Knowledge
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Sugammadex is pharmacologically great. A modified γ-cyclodextrin Selective Relaxant Binding Agent that reverses rocuronium muscle relaxation 10-times faster than neostigmine (see: Is sugammadex as good as we think?).
At launch, its biggest obvious disadvantage was simply the new drug's high cost. Now as sugammadex has become more widely used, sugammadex-anaphylaxis has risen as a new, prominent concern.
In Japan, where there was a uniquely rapid take-up of sugammadex, it became one of the commonest causes of anaphylaxis. Oriharia (2020) demonstrated an incidence of sugammadex anaphylaxis in Japan of 1 in 5,000 – a risk that most medically communities would consider too high for routine use of a drug with acceptable alternatives.
Given that in some regions (notably Australia & New Zeleand) rocuronium itself has a high-risk of anaphylaxis, the combination of rocuronium-sugammadex may present a greater risk than even old-school drugs such as suxamethonium.
In other countries, such as the United Kingdom, there has not been quite the same incidence of sugammadex-anaphylaxis. Is this simply because of the lower initial use than in Japan, or are there environmental and phenotypical differences as have been implicated for rocuronium anaphylaxis?
Worryingly, if the Japanese experience is representative, then for some locations the combination of rocuronium-sugammadex may in fact have a higher risk of anaphylaxis than using suxamethonium alone.
The true risk of sugammadex-anaphylaxis is still unclear for many populations. However with the looming expiry of the sugammadex patent in 2023, we will see a rapid increase in its use and subsequently reveal any latent anaphylaxis risk.
summary
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In Australia and New Zealand rocuronium is associated with a higher risk of anaphylaxis when compared to vecuronium or the benzylisoquinolinium NMBDs. This is not the case in North America or Europe.
pearl
...and 2 more notes
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Suxamethonium chloride (suxamethonium, succinylcholine or sux) is a depolarising muscle relaxant that produces rapid-onset, short-duration, deep muscle relaxation. First identified in 1906 and used medically in 1951, it is one of the oldest anaesthesia drugs still widely used. Due to its unique properties and low cost, it remains on the World Health Organisation's List of Essential Medicines
A. Physiochemistry
- (CH3)3-N-CH2CH2-OCO-CH2CH2-OCO-CH2CH2-N-(CH3)3
- pH 3.5
- Shelf life 3 years at 4°C, though only 'months' at 20°C.
B. Pharmacokinetics
- Dose - ED95 0.5 mg/kg, IV 1.5 mg/kg, IM 2.5-4 mg/kg.
- Absorption - IM, IV.
- Distribution - >0.2 L/kg; crosses placenta slightly but little effect on foetus.
- Protein binding ?
- Onset 30s IV, 2-3 min IM; Offset 3-5 min.
- Metabolism - PChE to succinylmonocholine (5% activity) & choline -> succinic acid & choline.
- tß½ 5 minutes
C. Pharmacodynamics
- Mechanism - binds to alpha subunit of nicotinic ACh receptor, producing persistent depolarisation (phase 1 & phase 2 blocks).
- CNS - ⇡ intra-ocular pressure (4-8 mmHg rise), ⇡ intra-celebral pressure (to 30 mmHg at 2-4 min).
- CVS - arrhythmias (both bradycardia & tachycardia possible), ⇡ systolic blood pressure, (both negative inotropic and chronotropic effects).
- Resp - 'sux apnoea' pharmacogenetic diversity (94% normal, 3.8% heterozyg (10 min duration of effect), <1% homozog (1-2h duration))
- Renal - hyperkalaemia due to K+ release from muscle; beware in neuromuscular conditions, denervation, and extensive burns.
- GIT - ⇡ intragastric pressure, ⇡ secretions, salivation.
- SEs - anaphylaxis, malignant hyperthermia, sux apnoea, muscle pains, masseter spasm.
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