Anti-Epileptic Drugs Flashcards
1
Q
What is a seizure?
A
A convulsion or transient abnormal event from episodic discharge of high frequency electrical activity in the brain
2
Q
What is epilepsy?
A
The continuing tendency to have seixures, even if long intervals seperate the attacks
3
Q
What is the prevalence of epilepsy?
A
0.5-1%
4
Q
What happens to neurones during a seizure?
A
Large groups of neurones are activated repetitively, unrestrictedly, and hyper-synchronously, with inhibitory neurones failing
5
Q
What is a partial (focal) seizure?
A
A seizure that is confined to one area of the cortex
6
Q
How can a partial seizure progress?
A
It can spread to cause a secondary generalisation
7
Q
What is it called when generalised seizures occur as a focal seizure?
A
A primary generalised major convulsion
8
Q
What are seizures classified into?
A
Generalised or partial seizures
9
Q
What are partial seizures further subdivided into?
A
Simple or complex
10
Q
What is a simple partial seizure?
A
One with no loss of consciousness
11
Q
What is a complex partial seizure?
A
One with loss of awareness
12
Q
What are the types of generalised seizures?
A
- Tonic-clonic seizures (grand mal seizures)
- Typical absenses (petit mal seizures)
13
Q
What happens in tonic phase of tonic-clonic seizures?
A
Following vague warning signs, the tonic phase commences, as the body becomes rigid and the patient commonly falls to the floor, tongue is bitten, and incontinence of both urine and faeces can occur
14
Q
What happens in the clonic phase of tonic-clonic seizures?
A
Begin with generalised convulsion, frothing at the mouth and rhythmic jerking of muscles
15
Q
What is the prognosis of a tonic-clonic seizure?
A
Normally self limiting
16
Q
What symptoms can follow tonic-clonic seizures?
A
Drowsiness, confusion, or a coma for several hours
17
Q
In what kind of epilepsy do typical absense seizures occur?
A
Generalised epilepsy that occurs in childhood
18
Q
What happens in typical absense seizures?
A
Patient will stare, eyelids may twitch, and a few muscle jerks occur
19
Q
What happens after a typical absense seizure?
A
Normal activity is resumed in children, but typical absense attacks are more likely to develop into generalised grand mal seizures in adults
20
Q
What does a partial seizure imply?
A
A specific area of the brain has generated abnormal electrical activity
21
Q
What do the symptoms reflect in partial seizures?
A
The areas involved
22
Q
What symptoms can occur with partial seizures?
A
- Involuntary motor disturbances
- Behavioural changes
- An aura developing
23
Q
How can the development of an aura present?
A
An unusual smell, tingling in a limb, or a strange inner feeling
24
Q
Give two examples of partial seizure types
A
- Jacksonian seizures
- Temporal lobe seizures
25
What are Jacksonian seizures?
Focal motor seizures
26
What are temporal lobes seizures?
Where sufferer develops feelings of 'deja vu' or 'jamais vu' (feeling of unfamiliarity)
27
What is the clinical importance of status epilepticus?
It is a medical emergency
28
What is status epilepticus?
When there are continuous seizures without a recovery period of consciousness
29
What can status epilepticus be defined as?
A single convulsion lasting more than 30 minutes, or convulsions occuring back to back with no recovery between them
30
Why is status epilepticus a medical emergency?
Because it has a high mortality rate
31
What % of cases of status epilepticus occur in people without a history of epilepsy?
50%
32
What may lead to status epilepticus?
Serial epilepsy
33
How will untreated status epilepticus cause damage?
* Physical injury resulting from fall/crash
* Hypoxia
* SUDEP (sudden death in epilepsy)
34
What are the neurological dangers of status epilepticus?
* Brain dysfunction
* Cognitive impairment
* Serious psychiatric disease
35
When is epilepsy defined as primary?
When there is no identifiable cause established
36
What % of cases of epilepsy are defined as primary?
65-70%
37
What is secondary epilepsy?
Epilepsy where an underlying medical condition causing the seizures has been identified
38
What kind of epilepsy is more common in elderly individuals?
