Epilepsy Flashcards
When choosing an antiepileptic drug, _________________ should first be considered
the presenting epilepsy syndrome
If the syndrome is not clear, the seizure type should determine the choice of treatment
What secondary factors contribute to the choice of anti-epileptic medication? (4)
- Concomitant medication
- Co-morbidity
- Age
- Sex
How is dosage frequency determined when treating epilepsy?
Often determined by plasma-drug half-life and should be kept as low as possible to encourage adherence with the drug regimen
Most antiepileptics, when used in the usual dosage, can be given _______ daily
twice
Which antiepileptics can be given once daily? (4)
- Lamotrigine
- Perampanel
- Phenobarbital
- Phenytoin
All have longer half-lives so once daily at bedtime is recommended
Why are large doses of antiepileptics given more frequently (divided doses)?
To avoid adverse effects associated with high peak plasma-drug concentration
When monotherapy with a first-line AED has failed, what should be tried?
Monotherapy with a second drug
What should be done before starting an alternative drug if the first drug showed lack of efficacy?
Check diagnosis
When changing from one AED to another, what should be kept in mind?
The change from one antiepileptic drug to another should be cautious, slowly withdrawing the first drug only when the new regimen has been established
What must be considered when prescribing combination therapy with multiple AEDs?
A single antiepileptic drug should be prescribed wherever possible.
Combination therapy with two or more antiepileptic drugs may be necessary, but the concurrent use of antiepileptic drugs increases the risk of adverse effects and drug interactions.
If combination therapy does not bring about worthwhile benefits, revert to the regimen (monotherapy or combination therapy) that provided the best balance between tolerability and efficacy.
Pharmacological management for epilepsy focuses on striking a balance between _________ and __________
Tolerability
efficacy
Thus, if combination therapy does not bring about worthwhile benefits, revert to the regimen (monotherapy or combination therapy) that provided the best balance between tolerability and efficacy. A single antiepileptic drug should be prescribed wherever possible.
A Europe-wide review concluded that ALL antiepileptic drugs may be associated with a small increased risk of _______________
suicidal thoughts and behavior
The MHRA has recommended that patients and their carers should be advised to seek medical advice if any mood changes, distressing thoughts, or feelings about suicide or self-harming develop, and that the patient should be referred for appropriate treatment if necessary
When do suicidal thoughts and behavior typically arise after initiating AED therapy?
May occur as early as 1 week after initiation of treatment
What advice should patients be given if they develop suicidal thoughts or behavior after initiating AED therapy? (2)
- Do NOT stop or switch AED treatment
2. Seek advice from a healthcare professional
For which AEDs are doctors advised to ensure that their patient is maintained on a specific manufacturer’s product (as opposed to switching to a generic) when treating epilepsy? (4)
- Carbamazepine
- Phenobarbital
- Phenytoin
- Primidone
For which drugs is it usually unnecessary to ensure that patients are maintained on a specific manufacturer’s AED for the treatment of epilepsy? (8)
- Brivaracetam
- Ethozuximide
- Gabapentin
- Lacosamide
- Levetiracetam
- Pregabalin
- Tiagabine
- Vigabatrin
In these cases, a generic will do; differences between alternative products (eg product name, packaging, appearance and taste) should not affect drug efficacy UNLESS it leads to patient dissatisfaction, dosing errors, and/or reduced adherence
What are the non-clinical factors that may affect the decision to switch a patient from a name-brand AED to a generic for the treatment of epilepsy? (6)
Differences between alternative products (e.g. product name, packaging, appearance, and taste) may be perceived negatively by patients and/or carers, and may lead to…
- Dissatisfaction
- Anxiety
- Confusion
- Dosing errors
- Reduced adherence
- Difficulties for patients with co-morbid autism, mental health problems, or learning disability
For which AEDs should the need for continued supply of a particular name-brand product be based on clinical judgement and consultation with the patient and/or carer? (10)
- Clobazam
- Clonazepam
- Eslicarbazepine acetate
- Lamotrigine
- Oxcarbazepine
- Perampanel
- Rufinamide
- Topiramate
- Valproate
- Zonisamide
Should take into account factors such as seizure frequency, treatment history, potential implications to the patient of having a breakthrough seizure
Why is there concern regarding switching AEDs in patients previously stabilized on a branded product to a generic?
