Nervous system Flashcards
Which classes of drugs have anitmuscarinic (anticholinergic) burden?
Antimuscarinic drugs result in cognitive impairment (use minimised in dementia)
- antidepressants (e.g. amitriptyline & paroxetine)
- antihistamines (e.g. chlorphenamine & promethazine)
- antipsychotics (e.g. olazapine & quetiapine)
- urinary spasmodics (solifenacin & tolterodine)
How do you treat cognitive symptoms in mild-moderate Alzheimer’s disease?
1st line: Acetylcholinesterase inhibitors - monotherapy with donepezil, galantamine, or rivastigmine
2nd line: memantine (in moderate AD)
How do you treat cognitive symptoms in severe Alzheimer’s disease?
1st line: memantine
If pt already receiving Acetylcholinesterse inhibitor already, the addition of memantine can be started in primary care
How do you treat cognitive symptoms in mild-to-moderate non-alzheimer’s dementia?
Donepezil or rivastigmine in mild-moderate non-alzheimer’s dementia with Lewy bodies
- if both not tolerated then galantamine can be considered
How do you treat cognitive symptoms in severe non-alzheimer’s dementia?
Donepezil or rivastigmine in severe non-alzheimer’s dementia with Lewy bodies
- C/I or not tolerated = memantine
When can memantine be considered to treat cognitive symptoms in non-alzheimer’s dementia?
In patients with vascular dementia if they have suspected co-morbid AD, parkinsons disease dementia or dementia with Lewy bodies
Who are acetylcholinesterase inhibitors and memantine contraindicated in?
Patient with frontotemportal dementia or cognitive impairment caused by multiple sclerosis
What should you consider before treating agitation, aggression, distress and psychosis in patient with dementia?
Antipsychotics should ONLY be considered if:
- Pt is at risk of harming themselves or others
- experiencing agitation, hallucinations or delusions that are causing severe distress
What is the MHRA warning for antipsychotics and dementia?
Increases risk of stroke and small increases risk of death when antipsychotics are used in elderly patient WITH dementia
Assess risks v benefits
- including previous history of stroke or TIA
- risk factors for cerebrovascular disease: e.g. hypertension, diabetes, smoking and AF
If antipsychotic medication is decided to commence in patients with dementia, when should they be reviewed?
Every 6 weeks
Treat with the lowest dose for the shortest period of time
What types of dementia do antipsychotics worsen?
Patient with dementia with lewy bodies or parkinsons disease dementia - antipsychotic drugs worsen motor features of condition and in some cases cause antipsychotic sensitivity reactions
How is depression and anxiety treated in dementia?
Psychological treatments for mild-moderate dementia - CBT, multi-sensory stimulation, relaxation or animal-assisted therapies
Antidepressants should be reserved for pre-existing severe mental health problems
What is the STOPP criteria for donepezil, galantamine and rivastigmine?
- known history of persistent bradycardia
- HR less than 60 beats per minute
- heart block
- recurrent unexplained syncope
- concurrent treatments with drugs that reduce HR
What is the patient and carer advise for galantamine?
Warn of the signs of serious skin reactions - advised to stop taking immediately and seek medical advise (steven-johnsons syndrome)
When should rivastigmine treatment be interrupted?
If dehydration resulting in prolonged vomiting or diarrhoea occurs and withheld until resolution - retitrate dose if necessary
What is the conversion between oral rivastigmine and transdermal patch?
Taking between 3-9mg orally = start with 4.6mg/24 hr patch
Taking 9mg orally = switch to 9.5mg/24hr patch
Taking 12mg orally = switch to 9.5mg/24 hr patch
Patch can be started the day following last oral dose
Transdermal patches less likely to cause side effects
Where do you apply the rivastigmine patch?
clean, dry, non-hairy, non-irritated skin on:
- back
- arm
- check
Removing after 24 hours
Avoid using the same area for 14 days
Which anti-epileptics have a long half-life and can be taken OD at night?
Lamotrigine
Perampanel
Phenobarbital
Phenytoin
What are the MHRA warnings for anti-epileptic drugs?
- risk of suicidal thoughts and behaviours (symptoms may occur as early as 1 week after starting treatment)
- advice on switching between different manufacturer’s products
- teratogenicity: valportate must not be used in females of child-bearing age unless conditions of the PPP are met and alternative treatments contraindicated or not appropriate
What anti-epileptic drugs are category 1 and should be prescribed and maintained on a specific brand?
Carbamazepine
Phenobarbital
Phenytoin
Primidone
What anti-epileptic drugs are category 2 and prescribing by brand is based on clinical judgment and the patient?
Clobazam
Clonazepam
Lamotrigine
Topiramate
Valporate
Which drugs is anti-epileptic hypersensitivity syndrome associated with?
Carbamazepine
Lacosamide
Lamotrigine
Oxcarbazepine
Phenobarbital
Primidone
Rufinamide
Symptoms start between 1-8 weeks of exposure
Withdraw drug immediately - do not re-expose
What are the symptoms of hypersensitivity syndrome?
common: fever, rash and lymphadenopathy
other systemic signs: liver dysfunction, haematological, renal and pulmonary abnormalities, vasculitis and multi-organ failure
Which anti-epileptics can precipitate severe rebound seizures if stopped abruptly?
Barbiturates
Benzodiiazepines
How do you withdraw anti-epileptic medication?
Patient should be seizure for 2 years at least
Assessment to determine seizure recurrence should be carried out
Withdrawal should do done over a minimum of 3 months
If a seizure occurs during this process - the last dose reduction should be reversed and clinicians must seek advise from epilepsy specialist
How long must patients who have had an unprovoked or single isolated seizure not drive for?
6 months
How long must patients with established epilepsy not drive for?
Must be seizure free for at least 1 year or have a pattern of seizures established for one year where there is no influence on their level of consciousness or their ability to act
They must also have no history of unprovoked seizures
What are the exemptions for people who have seizures while asleep?
