3 - Anti-Epileptic Drugs Flashcards
Seizure Defined
Transient altercation of behavior due to the disorderd, synchronous and rhythmic of brain neurons; sustained depolarization
Epilepsy Defined
Disorder of brain function characterized by the periodic and unpredictable occurrence of seizures
Epilepsy Classification/Generalized Seizures: Generalized Tonic Clonic (Both Hemispheres/Grand Mal): Tonic Phase (4)
Incontinence
Epileptic Cry
Cyanosis
Generalized stiffening of body and limbs, back arched
Epilepsy Classification/Generalized Seizures: Generalized Tonic Clonic (Both Hemispheres/Grand Mal): Clonic Phase (4)
Cyanosis
Eyes Blinking
Salivary Frothing
Clinic jerks of limbs, body and head
Epilepsy Classification/Generalized Seizures: Generalized Tonic Clonic (Grand Mal): Post-Ictal Confusional Fatigue (1)
Limbs and body limp
Epilepsy Classification/Generalized Seizures: Absence Seizures Defined (2)
Between seizures patient is normal
During Seizure: vacant stare, eyes roll up, eyelids flutter (3/seconds), cessation of activity, lack of response ; LOC
Epilepsy Classification/Generalized Seizures: Other (2)
Myoclonic Seizures –> shock like jerk of a group of muscle, no LOC
Atonic Seizures –> NO LOC
Partial Seizures: Simple Partial Seizures Defined
Originate from a single cortical side/single hemisphere
NO LOC, stiffening or jerking movements of limp
Partial Seizures: Complex Partial Seizures (Temporal Lobe Epilepsy/Psychomotor Seizures)
Originates in temporal lobe and involves limbic system
Hallucinations, aura signaling onset, autamatism (purposeless actions)
Localized onset, can involve both hemisphere
Partial Seizures: Partial with Secondarily Generalized (1)
Begins focally from a single cortical side and can become generalized
Epileptic Drugs: Phenobarbitone MOA (2)
Potentiation of synaptic inhibition through an action on GABA-A receptor; prolongs DURATION of channel opening events
Enhances GABA receptor mediated current by prolonging the opening of Cl- channels
Epileptic Drugs: Phenobarbitone At Higher Levels - MOA
Limits sustained repetitive firing of neurons through an action on Na+ conductance
Inhibits Ca2+ currents
Epileptic Drugs: Phenobarbitone Toxicity (5)
Sedation, initially
Nystagmus and Ataxia
Rashes
Megaloblastic anemia (long term use, interference with folic acid metabolism)
Osteomalacia (Vitamin D and K metabolism enhanced)
Epileptic Drugs: Phenobarbitone Use (4)
Generalized Tonic Clonic
Simple Partial
Complex Partial
3rd line drug for Status Epilepticus (IM/IV)
Epileptic Drugs: Phenytoin Mechanism (2)
Limits the sustained high frequency repetitive firing of action potentials
Slows the rate of recovery of voltage activated Na+ channels from inactivation (channels are inactivated for longer time)
Epileptic Drugs: Phenytoin Pharmacokinetics Low Doses (1) High Doses (1) and Implication (1)
Low doses: metabolism is capacity limited, follows first order kinetics (saturation kinetics; as you increase the dose, the metabolism also keeps up)
High doses: follows zero order kinetics (metabolism gets saturated, can’t keep up with increasing disease)
Implies that small increase may lead to disproportionate plasma levels; shifts kinetics
Epileptic Drugs: Phenytoin Adverse Affects at Therapeutic Levels (10-20 mcg/ml) (6)
Gum atrophy
Hirsutism (long term use)
Hypersensitivity Reactions (rashes, DLE, LAD)
Fetal Hydantoin Syndrome (contraindicated in pregnancy) –> cleft lip, etc.