Due to concerns regarding loss of seizure control and/or worsening of side-effects around the time of the switch
A study conducted by the CHM concluded that the reported effects could have been due to chance association but a causal role could not be ruled out in all cases
Different antiepileptic drugs vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers’ products of a particular drug may cause ___________ or _____________
adverse effects
loss of seizure control
What is antiepileptic hypersensitivity syndrome?
A rare but potentially fatal syndrome associated with some AEDs (carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, and rufinamide)
Symptoms usually start 1-8 weeks from onset of exposure and include:
- fever
- rash
- lymphadenopathy
- liver dysfunction
- hematological abnormalities
- renal abnormalities
- pulmonary abnormalities
- vasculitis
- multi-organ failure
Which drugs are known to cause antiepileptic hypersensitivity syndrome? (8)
- Carbamazepine
- Lacosamide
- Lamotrigine
- Oxcarbazepine
- Phenobarbital
- Phenytoin
- Primidone
- Rufinamide
When do symptoms of antiepileptic hypersensitivity syndrome usually appear?
Between 1-8 weeks after initiation of therapy
Interactions between antiepileptics are complex and may increase toxicity (with/without) a corresponding increase in antiepileptic effect. Interactions are usually caused by _______________
Without
hepatic enzyme induction or inhibition
Avoid abrupt withdrawal of AEDs, particularly of barbiturates and benzodiazepines, because this can precipitate __________________
severe rebound seizures
Which AEDs are strongly associated with severe rebound seizures upon abrupt withdrawal? (2)
- Benzodiazepines
- Barbiturates
Reduction in dosage should be gradual and, in the case of barbiturates, withdrawal of the drug may take months.
True or false: AEDs may be gradually withdrawn in patients who have been seizure-free for 12 months or more
False
The decision to withdraw antiepileptic drugs from a seizure-free patient, and its timing, is often difficult and depends on individual circumstances. Even in patients who have been seizure-free for several years, there is a significant risk of seizure recurrence on drug withdrawal.
How should drugs be withdrawn in patients who are taking several AEDs?
One at a time
If a driver has a seizure (of any type), how does this affect their license?
they must stop driving immediately and inform the Driver and Vehicle Licensing Agency (DVLA)
Patients who have had a first unprovoked epileptic seizure or a single isolated seizure must not drive for ____________
6 months
driving may then be resumed, provided the patient has been assessed by a specialist as fit to drive and investigations do NOT suggest a risk of further seizures
Patients with established epilepsy may drive a motor vehicle provided they are… (4)
- Not a danger to the public
- Are compliant with treatment and follow-up
- Have been seizure-free for at least one year
- Do NOT have a history of unprovoked seizures
additional criteria apply for drivers of large goods or passenger carrying vehicles—consult DVLA guidance
Patients who have had a seizure while asleep are not permitted to drive for one year from the date of each seizure, unless… (2)
- a history or pattern of sleep seizures occurring only ever while asleep has been established over the course of at least one year from the date of the first sleep seizure
OR
- an established pattern of purely asleep seizures can be demonstrated over the course of three years if the patient has previously had seizures whilst awake (or awake and asleep)
What is the DVLA recommendation regarding AEDs? (3)
Patients should not drive…
- During medication changes
- During medication withdrawal
- 6 months after their last dose
True or false: If a seizure occurs due to a prescribed change or withdrawal of epilepsy treatment, the patient will have their driving license revoked for 1 year
True
Although relicensing may be considered earlier if treatment has been reinstated for 6 months and no further seizures have occurred.
Are AEDs safe in pregnancy?
No, associated with teratogenicity especially if used in the first trimester and particularly in patients taking two or more AEDs
Which AED is considered most teratogenic?
Valproate; approximately 10% risk of congenital malformations and 30-40% risk of neurodevelopmental disorders
___________ should not be used first line in women of childbearing potential
Valproate
Valproate must not be used during pregnancy unless there is no other suitable alternative.
Which AEDs are considered safest in pregnancy? (2)
- Lamotrigine
2. Levetiracetam
Are carbamazepine, phenobarbital, phenytoin, and topiramate safe to use in pregnancy?
Associated with an increased risk of major congenital malformations in a dose-dependent fashion
+neurodevelopmental effects associated with phenobarbital and phenytoin
+intrauterine growth restriction associated with phenobarbital, topiramate, and zonisamide
What advice should be given to women who are taking AEDs and are planning a pregnancy? (2)
- Refer to a specialist
2. Offer folic acid
What advice should be given to women taking AEDs if they suspect they could be pregnant? (2)
- Do not stop their AED treatment without discussing this with their doctor
- Seek urgent medical advice
What additional considerations should be made regarding efficacy when prescribing AEDs in pregnancy?
