Epilepsy Flashcards
What class of drugs are generally used to treat Epilepsy?
A. Anti-epileptic drugs (AEDs)
B. Analgesics
C. Mood-stabilising drugs
D. Anti-histamines
A. Anti-epileptic drugs (AEDs)
What is the goal of anti-epileptic drugs (AEDs)?
- Drug decreasing frequency/severity of seizures in epileptics
- Treats Sx not disease
- Goal: Maximise QOL w/o SEs
- No anti-epileptogenic drugs
Are there any drugs that cure the cause of epilepsy?
• No anti-epileptogenic drugs
List the cellular mechanisms of seizure generation.
- EPSPs
- Na+ influx
- Ca2+ currents
- Paroxysmal depolarisation
List the genera treatment targets for AEDs, as a class.
- Increase inhibitory NT: GABA
- Decrease excitatory NT: Glutamate
- Block voltage-gated inward positive currents: Na+ or Ca2+
- Increase outward positive current: K+
List the two main Neurotransmitters of the brain regarding epilepsy.
1) GABA
2) Glutamate
What is the process by which the main inhibitory NT in the brain mediates its affects?
Which enzyme degrades this NT.
- GABA binds to GABA-r ≈ opening and influx of Cl- ≈ hyperpolarization
- GABA transaminase breaks down GABA
What is the process by which the main excitatory NT in the brain mediates its affects?
Which enzyme degrades this NT.
Glutamate
• 1º excitatory NT
2 Types of Receptor:
• Ionotropic (ion-channels): Fast synaptic
- NMDA, AMPA, Kainate
- Gated Ca2+ and Na+ channels
• Metabotropic (GPCR): Slow synaptic
- Regulation of second messengers (cAMP and IP3)
- Modulation of synaptic activity
List the AEDs acting on Inotropic Glutamate receptors.
Give the three examples of this type of receptor and what ions it is permeable to.
- Phenytoin: Block NaVg (voltage-dependent sodium channels)
- Carbamazepine: Block NaVg
- Oxcarbazepine: Block NaVg and affects KVg (K+ efflux)
- Zonisamide: Block NaVg and T-type calcium channel
- Lamotrigine
AMPA/Kainate/NMDA
Ca2+ and Na+
What is the MOA of Lamotrigine?
Give its SEs.
- MOA: Inhibit NaVg
- Broad therapeutic profile
- SEs: Hypersensitivity reactions (skin rashes)
What is the MOA of sodium valproate?
Give its SEs.
- MOA: Unknown; increase GABA content of brain via inhibition of GABA transaminase + effect on NaVg
- SEs: Hair loss, teratogenicity, foetal syndrome (avoid in pregnancy), liver damage (rare)
Which AED is especially contraindicated in pregnancy or pre-conception.
What syndrome can this cause? What symptoms does this entail.
Sodium Valproate
Foetal Valproate Syndrome (FVS)
–> Foetal Valproate Syndrome: Spina bifida, CHDs, Cleft lip/palate, genital abnormalities, skeletal abnormalities, developmental delay
What is the MOA of Carbamazepine?
List its SEs.
- MOA: Block NaVg
- Uses: Partial seizures + trigeminal neuralgia
- SE: sedation, ataxia, mental disturbances, water retention
Which drug is a less toxic version of carbamazepine. Give its MOA and SEs.
Oxcarbazepine
• MOA: Block NaVg + effects on K+
• SEs: sedation
• Less toxic cf carbamazepine
What is the MOA of Topiramate?
Give its SEs.
How may you mitigate against the side effects of Topiramate?
- MOA: Enhances inhibitory effect of GABA + block NaVg + block CaVg
- SE: teratogenesis
- Slow titration to avoid side effects
What is the MOA of Tiagabine?
What are its SEs.
- MOA: GABA-uptake inhibitor
* SE: Dizziness and confusion
What is the MOA of Phenytoin?