They must not drive for a year from last date of seizure unless:
- a history or pattern of sleep seizure’s occurring ONLY ever while asleep has been established over the course of at least one year from the date of the first sleep seizure
- an established pattern of purely asleep seizures can be demonstrated over the course of 3 years if the patient has previously had seizures whilst awake (or awake and asleep)
What should patients take if on anti-epileptics and becomes pregnant?
Folate especially during the first trimester is recommended
How do you minimise the risk of neonatal haemorrhage associated with anti-epileptics?
Routine injection of vitamin K
Who should pregnant females with epilepsy be encourages to notify?
Epilepsy and Pregnancy Register
Which anti-epileptics are readily transferred into breast-milk causing high infant serum-drug concentrations?
ethosuximide
Lamotrigine
primidone
zonisamide
Which anti-epileptics slow metabolism in infants causing it to accumulate?
Phenobarbital
Lamotrigine
Which anti-epileptics have established risk of drowsiness in breast-fed babies?
Primidone
Phenobarbital
Benzodiazepines
Which anti-epileptics may cause withdrawal effect if mother suddenly stops breast-feeding?
Phenobarbital
Primidone
Lamotrigine
How do you treat focal seizures with or without secondary generalisation?
1st line: monotherapy with lamotrigine or levetiracetam
2nd line: monotherapy with carbamazepine, oxcarbazepine or zonisamide
3rd line: lacosamide
Conjunctive therapy:
1st line: carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate
2nd line: brivaracetam, cenobamate, eslicarbazepine, perampanel, pregabalin, sodium valporate (in males and females unable to have children)
3rd line: phenobarbital, phenytoin, tiagabine, vigabatrin
How do you treat tonic-clonic generalised seizures?
Males or females unable to have children:
1st line: sodium valporate
2nd line: lamotrigine or levetiracetam
Females who are able to have children:
1st line: lamotrigine or levetiracetam
Adjunctive treatment
1st line: clobazam, lamotrigine, levetiracetam, perampanel, sodium valporate (men and females unable to have children), or topiramate
2nd line: brivaracetam, lacosamide, phenobarbital, primidone, zonisamide
How do you treat generalised absence seizures?
1st line: ethosuximide
2nd line: sodium valpoerate as monotherapy or adjunctive therapy for males and females unable to have children
3rd line: monotherapy or adjunctive therapy with lamotrigine or levetiracetam
How do you treat generalised myoclonic seizures?
1st line: sodium valporate
2nd line: levetiracetam (1st line if females of childbearing age) monotherapy or adjunctive
How do you treat generalised atonic or tonic seizures?
Usually seen in childhood
1st line: sodium valproate
2nd line: lamotrigine monotherapy or adjunctive (1st line in females of childbearing age)
Which type of epilepsy is associated with cerebral damage or learning difficulties?
Atonic or tonic seizures
How do you treat Dravet’s syndrome?
1st line: sodium valporate in all patients (ensure PPP)
If monotherapy fails, consider triple therapy: Sodium valporate + clobazam + stiripentol
Cannibidiol with clobazam may be considered as 2nd line in certain patients
How do you treat lennox gastaut syndrome?
1st line: sodium valporate in all patients (PPP)
2nd line: lamotrigine monotherapy or adjunctive therapy
3rd line: adjunctive therapy with cannabidiol + clobazam
What is considered as a repeated or cluster seizure?
3 or more self-terminating seizures in 24 hours
What is considered as a prolonged convulsive seizure?
A seizure that continued for 2 minutes longer than the usual patients seizure
What is considered as convulsive status epilepticus?
A seizure that lasts for 5 minutes or more - medical emergency
How are repeated/ cluster seizures or prolonged seizures treated?
1st line: individualised emergency management plan
2nd line: benzodiazepine e.g. clobazam or midazolam urgently considered
How do you treat convulsive status epilepticus?
- position to avoid injury
- support respiratory : provision or oxygen, maintaining BP and correction of any hypoglycaemia
- consider parenteral thiamine if alcohol abuse suspected
- patients individualised emergency plan
- urgent buccal midazolam or rectal diazepam if in community
- if resuscitation resources available then IV lorazepam
Call emergency services and if 1st dose doesnt work, provide a 2nd dose after 5-10 minutes
No response to 2 doses of benzodiazepines: levetiracetam, phenytoin or sodium valporate
3rd line: phenobarbital or general anaesthesia
How do you treat convulsive status epilepticus if caused by pyridoxine deficiency (vitamin B6)?
Pyridoxine hydrochloride
How do you treat non-convulsive status epilepticus?
Depends of severity of condition
If incomplete loss of awareness = usual antiepileptic therapy should be continued or restarted
Fail to respond/ lack of awareness = treat the same way as convulsive status epilepticus
Which antiepileptic drugs do MRHA suggest vitamin D supplementation in immobilised patients or those lacking exposure to sunlight or dietary intake of calcium?
Carbamazepine and phenytoin
What are the cautions for carbamazepine?
Blood, hepatic of skin disorders
HLA allele
What is the optimum plasma concentration response range for carbamazepine?
4-12mg/L OR
20-50micromol/L
Measured after 1-2 weeks
What additional MHRA warnings doses gabapentin have?
Risk of respiratory depression
Risk of abuse and dependence: now sch 3
What is a serious side effect of lamotrigine?
Serious skin reactions - Stevens-Johnson syndrome and toxic epidermal necrolysis have developed (especially in children)
Most rashes occur within 8 weeks
Factors associated with this: rapid dose increase, use with valporate and initial high dose
What is the additional MHRA warning for pregabalin?
Respiratory depression
What is the additional MHRA warning for phenytoin?
risk of death and severe harm from error with injectable phenytoin
What is the additional MHRA warning for topiramate?
Start of safety review triggered by a study reporting an increased risk of neurodevelopmental disabilities (e.g. autism) in children with prenatal exposure
When can drug treatment be commenced in ADHD?