Plasma concentrations of AEDs (particularly lamotrigine and phenytoin) can be affected by physiological changes during pregnancy and post-partum
Prescribers should consult product literature and relevant clinical guidance for dosing and monitoring recommendations
Females of childbearing potential who take antiepileptic drugs should be given advice about the need for a _______________
highly effective contraception method to avoid unplanned pregnancy
Some antiepileptic drugs can reduce the efficacy of hormonal contraceptives, and the efficacy of some antiepileptics may be affected by hormonal contraceptives
The likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations is at least ________
90%
True or false: Once an unplanned pregnancy is discovered it is usually too late for changes to be made to the treatment regimen
True
The risk of harm to the mother and fetus from convulsive seizures outweighs the risk of continued therapy
The likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations is at least 90%, and it is important that female patients do not stop taking essential treatment because of concern over harm to the fetus
To reduce the risk of neural tube defects, folate supplementation is advised throughout the first trimester.
Female patients who have seizures in the second half of pregnancy should be assessed for __________ before any change is made to antiepileptic treatment
eclampsia
How is Status epilepticus managed in pregnant women?
According to the standard protocol
_________ at birth minimises the risk of neonatal haemorrhage associated with antiepileptics.
Routine injection of vitamin K
Withdrawal effects of AEDs in the newborn may occur with some antiepileptic drugs, in particular __________ and __________
benzodiazepines
phenobarbital
True or false: Women taking antiepileptic monotherapy should generally be encouraged to breast-feed
True
However, if a woman is on combination therapy or if there are other risk factors, such as premature birth, specialist advice should be sought.
All infants breastfed by women taking AEDs should be monitored for: (4)
- Sedation
- Feeding difficulties
- Adequate weight gain
- Developmental milestones
Which AEDs are known to readily enter breast milk? (4)
- Ethosuximide
- Lamotrigine
- Primidone
- Zonisamide
Serum-drug concentration monitoring should be undertaken in breast-fed infants if suspected adverse reactions develop
Is it necessary to monitor serum-drug concentrations of babies being breastfed by mothers taking AEDs?
Only if adverse reactions are suspected; if toxicity develops it may be necessary to introduce formula feeds to limit the infant’s drug exposure, or to wean the infant off breast-milk altogether.
__________, __________, and __________ are associated with an established risk of drowsiness in breast-fed babies and caution is required.
Primidone
Phenobarbital
Benzodiazepines
Withdrawal effects may occur in infants if a mother suddenly stops breast-feeding, particularly if she is taking ____________, ____________, or ____________
phenobarbital
primidone
lamotrigine
What are the first line drugs for managing focal seizures with or without secondary generalization? (2)
- Carbamazepine
- Lamotrigine
Second line:
- oxcarbazepine
- valproate
- levetiracetam
If monotherapy is unsuccessful in the treatment of focal seizures with first-line antiepileptic drugs, what should be considered?
adjunctive treatment with a second AED:
- carbamazepine
- clobazam
- gabapenitn
- lamotrigine
- levetiracetam
- oxcarbazepine
- valproate
- topiramate
*if adjunctive treatment is ineffective or not tolerated, consult a specialist
What is the first-line treatment for newly diagnosed generalized tonic-clinic seizures?
Valproate EXCEPT in female patients of childbearing potential unless they are on LARC
Second line: lamotrigine (but may exacerbate Myoclonic seizures)
What is the first line AED treatment for patients with established epilepsy with generalized tonic-clinic seizures only? (2)
- Valproate
2. Lamotrigine
What are the drugs of choice for absence seizures? (2)
- Ethosuximide
- Valproate (except in females of childbearing potential)
Second line:
- lamotrigine
What is the drug of choice for managing newly diagnosed Myoclonic seizures?
Valproate (except in females of childbearing potential)
Second line:
- topiramate
- levetiracetam
What is the drug of choice for the treatment of atonic and tonic seizures?
Valproate (except in females of childbearing potential)
*lamotrigine can be added as adjunctive treatment
What is Dravet syndrome?
A rare drug-resistant epilepsy that begins in the first year of life in an otherwise healthy infant;
It is lifelong and usually presents with a prolonged seizure with fever that affects one side of the body
Most commonly caused by a severe SCN1A gene mutation
What is Lennox-Gastaut syndrome?
