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Pharm final > Antiepileptics > Flashcards

Antiepileptics Flashcards

1
Q

Nature and Mechanisms of Seizures

A

Experimental data shows that:
• Antagonists of the GABAA receptor trigger seizures.
• Agonists of glutamate receptors trigger seizures.
• Drugs that enhance GABAergic transmission inhibit seizures.
• Glutamate receptor antagonists inhibit seizures.

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2
Q

The principal mechanisms of action of antiseizure drugs involve:

A
  • Blockade of Voltage-Gated Ion Channels

* Modulation of Synaptic Transmission (newer drugs)

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3
Q

Drugs that Block Voltage-Gated Ion Channels

A
  1. Drugs that block Voltage-Gated Na+ channels - block AP
    • Phenytoin
    • Carbamazepine
    • Lamotrigine
    • Zonisamide
    - may contribute to effects of: Phenobarbital, Valproate, Topiramate
  2. Drugs that block T-type Ca2+ channels
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4
Q

DOC used to tx Absence seizures?

MOA?

A

Ethosuximide and valproate
• The T-type Ca2+ current governs oscillatory responses in thalamic neurons.
• If tonic-clonic seizures are present valproate is the drug of choice.
• Valproate is also preferred for atypical absence seizures.
• Lamotrigine is probably effective.

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5
Q

Drugs that Affect Synaptic Transmission

  1. Drugs that enhance GABAergic neurotransmission
A
  1. Direct action on the GABA receptor
    • Benzodiazepines
    • Barbiturates
    • Topiramate

Presynaptically:
• Inhibition of the reuptake of GABA: Tiagabine.
• Inhibition of degradation of GABA: Vigabatrin inhibits GABA aminotransferase

Postsynaptically:
• Phenobarbital & topiramate block glutamate receptors.

2

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6
Q

Drugs that Affect Synaptic Transmission

  1. Drugs that reduce glutamatergic neurotransmission
A

Presynaptically:
• Gabapentin and pregabalin decrease glutamate release by blocking presynaptic voltage-gated Ca2+ channels.
• Levetiracetam binds to synaptic vesicle glycoprotein 2A (SV2A). This may affect release of glutamate and GABA.

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7
Q

Choice of Drugs for the Therapy of the Epilepsies

- Partial and Secondarily Generalized Tonic-Clonic Seizures

A
  • Carbamazepine
  • Oxcarbazepine
  • Levetiracetam
  • Zonisamide
  • Phenytoin
  • Valproate
  • Lamotrigine
  • Topiramate
  • Phenobarbital
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8
Q

Generalized Seizures
Tonic-Clonic Seizures
• Main drugs used include:

A
  • Carbamazepine
  • Oxcarbazepine
  • Valproate
  • Lamotrigine
  • Phenytoin
  • Topiramate
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9
Q

Myoclonic Seizures DOC

A
  • Valproate is the drug of choice.
  • Topiramate is also used.
  • Levetiracetam is approved for adjunctive therapy.
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10
Q

Atonic Seizures

A
  • Atonic seizures are often refractory to all drugs.

* Valproate and lamotrigine may be beneficial

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11
Q

status Epilepticus managment algorythm

A

IV lorazepam-(seizure continues)->IV Phenytoin or Fosphenytoin-(s.c.)->IV phenobarbital-(s.c.)->General anesthesia w/ IV midazolam, propofol or barbs.

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12
Q

Drugs induced seizures tx?

A

controlled with diazepam, lorazepam or phenobarbital.

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13
Q

Breakthrough seizures tx?

A

Diazepam rectal gel is approved for breakthrough seizures.

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14
Q

AE: Induce cytochrome P450

A

• Carbamazepine
• Phenobarbital
• Phenytoin
Oxcarbazepine is a weak P450 inducer

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15
Q

Valproate AE

A
  • Hepatotoxicity.
  • Inhibits cytochrome P450.
  • Inhibits metabolism of several drugs.
  • Inhibits its own metabolism.
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16
Q

Phenytoin AE

A
  • Diplopia, ataxia.
  • Gingival hyperplasia.**
  • Coarsening of facial features in children.
  • Hirsutism.
  • Rash. Stevens-Johnson Syndrome.
  • Zero order kinetics of elimination.
17
Q

Carbamazepine AE

A
  • Aplastic anemia, agranulocytosis.

* Rash. Stevens-Johnson syndrome

18
Q

What drug has a BB warning for Rash and SJS

A

Lamotrigine

19
Q

Phenobarbtal similar to Primidone AE

A
  • Sedation, drowsiness.
  • Rash. Stevens-Johnson syndrome.
  • Tolerance, dependence.
  • Cognitive impairment, hyperactivity.
  • P450 inducer.
20
Q

What drugs causes Visual field loss as AE

A

Vigabatrin

21
Q

Felbamate AE:

A
  • Aplastic anemia
  • Hepatotoxicity
  • For refractory epilepsy
22
Q

Discontinuing Antiepileptic Therapy:

A
  • If a patient is seizure-free for 3-5 years discontinuation is warranted.
  • Discontinuation should be slow.
  • Benzodiazepines and barbiturates should be discontinued very gradually to avoid withdrawal seizures.
  • If the patient is on combination therapy, drugs should be withdrawn one at a time.
23
Q

Overdose Toxicity

A
  • Antiseizure drugs are rarely lethal.
  • The most dangerous effect after large overdoses is respiratory depression.
  • Treatment is supportive.
  • Stimulants should not be used.
24
Q

Rash and SJS high risk drugs:

A
  • Phenytoin
  • Lamotrigine
  • Carbamazepine
  • Phenobarbital
25
Q

Other Uses of Antiseizure Drugs:

A
  • Carbamazepine: Neuropathic pain; bipolar disorder.
  • Gabapentin: Neuropathic pain.
  • Lamotrigine: Bipolar Disorder.
  • Pregabalin: Neuropathic pain.
  • Topiramate: Migraine.
  • Valproate: Bipolar disorder; migraine.
  • Primidone: First line for essential tremor (propranolol is also first line).
26
Q

Nonpharmacologic Approaches

A

Ketogenic diet

Vagus nerve stimulation

27
Q

Antiepileptic Drugs and Pregnancy

A
  • Teratogenicity

* Newborn Hemorrhagic Disease

28
Q

Neuropathic pain tx:

A

Carbamazepine (also tx. Bipolar disorder)
Gabapentin
Pregabalin

29
Q

Bipolar disorder tx

A

Carbamazepine (also neuropathic pain)
Lamotrigine
Valproate (also migraine)

30
Q

Migraine tx

A

Topiramate

31
Q

First lines for essential tremor

A

Primidone

propranolol

Pharm final (19 decks)

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