Lecture 60 and 61: Antiepileptic Drugs

Card Set Information

Author:
dvb69339
ID:
16004
Filename:
Lecture 60 and 61: Antiepileptic Drugs
Updated:
2010-04-25 11:53:54
Tags:
Neuroscience
Folders:

Description:
Neuroscience Week 5
Show Answers:

Home > Flashcards > Print Preview

The flashcards below were created by user dvb69339 on FreezingBlue Flashcards. What would you like to do?


  1. What is epilepsy?
    A group of chronic CNS disorders that are characterized by recurrent seizures
  2. What are the causes for acute seizures?
    • trauma
    • stroke
    • encephalitis
    • drugs
    • withdrawl from antidepressants
    • tumor
    • high fever
    • hypoglycemia
    • extreme acidosis/alkadosis
    • Hypoatremia
    • Hypocalcemia
    • Idiopathic
  3. Are more seizures partial or generalized epilepsy?
    Partial (about 60%)
  4. Where is the common problem for partial seizures and what does it result in?
    • temporal lobe epilepsy
    • limbic, complex partial or psychomotor epilepsy)
  5. Inherited idiopathic epilepsies account for less than 1% of epilepsies in America. However, of the genetic links found in these inherited epilepsies, what do the mutations always affect?
    subunits of voltage or ligand-gated ion channels (Na+, K+, GluR, GABAR, and nAchR)
  6. What is the basic mechanism underlying epilepsy?
    dysregulation of either excitation or feed-back/forward inhibition
  7. What is an example of a gain of function mutation in epilepsy?
    • SCN1B mutation (generalized epilepsy w/ ferbile seizures)
    • increases sodium influx into the neuron, therefore too much depolarization, too often
  8. What is an example of a loss of function mutation in epilepsy?
    KCNQ2, KCNQ3 mutations where K+ cannot get out of the cell; therefore cannot hyperpolarize
  9. What kind of mutation is most severe/fatal in Na+ channels?
    Loss of function
  10. What are the 2 types of partial seizures?
    • Simple (did not lose consciousness)
    • Complex(did lose consciousness)
  11. What are the three strategies in treatment of epilepsy?
    • stabalize membrane potential and prevent depolarization by action on voltage-gated ion channels
    • increase GABAergic transmission
    • decrease excitatory amino acid transmission
  12. What are 5 different types of drugs that act on GABAergic synapses?
    What do they do?
    • GABA agonists: hyperpolarize the neuron
    • GABA antagonists: excitation/convulsion
    • Barbiturates: enhance GABA binding to GABAR
    • Benzodiazepines: enhance GABA binding to GABAR
    • GABA uptake inhibitors: allow GABA to stay out in the synapse longer, therefore having a greater effect
  13. The Glutamergic Synapse
    ligand
    co-agonist
    natural blocker
    ions that are transported
    • ligand: glutamate
    • co-agonist: glycine
    • natural blocker: magnessium
    • ions that are transported: Na+/Ca++ out and K+ in
  14. What are the ultimate goals of anti-epileptic drugs that target glutamergic synapses?
    decrease glutamate
  15. What are the ultimate goals of anti-epileptic drugs that target GABAergic synapses?
    increase GABA
  16. What is epileptogenesis?
    How is it caused?
    • the generating of more seizures
    • cause is not clear b/c pathways are unknown; we do know that influx of Ca++ inhibits:
    • -inhibitory transcription factors
    • -upregulates AMPAR
    • -down regulates GABA receptors
    • -increases Mossy Fiber growth (not sure about this one)
  17. The Ca++ channel is often targeted by drugs, what ligand-binding site on this channel is the target?
    • alpha 2 delta
    • Calcium is the regulator of pre-synaptic vessel release in pre-synaptic neurons. so it makes sense that if you can block this channel, there will be little intracellular Ca++ to let the NTs be released
  18. How does phenytoin work on Na+ channels?
    sustains sodium channel in the refractory state conformation so that it cannot return to resting state and subsequently cannot return to open state
  19. What are six drugs that will keep Na+ channels in the inactive conformation?
