Epilepsy Flashcards
What class of drugs are generally used to treat Epilepsy?
A. Anti-epileptic drugs (AEDs)
B. Analgesics
C. Mood-stabilising drugs
D. Anti-histamines
A. Anti-epileptic drugs (AEDs)
What is the goal of anti-epileptic drugs (AEDs)?
- Drug decreasing frequency/severity of seizures in epileptics
- Treats Sx not disease
- Goal: Maximise QOL w/o SEs
- No anti-epileptogenic drugs
Are there any drugs that cure the cause of epilepsy?
• No anti-epileptogenic drugs
List the cellular mechanisms of seizure generation.
- EPSPs
- Na+ influx
- Ca2+ currents
- Paroxysmal depolarisation
List the genera treatment targets for AEDs, as a class.
- Increase inhibitory NT: GABA
- Decrease excitatory NT: Glutamate
- Block voltage-gated inward positive currents: Na+ or Ca2+
- Increase outward positive current: K+
List the two main Neurotransmitters of the brain regarding epilepsy.
1) GABA
2) Glutamate
What is the process by which the main inhibitory NT in the brain mediates its affects?
Which enzyme degrades this NT.
- GABA binds to GABA-r ≈ opening and influx of Cl- ≈ hyperpolarization
- GABA transaminase breaks down GABA
What is the process by which the main excitatory NT in the brain mediates its affects?
Which enzyme degrades this NT.
Glutamate
• 1º excitatory NT
2 Types of Receptor:
• Ionotropic (ion-channels): Fast synaptic
- NMDA, AMPA, Kainate
- Gated Ca2+ and Na+ channels
• Metabotropic (GPCR): Slow synaptic
- Regulation of second messengers (cAMP and IP3)
- Modulation of synaptic activity
List the AEDs acting on Inotropic Glutamate receptors.
Give the three examples of this type of receptor and what ions it is permeable to.
- Phenytoin: Block NaVg (voltage-dependent sodium channels)
- Carbamazepine: Block NaVg
- Oxcarbazepine: Block NaVg and affects KVg (K+ efflux)
- Zonisamide: Block NaVg and T-type calcium channel
- Lamotrigine
AMPA/Kainate/NMDA
Ca2+ and Na+
What is the MOA of Lamotrigine?
Give its SEs.
- MOA: Inhibit NaVg
- Broad therapeutic profile
- SEs: Hypersensitivity reactions (skin rashes)
What is the MOA of sodium valproate?
Give its SEs.
- MOA: Unknown; increase GABA content of brain via inhibition of GABA transaminase + effect on NaVg
- SEs: Hair loss, teratogenicity, foetal syndrome (avoid in pregnancy), liver damage (rare)
Which AED is especially contraindicated in pregnancy or pre-conception.
What syndrome can this cause? What symptoms does this entail.
Sodium Valproate
Foetal Valproate Syndrome (FVS)
–> Foetal Valproate Syndrome: Spina bifida, CHDs, Cleft lip/palate, genital abnormalities, skeletal abnormalities, developmental delay
What is the MOA of Carbamazepine?
List its SEs.
- MOA: Block NaVg
- Uses: Partial seizures + trigeminal neuralgia
- SE: sedation, ataxia, mental disturbances, water retention
Which drug is a less toxic version of carbamazepine. Give its MOA and SEs.
Oxcarbazepine
• MOA: Block NaVg + effects on K+
• SEs: sedation
• Less toxic cf carbamazepine
What is the MOA of Topiramate?
Give its SEs.
How may you mitigate against the side effects of Topiramate?
- MOA: Enhances inhibitory effect of GABA + block NaVg + block CaVg
- SE: teratogenesis
- Slow titration to avoid side effects
What is the MOA of Tiagabine?
What are its SEs.
- MOA: GABA-uptake inhibitor
* SE: Dizziness and confusion
What is the MOA of Phenytoin?
Give the SEs of this drug.
- MOA: Block NaVg
- Uses: Most epilepsy and antidysrhythmic agent cf absence seizures
- Need monitoring: saturation kinetics thus monitoring needed
- Drug interactions common
- SEs: confusion, gum hyperplasia, skin rashes, anemia, teratogenesis, cerebellar syndrome, osteoporosis; Diplopia, Ataxia and Nystagmus (Vestibulocerebellar syndrome) = ‘DAN’
Which AED can cause Vestibulocerebellar syndrome?
Phenytoin
Diplopia
Ataxia
Nystagmus
–> DAN