Epilepsy- Generalised Flashcards
1
Q
For epilepsy tonic-clonic lasting more than 5 minutes
A
- Give buccal midazolam
2
Q
Benzodiazepines
Common indications
A
- Seizures and status epilepticus
- Alcohol withdrawal
- Sedation for interventional procedures
- Anxiety and insomnia short term
3
Q
Benzodiazepines
MOA
A
- Bz target the gamma-aminobutyric acid type A (GABA-A) receptors
- The GABA-A receptor is a chloride channel that opens in response to binding by GABA, the main inhibitory neurotransmitter in the brain
- Opening of the channel allows Cl- to flow into the cell, making them more resistant to depolarisation
- BZs facilitate and enhance the binding of GABA to GABA-A receptors
- This has a widespread depressant effect on the CNS (Synaptic transmission)= reduce anxiety, sleepiness, sedation and anticonvusive effects
- Ethanol also acts on GABA-A receptors- why this can be used for withdrawal
4
Q
Benzodiazepines
Warnings
A
- The elderly are more susceptible to the effects of BZs so should have a lower dose
- Avoid in respiratory impairment or neuromuscular disease
- They should be avoided in Liver failure as they may precipitate hepatic encephalopathy; if their use is essential, lorazepam may be the best choice= reduced liver clearance
5
Q
Benzodiazepines
Interactions
A
- The effect of BZs are additive to those of other sedating drugs, including alcohol and opioids
- Most depend on CYPP450 elimination. Therefore, Inhibitors (amiodarone, macrolides, fluconazole) may increase there effects
6
Q
Sodium Valproate
Common indications
A
- Epilepsy- a first choice drug for control of generalised or absence seizures and a treatment for focal seizures
- Bipolar disorder
7
Q
Sodium Valproate
MOA
A
- The mechanism of action of Sodium Valproate appears to be a weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability
- It also increases the brain content of GABA which increases inhibitory neurotransmission
8
Q
Sodium Valproate
Adverse effects
A
- The most common dose-related adverse effects are GI upset
- Neurological and psychiatric effects (tremor, ataxia and behaviour abnormalities)
- Thrombocytopenia and transient increase in liver enzymes
- Hypersensitivity reactions include hair loss, with subsequent regrowth being curlier than the original hair
- Rare, life-threatening idiosyncratic adverse effects include severe liver injury, pancreatitis, bone marrow failure and antiepileptic hypersensitivity reaction
9
Q
Sodium Valproate
Warnings
A
- Valproate should be avoided in women of child-bearing age, conception and first trimester of pregnancy
- The antiepileptic drug associated with fetal abnormalities including neural tube defects, craniofacial, cardiac and limb abnormalities
- Avoid in hepatic impairment, severe renal impairment
10
Q
Sodium Valproate
Interactions
A
- drugs metabolised by P450 enzymes- warfarin and other antiepileptic drugs
- P450 inducers (phenytoin, CBZ) -
- P450 inhibitors and drugs that displace valproate from binding site (e.g. aspirin)
- The efficacy of antiepileptic drugs is decreased by drugs which reduce seizure threshold (SSRI etc)
11
Q
Sodium Valproate
Communication
A
- Reduce GI upset by taking valproate with food
- Seek urgent medical advise- lethargy, loss of appetite, vomiting or abdominal pain (liver poisoning) OR bruising, high temperature or mouth ulcers (blood abnormalities)
- For women, discuss contraception and pregnancy
- Advise patients not to drive unless they have been seizure free for 12 months
*
12
Q
Valproate
Monitoring
A
- Monitor efficacy by comparing seizure frequency before and after starting a treatment or dose adjustment
- Monitor safety by patient report
- Measurement of liver function (including prothrombin time) before and during the first 6 months of treatment may be useful
- Plasma valproate concentrations (usually 40-100 mg/L) do not correlate well with therapeutic effect
- They should therefore only be measured to check or adherence or toxicity
13
Q
Phenytoin
Common indications
A
- To control seizures in status epilepticus where BZs are ineffective
- To reduce the frequency of generalised or focal seizures in epilepsy although drugs with fewer adverse effects and interactions
14
Q
Phenytoin
MOA
A
- The mechanism of action of phenytoin is incompletely understood
- Phenytoin reduces neuronal excitability and electrical conductance among brain cells, which inhibits the spread of seizure activity
- It appears to do this by binding to neuronal Na+ channels in their inactive state, prolonging inactivity and preventing Na+ influx into the neuron
- This prevents a drift in membrane potential from the resting (-70) to the threshold (-55) value required to trigger an action potential
- A similar effect in cardiac Purkinje fibres may account for both anti arrrhythmic and cardiotoxic effects of phenytoin
15
Q
Phenytoin
Adverse effects
A
- Long term phenytoin treatment can cause a change in appearance with skin coarsening, acne hirsutism and gum hypertrophy
- Dose-related Neurological effects include cerebellar toxicity (Ataxia, discoordination) Impaired cognition or consciousness
- Phenytoin can cause haematological disorders and osteomalacia by inducing folic acid and vitamin D metabolism
- Hypersensitivity reactions to phenytoin range from mild skin rash to the rare life-threatening antiepileptic hypersensitivity syndrome
- Phenytoin toxicity (due to overdose or injudicious IV infusion) can cause death through CV collapse and respiratory depression