Give the SEs of this drug.
- MOA: Block NaVg
- Uses: Most epilepsy and antidysrhythmic agent cf absence seizures
- Need monitoring: saturation kinetics thus monitoring needed
- Drug interactions common
- SEs: confusion, gum hyperplasia, skin rashes, anemia, teratogenesis, cerebellar syndrome, osteoporosis; Diplopia, Ataxia and Nystagmus (Vestibulocerebellar syndrome) = ‘DAN’
Which AED can cause Vestibulocerebellar syndrome?
Phenytoin
Diplopia
Ataxia
Nystagmus
–> DAN
What is the MOA of Ethosuximide? What are its SEs.
- MOA: Block T-type Calcium channels
- Uses: Absence seziures; may exacerbate other forms
- SEs: Nausea and anorexia
Which of the following AEDs works by inhibiting GABA-uptake?
A. Lamotrigine
B. Phenytoin
C. Tiagabine
D. Ethosuximide
C. Tiagabine
Which of the following AEDs works as an antagonist to NaVg of ionotropic Glutamate receptors?
A. Lamotrigine
B. Phenytoin
C. Tiagabine
D. Ethosuximide
A. Lamotrigine
B. Phenytoin
Which of the following AEDs works as an antagonist to T-type calcium channels as NMDA or AMPA glutamate receptors?
A. Lamotrigine
B. Phenytoin
C. Tiagabine
D. Ethosuximide
D. Ethosuximide
Which of the following AEDs works by inhibiting GABA-uptake?
A. Lamotrigine
B. Phenytoin
C. Sodium Valproate
D. Ethosuximide
C. Sodium Valproate
Which of the following AEDs has a side effect of hair loss?
A. Lamotrigine
B. Phenytoin
C. Sodium Valproate
D. Ethosuximide
C. Sodium Valproate
Which of the following AEDs works by inhibiting NaVg ionotropic glutamate channels?
Of these, which is safest?
A. Carbamazepine
B. Oxcarbazepine
C. Sodium Valproate
D. Ethosuximide
A. Carbamazepine
B. Oxcarbazepine
Safest:
B. Oxcarbazepine
Which of the following AEDs inhibits GABA transaminase to increase GABA? When would it be used? What are its Side Effects?
A. Carbamazepine
B. Oxcarbazepine
C. Vigabatrin
D. Phenytoin
C. Vigabatrin
Used if unresponsive to conventional drugs
• SE: drowsiness, behavioural and mood changes, retinal loss
Which of the following AEDs inhibits Calcium channels?
A. Phenytoin
B. Sodium valproate
C. Gabapentin
D. Vigabatrin
C. Gabapentin
What AED is used primarily for Absence Seizures?
A. Phenytoin
B. Ethosuximide
C. Lamotrigine
D. Oxcarbazepine
B. Ethosuximide
For primary generalised seizures, which AEDs can be used?
For all bar absence seizures:
- Valproic acid
- Lamotrigine
- Topiramate (GABA)
For simple complex seizures, what AEDs can be used?
- Carbamazepine
- Oxcarbamazepine
- Sodium valproate
- Lamotrigine
What is epilepsy?
Continuing tendency to have seizures (convulsion/transient abnormal event caused by paroxysmal discharge of cerebral neurons)
List 5 aetiological features of epilepsy.
TTTES
- Flashing lights
- Cerebrovascular disease
- Cerebral tumours
- Alcohol-related
- Post-traumatic epilepsy
- Metabolic disturbances: hypoglycemia, acute hypoxia, hyponatremia, uremia, hepatocellular failure ≈ convulsions
What steps can be useful in the evaluation of epilepsy?
1) Confirm diagnosis: Clinically
2) Seizure type: Generalised tonic-clonic seizures/Typical absence seizures/ Myoclonic, tonic and akinetic seizures/ Partial seizures
3) Identify cause: EEG; Brain imaging (CT/MRI)
List the information you would wish to gain from an epilepsy history.