A type of severe epilepsy beginning in childhood
May lead to tonic, atonic, absence, myoclonic
Commonly caused by unusual brain development, stroke, serious head injury, brain tumor, brain infection, brain hypoxia, tuberous sclerosis
What is the treatment of Dravet syndrome? (2)
- Valproate (except females of childbearing potential)
- Topiramate (unlicensed)
A tertiary specialist should be involved in decisions regarding treatment of Dravet syndrome
What is the treatment of choice in patients with Lennox-Gastaut Syndrome?
Valproate (except females of childbearing potential)
A tertiary specialist should be involved in decisions regarding treatment of Lennox-Gastaut syndrome
What are the main drugs used as anti-epileptics? (12)
- Carbamazepine (and related drugs oxcarbazepine, eslicarbazepine acetate)
- Ethosuximide
- Gabapentin and pregabalin
- Lamotrigine
- Levetiracetam and brivaracetam
- Phenobarbital and primidone
- Phenytoin
- Rufinamide
- Topiramate
- Valproate
- Zonisamide
- Benzodiazepine
Carbamazepine is the drug of choice for which types of seizures? (2)
Simple and complex focal seizures
Generalized tonic clonic seizures
___________ may exacerbate tonic, atonic, myoclonic and absence seizures and is therefore not recommended if these seizures are present
Carbamazepine
____________ is licensed as monotherapy or adjunctive therapy for the treatment of focal seizures with or without secondary generalised tonic-clonic seizures.
Oxcarbazepine
____________ is not recommended in tonic, atonic, absence or myoclonic seizures due to the risk of seizure exacerbation.
Oxcarbazepine
Also carbamazepine
What are the indications of eslicarbazepine acetate?
Licensed for adjunctive treatment in adults with focal seizures with or without secondary generalization
Ethosuximide is a first-line treatment option for ___________ seizures
Absence
Ethosuximide is also licensed for myoclonic seizures.
Gabapentin and pregabalin are used for the treatment of ___________
focal seizures with or without secondary generalisation
They are not recommended if tonic, atonic, absence or myoclonic seizures are present.
In addition to being used in the treatment of epilepsy, gabapentin and pregabalin are also licensed for the treatment of _____________
Neuropathic pain
Pregabalin is also licensed for the treatment of GAD
Lamotrigine is a first-line treatment for __________ and _____________
focal seizures
primary and secondary generalised tonic-clonic seizures
Lamotrigine is used either as sole treatment or as an adjunct to treatment with other antiepileptic drugs
Myoclonic seizures may be exacerbated by ___________ and it can cause serious rashes especially in children
lamotrigine
Valproate ___________ plasma-lamotrigine concentration, whereas the enzyme-inducing antiepileptics __________ it
increases
reduce
Levetiracetam is used for monotherapy and adjunctive treatment of ___________________, and for adjunctive treatment of ___________________ and ___________________
focal seizures with or without secondary generalisation
myoclonic seizures in patients with juvenile myoclonic epilepsy
primary generalised tonic-clonic seizures
Brivaracetam is used as adjunctive therapy in the treatment of __________________.
partial-onset seizures with or without secondary generalisation
Phenobarbital is effective for ___________ and ____________ but may be sedative in adults
tonic-clonic
focal seizures
Primidone is largely converted to ___________ and this is probably responsible for its antiepileptic action
phenobarbital
Phenytoin is licensed for _____________ and _________ seizures but may exacerbate absence or myoclonic seizures and should be avoided if these seizures are present.
tonic-clonic
focal
Phenytoin is licensed for tonic-clonic and focal seizures but may exacerbate __________ or ___________ seizures and should be avoided if these seizures are present.
absence
myoclonic
_____________ (AED) has a narrow therapeutic index and the relationship between dose and plasma-drug concentration is non-linear; small dosage increases in some patients may produce large increases in plasma concentration with acute toxic side-effects
Phenytoin
Similarly, a few missed doses or a small change in drug absorption may result in a marked change in plasma-drug concentration.
When only parenteral administration is possible, ____________, a pro-drug of phenytoin, may be convenient to give
fosphenytoin sodium
Phenytoin should ONLY be given intravenously, not IM
What is the route of administration for phenytoin?
