Anti-Convulsants Flashcards
Seizures defined
transient episodes of brain dysfunction and altered behavior due to ABNORMALLY EXCESSIVE, SYNCHRONOUS, AND RHYTHMIC FIRING of certain HYPEREXCITABLE NEURONS
Seizures Underlying Causes (3 primarily)
CNS injury
Congenital abnormalities
Genetic factors
Epilepsy defined
Two main subtypes?
CHRONIC NEUROLOGICAL DISORDER characterized by RECURRENT SEIZURES
Primary idiopathic
Secondary
Two main subtypes of Seizures?
PARTIAL - affect only parts of the brain
GENERALIZED - affect large areas and multiple areas of the brain
Partial Seizure IMPORTANT CHARACTERISTIC
ONLY PART OF THE BRAIN is involved
Partial Seizure Types (3)
Simple
Complex
Partial becoming generalized
Simple Partial Seizure
MINIMAL SPREAD OF ABNORMAL DISCHARGE
Complex Partial Seizure
STARTS IN SMALL BRIAN AREA but QUICKLY SPREADS TO OTHER AREAS
AUTOMATISMS
most common
Partial becoming generalized seizure
SPREAD THROUGHOUT BRAIN AND PROGRESS TO GENERALIZED
Generalized Seizures characteristic
two types?
involve THE ENTIRE BRAIN with global EEG change and BILATERAL MANIFESTATIONS
Petit mal (absence) Grand mal (tonic clonic)
Petit mal seizures
sudden onset, abrupt cessation
BRIEF LOSS OF CONSCIOUSNESS
typically observed in CHILDREN
Grand mal seizures characteristics
TONIC SPASMS AND MAJOR CONVULSIONS OF ENTIRE BODY
LOSS OF CONSCIOUSNESS
Grand mal seizures four phases
Aura
Tonic
Clonic
Stuporous state and sleep
Status epilepticus
CONTINOUS OR VERY RAPID RECURRING SEIZURES
MEDICAL EMERGENCY REQUIRING IMMEDIATE THERAPY
3 Stages of Mechanisms Generating Epileptic Seizures
Initiation
Synchronization of surrounding
Propagation - recruitment of normal neurons
EPSP
excitatory post-synaptic potential
temporary depolarization and excitation of post-synaptic membranes caused by flow of positively charged ions into the cell
Epilepsy Treatment Options
Anti-epileptic meds
Surgery
Vagus nerve stimulation
Anti-epileptic medication goal
RESTORE NORMAL PATTERNS OF ELECTRICAL ACTIVITY
inhibit seizures
partially effective at prophylaxis
Cyclic Ureides (5)
Phenytoin Fosphenytoin Primidone Phenobarbital Ethosuximide
Tricyclics (2)
Carbamazepine
Oxcarbazepine
Benzodiazepines (2)
Diazepam
Lorazepam
GABA Derivatives (2)
Gabapentin
Pregabalin
Other Anti-Seizure Drugs (5)
Valproic acid Lamotrigine Acetazolamide Tiagabine Topiramate
Drugs for Partial Seizures with or without secondary generalized (3)
Carabamazepine
Phenytoin
Valproate
Drugs for Tonic-clonic seizures (3)
Carbamazepine
Phenytoin
Valproate
Drugs for Absence seizures (petit mal)
Ethosuximide
Valproate
Drugs for myoclonic seizures (2)
Clonazepam
Valproate
Drugs for Status Epilepticus (4)
Diazepam
Lorazepam
Phenytoin
Fosphenytoin
Anti-Convulsant General MOA
3 options
INHIBIT FIRING
Decrease excitatory effects - BLOCK VOLTAGE GATED Na channels
Increase inhibitory effects of GABA
Alter neuronal activation by altering ion movement across membrane - INHIBITION OF VOLTAGE GATED Ca channels
