Anti-Epileptic Drugs Flashcards
Epilepsy can be classified into which two main types?
Partial seizures
Generalised seizures
What is another name for partial seizures?
Focal seizures
Partial seizures can be sub-divided into what categories?
What is the difference between the two?
Simple (conscious)
Complex (impaired consciousness)
During a focal seizure, symptoms reflect what?
The area affected by the seizure
Including involuntary motor disturbance, behavious change
Generalised seizures can be subdivided into which types?
How do these types differ
Tonic-clonic seizure: rigidity followed by muscle contraction
Absence seizure: no shaking, unable to respond to stimuli
What is status epilepticus?
A prolonged seizure beyond 5 minutes or as a series of seizures without any recovery interval
List some of the dangers associated with severe epilepsy
Injury relating to fall/crash
Hypoxia
Sudden death in epilepsy
What is the difference between primary and secondary epilepsy?
Primary: no identifiable cause (idiopathic)
Secondary: caused by another medical condiiton e.g. vascular disease, tumour
List some precipitating factors of epilepsy
Sensory stimuli: flashing lights
Brain disease/Trauma: head injury, stroke, drugs, lesion
Metabolic disturbance: Hypo-glycaemia,calcaemia,natraemia
Infections: febrile convulsions in infants
Therapeutics: AEDs + polypharma
What are the two established therapeutic targets for anti-epileptic drugs?
Voltage-gated sodium channel blockers
Enhanced GABA-mediated inhibition
Where do volatage gated sodium channel blockers bind to elicit their effect?
The inside of the membrane, on domain 1V
Briefly explain the mechanism of VGSC blockers in the treatment of epilepsy
VGSc blockers access the binding site during depolarisation- making it voltage dependent
This prolongs the inactivated state
Firing rate returns to normal
VGSCs have three states, what are they?
At which stage to VGSC blockers act?
- Open (resting)
- Closed (activated)
- Inactivated (closed to Na+ via inactivation gate)
What does Carbamezepine work?
It prolongs VGSC inactivation state to allow the firing rate to go back to normal
List some adverse drug reactions of carbemazepine
CNS effects: dizziness, drowsiness, ataxia, numbness, tingling
GI effects: vomiting
CVS: variation in BP
What feature of carbamezepine means that it can effect other drugs?
It is a strong inducer of CYP450
Which seiure types may be treated with carbamezepine?
All partial
Generalised: Tonic-clonic
Not: absence
At therapeutic levels, what pharmacokinetics does Phenytoin display?
What does this mean for its use clinically?
Non-linear
Has a very variable half life (6-24 hours)
Means that therapeutic dose is very variable
List some ADRs of Pheytoin
CNS: dizziness, headache, nervousness
Gingival hyperplasia (20%)
Rashes, hypersensitivity
What kind of monitoring is involved in the use of Phenytoin?
Monitoring of free concentration in plasma
Which type of seizure can be treated with Pheytoin?
Generalised tonic-clonic
All: partial seizures
NOT: absence seizures
Why is Lamotrigine increasingly being used as a first line drug, over Pheytoin and Carbamezepine, for the treatment of epilepsy?
It is well absorbed
It displays linear pharmacokinetics
Fewer ADRs and DDIs
May be safer in pregnancy
Which seizures can Lamotrigine be used to treat?
Partial seizures
Generalised: tonic-clonic AND absence seizures
+other subtypes
What is the general mechanism of GABA mediated inhibition of excitatory neurones?
GABA (or GABA agonist) binding increases the Cl- current into the neurone
This increases the threshold for AP generation
Making it harder for AP to be generated
What is Valporate’s mechanism of action?
1) It is a weak inhibitor of GABA inactivation enzymes and a weak activatory of GABA synthesising enymes which both lead to increased GABA
2) It is a VGSC blocker and a weak Ca2+ blocker- both of which decrease discharge firing
What kind of pharmacokinetics does Valporate display?
What is its half life?
Linear kinetics
Half life: 15 hours
What drug monitoring is required in patients that are treated with Valporate?
Monitor free plasma concentration- though this does not correlate well with efficacy
Blood, hepatic and metabolic function should be monitored
What types of epilepsy can be treated with Valporate?
Partial seizures
Generalised: tonic-clonic AND absence seizures
What is the mechanism of action of Benzodiazepines?
They are positive allosteric effectors of GABA receptors
Act on GABA receptor to increase Cl- current into neurone
Increases the threshold for AP generation
Harder to generate AP
List some adverse drug reactions of Benzodiazepines
Sedation
Tolerance with chronic use
Respiratory/CNS depression
Which epilepsy types can be treated using Benzodiazepines?
Status epilepeticus- only SHORT-term
Absence seizure- only SHORT-term
What are some importants things to consider when using anti-epileptic drugs during pregnancy?
To consider each patient individually
Take stage of pregnancy into account
Balance the risk of treatment with the risk of harm due to seizure
Valporate poses the risk of what if used during pregnancy?
Neural tube defects
The use of multiple AEDs during pregnancy is associated with an increased risk of what?
Tetatogenicity
Which dietary supplementation can be taken by women taking AEDs to reduce the risk of neural tube defects in the baby?
Folate
Which dietary supplementation can be taken by women taking AEDs to reduce the risk of coagulopathy and cerebral haemorrhage in the baby?
Vitamin K
What are the main priorities when dealing with a patient with status epilepticus?
ABCDE
Exclusion of hypoglycaemia
High AED doses may result in hypoventilation
ITU may be required: paralysis and ventilation
