Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder. Since the condition it treats is so rare, Nusinersen has so-called "orphan drug" designation in the United States and the European Union. Medical uses
The drug is used to treat spinal muscular atrophy associated with a mutation in the SMN1 gene. It is administered directly to the central nervous system (CNS) using intrathecal injection.In clinical trials, the drug halted the disease progression. In around 60% of infants affected by type 1 spinal muscular atrophy, it improves motor function. Side effects
People treated with nusinersen had an increased risk of upper and lower respiratory infections and congestion, ear infections, constipation, pulmonary aspiration, teething, and scoliosis. There is a risk that growth of infants and children might be stunted. In older clinical trial subjects, the most common adverse events were headache, back pain, and other adverse effects from the spinal injection, such as post-dural-puncture headache.Although not observed in the trial patients, a reduction in platelets as well as a risk of kidney damage are theoretical risks for antisense drugs and therefore platelets and kidney function should be monitored during treatment.In 2018, several cases of communicating hydrocephalus in children and adults treated with nusinersen emerged; it remains unclear whether this was drug related. Pharmacology
Spinal muscular atrophy is caused by loss-of-function mutations in the SMN1 gene which codes for survival motor neuron (SMN) protein.
The CO2 absorbent Baralyme, when dried, is most culpable for the production of carbon monoxide from desflurane degradation, although it is also seen with soda lime absorbent as well. Dry conditions in the carbon dioxide absorbent are conducive to this phenomenon, such as those resulting from high fresh gas flows. Pharmacology
As of 2005 the exact mechanism of the action of general anaesthetics has not been delineated. Desflurane is known to act as a positive allosteric modulator of the GABAA and glycine receptors, and as a negative allosteric modulator of the nicotinic acetylcholine receptor, as well as affecting other ligand-gated ion channels. Stereochemistry
Desflurane medications are a racemate of two enantiomers. Physical properties
Global-warming potential
Desflurane is a greenhouse gas. The twenty-year global-warming potential, GWP(20), for desflurane is 3714, meaning that one tonne of desflurane emitted is equivalent to 3714 tonnes of carbon dioxide in the atmosphere, much higher than sevoflurane or isoflurane. In addition to global warming potentials, drug potency and fresh gas flow rates must be considered for meaningful comparisons between anesthetic gases. When a steady state hourly amount of anesthetic necessary for 1 minimum alveolar concentration (MAC) at 2 liters per minute (LPM) for Sevoflurane, and 1 LPM for Desflurane and Isoflurane is weighted by the GWP, the clinically relevant quantities of each anesthetic can then be compared. On a per-MAC-hour basis, the total life cycle GHG impact of desflurane is more than 20 times higher than Isoflurane and Sevoflurane (1 minimal alveolar concentration-hour).