In patient with ADHD whose symptoms are still causing significant impairment in at least one area of function despite environmental modifications
How do you treat ADHD?
1st line: lisdexamfetamine or methylphenidate (6 week trial)
(dexamfetamine can be tried if the patient is having beneficial reponse to lisdexamfetamine but cannot tolerate its longer duration of effect
2nd lime: atomexetine
3rd line: guanfacine
What is the patient and carer advise for atomoxetine?
suicidal ideation
hepatic impairment
What are the administration instructions for guanfacine
avoid administration with hifh fat meals - may increase absorption
When should antidepressants be avoided in bipolar disporder?
In patients with rapid-cycling bipolar disorder, a recent history or mania or hypomania or with rapid mood fluctuations
What is used to treat acute episodes of mania or hypomania?
Antipsychotics: haloperidol, olanzapine, quetiapine and risperidone
if inadequate response: lithium or valporate may be added
How do you treat moderate to severe manic episodes associated with bipolar?
Asenapine - second generation antipsychotic
What is used for long-term management of bipolar?
Olanzapine - licensed for prevention of recurrence in patients whose manic episode has responded to olanzapine therapy
What is the minimum time antipsychotics should be discontinued over?
4 weeks
When are benzodiazepines used in bipolar?
(e.g. lorazepam)
May be helpful in initial stages of treatment for behavioural disturbance or agitation
Do not use for long periods due to risk of dependence
How long does the prophylactic effect of lithium take to occur?
6-12 months after initiating therpy
When is valproic acid used in bipolar?
Used for treatment of manic episodes associated with bipolar is lithium not tolerated or contraindicated
When is carbamazepine used in bipolar?
long-term management to prevent recurrence of acute episodes in patients unresponsive to lithium therapy
What are the specific side effects for valproic acid?
hepatic dysfunction - withdraw treatment immediately symptoms develop
Pancreatitis - discontinue if symptoms develop
What is the criteria for chronic depression?
for at least 2 years, either continually meet the criteria for diagnosis of major depression episodes, or have persistent subthreshold symptoms, or persistent low mood (with or without concurrent episodes of major depression)
What is the initial treatment for depression?
The use of antidepressants and/ or psychological or psychosocial treatment
When should patients on antidepressants be reviewed?
2-4 weeks for after initiation
Those at high risk of suicide or ages 18-25 should be reviewed 1 week after staring treatment or increasing dose
Effects seen within 4 weeks (6 weeks in elderly) and continue treatment for at least 6 months (12 months in elderly and patients being treated for anxiety)
How do you treat subthreshold or mild depression?
1st line: psychological and psychosocial therapy
2nd line: antidepressants if patient preference
- SSRI: citalopram, escitalopram, sertraline, fluoxetine, fluvoxamine or paroxetine
How do you treat moderate or severe depression?
1st line: combination therapy + antidepressants
- SSRI
2nd line: SNRI
- duloxetine or venlafaxine
Which class of antidepressants have the highest risk of overdose?
TCA
Which TCA has the best safety profile?
Lofepramine
What can be used in severe depression if rapid response is required?
electroconvulsive therapy
What can used if a patient has limited or no response to at least 2 antidepressants?
Vortioxetine
Which antidepressant is safest for patient who had recent MI or has unstable angina?
Sertraline
Which class of antidepressants have highest association with hyponatraemia?
SSRIs
consider hyponatraeia in all patients with symptoms including drowsiness, confusion, or convulsions
Which class of drugs is serotonin syndrome associated with?
MOAI
What are the symptoms of serotonin syndrome?
Neuromuscular hyperactivity - tremor, hyperreflexia, clonus, myoclonus, rigidity
Autonomic dysfunction - tachycardia, BP changes, hyperthermia, diaphoresis, shivering, diarrhoea
Altered mental state - agitation, confusion, mania
How do you treat anxiety?
usually benzodiazepines or buspirone
Chronic anxiety: antidepressant - can be combined with benzo until antidepressant takes effect
- SSRI e.g. escitalopram, paroxetine or sertraline
- 2nd line: SNRI - duloxetine ir venlafaxine
-3rd line: pregabaline
How do you treat panic disorders?
SSRI
2nd line: clomipramine or imipramine
Venlafaxine also licensed for panic disorders
How is OCD/ PTSD treated?
SSRI
2nd line: clomipramine
Which drug is licensed for social anxiety?
Moclobemide
Which tricyclics are more sedating?
Clomipramine
Dosulepin
Doxepin
Mianserin
Trazodone
Trimipramine
Which tricyclics are less sedating?
Imipramine
lofepramine
nortriptyline
Which MAOI has greater stimulant action is likely to cause hypertensive crisis?
Tranylcypromine
Which MAOI should be reserved for 2nd line?
Moclobemide (reversible MAOI)
What should be done when stopped an MAOI but started other antidepressants?
Do not start another antidepressant for 2 weeks after MAOI stopped but 3 weeks if staring clomipramine or imipramine
What should be done when stopping an antidepressant and starting an MAOI?
Do not start MAOI until:
- at least 2 weeks after previous MAOI has been stopped (then start at reduced dose)
- at least 7-14 days after tricyclic (3 weeks if clomipramine or imipramine) has been nstopped
- at least a week after am SSRI (5 weeks in the case of fluoxetine) has been stopped
What are the specific MAOI side effects?
Postural hypotension and hypertensive responses
Discontinue if palpitations or frequent headaches occur
What are the contraindicated of MAOIs?
Cerebrovascular disease
Not indicated for manic phase
Phaeochromocytoma
Severe cardiovascular disease
What is the patient and carer advise foe MAOIs?
Eat only fresh foods, avoid stale or going off foods
Danger of interaction persists for 2 weeks after stopping drug
Avoid alcoholic or de-alcoholised drinks
May cause drowsiness
Avoid foods and beverages containing tyramine - e.g. cheese, salami. herring, oxo, marmite, beers, largers, wines
What is the MHRA warning for SSRIs/SNRIs?
small increased risk of postpartum haemorrhage when used in the month before delivery
What are the contraindications of SSRIs?