ONLY IV
Rufinamide is licensed for the adjunctive treatment of seizures in ________________
Lennox-Gastaut syndrome
Topiramate can be given alone or as adjunctive treatment in ______________ or ______________ (seizures)
generalised tonic-clonic seizures
focal seizures with or without secondary generalisation
____________ is effective in controlling tonic-clonic seizures, particularly in primary generalised epilepsy
Valproate
Valproate is a drug of choice in ____________ seizures, ___________ seizures, ____________ and ___________ seizures, and can be tried in _________ seizures; it is the recommended first-line option in ________ and _________ seizures
primary generalised tonic-clonic
focal
generalised absences
myoclonic
atypical absence
Atonic
Tonic
Valproate has widespread metabolic effects and monitoring of ______________ and ______________ is essential
liver function tests
full blood count
Because of its high teratogenic potential, ___________ must not be used in females of childbearing potential unless the conditions of the Pregnancy Prevention Programme are met and alternative treatments are ineffective or not tolerated.
valproate
During pregnancy, it must not be used for epilepsy unless it is the only possible treatment.
What are the conditions of the Pregnancy Prevention Programme? (3)
Premenopausal female patients taking valproate:
- Have been told and understand the risks of use in pregnancy and have signed a Risk Acknowledgment Form
- Are on highly effective contraception if necessary
- See their specialist at least every year
*same conditions for other highly teratogenic drugs like thalidomide and isotretinoin
In addition to being used in the treatment of epilepsy, Valproate is also licensed for acute _______ associated with ___________
Mania
Bipolar disorder
Zonisamide can be used alone for the treatment of ______________ in adults with newly diagnosed epilepsy, and as adjunctive treatment for ________________ in adults and children aged 6 years and above
focal seizures with or without secondary generalisation
refractory focal seizures with or without secondary generalisation
Which benzodiazepines are used in the treatment of epilepsy? (2)
- Clobazam
2. Clonazepam
Clobazam may be used as adjunctive therapy in the treatment of __________ and _____________. It may be prescribed under the care of a specialist for ___________ and __________ seizures.
generalised tonic-clonic
refractory focal seizures
refractory absence
myoclonic
Clonazepam may be prescribed by a specialist for ____________ and ____________ seizures, but its sedative side-effects may be prominent
refractory absence
myoclonic
_____________, a carbonic anhydrase inhibitor, has a specific role in treating epilepsy associated with menstruation.
Acetazolamide
Piracetam is used as adjunctive treatment for __________
cortical myoclonus
What are the immediate measures to manage status epilepticus? (4)
- Position patient to avoid injury
- Support respiration including the provision of oxygen
- Maintain blood pressure
- Correct for hypoglycemia
+parenteral thiamine should be considered if alcohol abuse is suspected
+pyridoxine should be given if SE is caused by pyridoxine deficiency
Seizures lasting longer than 5 minutes should be treated urgently with intravenous ____________
lorazepam
In the treatment of seizures lasting longer than 5 minutes, lorazepam should be repeated after _______ minutes if seizures recur or fail to respond
10
Why is IV lorazepam preferred to IV diazepam in the treatment of SE?
Intravenous diazepam is effective but it carries a high risk of thrombophlebitis (reduced by using an emulsion formulation)
Why isn’t IM or rectal diazepam used in the treatment of SE?
Absorption is too slow
In the management of SE, patients should be monitored for what side effects after treatment with lorazepam or diazepam? (2)
- Respiratory depression
2. Hypotension
In the management of SE, where facilities for resuscitation are not immediately available, _______ can be administered as a rectal solution or ________ oromucosal solution can be given into the buccal cavity.
diazepam
midazolam
If, after initial treatment with benzodiazepines, seizures recur or fail to respond 25 minutes after onset, ___________, ______________, or ___________ should be used; contact intensive care unit if seizures continue. If these measures fail to control seizures 45 minutes after onset, anaesthesia with thiopental sodium, midazolam, or a non-barbiturate anaesthetic such as propofol [unlicensed indication], should be instituted with full intensive care support.
phenytoin sodium
fosphenytoin sodium
phenobarbital sodium
If, after initial treatment with benzodiazepines, seizures recur or fail to respond 25 minutes after onset, phenytoin sodium, fosphenytoin sodium, or phenobarbital sodium should be used; contact intensive care unit if seizures continue. If these measures fail to control seizures 45 minutes after onset, anaesthesia with ______________, ____________, or a non-barbiturate anaesthetic such as ____________ [unlicensed indication], should be instituted with full intensive care support.
thiopental sodium
midazolam
propofol
In the treatment of status epilepticus, how is fosphenytoin (a pro-drug of phenytoin) administered?
