Anti-epileptics Flashcards
What is epilepsy?
Episodic periodic discharge of abnormal high frequency electrical activity in brain leading to seizure (diagnosis requires recurrent seizures)
What is required for diagnosis?
A single seizure is not sufficient to make a diagnosis – you need recurrent seizures. This is because acute medical emergencies can present as tonic-clonic seizures – either following trauma, infection or metabolic disturbance.
What are partial seizures? Simple? Complex?
• Partial – discharges begin in a localised area of the brain, symptoms reflect the area affected.
Due to loss of local inhibitory homeostasis leading to focal discharges.
o Simple partial seizures – person remains conscious
o Complex partial seizures – impaired consciousness
What are symptoms of partial seizures?
- Involuntary motor disturbance
- Behavioural change
- Unusual smell or taste, déjà vu
- May become secondarily generalised
What are generalised seizures?
• Generalised – spread through both hemispheres with a loss of consciousness
o Grand mal (tonic clonic)
o Petit mal (absence)
Tonic-clonic
The person will usually emit a short, loud cry as the muscles in the chest contract and the air rushes between the vocal cods, making a sound. This cry does not indicate pain. The muscles will stiffen (tonic phase), causing him/her to fall to the floor. Increased pressure on the bladder and bowel may cause wetting (urinary incontinence) or soiling (fecal incontinence). The child may bite the tongue, which may cause bleeding.
The extremities will then jerk and twitch rhythmically (clonic phase). Saliva that has not bene swallowed during the seizure may froth at the mouth. Breathing may be irregular as the respiratory muscles may be affected. The person will regain consciousness slowly.
Absence
It consists of a period of unconsciousness with a blank stare. It may look like the person is daydreaming. The person may lose muscle control and make repetitive movements such as:
chewing movements rapid breathing rhythmic blinking slight movements or tugging at clothing Absence seizures are brief, usually lasting only two to 10 seconds. There is no confusion after the seizure, and the person can usually resume full activity immediately.
What os status epileptics? Treatment?
prolonged (over 5 minutes) seizure that is a medical emergency, untreated status epilepticus can lead to brain damage or death (SUDEP – sudden death in epilepsy)
In this situation ABC should be prioritised and hypoglycaemia ruled out. Lorazepam is the first line drug in this acute situation (or can be rectal diazepam but its half-life is shorter or buccal midazolam). IV Phenytoin can be given if no repsonse but requires careful cardiac monitoring. If still no response then referral to ITU, sedation and ventilation is the last resort.
What can severe epilepsy lead to?
- Physical trauma from falling/seizing
- Hypoxia
- SUDEP
- Brain damage
- Psychiatric disorder
- ADRs to medication
- Suffering stigma of the condition and loss of livelihood (eg unable to do certain things because of worry of seizure – particularly driving)
What can precipitate seizures in epilepsy?
• Sensory stimuli
o Flashing lights and strobes, other periodic sensory stimuli
• Brain disease and trauma o Brian injury o Stroke & haemorrhage o Drugs & alcohol o Structural abnormalities and lesions
• Metabolic disturbances
o Hypoglycaemia
o Hypocalcaemia
o Hyponatreamia
• Infections
o Which lead to febrile convulsions in infants
• Therapeutics
o Some drugs lower seizure thresholds
o Polypharmacy can lower levels of AEDs and decrease efficacy
What are primary and secondary epilepsy
Primary causes of epilepsy is just the individual having a tendency towards seizures (this is about 2/3 of epileptics) – there is no identifiable cause, may be due to channelopathies
Secondary epilepsy is when there is a distinct cause, such as metabolic disturbance, stroke, meningitis, tumour.
What are the main types of anti-epilepsy drugs? Examples?
Voltage Gated Sodium Channel Blockers (lamotrigine, phenytoin, carbamazepine, valproate)
Enhancing GABA mediated (barbiturates, benzodiazepines, sodium valproate)
Describe the action of volatge gated sodium channel blockers
• Drug will bind to VGSC on the inside when it is in the inactivated state and keep it in that inactivated state preventing it from becoming active and transmitting sodium therefore reducing activity in highly active neurones. Once electrical activity returns to normal it will unbind
Reduces the probability of spiking activity by prolonging the inactivation state.
What are uses of the voltage gated sodium channel blockers?
Generalised Tonic-Clonic seizures
Partial seizures
NOT absence seizures
describe pharcokinetics of carbamazepine?
Well absorbed, protein bound, linear excretion.
Half life falls with use as it induces the CYP450 enzymes which metabolise it – dose to effect
CYP450 also metabolises it so the longer it is taken for the shorter the half-life becomes
What are ADRs of carbamazepine?
Dizziness Drowsiness Ataxia Motor disturbance Numbness Tingling GI upset and vomiting Variation in BP Contraindicated in AV conduction problems Rashes Hyponatraemia Neutropenia
What are DDIs of carbemazepine
CYP inducer – decreases the efficacy of warfarin, phenytoin (which also increases the plasma concentration of carbamazepine by competitive protein binding), systemic corticosteroids, oral contraceptives
Antidepressants (SSRIs, MAOIs, tricyclics) interfere with its action)
Describe the pharmacokinetics of phenytoin
Well absorbed.
Highly protein bound (90%).
Induces CYP450 but different enzymes induced to those which metabolism phenytoin
Non-linear elimination at therapeutic dose, variable half-life
ADRs of phenytoin
Many – CNS include dizziness, ataxia, headache, nystagmus, nervousness
Gingival hyperplasia
Hypersensitivity and Stevens Johnson
DDIs of phenytoin
Competitive binding with valproate so mono therapy better, NSAIDs, salicylate – increases plasma levels.
Decreases effect of oral contraceptives.
Cimetidine increases the effect of phenytoin.
Describe the pharmacokinetics of lamotrigine
well absorbed with linear PKs and a half-life around 24 hours
o No CYP450 induction
ADRs of lamotrigine
less marked – dizziness, ataxia, somnolence, nausea, rashes
Seems safer in pregnancy
DDIs of lamotrigine
Oral contraceptives reduce plasma level.
Valproate increases plasma level due to competitive binding.
What is used as first line
Lamotrigine
GABA medicated inhibitor drugs are not first line due to side effects
What is the function of enhancing GABA medicated inhibition?
Post-synaptic inhibition – by potentiating the action of GABA (positive allosteric binding). This increases the chloride current into the cell, therefore hyper polarising the neurone and increasing the threshold for action potential generation and makes the membrane potential more negative
REduces likelihood of epileptic acitivty
MOA of benzodiazepine?
Post-synaptic inhibition – by potentiating the action of GABA (positive allosteric binding). This increases the chloride current into the cell, increasing the threshold for action potential generation and makes the membrane potential more negative
