CNS bits and pieces! Flashcards
Prophylaxis and treatment of NV?
Antihistamines (cyclizine and promethazine)
Phenothiazines (prochlorperazine)
NV in pregnancy
Avoid drug therapy
PROMETHAZINE
Post-operative NV
5HT3 receptor antagonist (ONDANSETRON)
Dexamethasone
Pre-operative anticipatory NV?
Lorazepam
Motion sickness?
Hyoscine HYDRObromide
Palliative care NV WITH OPIOID therapy?
Antipsychotic (Haloperidol and Levomepromazine)
Pts with PD NV?
Domperidone
DOMPERIDONE - DA receptor antagonist
Doesn’t cross BBB, thus, good for PD
10mg TDS for 7 days maximum use
Only for 12+
Pts should be 35kg+
Causes QT prolongation
METOCLOPRAMIDE - DA receptor antagonist
MHRA/CHM advice—Metoclopramide: risk of neurological adverse effects—restricted dose and duration of use
Causes extrapyramidal SEs - don’t use in PD
10mg TDS for a maximum of 5 days
18+
Metoclopramide can induce acute dystonic reactions involving facial and skeletal muscle spasms and oculogyric crises. These dystonic effects are more common in the young (especially girls and young women) and the very old; they usually occur shortly after starting treatment with metoclopramide and subside within 24 hours of stopping it.
Bipolar Disorder
Acute:
- Benzodiazepines
- Antipsychotic drugs => usually 2nd gen: Quetiapine, Olanzapine, or Risperidone
- Add in Li or Na Valproate
Prophylaxis:
- Carbamazepine, Na Valproate or Lithium
Lithium - SICK + TREMOR
Acute episodes = 0.8 - 1mmol/L
Therapeutic range = 0.4 - 1mmol/L
Measure levels 12h post dose
Monitor: weekly until stable, then 3 monthly for year 1, and then 6 monthly after that
Toxicity: REVeNG
Renal impairment - incontinence
Extrapyramidal SE - tremors
Visual Disturbances - blurred vision
Nervous System disorder - confusion and restlessness
GI disorder - diarrhoea and vomiting
SE:
- Thyroid disorder
- Nephrotoxicity
- Rhabdomyolysis
- QT prolongation
- Benign intracranial HTN
- 1st trimester - TERATOGENIC
Interactions:
- Hyponatraemia increases risk of toxicity - diuretics
- Salt imbalance
- Serotonin syndrome
- Extrapyridamil SEs
- QT prolongation
- Renally cleared drugs - increase risk of toxicity
- Reduced seizure threshold
- hypokalemia
Dementia - TREATMENT - due to increasing ACh
Mild - moderate dementia = Acetylcholinesterase inhibitors:
- DONEPEZIL - neuroleptic malignant syndrome, take ON, can cause bradycardia - monitor pulse
- Rivastigmine - GI SEs (reduced in transdermal formulation)
- Galantamine - SJS, SCARs (Severe Cutaneous Adverse Reactions)
Moderate-severe dementia:
- Memantine
SE = balance disorders, constipation, dizziness/drowsiness
Aggravation treated with BENZODIAZEPINES (lorazepam) or ANTIPSYCHOTICS (risperidone)
SE: Increased ACh => parasympathetic SEs
Diarrhoea
Urinary incontinence
Muscle weakness
Bradycardia
Bronchospasms
Emesis
Lacrimation
Salivation
Stop treatment, treat the dehydration before reinitiating, amend the dose if needed
PD - due to alleviating DA
- Pts whose motor symptoms DECREASE their quality of life:
LEVODOPA + CARBIDOPA / BENSERAZIDE - Pts whose motor symptoms don’t affect their quality of life:
LEVODOPA
NON-ERGOT-DERIVED DA RECEPTOR = pramipexole, ropinirole, rotigotine
MOA-B INHIBITORS - selegiline - Pts who develop dyskinesia or motor fluctuations despite optimal levodopa therapy should add an adjuvant to the levodopa:
- non-ergot DA receptor agonists, MAOI-B inhibitors
- COMT inhibitors - If symptoms are not adequately controlled with a non-ergot-derived DA receptor agonist as an adjunct to levodopa:
- Ergot-derived DA receptor agonists
LEVODOPA
Carbidopa / benserazide is added in order to prevent the breakdown of levodopa before it crosses into the brain
- Impulse disorders = pathological gambling; binge eating; hypersexuality
- end of dose deterioration (wearing off) - effects of levodopa wear off before the next dose is due. If too much off-periods, use MR preps
Apomorphine is used in advanced disease for predictable “off” periods - as it has a high incidence of NV, thus, put pt on domperidone (peripheral D2 blocker) at least 2 days prior to starting. MHRA warning as if QT prolongation is found, STOP ASAP - must assess cardiac risk factors and ECG monitoring.
