Nitrous oxide (medication)

Pure N2O was first used as a medical analgesic in December 1844, when Horace Wells made the first 12–15 dental operations with the gas in Hartford. Its debut as a generally accepted method, however, came in 1863, when Gardner Quincy Colton introduced it more broadly at all the Colton Dental Association clinics, that he founded in New Haven and New York City. The first devices used in dentistry to administer the gas consisted of a simple breathing bag made of rubber cloth. Breathing the pure gas often caused hypoxia (oxygen insufficiency) and sometimes death by asphyxiation. Eventually practitioners became aware of the need to provide at least 21% oxygen content in the gas (the same percentage as in air). Today the nitrous oxide is administered in hospitals by a relative analgesia machine, which includes several improvements such as flowmeters and constant-flow regulators, an anaesthetic vaporiser, a medical ventilator, and a scavenger system, and delivers a precisely dosed and breath-actuated flow of nitrous oxide mixed with oxygen. The machine used in dentistry is much simpler, and is meant to be used by the patient in a fully conscious state. The gas is delivered through a demand-valve inhaler over the nose, which will only release gas when the patient inhales through it. ==Medical uses==

Nitrous oxide (N2O) is itself active (does not require any changes in the body to become active), and so has an onset in roughly the lung–brain circulation time with peak action 30 seconds after the start of administration. Nitrous oxide has been shown to be an effective and safe treatment for alcohol withdrawal. Nitrous oxide is more soluble than oxygen and nitrogen, so will tend to diffuse into any air spaces within the body. This makes it dangerous to use in patients with pneumothorax or those who have recently been scuba diving, and there are cautions over its use with any bowel obstruction. Its analgesic effect is strong (equivalent to 15 mg of subcutaneous route morphine and characterised by rapid onset and offset, i.e. it is very fast-acting and wears off very quickly. When used in combination with other anesthetics gases, nitrous oxide causes a dose dependent increased respiratory rate and decreased tidal volumes, the net effect is a lower minute ventilation. Like volatile anesthetics, it increases cerebral blood flow and intracranial pressure. However, contrary to volatile anesthetics, it leads to an increase in cerebral metabolic rate of oxygen. ==Contraindications==

N2O should not be used in patients with bowel obstruction, pneumothorax, or middle ear or sinus disease, and should also not be used on any patient who has been scuba diving within the preceding 24 hours or in violently disturbed psychiatric patients. There are also clinical cautions in place for the first two trimesters of pregnancy and in patients with decreased levels of consciousness. ==Composition==

The gas is a mixture of half nitrous oxide (N2O) and half oxygen (O2). This occurs most easily with partially used / lower pressure cylinders. Even after warming the contents back into a gaseous state, they may remain nonhomogenous for days. Thus it is typically instructed to warm cylinders in a horizontal orientation (to maximize heat transfer) for a 48 hour period, then rehomogenize the gas by inverting the cylinder three times. File:Entonox Shoulder.png|Distinct blue and white cap of an Entonox cylinder File:Entonox schrader valve.png|Typical Schrader valve attachment, making the gas usable only with demand based giving sets ==Administration==

operating on an anaesthetised soldier during World War I. In the foreground, the anaesthetist is holding a mask in front of the patient's face. The gas is self-administered through a demand valve, using a mouthpiece, bite block or face mask. Self-administration of Entonox is safe because if enough is inhaled to start to induce anaesthesia, the patient becomes unable to hold the valve, and so will drop it and soon exhale the residual gas. This means that unlike other anaesthetic gases, it does not require the presence of an anaesthetist for administration. The 50% oxygen in Entonox ensures the person will have sufficient oxygen in their alveoli and conducting airways for a short period of apnea to be safe. == Mechanism of action ==

The pharmacological mechanism of action of in medicine is not fully known. However, it has been shown to directly modulate a broad range of ligand-gated ion channels, and this likely plays a major role in many of its effects. It moderately blocks NMDAR and β-subunit-containing nACh channels, weakly inhibits AMPA, kainate, GABA and 5-HT receptors, and slightly potentiates GABA and glycine receptors. It also has been shown to activate two-pore-domain channels. While affects quite a few ion channels, its anesthetic, hallucinogenic and euphoriant effects are likely caused predominantly, or fully, via inhibition of NMDA receptor-mediated currents. In addition to its effects on ion channels, may act to imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and anxiolytic properties. Nitrous oxide is 30 to 40 times more soluble than nitrogen. ==Society and culture==

Nitronox was a registered trademark of the BOC Group between 1966 and 1999, and was reregistered by Hs Tm Inc since 2005 It is also colloquially known as "gas and air" in the United Kingdom. ==Research==

Investigational trials show potential for antidepressant applications of N2O, especially for treatment-resistant forms of depression, and it is rapid-acting. In a phase 2 clinical trial, a treatment with 25% nitrous oxide had comparable efficacy to 50% nitrous oxide but was associated with significantly fewer adverse effects. == References ==