Epilepsy Flashcards
What percentage of the population is estimated to have epilepsy?
~0.5%
What characterises epilepsy?
Abnormal high-frequency discharge of neurons
Unconsciousness during an epileptic episode often occurs when which brain region is involved?
The reticular formation
What is often thought to be the cause of abnormal discharge at the neuronal level?
The homeostasis of the neuro is unstable, leading it to reach a depolarising threshold more easily- this is a hyperexcitable state.
This may apply to enhance excitable neuronal activity or to dampen inhibitory neuron activity
What are two theories thought to cause a hyperexcitable state in neurons?
1) Na+, K+, Ca2+ and Cl- ion channels having mutations causing them to not maintain an appropriate resting membrane potential
2) ATPase is not fully functional meaning that ion pumps cannot maintain a stable electrochemical gradient and resting membrane potential
What is a partial seizure?
Abnormal neuronal discharge that begins and remains locally
What is a general seizure?
Abnormal neuronal discharge that spreads to encompass significant brain areas, including both hemispheres, and often involves a loss of conciousness
Name other classifications of seizures.
Complex, simple, tonic, clonic, atonic, myoclonic and absent
What are conditions that are similar to epilepsy?
Infantile seizures and epileptic syndrome
What is status epilepticus?
Continued and uninterrupted high-frequency discharge. This is life-threatening
What is excitotoxicity?
The repeated high frequency discharge of neurons can cause complex intracellular cascades that ultimately result in the death of the neuron
What percentage of patients are AEDs beneficial for?
Between 70-80%
How do AEDs work to decrease seizure activity?
They reduce the electrical excitability of the membranes
How do AEDs exert their effect?
By enhancing GABAs properties (increased production, decreased breakdown, synthetic agonists and increase GABA potentiation)
Another mechanism is to block T-type Ca2+ channels
What is a common issue with AEDs?
They can have severely harmful effects on developing foetuses
What is a common issue with AEDs?
They can have severely harmful effects on developing foetuses
Name 4 common AEDs
Phenytoin, carbamazepine, valproate and ethosuxamide
Comment on the use of Phenobarbitone as an AED
Not commonly used as it is toxic and a sedative
Comment on the use of Phenobarbitone as an AED
Not commonly used as it is toxic and a sedative
What is the mechanism of action of phenytoin?
It stabilises the membrane and inhibits post-tetanic potentiation by blocking voltage-dependent Na+ and Ca2+ channels. It also effects Ca2+ secretory processes
What is an issue with the administration of phenytoin?
It is a weak acid and consequently its intestinal absorption is highly variable; the plasma concentration is variable.
How is phenytoin metabolised?
By the microsomal system and then excreted in bile and urine
Which other conditions is phenytoin useful for?
Peripheral neuralgia
Name some drug that phenytoin can interact with
Chloramphenicol, isoniazid, cimetidine and dicumarol
Name some of the adverse effects that phenytoin has
Toxic to the foetus, ataxia, diplopia, hirsutism, gingival hyperplasia and blood dyscrasia
What is carbamazepine structurally similar to?
Tricyclic antidepressants
When is carbamazepine useful?
Useful in psychomotor seizures, trigeminal neuralgia and mania
Does carbamazepine have adverse effects?
yes
What is the mechanism of action of valproate?
It facilitates glutamic acid decarboxylase and inhibits GABA transaminase
What is valproate useful for treating?
Absent seizures
What are the serious adverse effects of valproate?
It is hepatotoxic and teratogenic
What are other adverse effects of valproate?
Nausea and anorexia
What is the mechanism of action of ethosuximide?
It blocks T-type Ca2+ channels
What are some side effects of ethosuximide?
Nausea and anorexia
Name three benzodiazepine AEDs
Diazepam, nitrazepam and clonazepam
When is diazepam useful?
In status epilepticus
When is nitrazepam useful?
Partial, myoclonic and infantile seizures
When is clonazepam useful?
Effective at treating myoclonic seizures and can be used for partial seizures and status epilepticus
What is a common barbiturate?
Phenobarbitol, also known as luminal
When is phenobarbitol useful?
In treating general tonic-clonic seizures and status epilepticus
What is the primary mechanism of action of phenobarbitol?
Blocking presynaptic Ca2+ currents thus reducing neurotransmitter release
What is the secondary mechanism of action of phenobarbitol?
It prolongs the time the Cl- channel is open in the post synaptic membrane
What are some adverse effects of phenobarbitol?
It acts as a sedative and depressant. It also has significant drug interactions
Vigabatrin is a new AED. What is its mechanism of action?
Covalently binds to and blocks GABA transaminase
Lamotrigine is a new AED. What is its mechanism of action?
Reduces Na+ and Ca2+ activity as well as reducing EAA release
Tiagabine is a new AED. What is its mechanism of action?
Prevents the uptake of GABA
What are two more new AEDs?
Gabapentin and pregabilin
Which drugs are useful in tonic clinic (GM) seizures?
Carbamazepine, phenytoin and valproate
Which drugs are useful for partial/focal seizures?
Carbamazepine, phenytoin, valproate and clonazepam
Which drugs are useful in Absence seizures (PM)
Ethosuximide and valproate
Which drugs are useful in myoclonic seizures
Valproate and clonazepam
Which drugs are useful in status epilepticus?
IV diazepam
What non-epileptic uses are there for AEDs?
Anxiety, mania, chronic and neuropathic pain
List 6 antispasmodics
Baclofen, Benzodiazepine, Tizanedine, Botox, Dantrolene and Cannabis