- Sudden onset of sleep = treat with modafinil (increased risk of congenital malformations if used during pregnancy)
SE: N (can take with food), postural hypotension, somnolence, urine discolouration etc.
- red urine
Non-ergot-derived DA receptor
Pramipexole, ropinorole, rotigotine
- impulse disorders
- sudden onset of sleep
- hypotension
This can be added to levodopa therapy to increase the “on” time.
MAOI-B inhibitors
Selegiline - may cause insomnia due to amphetamine-like metabolites, Rasagiline
- causes hypertensive crisis if given with phenylephrine pseudoephedrine, xylometazoline
Interacts with tyramine-rich foods:
- Mature cheese
- Salami
- Marmite
- Yeast
- Tofu
SSRIs = can cause serotonin syndrome
SE = can increase levodopa SEs, thus, reduce levodopa dose
COMT inhibitors
Entacapone - red-brown urine, tolcapone - hepatotoxic; taken 2 - 3h apart from iron preps
Increases sympathetic SEs - increase in CVD effects
Ergot-derived DA receptor agonists
Bromocriptine, Cabergoline - licensed to suppress lactation
Pulmonary reactions = report SoB, chest pain, cough
Pericardial reactions = chest pain
Non-motor symptoms in PD
- daytime sleepiness and sudden onset of sleep
MODAFINIL - Nocturnal akinesia
1st line: LEVODOPA or PO DA-receptor agonists
2nd line: rotigotine - Postural hypotension
MIDODRINE
2nd (unlicensed): fludrocortisone - Psychotic symptoms
No cognitive impairment: QUETIAPINE (unlicensed)
If standard treatment isn’t effective: CLOZAPINE - Rapid eye movement sleep behaviour disorder
CLONAZEPAM or MELATONIN (unlicensed indications) - Drooling of saliva
1st line: GLYCOPYRRONIUM BROMIDE (unlicensed indication)
2nd line: Botox (botulinum toxin type A) - PD Dementia
1st line: acetylcholinesterase inhibitors
2nd line: memantine
Psychosis and Schizophrenia
Positive: delusions, hallucinations, disorganization
Negative: Social withdrawal, neglect, poor hygiene
2nd gen antipsychotics
Amisulpride
Aripiprazole
Clozapine
Olanzapine
Quetiapine
Risperidone
Psychosis and Schizophrenia - 1st gen antipsychotics - PHENOTHIAZINES
Group 1: Chlorpromazine, Levomepromazine, promazine
MOST SEDATION, moderate antimuscarinic and EPSEs
Group 2: Pericyazine
Moderate sedation, LEAST EPSEs
Group 3: Fluphenazine, prochlorperazine and trifluoperazine
Moderate sedation, HIGH EPSEs
Psychosis and Schizophrenia - 1st gen antipsychotics - THIOXANTHENES
Flupentixol, Zuclopenthixol
Moderate sedation, antimuscarinic effects, EPSEs
Psychosis and Schizophrenia - 1st gen antipsychotics - BUTYROPHENONES
Benperidol, Haloperidol
Moderate sedation, HIGH EPSEs (similar to Phenothiazines Group 3)
Psychosis and Schizophrenia - 1st gen antipsychotics - Others
Pimozide, sulpiride
Reduced sedation, antimuscarinic effects and EPSEs
Antipsychotics SEs
Extrapyramidal SEs: Most in phenothiazine group 3 (prochlorperazine) and butyrophenones (Haloperidol)
Hyperprolactinaemia: Least in ARIPIPRAZOLE. Risperidone, amisulpride, sulpiride, and first-generation antipsychotic drugs are most likely to cause symptomatic hyperprolactinaemia. Hyperprolactinaemia is very rare with aripiprazole, asenapine, cariprazine, clozapine, and quetiapine treatment.
Sexual dysfunction: ALL antipsychotics => Risperidone, haloperidol, and olanzapine have a higher prevalence to cause sexual dysfunction. The antipsychotic drugs with the lowest risk of sexual dysfunction are aripiprazole and quetiapine.