Megaloblastic Anemia
Osteomalacia
Epileptic Drugs: Phenytoin Adverse Affects at High Plasma Levels (2, second about nystagmus)
Cerebellar and Vestibular Manifestations: Ataxia, Vertigo, Diplopia, and Nystagmus
Nystagmus occurs early, sign that plasma concentrations exceeding therapeutic levels)
Epileptic Drugs: Phenytoin Drug Interactions (1)
Induce microsomal enzymes responsible for the metabolism of a number of drugs
Epileptic Drugs: Phenytoin Uses (4)
GTC (first line drug)
Simple and Complex Seizures (first line drug)
Status Epileptics (second line drug)
Trigeminal Neuralgia
Epileptic Drugs: Carbamazepine MOA (1)
Inhibits high frequency repetitive firing by prolonging the inactivated state of Na+ channels
Same as Phenytoin
Epileptic Drugs: Carbamazepine Adverse Effects (6)
Vertigo
Diplopia
Ataxa
Drowsiness (higher doses ONLY)
Hyponatremia and water intoxication (SIADH)
Agranulocytosis –> rarely, but patient dependent
Epileptic Drugs: Carbamazepine Use (5)
- Most Effective for complex partial seizures, with psychotic symptoms*
- GTC and SPS –>FIRST CHOICE DRUG*
Neuralgias (Neurosyphilis, Tabes Dorsalis)
Manic-Depressive
Acute Mania
Epileptic Drugs: Carbamazepine - Oxcarbazepine (3)
Less potent
Shorter acting
Better toxicity profile –> less likely to cause agranulocytosis
Epileptic Drugs: Ethosuximide MOA (3)
Primary site of action on THALAMOCORTICAL system
Selectively inhibits low threshold, high amplitude T(ransient) type Ca2+ current; impulses die down
EEG: 3 per second spike and wave pattern (absence seizures)
Epileptic Drugs: Ethosuximide Toxicity (4)
Gastric: Pain, Nausea and Vomiting
Lethargy and fatigue
Hypersensitivity (rashes, DLE)
Epileptic Drugs: Ethosuximide Use (1)
Absence seizure ONLY
Epileptic Drugs: *Valproic Acid/Sodium Valproate MOA (3)
Inhibits sustained repetitive firing (like phenytoin)
Reduces low threshold T type Ca2+ current (like ethosuximide)
Increases levels of GABA (like phenobarbitone)
Epileptic Drugs: Valproic Acid/Sodium Valproate Toxicity (A lot)
Transient GI: Anorexia, Nausea, and Vomiting
Alopecia, hair curling, rashes, appetite stimulation
*Fulminant hepatitis below the age of 2, can be fatal
Neural tube defects in pregnancy (Spina Bifida, Anencephaly, and Encephalocele)
Epileptic Drugs: Valproic Acid/Sodium Valproate Uses (4 with pairs)
Absence seizure
Alternative/adjuvant - GTC, SPS, CPS
Myoclonic and atonic seizures
MDP and mania
Epileptic Drugs: IV Diazepam (2)
Emergency control of convulsions: e.g. status epilepticua, tetanus, eclampsia
Can cause sedation
Epileptic Drugs: Clonazepam (2)
Used in absence seizures and some cases of myoclonic seizsures and infantile spasms (West Syndrome; childhood epileptic syndrome)
Sedation is prominent
Epileptic Drugs: Gabapentin/Pregabalin (5)
Add on drugs, not used alone
2 DIFFERENT drugs, but SAME MOA
Analogs of GABA (amino acid)
Add on - partial and GTC
Also used in neuropathic pain
Epileptic Drugs: Lamotrigine (4)
Blocks Na+ channels and prevents the release of excitatory neurotransmitters (glutamate)
Add on - refractory cases of partial and secondarily generalized
Skin rash can occur (Steven-Johnson Syndrome)
Epileptic Drugs: Vigabatrin (3)
Inhibitor of GABA transaminase
Add on-refractory cases of partial seizsures
*Visual disturbances may develop** –> tunnel vision and bluish vision
Epileptic Drugs: Tiagabine (2)
Inhibitor of GABA UPTAKE
Adjuvant in partial seizures
Epileptic Drugs: Zonisamide (2)
Acts on Sodium Channel (like phenytoin)
Partial and GTC
Epileptic Drugs: Levetiracetam (1)
Partical Seizures
Epileptic Drugs: Topiramate (5)
Blocks repetitive firing
GTC and partial
Migraine
Can cause kidney stones
Lennox Gestaut Syndrome –> childhood epileptic syndrome
See Slide 29 For
Table
Epileptic Drugs: Felbamate MOA (1)
Blocks NMDA receptor
Epileptic Drugs: Felbamate Adverse Effects (2)
Aplastic Anemia
Severe Hepatitis
Epileptic Drugs: Felbamate Use (1)
Third-line drug for refractory cases of partial seizures
