnancy prevention programme.
3. Use of valproate in migraine and bipolar is contra-indicated in pregnant women.
4. Consider Vitamin D supplements in long term immobilised patients, inadequate sun exposure or dietary calcium intake.
5. Liver toxicity can occur. Patients told to monitor for signs and seek immediate medical attention. Withdrawl may be required.
6. Pancreatitis - seek medical attention if symptoms develop. Discontinuation of treatment maybe required.
7. 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.
8. Monitoring of FBC and LFT (Before and during the first 6 months).
36
Topiramate
1. Risk of suicidal thoughts
2. 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.
3. Contraception - Highly effective contraception is required.
4. Perform pregnancy test before initiating
5. Pregnancy - If used in pregnancy - major congenital abnormalities and intrauterine growth restrictions.
6. 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.
37
Vigabatran
1) Visual field defects
2) encephalopathic symptoms - symptoms include marked sedation, stupor, confusion
38
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
39
Phenobarbital
1. Risk of suicidal thought and behaviour
2. Brand specific
3. Vitamin D supplementation
4. Anti-epileptic hypersensitivity syndrome
5. Pregnancy - increased risk of major congenital abnormalities and intrauterine growth restriction and possibility of adverse effect on neurodevelopment.
5. Monitoring plasma concentration - therapeutic range for optimum response is 15-40mg/L
6. To avoid abrupt withdrawl.
40
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.
41
Primidone
This is partially converted to phenobarbital. Also has some anti-epileptic properties of its own.
42
Withdrawl of benzodiazepine- suggested protocol.
How is withdrawl of benzodiazepines carried out?
1. Transfer the patient stepwise. A dose at a time over a week. To equivalent dose of diazepam taken at night time
2. Reduce dose of diazepam 1-2mg every 2-4 weeks (if withdrawl symptoms occur, maintain this dose until symptoms lesson)
3. 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.
43
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
44
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
45
Zolpidem and zopiclone
- act at the benzodiazepine receptors.
- not licensed for long-term use
- short duration of action
46
Clomethiazole
- useful hypnotic in elderly due to no hangover symptoms
- long term use is not desirable
- dependance can occur
47
Promethazine
- sedating anti-histamine
- prolonged duration of action and can cause drowsiness the following day.
- associated side-effects - headache, pychomotor impairment and antimuscurinic effects.
48
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.
49
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.
50
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.
51
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
52
What drugs are used for opioid substitution therapy?
Methadone
Buprenorphine
53
Duration of opioid substitution in in-patient/ residential setting/community setting?
Inpatient/residential = 4 weeks
Community setting = 12 weeks
54
After successful opioid withdrawal, how long do you monitor the patients?
At least 6 months.
55
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
56
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.
57
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.
58
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.
59
Buprenorphine with naloxone - suboxone
Given to patients who are at high risk of dose diversion - when they may take the buprenorphine parenterally.
60
Buprenorphine - who/why it may be better
1. Less sedating
2. Suitable for employed patients or skilled tasks like driving
3. Safer than methadone
4. Can be used with other sedating drugs
5. Less drug interactions
6. Dose reductions may be easier than with methadone
7. Withdrawal symptoms are milder
8. Lower risk of overdose
9. Shorter drug free period is required than with methadone before giving the patient naltrexone for prevention of relapse.
10. With patches, hear can increase the rate of absorption.
61
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
62
Methadone - who/why it may be preferable?
1. Long-acting opioid agonist
2. Preferred in pt who require a sedative effect like those who use other sedating drugs, become anxious at wothdrawl.
3. Initiate at 8 hours after last heroin dose but patient should be experiencing symptoms of withdrawl.
4. Due to the long half-life, plasma concentration rise rapidly. So a dose tolerated on day 1 can become toxic on day 3.
5. 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.
63
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.
64
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)
65
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
66
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
67
Naloxone
Opioid receptor antagonist
Used in the case of accidental overdose
Short duration of action - repeated doses may be required
68
Symptoms of abrupt withdrawal from alcohol in patients who are alcohol dependant?
Seizures, delirium tremens and death.
69
Settings for treatment of alcohol dependence is based on the severity.
Mild - doesn’t require assisted alcohol withdrawal
Moderate - treated in community unless high risk of developing withdrawal seizures of delirium tremens
Severe dependence - inpatient settings
Pts with decompensated liver disease - under specialist supervision
70
Assisted alcohol withdrawal. What medication is used to help with the attenuate alcohol withdrawal symptoms?
1. Long acting benzodiazepines - chlordiazepoxide, diazepam
2. Carbamazipine
3. Clomethiazole
71
Types of regimen used in inpatient/residential settings?
1. Fixed dose reducing regimen
Started by using a standard, initial dose dependent on the severity of alcohol consumption/dependence. Then reduce to zero over 7-10 days.
2. Symptom triggered regimen
Tailoring the drug regimen to the severity of withdrawal and any complications in an individual.
72
Clomethiazole
Only considered in inpatient setting and should not be prescribed in those who are liable to continue drinking.
Alcohol + Clomethiazole in patients with cirrhosis can lead to fatal respiratory depression.
73
Managing patients with benzodiazepine and alcohol dependence?
The dose of benzodiazepine used for withdrawal should be increased.