Cardiovascular SEs: QT prolongation most common with PIMOZIDE and HALOPERIDOL
Hypotension: CLOZAPINE and QUETIAPINE
Hyperglycaemia: (CiROQ) - Clozapine, Risperidone, Olanzapine, Quetiapine. Of the first-generation antipsychotic drugs, fluphenazine decanoate and HALOPERIDOL have the lowest risk. AMISULPIRIDE and ARIPIPRAZOLE have the lowest risk of diabetes of second-generation antipsychotic drugs.
Weight gain: (COW) Clozapine and Olanzapine = Weight gain
Neruleptic Malignant Syndrome: Stop treatment => treat with BROMOCRIPTINE => Should resolve in 5 - 7 days
Antipsychotic monitoring
Weight: Start, weekly for the first 6 weeks, at 12 weeks, at 1 year, then yearly
Fasting blood glucose, HbA1c and blood lipid concentrations: Start, at 12 weeks, at 1 year, and then yearly
ECG: Before initiation
BP: Start, at 12 weeks, at 1 year, then yearly
FBC, U&Es and LFTs: Start, then yearly
CLOZAPINE - used in resistant schizophrenia: only used when 2+ antipsychotics including one 2nd gen has been used for 6-8 wks each!
If missed more than 2 doses - specialist reinitation
Monitor leucocyte and differential blood counts:
- weekly for 18 weeks
- fortnightly until 1 year
- monthly
Blood lipids and weight:
- baseline
- 3 months for the 1st year
- Yearly
Fasting blood glucose:
- baseline
- then every 4-6 months
- yearly
SEs:
- Myocarditis and Cardiomyopathy => report and stop on tachycardia, most common in first 2 months
- Agranulocytes and Neutropenia => Monitor leucocyte and differential blood counts as previously mentioned
- GI disturbances: Report and stop on CONSTIPATION => intestinal block!
Common SE:
- feeling drowsy
- making extra saliva and dribbling, or a dry mouth
- loss of appetite
- fast HR
- feeling sick
- constipation
- gaining weight
- being able to hold your urine, alt. hard going to the toilet
- dizziness
- jerking or fits
- blurred vision
- Avoid alcohol as can make you more drowsy
- Changing the amount of caffeine that I drink (tea, coffee, or cola) can affect the amount in the blood.
- Initial treatment - avoid driving
- Smoker = increase dose; stop smoking = decrease dose at cigarette smoke breaks down the drug more quickly.
On planned withdrawal reduce dose over 1–2 weeks to avoid risk of rebound psychosis. If abrupt withdrawal necessary observe patient carefully.
Anxiety - Treatment
Acute: Benzodiazepines
Chronic: SSRI - Sertraline, Citalopram, Escitalopram, Fluoxetine; Propranolol - alleviates PHYSICAL symptoms only
Benzodiazepines
Long acting benzodiazepines => diazepam, alprazolam, chlordiazepoxide, clobazam
Short-acting benzodiazepines => lorazepam, oxazepam
- These preferred in pts with hepatic impairment and elderly
- They carry a GREATER RISK OF WITHDRAWAL symptoms (use for 2-4 weeks)
Can induced HEPATIC COMA, esp in long-acting benzos => treat with lowest dose for shortest period
Can cause PARADOXICAL effects: aggression, hostility, talkative, anxious, excited
Sedation increased with use of alcohol, CNS depressants or CYP enzyme inhibitors - avoided in concomitant use
Avoid driving if feeling drowsy => they’ve a legal driving limit (COLD FeeT) = Clonazepam, Oazapam, Lorazepam, Diazepam, Flunitrazepam and Temazepam
Overdose treated by FLUMAZENIL
Benzodiazepines withdrawal
Dependence = anxiety, sweating, weight loss, tremors, loss of appetite
1) Convert all meds to ON dose of diazepam
2) Reduce by 1-2mg (1/10th on larger doses) every 2-4 weeks - only further withdraw if the pt has overcome any withdrawal symptoms
3) Reduce further (0.5mg near the end)
Sleep disorders - Benzos and Z-drugs
Long-acting benzodiazepines = Nitrazepam, diazepam and flurazepam
- Higher hangover effect on the following day
- Sleep maintenance
Short-acting benzodiazepines = loprazolam, lormetazepam, and temazepam
- Little or no hangover effect
- Used for sleep onset
- Higher chance of withdrawal symptoms
Z-drugs = Zolpidem, Zopiclone
- increases GABA => CNS depression
- Dependency occurs within 3-14 days of use
- should be used for 4 wks max
- should be taken intermittently
- Benzos + Z-drugs => avoid in the elderly due to risk of falls and injury
- Paradoxical SEs = staying awake at night
- Drowsiness
- Dependence
ADHD - Treatment
Kid > 5 years:
1. Methylphenidate
2. If a 6-week trial of M at the max tolerated dose doesn’t reduce symptoms - switch to Lisdexamfetamine
Kids who are intolerant of both M and L:
3. Atomoxetine or Guanfacine
Adults:
1. Methylphenidate or Lisdexafetamine - Dexamfetaine if pt can’t tolerate long duration of action
2. Atomoxetine - causes QT prolongation, hepatotoxicity and suicidal idealation
MR preps are preferred due to their pharmacokinetic profile, convenience and improved adherence
MR preps should be prescribed by BRAND!
