1. Acetazolamide (Diamox)
    • Carbonic anhydrase inhibitors
    • Active against absence seizures (Rapid development of tolerance for use)
    • Adverse effects are minimal when it is used in moderate dosage for limited periods
  2. Rufinamide (Banzel)
    • MOA
    • → Enhances slow inactivation of voltage gated Na+ channels
    • → Reduce repetitive firing, the firing pattern characteristic of partial seizures
    • Therapeutic Use
    • → Lennox-Gastaut syndrome
  3. Lacosamide (Vimpat)
    • MOA
    • → Enhances slow inactivation of voltage-gated Na+ channels and limits sustained repetitive firing, the neuronal firing pattern characteristic of partial seizures
    • Therapeutic Use
    • Partial-onset seizures (Refractory partial seizures)
  4. Zonisamide (Zonegran)
    • MOA
    • → Sulfonamide
    • → Inhibits the T-type Ca2+ currents
    • → Inhibits the sustained, repetitive firing of spinal cord neurons, presumably by prolonging the inactivated state of voltage-gated Na+ channels (similar to actions of phenytoin and carbamazepine)
    • Therapeutic Use
    • → Partial seizures in adults
    • ADR
    • → Somnolence, ataxia, anorexia, nervousness, fatigue
    • → Renal calculi (due to inhibition of carbonic anhydrase)
    • PK
    • → Completely absorbed t½  (~63 hours), and is ~40% bound to plasma protein.
    • → Approximately 85% of an oral dose is excreted in the urine
    • → Metabolism by CYP3A4
  5. Topiramate (Topamax)
    • MOA
    • → Reduces voltage-gated Na+ currents in cerebellar granule cells
    • → Activates a hyperpolarizing K+ current, enhances postsynaptic GABAA-receptor currents, and limits activation of the AMPA-kainate-subtype(s) of glutamate receptor
    • → Weak carbonic anhydrase inhibitor
    • Therapeutic Use
    • → Pediatric patients 2 yrs or older for:
    •     ¤ Partial-onset or primary generalized tonic-clonic seizures
    •     ¤ Lennox-Gastaut syndrome in patients 2 yrs or older
    • → Adults
    •     ¤ Migraine headache prophylaxis
    • ADR
    • → Somnolence, fatigue, weight loss, and nervousness
    • → Precipitate renal calculi (due to inhibition of carbonic anhydrase)
    • → Cognitive impairment
    • → Change in the taste of carbonated beverages
    • PK
    • → Well absorbed orally
    • → Little (10-20%) binding to plasma proteins
    • → Excreted unchanged in the urine t1/2 is ~1 day.
  6. Vigabatrin (Sabril)
    • MOA
    • → Structural analog of GABA
    • → Irreversibly inhibits the major degradative enzyme for GABA, GABA-T (transaminase)
    • → Increase concentrations of GABA in the brain
    • Therapeutic Use
    • → Approved for Partial complex seizures in adults
  7. Tiagabine (Gabitril)
    • MOA
    • → Inhibits the GABA transporter, GAT-1, and thereby reduces GABA uptake into neurons and glia
    • → Thus prolong the effect of GABA at inhibitory synapses through reducing its reuptake by GAT-1
    • Therapeutic Use
    • → Approved by the FDA as adjunct therapy for partial seizures with or without secondary generalization in adults
    • ADR
    • → Dizziness, somnolence, and tremor (mild to moderate)
    • → CI: generalized absence epilepsy
    • PK
    • → Well absorbed
    • → Extensively bound to serum or plasma proteins
    • → Hepatic metabolism: by CYP3A
  8. Levetiracetam (Keppra)
    • MOA
    • → No evidence for an action on voltage-gated Na+ channels or either GABA- or glutamate-mediated synaptic transmission
    • → Strong affinity to synaptic vesicle protein, SV2A
    • → Effective against audio-induced convulsion model
    • → Not clearly as how binding of levetiracetam to SV2A might affect neuronal excitability
    • Therapeutic Use
    • → FDA-approved
