eLFH - Drugs used to treat Epilepsy Flashcards
Cause of seizures
Repetitive neuronal discharges in CNS
Two main mechanisms of action of anticonvulsants
Action on CNS Na+ channels
Potentiating neurotransmitter GABA
Two main mechanisms for anticonvulsants acting on CNS Na+ channels
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
Drugs which inhibit inactive fast Na+ channels examples
Phenytoin
Sodium valproate
Drugs which stabilise presynaptic Na+ channels examples
Lamotrigine
Three main mechanisms for anticonvulsants to potentiate GABA
Facilitating GABA
GABA agonists
Inhibiting GABA transaminase
Facilitating GABA mechanism
Opening Cl- channels causes cell hyperpolarisation
Therefore less excitable and reduces neuronal transmission
Example of drugs which facilitate GABA
Benzodiazepines
Barbiturates
GABA agonist examples
Baclofen
Acamprosate
Used for their other effects
Inhibiting GABA transaminase mechanism
GABA transaminase is the enzyme which catalyses GABA breakdown
Example of drugs which inhibit GABA transaminase
Sodium valproate
Vigabatrin
Phenytoin mechanism of action
Binds to inactive or refractory fast Na+ channels after opening
Therefore most effective against channels opening and closing at high frequency
Phenytoin administration
PO or IV
Phenytoin monitoring
Narrow therapeutic window
Monitor plasma levels
Phenytoin uses
Generalised seizures
Partial seizures
Status epilepticus
Trigeminal neuralgia
Class 1b anti-arrhythmic - used for digoxin toxicity arrhythmias
Side effects of phenytoin
Hirsutism
Gum hyperplasia
Acne
Peripheral neuropathy
Megaloblastic anaemia
Symptoms of phenytoin toxicity
Ataxia
Nystagmus
Paraesthesia
Slurred speech
Cautions for phenytoin use
Teratogenic
cP450 inducer
Phenytoin pharmacokinetics
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
Phenytoin half life
~ 24 hours
Sodium valproate administration
IV or PO
Sodium valproate uses
Partial seizures
Generalised seizures
Myoclonic seizures
Chronic pain - trigeminal neuralgia
Sodium valproate mechanism of action
Binds to inactive fast Na+ channels after opening
AND
Inhibits GABA transaminase
Side effects of sodium valproate
Liver dysfunction
GI upset
Alopecia
Thrombocytopenia
Teratogenic - neural tube defects
Sodium valproate pharmacokinetics
90% protein bound
Liver metabolism
Renal excretion
Use of Lamotrigine
In pregnancy - less teratogenic
Gabapentin mechanism of action
Increases GABA synthesis in brain
Modulates voltage gated Ca2+ channels
Inhibits excitatory glutamate
Increases 5-HT (serotonin) levels in CNS
Gabapentin use
Almost exclusively used in chronic pain
Types of GABA receptor
GABA A - chloride ion channel increasing intracellular Cl-
GABA B - G protein coupled receptor which increases intracellular K+
Benzodiazepine pharmacokinetics
Lipid soluble
Active and inactive metabolites
Renally excreted
Benzodiazepine effects on respiratory system
Depressant
Reduces TV and RR
Benzodiazepine effect on cardiovascular system
Relatively cardio stable
Slight reduction in SVR but slight increase in HR