Secondary
39
What are the main causes of secondary epilepsy? q
* Brain injury and hypoxia
* Pyrexia
* Brain tumours
* Alcohol, drugs, and drug withdrawal
* Encephalitis and inflammatory conditions
* Metabolic abnormalities
* Provoked seizures
40
What brain injuries can cause epilepsy?
* Perinatal trauma
* Depressed skull fracture
* Intracranial haematoma
* Cerebral contusion
41
In whom is pyrexia causing seizures common?
Children
42
Is reoccurance of seizures caused by pyrexia common?
No, it is rare
43
What kind of seizures will brain tumours cause?
Parial focal or secondary generalised seizures
44
Give two examples of inflammatory conditions that can cause epilepsy
* Cerebral absesses
* Neurosyphillis
45
Give three examples of metabolic abnormalities that can cause epilepsy
* Hypocalcaemia
* Hypoglycaemia
* Hyponatraemia
46
What causes provoked seizures?
Flashing lights
47
What is it called when seizures are provoked by flashing lights?
Photosensitivity
48
What are the main mechanisms important in anti-epileptic drugs (AEDs)?
* Enhancement of GABAA action
* Inhibition of sodium channel function
* Inhibition of calcium channel function
* Inhibition of glutamate release
49
Give 3 drugs that enhance GABAA action
* Benzodiazepines
* Valproate
* Phenobarbitone
50
Give 3 drugs that inhibit sodium channel function
* Phenytoin
* Carbemezepine
* Lamotrigine
51
Give a drug that inhibits calcium channel function
Gabapentin
52
What are the main AEDs used in clinical practice?
* Carbamezepine
* Valproate sodium
* Benzodiazepines
* Phenytoin
* Lamotrigene
53
What AEDs can be used in clinical practice, but are more done so by a neurology specialist?
* Gabapentin
* Barbituates
* Vigabatrin
* Clonezepam
54
What are the two main classes of AEDs that are prescribed?
* Voltage-gated sodium channel blockers
* Enhancing GABA mediated inhibition
55
Give 3 AEDs that are voltage-gated sodium channel blockers
* Carbemezepine
* Phenytoin
* Lamotrigine
56
Give 2 AEDs that enhance GABA mediated inhibition
* Valproate sodium
* Benzodiazepines
57
What do voltage-gated sodium channel blockers bind to?
The internal face of the sodium channel,
58
When do VGSC blockers bind to the internal face of the sodium channel?
When the channel is in its inactivated state
59
How do VGSC blockers work as anti-epileptics?
They act preferentially on the neurones causing the high frequency discharge that occurs in an epileptic fit, whilst not interfering with the low-frequency firing neurones in their normal state.
## Footnote
*Depolarisation of a neurone increases the proportion of sodium channels in their inactivated state, and VGSC blockers bind preferentially to these channels, preventing them from returning to a resting state where they could continue to depolarise the neurone. They thus reduce the number of functional channels available to generate action potentials*
60
Pharmacokinetically, why is carbamezepine one of the most widely used anti-epileptics?
Well absorbed, has a linear PK
61
What is the half life of carbamezepine?
Initially, 30 hours, but with repeated use, becomes 15 hours
62
Why does the half life of carbamezepine decrease with repeated use?
Because it is a strong inducer of CYP450, which metabolises it
63
What is carbamezepine used to treat?
Generalised tonic-clonic and partial seizures, *but not absense seizures*
64
What are the CNS ADRs of carbamezepine?
* Drowsiness
* Dizziness
* Ataxia
* Motor disturbances
* Paresthesia
* Anasthesia
65
What are the GI ADRs of carbamezepine?
* Nausea
* Vomiting
66
What are the CVS ADRs of carbamezepine?
Variations in BP
67
What are the other ADRs of carbamezepine?
* Rashes
* Bone marrow suppression *causing potential neutropenia*
68
What are the DDIs of carbamezepine mainly based around?
Its CYP450 inducing effects
69
What are the DDIs of carbamezepine?
Reduces the levels of;
* Phenytoin
* Warfarin
* Corticosteroids
* Oral contraceptive
70
What drugs interfere with the action of carbamezepine?