Inpatient withdrawal - should last for 2-3 weeks or longer depending on the severity of benzodiazepine dependence.
Outpatient withdrawal - should last for a minimum of 3 weeks
74
Alcohol withdrawal seizures - management
Fact acting benzodiazepine - Lorazepam
Withdrawal drug regimen should be reviewed.
75
Delirium tremens in alcohol withdrawal - management?
Medical emergency. Should always be managed inpatient.
Treatment options
1st line - oral lorazepam
2nd line - parenteral lorazepam or haloperidol
Review withdrawal drug-regimen
76
Symptoms of delirium tremens?
Agitation, confusion, paranoid, visual and auditory hallucinations.
77
Management of alcohol dependence
1st line - psychological intervention
2nd line - pharmacological intervention
Pharmacological intervention
- acamprosate
- oral naltrexone (opioid antagonist)
- disulifram (need to know the risks)
- nalmefene
78
Nalmefene
Opioid receptor antagonist
Recommended for reduction of alcohol consumption
Used in alcohol dependence when patient has high drinking risk levels without at withdrawal symptoms who also don’t need immediate detox
79
Disulifram
What is it used in?
What are the symptoms of disulfifram-alcohol reaction?
Used to prevent relapse in alcohol dependent patients.
Disulifram-alcohol reaction
Symptoms - nausea, flushing, palpitations, arrhythmia, hypotension, respiratory depression and coma.
Signs of hepatotoxicity - feel unwell, fever or jaundice - discontinue and seek immediate medical help.
80
Complications that can occur with alcohol and how to manage?
Alcohol related-hepatitis
- corticosteroids (improves survival in the short term - 1 month)
Chronic alcohol related-pancreatitis
- nutritional support
Steatorrhoea/exocrine pancreatic insufficiency
- pancreatic enzyme supplements
Wernickes encephalopathy
- parenteral thiamine followed by oral thiamine
81
Symptoms of withdrawal from smoking?
Nicotine cravings, irritability, restlessness, poor concentration, light headedness, sleep disturbances, depression.
Increased appetite and weight gain
82
Types of approach for stopping smoking?
What is a ‘stop in one go’ and ‘harm reduction approach’ in smoking cessation?
‘Stop in one go’
Creating a stop date and then not smoking after. Most effective and best chance of lasting success.
‘Harm reduction approach’
This is when you cut down before stopping, reducing smoking or temporarily not smoking. NRT can be used as part of this approach to prevent smoking cigarettes.
83
Drug treatments for smoking cessation?
1. NRT
2. Varenicline (not available in the UK)
3. Bupropion (SNRI - MHRA risk of serotonin syndrome)
Alongside behavioural support
Cannot use combination of these options.
84
NRT options
- Patches
16 hours - removed over night. Good when pts experience sleep disturbances
24 hours - strong nicotine cravings on waking
Short acting nicotine
(Used when there is an urge to smoke)
- nasal sprays
- oral spray (avoid acidic beverages for 15 minutes after oral formulations - decreases absorption of nicotine)
- sublingual tablets
- lozenges (last 10-30 minutes)
- cartridge inhalation
- medicated chewing gum
85
Smoking in pregnancy
Avoid. Advise to stop completely.
NRT alongside behavioural support at the earliest opportunity. Using NRT is less addictive because of the lower amounts of nicotine and less risk.
86
Symptoms of nicotine withdrawal
Malaise, headache, dizziness, dowsiness, sleep disturbances, irritability, restlessness
Impaired concentration
Coughing, flu like symptoms, ulcers
Depression, anxiety
Increased appetite, weight gain
Decreased heart rate
87
How do you consider which anti-emetic to use in patients?
Cause of the vomiting. (Aetiology)
88
Anti-emetics and causes
1. Chemotherapy induced and radiation induced nausea and vomiting
- prochlorperazine (phenothiazine - dopamine antagonist - block the chemoreceptor trigger zone)
- dexamethasone
- Aprepitant (neurokinin 1 receptor antagonist)
- Ondansetron (5HT3 receptor antagonist)
Drugs are often used in combination for chemotherapy.
- Nabilone (cannabinoid - used when other drugs in chemotherapy are unresponsive)
2. Nausea and vomiting in palliative care
- haloperidol
- levopromazine (1st gen antipsychotic)
3. Gastrointestinal or biliary diseases related nausea and vomiting
- metoclopromide (like phenothiazine - chemoreceptor trigger zone and also work on gastric smooth muscle stimulating gastric emptying)
4. In Parkinson’s when domaninergic drugs cause nausea
- domperidone - doesn’t cross the blood brain barrier so less sedation and dystonia reactions. Also works on chemoreceptor trigger zone.
5. Nausea and vomiting in patients receiving cytotoxics
- ondansetron (5HT3 receptor antagonist )
6. Postoperative nausea and vomiting
- 5HT3 receptor antagonist - ondansetron
- dexemathasone
- haloperidol
- Cyclizine
- prochlorperazine
7. Motion sickness
Anti-emetics are given to prevent motion sickness rather than after they develop.
- hyoscine hydrobromide (nausea, vomiting and vertigo)
- antihistamines - Cyclizine and cinnarazine (non sedating) promethazine (sedating)
Others are ineffective in motion sickness.