    •     ¤ For adjunctive therapy for myoclonic, partial-onset, and
    •     ¤ Primary generalized tonic-clonic seizures in adults and children as young as 4 years old
    • ADR
    • → Well tolerated
    • → Somnolence, asthenia, and dizziness
    • PK
    • → Absorption: Rapid and almost complete PO
    • → 95% of the drug and its inactive metabolite are excreted in the urine, 65% of which is unchanged drug
    • → 24% of the drug is metabolized by hydrolysis of the acetamide group
  9. Lamotrigine (Lamictal)
    • → Blocks sustained repetitive firing of mouse spinal cord neurons
    • → Delays the recovery from inactivation of recombinant Na+ channels 
    • → Drug has broad spectrum of action due to inhibition of glutamate release acting at Na+ channels
  10. Lamotrigine (Lamictal) Antiseizure Effects
    • Suppresses tonic hind limb extension in the maximal electroshock model
    • Inhibit partial and secondarily generalized seizures in the kindling model
    • Does not inhibit clonic motor seizures induced by pentylenetetrazol
  11. Lamotrigine (Lamictal) Therapeutic Use
    • Monotherapy and add-on therapy
    • Partial and secondarily generalized tonic-clonic seizures in adults
    • Lennox-Gastaut syndrome in both children and adults
  12. Lamotrigine (Lamictal) ADR
    • Dizziness, ataxia, blurred or double vision, nausea, vomiting, and rash when lamotrigine was added to another anti-seizure drug
    • A few cases of Stevens-Johnson syndrome and disseminated intravascular coagulation have been reported
  13. Lamotrigine (Lamictal) PK
    • Completely absorbed
    • Metabolized primarily by glucuronidation.
    • The plasma t1/2 of a single dose is 24-30 h
    • Phenytoin, carbamazepine, or phenobarbital reduces the t½ and plasma concentrations of lamotrigine
    • Valproate markedly increases plasma concentrations of lamotrigine, likely by inhibiting glucuronidation
  14. Lennox-Gastaut Syndrome
    Disorder of childhood characterized by multiple seizure types, mental retardation, and refractoriness to anti-seizure medication
  15. Gabapentin (Neurontin) and Pregabalin (Lyrica)
    • Inhibits tonic hind limb extension in the electroshock seizure model
    • Inhibits pentylenetetrazol – induced clonic seizures
  16. Gabapentin (Neurontin) and Pregabalin (Lyrica) MOA
    • Despite being GABA agonists, neither mimics GABA when iontophoretically applied to neurons in primary culture
    • Bind selectively to high affinity to Ca2+ channel subunit α2δ-1 protein in cortical membrane
  17. Gabapentin (Neurontin) and Pregabalin (Lyrica) Therapeutic Use
    • Partial seizures, with and without other anti-seizure drugs
    • Also indicated for
    • → Migraine
    • → Chronic pain
    • → Bipolar disorder
  18. Gabapentin (Neurontin) and Pregabalin (Lyrica) ADR
    • Mild to moderate: Somnolence, dizziness, ataxia, and fatigue (resolve within 2 weeks of onset)
    • Pregnancy category C
  19. Gabapentin (Neurontin) and Pregabalin (Lyrica) PK
    • Well absorbed orally
    • Not metabolized in humans
    • Do not bound to plasma proteins and are excreted unchanged, mainly in the urine
    • T½ approximate 6 h
    • No known interactions with other anti-seizure drugs
  20. Clonazepam (Klonopin)
    Absence seizures as well as myoclonic seizures in children (tolerance to its anti-seizure effects usually develops after 1-6 months of administration)
  21. Diazepam (Valium) and Lorazepam (Ativan)
    • Status Epilepticus
    • Lorazepam- due to its short duration of action is a disadvantage, leading to the more frequent use of lorazepam
  22. Clorazepate (Tranxene)
    Effective in combination with certain other drugs in the treatment of partial seizures
