Anticonvulsants Flashcards
How do anticonvulsants work
Reducing high frequency neuronal firing by modifying activity of neurotransmitters
1. Increasing GABA activity (main inhibitory neurotransmitter)
2. Decreasing excitatory glutamate
Modifying activity of ion channels
1. Voltage gated sodium channels
2. Calcium channels
How do anticonvulsants work
Reducing high frequency neuronal firing by modifying activity of neurotransmitters
1. Increasing GABA activity (main inhibitory neurotransmitter)
2. Decreasing excitatory glutamate
Modifying activity of ion channels
1. Voltage gated sodium channels
2. Calcium channels
Adverse effects of phenobarbital
Hypersensitivity in children
Agitation and confusion in elderly
Systemic hypersensitivity reaction
Sedation (decreases over time)
Indications of phenobarbital
All epilepsy except ABSENCE and MYOCLONIC seizures
MOA of phenobarbital
GABA receptor mediated
Drug interactions of phenobarbital
Strong inducer of drug metabolising enzymes and transporters
Adverse effects of phenytoin
Systemic hypersensitivity reaction
Cardiac arrhythmia
Cerebella signs (nystagmus, ataxia)
Gum hypertrophy
Hirsutism and acne
MOA of phenytoin
Prolongs inactivation of voltage sensitive Na channel
Which anticonvulsants increases drug concentration exponentially in plasma
Phenytoin
-non linear kinetics, zero order
=toxicity
Dose of phenytoin in our institution
300mg/day (yields 10mcg/ml), if seizures continues add 25-30 mg
MOA of Carbamezapine
Prolongs inactivation of volatage gated sensitive Na channel
Potentials postsynaptic actions of GABA
Adverse reactions of Carbamezapine
Aplastic anaemia (haematological toxicity)
Systemic hypersensitivity reaction
Drowsiness
Vertigo
Ataxia
Diplopia
Blurred vision
MOA of sodium valproate
Prolongs inactivation of voltage-sensitive Na channels
Increases GABA synthesis
Adverse effects of NaValproate
Teratogenic
Idosynthetic Hepatotoxicity
PCOS and menstrual irregularities
Alopecia
Ataxia
Sedation
Bone marrow suppression
Which anticonvulsants can be used in absence seizures
Valproate
Drug interaction of valproate
Inhibits glucuronidation (potent inhibitor)
What to consider before starting ACD in a patient with first time seizure
Risk of recurrence
Benefit expected from immediate anticonvulsant drug therapy on the risk of recurrent seizure
Side effect profile of various ACD based on individuals age and comorbidities
Patient values and preference
Risk of seizure recurrence after first unprovoked seizure in epilepsy
21-45% in the first 2 years
ACD reduces risk of recurrence but lowers quality of life
Risk of seizure recurrence after first unprovoked seizure in epilepsy
21-45% in the first 2 years
RF for recurrence of seizures
Structural brain lesions
Abnormal Neuro exam
Presenting with status epilepticus
Strong family history
Epileptiform abnormalities on EEG (EEG is specific for epilepsy)
Factors to consider when choosing ACD
Type of seizure
Drug-drug potential interactions
Comorbidities conditions
Pregnancy risk
Cost of drug
(Commence at low dose and gradually build to therapeutic dose)
What do you do if there is failure to control on initial management
Confirm adherence
Is drug concentration therapeutic
If so then taper off slowly and slowly introduce alternative drug
Combination therapy should be a last resort by a specialist
Which anticonvulsants are safe in childbearing
Carbamezapine
Folate supplementation needed before conception
Pregnancy reduces concentration in 2nd and 3rd trimester, adjust dose according to concentration results
Potential drug-drug interaction of ACDs
Strong inducers and oral contraceptives
Strong inducers and many ARVs
Valproate inhibits glucoronidation of lamotrigine
When to discontinue anticonvulsant
Pt that have been seizure free for >2years
What is status epilepticus
Seizure lasting more than 30min with no intervening periods of recovering consciousness
Indications of lamotrigine
Partial and generalised
Focal
Juvenile myoclonic epilepsy (JME)
Lennox Gastaut
Definition of epilepsy
Atleast 2 unprovoked seizures occurring more than 24hours apart
1 unprovoked seizure and a >60% probability of further seizures occurring over the next 10years