Antidepressants
71
Is phenytoin well absorbed?
Yes
72
What is the % binding to plasma proteins of phenytoin?
90%
73
Does phenytoin act as a CYP450 inducer?
Yes
74
Describe the PK of phenytoin
Has a non-linear PK at therapeutic levels, but a linear PK at sub-therapeutic levels
75
What is the half life of phenytoin?
6-24 hours
76
What is the result of the variable half life of phenytoin?
Levels needs to be watched very carefully
77
What is phenytoin used to treat?
Generalised tonic-clonic and partial seizures, but not absense seizures
78
What are the CNS ADRs of phenytoin?
* Dizziness
* Ataxia
* Headaches
* Nystagmus
79
What are the other ADRs of phenytoin?
* Gingival hyperplasia
* Hypersensitivity rashes, *including Stevens Johnson syndrome*
80
In what % of patients taking phenytoin does gingival hyperplasia occur?
20%
81
What are the DDIs of phenytoin?
* Valproate
* Oral contraceptive
* Cimetidine
82
What happens when phenytoin and valproate are given together?
Phenytoin competitively binds, increasing plasma levels of valproate
83
What effect does phenytoin have on the oral contraceptive?
Reduces levels
84
What effect does phenytoin have on cimetidine?
Increases levels
85
What must be done when giving any other drugs in combination with phenytoin?
The BNF must be checked
86
Is lamotrigine well absorbed?
Yes
87
Describe the PK of lamotrigine?
Linear
88
What is the half life of lamotrigine?
24 hours
89
Does lamotrigine induce CYP450?
No
90
What is the result of lamotrigine not inducing CYP450?
It has less DDIs
91
What is lamotrigine used to treat?
Generalised tonic-clonic, partial seizures, and absense seizures
92
What are the CNS ADRs of lamotrigine?
* Dizziness
* Ataxia
* Somnolence
93
What are the GI ADRs of lamotrigine?
Nausea
94
What are the other ADRs of lamotrigine?
Skin rashes
95
What are the DDIs of lamotrigine?
* Adjunct therapy with other AEDs
* Oral contraceptives
* Valproate
96
What effect do oral contraceptives have on lamotrigine?
Reduce lamotrigine plasma levels
97
What effect does lamotrigine have on valproate?
Valproate levels in plasma increase *due to competitive binding*
98
What % of the synapses of the brain are GABA-ergic?
40%
99
What is the importance of GABA receptors in anti-epileptic drugs?
Several anti-epileptic drugs enhance the activation of GABAA receptors
100
What does the enhanced activation of GABAA receptors by anti-epileptic drugs facilitate?
The GABA-mediated opening of chloride ion channels
101
What are the main examples of AEDs that act as GABA-agonists?
* Benzodiazepines
* Valproate sodium
102
What effect will the opening of chloride ion channels have in epilepsy?
It will cause an inhibitory effect on neurones, and hence can be used as an anti-convulsant
103
Why does opening chloride ion channels cause an inhibitory effect on neurones?
Because increasing chloride current increases the threshold for action potential generation
104
How does valproate sodium act?
By increasing the GABA content of the brain by stimulating GABA synthesising enzymes and inhibiting GABA inactivating enzymes
105
Is valproate sodium absorbed well?
Yes
106
Is valproate sodium protein bound?
Yes
107
Describe the PK of valproate sodium
Linear
108
What is the half life of valproate sodium?
15 hours
109
What is valproate sodium used to treat?
Partial and generalised seizures
110
How do the ADRs of valproate sodium compare to other AEDs?
They are generally less severe
111
What are the CNS ADRs of valproate sodium?
* Ataxia
* Tremor
112
What are the hepatic ADRs of valproate sodium?
Increases transaminases
113
What do the DDIs of valproate sodium revolve around?
Adjunct therapies affecting PKd
114
What drugs does valproate sodium interact with?
* Antidepressants
* Antipsychotics
* Aspirin
115
What effect do antidepressants and antipsychotics have on valproate sodium?
They antagonise its action
116
What effect does aspirin have on valproate sodium?
Aspirin competitively binds against it
117
What monitoring is important when a patient is taking valproate sodium?
