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Pharma 4: ANTIEPILEPTIC DRUGS Flashcards

1
Q

The Na channel blockers

A
  1. Phenytoin
  2. Carbamazepine
  3. Valproate?
  4. Iamotrigine
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2
Q

The Ca channel blockers

A
  1. Ethosuximide

2. Pregabalin

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3
Q

Enhancers of GABA-mediated synaptic inhibition

A
  1. BZDs
  2. Vigabatrin
  3. Tiagabin
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4
Q

Those that affect GLUTAMATE levels and NMDA receptors

A
  1. Iamotrigine
  2. Valproate

(Also Na channel blockers?)

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5
Q

PHENYTOIN

Use

A

PHENYTOIN

Uses:

  1. All partial seizures, whether simple or complex
  2. In tonic-clonic seizures
  3. Status epilepticus
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6
Q

PHENYTOIN

Adminstration

A

PHENYTOIN

Administered:

  1. Orally
  2. In case of STATUS EPILEPTICUS—>I.V
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7
Q

PHENYTOIN

MOA

A

PHENYTOIN

MOA: Na channel blocker

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8
Q

PHENYTOIN

Side effects

A

PHENYTOIN

Side effects:

  1. Nystagmus
  2. Ataxia
  3. Gingival hyperplasia (esp. in children)
  4. Fetal malformations ie. TERATOGENIC
    eg. cleft palate
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9
Q

PHENYTOIN

May worsen which condition?

A

ABSENCE SEIZURE

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10
Q

PHENYTOIN

Drug interactions

A

PHENYTOIN

Drug interaction:

  1. SALICYLATES competitively inhibit plasma albumin binding
  2. INDUCE HEPATIC ENZYMES—> increase
    metabolism of:
    A- antiepileptics
    B- anticoagulants
    C- oral contraceptives
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11
Q

CARBAMAZEPINE

Administered

A

CARBAMAZEPINE

Administered: ORALLY

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12
Q

CARBAMAZEPINE

Precautions

A

CARBAMAZEPINE

Precautions:

  1. Start with a low dose with gradual build up to avoid dose-related toxicity
  2. Frequent liver tests
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13
Q

CARBAMAZEPINE

Uses

A

CARBAMAZEPINE

Uses:

  1. DRUG OF CHOICE in all partial seizures
  2. Tonic-clonic seizures

(Like phenytoin, minus the status epilepticus)

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14
Q

CARBAMAZEPINE

MOA

A

CARBAMAZEPINE

MOA:

Na channel blocker

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15
Q

CARBAMAZEPINE

Side effects

A

CARBAMAZEPINE

Side effects:

A- After chronic use:

i. Stupor
ii. Coma
iii. Resp depression

B- liver toxicity (frequent liver test)

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16
Q

VALPROATE

Administered

A

VALPROATE

Administered: ORALLY

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17
Q

VALPROATE

MOA

A

VALPROATE

MOA:

  1. BLOCK VOLTAGE GATED Na CHANNEL
  2. BLOCK NMDA RECEPTOR MEDIATED EXCITATION
  3. GABA POTENTIATION
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18
Q

VALPROATE

Therapeutic use

A

VALPROATE

Therapeutic uses:

  1. Infantile epilepsy
  2. In YA where grand and petit grand mal coexist because its effective against both grand mal and petit (peculiar to valproate)
  3. Myoclonic seizures
  4. Absence seizures + generalized tonic-colic attacks
  5. Reduce incidence and severity of tonic-colic siezure
19
Q

VALPROATE

Side effects

A

VALPROATE

Side effects:

  1. Ataxia ( like phenytoin)
  2. Tremors
  3. Idiosyncratic fatal? liver toxicity (carbamazepine)
  4. Teratogenic—> spina bifida (Phenytoin)
20
Q

ETHOSUXIMIDE

Drug of choice in

A

ETHOSUXIMIDE

Drug of choice in:

ABSENCE SEIZURES (+ carbamazepine,,, phenytoin)

21
Q

ETHOSUXIMIDE

MOA

A

ETHOSUXIMIDE

MOA:

Inhibits T-type Ca channels which are involved in the rhythmic discharge associated with absence seizures

22
Q

ETHOSUXIMIDE

Side effects

A

ETHOSUXIMIDE

Side effects:

  1. Nausea
  2. ANOREXIA
  3. In sensitive indv.—> LEUKOPENIA, APLASTIC ANEMIA
  4. In susceptible pt. —> TONIC-COLIC SEIZURE
23
Q

