anticonvulsants Flashcards
define seizures
- Sudden, transient episodes of brain dysfunction and altered of behavrior due to ABNORMALLY EXCESSIVE, SYNCHRONOUS, and RHYTHMIC FIRING (electrical discharge) of certian populations of hyper-excitable neurons in the brain
describe the underlying causes of seizures
- Altered excitation thresholds of cerebral neurons due to CNS INJURY (head trauma, stroke, tumors, etc)
- Congenital abnormalities (birth trauma)
- Genetic factors
–> defective genes coding for voltage-gated ion channels or GABA receptors, etc
define Epilepsy
- CHRONIC NEUROLOGICAL DISORDER CHARACTERIZED BY RECURRENT SEIZURES
- Types:
–> primary (idiopathic) epilepsy = unknown origin
–> secondary epilepsy = identifiable cause
Describe Partial epileptic sizures (types)
Starts in a SPECIFIC LOCATION OF BRAIN and usually REMAIN THERES
1) Simple partial seizure = minimal spread of abnormal neuronal discharge
–> NO LOSS OF CONSCIOUSNESS, limited motor/sensory manifestations
2) Complex Partial seizure = Starts in a small brain area but quickly spreads to other areas
–> Altered consciousness (staring, staggering) with potential AUTOMATIsM (lip smacking, fumbling, swallowing) lasts 30-120 secs
3) Partial becoming generalized = partial seizure that SPREADS THROUGHOUT THE BRAIN AND PROGRESS TO A GENERALIZED SEIZURE
define generalized epileptic seizure
- Involve the entire rain with global EEG chagne and bilateral manifestations
Define Abscence (petit mal) generalized seizure
- Sudden onset and abrupt cessation (10-45 secs), can occur frequently
- Brief loss of consciousness (range from no motor signs to symmetrical jerking movements or entire body)
- typically observed in children (<15) –> may devleop into tonic-clonic seizure
- Induce by hyperventilation, stress or flash light
describe tonic-clonic (grand mal) epileptic seizure
- Tonic spasms and major convulsions of enire body (Bilateral)
- Loss of consciousness, profound CNS depression after seizure
Seizure progression
1) the aura = sense of impeding development of seizure
2) Tonic phase = muscle tensing and rigidity of all extremities, followed by tremor
3) Clonic phase = convulsions due to rapid and repeating muscle contractions and relaxing –> uncontrolled shaking of body
4) stuporous state and slee
Describe status epilepticus type of epileptic seizures
- continuous or very rapid recurring seizures, usually of the tonic-clonic type
- Medical emergency requiring immediate therapy
what is the sequence of generating epileptic seizures
- Initiation (Ca++, GABA, Na+
- synchronization of surrounding (Na+, pH, glutamate)
- propagation –> recruitment of normal neurons (glutamate, pH)
describe the tx option for epilepsy
- Antiepileptic medications
–> Goal is to RESTORE NORMAL PATTERNS OF ELECTRICAL ACTIVITY
–> inhibit seizures, not effective as prophylasis, not a cure
- Surgery = resection, particularly in temporal lobe
- Vagus nerve stimualtion (VNS) = drug-resistant patients with partial seizures
define Spasticity
- primarily an exaggerated muscle stretch reflex syndrome that occurs following nijury to CNS
- goal of therapy is to normalize muscle excitability
define spasm
- an increase in muscle tension seen after certain musculoskeletal injuries and inflammation (injury is local and not in the CNS)
- goal of therapy is to normalize muscle excitability
Describe the general mechanisms of anticonvulsant agents
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Goal: avoid the uncontrolled recurrence of seizures to prevent futher CNS damage
- INHIBIT FIRING of certain hyperexcitabile cerebral neurons VIA:
1) decrease excitatory effects of glutamate and repetitive firing neurons (BLOCK VOLTAGE-GATED Na+ channels)
2) INcrease inhibitory effects of GABA
3) Alter neuronal activation by altering movement of ions (Na+, Ca+ across neuronal membrane (inhibition of voltage-gated Ca+ channels responsible for T-type Ca+ current)
Describe the targets for diminishing glutamate release by anticonvulsant agents
PRESYNPATIC
- Inactivation of VG Na+ channles (phenytoin, carbamazepine, lamotrigine)
- Inactivation of VG Ca+ channels (ethosuximide, lamotrigine, gabapentin, etc)
POSTSYNPATIC
- Blockade of AMPA receptors (phenobarbital, topiramate, lamotrigine)
- Blockade of NMDA receptors (Felbamate)
Why do anticonvulsants agents inactivate Na+ channels
- Antiseizure agents bind to Na+ channels in the INACTIVE state and prevent their conversion back to resting state
–> prolong Na+ channels inactivation
–> neuronal membrane beocmes less excitable
–> DECREASE IN SUSTAINED, HIGH FREQUENCY, REPTITIVE DISCHARGE