89
Nausea and vomiting in pregnancy - options
1. Rest, oral hydration and dietary changes
2. Non pharmacological - ginger
3. pharmacological changes
- chlorpromazine
- Cyclizine
- doxylamine with pyridoxine
- metoclopromide
- prochlorperazine
- promethazine
- ondansetron (oral cleft formulation if used in the first 12 weeks of pregnancy)
Assess response after 24 hours if inadequate change to a different drug class.
90
Hyperemisis gravidarum
Drug treatment + iv fluids + electrolytes + sometimes nutritional support.
Supplementation with thiamine to reduce risk of wernicks encephalopathy
91
Domperidone
Dopamine receptor antagonist
- doesn’t readily cross the blood brain barrier. So less sedation and dystonia reactions.
- used in Parkinson’s disease
- acts on the chemoreceptors trigger zone.
MHRA
- not used in children under 12
- not used in those who weight < 35kg
Treatment should be lowest effective dose for upto 1 week.
Arrrythmias
- patients should seek medical attention if palpitations or syncope develop.
92
Metoclopromide
Works on the chemoreceptor trigger zone. Also acts directly on the gastric smooth muscle stimulating gastric emptying.
MHRA
- risk of neurological adverse effects
(Extrapyramidal disorders and tradive dyskinesia)
- adults over 18 years should only be used for chemotherapy induced, prevention of postoperative n&v and acute migraines.
- short term use upto 5 days
- iv doses administered as slow bolus over 3 minutes
Inappropriate in Parkinson’s. Use domperidone.
Side-effect
Can induce dystonic reactions involving facial and skeletal muscle spasms.
Anti-Parkinsonian drugs - procyclidine will abort any dystonia attacks.
93
Ondansetron
5HT3 receptor antagonist - blocks the receptors in the GI tract and the CNS.
MHRA
Small increased risk of oral clefts following use in the first 12 weeks of pregnancy
94
Parkinson’s disease
Motor symptoms?
Non motor symptoms?
Motor symptoms
- hypokinesia
- bradykinesia
- rigidity
- rest tremor
- postural instability
Non-motor symptoms
- dementia
- depression
- sleep disturbances
- bladder and bowel dysfunction
- speech and language changes
- swallowing problems
- weight loss
95
Management of Parkinson’s with drug treatment?
Option - affecting quality of life
Levodopa with carbidopa/benserazide
Option - not affecting quality of life
- levodopa
- non-ergot derived dopamine receptor antagonist (ropinorole)
- monoamine oxidase inhibitor (rasageline/selegaline)
Adjunct for improvement
- non-ergot derived dopamine agonist (ropinorole, rotigotine, pramipexole)
- monamine oxidase B inhibitor (rasageline, selegiline)
- COMT inhibitor (entacapone, tolcapone)
Option 3
Ergot derived dopamine agonists should only be considered if non-ergot do not control the symptoms. (Cabergoline, perfolide, bromocriptine)
Option 4
- Amantadine - if the dyskinesia is still not adequately managed with existing treatment options.
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What are the side-effects to anti-Parkinsonian medication?
- psychotic symptoms
- excessive sleepiness
- sudden onset of sleep
- impulse control disorders
97
Levodopa
- can cause response fluctuation - on and off period. On = normal function and Off = weakness and restricted mobility.
Can also cause dyskinesia (uncontrolled involuntary muscle movement)
- MR preparations can help with end of dose deterioration and nocturnal immobility
Important safety info
- impulse control disorder
Treatment cessation
- avoid abrupt withdrawal - risk of neuroleptic malignant syndrome
Patient advice
- dopamine dysregulation syndrome
- excessive daytime sleepiness/sudden onset of sleep (driving and skilled task)
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Levodopa vs dopamine receptor agonists (amantadine, apomorphine, bromocriptine, carbergoline, pramipexol, ropinorole, rotigotine)
Levodopa
- motor performance is more noticeable
(Better improvement in motor symptoms)
- more motor complications ( end of dose symptoms)
-
Dopamine receptor agonists
- less motor complications
- more likely to cause excessive sleepiness, hallucinations and impulse control disorders.
99
Neuroleptic malignant syndrome
Symptoms
- hyperthermia
- fluctuating levels of consciousness
- muscle rigidity
- autonomic dysfunction with fever, tachycardia and labile BP.
- sweating.
Discontinue for 5 days or longer.
Symptoms to be allowed to resolve completely
Treatment is bromocriptine and dantrolene.
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Management of non-motor symptoms in Parkinson’s
Daytime sleepiness & sudden onset of sleep
- adjust Parkinson medication
- Modafanil (review atleast every 12 months)
- not drive and inform DVLA
Nocturnal Akinesia
- levodopa or oral dopamine receptor agonists
- rotigotine (non-ergot) - patches
Postural hypotension
- review medication
- midodrine
- fludrocortisone (unlicensed)
Depression
- normal management
Psychotic symptoms
- review medication
- quetiapine
- clozapine
REMEMBER - other antipsychotics like phenothiazine can worsen the motor symptoms
Rapid eye movement sleep behaviour disorder
- clonazepam
- melatonin
Drooling if saliva
- glycopyronium bromide
- botulinum toxin type A
REMEMBER - other antimuscurinic can worsen the cognitive symptoms.