ADHD - Methylphenidate (CD-2)
CNS stimulant
High BP, tachycardia, arrhythmias
Behaviour / mood changes, drowsiness and sleep disorders
Decreased appetite, growth retardation and Wt loss
Monitor: pulse, BP, psychiatric symptoms, appetite, weight and height initiation - recorded at initiation of therapy, following each dose adjustment, and at least 6 monthly thereafter
ADHD - Lisdexamfetamine (CD-2) and Dexamfetamine (CD-2)
Similar SE to M.
Overdose:
- causes: wakefulness, excessive activity, paranoia, hallucinations and HTN
- followed by: exhaustion, convulsions, hyperthermia and coma
Similar monitoring to M.
Depression - Treatment
Mild: CBT
Moderate-Severe: Antidepressants
Pt may feel worse in the first 1-2 weeks
Should be taken for 4 weeks (6 weeks in the elderly) b4 deemed ineffective
Take for 6 months after remission, 1 year in elderly, 2 years in recurrent
Depression - Antidepressants
1st: SSRI
2nd: Increase SSRI dosage, change SSRI, Mirtazapine, MAOI (specialist), TCA or Venlafaxine (severe)
3rd: Add in another class: Li or antipsychotic
Use electroconvulsive therapy in severe refractory depression
SSRIs - better tolerated and safer in overdose
Max OD doses:
Sertraline: 200mg
Fluoxetine: 60mg
Citalopram: 40mg (20mg in elderly)
Paroxetine: 50mg (40mg in elderly)
1st line for treating depression
Sertraline = safest in pts with cardiac events
Fluoxetine for kids < 17 years
CI: poorly controlled epilepsy
SE:
- GI - diarrhoea and V
- appetite and weight gain
- sexual dysfunction
- risk of bleed
- insomnia - take OM
- QT prolongation - Esp with citalopram and escitalopram
Interactions:
- CYP enzyme inhibitors => AVOID grapefruit!
- CYP enzyme inducers
- QT prolongation drugs - amiodarone, sotolol, quinolones
- Drugs increase the risk of bleed
- Hyponatraemia - carbazmazepine and diuretics
- Serotonin syndrome = St John’s Wort, Triptans, Opioids
- Tamoxifen = avoid with FLUOXETINE and PAROXETINE as it decreases the efficacy of Tamoxifen
Serotonin syndrome:
- Cognitive effects = headache, agitation, hypomania, coma, confusion
- autonomic effects = sweating, hyperthermia, N, diarrhoea
- neuromuscular excitation = myoclonus, tremor, teeth grinding
Caused by:
- SSRIs, TCAs, MAOIs
- Triptans
- Tramadol
- Li
TCAs
Sedating - better for agitated and anxious pts
- Amitriptyline, Clomipramine, Dosulepin and Trazodone
Less sedating - better for withdrawn and apathetic pts
- Imipramine, Lofepramine and Nortiptyline
Amitriptyline + Dosulepin = dangerous in overdosage - not recommended for the treatment of depression
SE: CASHH
- Cardiac events
- Anti-muscarinic
- Seizures
- Hypotension
- Hallucinations
DANGEROUS IN OVERDOSE
Interactions:
- CYP enzymes inhibitors
- CYP enzymes inducers
- QT prolongation = amiodarone, sotalol, quinolones
- anti-muscarinic drugs
- anti-hypertensive drugs
- serotonin syndrome
MAOIs - specialist use only!