  23. Phenytoin (Dilantin)
    • Blocks sustained high-frequency repetitive firing of action potentials
    • Decreases the synaptic release of glutamate and enhances the release of GABA
    • Phenytoin paradoxically causes excitation in some cerebral neurons due to
    • →A reduction of calcium permeability, with inhibition of calcium influx across the cell membrane
    • Summary: Alters Na+, K+, and Ca2+ conductance, membrane potentials, and the concentrations of amino acids and the neurotransmitters norepinephrine, acetylcholine, and γ-aminobutyric acid (GABA)
  24. Phenytoin (Dilantin) MOA
    • Limits the repetitive firing of action potentials evoked by a sustained depolarization of mouse spinal cord neurons maintained in vitro
    • At therapeutic drug concentrations in cerebrospinal fluid (CSF)
    • → Selectively, slows the rate of recovery (delays recovery) of voltage-activated Na+ channels from inactivation, an action that is both voltage- and use-dependent (without affecting GABA or glutamate)
    • At concentrations 5- to 10-fold higher
    • → Reduction of spontaneous activity
    • → Enhancement of responses to GABA (some of the unwanted toxicity associated with high levels of phenytoin)
  25. Phenytoin (Dilantin) PK
    • Phenytoin is extensively bound (~90%) to serum proteins, mainly albumin
    • → Hypoalbuminemia in neonates and in uremic patients (increased levels of free drugs can become evident)
    • → Some agents can compete with phenytoin for binding sites on plasma proteins and increase free phenytoin (usually this effect short lived unless the drug may affect metabolism s well)
    • Nonlinearity elimination kinetics (t½ 6-24 h at conc. < 10 ug/mL)
    • The majority (95%) of phenytoin is metabolized in the hepatic endoplasmic reticulum by CYP2C9/10 and to a lesser extent CYP2C19
    • Valproate competes for protein binding sites and inhibits phenytoin metabolism, resulting in marked and sustained increases in free phenytoin
  26. Phenytoin (Dilantin) and Fosphenytoin (Cerebyx)
    • Phenytoin has low solubility thus can’t be used intravenously
    • Fosphenytoin (cerebyx) is a water-soluble prodrug
    • → Converted into phenytoin by phosphatases in liver and red blood cells with a t1/2 of 8-15 minutes.
    • → Extensively protein (albumin) bound (95-99%)- Saturable and displaces phenytoin from protein-binding sites
    • → Useful for adults with partial or generalized seizures when intravenous or intramuscular administration is indicated
  27. Phenytoin (Dilantin) ADR
    • Depend on the route of administration, the duration of exposure, and the dosage
    • Toxic signs when used in emergency:
    • → Cardiac arrhythmias with or without hypotension and/or CNS depression
    • Chronic use:
    • → Increased frequency of seizures
    • → GI symptoms, gingival hyperplasia, osteomalacia, and megaloblastic anemia
    • → Hirsutism
    • Inhibits anti-diuretic hormone (ADH)
    • Inhibits insulin secretion causing hyperglycemia and glycosuria
    • Altered metabolism of vitamin D
    • → Osteomalacia, with hypocalcemia
    • Elevated alkaline phosphatase activity
    • → Hypersensitivity reactions
    • → Morbilliform rash in 2-5% of patients and skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis
    • Hematological reactions
    • → Neutropenia and leukopenia
    • Reduced immunoglobulin A (IgA) production cause
    • → Lymphadenopathy, resembling Hodgkin's disease and malignant lymphoma
  28. Phenytoin (Dilantin) Clinical Use
    • Partial and tonic-clonic but not absence seizures
    • → Phenytoin preparations differ significantly in bioavailability and rate of absorption.