Parkinson’s disease dementia
- acetylcholinesterase inhibitor (unlicensed in severe)
- memantine (unlicensed)
Impulse control disorder
Can occur with dopamine receptor agonist. - reduce dose or stop if becomes problematic. To be reduced gradually.
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Advanced Parkinson’s disease management
1. Apomorphine - intermittent injections or continuous subcutaneous injections.
2. Domperidone for nausea/ vomiting associated with apomorphine. Start 2 days before.
Apomorphine + domperidone = QT PROLONGATION.
MHRA Recommendation - assess cardiac risk factors and ECG monitoring for benifits > risk
3. Levodopa-carbidopa intestinal gel (portable pump). Given directly into the duodenum or upper jejunum.
4. Deep brain stimulation
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COMT inhibitor
Examples?
How it works?
Entacapone (may discolour the urine red-brown)
Opicapone
Tolcapone (hepatotoxicity)
Works by inhibiting the breakdown of levodopa allowing more to reach the brain
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Dopamine receptor agonists
Ergot and non ergot derived dopamine agonists
Amantadine
Apomorphine
Ergot derived dopamine agonists
- Bromocriptine (fibrotic reactions)
- Cabergoline
Non-ergot derived dopamine agonists
- pramipexole
- ropinorole
- rotigotine
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Non-ergot derived dopamine agonists
Examples
- pramipexole
- ropinorole (re-titration if dose is interrupted)
- rotigotine
- Important safety info - impulse control disorders
- avoid abrupt withdrawal (risk of neuroleptic malignant syndrome)
- dopamine dysregulation syndrome
- sudden onset of sleep & excessive daytime sleepiness
- hypotensive reactions (particularly problematic during the first few days)
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Ergot derived dopamine receptor agonists
Examples
- bromocriptine (withdraw if GI bleed occurs)
- Cabergoline
- inhibits the release of prolactin from pituitary glands
- Important safety info
1. impulse control disorders
2. Fibrotic reactions - patients should be monitored for dyspnea, persistent cough, chest pain, cardiac failure, abdominal pain or tenderness.
- avoid abrupt withdrawal (risk of neuroleptic malignant syndrome)
- dopamine dysregulation syndrome
- monitor - blood pressure and fibrotic disease.
- sudden onset of sleep & excessive daytime sleepiness
- hypotensive reactions (particularly problematic during the first few days)
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Schizophrenia
Positive and negative symptoms
Positive symptoms - hallucinations and delusions
Negative symptoms - emotional apathy and social withdrawal
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The choice of anti-psychotics depend on certain factors. What are these factors?
1. Potential to cause EPS
2. Cardiovascular effects
3. Metabolic adverse effects (weight gain and diabetes)
4. Hormonal adverse effects (increase in prolactin)
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How long does the patient need to be on a antipsychotic before saying the drug is ineffective?
4-6 weeks.
Not to prescribe more than 1 anti-psychotic at a time. Why?
Increase risk of adverse effects - EPS, QT prolongation, and sudden cardiac death.
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Clozapine - when is it considered?
Offered once at least 2 anti-psychotics are used for an adequate duration.
If symptoms do not respond to clozapine consider reasons why not responding (adherence to therapy), review diagnosis, check plasma clozapine concentration before adding another anti-psychotic. Allow 8-10 weeks to assess response.
Patients need to be registered with ‘clozapine patient monitoring service’
MHRA
- potential fatal risk of intestinal obstruction, faecal impaction and paralytic lieu’s. Seek immediate medical attention before taking the next dose is constipation occurs
- monitor blood concentration for toxicity.
Caution; further info
- Agranulocytosis - leucocytes and differential blood should be normal before starting
- myocarditis and cardiomyopathy - fatal myocarditis most commonly in the first 2 months.
- intestinal obstruction- caution in pts on other medication that increase risk of constipation. Any constipation needs to be treated.
Side-effects
- hyper-salivation associated with clozepine can be treated with hyoscine hydrobromide.
Monitoring
- FBC
- blood lipids and weight
- fasting blood glucose
Treatment cessation
- withdraw the dose over 1-2 weeks
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1st and 2nd generation anti-psychotics
Examples?
Side-effects?
1st generation - work on the dopamine d2 receptors in the brain.
Examples
- phenothiazines (chlorpromazine, prochlorperazine, levomepromazine)
- butyrophenones (haloperidol)
- thiozanthenes (flupentixol)
Side-effects
- extra-pyramidal side effects
- hyperprolactinaemia
2nd generation antipsychotics - act on a range of receptors
Examples
- amisulpride
- aripiprazole
- clozapine
- olanzapine
- quetiapine
- risperidone
Side-effects
- weight gain
- glucose intolerance
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What does a high-dose anti-psychotic drug mean?
1. Total daily dose of a singe antipsychotic drug which exceeds the maximum licensed dose for the pt of age and certain indication
2. Total daily dose of two or more antipsychotic that exceeds the maximum licensed dose using a percentage method.
- high doses are more effective
- higher doses also have greater side-effects
- monitor the patient every 15 minutes if high doses are given.
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Anti-psychotic prescribing in elderly?
Small increased risk of mortality and an increased risk of stroke and TIA. Patients are also more susceptible to postural hypotension.