    • carbamazepine
    • phenytoin
    • topiramate
    • lamotrigine
    • valproate
    • zonisamide
  20. What is a major drawback, besides side effects, for anti-epileptic drugs (AED)?
    that there operating range is minimal or non-exisitent; effective levels and toxic levels overlap
  21. Phenytoin
    MOA
    Side Effects
    Special Interests
    • MOA: targets Na+ channels primarily, K+/Ca++ channels secondarily decreasing frequency of APs
    • Side Effects: ataxia, nystagmus, cognitive impairment, hirsutism (female hair in places where it shouldnot be), gingival hyperplasia, coarsining of facial features, exacerbates absence features, tetarogen
    • Special Interests: do not give to pregnant women or absence epileptics, 0th order kinetics, oldest non-sedative epileptic, has a parenteral sister drug: Fosphenytoin
  22. Carbamezepine
    MOA
    Side Effects
    Special Interests
    • MOA: blocks Na+ channels, therefore decreasing the frequency of APs
    • Side Effects: Aplastic Anemia, Nausea and visual disturbances, autoinduction of metabolism
    • Special Interests: Do not give to Absence epileptics, most effective against partial seizures and has less side effects than phenytoin, Active metabolite
  23. Oxcarbazepine
    MOA
    Side Effects
    Special Interests
    • MOA: alters Na+ conductance and decreases the frequency of APs
    • Side Effects: Hyponatremia
    • Special Interests: very similar to carbamazepine but better side effects and less effectivity, Active metabolite
  24. Phenobarbital
    MOA
    Side Effects
    Special Interests
    • MOA: prolongs opening of GABA-gated Cl- channels
    • Side Effects: sedation, cognitive impairment, induction of liver enzymes, may worsen absence seizures/atonic seizures
    • Special Interests: drug of choice for febrile seizures in infants, useful for partial and generalized tonic-clonic seizures, considered a very safe drug, one of the oldest AEDs
  25. Primidone
    MOA
    Side Effects
    Special Interests
    • MOA: not really known, but probably like phenytoin
    • Side Effects: sedation, cognitive impairment, induction of liver enzymes, may worsen absence/atonic seizures, also GI complaints
    • Special Interests: absorbed completely, should be administered slowly, metabolized into 2 metabolites: phenobarbital and phenylethylmalonamide (PEMA)
  26. Valproate
    MOA
    Side Effects
    Special Interests
    • MOA: inhibits succinate semialdehyde dehydrogenase and GABA transanimase, therefore increasing levels of GABA in the brain. Also increases potassium conductance
    • Side Effects: elevated liver enzymes, nausea, vomiting, abdominal pain, heartburn, tremor, alopecia, weight gain, teratogen (spina bifida)
    • Special Interests: used to treat absence and myoclonic seizures, good for controlling generalized seizures
  27. Ethosuximide
    MOA
    Side Effects
    Special Interests
    • MOA: reducing low-level threshold Ca++ channel current (T-type) in the thalamus
    • Side Effects: gastric distress (nausea, pain, vomiting), lethargy, fatigue, hiccups, headaches, skin rashes
    • Special Interests: drug of choice for absence seizures, very safe, little/no binding to plasma proteins
  28. Clonazepam
    MOA
    Side Effects
    Special Interests
    • MOA: increases the frequency of GABA-gated Cl- channels being open
    • Side Effects: sedation, ataxia
    • Special Interests: a Benzodiazepine, long-lasting drug for absence seizures and sometimes for myoclonic seizures
  29. Vigabatrin
    MOA
    Side Effects
    Special Interests
    • MOA: irreversible inhibitor of GABA-transaminase, therefore increases inhibitory effects of GABA in synaptic cleft
    • Side Effects: drowsiness, dizziness, weight gain, agitation, confusion, psychosis
    • Special Interests: contraindicated for mentally ill patients, good for partial seizures
  30. Lamotrigine
    MOA
    Side Effects
    Special Interests
    • MOA: inactivates sodium channels and suppresses rapid firing of neurons
    • Side Effects: dizziness, headache, diploia, nausea, somnolence, rash
