16 Antiseizure drugs Flashcards
Seizures are transient alterations in behaviour due to __________ and ____________
Seizures are transient alterations in behaviour due to abnormally excessive and synchronous neuronal activity in the brain
What does it mean that epilepsy can be symtomatic or asymptomatic?
Symptomatic: occur due to a known event (eg head trauma or cancer)
Asymptomatic: unknown, but believed to be due to genetic factors
Normally, neurons fire _______ in the brain.
Whereas seizures are:
Normally, neurons fire asynchronously in the brain
Seizures are: an extreme form of synchronous brain activity
What is surround inhibition?
The physiological mechanism that focuses neuronal activity in the CNS
What are the three ‘steps’ that a seizure can be divided into?
- initiation
- propogation
- termination
What two events characterize Seizure initiation?
- high frequency bursts of action potentials (recruit NMDA receptors)
- hyper synchronization of a neuronal population
*This sustained neuronal depolarization results in a burst of AP’s driven by Ca2+ influx through NMDA receptors
What normally prevents propagation of bursting activity
Hyperpolarization and surround inhibition
What are three ways that propagation/bursting activity can occur (ie how to overcome hyperpolarization and surround inhibition)?
- increasing extracellular K+
- blunts the hyperpolarizing outward potassium currents
- Accumulation of Ca2+ in presynaptic terminals leading to enhanced NT release
- Depolarization induced activation of NMDA receptor
- causes more Ca2+ influx and neuronal activation
Seizures generallly resolve _______ and the mechanisms that terminate a seizure are not well known but likely involve what 4 processes?
Seizures generallly resolve spontaneously and the mechanisms that terminate a seizure are not well known but likely involve what 4 processes?
- loss of ionic gradients (eg Na+ depleted = can’t maintain AP)
- depletion of ATP (low cell. resp.)
- depletion of NT’s (eg glutamate)
- Activation of inhibitory circuits (GABA)
Define status epilepticus
A seizure lasting longer than 5 minutes
or
if you have more than 1 seizure in a 5-minute period
Life-threatening
What is the postictal period and how long does it last?
The postictal period lasts 5-30 minutes after a seizure and is characterized by drowiness, confusion, depression/anxiety, and sometimes psychosis
What are two determining factors of seizure classification?
Different types of seizures depending on where in the brain they initiate and how widely they propagate
What are three classes of seizures?
- focal seizures
- simple
- complex
- generalized seizures
- several types including
- tonic clonic
- myoclonic
- several types including
- non-convulsive (absence) seizures
- absence
- atonic
What are focal seizures and what are the two types?
- Activation in a specific area of the brain (focussed)
- Diverse manifestations depending on where in the brain it originates (visual, psychic, auditory, autonomic, olfactory, or motor)
- Two types:
- simple (retain consciousness)
- complex (loss of consciousness)
What is jacksonian march?
Associated with focal seizures; jerking activity that starts in a specific muscle group and then spreads to surrounding muscle groups
What are automatisms?
Associated with Focal seizures; unusual activities that are not consciously created (eg smacking the lips)
What are generalized seizures? What are the two type mentioned in lecture?
- Seizure that migrates/propogates throughout entire brain
- All involve loss of consciousness and typically happen without warning
- Two types:
- tonic-clonic
- myoclonic
What type of seizure involves sustained muscle contraction throughout the body (15-20 seconds) followed by periods of alternating muscle cotnraction and relaxation?
Tonic-clonic
(used to be called grand mal)
What is a myoclonic seizure?
Brief (~1sec) shock-like contraction of muscles that may be localized or generalized
What are non-convulsive seizures and what are the two types mentioned in lecture?
No shaking or motor response at all
- Absence Seizures:
- abrupt onset of impaired consciousness
- can be subtle (look like “zoning out”)
- may return to normal right after seizure ends or have period of postictal disorientation (petit mal)
- Atonic Seizures:
- sudden loss of muscle strength
- usually consciousness is maintained, though the person may fall down
What are three situations that might warrant the use of antiseizure drugs?
- chronic use to prevent the occurrence of seizures in individuals with epilepsy
- used in people who do not have epilepsy to prevent seizures that may result as part of an acute illness (eg meningitis) or in early period following either neurosurgery or traumatic brain injury
- terminate ongoing seizures such as in status epilepticus or prolonged febrile seizures or following exposure to seizure inducing nerve toxins
Seizures are occasionally caused by an acute underlying toxic or metabolic disorder such as ________. Would antiseizure drugs be effective tx?
Seizures are occasionally caused by an acute underlying toxic or metabolic disorder such as hypocalcemia. Would antiseizure drugs be effective tx?
- no, in cases like this it would be more appropriate to treat the specific abnormality
How do antiseizure drugs act?
Antiseizure drugs act by either enhancing inhibitory (GABAergic) neurotransmission or diminishing excitatory (glutamatergic) neurotransmission
What are three ways in which antiseizure drugs either enhance GABAergic neurotransmission (inhibitory) or diminish glutamatergic (excitatory) neurotransmission?
- blocking ionic conductance (particularly sodium, calcium, and potassium)
- Blocking NT release
- Inhibiting/activating the postsynaptic membrane
One drug may have multiple targets that reduce liklihood of seizures