Poorly controlled epilepsy
Should not be used if patients enters manic phase
What are the specific side effects of SSRIs?
Sexual dysfunction may persist after treatment has stopped
SSRIs can cause GI bleeds
Which the contraindication for citalopram and escitalopram?
Prolonged QT
What is the maximum citalopram dose in hepatic impairment?
20mg
Which SSRI has a higher risk of withdrawal reactions?
Paroxetine
What is the contraindication for venlafaxine
uncontrolled hypertension
What are the contraindications for amitriptyline?
Arrhythmias
During manic phase of bipolar
heart block
Immediate recovery period after MI
Which drug is used for control of deviant antisocial sexual behaviours?
Benperidol
What are the positive symptoms of psychosis?
Hallucinations
Delusions
What are the negative symptoms of psychosis?
Emotional empathy
Social withdrawal
Which psychosis symptoms are antipsychotics better at alleviating?
Positive symptoms
How long do patients need to be on antipsychotics before they are deemed unsuccessful?
At optimum dose frr 4-6 weeks
When is the only time 2 antipsychotics can be prescribed at the same time?
Clozapine augmentation OR
when changing medication during titration
What are the risks associated with prescribing 2 antipsychotics?
Extrapyrimadol side effects
QT prolongation
Sudeen cardiac death
When can clozapine be prescribed for schizophrenia?
When there has been sequential use of at least 2 different antipsychotics (1 of which should be 2nd generation antipsychotic) each for an adequate time and could not control schizophrenia
Allow 8-10 weeks to assess response - patient must be registered with clozapine patient monitoring service
What would you consider if patient not adhering to antipsychotic for psychosis and schizophrenia?
Long-acting depot injectable antipsychotic drugs
Which antipsychotics are more likely to cause extrapyramidal symptoms and hyperprolactinaemia?
first-generation antipsychotic drugs
e.g. piperazine
Phenothiazines
butyrophenones
Depot preparations
Name some 1st generation antipsychotics (typical/conventional)
Phenothiazine derivatives - chlorpromazine, fluphenazine, levomepromazine, pericyazine, prochlorperazine, promazine, trifluperazine
Butyrophenones - benperidol, haloperidol
Thioxanthenes - flupentixol, zuclopenthixol
Diphenylbutylpiperidines - pimozide
Substituted benzamides - sulpiride
Name some 2nd generation antipsychotics (atypical)
Amisulpride
Aripiprazole
Asenapine
Cariprazine
Clozapine
Paliperidone
Quetiapine
Risperidone
What adverse effects are 2nd generation antipsychotics associated with?
Glucose intolerance
Weight gain
How should antipsychotics be prescribed in emergency situations?
Initial prescription should be written as a single dose
oral and IM drugs should be prescribed separately
What are the risks of antipsychotics in elderly patients with dementia?
Increased risk of mortality
Increased risk of stroke and TIA
Higher risk of postural hypotension
When can antipsychotics be used in elderly patients with dementia?
When there is a risk of harming themselves or others, or experiencing agitation, hallucinations or delusions that are causing themselves severe distress
Lowest effective dose for shortest time
Patient should be reviewed at least every 6 weeks
What should be considered in patients with learning disabilities taking antipsychotics but not experiencing psychotic symptoms?
- reduction in dose or discontinuation
- reviewing patients condition after dose reduction or discontinuation
- refer to psychiatrist experienced in working with the patient
- annual documentation of reasons for continuing and not reducing or discontinuing
Which 2nd generation antipsychotics are associated with late-onset extrapyramidal symptoms?
Clozapine
Olanzapine
Quetiapine
Aripiprazole
What are extrapyramidal parkinsonian symptoms?
Bradykineasia - slow movement and speed
Tremor
Who are extrapyramidal parkinsonian symptoms more common in?
Female elderly patients
Those with pre-existing neurological damage e.g. stroke and may appear gradually
What are extrapyramidal dystonia symptoms?
Uncontrolled muscle spasms in any part of the body
Who are extrapyramidal dystonia symptoms more common in?
Young males
Can appear within hours of starting antipsychotics
What are extrapyramidal akathisia symptoms?
Restlessness - start within hours to weeks of starting antipsychotics or dose increase and can be mistaken for psychotic agitation
What are extrapyramidal tardive dyskinesia symptoms?
Abnormal involuntary movements of lips, tongue, face and jaw - can develop on long-term or high-dose therapy, or even after discontinuation
in some patients, it can irreversible
More common in elderly females
Which antipsychotic drugs are most likely to cause hyperprolactinaemia?
Risperadone
Amisulpride
Sulpiride
First generation antipsychotics
Which antipsychotic reduces prolactin concentration in a dose-dependent manner?
Aripiprazole
What are the symptoms of hyperprolactinaemia?
Sexual dysfunction
Reduced bone mineral density
Menstrual disturbances
Breast enlargement
Galactorrhoea
Increased risk of breast cancer
Which antipsychotic drugs have a lowest association with sexual dysfunction?
Aripiprazole
Quetiapine
Which antipsychotic drugs have a highest association with sexual dysfunction?
Riseperidone
Haloperidol
Olanzapine
Which cardiovascular side effects are associated with antipsychotics?
Tachycardia
Arrhythmias
Hypotension
Which antipsychotic is concerned with QT prolongation
pimozide
Also high risk in patients using IV antipsychotics or combination of antipsychotics whose doses exceed recommended amount
Which type of antipsychotics are most likely to cause postural hypotension?
2nd generation - clozapine and quetiapine
Which type of antipsychotics is most likely to cause diabetes?
2nd generation are more likely to cause diabetes
- amisulpride and aripiprazole have the lowest risk
From 1st generation antipsychotics - fluphenazine and haloperidol have the lowest risk of this
Which antipsychotics are associated with weight gain?
