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Pharmacology > Anti-epileptics > Flashcards

Anti-epileptics Flashcards

1
Q

Epilepsy

A

Chronic disorder of recurrent seizures

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2
Q

Seizures

A

Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons

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3
Q

Classification of Seizures

A
  1. Partial seizures
    - Simple partial seizures
    - Complex partial seizures
    - Partial w/ secondary generalized tonic-clonic seizures
  2. Generalized seizures
    - Tonic-clonic seizures
    - Absence seizures
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4
Q

Simple partial seizures

A
  • NO loss of consciousness

- Abnormal activity of 1 limb or muscle group

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5
Q

Complex partial

A
  • Loss of consciousness

- Motor dysfunction- chewing, movements, diarrhea & urination

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6
Q

Partial w. Secondary Generalized Tonic-Clonic Seizure

A

Partial seizure –> Tonic-clonic seizure

- Loss of consciousness

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7
Q

Generalized

A
  • IMMEDIATE loss of consciousness

- Convulsive or non-convulsive

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8
Q

Generalized Tonic-clonic

A
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9
Q

Absent seizures (Petit mal)

A
  • Brief & abrupt self-limiting loss of consciousness
  • Stares & has rapid eye-blinking
  • Usually children
  • 3Hz spike & wave pattern emerges abruptly & ceases after a few seconds on EEG
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10
Q

Other Generalized seizures

A
  • Atonic
  • Tonic
  • Clonic
  • Myoclonic
  • Febrile
  • Status epilepticus
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11
Q

Mechanism of seizures

A

Dec inhibitory synaptic activity (GABA) OR Inc excitatory activity (Glutamate)

  • GABAa antagonist & Glutamate agonist triggers seizures
  • Glutamate receptor antagonists & drugs that enhance GABAergic transmission inhibits seizure
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12
Q

MOA of Antiepileptic drugs

A
  1. Block Voltage-gated Ion Channels
    - Na+ channels
    - T-type Ca2+ channels
  2. Modulate Synaptic Transmission
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13
Q

Drugs that block Na+ channels

A
  • Phenytoin
  • Carbamazepine
  • Lamotrigine
  • Zonisamide
  • Oxcarbazepine

(May contribute to the effects of Phenobarbital, Valproate & Topiramate)

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14
Q

Drugs that block T-type Ca2+ channels

A
  • Ethosuximide
  • Valproate

Used for absent seizures (oscillatory neuronal activity between thalamus & cortex)

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15
Q

Drugs that enhance GABAergic transmission post-synaptically

A
  • Benzos
  • Barbiturates
  • Topiramate

Direct action on GABA receptors

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16
Q

Drugs that enhance GABAergic transmission pre-synaptically

A
  1. Tiagabine - Inhibits GABA reuptake

2. Vigabatrin - Inhibits GABA aminotransferase

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17
Q

Drugs that Reduce Glutamatergic Neurotransmission Post-synaptically

A
  • Phenobarbital
  • Topiramate

Blocks Glutamate receptors

18
Q

Drugs that Reduce Glutamatergic Neurotransmission Pre-synaptically

A
  • Gabapentin
  • Pregabalin
    Dec Glutamate release by blocking presynaptic voltage-gated Ca2+ channels
  • Levetiracetam
    Binds to Synaptic Vesicle Glycoprotein 2A (SV2A) –> Release of Glutamate & GABA
19
Q

Tonic-clonic seizure management

A
  • Carbamazepine
  • Oxcarbazepine
  • Valproate
  • Lamotrigine
  • Phenytoin
  • Topiramate
20
Q

Absent seizure management

A

Ethosuximide & Valproate (DOC)

  • If tonic-clonic is present use Valproate as DOC
  • Atypical absent seizure - Valproate

Lamotrigine also effective

21
Q

Myoclonic seizure management

A

Valproate (DOC)
Topiramate
Levetiracetam - Adjunctive therapy

22
Q

Atonic seizure management

A

Refractory to all drugs

- Valproate & Lamotrigine may be effective

23
Q

Febrile Convulsions management

A

Seizure <15 minutes = Supportive treatment

Seizure > 15 minutes = Diazepam (IV or Rectal)

