Week 12 Epilepsy Flashcards
What is epilepsy
a group of diseases
affects 1-3% population
characterised by unprovoked and provoked reccurring seizures
seizure is characterised by hypersynchronus hyperexcitability of groups of neurons
diagnosed by EEG (electroencephalography)
what is EEG
Electroencephalography
records electrical activity between two electrodes, namely the potential difference between two points.
it records to summated activity of groups of neurons
three main types of seizure
- Focal onset
- people are aware/conscious or the awareness is impaired - Generalised onset
- people are not aware - unknown onset
Generalised seizures
Absense
Tonic-Clonic
(also Myoclonic and Atonic)
the seizures look different and its depending on which neurons fire excessively
Tonic-Clonic seizures
Tonic seizures have strong contraction of all of the muscles (they all stiffen)
- loss of awareness
- might cry or groan
- potential stop of respiration (go blue)
- increased salivation/foaming
- sometimes loss of bladder control
Clonic seizures have strong or violent jerking that can last several minutes
(they often follow tonic seizures which is why these are called clonic-tonic)
injuries can occur in both
slow recovery, confusion + drowsiness
Absences
Also generalised seizures because the whole brain is involved
typically in childhood
- sudden loss of awareness but retain motor function
e.g. stop playing and stare at nothing or have fluttering of eyes and then resume what they were doing and have no memory of the event
well described in the EEG: absences due to abnormalities in the t-type calcium channels leading to characteristic EEG with 3 spikes per sec
TREATMENT: valproate (calcium channel blockers)
Genetic basis of epilepsy
> 30% of epilepsies have a genetic component
certain mutations in single genes have been identified for certain rare epileptic syndromes
many epilepsies are multi-genetic - several genes are involved
Focal seizures
initiated by simultaneous firing of a group of neurons in the brain (epileptic focus)
the site of pathological discharge determines the symptoms (e.g. motor vs sensory cortex)
seizure generalisation is possible
not genetic but we can point it towards certain things have have happened in the past e.g.
anoxia or hypoglycemia in birth
meningitis, fever, brain trauma, tumours, stroke, drug abuse, lack of sleep, flashing lights,
human temporal lobe epilepsy
focal seizure
often originates in the termporal lobe
you see strong emotions or have dreams or drowsiness
this type is hard to treat with drugs so many people choose surgery
Status epilepticus
life-threatening/ high mortality
defined as 5 mins or longer of a continuous seizure
or when someone has two or more sequential seizures without recovering in-between
(with epilepsy you generally know how long the seizures last per person so if it last longer call for help)
consequences for patient
- anxiety or depression
- social discrimination
- no driving, jobs etc
- no flashing lights or alcohol
- often life long treatment with epileptic drugs
- fetal risk
Mechanism of action of antiepileptic drugs
1.Strengthening of inhibitory
(GABAergic) input
- Blockade of sodium channels which are required for impulse transmission
- Blockade of calcium channels (to block synaptic release of
neurotransmitters) - Blockade of excitatory
(glutamatergic) input
Pharmacodynamic properties of classical AED
Narrow therapeutic index
CNS depression („neurotoxicity“) reflected in sleepiness, dizziness, ataxia …
Hypersensitivity reactions
rare but present with most AED
often manifest as skin reactions or hematotoxicity
Teratogenicity (don’t use while pregnant)
e.g. valproic acid, phenytoin, carbamazepine
Long half-lives (>12hrs), dose-finding difficult
The drugs interfere with other drugs, especially contraceptives
[Modulation of cytochrome P-450 activities
Induction by phenobarbital, phenytoin, carbamazepine
Inhibition by valproic acid
Requires dose adjustments and causes interactions with other drugs ]
Poor compliance
Therapeutic drug monitoring (TDM) recommended
Benzodiazepines
Allosteric modulators of the GABAA receptor increasing the action of GABA at the GABAA–receptor => opening probability increases
Used as anxiolytics, sleeping aids, anti-seizure drugs, induction of anaesthesia
1st choice for status epilepticus or as rescue medication
Clobazam approved for long-term treatment of certain seizure disorders
Other effects:
sedation (synergistic with ethanol), lethargy, confusion
muscular incoordination, ataxia
i.v.: respiratory and cardiovascular depression
tolerance may develop
Barbiturates - phenobarbital
Allosteric modulator of GABAA receptors
increase receptor pore opening time of GABAA receptor
Drug of choice for neonatal seizures, also sedative
Last resort drug for pts unresponsive to other drugs
May be used for refractory status epilepticus
Least expensive drug (used for dogs with epilepsy)
PK:
CYP-dependent elimination
Strong inducer of CYPs (! Contraceptives)
Adverse effects:
Strong sedative effects at initiation of therapy, later tolerance
Rashes, hematological problems
Used for capital punishment on death row