To use lowest effective dose for shortest period of time.
Review at least every 6 weeks
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Anti-psychotic prescribing in patients with learning difficulties
For patients who have learning difficulties and not experiencing psychotic symptoms, consider the following;
- reduction of dose or discontinuation of long-term anti-psychotic
- review of the patients condition after dose reduction or discontinuation.
- keep an annual documentation of the reasons for continuing prescription
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Side-effects of anti-psychotics?
1. Extrapyramidal symptoms
Most common with first generation (haloperidol). Least common with second generation - aripiprazole, clozapine, Olanzapine and quetiapine.
- parkinsonism symptoms (bradykinesia and tremor)
- dystonia (uncontrolled muscle spasm)
- akathesia (restlessness)
- tardive dyskinesia (involuntary movement of lips, tongue, face and jaw)
2. Hyperprolactinaemia
Both first and second generation. Most common drugs; amisulpride, sulpiride and risperidone. Least common Aripiprazole, clozapine and quetiapine.
Symptoms:
- sexual dysfunction
- reduced bone mineral density
- menstrual disturbances
- breast enlargement and galactorrhoea
- increased risk of breast cancer.
3. Sexual dysfunction
Most common with haloperidol, Olanzapine, risperidone.
Least common with Aripiprazole and quetiapine.
4. Cardiovascular side-effect
- tachycardia
- arrhythmias
- hypotension
- QT interval prolongation
Drugs with low tendency to prolong QT interval prolongation Aripiprazole, clozapine, Olanzapine, prochlorperazine, risperidone and sulphide.
5. Hypotension
Presents acutely during the initial dose titration. Slow dose titration can be used to minimise postural hypotension.
Drugs most likely to cause postural hypotension are clozepine and quetiapine.
6. Hyperglycaemia and diabetes
Schizophrenia is associated with insulin resistance and diabetes.
First generation haloperidol are least likely and of the second generation amisulpride and aripiprazole have the lowest risk of diabetes.
7. Weight gain
All antipsychotics cause weight gain. Mostly likely to cause weight gain are clozepine and Olanzapine. Least likely drugs to cause weight gain are amisulpride, aripiprazole, haloperidol.
8. Neuroleptic malignant syndrome
Can occur with all antipsychotics. Discontinue medication for 5 days or longer. Can use bromocriptine (dopamine d2 receptor agonist) or dantroline can be used to treat.
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Monitoring in anti-psychotics
1. Weight - before, weekly for 6 weeks, at 12 weeks, a 1 year, then yearly.
2. Fasting blood glucose, HBA1c and blood lipids - baseline, at 12 weeks, at 1 year then yearly.
3. Prolactin concentration - at baseline.
4. ECG - if history of cardiovascular disease.
5. Blood pressure - before, at 12 weeks, a 1 year then yearly.
6. Full blood count - before and then yearly
7. Urea and electrolyte - before and yearly
8. Liver function - before and then yearly.
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Anti-psychotics drugs
1st generations - EPS side-effects are more common
2nd generations - more likely to cause other side-effects and less risk of EPS side effects.
Cautioned; further info -
- cardiovascular - ECG required if physical examination identified CVD. Or if pt history shows cardiovascular effects.
- elderly pt - potentially inappropriate - STOPP criteria
Side-effects
- EPS
- hyperprolactinaemia
- diabetes and hyperglycaemia
- weight gain
- sexual dysfunction
- cardiovascular side-effects
- hypotension
Neuroleptic malignant syndrome
Monitoring
- weight
- fasting blood glucose, HB1Ac
- blood lipid concentration
- ECG
- blood pressure
- full blood count
- urea and electrolytes
- liver function tests
Treatment cessation
- high risk of relapse if medication is stopped after 1-2 years
- gradual withdrawal and closely monitor. Monitor for 2 years after
Patient and carer advice
- drowsiness. Effects maybe enhanced by alcohol.
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What is chronic pain?
Pain present for more than 12 weeks.
Depression is a common comorbidity.
118
Pain can be either primary or secondary?
Primary pain - pain that has no clear underlying condition or where the pain appears to be out of proportion to any injury or disease. Examples include fibromyalgia
Secondary pain - caused by an underwing condition. Examples are endometriosis, osteoarthritis, rheumatoid arthiritis and ulcerative colitis.
119
Non drug treatment options for pain?
1. Exercise
2. Transcutaneous Electical nerve stimulation (TENS) - either as high or low frequency.
3. Referral to pain management programme and psychologically based intervention such as CBT.
120
Drug treatment options for pain?
1. Paracetamol
2. NSAIDs (oral and topical)
3. Codeine for mild to moderate pain
4. Morphine/oxycodone for moderate-severe pain.
Doses of opioids should be reviewed annually.
Pain specialist advice or review should be sought for individuals taking doses >90mg/day morphine or equivalent.
Adjuvant analgesics
- anti-depressants
- anti-epileptics
- benzodiazepines
- muscle relaxants
- bone-modulating drugs
- corticosteroids
- topical capsaicin
- lidocaine
- rubefacients
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What analgesics are best suited for pain in musculoskeletal conditions?
Paracetamol
Aspirin
NSAIDs
122
What analgesics do you use for visceral pain?
Opioids.