    • → Patients should consistently be treated with the same drug from a single manufacturer. However, if it becomes necessary to temporarily switch between products, care should be taken to select a therapeutically equivalent product and patients should be monitored for loss of seizure control or onset of new toxicities
    • Other Uses
    • → Trigeminal and related neuralgias occasionally respond to phenytoin, but carbamazepine may be preferable
    • → Cardiac arrhythmias
  29. Phenobarbital (Luminal) Therapeutic Use
    • Generalized tonic-clonic and partial seizures
    • → Commonly used in adults due to efficacy, low toxicity, inexpensive
    • Sedative effect that disturb behavior in children
    • It is not effective for absence seizures
  30. Phenobarbital (Luminal) MOA
    • Potentiation of GABAA receptor-mediated synaptic inhibition
    • Phenobarbital increased the GABAA receptor–mediated current by increasing the duration of bursts of GABAA receptor–mediated currents without changing the frequency of bursts
    • Limits sustained repetitive firing during therapy of status epilepticus
  31. Phenobarbital (Luminal) PK
    • Oral absorption of phenobarbital is complete but somewhat slow
    • 40-60% bound to plasma proteins and bound to a similar extent in tissues, including brain
    • Renal excretion- 25% unchanged drug
    • Inactivated by hepatic CYP2C9 isoform of cyp450 microsomal enzymes, along with CYP2C19 and CYP2E1
    • Induces uridine diphosphate-glucuronosyltransferase (UGT) enzymes as well as the CYP2C and CYP3A subfamilies
  32. Phenobarbital (Luminal) ADR
    • Sedation--but tolerance develops during chronic medication
    • Nystagmus and ataxia occur at excessive dosage
    • Irritability and hyperactivity in children
    • Agitation and confusion in the elderly
    • Drug allergy: Scarlatiniform or morbilliform rash (1-2% of patients)
    • Hypoprothrombinemia with hemorrhage has been observed in the newborns of mothers (treated with vitamin K)
    • Megaloblastic anemia (treated with folate)
    • Osteomalacia (treated with high doses of vitamin D)
  33. Carbamazepine (Tegretol) Therapeutic Use
    • Primary drug for the treatment of generalized tonic-clonic and both simple and complex partial seizures
    • → Renal and hepatic function and hematological parameters should be monitored
    • Primary agent for treatment of trigeminal and glossopharyngeal neuralgias
    • It is also effective for lightning-type ("tabetic") pain associated with bodily wasting
    • → Adverse effects require discontinuation of medication in 5-20% of patients
    • Bipolar affective disorders
  34. Carbamazepine (Tegretol) MOA
    • Limits the repetitive firing of action potentials evoked by a sustained depolarization of mouse spinal cord or cortical neurons maintained in
    • Selectively, slows the rate of recovery of voltage-activated Na+ channels from inactivation
    • Carbamazepine metabolite, 10,11-epoxycarbamazepine, also limits sustained repetitive firing at therapeutically relevant concentrations, suggesting that this metabolite may contribute to the anti-seizure efficacy of carbamazepine.
  35. Carbamazepine (Tegretol) PK
    • Absorption: slow and erratic after oral administration. Peak in 4-8 h but may be delayed by as much as 24 hours, especially following the administration of a large dose.
    • Distribution: The drug distributes rapidly into all tissues.
    • Plasma protein binding: 75% of carbamazepine binds to plasma proteins
    • Metabolism:
    • → Convert 10,11-epoxide and active metabolite
    • → The 10,11-epoxide is metabolized further to inactive compounds, which are excreted in the urine principally as glucuronides.
    • → Inactivated by conjugation and hydroxylation
    •     ¤ Hepatic CYP3A4 (sedative hypnotics)
    •     ¤ Carbamazepine induces CYP2C, CYP3A, and UGT
  36. Carbamazepine (Tegretol) ADR
    • Acute intoxication
    • → Stupor or coma, hyperirritability, convulsions, and respiratory depression.