24
Q

Status Epilepticus

A
  1. Single seizure lasting >5 minutes
    OR
  2. 2 or more seizures w/o recovery of consciousness
  • Convulsive or non-convulsive
  • Usually generalized tonic-clonic seizures
25
Q

Status Epilepticus Management

A

Initial therapy 5-20 mins
- Midazolam (IM) OR Lorazepam OR Diazepam (IV)

Second therapy 20-40 mins

  • (IV) Fosphenytoin OR Valproic acid OR Levetiracetam
  • 2nd line = IV Phenobarbital

Third therapy 40+ mins

  • Repeat 2nd therapy OR
  • IV Thiopental, Midazolam, Phenobarbital OR Propofol
26
Q

Drug-induced seizure management in non-epileptics pts

A
  • Diazepam
  • Lorazepam
  • Phenobarbital
27
Q

Drugs that induce Cytochrome P450

A
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • Oxcarbazepine (weak)
28
Q

Adverse effects of valproate

A
  • Hepatotoxicity

NB: It inhibits Cytochrome P450, metabolism of other drugs and itself

29
Q

Adverse effects of Phenytoin

A
  • Diplopia & ataxia
  • Gingival hyperplasia
  • Coarsening of facial features in children
  • Hirsutism
  • Rash (SJS)

NOT given to children due to AE
NB: Zero order kinetics of elimination

30
Q

Adverse effects of Carbamazepine

A
  • Aplastic anemia
  • Agranulocytosis
  • Rash (SJS)
31
Q

Stevens- Johnson Syndrome & Toxic Epidermal Necrolysis (SJS/TEN)

A
  • Phenytoin, Lamotrigine & Carbamazepine

Discontinues at the 1st sign of rash when using Lamotrigine & Carbamazepine because of Black box warnings

32
Q

Adverse effects of Phenobarbital

A
  • Sedation & drowsiness
  • Tolerance & Dependence
  • Cognitive impairment
  • Hyperactivity
  • Rash (SJS)

P450 inducer

33
Q

Adverse effects of Primidone

A

Similar to its metabolite (phenobarbital)

  • Sedation & drowsiness
  • Tolerance & Dependence
  • Cognitive impairment
  • Hyperactivity
  • Rash (SJS)

P450 inducer

34
Q

Adverse effects of Vigabatrin

A

Visual field loss

35
Q

Adverse effects of Felbamate

A
  • Aplastic anemia
  • Hepatotoxicity

USED for refractory epilepsy

36
Q

Discontinuation of Anti-epileptic therapy

A
  • 3-5 years seizure free

Discontinuation should be slow and withdrawn gradually to avoid withdrawal seizures.

If the pt. is on combination therapy, withdraw drugs one at a time

37
Q

Overdose

A

Rarely lethal

  • Barbiturates may cause Resp. depression
  • Treatment is supportive

Do NOT use Stimulants

38
Q

Which drugs is Teratogenic

A

Valproate most risk of congenital malformation in infants

NB: Folic acid dec. incidence of Neural tube defects but does not prevent it

39
Q

Newborn Hemorrhagic Disease

A

Enzyme-inducing drugs that inc. Vit. K degradation in fetus –> Bleeding in fetus

Vit. K supplement is recommended for mother in the final month of pregnancy

40
Q

Other uses Of Anti-epileptic drugs

A
  1. Carbamazepine = Neuropathic pain & bipolar
  2. Gabapentin = Neuropathic pain
  3. Lamotrigine = Bipolar Disorder
  4. Pregabalin = Neuropathic pain
  5. Topiramate = Migraine
  6. Valproate = Bipolar disorder & Migraine
  7. Primidone = DOC for essential tremor along with Propranolol
41
Q

Non-pharmacologic approaches to Epilepsy

A
  1. Surgery- resection of local area of brain
  2. Ketogenic diet - 4:1:1 fat: protein: carbohydrate
  3. Vagus nerve stimulation - stimulation of left vagus with implanted pace-maker-like device

Pharmacology (16 decks)

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