123
Pethidine
- short half life so required frequent injections
- should be avoided if possible. Accumulation of neurotoxic metabolite can precipitate seizures.
124
Management of pain in sickle cell crisis?
Options include
- paracetamol
- NSAIDs
- codeine
- dihydrocodeine
- opioids like morphine and diamorphine in severe crises.
125
Management of pain in dental or orofacial pain?
- treat the cause - infection
Provide drainage, restorative procedures
- oral benzydamine (wash or spray)
- paracetamol
- ibuprofen
- aspirin
- dihydrocodeine for moderate to severe pain.
Any analgesic that’s given before a procedure should have a low risk of increasing postoperative bleeding.
Taking the painkiller before the effects of local anaesthetic has worn off can improve control.
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Management of temporomandibular dysfunction.
Can be related to anxiety in some patients who may clench or grind their teeth.
- diazepam which has a muscle relaxant as well as anxiolytic properties. Only short term.
- aspirin/ ibuprofen may also be required.
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Management of pain in dysmenorrhea?
- oral contraceptives
- paracetamol or a NSAIDs
- anti-emetic in addition to analgesics for pts with vomiting with severe pain due to endometriosis.
- anti-spasmodics (alverine)
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Nefopam
Relief of persistent pain unresponsive to other non-opioids. It causes little or no respiratory depression. Has sympathomimetic and anti-muscuranic side-effects.
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Tapentadol
Mechansim?
Side effects?
Two mechanisms - opioid receptor agonist and inhibits noradrenaline reuptake.
Nausea vomiting and constipation are less likely to occur.
MHRA - risk of seizures and serotonin syndrome. Lowers seizure threshold. Cautioned in patients with history of seizure or epilepsy.
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Tramadol
Mechansim?
Side-effects?
Two mechanisms - opioid effect and an enhancement of seratonergic and adrenergic pathways.
Fewer opioid side-effects - less respiratory depression, less constipation and less addiction potential.
Caution;further info
- variation in metabolism - metabolised by CYP2D6
- post-operative use - extreme caution in children. Life threatening adverse events after tonsillectomy and adenoidectomy for obstructive sleep apnoea.
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Paracetamol doses in children
Paracetamol doses in children.
3-5months - 60 mg QDS
6-23 months - 120mg QDS
2-3 years - 180mg QDS
4-5 years - 240mg QDS
6-7 years - 240-250mg QDS
8-9 years - 360-375mg QDS
10-11 years - 480-500mg QDS
12-15 years - 480-750mg QDS
16-17 years + adults - 0.5-1g QDS
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Opioids in general?
1. Risk of potentially fatal respiratory depression when co- prescribed with benzos. Patient to be monitored for at least 2 weeks after initiation or changes in prescribing.
Respiratory depression - treated with artificial ventilation or be reversed by naloxone.
2. Risk of dependance and addition even at therapeutic doses
3. Central sleep apnoea. Consider total opioid dose reduction
4. Common side effects - nausea and vomiting, constipation, dry mouth, respiratory depression.
5. Overdose - respiratory depression, pinpoint pupils and coma
6. Antidote = naloxone.
7. Driving and skilled tasks. - affect performance. Effects may be enhanced by alcohol.
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Fentanyl
1. Life threatening risk and fatal opioid toxicity from accidental exposure particularly in children.
- not to cut patched
- avoid exposure of patches to heat
2. Transdermal patches for non cancer pain; not to use in opioid naive patients. Contra-indicated in opioid naive patients: other analgesics or opioids to be used.
3. Caution; further info - not suitable for acute pain or in those where the requirements keep changing. Because the long terms steady state prevents rapid titration of dose.
4. Side effect; muscle rigidity - with IV administration. May also involve the thoracic muscles. Manufactures recommend to AVOID administration by slow IV injection.
- high doses may require pre-medication with benzos and muscle relaxants
5. With transdermal use; monitor for side effects in patients with fever. Avoid exposure to heat.
6. Signs and symptoms where you need to remove patch immediately and seek medical help - breathing difficulties, marked drowsiness, confusion, dizziness and impaired speech.
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Oxycodone
Nothing!!!
135
Opioids safe to use in patients with renal impairment?
- alfentanil
- fentanyl
- buprenorphine
AVOID morphine and diamorphine (codeine)
CAUTION oxycodone
136
Paracetamol
Caution; further info.
Increased risk of experiencing toxicity at therapeutic doses. Particularly it patients who weight less than 50kg and those with risk of hepatotoxicity.
Overdose
Liver damage and less frequently renal damage.
Early symptoms are nausea and vomiting. Last upto 24 hours
Hepatic necrosis symptoms = right subcostal pain and tenderness.
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Co-codamol - metabolism in certain patients
Variation in metabolism- the capacity to metabolise codeine to morphine varies.
- CYP2D6 ultra rapid metabolisers - more conversion of codeine to morphine = increased toxicity
- poor codeine metabolisers = reduced therapeutic effect
138
Codeine
MHRA/CHM important safety info -
1. Only be used to relieve acute moderate pain in over 12 years if other pain killers do not work.
2. In children aged 12-18years max daily dose should not exceed 240mg. Intervals of no less than 6 hours.
3. Contra-indicated in ALL CHILDREN under 18 after removal of tonsils or adenoids for the treatment of obstructive sleep apnoea/breathing problems
4. Contra-indicated in ALL PATIENTS who are CYP2D6 ultra rapid metabolisers.
5. Should NOT be used in BREASTFEEDING mothers
6. Recognise signs of morphine toxicity.
- Variation in metabolism
139
Dihydrocodeine
MHRA/CHM - prescribe and dispensed by strengths. To minimise risk of accidental opioid overdose.
