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CNS > Pharma 4: ANTIEPILEPTIC DRUGS > Flashcards

Pharma 4: ANTIEPILEPTIC DRUGS Flashcards

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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

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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

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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

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A

ETHOSUXIMIDE

Drug of choice in:

ABSENCE SEIZURES (+ carbamazepine,,, phenytoin)

21
Q

ETHOSUXIMIDE

MOA

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A

ETHOSUXIMIDE

MOA:

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

22
Q

ETHOSUXIMIDE

Side effects

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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

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A

BZDs: Bind to modulatory site on GABA-A receptor

Tiagabine: Inhibit GABA uptake

Vigabatrin: Inhibit GABA TRANSAMINASE (inactivates GABA)

24
Q

BZDs

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A

DIAZEPAM

CLONAZEPAM

CLOBAZAM

25
BZDs MOA
BZDs MOA: Enhance activation of GABA receptors—> facilitate GABA MEDIATED Cl channel opening
26
DIAZEPAM Use
DIAZEPAM Use: Status Epilepticus
27
DIAZEPAM Administered
DIAZEPAM Administered: IV, RECTALLY ACUTE
28
DIAZEPAM Side effects
DIAZEPAM Side effects: 1. Drowsiness 2. Ataxia (like valproate and phenytoin) 3. Resp and cardiac depression if given IV acutely
29
CLONAZEPAM &CLOBAZAM Side effects in chronic treatment
Side effect: DROWSINESS MAY CAUSE: withdrawal syndrome if stopped abruptly
30
VIGABATRIN MOA
VIGABATRIN MOA: - irreversible inhibitor of GABA-T - may inhibit vesicular GABA TRANSPORTER—> sustained increase in EXTRAcellular GABA conc in brain
31
VIGABATRIN Therapeutic use
VIGABATRIN Therapeutic use: 1. Adjunct in "refractory complex partial seizures" 2. WEST’S SYNDROME (infantile spasms)......(valproate—
32
VIGABATRIN Side effects
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
TIAGABINE MOA
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
TIAGABINE Therapeutic use
TIAGABINE Therapeutic use: adjunct to treatment of partial seizures (+vigabatrin)
35
TIGABINE Side effects
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
LAMOTRIGINE Administered
LAMOTRIGINE Administered: Orally
37
LAMOTRIGINE MOA
LAMOTRIGINE MOA: - Voltage and use dependent inactivation of Na channels - decrease release fo GLUTAMATE
38
LAMOTRIGINE Therapeutic uses
LAMOTRIGINE USES: add on or mono-therapy 1. In childhood—> primary generalized seizures like absence seizures and myoclonic seizures 2. Partial seizures
39
LAMOTRIGINE Side effects
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
PREGABALIN use
PREGABALIN Use: add on ONLY 1. Partial seizures w/ or w/out 2ry generalization
41
PREGABALIN MOA
PREGABALIN MOA: Bind a2s subunit of Ca channel—> inhibit release of NT and neuromodulators ie decrease release of glutamate threre4 anti epileptic
42
PEEGABALIN Side effects
PREGABALIN Side effects: 1. Somnolence 2. Dizziness 3. Ataxia 4. Headache 5. Tremor
43
Pharmacokinetics of anti-epileptic drugs
- 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

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