    • During long-term therapy
    • → Drowsiness, vertigo, ataxia, diplopia, and blurred vision
    • → The frequency of seizures may increase, especially with overdosage
    • → Other adverse effects include nausea, vomiting
    • → Hematological toxicity (aplastic anemia, agranulocytosis)
    • → Hypersensitivity reactions (dangerous skin reactions, eosinophilia, lymphadenopathy, splenomegaly)
    • → A late complication of therapy: Retention of water, with decreased osmolality and concentration of → Na+ in plasma, especially in elderly patients with cardiac disease
    • → Tolerance develops to the neurotoxic effects of carbamazepine
    • Hepatic or pancreatic abnormalities
    • Mild transient leukopenia occurs in ~10% of patients
    • → A persistent leukopenia may develop that requires withdrawal of the drug
  37. Oxcarbazepine (Trileptal)
    • Similar to carbamazepine
    • Oxcarbazepine is a less potent enzyme inducer than carbamazepine.
    • → Oxcarbazepine does not induce the hepatic enzymes involved in its own degradation.
    • → Induces CYP3A and reduces plasma levels of steroid oral contraceptives
    • Substitution of oxcarbazepine for carbamazepine causes increased levels of phenytoin and valproic acid
    • Approved for mono- /adjunct-therapy for partial seizures in adults
    • Monotherapy for partial seizures in children ages 4-16
    • Adjunctive therapy in children 2 years of age and older ith epilepsy.
  38. Ethosuximide (Zarontin) MOA
    • The thalamus plays an important role in generation of 3-Hz spike-and-wave rhythms typical of absence seizures
    • → Reduces low threshold Ca2+ currents (T-type currents) in thalamic neurons
    • At clinically relevant concentrations, ethosuximide inhibits the T-type current
    • Ethosuximide does not inhibit sustained repetitive firing or enhance GABA responses at clinically relevant concentrations.
  39. Ethosuximide (Zarontin) Pharmacologic Effects
    • At nontoxic doses is protection against clonic motor seizures induced by pentylenetetrazol
    • At nontoxic doses ethosuximide does not inhibit tonic hind limb extension of electroshock seizures or kindled seizures
    • Effective ONLY against absence seizures
  40. Ethosuximide (Zarontin) PK
    • Absorption: Complete (Peak in plasma within ~3 h) after a single oral dose.
    • Plasma protein binding: No
    • Approximately 25% of the drug is excreted unchanged in the urine.
    • Metabolism: Hepatic microsomal enzymes (CYP unknown)
    • → Hydroxyethyl derivative is inactive metabolite and is excreted as such and as the glucuronide in the urine.
    • → T½ averages between 40 - 50 h in adults and ~30 h in children
  41. Ethosuximide (Zarontin) ADR
    • GI: nausea, vomiting, and anorexia
    • CNS: drowsiness, lethargy, euphoria, dizziness, headache, and hiccup (tolerance develops)
    • Parkinson-like symptoms and photophobia
    • In patients with psychiatric disturbance: Restlessness, agitation, anxiety, aggressiveness, inability to concentrate, and other behavioral effects
    • Urticaria and other skin reactions, including Stevens-Johnson syndrome, as well as systemic lupus erythematosus, eosinophilia, leukopenia, thrombocytopenia, pancytopenia, and aplastic anemia
    • Bone marrow depressions leading to death
  42. Valproic Acid (Depakote) MOA
    • Similar to those of phenytoin and ethosuximide 
    • At therapeutically relevant concentrations
    • → Inhibits sustained repetitive firing induced by depolarization of mouse cortical or spinal cord neurons
    • → The T-type currents is similar to that of ethosuximide in thalamic neurons
    • → Together, these actions of limiting sustained repetitive firing and reducing T-type currents may contribute to the effectiveness of valproic acid against partial and tonic-clonic seizures and absence seizures, respectively.
