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Neurology > Pharmacology Of Epilepsies And Seizures > Flashcards

Pharmacology Of Epilepsies And Seizures Flashcards

1
Q

Definition of a seizure

A

Episode of abnormal neuronal excitation and discharge in the CNS

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2
Q

Definition of status epilepticus

A

A seizure that lasts greater than 5 min or 2 seizures within 24 hrs

medical emergency

more acute

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3
Q

Definition of epilepsy

A

Recurrent seizures

prolonged activity can result in neuron death and damage

more chronic

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4
Q

Surface etiology of seizures

A

Is disruption off the balance in inhibitory and excitatory neurons
- CAN BE EITHER, bout its usually GABA inhibition and glutamate abundance.

Pharmacology Management is to:

  • decrease activity of excitatory neurons
  • increase activity of inhibitory neurons
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5
Q

How does surround inhibition work in the normal nervous system

A

GABAergic neurons surrounding the activated circuit are simultaneously activated when a 1st order neuron is excited

Allows for neurons outside of the designated circuit to be inhibited, funneling the signal through the proper circuit
- many structures have many nerves attached to each other to various pathways. It’s important for GABA neurons to be able to funnel a signal through a proper pathway

**loss of surround inhibition results in seizures (since multiple pathways are activated at once)

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6
Q

Classifications of seizures

A

1) Partial seizures = focal seizures
- Simple partial = focal aware
* no loss of consciousness
- Complex partial = focal impaired
* loss of consciousness

2) Grand mal = generalized tonic-clonic
3) Petit mal = generalized absence
4) Partial seizures that progress to grand mal = focal-to-bilateral tonic-clonic

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7
Q

Symptoms of a simple partial (focal aware seizure)

A

Involuntary repetitive movements

Paresthesia

Flashing lights

*consiousness is preserved

**all symptoms are ipsilateral

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8
Q

Symptoms of a complex partial (focal imparied) seizure

A

Abnormal activity of the temporal lobe

Involuntary repetitive movements (automatisms)

*consciousness is impaired

** very classically preceded by an aura

*** is ipsilateral

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9
Q

Symptoms of a petit mal (generalized absence)seizure

A

Sudden brief interruption of consiousness

Recurrent and can occur up to 200/day

Blank stares, eyes roll upward, eyelids flutter and complete cessation fo activity for about 3-20 seconds
- looks like weird daydreaming

Involuntary Repetitive movements may/may not occur

More common in children and adolescents (can be outgrown as an adult)

Possess “sleep spindle” patterns (3-Hz spike wave discharge which mimics slow-wave sleep)

  • is not proceeded by an aura

** patients have no memory of these incidents and often negatively impacts school performances

*** symptoms are ipsilateral

** best treated with T-type calcium channel blockers

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10
Q

Symptoms of a grand mal (generalized tonic-clonic) seizure

A

Brief violent muscle contractions all over the body or individual muscles

Loss of consciousness.

*Is not proceeded by a focal seizure

** almost always presents secondary to another pathology

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11
Q

Etiologies of focal (partial) seizures

A

Caused by increases in electrical activity at the cellular level which causes inappropriate depolarization
- paroxysmal depolarizing shift (PDS)

Surround inhibition keeps this PDS within a focal point/region of the brain

Can cause a “Jacksonian march” effect if the PDS is very strong and overcomes surround inhibition
- this is an aura or feeling of anxiety/dread as the seizure continues

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12
Q

Etiology of secondary generalized seizures (focal-to-bilateral tonic-clinic seizures)

A

Is a focal seizure that escalates to the point where it involves BOTH hemispheres of the brain

Causes the uncontrolled depolarization to spread throughout connecting circuits:

  • U fibers in cortical regions
  • corpus callosum
  • thalamocortical projections

Is almost always preceded by an aura

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13
Q

Etiology of primary generalized seizures (grand mal/petit mal)

A

Generalized seizures that tend to originate in well-connected areas within the CNS
- such as thalamus

  • there is NO aura or warning signs
  • can however be accompanied by a preceding feeling of apprehension or jerking of one arm
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14
Q

Specific differences between status epilepticus and general epilepsy

A

Status epilepticus
- patient is currently seizing for greater than 5 minutes or has had 2 or more seizures, or has not return to baseline brain activity after a recent seizure.