Clozapine and olanzapine
What are the symptoms of neuroleptic malignant syndrome?
Rare but fatal side effect of all antipsychotics
Hyperthermia. fluctuating level of consciousness, muscle rigidity, autonomic dysfunction with fever, tachycardia, liable BP and sweating
How should you act if neuroleptic malignant syndrome is suspected with antipsychotics?
Discontinue drug for at least 5 days preferably longer - symptoms should be allowed to resolve completely
Bromocriptine and dantrolene have been used for treatment
What is the monitoring requirements for antipsychotics?
Weight - baseline then weekly for 6 weeks then 12 weeks then yearly
Fasting glucose, HbA1c, blood lipid concentration - baseline, 12 weeks, yearly
Prolactin - baseline, 6 months then yearly
ECG - before treatment
BP - before treatment, 12 weeks, yearly
FBC, urea, electrolytes, LFTs - start of therapy and yearly
What if the MHRA warning for clozapine and other antipsychotics?
Monitoring blood concentration for toxicity
Which antipsychotic should pharmacists, nurses and other HCP be warned about handling?
chlorpromazine - risk of contact sensation
What are the safety and MHRA warnings for haloperidol?
Safety - no to confuse the IM/SC injections with depot preparations of haloperidol decanoate
MHRA - risks when used in elderly patients for acute treatment of delirium: increased risk of adverse neurological and cardiac effects
What are the oral and parenteral specific side effects for haloperidol?
Oral - angioedema
Parenteral - hypertension and severe cutaneous adverse reactions (SCARs)
What is the specific caution for prochlorperazine?
Hypothyroidism
What are the specific side effects for prochlorperazine?
With buccal use: blood disorders and hepatic disorders
Which 1st generation antipsychotics are available as depot injections?
No more than 2-3ml of oily injection at any one site
Flupentixol deconate
Haloperidol deconate
Zuclopenthixol deconate
What are the MHRA warnings for clozapine?
Potential fatal risk of intestinal obstruction, faecal impaction and paralytic ileus
Monitoring blood concentrations for toxicity
What is a specific caution for clozapine?
Agranulocytosis - neutropenia and potentially fatal agranulocytosis
Myocarditis and cardiomyopathy (most common in first 2 months)
Intestinal obstruction
How do you teat hypersalvation with clozapine?
hyoscine hydrobromide provided that the patient is not at risk of additive antimuscarinic side effects
What are common specific side effects of olanzapine?
IM: dyslipidaemia
Oral: hypersomnia
Which 2nd generation antipsychotics are available as depot injections?
Olanzapine embonate
How do you treat muscular symptoms of motor neurone disease?
1st line: Quinine
2nd line: baclofen
Subsequent treatment: tizanidine, dantrolene or gabapentin
How do you treat saliva problems in motor neurone disease?
Trial of antimuscarinic for excessive drooling of saliva
- glycopyrronium recommended in patients who have cognitive impairment as has fewer central nervous system side effects
2nd line: botulinum toxin type A
Treating thick, tenacious saliva - humidification, nebulisers and carboscisteinne
How do you treat breathlessness in motor neurone disease?
benzodiazepines or opioids
How do you treat amyotrophic lateral sclerosis in motor neurone disease?
Riluzole
What is used to control movement disorders in Huntington’s chorea and related disorders?
Terabenazine - also used for tardive dyskinesia if switching or withdrawing causative antipsychotic
Haloperidol, olanzapine, risperidone, quetiapine - also used to suppress chorea in Huntington’s disease
What is used to treat tourette’s syndrome and related choreas?
Haloperidol - improves motor tics
Pimozide (ECG monitoring required), clonidine, sulpiride,
How do you relieve intractable hiccups?
Chlorpromazine and haloperidol
How do you treat tremors associated with anxiety and thyrotoxicosis?
Propranolol and other beta blockers
Benginin essential tremor - primidone
What is the first line management of Parkinson’s disease in patients who’s motor symptoms are decreasing their QoL?
Levodopa combined with either carbidopa or benserazide (co-careldopa or co-benldopa)
What is the first line management of Parkinson’s disease in patients whos motor symptoms are NOT decreasing their QoL?
Levodopa OR
non-ergot-derived dopamine-receptor agonists: pramipexole, ropinirole, rotigotine OR
Monoamine-oxidase-B inhibitors: rasagiline or selegiline
What type of side effects are expected with antiparkinsonian drugs?
Psychotic symptoms
Excessive sleepiness
Sudden onset of sleep - especially dopamine receptor agonists
Impulse control
What motor complication is levadopa associated with?
Response fluctuations and dyskinesia
If end-of-dose deterioration = MR tablets
How do you treat daytime sleepiness and sudden onset of sleep in parkinsons?
Modafinil - review every 12 months
How do you treat nocturnal akinesia in parkinsons?
1st line: levodopa or oral dopamine-receptor agonists
2nd line: rotigotine
How do you treat postural hypotension in parkinsons?
1st line: midodrine
2nd line: fludrocortisone
How do you treat hallucinations and delusions and parkinsons?
patient with no cognitive impairment:
- 1st: quetiapine
- 2nd: clozapine
How do you treat rapid eye movement sleep disorder behaviour in parkinsons?
clonazapam
How do you treat drooling of saliva in parkinsons?
1st line: glycopyrronium
2nd line: botulinium toxin type A
Risk of cognitive adverse effects
- topical atropine
Which antiemetic can be used for chemo and radiotherapy induced N/V and is less sedating?
Prochlorperazine
Which antiemetic is used for N/V in palliative care?
Haloperidol
Which antiemetic is less likely to cause central effects?
Domperidone - it does not cross the BBB
Central effects examples:
- sedation
- dystonic reactions
Which antiemetic is used to treat N/V in parkinsons caused by dopaminergic drugs?
Domperidone
Which anti-emetics are used to prevent N/V from cytotoxics?
