Drugs for Epilepsy Flashcards
What is epilepsy?
a disorder of the brain characterised by repeated/recurrent seizures
What is a seizure?
an episodic/single sudden abnormal excessive and synchronous discharge of a group of neurons in the brain
What does abnormal electrical activity across the brain result in?
- loss of consciousness
- abnormal movements
- atypical or odd behaviour
- distorted perceptions
What are causes of epilepsy?
- genetic
- developmental defects/congenital abnormalities
- infection
- trauma/injury
- degenerative diseases
- pregnancy (eclampsia)
- psychogenic seizures
What are symptoms of epilepsy?
- sudden falls
- uncontrollable jerking movements
- strange sensations and emotions
- loss of consciousness and awareness
- staring
- aura
- confusion
What are the types of epileptic seizures?
focal/partial and generalised
What are the symptom types of focal seizures in the different lobes of the brain?
- frontal - movement, emotions, memory, language, behaviour and personality
- temporal - hearing, speech, memory and emotions
- parietal - bodily sensations
- occipital - processing vision
What are focal seizures divided into?
simple and complex
What is a simple focal seizure?
abnormal activity confined to a single locus in the brain, does not spread and presents as abnormal activity of single muscle or limb
What is a complex focal seizure?
complex sensory hallucinations and mental distortion that presents as motor dysfunction e.g. chewing mvts, diarrhoea and urination
What do generalised seizures involve?
abnormal electrical discharge throughout the brain (can be convulsive or non-convulsive with immediate loss of consciousness)
What are the 5 types of generalised seizures?
- generalised tonic-clonic
- absence seizures
- generalised-myoclonic
- febrile seizures
- status epilepticus
How can epilepsy be diagnosed?
- neurological examination (physical signs)
- EEG
- MRI
- PET
- SPECT
What are the neural mechanisms of epilepsy associated with?
- enhanced excitatory neurotransmission
- impaired inhibitory neurotransmission
- abnormal electrical activity of affected cells
- several susceptibilities of genes encoding neuronal ion channels
- excitotoxicity
In an epileptic brain, what is the imbalance?
more excitation than inhibition
What are the 2 main mechanisms involved in epilepsy?
- EPSP in the brain by sodium and calcium channel functions and glutamate and AMPA/NMDA receptor neurotransmission
- IPSP in the brain by GABA neurotransmission
What causes generalised seizures?
prolonged neuronal excitability
What 2 mechanisms cause prolonged neuronal excitability?
- dysfunction in sodium channels
- abnormal potassium channels slowing the rapid efflux of potassium
What do antiepileptic drugs aim to do?
inhibit neuronal discharge by decreasing excitation in the brain
What are the main mechanisms of anticonvulsant drugs?
- inhibition of voltage gated sodium and calcium channels
- increased activity of voltage gated potassium channels
- inhibition of neurotransmitter release
- inhibition of AMPAR
- increased activity of GABA receptor
What are all first generation antiepileptic drugs metabolised by?
cytochrome P450
What is the MOA of phenobarbital?
- increases duration of bursts of GABA A receptor mediated current
- enhances GABA action
What are the side effects of phenobarbital?
respiratory depression, Vitamin D and folic acid deficiency
What is the MOA of phenytoin?
- blocks sodium channels
- prevents repetitive firing by slowing the rate of recovery of voltage activated sodium channels from inactivation
What are side effects of phenytoin?
gingival hypertrophy, hepatitis, hirsutism, folic acid deficiency, osteomalacia, SJS
What are clinical uses of phenytoin?
all kinds of seizures except absence seizures
What is the MOA of ethosuximide?
- reduce T-type calcium currents in the thalamus
- blocks synchronised thalamic firing
What are side effects of ethosuximide?
nausea and vomiting, headache, dizzinesss, drowsiness, behaviour changes
What are clinical uses of ethosuximide?
absence seizures
What is the MOA of carbamazepine?
blocks sodium channels which slows their rate of recovery after inactivation
What are side effects of carbamazepine?
neurotoxicity, hypersensitivity, hepatitis, agranulocytosis
What are clinical uses of carbamazepine?
all seizures except absence, trigeminal neuralgia and bipolar disorder
What is the MOA of valproate?
- increases CNS GABA levels by increased synthesis and reduced catabolism
- blocks T-type calcium current
- enhances sodium channel inactivation
What are side effects of valproate?
hair loss, tremors, weight gain, hepatotoxicity
What are clinical uses of valproate?
all seizures and bipolar disorder
What is the MOA of barbiturates?
- act on a subset of GABA A receptors and increase frequency of opening of chloride channels
- GABA potentiation
What are clinical uses of barbiturates?
status epilepticus (not used for acute treatments of seizures)
What do newer antiseizure drugs target?
synaptic release
Which second/third generation antiseizure drugs decrease excitatory synaptic activity?
felbamate, topiramate, levetiracetam
What does lacosamide do?
block sodium channels to allow neurons to recover from prolonged depolarisation
What does retigabine do?
cause hyperpolarisation and stabilisation of resting membrane potential by potassium channel activation
Which second/third generation antiseizure drugs enhance GABA neurotransmission?
gabapentin and vigabatrin
What are screening methods for new antiseizure drugs?
- enhancement of GABA transmission
- diminution of excitatory transmission
- modification of ionic conductance
