week 5- Drugs used in Epilepsy and TDM Flashcards
how is epilepsy manage? drugs, failed
- Anti-epileptic treatment is individualised to the patient dependant on type of seizure, other medication, sex and preference
- given a care plan agreed by patient and care giver
- anti-epileptic therapy only started after diagnosis unless special case
- aim is monotherapy less chance of SE and interactions with other medication, start low titrate up
- if 1st AED fails switch to another after having titrated up
- if 2nd fails then combination is considered only monotherapy cant control symptoms
what are some of the therapeutic drug monitoring for epilepsy drugs? need for blood test?
• This is relevant in managing epilepsy in certain circumstances and
with certain medications (but not all AEDs).
• Regular blood tests are not generally recommended and should only
be undertaken if it is clinically needed and recommended by the
specialist.
• Generally, the main reasons for doing a blood test would be(1):
• To identify non-adherence
• Investigate suspected toxicity
• Adjustment of phenytoin doses
• Managing interactions with other medication
• For specific clinical conditions – e.g. organ failure, pregnancy
what are some points to be aware of with AEDs? sympotms?
-some ppl have suidicidal thoughts, if patients have change in mood or dissress should seek help
-Antiepileptic hypersensitivity syndrome though very rare is associated with
some AEDs and can be fatal and the drug should be stopped immediately if
symptoms occur
-Many of the AEDs in the BNF mention patients may need vitamin D
supplementation if they are immobile for long periods of time, or have
inadequate sun exposure or dietary intake.
what are some antiepileptic drugs?
- Sodium Valproate
- Carbamazepine
- Ethosuximide
- Lamotrigine
- Levetiracetam
- Phenobarbital
- Phenytoin
what are the cautions when using soduim valporate with women of child bearing age ?
- can cause birth defects and development disorder
- should prescribe to women
what is the primary indication of sodium valoprate?
-first line for ppl not of child bearing potnetial or PPP for Generalised Tonic-clonic seizures, Absence Seizures, Myoclonic seizures, Tonic or Atonic seizures, Can be used as a 1st line agent in Focal seizures if other AEDs are not suitable or not tolerated
• Potential 1st line agent for Dravet’s syndrome, Lennox-Gastaut syndrome
• Adjunctive to other AEDs in certain epilepsies.
other indications
• Migraine prophylaxis (unlicensed)
Mania in Bipolar disorder (either as sodium valproate or as semi-sodium valproate)
what are some adverse effects of sodium valporate?
- Nausea, weight gain
* Transient elevation of LFTs, blood dyscrasias alopecia (hair loss), Liver toxicity and pancreatitis (v.rare).
what are the pharmokinetics of sodium valporate?
- Crosses into through the placenta (therefore causing birth defects or developmental disorders)
- Half-life ranges between 8-20hours (Usually shorter in children)
- Metabolised through the liver mainly via glucuronidation(5)
- Enzyme Inhibitor of a few CYP enzymes (6)
what are some of the monitoring needed for using sodium valporate?
• Liver function tests are conducted before starting Sodium valproate, and within 6months of starting
treatment.
• Full blood count done as well before starting treatment to ensure no potential for bleeding.
• Blood dyscrasias
• Liver disorders – jaundice, and other non-specific symptoms that could be sudden in onset – general
tiredness/lethargy/drowsiness/or loss of strength, anorexia, swelling (sometimes associated with
repeated vomiting and abdominal pain)
• Pancreatitis (5)
what is the primary indication for carbamazepine?
• 1st Line – focal seizures, other types of epilepsy that include benign epilepsy with centrotemporal spikes,
Panayiotopoulos syndrome or late-onset childhood occipital epilepsy (Gastaut type).
• Can be considered in generalised tonic clonic seizures (but be aware it can exacerbate myoclonic and
absence seizures – if these are present this is not suitable)
• Adjunctive in focal seizures
other indictaion
• Prophylaxis in Bipolar disorder unresponsive to lithium
• Trigeminal neuralgia
• Adjunct to acute alcohol withdrawal (unlicensed)
• Diabetic neuropathy (unlicensed)
what are some adverse side effects of carbamazepine?
- Drowsiness, dry mouth, nausea, vision disorders
- Blood disorders – leucopenia, eosinophilia, thrombocytopenia
- Hyponatraemia
- Skin disorders
what are the pharmacokinetcis of carbamazepine?
