COMMONEST ASMs
This page doesn’t discuss all ASMs and isn’t an exhaustive pharmacology resource.
Focus is on the common medications and practically important aspects.
Epilepsy.com is more expansive resource with more ASMs
TIER 1 ASMS
BENZODIAZEPINES
> Mechanism: bind to GABA-A receptor and increase membrane permeability to Cl-
> This magnifies the inhibitory action of GABA on neuronal excitability
> Cannot be used in the long term due to the development of tolerance
> Sudden discontinuation of long term benzodiazepines can cause withdrawal seizures
> Side effects: drowsiness/sedation, tolerance, hypotension, respiratory depression / airway compromise, confusion, delirium, amnesia
> Need to be given over at least 2 minutes, as rapid injection can cause respiratory depression or hypotension
DOSE
5-10 mg IV/IM OR 5-10 mg buccally/ intranasally over 2 minutes
PROS
Can be given when IV access is not available
CONS
Confusion, delirium
In higher doses causes airway compromise
Duration of action means neuro exam confounded for a while after administering
Amnestic properties
DOSE
4 mg or 0.1 mg/kg IV over 2 minutes, repeat after 5 minutes if required
PROS
Longer acting than others in class, so decreases risk of seizure recurrence
CONS
Not readily available in Australia in injectable form
DOSE
10 mg IV OR 10-20 mg rectally, repeat after 10-15 minutes if required.
Over 2 minutes. Rapid injection can cause respiratory depression or hypotension
PROS
Can be given when IV access is not available
CONS
Delayed respiratory depression can occur with rectal administration
DOSE
1 mg IV
Dilute in 1 mL of water, then give over 2 minutes
TIER 2 ASMS
Mechanism
Unknown. May modulate GABA and glutamate release. May bind to synaptic vesicle protein 2A
Dose
For ongoing SE, 60 mg/kg IV (max 4.5 g) over 15 minutes
Pros
Minimal drug interactions
Less side effects than other Tier 2 therapies
Cons
May cause:
> Dizziness
> Headache
> Irritability, mood changes including suicidal ideation
> Loss of strength and energy, lethargy
> Loss of coordination
Rare but more serious:
> Anaphylaxis
> Stevens-Johnson syndrome, toxic epidermal necrolysis
Mechanism
Sodium channel blockade. Thus prevents repetitive neuronal discharge.
Dose
20mg/kg IV, no faster than 50 mg /min (e.g. over 45 minutes)
Pros
Minimal drug interactions
Less side effects than other Tier 2 therapies
Cons
IV formulation in 40% propylene glycol; this causes hypotension & arrhythmia, hence need for slow administration
Many interactions SEE
May cause:
> Nystagmus
> Decreased coordination
> Shaking of the hands
> Slowed thinking and movement
> Memory problems
> Slurred speech
> Poor concentration
> 10% get rash
> Deranged LFT’s
Rare but more serious:
> Anaphylaxis
Mechanism
Increases sodium channel inactivation.
Increases GABA by inhibiting GABA transaminase. May increase GABA synthesis by activating GAD
Dose
40 mg/kg IV (max 3 g) over 5-10 minutes
Pros
Non-sedating
Most have no side effects
Cons
Should be avoided in hepatic impairment.
May cause:
> Lethargy, mental slowing
> Dizziness
> GI upset including vomiting
> Tremor
> Hair loss
> Weight gain
> Changes in behavior (depression in adults, irritability in children)
Rare but more serious:
> Liver failure
> Thrombocytopenia and bleeding
> Hyperammonaemic encephalopathy
> Pancreatitis
> Anaphylaxis
TIER 3 ASMS
Mechanism
GABA-A agonist
Dose
1-2 mg/kg IV over 5 min. Repeat 0.5-2 mg/kg boluses q3-5 min until seizures stop. Max loading 10 mg/kg
Often limited by hypotension
Infusion: 1 mg/kg/h (80 kg = 8 ml/h), then titrate up to max 4 mg/kg/h (80 kg = 32 ml/h)
>4 mg/kg/h risks PRIS (80 kg = 32 ml/h)
Pros
> Rapid acting
> Terminates seizures
> Reduces cerebral metabolic rate
> Reduces ICP
> Wears off fast so neurological assessment possible
> Very few drug interactions
Cons
> Hypotension
> Respiratory depression, usually necessitates intubation and ventilation at these doses
> May get rebound seizures with abrupt cessation
> At high doses (>4 mg/kg/h) risk of Propofol infusion syndrome PRIS
More info here
Mechanism
Enhances the slow inactivation of Na channels thus stabilising hyperexcitable neuronal membranes and preventing repetitive neuronal firing
Dose
Loading dose: 400-600 mg IV over 15 minutes REF
Then 200 mg BD
IV and enteral formulations available
Pros
> Effective
> Non-sedating, ideal if trying to avoid general anaesthesia
> Safety: few patients have side effects
Cons
Possible side effects:
> Deranged LFTs so monitor
> Neutropenia, anaemia
> Increased PR on ECGs so do daily ECGs
> Increased risk of atrial fibrillation
> Coordination problems, unsteady gait
> Dizziness, double vision
> Headache
> Nausea, vomiting
> Lethargy
TIER 4 ASMS
Mechanism
NMDA receptor antagonist
Dose
Load: 1-2 mg/kg, max 4.5 mg/kg
Infusion: 1-10 mg/kg/h
Pros
Much more haemodynamically stable than propofol, midazolam or thiopentone
Doesn’t cause respiratory depression
Relatively safe
Cons
Efficacy in terminating refractory SE is really unknown REVIEW
May cause:
> Tachyarrhythmias
> Hypertension
> Hypersalivation
> Hallucinations
> Ulcerative cystitis, secondary renal damage and hepatic failure can occur with high doses of oral ketamine, not reported from use in critical care
Mechanism
GABA-A agonist. Highly lipid soluble.
Dose
Load: 2-7 mg/kg over 50 mg/min, with additional boluses 1-2 mg/kg as required
Infusion: 0.5-5 mg/kg/h titrate to seizure control on EEG
Pros
> Effective anti-seizure medication
> Rapid onset
> Reduces cerebral metabolic rate
> Reduces ICP
Cons
Many.
You are committing to a long course of management with several potential life threatening complications.
Causes profound anaesthesia and when high doses given with a prolonged infusion takes days to weeks to wear off.
> Hypotension usually requires noradrenaline to offset
> Hypokalaemia due to intracellular shift with associated arrhythmia
> Rebound hyperkalaemia when thio stopped with associated arrhythmia
> Immunosuppression, pneumonia common
> Ileus guaranteed, often refractory until thio stopped
Sharon has been treated with midazolam and levetiracetam.
It’s suggested to you that you should have used fosphenytoin as it’s better at controlling seizures.
What do you reply?