    • Special Interests: BS-drug, can be used with valproate, especially good for depressed patients (with bi-polar disorder), must be titrated slowly to avoid rash
  31. Felbamate
    MOA
    Side Effects
    Special Interests
    • MOA: Antagonist for Na+ channels and NMDA receptors at glycine site
    • Side Effects: severe! aplastic anemia, severe hepatitis, lethargy, anorexia, nausea, vomiting, headache, dizziness, insomnia
    • Special Interests: not first line medication! BS-drug, has black box warning for side effects
  32. Topiramate
    MOA
    Side Effects
    Special Interests
    • MOA: block voltage gated sodium channels, antagonist for glutamate receptors
    • Side Effects: somnolence, fatigue, dizziness, cognitive slowing, altered verbal fluency, decreased appetite
    • Special Interests: BS-drug, may help with migranes, teratogenic in animals
  33. Tiagabine
    MOA
    Side Effects
    Special Interests
    • MOA: GABA uptake inhibitor
    • Side Effects: dizziness, tremor, difficulty concentrating, depression, asthenia, emotional liability, skin rash
    • Special Interests: BS-Drug
  34. Zonisamide
    MOA
    Side Effects
    Special Interests
    • MOA: voltage gated Na+ channels and T-Type Ca++ channels
    • Side Effects: drowsiness, rash, cognitive impairment, weight loss, renal stones
    • Special Interests: BS-Drug, sulfonamide deravitive
  35. Gabapentin
    MOA
    Side Effects
    Special Interests
    • MOA: GABA-like molecule that does not act on GABA receptors, but rather acts on alpha2-delta subunits of Ca++ channels preventing GABA release
    • Side Effects: Somnolence, dizziness, ataxia, weight-gain, behavioral changes
    • Special Interests: used for adjunctive therapy to treat partial seizures w or w/o secondary generation
  36. Levetiracetam
    MOA
    Side Effects
    Special Interests
    • MOA: unknown
    • Side Effects: very safe: somnolence, asthenia, behavioral disturbances, headaches
    • Special Interests: used as an adjunctive for partial seizures
  37. Pregabalin
    MOA
    Side Effects
    Special Interests
    • MOA: very similar to Gabepentin, binds alpha2-delta subunit of calcium channel, thereby inactivating it and reducing NT release
    • Side Effects: none
    • Special Interests: also used for fibromyalgia and spinal cord injuries
  38. Diazepam (Valium)
    MOA
    Side Effects
    Special Interests
    • MOA: potentiates GABA function
    • Side Effects: sedation, paradoxical hyperactivity in children, tolerance
    • Special Interests: a benzodiazepine, primary for status epilepticus
  39. Lorazepam (Ativan)
    MOA
    Side Effects
    Special Interests
    • MOA: potentiates GABA function
    • Side Effects: sedation, paradoxical hyperactivity in children, tolerance
    • Special Interests: a benzodiazepine, primary for status epilepticus
  40. What is status epilepticus?
    a condition where seizures recur within a short period of time for at least 30 minutes and such that baseline consciousness is never regained
  41. What is both the initial treatment of Status Epilepticus and what is the follow up treatment?
    • Initial: Diazepam/Lorazepam
    • Follow Up: Phenytoin, Phenobarbitol
  42. What are 5 BS AEDs we learned about?
    • valproate
    • lamotrigine
    • topiramate
    • levetiracetam
    • zonisamide
  43. What are 6 NS AEDs we learned about?
    • carbazepine
    • phenytoin
    • gabapentin
    • tiagabine
    • oxcarbazepine
    • pregabalin
  44. What two drugs can be administered with carbamazepine to increase the effect?
    • phenytoin: increased metabolism of carbamazepine pharmakokinetic
    • Phenylbarbital: increased production of epoxide pharmakodynamic
  45. What drug can administered with phenytoin?
    primidone: it increases the conversion to phenobarbital
  46. What two drugs should valproic acid not be administered with?
    • phenobarbitol: decreased metabolism, increased toxicity
    • phenytoin: displacement from binding, increased toxicity

What would you like to do?

Home > Flashcards > Print Preview