• History: Patient + Collateral
- Aura/Warning
- Abnormal movements
- Colour
- Position
- When?
- Duration
- After effects: Confused/Headache/Disorientated
Outline the investigations for a patient experiencing seizures.
Are investigations required?
- Examination usually normal
- ECG
- EEG
- MRI
Note: Epilepsy is a clinical diagnosis
Outline the management of Seizures.
Management: Aim for monotherapy; routine measurement necessary for phenytoin and phenobarbital.
• AEDs: Sodium valproate (Generalised tonic-clonic); Sodium valproate (petit mal); Lamotrigine/Carbamazepine (Partial seizures)
- Withdraw drugs once under control and seizure-free for 2 years
- Neurosurgery: e.g. Amputation of anterior temporal lobe
- Advice: Avoid dangerous sports/leave door open when taking a bath/ don’t swim alone/ don’t drive alone/don’t drive (be seizure-free for a year)/don’t drive HGV (seizure-free and off AEDs for 10+ years)
What advice would you give to a patient for the management of Seizures?
Avoid dangerous sports/leave door open when taking a bath/ don’t swim alone/ don’t drive alone/don’t drive (be seizure-free for a year)/don’t drive HGV (seizure-free and off AEDs for 10+ years)
List the main types of seizure.
1) Generalised tonic-clonic: Rigid tonic phase + jerking (clonic phase) then stuporous state
2) Typical absence seizures: Cease activity, stares and pales for a few seconds
3) Myoclonic, tonic and akinetic seizures: myoclonic, tonic and akinetic ± loss of consciousness
4) Partial Seizures:
i) Focal seizures: Sx depend on site of brain affected
ii) Secondary generalised seizures: Seizure can become secondarily generalised
What type of seizure involves:
Jerking movements, corner of the mouth or thumb and index finger spreading to involve limbs on the contralateral side of the epileptic focus?
What is the term for this if it occurs for several hours?
Jacksonian Seizure
Todd’s Paralysis
What seizure type involves olfactory and visual hallucinations, blank staring, feeling of unreality and undue familiarity with surroundings?
What are the last two symptoms termed?
Temporal lobe seizures
Jamais-Vu
Deja-Vu
Should a seizure continue for ≥ 30 minted or 2 seizures without recovery of consciousness between them, what is the term for this?
Status Epilepticus
What is Status Epilepticus?
medical emergency whereby continuous seizures occur for ≥ 30 minutes OR 2 or more seizures without recovery of consciousness between them or over a similar period
What are the precipitating factors for Status Epilepticus?
- Stopping AEDs
- Intercurrent illness
- Alcohol abuse
- Poor compliance with therapy
Outline the investigations you would conduct for Status Epilepticus.
Investigations:
• Brain-CT
• LP
• Blood cultures
Outline the management of a patient with Status Epilepticus
i) Out of hospital
• Diazepam: rectal
Midazolam: 10mg buccal
ii) In Hospital
• Supportive: Oxygen; venous access (anti-convulsants cause phlebitis)
• Thiamine: 250mg IV for 10 minutes
• 1º: Lorazepam: 4mg IV at 2mg/min repeated at 10 mins if no response
• 1º (no IV access) Diazepam (10-20mg) rectal if no IV access
• 2º Phenytoin: 15rmg/kg IV 50mg/min
• 3º Phenobarbital: 10mg/kg at rate < 100mg/kg at repeated 6-8 hours
• 3º Sodium valproate: 25mg/kg IV
What is the first line therapy for Status Epiepticus?
- Supportive: Oxygen; venous access (anti-convulsants cause phlebitis)
- Thiamine: 250mg IV for 10 minutes
- 1º: Lorazepam: 4mg IV at 2mg/min repeated at 10 mins if no response
- 1º (no IV access) Diazepam (10-20mg) rectal if no IV access