140
Treatment of cluster headache
Rarely respond to analgesics
Treatment options -
1. Subcut sumatriptan
2. Intranasal sumatriptan
3. Intranasal zolmitriptan
Prophylaxis
- if the attacks are frequent
- last over 3 weeks
- cannot be treated effectively
1. Verapamil
2. Lithium
3. Prednisolone alone or with verapamil. (Short-term prophylaxis of episodic cluster headaches)
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What is a migraine?
Migraine with aura
Episodic
Chronic
Headache is unilateral, pulsating and aggravated by routine physical activity. Accompanied with nausea and vomiting, photophobia and phonophobia.
Migraine with aura - consist of visual symptoms, sensory symptoms, or dysphasia. Symptoms usually develop gradually and resolve within an hour.
Episodic migraine - less than 15 days per month. Low frequency = 1-9 days and high frequency = 10-14 days/ month
Chronic migraine - at least 15 days/month. Or 8 days per month for 3 months.
Some women can get it due to a drop in oestrogen level just before menstruation.
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Life style advice for migraines
- eat regular meals
- hydration
- relaxation after stress (stress is a trigger)
- sleep
- exercise
- certain foods and drink can cause migraines. Keep a diary and avoid triggers
- bright light is a trigger.
143
Management of an acute migraine?
1st line options
- aspirin
- ibuprofen
- triptan (5HT1 receptor agonist)
Aura with migraine
- triptan - take at the start of the headache and not a start of the aura.
Triptan - can be repeated after 2 hours if inadequate response.
2nd line - if monotherapy fails.
- combination of sumatriptan+Naproxen
Menstrual migraine
- mefenamic acid
144
First line treatment?
- sumatriptan
If does not respond to this, then can try another one.
If severe or vomiting…
- nasal zolmitriptan
- subcutaneous sumatriptan
145
Which anti-emetics can be used in migraines for nausea and vomiting?
- metoclopromide
- prochlorperazine
- domperidone
146
Preventative options for migraine (prophylaxis)?
1. Propranolol
Other beta blockers that can be used are
Metoprolol, atenolol, nadolol, timolol (manT)
Bisoprolol can be used if already using for cardiac related issues.
2. Topiramate (not in pregnancy)
3. Amitriptyline
4. Candesartan (limited evidence to support its use)
5. Sodium valproate (pregnancy)
6. Flunarizine
7. Pizotifen (limited evidence on its use)
Tried for atleast 3 months before deciding it’s not working.
A good response is when there is a 50% reduction in the severity and frequency.
Review after 6-12 months.
Specialist referral if failed with 3 or more drugs.
8. Botulinum toxin type A (specialist)
9. Calcitonin gene-related peptide inhibitor.
147
Menstrual migraine prophylaxis?
- frovatriptan
2 days before and 3 days after
Alternative options
- zolmitriptan
- naratriptan
Patients menstrual cycle must be regular.
148
Medication overuse headache.
Withdrawing overused medication. Sometimes often associated with transient worsening. If no improvement could be poor control migraines.
149
Triptans
5HT3 receptor agonists
Side-effects
Discontinue if symptoms of heat, heaviness, pressure or tightness (including the throat and chest) develop.
Can’t take a second dose for the same attack if the first dose didn’t work.
Sumatriptan 50mg can be sold as a P.
Max daily dose OTC is 100mg.
Prescription is 300mg/day.
150
Treatment options for neuropathic pain
1. TCA - Amitriptyline
2. Pregablin
Amitriptyline and pregablin can be combined if monotherapy with both is not effective alone.
3. Gabapentin
4. Nortriptyline (unlicensed - maybe more tolerated than Amitriptyline)
5. Tramadol - if other treatments are unsuccessful
6. Morphine / oxycodone - initiated under specialists.
7. Capsaicin- licensed for neuropathic pain
8. Lidocaine plasters - localised pain unable to take oral medication.
9. Corticosteroid - relieve pressure in compression neuropathy.
151
Trigeminal neuralgia - treatment options
- carbamazipine (taken during an acute attack can reduce the frequency and severity of attacks)
Monitor blood count and electrolyte with high doses.
- phenytoin (Iv infusion) - in a crisis.
152
What is ADHD?
Characterise by hyperactivity, impulsivity and Inattention.
Appears in children aged 3-7 years
Maybe not recognised until after 7 years.
More likely in male than females
153
Non drug treatment options for patients with ADHD?
- environmental modifications.
Involves changes to seating, lighting and noise, reducing distraction, optimising work or education by having shorter periods of focus.
- Cognitive behavioural therapy
154
Pharmacological treatment options for ADHD.
Initiated by specialist.
First line options
1. Lisdexamphetamine (long duration of action)
2. Methylphenidate
(Try alternative if the other is not effective)
6 weeks trial with medications.