Causes HEPATOTOXICITY - Phenelzine + isocarboxazid
Hypertensive crisis - don’t give OTC pseudoephedrine!
Avoid tyramine-rich foods!
Tranylcypromine + Clomipramine = FATAL! severe toxic reaction when given with Tranylcypromine. Manufacturer advises avoid and for 14 days after stopping the MAOI.
MAOI washout periods!
MAOI => 2 weeks => Other antidepressants
MAOI => 3 weeks => Clomipramine or imipramine
MAOI => 2 weeks => new MAOI
Moclobemide => 0 weeks => new MAOI
TCA or related antidepressant => 1-2 weeks => MAOI
Clomipramine or imipramine => 3 weeks => MAOI
SSRI or related antidepressant => 1 week => MAOI
Fluoxetine => 5 weeks => MAOI
? Sertraline => 2 weeks => MAOI
Mirtazapine
Max dose: 45mg
ADR: Blood dyscrasias, Exanthema, Sedation
CI: x < 18 years
Interactions:
- Increase mirtazapine levels => Antifungals, cimetidine, erythromycin
SNRIs - Serotonin and NA re-uptake inhibitors
Max dose:
Venlafaxine: 375mg
Duloxetine: 60mg
MHRA: SSRI/SNSRI antidepressant medicines: small increased risk of postpartum haemorrhage when used in the month before delivery - venlafaxine.
ADR: Hypertension, somnolence
C/I: Uncontrolled hypertension
Interactions:
- Diltiazem, Verapamil => venlafaxine levels increase!
- Drugs increasing QT interval
- Drugs increasing bleeding risk
Alcohol dependence - Treatment
CBT or ACAMPROSATE or NALTREXONE (Alt: disulfram)
Withdrawal symptoms = Long-acting benzos, for example, CHLORDIAZEPOXIDE or DIAZEPAM (Alt: Carbamazepine or Clomethiazole)
Delirium = LORAZEPAM
Wernicke’s Encephalopathy: Thiamine (Vit B1)
Nicotine Dependence - Treatment
VARENICLINE
- avoid in epilepsy, CVS disease and psychiatric illness
BUPROPION
- Avoid in psychiatric illness, seizures and eating disorders
- causes serotonin syndrome
NRT:
- Patch (16h patch if pregnant or experiencing nightmares) AND
- Short-term reliever = lozenges, gum, sublingual tabs, inhalator, nasal spray and oral spray
Opioid dependence - treatment
Treatment for opioid dependence should be initiated under the supervision of an appropriately qualified prescriber
On FP10MDA form - max supply of 14 DAYS
3 or more missed doses = refer pt back to the specialist
Treatment should be continued throughout pregnancy
NALOXONE can be prescribed as well if the pt is at a high risk of overdose
Buprenorphine:
- less sedating than methadone
- milder withdrawal symptoms
- lower risk of overdose
- SUBOXONE - buprenorphine with naloxone - when there’s a risk of injecting
Methadone:
- causes QT prolongation
- carefully titrated according to pt’s needs
Migraines - ACUTE treatment
Treat with ASPIRIN, IBUPROFEN, or a 5HT1-receptor agonist (SUMATRIPTAN favourable)
Take as soon as the pt knows that they are developing a migraine
With aura: Triptan taken at the start of the headache and not at the start of the aura
Triptan can be repeated after 2h (4h in Naratriptan) ONLY if there has been a response to first dose but not fully adequate
Use SOLUBLE PARACETAMOL if unable to take first line options
Antiemetics may be require: EMTOCLOPRAMIDE or PROCHLORPERAZINE
Migraine - PROPHYLAXIS TREATMENT
1st: PROPRANOLOL
If CI, use METOPROLOL or NADOLOL
AMITRIPTYLINE is effective
- use less sedating TCA if amitriptyline is not tolerated
Na Valproate, Pizotifen or Botox used normally under specialist
Headache types - Cluster, Trigeminal neuralgia, Tension
Cluster headaches
- Intense unilateral pain in or around ONE eye
- Acute: SC SUMATRIPTAN (Nasal sumatriptan / Zolmitriptan given if unavailable)
- Prophylaxis: Verapamil, Li, Prednisolone or Ergotamine tartate (rarely use)
Trigeminal Neuralgia:
- Severe facial pain like having an electric shock in the jaw, teeth or gums
- Treat with CARBAMAZEPINE
Tension headache:
- Bilateral throbbing pain like a tight band around your head
- PARACETAMOL or IBUPROFEN
Epilepsy - FOCAL SEIZURES (April 2022)
1st: Lamotrigine or Levetiracetam (added)
2nd: Zonisamide, Oxcarbazepine, Carbamazepine
ZOCALL.