Monitoring of drug levels
118
How do benzodiazepines act?
They act on a distinct receptor site of the GABAA-receptor channels, which also bring about a positive allosteric effect, so GABA and BZDs enhance on another
119
Are benzodiazepines well absorbed?
Yes
120
Are benzodiazepines bound to plasma proteins?
Yes, highly
121
Describe the PK of benzodiazepines
Linear
122
What is the half life of benzodiazepines?
15-45 hours
123
What are benzodiazepines used to treat?
Status epilepticus and absense seizures *in short term use*
124
Why are benzodiazepines not used as a first line therapy?
As they produce a wide range of ADRs
125
What are the ADRs of benzodiazepines?
* Sedation
* Tolerance with chronic use
* Confusion
* Impaired coordination
* Aggression
* Act as abrupt withdrawal seizure triggers
* Respiratory depression
* CNS depression
126
What should the choice of anti-epileptic drug be based on\>
* The patient and their syndrome
* The side effect profile of the drug
127
What should always be aimed for in the treatment of epilepsy?
Monotherapy
128
At what doses should anti-epilepsy drugs be given?
Treatment should be started at a low dose, and increased only to maximise effect
129
What happens if the first-line drug is ineffective, despite adequate compliance?
It should be replaced by a second drug before any combined therapy is attempted
130
How can significant seizures be treated?
* Paralysis
* Sedation
* Intubation
131
What is the first line therapy for primary generalised seizures?
Valproate sodium
132
What is the first line therapy for partial seizures?
Carbamezepine
133
When is lamotrigine the drug of choice?
In generalised and partial seizures in women of childbearing age
134
Why is lamotrigine the drug of choice in women of child bearing age?
Due to reduced teratogenic effects, and affect on oral contraceptives
135
What is used for acute life-threatening status epilepticus?
Benzodiazepines or phenytoin
136
What are the main points to consider when managing epilepsy in pregnancy?
* Risk of seizures to mother and fetus if the treatment is stopped
* Certain anti-epileptic drugs have been associated with congenital malformations
137
Why is a careful history required when a pregnant woman has epilepsy?
To ascertain frequency and severity of seizures in the patient
138
Why is it important to ascertain frequency and severity of seizures in a epileptic pregnant woman?
As those with frequent seizures run the risk of status epilepticus, and cause harm to both themselves and the baby if treatment is stopped, yet the scenario would be different if seizures were mild and rare
139
How does the risk of fetal abnormalities compare in normal pregnancies, compared to when taking valproate?
2% in normal, 8% with valproate
140
What can teratogenicity from anti-epileptic drugs in pregnancy cause?
* Congenital malformations
* Neural tube defects
* Facial and digital hypoplasia
* Learning difficulties
141
Which drug in particular is there a risk of neural tube defects?
Valproate
142
What is the result of the risks of taking AEDs in pregnancy?
Normally, a single AED is prescribed if possible, and valproate is best avoided
143
What can be given during pregnancy to reduce the risk of teratogenic effects of AEDs?
* Folate supplements
* Vitamin K suplements
144
What is the purpose of folate supplements in pregnancy of a woman taking AEDs?
Reduce risk of neural tube defects
145
What is the purpose of vitamin K supplements in a pregnant woman taking AEDs?
Reduce risk of cerebral haemorrhage and coagulopathy associated with AED-linked vitamin K deficiency
146
What should be done in emergency treatment of epilepsy?
ABCs should be initially assessed, as well as attempting to treat underlying cause
147
What investigations should be done in the emergency treatment of epilepsy?
* Blood glucose
* U&Es
* Plasma calcium
* Blood gases
* Imaging
## Footnote
*Potentially should be done at a later stage*
148
What is the first line emergency treatment of seizures?
Benzodiazepines and then IV phenytoin
149
Give an example of a benzodiazepine
Lorazepam
150
Why can phenytoin be used in the acute seizure scenario?
As its zero order kinetics means that therapeutic levels can be reached quicker
151
What will be required if initial pharmacological measures to treat seizures fail?
* ITU referral with paralsysis
* Sedation
* Intubation