2nd line
3. Dexamphetamines (if responsive to lisdex but cannot tolerate it’s longer duration of effects)
3rd line option
4. Atomoxetine
Seek specialist advice if not responsive.
5. Guanfacine (unlicensed) in addition to stimulants. Seek specialist advice.
155
Modified release preparation vs immediate release preparations CNS for stimulate - lisdexamphetamines, methylphenidate
Modified release preparations preferred
- pharmacokinetic profile
- convenience
- improved adherence
- reduced risk of drug diversion
- lack of need to take it to work
Immediate release is preferred
- more flexible dosing regimen.
- during initial dose titration
156
Monitoring in patients with ADHD on treatment?
- effectiveness
- side-effects
- changes in sleep pattern
- sexual dysfunction (more commonly associated with atomoxetine)
- stimulant diversion or misuse.
- If the patients develops seizure, review drug treatment or stop
- monitor patients for development of tics. If stimulant related, consider dose reduction, stop treatment or change to a non stimulant.
- worsening of behaviour - adjust dose.
Review treatment atleast once a year
157
Guanfacine (ADHD)
Alpha2 adrenoreceptor agonist
Side-effects
Somnolence and sedation may occur. Predominantly in the first 2-3 weeks and with dose increases
Overdose
- hypotension, initial hypertension, bradycardia
- lethargy and respiratory depression.
If lethargy develop, should be observed for development of more serious toxicity for upto 24 weeks
Monitoring
- conduct a baseline evaluation to identify patients at risk of somnolence, sedation, hypotension, bradycardia, QT Prolongation and arrhythmia.
- blood pressure and pulse
Missed doses
Inform prescriber if more than 1 dose is missed. Dose may need retitrating
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Atomoxetine
CNS stimulant - 3rd like option
Monitoring
- Appearance or worsening of anxiety, depression or tics
- pulse, BP
- psychiatric symptoms
- appetite
- weight and height
Patient and carer advice
- suicidal ideation
- hepatic impairment - how to recognise symptoms (abdominal pain, unexplained nausea, malaise, darkening of urine or jaundice)
159
Methylphenidate
MHRA/CHM Important safety info
Caution when switching between products. All long acting preparations contain an immediate release component and a modified release component. The amounts are different in different preparations. To prescribe by brand.
Monitoring
- psychiatric disorder
- pulse, Bp
- appetite
- weight and height
160
Dexamphetamines
Psychiatric disorders
Includes severe depression, schizophrenia, borderline personality disorder and uncontrolled bipolar disorder. Co-morbidity with psychiatric symptoms is common. Manufacture advises if new psychiatric symptoms develop or exacerbates - continue use only if benefits outweigh risk
Tics and tourette syndrome
Discontinue if tics occur
Growth restrictions in children
Monitor height and weight. Growth restrictions can occur with prolonged use. Drug free period may allow for a catch up.
Overdose symptoms
- wakefulness, excessive activity
- paranoia, hallucinations
- hypertension, hyperthermia
- exhausting
- convulsion
- coma
Monitoring
- growth in children
- aggressive behaviour and hostility
- pulse, BP, appetites weight and height.
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Lisdexamphetamine
Prodrug of Dexamphetamine
Cardiovascular disease
Caution in patients with underlying condition that might be compromising by increase in blood pressure and heart rate.
Overdose symptoms
- wakefulness, excessive activity
- paranoia, hallucinations
- hypertension, hyperthermia
- exhausting
- convulsion
- coma
Monitoring
- growth in children
- aggressive behaviour and hostility
- pulse, BP, appetites weight and height.
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Treatment options for acute mania? Manic episode
1. Anti-psychotic (haloperidol, Olanzapine, quetiapine, risperidone)
Response inadequate
2. + Lithium or +valproate
In patients already taking lithium/valproate for prevention of manic episode
3. Increase dose of existing drug
If no improvement with optimum dose of lithium/valproate
4. Add antipsychotic
Moderate to severe mania
5. Asenapine (2nd generation)
163
Options for long term management in bipolar to prevent an acute attack
- lithium - full prophylactic effect of lithium mar not occur for 6-12 months after the initiation of therapy.
- valproate - alternative to lithium. Used either alone or in combination with lithium.
- olanzapine - used when patients manic episode have responded to the olanzapine. So follow on treatment.
- carbamazipine - used when patients are unresponsive to lithium.
164
What do you do in patients who have rapid cycling bipolar disorder, a recent history of mania or hypomania or with rapid mood fluctuations?
AVOID anti-depressants
Antidepressants can be used for co-existing bipolar depression.
165
Use of benzodiazepines in bipolar disorder?
Short-term use.
During the initial stages of treatment for behavioural disturbances or agitation
166
Valproic acid
1. Risk of suicidal thoughts
2. Contra-indicated in women of child-bearing age unless the conditions of the pregnancy prevention programme are met.
3. Pregnancy
Use of valproate is contra-indicated in patients being treated for migraine prophylaxis and bipolar
4. Liver toxicity - withdraw treatment immediately if pts develop symptoms of persistent vomiting and abdominal pain, anorexia, jaundice, odema, malaise, drowsiness or loss of seizure control.
5. Pancreatitis
Discontinue treatment if symptoms of pancreatitis develop.
6. Vitamin D supplements in pts who are immobilised for long periods.
167
Lithium