IV
IM fosphenytoin is absorbed too slowly for the treatment of SE
The urgency to treat non-convulsive status epilepticus depends on the severity of the patient’s condition. If there is incomplete loss of awareness, ________________ therapy should be continued or restarted
usual oral antiepileptic
The urgency to treat non-convulsive status epilepticus depends on the severity of the patient’s condition. Patients who fail to respond to oral antiepileptic therapy or have complete lack of awareness can be treated ________________
in the same way as for convulsive status epilepticus, although anaesthesia is rarely needed
What is the treatment of brief febrile convulsions?
No specific treatment needed; antipyretic mediation (paracetamol) is commonly used to reduce fever and prevent further convulsions but evidence to support this practice is lacking
What is the treatment of prolonged (lasting 5 min or longer) or recurrent febrile convulsions without recovery?
Active treatment, as for SE
Is long-term anticonvulsant prophylaxis indicated for febrile convulsions?
Rarely
What is the effect of carbamazepine on CYP450?
Inducer
Which AEDs induce CYP450? (3)
- Phenytoin
- Phenobarbital
- Carbamazepine
Which AED is an inhibitor of CYP450?
Valproate
What are the contraindications for the use of carbamazepine? (3)
- Acute porphyrias
- AV conduction abnormalities (unless paced)
- History of bone marrow suppression
What are the common side effects of carbamazepine? (10)
- Dizziness, drowsiness, fatigue
- Dry mouth
- Eosinophilia, leukopenia, thrombocytopenia
- Fluid imbalance, hyponatremia, edema
- GI discomfort, N/V
- Movement disorders
- Vision disorders
- Skin reactions
- Weight gain
- Headache
The list of rare or very rare side effects of carbamazepine is enormous and many of the listed effects are dangerous. However, which two particular scenarios should you be on the lookout for?
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
In patients with allergy to carbamazepine, you should be weary of cross-sensitivity reported in which other AEDs when prescribing? (4)
- Oxcarbazepine
- Phenytoin
- Primidone
- Phenobarbital
What pre-treatment screening should be used in patients of Han Chinese or Thai origin when starting carbamazepine?
Test for HLA-B1502; increased risk of Stevens-Johnson syndrome
Avoid unless no alternative
When should plasma levels of carbamazepine be measured after initiating treatment?
1-2 weeks
What additional information should be given to patients or carers regarding carbamazepine?
Patients or their carers should be told how to recognise signs of blood, liver, or skin disorders, and advised to seek immediate medical attention if symptoms such as fever, rash, mouth ulcers, bruising, or bleeding develop.
What additional information should be given to patients or carers regarding ethosuximide?
Patients or their carers should be told how to recognise signs of blood disorders, and advised to seek immediate medical attention if symptoms such as fever, mouth ulcers, bruising, or bleeding develop.
Gabapentin should be prescribed with caution in which patients? (6)
- DM
- Elderly
- High doses of oral solution in adolescents and adults with low body-weight
- History of substance abuse
- Mixed seizures (including absence)
- Respiratory depression
Gabapentin has been associated with a rare risk of severe ______________ even without concomitant opioid medicines
respiratory depression;
Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of central nervous system (CNS) depressants, and elderly people might be at higher risk of experiencing severe respiratory depression and dose adjustments may be necessary in these patients.
Following concerns about abuse, ________ (AED) has been reclassified as a Class C controlled substance and is now a Schedule 3 drug, but is exempt from safe custody requirements. Healthcare professionals should evaluate patients carefully for a history of drug abuse before prescribing ____________, and observe patients for signs of abuse and dependence.
gabapentin
Patients should be informed of the potentially fatal risks of interactions between _________ and alcohol, and with other medicines that cause CNS depression, particularly opioids.
gabapentin
Does gabapentin dose need to be adjusted in renal impairment and/or hepatic impairment?
Renal impairment only
Following concerns about abuse, _________ has been reclassified as a Class C controlled substance and is now a Schedule 3 drug, but is exempt from safe custody requirements. Healthcare professionals should evaluate patients carefully for a history of drug abuse before prescribing ____________, and observe patients for signs of abuse and dependence.
pregabalin
Also gabapentin
Patients should be informed of the potentially fatal risks of interactions between _________ and alcohol, and with other medicines that cause CNS depression, particularly opioids.
pregabalin
Also gabapentin
A European review of ___________ safety data identified worldwide reports of severe respiratory depression, in some cases without concomitant opioid treatment. Healthcare professionals are advised to consider whether adjustments in dose or dosing regimen are necessary in patients at higher risk of respiratory depression
pregabalin
Which patients are considered at higher risk of respiratory depression? (3)
- Compromised respiratory function, respiratory or neurological disease, or renal impairment
- Taking other CNS depressants (including opioid-containing medicines)
- Aged older than 65 yo
Should dosage of pregabalin be adjusted in renal and/or hepatic impairment?