Ondansetron
Granisetron
Palonosetron
Palonosetron with netupitant
Which antiemetics are used in chemo-therapy induced N/V?
dexamethasone
aprepitant
What drug can be considered as add-on therapy for chemotherapy induced N/V when unresponsive to conventional antiemetic?
Nabilone - a synthetic cannabinoid with antiemetic properties
Which food can be helpful for pregnant women experiencing prolonged N/V?
Ginger
Which antiemetic options are there for N/V in pregnancy?
Chlorpromazine
Metoclopramide
Cyclizine
Doxylamine with pyridoxine
Prochlorperazine
Promethazine *
Ondansetron
Which antiemetics are used for post-operative N/V?
Granisetron
Ondansetron
Dexamethasone
Droperidol
Cyclizine - licensed for prevention and treatment of post-op N/V caused by opioids and general anaesthesia
Which antiemetic is licensed for motion sickness?
Hyoscine
Antihistamines
What is the MHRA warning for metoclopramide?
risk of neurological adverse effects - use only for 5 days
10mg TDS
Which antiemetic should be avoided in GI problems or obstruction?
Metoclopramide
(3-4 days after GI surgery)
What is the MHRA warning for ondansetron?
small increased risk of oral clefts following use in first 12 weeks of pregnancy
What is the definition of chronic pain?
Pain that persists more than 12 weels
What is a common co-morbidity of chronic pain?
Depression
Which analgesic should be avoided in pain in sickle-cell disease?
Pethidine because accumulation of neurotoxic metabolite can precipitate seizures
Which analgesic does naloxone only partially reverse?
Buprenorphine
Which analgesic has greater solubility and so allowed effective doses to be injected in smaller volumes?
Diamorphine hydrochloride (heroin)
What is the maximum number of times methadone can be administered per day?
twice to avoid risk of accumulation
How do you treat a cluster headache?
Sumatriptan s/c
if unsuitable - sumatriptan nasal spray or zolmitriptan nasal spray
What is considered as prophylaxis of cluster headache?
frequent attacks last of 3 weeks
What is the treatment for prophylaxis cluster headache?
Verapamil or lithium
What is used short-term for prophylaxis of episodic cluster headaches?
Prednisolone monotherapy or in combination with verapamil
What are the characteristics of a migraine?
Recurrent attacks of typically moderate-severe headaches lasting between 4-72 hours
Unilateral, pulsating, aggravated by routine physical activity
Usually accompanied by N/V, photophobia and phonophobia or both
What is a migraine WITH aura?
Consists of visual symptoms
- zigzag/ flickering lights, spots, lines or loss of vision
- dysphasia
- sensory symptoms e.g. pins and needles and numbness
What is considered as an episodic migraine?
headache which occurs less than 15 days per month
- low frequency = 1-9 days
- high frequency 10-14 days
What is considered as a chronic migraine?
Headache which occurs on at least 15 days per month and has characteristics of a migraine on at least 8 days per month for greater than 3 months
What is the first line treatment for acute migraine?
aspirin, ibuprofen or a triptan (sumatriptan drug of choice)
Should be taken as soon as patient knows they are developing a migraine
How should patients with migraines with aura take triptans?
Take at the start of the headache and not at the start of aura unless they both happen at the same time
Treatment can be repeated after 2 hours with the same or different drug if there was inadequate response
What should be used in patients presenting with severe N/V in acute migraines?
diclofenac sodium suppositories
What should be given to patients with acute migraines if they fail to response to monotherapy?
Sumatriptan and naproxen
Which antiemetics can be given to relieve N/V in acute migraines?
Metoclopramide or prochlorperazine
Domperidone - alternative
What is recommended treatment for preventative migraine treatment?
1st line: Propranolol - episodic or chronic migraine
- unsuitable: other beta blockers
2nd line: topiramate (risks of birth defects - highly effective contraception)
other drugs that can be used
- amitriptyline
- candesartan
These should be used for at least 3 months before considering it ineffective - a good response is a 50% reduction in severity and frequency of migraines
3 or more prophylactic treatments ineffective - botox
How do you treat menstrual migraine prophylaxis?
Frovatriptan - instead of or in addition to standard prophylactic treatment
- 2 days before until 3 days after menstruation starts
Alternatives: zolmitriptan or naratriptan
Patient must have regular cycle for medication to be effective
What is recommended for postherpetic neuralgia?
Capsaicin
What is recommended for trigeminal neuralgia?
Carbamazepine - reduces frequency and severity of attachs
What are the characteristics of benzodiazepines withdrawal syndrome?
isnomnia
anxiety
loss of appetite and body weight
tremor
perspiration
tinnitus
perceptual disturbances
Can occur up to 3 weeks after stopping
What is the recommended withdrawal regimen for diazepam?
reduce by 1-2mg every 2-4 weeks: in patients taking higher doses it may be suitable to reduce by 1/10th every 1-2 weeks
Towards end of withdrawal may be necessary to reduce in steps of2 500mcg
What are the risks of hypnotics and z-drugs in elderly patients?
risk of becoming ataxic and confused leading to falls and injury
Which benzodiazepines are used as hypnotics?
Nitrazepam and flurazepam - longer acting
Loprazolam, lormetazepam and temazepam - shorted acting (little to no hangover effect)
Which hypnotic is referred in elderly?
Clomethiazole - freedom from hangover
What is the treatment for precipitated withdrawal with buprenorphine?
Lofexidine if symptoms are severe
How do you reduce the risk of precipitated withdrawal?
first dose of buprenorphine should be given when patient is exhibiting signs of withdrawal or 6-12 hours after last use of heroin or 24-48 hours after last dose of methadone
When is methadone initiated?
at least 8 hours after last heroin dose
When is methadone and buprenorphine withdrawal preferable in pregnancy?
during second trimester with dose reductions made every 3-5 days
- first trimester poses a risk of spontaneous miscarriage
- third trimester not recommended because of maternal withdrawal
What are the symptoms of neonatal withdrawal?
