eLFH - Drugs used to treat Epilepsy

Question 1

Cause of seizures

Answer 1

Repetitive neuronal discharges in CNS

Question 2

Two main mechanisms of action of anticonvulsants

Answer 2

Action on CNS Na+ channels

Potentiating neurotransmitter GABA

Question 3

Two main mechanisms for anticonvulsants acting on CNS Na+ channels

Answer 3

Inhibiting inactive fast Na+ channels - selective for abnormal neuronal discharges as these drugs have affinity for Na+ channels that are opening and closing rapidly

Stabilising presynaptic Na+ channels by inhibiting release of excitatory neurotransmitters

Question 4

Drugs which inhibit inactive fast Na+ channels examples

Answer 4

Phenytoin

Sodium valproate

Question 5

Drugs which stabilise presynaptic Na+ channels examples

Answer 5

Lamotrigine

Question 6

Three main mechanisms for anticonvulsants to potentiate GABA

Answer 6

Facilitating GABA

GABA agonists

Inhibiting GABA transaminase

Question 7

Facilitating GABA mechanism

Answer 7

Opening Cl- channels causes cell hyperpolarisation

Therefore less excitable and reduces neuronal transmission

Question 8

Example of drugs which facilitate GABA

Answer 8

Benzodiazepines

Barbiturates

Question 9

GABA agonist examples

Answer 9

Baclofen

Acamprosate

Used for their other effects

Question 10

Inhibiting GABA transaminase mechanism

Answer 10

GABA transaminase is the enzyme which catalyses GABA breakdown

Question 11

Example of drugs which inhibit GABA transaminase

Answer 11

Sodium valproate

Vigabatrin

Question 12

Phenytoin mechanism of action

Answer 12

Binds to inactive or refractory fast Na+ channels after opening

Therefore most effective against channels opening and closing at high frequency

Question 13

Phenytoin administration

Answer 13

PO or IV

Question 14

Phenytoin monitoring

Answer 14

Narrow therapeutic window

Monitor plasma levels

Question 15

Phenytoin uses

Answer 15

Generalised seizures

Partial seizures

Status epilepticus

Trigeminal neuralgia

Class 1b anti-arrhythmic - used for digoxin toxicity arrhythmias

Question 16

Side effects of phenytoin

Answer 16

Hirsutism

Gum hyperplasia

Acne

Peripheral neuropathy

Megaloblastic anaemia

Question 17

Symptoms of phenytoin toxicity

Answer 17

Ataxia

Nystagmus

Paraesthesia

Slurred speech

Question 18

Cautions for phenytoin use

Answer 18

Teratogenic

cP450 inducer

Question 19

Phenytoin pharmacokinetics

Answer 19

90% protein bound

Liver metabolism to inactive metabolites

Renal excretion

Zero order kinetics replace First order kinetics at high drug concentrations due to enzyme saturation

Question 20

Phenytoin half life

Answer 20

~ 24 hours

Question 21

Sodium valproate administration

Answer 21

IV or PO

Question 22

Sodium valproate uses

Answer 22

Partial seizures

Generalised seizures

Myoclonic seizures

Chronic pain - trigeminal neuralgia

Question 23

Sodium valproate mechanism of action

Answer 23

Binds to inactive fast Na+ channels after opening

AND

Inhibits GABA transaminase

Question 24

Side effects of sodium valproate

Answer 24

Liver dysfunction
GI upset
Alopecia
Thrombocytopenia
Teratogenic - neural tube defects

Question 25

Sodium valproate pharmacokinetics

Answer 25

90% protein bound Liver metabolism Renal excretion

Question 26

Use of Lamotrigine

Answer 26

In pregnancy - less teratogenic

Question 27

Gabapentin mechanism of action

Answer 27

Increases GABA synthesis in brain Modulates voltage gated Ca2+ channels Inhibits excitatory glutamate Increases 5-HT (serotonin) levels in CNS

Question 28

Gabapentin use

Answer 28

Almost exclusively used in chronic pain

Question 29

Types of GABA receptor

Answer 29

GABA A - chloride ion channel increasing intracellular Cl- GABA B - G protein coupled receptor which increases intracellular K+

Question 30

Benzodiazepine pharmacokinetics

Answer 30

Lipid soluble Active and inactive metabolites Renally excreted

Question 31

Benzodiazepine effects on respiratory system

Answer 31

Depressant Reduces TV and RR

Question 32

Benzodiazepine effect on cardiovascular system

Answer 32

Relatively cardio stable Slight reduction in SVR but slight increase in HR