P20: Anticonvulsant Therapy Flashcards
What happens to neurones when someone has epilepsy?
- Large groups of neurones are activated repetitively and hypersynchronously
- The inhibitory synapses between neurones also fail
What are the 2 main clinically defined classes of seizures?
Partial and generalised
During a partial seizure where in the brain does the discharge occur?
Discharge is confined to one part of the brain (e.g. cortex)
What are the two types of partial seizures?
- Simple (no loss in consciousness)
- Complex (loss of consciousness to some degree)
Partial seizures that effect the motor cortex are termed?
Jacksonian seizure
Partial seizures that effect the Temporal lobe (mood) are termed?
Psychomotor seizure
Absence seizure (aka petit mal)
Loss of consciousness, vacancy and unresponsiveness <30s
Myoclonic seizure
Extremely brief (< 0.1 second) muscle contraction, jerky movements
Clonic seizure
Regularly repeating myoclonic seizures, typically of 2-3 /sec
Tonic-clonic seizure (aka Grand mal)
- Initial muscle contraction (tonic phase), which may include tongue biting, urinary incontinence and absence of breathing
- Followed by rhythmic muscle contractions (clonic phase)
Atonic seizure (aka petit mal)
Loss of muscle tone, causing collapse
What are some acquired causes of epilepsy
- Trauma
- Stroke
- Tumours
- Infection-induced
Generally how does epilepsy treatment work?
- Suppressing excessive synaptic activity
OR - Enhancing inhibitory neurotransmitter function
Name some epilepsy treatment drugs that interact with sodium channels to reduce activity
- Phenytoin
- Carbamazepine
- lamotrigine
Name some epilepsy treatment drugs that enhance GABA activity
- Phenobarbitone
- Diazepam/lorezepam
- Tiagebine
- Gabapentine
Name some epilepsy treatment drugs that treat absence/petit mal seizures
- Ethosuximide
- Valproic acid
What is Phenytoin? (3)
- Sodium channel modifier
- Bind to inactive sodium channels that regulate membrane excitability and keep them closed for longer
- USE DEPENDANT so more active a neurone is the most effective it is
- Used for all seizures except petit mal seizures
What is Carbamazepine? (3)
- Sodium channel modifiers
- Prolongation of Na+ channel inactive state
- For grand mal and psychomotor partial seizures
What are the adverse effects of using Carbamazepine?
- Acute intoxication: coma, convulsions, respiratory depression
- Chronic use: ataxia, vertigo, vomiting, hypersensitivity, hyponatraemia
- May worsen petit mal seizures
What is Phenobarbitone? (4)
- GABA modifier, Barbiturate
- Prolonging GABAa opening (hyperpolarisng post synaptic membrane)
- Reduction in glutamate excitation
- affective against all but absence seizures
What are the adverse effects of using Phenobarbitone?
- Sedation
- Megaloblastic anaemia (give folic acid)
- Osteomalacia (bone softening; give vitamin D)
- Overactivity in children
What is Diazepam/lorezepam? (2)
- Promote GABAA opening
- Increases Cl- channel opening
- used in status epilepticus, i.v. diazepam is fast but sedative
What is Tiagabine? (4)
- Selective GABA reuptake inhibitor
- Blocks GAT-1 transporter
- So GABA not re-uptaken
- Partial seizures only, may induce status epilepticus
What are the side effects of Tiagabine?
- Ataxia
- Dizziness
- Tremor
- Depression
What is Ethosuximide? (2)
- Inhibits neuronal T-type voltage gated Ca2+ channels, reducing Ca2+ influx
- Petit mal
- These currents are important in bursting behaviour of thalamic neurones – common site for initiation of epileptiform waves
What are the side effects of Ethosuximide?
- Drowsiness
- Euphoria
- Ataxia
- Anxiety
- Aggressiveness
What is Valproic Acid?
- suitable for grand and petit mal
- Inhibits GABA transaminase, increasing synaptic GABA
- may also increase rate of GABA synthesis
- Hyperpolarisng post synaptic membrane
- Use-dependently inhibits voltage-gated Na+ channel activity
What are the side effects of Valproic Acid?
- Acute: nausea, vomiting
- Chronic: weight gain, hair loss, thrombocytopaenia, tremor
How is phenytoin administered, and eliminated
orally well absorbed
eliminated by hepatic metabolism
What are the adverse effects of phenytoin
- Megaloblastic anaemia(folic acid given)
- Hirsutism (hair growth following androgen release)
- Gum hyperplasia
What effect does carbamazepine inducing hepatic enzymes have
Reduces the effect of phenytoin, oral contraceptives and warfarin
What does excessive and insufficient inhibitory transmission cause
excessive - loss of consciousness
insufficient - seizures
What effect does phenobarbitone have on children
Hyperactivity
What does tiagabine act on
Pre-synaptically and on glia
What effect do barbiturates and benzodiazepines have on inhibitory GABA signalling
enhance GABAA Cl- channel flux