Epilepsy - Generalised Seizures (April 2022) M.A.T.T.A.
Myoclonic:
1st: Na Val
2nd: Levetiracetam
Atonic:
1st: Na Val
2nd: Lamotrigine
Add-on options:
- Rufinamide
- Clobazam
- Topiramate
Tonic:
1st: Na Val
2nd: Lamotrigine
Add-on options:
- Rufinamide
- Clobazam
- Topiramate
Tonic-Clonic:
1st: Na Valproate
2nd: Lamotrigine or Levetiracetam (added unlicensed use)
Add on treatment if mono-therapy is unsuccessful:
- Clobazam
- Lamotrigine
- Levetiracetam
- Perampanel
- Na Val => except in women/girls of childbearing age
- Topiramate
Absence:
1st: Ethosuximide
2nd or add on: Na Val (if they present with tonic or clonic seizures with the absence seizure)
3rd or add on: Lamotrigine or Levetiracetam
Status Epilepticus (April 2022)
Seizures lasting longer than 5 mins:
- IV LORAZEPAM (repeated once within 5 - 10mins if seizures recur or fail to respond)
- IV diazepam (avoid due to high risk of thrombophlebitis)
If seizure fails to respond 25 mins after onset:
- IV: PHENYTOIN SODIUM, Na Val, Levetiracetam (this drug has fewer AE’s and a quicker administering rate)
If these measures fail to control seizures 45mins:
- Phenobarbital or general anaesthetic such as Propofol
If in community/resus not available:
- BUCCAL MIDAZOLAM or RECTAL DIAZEPAM
Add on drugs:
- parenteral THIAMINE given if alcohol abuse is suspected
- Give PYRIDOXINE if cause by pyridoxine deficiency
Epilepsy - Pregnancy
- Folic acid given to reducce risk of neural tube defects in first trimester
- Vit K injection administered at birth to minimise risk of neonatal haemorrhage
- Most risk = Na Val (PPP)
- Topiramate = Cleft Palate!!!
Epilepsy - Breastfeeding
Encouraged to breast feed
High presence in milk (PLEZ) = Primidone, Lamotrigine, Ethosuximide, Zonisamide
Risk of drowsiness (BPP) = Benzodiazepines, Phenobarbital, Primidone
Withdrawal effects (mum suddenly stops breastfeeding) (BPPL) = Benzodiazepines, Phenobarbital, Primidone, Lamotrigine
Epilepsy - Driving
Driver must stop driving STAT and inform DVLA
First unprovoked / single isolated = 6 MONTHS
Established epilepsy = 1 YEAR (or pattern of seizures established for 1 year wit no impact on consciousness)
Medication change / withdrawal:
- shouldn’t drive for 6 MONTHS AFTER LAST DOSE
- Seizure occurs: license revoked for 1 year, reinstated for after 6 months if treatment resumed and no further seizures occurred
Epilepsy - Antiepileptic drugs
CAT 1: CPPP
CAT 2: Clobazam, Clonazepam, Lamotrigine, Oxcarbazepine, Perampanel, Fufinamide, Topiramate, Valproate, Zonisamide
CAT 3: No need to be on brand => Brivaracetam, Ethosuximide, Gabapentin, Lacosamide, Levetiracetam, Pregabalin, Tiagabine, Vigabatrin
Carbamazepine - 4 - 12mg/L
Pre-treatment screening:
Test for HLA-B1502 allele in individuals of Han Chinese or Thai origin (avoid unless no alternative—risk of Stevens-Johnson syndrome in presence of HLA-B1502 allele).
Caution—cross-sensitivity reported with oxcarbazepine, phenytoin, primidone, and phenobarbital
Toxicity: HANDBAG
Hyponatraemia
Ataxia
Nystagmus
Drowsiness
Blurred vision
Arrhythmias
GI disturbances
Consider vitamin D supplementation in patients who are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
Blood, hepatic, or skin disorders:
Carbamazepine should be withdrawn immediately in cases of aggravated liver dysfunction or acute liver disease. Leucopenia that is severe, progressive, or associated with clinical symptoms requires withdrawal (if necessary under cover of a suitable alternative).
