Anticonvulsants HR Flashcards
What is the prevalence of epilepsy in the UK?
7-9% of the population
Recall the 5 types of GENERALISED seizure
- Tonic/clonic
- Absence
- Tonic/atonic
- Myoclonic
- Status epilepticus
Describe the order of events of a tonic/clonic seizure
loss of consciousness muscle stiffening (hence tonic) jerking/twitching (hence clonic) deep sleep wakes up (this seizure is what most people see in films etc)
What is the most common type of generalised seizure?
Tonic/clonic
Describe the presentation of an absence seizure
brief staring episodes with behavioural arrest (NO JERKY MOVEMENTS etc. its essentially just someone going into a ‘quiet state’ staring at something)
Describe the presentation of a tonic/atonic seizure
"Tonic" = sudden stiffening of muscles "Atonic" = loss of muscle control
basically tonic seizure but with just the muscle parts
Describe the presentation of a myoclonic seizure
Sudden, brief muscle contractions
BTEC tonic seizure
How can tonic/atonic seizures and myoclonic seizures be differentiated
Presentations similar therefore use EEG
Describe the presentation of a status epilepticus
More than 5 mins of chronic seizure activity
What is a partial/ focal seizure?
Seizure that begins within a particular area of brain and may spread out
Recall the types of partial/ focal seizure
Retained awareness = simple
Impaired awareness = complex
Briefly summarise the transmission events at glutaminergic synapses
VGSC and VGKC action –> AP
Glu stored in vesicle which is bound to presynaptic membrane via SV2A
Upon release, acts on excitatory receptors
Recall 4 approaches to inhibiting the excitatory effect of glutamate
Inhibit VGSCs
Inhibit VGCCs
inhibit SV2A docking protein
glutamate receptor antagonist
Give 2 examples of drugs that inihibit VGSCs in glutaminerguc neurons
Carbamazepine
Lamotrigine
Recall the MOA of carbamazepine
Stabilises VGSC in its inactive state
Pharmacokinetics of carbamazepine? -onset - DOA Selectivity of carbamazepine? Side effects?
Advantages: 1. Fast onset 2. Long DOA Disadvantages: 1. Low selectivity 2. Enzyme inducer ie activates many enzymes--> many DDIs (drug drug interactions)
Recall the indications for carbamazepine
Tonic/clonic seizures and partial/focal seizures
What are the side effects associated with carbamazepine in individuals with a certain HLA haplotype, and what is this HLA allele?
HLA-B*1502
Severe skin conditions
Stephen Johnson syndrome
Toxic epidermal necrolysis
Recall the MOA of lamotrigine
Pushes VGSCs into the inactive state
Suggest an advantage of lamotrigine over carbamazepine as an anticonvulsant
Lamotrigine has higher specificity for Glu neurons
Recall the indications for lamotrigine
Tonic/clonic seizures and absence seizures
Recall an anticonvulsant that acts by inhibiting Glu vesicle docking
Levetiracetam
Recall the MOA of levetirecetam
Binds SV2A to prevent Glu release
Recall the MOA of topiramate
Inhibits NMDA and kainate Glu receptors
Recall the indications for topiramate
Myoclonic seizures
Recall the general PK of anticonvulsant drugs
Fast onset and long t1/2 (long DOA)
Recall 2 anticonvulsant drugs that work by interacting with GABA transmission
Diazepam
Sodium valporate
What is the MOA of valporate?
Inhibits GABA-T (NOT GAT) to increase synaptic GABA levels
How is diazepam usually administered in a seizure?
Rectal gel
Recall the indications for diazepam
Status epilepticus
Recall the indications for valporate
All forms of epilepsy apart from SE
Recall the drugs that are indicated for tonic/clonic seizure treatment
Carbamazepine
Lamotrigine
Valporate
Recall the drugs that are indicated for absence seizure treatment
Ethosuximide
Lamotrigine
Valporate
Recall an anticonvulsant that acts via VGCC interference
Ethosuximide
What type of VGCC are found in the CNS?
T-type (transient)
Recall the indications for ethosuximide
ONLY absence seizures
Recall the drugs that are indicated for tonic/atonic seizure treatment
Valporate
Recall the drugs that are indicated for myoclonic seizure treatment
Levetiracetam
Topiramate
Valporate
Recall the drugs that are indicated for simple partial seizure treatment
Valporate
Carbamazepine
Lamotrigine
Levetiracetam
What is a seizure?
What is epilepsy?
Seizures are sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex ie UNCOORDINATED rapid firing of neurones in the brain (caused by INCREASE in EXcitatory neurotransmission or DECREASE in INhibitory neurotransmission)
Epilepsy is the tendency to get recurrent unprovoked seizures
When are the two peaks in incidence of epilepsy and what are they usually caused by?
Young adults – where genetic predispositions begin to manifest
Later years – when patients start getting brain injuries e.g. stroke can cause seizures after the stroke due to brain damage
Summarise the main mechanisms of anti-convulsants
Inhibit Glutamate mediated excitation
- VGSC inhibitor
- VGCC inhibitor
- SV2A inhibitor (synaptic vesicle protein)
- glutamate receptor antagonist
Enhancing GABA mediated inhibition
- benzodiazepines (Positive Allosteric Modulators)
- GABA transaminase inhibitors (stop GABA breakdown)
