Anticonvulsant Drugs

Front 1

Anticonvulsants: Mechanism of Action

Back 1

(i) enhancement of GABAergic transmission in epileptic foci
(ii) dimunition of neuronal membrane excitability and ion permeability**most drugs

Front 2

Potassium Bromide
1.half life
2.MOA
3.toxicity
4.examples

Back 2

1.very long half-life (25 days!!) thus steady state levels are achieved after only about 7-10 weeks (~3-4 half lives)
2.Br replaces Cl resulting in neuronal hyperpolarisation
3. toxicity includes vomiting, anorexia, constipation, sedation and ataxia
4. 'Bromapex' liquid; 'Epibrom' tablets

Front 3

Phenobarbitone
1.MOA
2.Major Effects
3.Absorption/Fate
4.Toxicity

Back 3

1. agonistic at GABA receptor gated chloride channel, influx of chloride ion results in neuronal hyperpolarisation
2.control epilepsies which do not cause obvious sedation; limits spread of discharges and elevats thrshold for excitation; depresses all parts of CNS-most effective at brain stem and spinal chord; motor discharges are inhibited at doses which leave sensory function intact
3. PO complete (variable); excreted 25% unchanged (alkaline urine enhances excretion); can produce tolerance and dependance;
4.liver disfunction-elevated liver enzymes (ALT and ALP)

Front 4

Give 7 examples of Anticonvulsants.

Back 4

1. Potassium Bromide
2. Phenobarbitone
3. Methylphenobarbitone
4. Primidone
5. Diphenylhydantoin ("Dilantin")
6. Clonazepam ("Rivitrol")
7. Valproic Acid ("Valpro")

Front 5

Methylphenobarbitone
1.differences to phenobarbitone?

Back 5

1. methyl derivative;
releases phenobarbitone on hepatic demethylation;
dose administered approximately the same but plasma levels may be lower (particularily after PO admin)

Front 6

Primidone ("Mysoline")
1.Absorption
2.adverse effects
3.toxicity

Back 6

1. absorption is rapid and complete; drug converted in vivo to phenobarbitone and PEMA (active)-both are anticonvulsants (PEMA=low potency)
2. causes greater hepatotoxicity and behavioural effects
3. anorexia, ataxia, tachycardia, hyperventilation, progressive hepatic damage, polyphagia, polydipsia, polyuria

Front 7

Diphenylhydantoin ("Dilantin")
1.MOA
2.Absorption (why is it hard to use in the dog?)
3. Alternative use

Back 7

1. inhibits flux of sodium in the resting state and during an action potential (similar to local anaesthetics)
2. absorption slow and variable + rapidly metabolized and excreted
3. used also as an antiarrythmetic agent

Front 8

Clonazepam ("Rivitrol")
1. benefits
2. suitable for maintenence use?

Back 8

1. plasma concentrations can be maintained at adequate levels
2. no-tolerance develops withing days/weeks (slower than Diazepam)

Front 9

Valproic Acid ("Valpro")
1. MOA
2. Uses
3. Disadv.

Back 9

1. product of rational drug design-potentiates GABA function through inhibition of GABA metabolism (INHIBITS GABA TRANSAMINASE); some action at sodium channels and inhibits HMEs
2. used in humans for "add-on" seizure control and mania
3. multiple side effects