Anticonvulsants Flashcards
What is a seizure?
A failure of conscious intent to control brain function.
What are convulsions?
Failure to inhibit motor output
What are absence seizures?
Inability to generate motor output
T/F Seizures may be idiopathic or secondary to various conditions.
TRUE
When would chronic pharmacological treatment be warranted?
If the seizure was of an unknown cause and recurring (epilepsy). Similar therapy may be needed in the aftermath of a known cause.
What are the 3 stages typically seen in seizures?
(1) Focal discharge (paroxysmal depolarization)
(2) Spread
(3) Termination
What is the prevalence of epilepsy?
about 1-2%, second most common neurological disorder (after stroke)
What are the three ways in which anticonvulsants work?
(1) Decrease excitation: glutamate receptors and glutamate release (calcium channels)
(2) Increase inhibition: GABA receptors GABA synthesis and release
(3) Decrease impulse generation and propogation: Na channels (K channels)
What are the main causes of provoking seizures?
- Things that are stressful
- Dehydration
- Sleep deprivation
- Head injury
- Infection
- Fever
- Intoxication of drugs
- Space occupying lesions in the brain
Anticonvulsants: Mechanism of action
- Seizure spread through brain depends on action potentials (sodium channels) and release of excitatory transmitters (mostly glutamate) (calcium channels). It is prevented by inhibitory neurotransmitters, especially GABA
Anti-seizure drugs suppress spread of abnormal electrical activity (rather than eliminate its cause) by these 4 things:
(1) Blocking actions potentials (sodium channel block)
(2) Increasing the inhibitory tone of the brain (increasing GABA transmission)
(3) Reducing neurotransmitter release (calcium channel block)
(4) Reducing excitatory neurotransmission (decreasing glutamate neurotransmission)
What are the two types of partial seizures?
Simple partial and Complex partial
What are the major manifestations of simple partial seizures? (2)
(1) Various manifestations, depending upon the affected brain region
(2) Key feature is preservation of consciousness
What are the major manifestations of complex partial seizures? (4)
(1) Localized onset followed by widespread discharges (usually bilateral)
(2) Confused behavior, impairment of consciousness
(3) Most arise form the temporal lobe
(4) Almost always involves the limbic system
What are the two types of generalized seizures?
Tonic-clonic (Grand mal) and Absence (Petit mal)
What are the major manifestations of tonic-clonic seizures? (2)
(1) Major convulsions (tonic body muscle spasms followed by synchronous clonic jerking)
(2) Prolonged depression of all central functions after seizures (postictal depression)
What are the major manifestations of absence seizures? (4)
(1) Sudden onset, abrupt cessation (usually less than 10 sec)
(2) Brief loss of consciousness, sometimes with motor involvement
(3) Occurs in childhood and often disappears during maturation; may be frequent
(4) Characteristic 3 Hz spike and wave EEG
What are the animal models take home messages for the exam? (3)
(1) Some models may relate to epilepsy if the animals have spontaneous recurrent seizures (seizure prone genetic strain, “kindled” animals)
(2) Most models related better to acute seizures, either partial or general
(3) Animal models are most useful for screening for new drugs or testing drug combination
What are the Anticonvulsants that are sodium channel blockers? What are they generally effective against?
(1) Phenytoin
(2) Carbamazepine
(3) Lamotrigine
- generally effective against partial seizures and generalized tonic clonic seizures
T/F (Sodium channel blockers) Anticonvulsants inhibit high frequency seizure activities without affecting normal action potentials.
TRUE; specifically bind to and prolong the inactivated state of voltage-activated sodium channels
What are the common side effects of sodium channel blockers?
(1) Nystagmus
(2) Diplopia
(3) Ataxia
What are the anticonvulsant drugs that enhance GABA neurotransmission?
(1) GABAa receptor modulators (postsynaptic)
- barbituates (phenobarbital)
- benzodiazepines (diazepam, lorazepam)
(2) Drugs that increase synaptic GABA levels (presynaptic)
- valproic acid, tiagabine, gabapentin
What are the calcium channel blockers? What do they do?
- ethosuximide and valproic acid: inhibit “T-type” calcium channels that are enriched in thalamic neurons and involved in the generation of rhythmic action potentials responsible for absence seizures
- lamotrigine: inhibits another type (high voltage activated) or calcium channels