    • Increase the amount of GABA in animal brains
    • In vitro, valproate can stimulate the activity of the GABA synthetic enzyme, glutamic acid decarboxylase, and inhibit GABA degradative enzymes, GABA transaminase and succinic semialdehyde dehydrogenase.
    • It is still controversial to relate the increased GABA levels by valproic acid to its anti-seizure activity
  43. Valproic Acid (Depakote) PK
    • Rapid and complete after oral administration (Peak concentration in plasma is observed in 1-4 h but delayed in enteric-coated tablets or if ingested with meals)
    • Hepatic (95%), with < 5% excreted unchanged in urine.
    • Hepatic metabolism: substrate for CYP2C9 and CYP2C19
    • Active Metabolites:
    • → 2-propyl-2-pentenoic acid and 2-propyl-4-pentenoic acid
    • → Only 2-propyl-2-pentenoic acid accumulates in plasma and brain to a potentially significant extent
  44. Valproic Acid (Depakote) Therapeutic Use
    • Broad-spectrum anti-seizure drug effective in the treatment of
    • → Absence
    • → Myoclonic
    • → Partial
    • → Tonic-clonic seizures
  45. Benzodiazepines
    • BZs for Long term treatment of certain types of seizures:
    • → clonazepam (Klonopin)
    • → clorazepate (Tranxene)
    • Midazolam was designated an orphan drug in 2006 for intermittent treatment of bouts of increased seizure activity in refractory patients with epilepsy who are on stable regimens of anti-seizure drugs. 
    • BZs for management of status epilepticus
    • → Diazepam (Valium) longer duration of action
    • → Lorazepam (Ativan) IV- short duration of action
  46. Benzodiazepines Anti-seizure Properties
    • In animal models
    • → Inhibition of pentylenetetrazol-induced seizures by the benzodiazepines
    • → Maximal electroshock seizure pattern
    • Clonazepam is unusually potent in antagonizing the effects of pentylenetetrazol, but it is almost without action on seizures induced by maximal electroshock.
    • BZs, including clonazepam, suppress the spread of kindled seizures and generalized convulsions produced by stimulation of the amygdala, but do not abolish the abnormal discharge at the site of stimulation
  47. Benzodiazepines MOA
    • Non-sedating doses: enhance GABAA-mediated synaptic inhibition
    • At therapeutically relevant concentrations:
    • → BZDs act at subsets of GABAA receptors and increase the frequency, but not duration, of openings at GABA-activated Cl– channels
    • At higher concentrations:  diazepam and other benzodiazepines reduce sustained high-frequency firing of neurons, similar to the effects of phenytoin, carbamazepine, and valproate
  48. Antiseizure Drugs MOA
    • The mechanisms of action of anti-seizure drugs fall into three major categories.
    • 1) Limit the sustained, repetitive firing of neurons, an effect mediated by promoting the inactivated state of voltage-activated Na+ channels.
    • 2) GABA–mediated synaptic inhibition, an effect mediated either by a presynaptic or postsynaptic action. Drugs effective against the most common forms of epileptic seizures, partial and secondarily generalized tonic-clonic seizures, appear to work by one of these two mechanisms.
    • 3) Drugs effective against absence seizure, a less common form of epileptic seizure, work by a third mechanism, inhibition of voltage-activated Ca2+channels responsible for T-type Ca2+ currents.
