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Pharmacology (5th year) > Anti-epileptic > Flashcards

Anti-epileptic Flashcards

1
Q

Definition of epilepsy

A

Recurrent seizures unprovoked by any systemic or acute neurologic insults

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2
Q

Diagnosis of epilepsy

A
  • exclude metabolic or toxic cause
  • LP
  • EEG
  • neuroimaging
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3
Q

Pathophysiology of epilepsy

A

Imbalance between excitatory and inhibitory processes

  • decreased GABA
  • increased glutamate
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4
Q

What is GABA synthesised from?

A

Amino acid, L-Glutamic acid

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5
Q

How is GABA synthesised?

A

Glutamic acid decarboxylase (GAD) is presen in neurons

- causes removal of a-carboxyl group

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6
Q

How does GABA inhibit?

A
  • activated GABA A receptor mediates increase in conductance
  • increase influx of Cl- ions causes membrane hyperpolerisation
  • increase in threshold for generating action potential
  • inhibitory action
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7
Q

Goals of therapy in epilepsy

A
  • control seizures
  • restore quality of life
  • restore neuronal function
  • minimize drug adverse effects
  • identify and avoid precipitating factors
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8
Q

Excitation ions and neurotransmitter

A
  • inward Na+, Ca++

- glutamate, aspartate

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9
Q

Inhibition ions and neurotransmitter

A
  • inward Cl-
  • outward K+
  • GABA
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10
Q

MOA of anti-epileptics

A
  • prolong Na+ channel inactivation
  • increase Cl- channel
  • glutamate receptor antagonism
  • Inhibition of T-type Ca++ current
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11
Q

How to choose an anti-epileptic

A
  • based on seizure classification
  • patient-specific variables
  • characteristics of drug
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12
Q

Drugs that inhibit axonal transmission

A
  • phenytoin
  • carbamazepine
  • valproate
  • lamotrigine
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13
Q

Drugs that potentiate GABA receptors

A
  • benzos

- phenobarb

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14
Q

Why do therapeutic drug monitoring?

A
  • avoid toxicity
  • optimize drug/ therapeutic response
  • detect changes in pharmacokinetics
  • monitor compliance
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15
Q

Classical AEDs

A
  • phenytoin
  • phenobarb
  • carbamazepine
  • valproate
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16
Q

Newer AEDs

A
  • lamotrigine

- Levetiracetam

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17
Q

Drugs that modulate volatge dependent ion channels

A
  • carbamazepine
  • phenytoin
  • valproid acid
18
Q

How do benzos work?

A
  • increase the frequency of GABA-mediated chloride channel openings
19
Q

How does phenobarb work?

A
  • prolongs GABA-mediated chloride channel openings

- block the voltage-dependent sodium channels

20
Q

Pleiotropic AEDs

A
  • Lamotrigine

- valproate

21
Q

How does lamotrigine work?

A
  • blocks sodium channels
  • may interfere with glutamate release
  • inhibits Ca ++ channels
22
Q

How does valproate work?

A
  • enhances GABA transmission
  • blocks sodium channels
  • augment K+ channels
23
Q

Inducers of Cyt p450

A
  • phenobarb
  • phenytoin
  • carbamazepine
24
Q

Inhibitor of Cyt p450

A

Sodium valproate

25
Q

How does phenytoin work?

A
  • inhibits Na+ channels to inhibit generation of rapid AP
26
Q

Adverse effects of phenytoin

A
  • CNS sedation
  • gum hyperplasia
  • hirsuitism
  • skin rash hypersensitivity
27
Q

Interactions with phenytoin

A
  • valproate displaces phenytoin from plasma proteins

- increase cyt p450

28
Q

Adverse effects of carbamazapine

A
  • diplopia and ataxia
  • idiosyncratic skin reaction
  • agranulocytosis and aplastic anaemia
29
Q

Interactions with carbamazepine

A
  • induces microsomal enzymes

- stimulates its own metabolism

30
Q

Adverse effects of phenobarb

A
  • CNS sedation
  • skin rashes if allergic
  • tolerance and physical dependence
31
Q

Interactions with phenobarb

A
  • stimulates cyt p450

- CNS depression with in combo with benzos

32
Q

Adverse effects of valproate

A
  • elevation of liver enzymes

- birth defects

33
Q

Interactions with valproate

A
  • displaces phenytoin from plasma proteins

- p450 inhibitor

34
Q

Adverse effects of lamotrigine

A
  • less CNS sedative

- potentially life-threatening dermatitis

35
Q

Why might patient have cross-sensitivity to multiple AEDs?

A
  • carbamazepine
  • phenytoin
  • phenobarb
    Are all aromatic AED
  • get oxidised to arene oxide (which is toxic)
36
Q

Adverse effects of benzos

A
  • CNS sedative

- tolerance, dependence

37
Q

Definition of status epilepticus

A

5 minutes or more of continuous

  • clinical or electrographic seizure activity
  • recurrent seizure activity without recovery between
38
Q

General measure in status epilepticus

A
  • start treatment immediately
  • ABCs
  • blood glucose
  • electrolytes and anticonvulsant levels
39
Q

Stepwise management of status epilepticus

A
  • benzodiazepine
  • phenytoin (20mg/kg)
  • phenobarbital (20-39mg/kg)
  • RSI (propofol) (2-5mg/kg, then infusion)
40
Q

Problems with AEDs in pregnancy

A
  • sodium valproate higher teratogenic potential
  • folate supplementation before pregnancy considered
  • pharmacokinetics change, so adjust dose
41
Q

Problems with ARVs and epilepsy

A
  • phenytoin and carbamazepine are enzyme inducing
  • potential drug interactions
  • in HIV-infected women of child bearing age, lamotrigine is preferred to valproate

Pharmacology (5th year) (15 decks)

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