• Enzyme inducer – induces multiple CYP enzymes in the liver.
• Has multiple formulations (immediate release tablets, MR release, liquid. However different
preparations are NOT bioequivalent(7)
• It is metabolised in the liver and its clearance can be affected not only by other drugs causing enzyme
induction/inhibition but also by autoinduction of its own metabolism – thus altering the half-life of the
drug after continued administration(7,8).
• Interacts with other AEDs
what is the monitoring needed for carbamazepine?
• Pre-treatment screening is necessary in patients of Han Chinese or Thai origin for the allele HLA-B*1502
allele – due to the increased risk of Steven-Johnson Syndrome in patients with this allele(9).
• Plasma concentration for optimum response 4-12mg/L measured after 1-2 weeks
• Manufacturer recommends blood counts, liver and renal function tests – however the actual value of
these tests is not known(9)
• Monitor for any blood dyscrasias, liver or skin disorders
wha are some AED that are related to carbamazepine?
-Oxcarbazepine
• Analogue of carbamazepine. It is a prodrug that is converted in the liver into its active metabolite.
• Is a weak enzyme inducer of CYP enzymes (CYP3A4 and 3A5); also enzyme inhibitor of CYP2C19
• Patients that are allergic hypersensitivity to carbamazepine have a 25-30% chance of experiencing
a similar reaction to oxcarbazepine.
• Has more linear pharmacokinetics – no self-induction of metabolism(10)
-Eslicarbazepine
• Like that of Oxcarbazepine – weak inhibitor and inducer of certain CYP enzymes
• Does not affect its own metabolism or clearance
• Long half-life therefore once daily dosing(11)
• Risk of hypersensitivity reactions
• Similar side effects to oxcarbemazepine – but can also prolong the PR interval and therefore
caution should be used in associated medical conditions(12).
what are the primary indications, other indications, adverse effects , pharmacokinetcis and monitoring for ethosuximide?
-primary indication
1st Line for absences seizures, childhood absence epilepsy, and other absence epilepsy syndromes(1).
- Adjunctive for absences seizures and other absence epilepsy syndromes
- It is also licensed for myoclonic seizures(2) .
Adverse side effects
Other indications - None
- GI discomfort (nausea, vomiting, diarrhoea, constipation), anxiety, sleep disturbances, behavioural disorders, ataxia
(uncoordinated movements and balance), drowsiness.
- Blood disorders, rash (Steven-Johnson syndrome)
Notable pharmacokinetics
- Absorbed well orally, metabolised in the liver(13).
- Available in soft capsule or syrup forms.
- Generally, there is no notable interactions with other AEDs (14, 15).
Monitioring
- Monitor for any blood dyscrasias:
oPatients/carers should be told how to recognise the signs – to seek medical attention if they experience a fever, rash,
mouth ulcers, bruising or bleeding develop(16)
- Monitor for suicidal behaviours
Patients/carers should report any signs or symptoms of suicidal thoughts or behaviour. (13)
what are the primary indications, other indications, adverse effects , pharmacokinetcis and monitoring for lamotrigine?
primary indication
-1st Line and can be used as an adjunctive for Focal Seizures, generalised tonic-clonic seizures, absence seizures (if
ethosuximide or sodium valproate not suitable/tolerated), idiopathic generalised epilepsy. Also benign epilepsy
with centrotemporal spikes, Panayiotopoulos syndrome or late-onset childhood occipital epilepsy (Gastaut type).(1)
other indication
- Bipolar disorder (monotherapy and as an adjunctive)
adverse SE
- Dizziness, drowsiness, headache dry mouth, diplopia (double vision), rash (more common when given with other AEDs or in too rapid dose titration), hypersensitivity syndrome, suicidal ideation, blood disorders. (17)
Notable pharmacokinetcis
-When given with drugs that are hepatic enzyme inducers or inhibitors, the half life of the drug is altered.
Therefore, dosage of the drug needs to be adjusted to accommodate for this.(11)
- Does induce its own metabolism but does not affect other AEDs pharmacokinetics(17).
monitoring
-Counselling of patients around (17)
oSkin reactions – to report signs and symptoms of a rash or hypersensitivity syndrome immediately to the their doctor
-Bone marrow failure – anaemia, bruising or infection