Anti-epileptic Flashcards Preview

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

Flashcards in Anti-epileptic Deck (41):
1

Definition of epilepsy

Recurrent seizures unprovoked by any systemic or acute neurologic insults

2

Diagnosis of epilepsy

- exclude metabolic or toxic cause
- LP
- EEG
- neuroimaging

3

Pathophysiology of epilepsy

Imbalance between excitatory and inhibitory processes
- decreased GABA
- increased glutamate

4

What is GABA synthesised from?

Amino acid, L-Glutamic acid

5

How is GABA synthesised?

Glutamic acid decarboxylase (GAD) is presen in neurons
- causes removal of a-carboxyl group

6

How does GABA inhibit?

- 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

7

Goals of therapy in epilepsy

- control seizures
- restore quality of life
- restore neuronal function
- minimize drug adverse effects
- identify and avoid precipitating factors

8

Excitation ions and neurotransmitter

- inward Na+, Ca++
- glutamate, aspartate

9

Inhibition ions and neurotransmitter

- inward Cl-
- outward K+
- GABA

10

MOA of anti-epileptics

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

11

How to choose an anti-epileptic

- based on seizure classification
- patient-specific variables
- characteristics of drug

12

Drugs that inhibit axonal transmission

- phenytoin
- carbamazepine
- valproate
- lamotrigine

13

Drugs that potentiate GABA receptors

- benzos
- phenobarb

14

Why do therapeutic drug monitoring?

- avoid toxicity
- optimize drug/ therapeutic response
- detect changes in pharmacokinetics
- monitor compliance

15

Classical AEDs

- phenytoin
- phenobarb
- carbamazepine
- valproate

16

Newer AEDs

- lamotrigine
- Levetiracetam

17

Drugs that modulate volatge dependent ion channels

- carbamazepine
- phenytoin
- valproid acid

18

How do benzos work?

- increase the frequency of GABA-mediated chloride channel openings

19

How does phenobarb work?

- prolongs GABA-mediated chloride channel openings
- block the voltage-dependent sodium channels

20

Pleiotropic AEDs

-Lamotrigine
- valproate

21

How does lamotrigine work?

- blocks sodium channels
- may interfere with glutamate release
- inhibits Ca ++ channels

22

How does valproate work?

- enhances GABA transmission
- blocks sodium channels
- augment K+ channels

23

Inducers of Cyt p450

- phenobarb
- phenytoin
- carbamazepine

24

Inhibitor of Cyt p450

Sodium valproate

25

How does phenytoin work?

- inhibits Na+ channels to inhibit generation of rapid AP

26

Adverse effects of phenytoin

- CNS sedation
- gum hyperplasia
- hirsuitism
- skin rash hypersensitivity

27

Interactions with phenytoin

- valproate displaces phenytoin from plasma proteins
- increase cyt p450

28

Adverse effects of carbamazapine

- diplopia and ataxia
- idiosyncratic skin reaction
- agranulocytosis and aplastic anaemia

29

Interactions with carbamazepine

- induces microsomal enzymes
- stimulates its own metabolism

30

Adverse effects of phenobarb

- CNS sedation
- skin rashes if allergic
- tolerance and physical dependence

31

Interactions with phenobarb

- stimulates cyt p450
- CNS depression with in combo with benzos

32

Adverse effects of valproate

- elevation of liver enzymes
- birth defects

33

Interactions with valproate

- displaces phenytoin from plasma proteins
- p450 inhibitor

34

Adverse effects of lamotrigine

- less CNS sedative
- potentially life-threatening dermatitis

35

Why might patient have cross-sensitivity to multiple AEDs?

- carbamazepine
- phenytoin
- phenobarb
Are all aromatic AED
- get oxidised to arene oxide (which is toxic)

36

Adverse effects of benzos

- CNS sedative
- tolerance, dependence

37

Definition of status epilepticus

5 minutes or more of continuous
- clinical or electrographic seizure activity
- recurrent seizure activity without recovery between

38

General measure in status epilepticus

- start treatment immediately
- ABCs
- blood glucose
- electrolytes and anticonvulsant levels

39

Stepwise management of status epilepticus

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

40

Problems with AEDs in pregnancy

- sodium valproate higher teratogenic potential
- folate supplementation before pregnancy considered
- pharmacokinetics change, so adjust dose

41

Problems with ARVs and epilepsy

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