Renal only
When is monitoring required in patients using pregabalin?
Only if there are signs of abuse
How is treatment cessation with pregabalin managed?
Avoid abrupt withdrawal, taper over at least 1 week
Cessation of pregabalin should be tapered over at least __________.
1 week
What flavor of oral liquid formula does pregabalin come in :)
Strawberry mmmmm <3
What additional information should be provided to patients regarding pregabalin?
Should be counseled on the effects on driving and performance of skilled tasks—increased risk of dizziness or vision disorders
What are the common or very common side effects of pregabalin? (4)
- GI disorders, abdominal distension, abnormal appetite, constipation, diarrhea, dry mouth
- Neurological: asthenia, impaired concentration, confusion, dizziness, drowsiness, gait abnormalities, headache, memory loss, altered mood, pain, sexual dysfunction, sleep disorders, speech impairment, vertigo, vision disorders (think, all symptoms like the person is drunk)
- MSK: joint disorders, cervical spasm,
- Increased risk of infection
Lamotrigine should be prescribed with caution in which patients? (3)
- Brugada syndrome
- Myoclonic seizures (may be exacerbated)
- Parkinson’s (may be exacerbated)
What are the common or very common side effects of lamotrigine? (10)
- Aggression, irritability
- Agitation
- Arthralgia
- Diarrhea
- Dizziness
- N/V
- Pain
- Rash
- Sleep disorders
- Tremor
**also suicidal behavior (as in all AEDs)
When is monitoring of lamotrigine drug-plasma levels advised in pregnancy?
Before, during, and after pregnancy, including shortly after birth
Adjust dose according to response (plasma levels alter during pregnancy and may increase rapidly after birth)
Is lamotrigine dose adjusted in hepatic and/or renal impairment?
Hepatic impairment; 50% in moderate impairment, 75% in severe adjust according to response
Consider reducing maintenance dose in significant renal impairment; metabolite may accumulate
Lamotrigine cessation should be tapered over _____________ or longer
2 weeks
Unless serious skin reaction occurs
What additional advice should be given to patients and carers regarding lamotrigine? (2)
- Warn patients and carers to see their doctor immediately if rash or signs or symptoms of hypersensitivity syndrome develop
- Patients and their carers should be alert for symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, or infection. Aplastic anaemia, bone-marrow depression, and pancytopenia have been associated rarely with lamotrigine.
What are the common or very common side effects of levetiracetam? (4)
- Neuro: anxiety, asthenia, abnormal behavior, depression, dizziness, drowsiness, headache, insomnia, altered mood, movement disorders, vertigo
- GI: decreased appetite, diarrhea, pain, N/V
- Increased risk of infection
- Skin reactions
**greater risk of depression than lamotrigine
Should levetiracetam dose be adjusted in hepatic and/or renal impairment?
Both
Phenobarbital should be prescribed with caution in which patients? (6)
- Children
- Avoid in acute porphyrias
- Debilitated patients
- Elderly
- History of alcohol or drug abuse
- Respiratory depression (if severe)
What are the general side effects of phenobarbital? (13)
- Agranulocytosis
- Anticonvulsant hypersensitivity syndrome
- Abnormal behavior
- Bone disorders and fracture
- Cognitive impairment, confusion, memory loss
- Depression
- Folate deficiency
- Hepatic disorders
- Movement disorders
- Nystagmus
- Respiratory depression
- Suicidal behavior
- Skin reactions
What are the specific side effects associated with oral phenobarbital use? (5)
- Anxiety
- Hallucinations
- Hypotension
- Megaloblastic anemia
- Thrombocytopenia
What are the specific side effects associated with parenteral phenobarbital use? (4)
- Agitation, irritability
- Aplastic anemia
- Dupuytren’s contracture
- Hypocalcemia
Is dose of phenobarbital recommended for renal and/or hepatic impairment?