High-pitched cry
Rapid breathing
Hungry but ineffective suckling
Excessive wakefulness
Severe but rare symptoms include - hypertonicity and convulsions
What is used to attenuate alcohol withdrawal symptoms?
Chlordiazepoxide or diazepam
Carbamazepine
Clomethiazole - if taking with alcohol can lead to fatal respiratory depression (particularly with cirrhosis)
What is used first line for delirium tremens and alcohol-induced seizure?
Lorazepam
What should be used in patients with mild alcohol dependence where psychological intervention alone not successful?
Acamprosate calcium or oral naltrexone
What is recommended for reducing alcohol consuming in patients who have a high risk drinking level?
Nalmefene
What are the preferred options for stop smoking drug treatment?
Varenicline (unavailable in the UK)
Long-acting NRT - patch
Short-acting NRT - lozenges, gum, sublingual tablets, inhalator, nasal and oral spray
If not appropriate - use bupropion or single therapy NRT
Do not combine therapies
What is the MHRA warning for bupropion?
risk of serotonin syndrome when used with other serotonergic drugs
What is the treatment for depression in childnre?
1st line: fluxoetine 10mg (Can be increased up to 20mg after a week if required)
2nd line: sertraline ot citalopram
Which drugs should NOT be used in the treatment of depression in children and young people?
Paroxetine
Venlafaxine
TCAs
What is the normal serum lithium concentration?
0.4-1 mmol/L
Target in acute mania: 0.8-1 mmol/L
What do MAOIs interact with to cause hypertensive crisis?
Tyramine rich food
Ephedrine or pseudoephedrine
Levodopa
Stimulants e.g. methylphenidate and amphetamine
What predisposes patients to seratonin syndrome with MAOIs?
Tramadol
Other antidepressants
What predisposes patients to CNS excitation or depression with MAOIs?
Tramadol
Pholcodine
Opioids
Avoid the above during MAOI treatment and for 14 days after stopping the MAOI
What are the side effects of methylphenidate?
Decreased appetite
Growth retardation
CV abnormalities
Psychiatric symptoms
Hypertension
Arrhythmia
In children - monitor weight and height every 6 months
Which benzodiazepines are short-acting?
<1-12 hours
Midazolam
Oxazepam
Triazolam
Which benzodiazepines are intermediate acting?
12-24 hours
Flunitrazepam
Lorazepam
Alprazolam
Clonazepam
Temazepam
Which benzodiazepines are long-acting?
> 24 hours
Flurazepam
Nitrazepam
Chlordiazepoxide
Diazepam
What are the anti-cholinergic side effects?
Dry mouth
Blurred vision
Urinary retention
Constipation
What is used for extrapyrimadole side effects?
Procyclidine
What are the ADRs of atypical antipsychotics?
Weight gain
Dyslipidaemia
Diabetes
Drowsiness
Reduced seizure threshold
Anticholinergic side effects
Hyperprolactinaemia
- ED
- Galactorrhoea
- Gynaecomastia
CV effects
- Postural hypotension
- QT prolongation
What are the ADRs of clozapine?
Agranulocytosis
Neutropenia
Hypersalivation
Constipation
Cardiomyopathy
Myocarditis
Intestinal obstruction
What are the SSRI interactions?
NSAIDs - risk of bleeding (PPI if given together)
Warfarin/Heparin/NOAC - risk of bleeding
Aspirin - risk of bleeding
Triptans - risk of sertonin syndrome
MAOIs - risk of sertonin syndrome
Drugs that prolonged QT with citalopram e.g. antipsychotics
What is antidote for benzodiazepines?
Flumazenil
What is antidote for antidepressants?
Activated charcoal
IV loarzepam od diazepam
Sodium bicarbonate
What is antidote for lithium?
Haemodialysis
Gastric lavage
What is antidote for stimulant drugs?
Diazepam or lorazepam
What is antidote for iron?
Desfferioxamine
For which drugs do you need to screen test for HLA-B*1502 allele in Han-chinese and thai patients before treatment?
Carbamazepines
Phenytoin
Higher risk of stevens-johnson syndrome
What are the interactions of lithium?
Diuretics especially thiazides - increases lithium concentration
ACEi/ARBs - increases lithium concentration
NSAIDs - increases lithium concentration
Metronidazole - increases lithium concentration
Iodine salts - risk of hypothyroidism
Carbamazepine - risk of neurotoxicity
Antipsychotics - QT prolongation
Which anti-epileptic can be prescribed by a dentist?
Carbamazepine for forms of neuralgia
What are the side effects of carbamazepine?
GI upset - N/V
Neurological effects - ataxia and dizziness
Oedema
Hyponatraemia
Which parkinsons medication turns urine colour reddish-brown?
Entacapone
Which antiepileptics are enzyme inducers?
Carbamazepine
Phenobarbital
Eslicarbazepine
Oxcarbazepine
Phenytoin
Primidone
What is the contraindication of tramadol?
Uncontrolled epilsepsy
Which anti-epileptic drugs does not reduce the effectiveness of oral contraception?
Lamotrigine
What is the maximum dose of citalopram in patients ages 65+?
20mg
Which OTC product reduces lithium concentrations?
Antacids containing sodium bicarbonate increase lithium excretion
What records are kept in the lithium therapy record book?
Lithium blood results
TFTs
Renal checks
Weight/ BMI
What is the maximum total duration of therapy when using clomethiazole for alcohol withdrawal?
9 days
Which antiemetic is considered safe in parkinsons diease?
Domperidone - doesn’t cross BBB
2nd line - ondansetron but causes constipation
Which antiemetics worsen parkinsons disease?
Metoclopramide
Haloperidol
Prochlorperazine
Which test should be done monthly before supple of clozapine
White blood cells - due to risk of fatal agranulocytosis
What is donepezil associated with?
Neuroleptic malignant syndrome
What is galantamine associated with?
Serious skin reactions - stop at first sign of rash (stevens-johnson syndrome)
What is rivastigmine associated with?