  • is a medical emergency and can be fatal, requires immediate acute intervention
  • goal is to stop current seizure
  • first line agent is chosen by efficacy and the dosage is managed in high quantity with both IV or IM

Epilepsy
- patient has recurring seizures, but not currently

  • not an emergency, but can leads to status epilepticus
  • goal of treatment is to prevent a breakout
  • first line agency is chosen based on efficacy: ADR ratios and is managed in low doses orally.
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15
Q

General principles of epilepsy treatment

A

Must take into consider patient factors

  • age/gender
  • pregnancy or wants to be pregnant
  • comorbidites
  • insurance
  • adherence
  • current meds they are on

Goal is to use just 1 drug
- only use 2 if you absolutely must (refractory seizures)

many drugs have narrow therapeutic indices and are given daily orally

** must ALWAYS titrations dose when beginning a new anti seizure drug and the blood levels of the drugs need to monitor consistently

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16
Q

Intractable epilepsies

A

Epilepsies that even with pharmacokinetic therapy, still get epilepsies
- “ untraceable seizures”

In children with these epilepsies, often see progressive brain damage

Finite treatment can be surgical resection of the affected brain region, however this is very traumatic life altering and needs to really be justified.

17
Q

Generalized ADRs in all epileptic drugs

A

Dose dependent:

  • nausea/vomiting
  • dizziness/vertigo feeling
  • headaches
  • CNS depression

Non-adherence specific:

  • rashes
  • hyponatremia

Just occur sometimes:

  • ocular dysfunction
  • ataxia
  • fatigue
  • weakness

almost all are teratogenic

18
Q

What must you do when switching drugs for epilepsy treatment

A

First drugs is always chosen based on type of seizure, patient characteristics and ADRs
- this drug is titrated to find proper dose

If the first line doesnt work:
- ALWAYS titrations the new drug while the 1st drug is being tapered slowly

  • if second line fails, can use rational combinations or surgery if needed*
19
Q

Carbamazepine

A

MOA: blocks sodium channels in epileptiform presynaptic neuron terminals

NOT a BENZO

Indications:

  • focal seizures
  • focal-to-bilateral tonic clinic seizures

Contraindications
- aggregates absence and myoclonic seizures

ADRs: most are dose dependent

  • GI discomfort
  • blurred vision
  • hyponatremia
  • rash
  • Stevens-Johnson’s (asians and HLA-B*1502 allele patients have to worry about this more)

*strong inducer of CYP450 enzymes so must monitor when combining with drugs

20
Q

Lacosamide

A

MOA: blocks sodium channels ion epileptiform presynaptic neurons

Indications:

  • focal seizures ( only age 17+)
  • focal-to-bilateral tonic-clinic seizures (requires high dose)

Contraindicated:
- patients who have phenylketonuria

Only given oral or IV

ADRs:
Pretty low tolerable 
- nausea/vomiting 
- diplopia 
- headache
21
Q

Phenytoin and fosphenytoin

Hydantoins

A

MOA: blocks sodium channels in epileptiform presynaptic neurons

Indications:

  • focal seizures
  • focal-to-bilateral tonic-clonic seizures
  • *used in status epilepticus (high doses)

Contraindications:

  • absence seizures
  • pregnancy (develops fetal hydantoin)

Is IV/IM form only and is pretty painful to inject

  • very relevant for displacement in blood concentrations
  • must monitor closely for patients with hyperbillirubinemia, hypoproteinuria, warfarin and Valproic acid*

** changes kinetics based on doseage
- first-order = low concentrations
- zero-order = high concentrations
(Because of this, must be very careful in upper dose amount DONT BE TOO QUICK)

ADRs:

  • nystagmus
  • diplopia
  • ataxia
  • long term use only*
  • gingival hyperplasia
  • hirsustism (increase in body hair growth)
  • peripheral neuropathy
  • osteomalacia (lowers metabolism of Vit. D)
  • agranulocytosis w/ fever and rash
22
Q

Lamotrigine

A

MOA: blocks sodium channels in epileptiform presynaptic neurons

Indications:

  • focal seizures
  • absence seizures

very good choice for pregnant patients

ADRs:

  • rash
  • nausea/vomiting
23
Q

Oxcarbazepine

A

MOA: blocks sodium channels in epileptiform presynaptic neuron terminals

NOT a BENZO

Indications:

  • focal seizures
  • focal-to-bilateral tonic clinic seizures
  • especially useful if non-response to carbamazepine (since its prodrug)

Contraindications
- aggregates absence and myoclonic seizures

ADRs: most are dose dependent

  • GI discomfort
  • blurred vision
  • hyponatremia
  • rash (cross reactive with carbamazepine)
  • Stevens-Johnson’s (asians and HLA-B*1502 allele patients have to worry about this more)
  • CNS effects in elderly
  • drug tends to do worse overall in elderly populations
24
Q

Gabapentin and pregabalin

A

MOA: blocks high-voltage Ca2+ channels by binding to a2d subunit

DOESN’T AFFECT GABA CONCENTRATIONS

Indications:

  • focal seizures
  • neuralgias
  • diabetic neuropathy
  • anxiety

Contraindications:
- absence and myoclonic seizures

very good in elderly patients if levetiracetam fails

ADRs:

  • somnolence
  • dizziness
  • ataxia
  • headache
  • permanent weight gain and peripheral edema
  • Tremor
25
Q

Pregabalin

A

MOA: blocks high-voltage Ca2+ channels

DOESN’T AFFECT GABA CONCENTRATIONS

Indications:
- focal seizures

Contraindications:

ADRs:

26
Q

Ethosuximide

A

MOA: blocks thalamic T-type calcium channels specifically

indications:
- absence seizures (1st line in children)

contraindications:

ADRs:

  • gastric distress
  • general pain
  • nausea/vomiting
  • hiccups
  • euphoria
27
Q

Perampanel

A

MOA: blocks AMPA receptors

Indications:

  • focal seizures
  • primary tonic-clonic seizures
  • idiopathic seizures

Contraindications
- N/A

ADRs:

  • most are behavioral
  • can cause falls and imbalance/ataxia at higher doses
28
Q

Felbamate

A

MOA: Blocks NMDA receptors

Indications:

  • focal refractory seizures only
  • Lennox-gastaut syndrome

Contraindications:
- patients with liver issues/ hepatitis

ADRs:
- causes aplastic anemia and hepatitis if prolonged use

29
Q

Levetiracetam

A

MOA: blocks presynaptic vesicle release mechanisms
- idiopathic But binds to SV2A proteins on vesicles

Indications:

  • broad spectrum of seizures (1st line in elderly)
  • juvenile myoclonic epilepsies

ADRs:

  • mood and behavioral issues (serious if occur)
  • somnolence
  • asthenia
  • ataxia
  • dizziness
    • increases odds of getting common cold*
30
Q

Vigabatrin

A

MOA: inhibits GABA transaminase enzymes

indications:
- focal seizures only

Contraindications:

  • patients with mental status issues/ illnesses
  • generalized seizures
  • infantile spasms

ADRs:

  • can cause irreversible vision last (last line therapy because of this)
  • headaches
  • mental status issues
  • psychosis
  • weight gain
31
Q

Tiagabine

A

MOA: GAT-1 inhibitor

Indications:

  • focal seizures
  • secondary generalized seizures
  • usually an adjunctive agent (not used by itself or first line)

ADRs:

  • dizziness
  • tremors
  • depression
  • mental status issues
    • can actually induce other types of seizures
  • psychosis
  • rashes
32
Q

Phenobarbital

A

MOA: agonist for GABA and mimics GABA

Indications:

  • focal seizures
  • generalized tonic-clinic seizures
    • first line in all infantile seizures (except absence)
    • pentobarbital prodrug is used to induce general anesthesia in drug-refractory status epilepticus

Contraindicated

  • any absence seizures
  • infantile spams (west syndrome)

ADRs: (not first line in any population other than infants)

  • respiratory depression
  • hypotension
  • cardiac arrhythmias
  • shivering and tremors
  • bronchospasms
  • abuse potential is present and often develops dependence even at normal doses in adults
33
Q

Benzos

A

MOA: positive allosteric modulator of GABA(a) receptors

Indications:

  • acute seizures (all)
    • very good for status epilepticus (all)
  • absence seizures (clonazepam only)
  • myoclonic seizures (clonazepam only)
  • atonic seizures (clonazepam and clobazam only)
  • only clonazepam and clobazam can be used for long term
  • clonazepam is the most potent seizure med known

ADRs:

  • sedative effects
  • can develop tolerance and withdrawal symptoms
  • hyperactivity in kids
34
Q

Topiramate

A

MOA: blocks NA, GABA(a), AMPA and kainate receptors

Indications:

  • broad spectrum seizures
  • migraine prophylaxis agent
  • juvenile myoclonic syndrome
  • Lennox-gastaut syndrome

Contraindications:

  • pregnancy (develops cleft palate)
  • patients with glaucoma and myopia present already

ADRs:

  • paresthesia
  • somnolence
  • fatigue
  • vomiting
  • weight loss (long term only)
  • kidney stones (men only)
  • induces/exacerbates glaucoma and myopia
35
Q

Valproate/ valproic acid

A

MOA: blocks sodium and calcium channels, GAT-1 and carbonic anhydrase enzymes

Indications:

  • broad spectrum seizures
  • bipolar mania
  • prophylaxis for migraines

Contraindications:

  • patients that are already experiencing affects to any (*) symptom below
  • pregnancy (causes severe cognitive impairments)

ADRs:

  • alopecia
  • pancreatitis*
  • hepatotoxicity*
  • thrombocytopenia*
36
Q

What are common but important DDIs with anti seizure meds

A

Carbamazepine:
- reduces efficacy of all other ASD drugs that require CYP metabolism

Phenytoin
- any CYP2C19 inhibitor will send normal concentrations of this drug to toxic levels

Neurology (65 decks)

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