Avoid in severe impairment of either
Phenytoin is contraindicated in which patients? (5)
- Acute porphyrias
- Second and third degree heart block
- Sino-atrial block
- Sinus bradycardia
- Stokes-Adams syndrome
What are the side effects associated with phenytoin? (15)
- Agranulocytosis, eosinophilia, granulocytopenia, megaloblastic anemia, leukopenia
- Bone disorders (bone marrow and fractures)
- Cerebrovascular insufficiency
- Coarsening of facial features
- Neuro: confusion, dizziness, drowsiness, dysarthria, insomnia, movement disorders, nervousness, paresthesias, suicidal behavior, taste altered
- GI: constipation, hepatic disorders
- Dupuytren’s contracture
- MSK: joint disorders, muscle twitching
- Gingival hyperplasia
- Pseudo lymphoma, neoplasms
- Peyronie’s disease
- SLE
- Skin reactions
- PAN
- Fever
What are the symptoms of phenytoin toxicity? (6)
- Nystagmus
- Diplopia
- Slurred speech
- Ataxia
- Confusion
- Hyperglycemia
Should phenytoin dose be adjusted in hepatic and/or renal impairment?
Consider dose reduction in hepatic impairment
What pre-treatment screening should be undertaken before starting patients of Han Chinese or Thai origin on phenytoin?
HLAB1502 (increased risk of SJS)
Is plasma drug monitoring require in patients taking phenytoin?
Yes
Also monitor ECG and BP if IV use
What additional information should be given to patients and carers regarding phenytoin?
Patients or their carers should be told how to recognise signs of blood or skin disorders, and advised to seek immediate medical attention if symptoms such as fever, rash, mouth ulcers, bruising, or bleeding develop. Leucopenia that is severe, progressive, or associated with clinical symptoms requires withdrawal (if necessary under cover of a suitable alternative).
Valproate is contraindicated in which patients? (4)
- Acute porphyrias
- Known or suspected mitochondrial disorders (higher rate of acute liver failure and related deaths)
- Personal or family history of severe hepatic dysfunction
- Urea cycle disorders (risk of hyperammonemia)
Also caution in SLE
Raised liver enzymes during __________ treatment are usually transient but patients should be reassessed clinically and liver function (including prothrombin time) monitored until return to normal—discontinue if abnormally prolonged prothrombin time (particularly in association with other relevant abnormalities)
valproate
What are the common or very common side effects of valproate?
- GI: pain, diarrhea, hepatic disorders, N/V
- Neuro: agitation, abnormal behavior, impaired concentration, confusion, headache, deafness, hallucinations, memory loss, movement disorders, nystagmus, seizures, stupor, tremor
- Alopecia (regrowth may be curly), nail disorders
- Menstrual cycle irregularities
- Hemorrhage, thrombocytopenia
- Urinary disorders
- Hyponatremia
*also suicidal behavior (like other AEDs)
Valproate should be withdrawn immediately under which 2 conditions?
- Hepatic dysfunction including: persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness, or loss of seizure control.
- Pancreatitis
Is routine plasma drug concentration monitoring required for valproate?
No, plasma concentrations are not a useful index of efficacy, therefore routine monitoring is unhelpful
What monitoring may be helpful for patients taking valproate? (2)
LFTs (during first 6 months)
FBC
What effect does valproate have on urine testing?
False positive for ketones
Cessation for valproate should be tapered over at least __________
4 weeks
What additional information should be given to patients and carers regarding valproate? (4)
- The MHRA advises women and girls should not stop taking valproate without first discussing it with their doctor.
- 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.
- Pharmacists must ensure that female patients have a patient card regarding the Pregnancy Prevention Programme
What is the mechanism of action of lamotrigine?
Na channel inhibitor, suppresses the release of excitatory amino acid glutamate
What is the mechanism of action of levetiracetam?
Modulation of synaptic NT release through binding to the synaptic vesicle protein SV2A to slow down electrical impulses
What is the mechanism of action of phenytoin?
Blockage of voltage-gated Na channels to inhibit neuronal propagation
What is the mechanism of action of phenobarbital?
Stimulates GABA-A receptors to increase synaptic inhibition thereby elevating the seizure threshold
What is the mechanism of action of valproate?
Increases neurotransmitter GABA levels in the brain to inhibit brain cell activity (may do this by blocking reuptake of GABA from synapses)
What is the mechanism of action of gabapentin?
Inhibits the release of excitatory NTs in the presynaptic area
Also an agonist at GABA-B receptors
What is the mechanism of action of ethosuximide?
Inhibits NADPH-like aldehyde reductase
What is the mechanism of action of carbamazepine?
Na channel blocker
Prevents repetitive and sustained firing of action potentials