GI problems - withhold
What are cholinergic side effects?
DUMB BELS
Diarrhoea
Urination
Muscle weakness/ miosis (small pupils)
Bronchospasm
Bradycardia
Emesis (vomiting)
Lacrimation (tears)
Salivation
(opposite of antimuscarinic effects)
Which antiepileptic drugs are in high amounts in breastmilk?
ZELP
Zosinamide
Ethosuximide
Lamotrigine
Primidone
What is the treatment for menstruation epilepsy?
Acetazolamide
What is the only benzodiazepine that can be prescribed for alcohol withdrawal?
Chlordiazepoxide hydrochloride
What is the interaction between phenytoin and ciprofloxacin?
Can increase or decrease the concentration of phenytoin
What if the interaction between phenytoin and St Johns Worts?
Decrease in phenytoin serum concentration
Which triptan drug requires dose adjustments when given with propranolol?
Rizatriptan
What is a common SSRI electrolyte imbalance?
Hyponatraemia
- n/v
- confusion
- headache
When is a lithium level taken?
12 hours after dose otherwise levels may be too high but not accurate
What needs to be monitored for clozepine?
Neutropenia
is the maintenance dose of donepezil?
10mg ON
Which acetylcholinesterase causes sleep probelms?
Donepezil - try changing dose to the morning time
What do you do if the patient is experiencing bradycardia with donepezil?
Stop donepezil and start memantine - giving them another acetylcholinesterase is not helpful because they have the similar side effects
What is the therapeutic range for phenytoin?
10-20mg/L
What increases the risk of phenytoin toxicity?
Hypoalbuminaemia
Hepatic impairment
Hyperbilirubinaemia
What are the signs of phenytoin toxicity?
- nystagmus (involuntary movement of the eyes)
- diplopia/blurred vision
- slurred speech
- ataxia
- confusion
- hyperglycaemia
Which antidepressant used for chronic pain has an anticholinergic burden?
Amitriptyline (TCAs)
What are the side effects of phenytoin?
- Agranulocytosis
- Skin rashes, toxic epidermal necrolysis
- Suicidal thoughts
- Low vitamin D- rickets, osteomalacia
Which drug causes a sudden onset of sleep?
Levodopa
How much time should be left in between different levodopa preperations?
At least 12 hours
Which drug requires regular monitoring of neutrophils and leucocytes?
Clozapine
What is a licensed treatment for behavioural and psychological symptoms of Alzeihmers disease?
Risperidone
Which antidepressant is associated with weight gain?
Mirtazapine
Which anti-emetic is associated with muscle-rigidity, movement disorders, tremor and parkinsonism?
Droperidol
What factors slow down metabolism of antipsychotics?
Females
Geriatric age
Non-smokig status
How long should remission period last for antidepressants?
6 months
12 months - in elderly and those being treated for generalised anxiety
2 years in patients with recurrent remission
Which TCA has more marked anti-muscarinic effects?
Imipramine
What is the counselling for antipsychotics?
Photosensitisation may occur with higher doses - avoid direct sunlight
Which drugs can aid smoking cessation and be used alongside behavioural support?
Varenicline and bupropion
Which Parkinson’s Medication is more likely to cause impulse reactions?
Non-ergot derived! More than levodopa
E.g. pramipexole, ropinirole, rotigotine
Which CNS drugs tend to cause hyponatraemia?
SSRIs
Carbamazepine
(diuretics and desmopressin too)
What side effects do non-ergot derived drugs cause?
Pramipexole, ropinirole, rotigotine
- impulse disorders
- sudden onset of bleed
- hypotensio
What is usually prescribed for wernicke’s encephalopathy?
thiamine (b1)
What are paradoxical side effects of benzodiazepines and how is it treated?
SE: increase talkativeness, emotional release, excitement, excessive movement, hostility and aggression
It is essentially benzodiazepine toxicity = treat with flumazenil
How often is clozapine monitored?
weekly for first 18 weeks
fortnightly from 18 weeks - 52 weeks
Then monthly
Blood lipids and weight - baseline then every 3 months
Fasting blood glucose - at baseline, after 1 month then every 4-6 months
What is the age restriction for domperidone?
12+
What is offered for advanced parkinsons disease with ‘off episodes’?
apomorphine hydrochloride as intermittent injections or continuous subcutaneous infusions
- if pt experiences nausea and vomiting with this = domperidone started 2 days before apomorphine
–> assess cardiac risk factor first due serious arrhythmia from to prolonged QT
What are some important methadone interactions?
Citalopram, amiodarone, aripiprazole, tetracyclines - QT prolongation
Clarithromycin increases methadone exposure
Bendroflumethiazide, budesonide, betamethasone - hypokalaemia
Which drugs are likely to cause seratonin syndrome?
SSRI
TCA
Triptans
Tramadol
Lithium
Which benzodiazepines have a driving limit?
COLD FeeT
Clonazepam
Oxazepam
Lorazepam
Diazepam
Flunitrazepam
Temazepam
What are the signs of carbamazepine toxicity?
HANGBAGS
Hyponatraemia
Ataxia
Nystagmus
Drowsiness
Blurred vision
Arrhythmia
GI disturbances
Which 1st generation antipsychotics have the least extrapyramidal side effects?
Group 2 phenothiazines:
pericyazine
Which 1st generation antipsychotics have the highest risk of extrapyramimdal side effects?
Group 3 phenothiazines:
fluphenazine, prochlorperazine and trifluoperazine
Also:
Benperidol and haloperidol
What antidepressants does tamoxifen interact with?
Fluoxetine and paroxetine - they decrease efficacy of tamoxifen
Which drug reduces your visual field?
Vigabatrin
Which benzodiazepine is not associated with blood dyscrasias?
Clonazepam
What colour can amitriptyline colour urine?
Greenish-blue
Which drug is licensed for treating Meniere’s disease?
prochlorperazine