  49. Causes of Seizures
    • Neurologic diseases- from infection to neoplasm and head injury
    • Heredity has proved to be a predominant factor
    • Gene defects, usually of an autosomal dominant nature involving genes coding voltage-gated ion channels or GABAA receptors, have been shown to account for a small number of familial generalized epilepsies
  50. Electroencephalogram (EEG)
    • The interictal (or between-seizures) spike is a sharp waveform recorded in the EEG of patients with epilepsy
    • The extracellular recording was made through a high-pass filter
    • The high-frequency firing of the neuron evident in both extracellular and intracellular recording during the paroxysmal depolarization shift (PDS)
  51. Simple Partial Seizure
    • Diverse manifestations determined by the region of cortex activated by the seizure
    • Motor cortex representing left thumb -- clonic jerking of left thumb results
    • Somatosensory cortex representing left thumb, paresthesia of left thumb results)- lasting 20-60 secs
    • Key feature is preservation of consciousness
    • Conventional Tx: Carbamazepine, Phenytoin, Valproate
    • New Tx: Gapapentin, Lacosamide, Lamotrigine, Levetiracetam, Rufinamide, Tiagabine, Topiramate, Zonisamide
  52. Complex Partial Seizure
    • Impaired consciousness lasting 30 sec - 2 mins
    • → Ex. Purposeless movements such as lip smacking or hand wringing
    • Conventional Tx: Carbamazepine, Phenytoin, Valproate
    • New Tx: Gapapentin, Lacosamide, Lamotrigine, Levetiracetam, Rufinamide, Tiagabine, Topiramate, Zonisamide
  53. Partial with secondarily generalized tonic-clonic seizure
    • Simple or complex partial seizure evolves into a tonic-clonic seizure with loss of consciousness and sustained contractions (tonic) of muscles throughout the body followed by periods of muscle contraction alternating with periods of relaxation (clonic), typically lasting 1-2 minutes
    • Conventional Tx: Carbamazepine, Phenobarbital, Phenytoin, Primidone, Valproate
    • New Tx: Gapapentin, Lacosamide, Lamotrigine, Levetiracetam, Rufinamide, Tiagabine, Topiramate, Zonisamide
  54. Absence Seizure
    • Generalized Seizure
    • Abrupt onset of impaired consciousness
    • → Lasting less than 30 seconds
    • → Staring
    • → Cessation of ongoing activities typically
    • Conventional Tx: Ethosuximide, Valproate, Clonazepam
    • New Tx: Lamotrigine
  55. Myoclonic Seizure
    • Generalized Seizure
    • A brief (perhaps a second), shock like contraction of muscles that may be restricted to part of one extremity or may be generalized
    • Conventional Tx: Valproate, Clonazepam
    • New Tx: Levetiracetam
  56. Tonic-clonic Seizure
    • Generalized Seizure
    • Loss of consciousness and sustained contractions (tonic) of muscles throughout the body followed by periods of muscle contraction alternating with periods of relaxation (clonic), typically lasting 1-2 minutes
    • Conventional Tx: Carbamazepine, Phenobarbital, Phenytoin, Primidone, Valproate
    • New Tx: Lamotrigine, Levetiracetam, Topiramate
  57. Juvenile Myoclonic Epilepsy
    • Most common generalized epilepsy
    • ~10% of all epileptic syndromes
    • → Age of onset is in the early teens, and the condition is characterized by myoclonic, tonic-clonic, and often absence seizures
    • → Complex genetic disorder that is probably due to inheritance of multiple susceptibility genes
  58. Hyperpolarization-activated cation channels (HCN channels)
    • H-channels are key regulators of neuronal excitation and inhibition, and have a rich diversity of subunit composition, distribution, modulation and function
    • Recent results indicate that the behavior of h-channels can be altered significantly by seizures
    • The activity-dependent, short-term and long-term plasticity of h-channels can, in turn, modulate neuronal excitability
    • The reciprocal interactions between neuronal activity and h-channels indicate that these ion channels could be promising novel targets for anti-epileptic therapies
  59. Maximal Electroshock Model (MES)
    • Tonic-clonic seizure
    • Generalized tonic clonic antiseizure drugs – complex partial seizure
  60. Pentylenetetrazole Seizure Model
    Clonic seizure
  61. Amygdala Kindling Seizure Model
    • Partial epilepsy
    • Drug resistant seizure
  62. Strasbourg Seizure Model
    Genetic Absence Epilepsy
Card Set
IT 2 (MT 3): Anti-epileptics