| Class |
Selective binding agent
|
| Chemistry |
A hydantoin derivative, like phenytoin, but without antiepileptic activity
|
| Routes of administration |
Oral and IV (yes, there is an oral version, used to treat chronic muscle spasticity)
|
| Absorption |
70% oral bioavailability after oral administration.
|
| Solubility |
pKa= 7.5, slightly soluble in water, highly lipophilic - in fact total paralysis cannot be obtained with dantrolene sodium regardless of the dose, because of the poor water solubility. Needs to be presented as a solution with pH 9.5.
|
| Distribution |
VOD=0.51 L/kg; highly protein-bound
|
| Metabolism |
Mostly hepatic metabolism into 5-hydroxydantrolene, which has muscle relaxant activity
|
| Elimination |
Metabolite is cleared renally
|
| Time course of action |
Elimination half-life is about 12 hours; onset of peak effect is within about 6 hours. So, not exactly suitable for rapid sequence induction.
|
| Target receptor |
Dantrolene directly inhibits the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum.
|
| Mechanism of action |
Blocking calcium release from intracellular storage in the sarcoplasmic reticulum results in decreased muscle contraction, without any effect on the action potential or the neuromuscular junction.
|
| Clinical effects |
Skeletal muscle paralysis (incomplete)
Acute IV administration can cause phlebitis because of the extremely alkaline solution
Chronic oral therapy can cause LFT derangement
Accidental extravascular infusion causes severe tissue necrosis.
|
| Literature reference |
|
| CICM details of understanding |
Level 3
|
| Mentioned around Deranged Physiology |
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| Related SAQs |
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