Central Nervous System Flashcards
How is Suxamethonium metabolised?
Why may a patient have a prolonged paralysis following Sux?
Suxamethonium (aka succinylcholine) is a depolarizing muscle relaxant drug.
Rapid phase 1 hydrolysis by butyrylcholinesterase (BCHE) and pseudocholinesterase in liver and plasma, hence it’s extremely short duration of action (5-10 mins)
Genetically deficient in BCHE so slowed metabolism
Describe the volume of distribution of TCAs.
TCAs have a large Vd (5-30L/kg)
Tissue concentrations are high especially in well perfused organs such as the brain and heart.
What type of drug is amitriptyline?
Amitriptyline is one of the most commonly used tricyclic antidepressants.
Their main therapeutic effect is thought to be due to inhibition of both noradrenaline and serotonin reuptake and is thought to lead to increased activity at their specific post-synaptic receptors.
Tricyclics also block inactivated fast sodium channels. Tricyclics are also similar in structure to phenothiazines and thus share many of their properties (serotonin and noradrenaline reuptake inhibition, alpha-2-adrenoreceptor blockade, muscarinic receptor blockade etc.)
Describe the toxicokinetics of amitriptyline.
- *Absorption:**
- Rapidly absorbed following oral administration. Time to peak levels is 2 hours
- *Distribution:**
- Large volume of distribution (5-20L/kg).
- Highly bound to plasma and tissue proteins
- *Metabolism:**
- Undergoes hepatic metabolism by oxidation via Cytochrome p450 to active metabolites such as nortriptyline
- *Excretion:**
- Mainly in the urine as metabolites. Very little is excreted unchanged
What therapies for TCA toxicity might reduce their tissue distribution?
Alkalinisation (sodium bicarbonate or hyperventilation, aim for pH 7.50-7.55) increases plasma protein binding of the free drug
Removing it from tissues reducing its toxicity