Mechanism of GABA action potentiation with drug example

A

BZDs: Bind to modulatory site on GABA-A receptor

Tiagabine: Inhibit GABA uptake

Vigabatrin: Inhibit GABA TRANSAMINASE (inactivates GABA)

24
Q

BZDs

A

DIAZEPAM

CLONAZEPAM

CLOBAZAM

25
Q

BZDs

MOA

A

BZDs

MOA:

Enhance activation of GABA receptors—> facilitate GABA MEDIATED Cl channel opening

26
Q

DIAZEPAM

Use

A

DIAZEPAM

Use: Status Epilepticus

27
Q

DIAZEPAM

Administered

A

DIAZEPAM

Administered: IV, RECTALLY ACUTE

28
Q

DIAZEPAM

Side effects

A

DIAZEPAM

Side effects:

  1. Drowsiness
  2. Ataxia (like valproate and phenytoin)
  3. Resp and cardiac depression if given IV acutely
29
Q

CLONAZEPAM &CLOBAZAM

Side effects in chronic treatment

A

Side effect: DROWSINESS

MAY CAUSE: withdrawal syndrome if stopped abruptly

30
Q

VIGABATRIN

MOA

A

VIGABATRIN

MOA:

  • irreversible inhibitor of GABA-T
  • may inhibit vesicular GABA TRANSPORTER—> sustained increase in EXTRAcellular GABA conc in brain
31
Q

VIGABATRIN

Therapeutic use

A

VIGABATRIN

Therapeutic use:
1. Adjunct in “refractory complex partial seizures”

  1. WEST’S SYNDROME (infantile spasms)……(valproate—
32
Q

VIGABATRIN

Side effects

A

VIGABATRIN

Side effects:

  1. Drowsiness
  2. Dizziness
  3. Weight gain
  4. INFANTS—> intramyelinic edema
  5. LONG TERM THERAPY—> 1/3 of pts experience irreversible visual field defects

There4 used for refractory pts like infantile spasms

33
Q

TIAGABINE

MOA

A

TIAGABINE

MOA: Inhibits GABA uptake in neurons &GLIA
which increases EXTRAcellular GABA LEVELS (+vigabatrin)

High GABA levels potentiate tonic inhibition and prolongs inhibitory action

34
Q

TIAGABINE

Therapeutic use

A

TIAGABINE

Therapeutic use: adjunct to treatment of partial seizures (+vigabatrin)

35
Q

TIGABINE

Side effects

A

TIAGABINE

Side effects:
Well tolerated but dose related SE include
1. Nervousness, dizziness, tremor
2. Excessive confusion or ataxia which would warrant discontinuation of drug

may cause seizure in pt on other meds

36
Q

LAMOTRIGINE

Administered

A

LAMOTRIGINE

Administered: Orally

37
Q

LAMOTRIGINE

MOA

A

LAMOTRIGINE

MOA:

  • Voltage and use dependent inactivation of Na channels
  • decrease release fo GLUTAMATE
38
Q

LAMOTRIGINE

Therapeutic uses

A

LAMOTRIGINE

USES: add on or mono-therapy
1. In childhood—> primary generalized seizures like absence seizures and myoclonic seizures

  1. Partial seizures
39
Q

LAMOTRIGINE

Side effects

A

LAMOTRIGINE

Side effects:

  1. Dizziness
  2. Headache
  3. ”DIPLOPIA”
  4. Skin rash (diminished with low introduction of drug)
  5. Life threatening dermatitis (1-2%) of peds
40
Q

PREGABALIN

use

A

PREGABALIN

Use: add on ONLY
1. Partial seizures w/ or w/out 2ry generalization

41
Q

PREGABALIN

MOA

A

PREGABALIN

MOA:
Bind a2s subunit of Ca channel—> inhibit release of NT and neuromodulators ie decrease release of glutamate threre4 anti epileptic

42
Q

PEEGABALIN

Side effects

A

PREGABALIN

Side effects:

  1. Somnolence
  2. Dizziness
  3. Ataxia
  4. Headache
  5. Tremor
43
Q

Pharmacokinetics of anti-epileptic drugs

A
  • Orally available
  • Penetrate CNS
  • 80-100% of dose in circulation
  • Not highly bound to plasma except PHENYTOIN & VALPROATE
  • Cleared by hepatic mechanisms—> active metabolites cleared by liver
  • Medium long acting ie. >12 hrs
  • Older ones are potent inducers of hepatic enzymes (phenytoin and carbamazepine)
  • extended release formulations administered 1-2/day improve compliance

CNS (28 decks)

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