Overdose = use activated charcoal!
Therapeutic drug monitoring:
Plasma concentration for optimum response 4–12 mg/litre (20–50 micromol/litre) measured after 1–2 weeks.
Monitoring of patient parameters:
Manufacturer recommends blood counts and hepatic and renal function tests
Phenytoin - 10 - 20 mg/L
100 mg of phenytoin sodium = 92 mg phenytoin base.
Pre-treatment screening:
HLAB* 1502 allele in individuals of Han Chinese or Thai origin—avoid unless essential (increased risk of Stevens- Johnson syndrome).
Cross-sensitivity reported with carbamazepine.
Toxicity: SNACHD
Slurred speech
Nystagmus
Ataxia
Confusion
Hyperglycaemia
Double vision - diplopia
Enteral feeding = interrupt feeding for 2 hours before and after dose
MHRA advises consider vitamin D supplementation in patients who are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
IM phenytoin should not be used (absorption is slow and erratic)
Monitoring of patient parameters:
- Manufacturer recommends blood counts (but evidence of practical value uncertain).
With intravenous use:
- Monitor ECG and BP
Na Valproate
MHRA/CHM advice: Valproate medicines: contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met
MHRA/CHM advice: Valproate medicines and serious harms in pregnancy: new Annual Risk Acknowledgement Form and clinical guidance from professional bodies to support compliance with the Pregnancy Prevention Programme
CI: Acute porphyrias
Cautions: SLE
The MHRA advises consider vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
Hepatic dysfunction:
Withdraw treatment immediately if persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness, or loss of seizure control.
Pancreatitis:
Discontinue treatment if symptoms of pancreatitis develop.
Monitoring of patient parameters:
- Monitor liver function before therapy and during first 6 months especially in patients most at risk.
- Measure full blood count and ensure no undue potential for bleeding before starting and before surgery.
Patients or their carers should be told how to recognise signs and symptoms of blood or liver disorders and advised to seek immediate medical attention if symptoms develop.
Patients or their carers should be told how to recognise signs and symptoms of pancreatitis and advised to seek immediate medical attention if symptoms such as abdominal pain, nausea, or vomiting develop.
Effect on laboratory tests = False-positive urine tests for ketones.
Treatment cessation:
Avoid abrupt withdrawal; if treatment with valproate is stopped, reduce the dose gradually over at least 4 weeks.
Anti-epileptic interactions - Carbamazepine, Phenytoin & Na Valproate
Hepatotoxicty = Amiodarone, Itraconazole, Macrolides, Alcohol
CYP Enzyme = Inducers (Phenytoin, Phenobarbital, Carbamazepine); Inhibitors (Na Valproate)
Drugs that lower the seizure threshold: Tramadol, Theophylline, Quinolones
Carbamazepine = hyponatraemic drug (SSRIs, Diuretics)
Phenytoin = Anti-folate (Methotrexate, Trimethoprim)
Anti-epileptic SEs = Carbamazepine, Phenytoin, Na Valproate
ALL:
- MHRA: Depression and suicide
- Hepatotoxicity
- Hypersensitivity
- Blood dyscrasia
- Vitamin D deficiency
Carbamazepine = Hyponatraemia, odema
Phenytoin = Coarsening appearance, facial hair (hirsutism)
Na Val = Pancreatitis, teratogenic
Anti-epileptic SEs - other drugs
Hypersensitivity (CP3L) = Carbamazepine, Phenytoin, Phenobarbital, Primidone, Lamotrigine
Skin rash = Lamotrigine => SJS
Blood dyscrasis (C.VET.PLZ) = Carbamazepine, Valproate, Ethosuximide, Topiramte, Phenytoin, Lamotrigine, Zonisamide
Eye disorder = Vigabatrin (reduced visual field); Topiramate (secondary glaucoma)
Encephalopathy = Vigabatrin
Resp depression = Gabapentin, Pregabalin
Topiramate SE?
Increased risk of kidney stones
Wt loss
Cognitive slowing
Speech impairment
Pins and needles (paraesthesia)
MHRA: Topamax - start of safety review triggered by a study reporting an increased risk of neurodevelopmental disabilities in children with prenatal exposure - dose-dependent association between prenatal exposure and an increased risk of autism spectrum disorders, intellectual disability, and neurodevelopmental disorders in children.
Levetiracetam
Aggression - KEPPRA RAGE
Nasopharyngitis