Inactivation of Na Channels causes
DECREASE IN SUSTAINED, HIGH FREQUENCY, REPETITIVE DISCHARGE
prolongs inactivation
Reduced calcium influx causes
DECREASED NEUROTRANSMITTER RELEASE
prevent neuronal excitability
Anti-convulsant side effects
Sedation Diplopia Nystagmus Ataxia GI Upset
Anti-convulsant important considerations
AVOID ABRUPT WITHDRAWAL
DECREASE EFFICACY OF ORAL CONTRACEPTIVES
TERATOGENIC
PHENOBARBITAL - safest during pregnancy
Fosphenytoin unique
newer, more soluble PRODRUG OF PHENYTOIN
used for parenteral routes**
Phenytoin absorption
VARIABLE
FORMULATION DEPENDENT
Phenytoin pharmacokinetics
Metabolized in LIVER
DOSE-DEPENDENT - ZERO ORDER elimination
CAN BE SATURATED
Phenytoin MOA
blocks and prolongs INACTIVATED STATE OF Na Channels
Enhances GABA release
Prevents seizure PROPAGATION
Phenytoin clinical uses (3)
Generalized tonic-clonic
Partial seizures
Status epilepticus
Phenytoin Idiosyncratic Side Effects
Hirsutism GINGIVAL HYPERPLASIA Osteomalacia Megaloblastic Anemia Fetal hydantoin syndrome
Carbamazepine MOA
INHIBITION OF VOLTAGE GATED Na Channels
blocks high frequency firing
decreases glutamate release
Carbamazepine Metabolism
INDUCES P450 enzymes
induces it’s own metabolism
Oxacarbazepine
NEWER drug similar to carbamazepine
ACTIVE METABOLITE HAS LONGER DURATION, fewer drug interactions
Carbamazepine clinical uses
TONIC CLONIC SEIZURES
PARTIAL SEIZURES
drug of choice for TRIGEMINAL NEURALGIA
Carbamazepine Important Side effects (2)
SIADH - syndrome of inappropriate ADH secretion
teratogenic –> SPINA BIFIDA
Barbiturates (phenobarbital) MOA
Important clinical use?
Enhances GABA-A RECEPTOR RESPONSES
increases opening time of Cl- channel
STATUS EPILEPTICUS
Primidone
metabolized by LIVER to PHENOBARBITAL and PEMA
Ethosuximide MOA
Primary clinical use?
BLOCKS PRE-SYNAPTIC Ca Channels
ABSENCE SEIZURES - drug of choice***
Valproic acid MOA
INHIBITION OF Ca Channels
Inhibition of GABA transaminase
Absence Seizures - drug of choice***
bipolar disorder as well
Valproic acid adverse effects
HEPATOTOXIC SYNDROME - d/t toxic metabolite
TERATOGENIC - spina bifida
Diazepam MOA
Great choice clinically for?
POTENTIATES GABA-A RESPONSE
increases Cl- channel opening
STATUS EPILEPTICUS
Diazepam vs Lorazepam
Diazepam effects are MUCH SHORTER - cannot be used by itself
Lorazepam has LONGER DURATION OF ACTION - can be used by itself
Gabapentin MOA
Clinical uses (2)
GABA analog
BLOCKS PRE-SYNAPTIC Ca Channels
PARTIAL SEIZURES
TONIC-CLONIC SEIZURES
NEUROPATHIC PAIN***
Pregabalin
similar to gabapentin
GABA Analog
Lamotrigine MOA
Important side effect?
BLOCKS PRE-SYNAPTIC VOLTAGE GATED Na and Ca channels
Stevens-Johnson Syndrome
Felbamate MOA
BLOCKS Na Channels and GLUTAMATE RECEPTORS
Tiagabine MOA
specifically designed as GABA UPTAKE INHIBITOR
Centrally Acting Muscle Relaxants (2)
Baclofen
Benzodiazepine
Baclofen MOA
GABA-B AGONIST
increased K conduction, decrease Ca influx
results in HYPERPOLARIZATION
Reduction in excitatory transmitter release
