Nitrous oxide Inhalational anaesthetics

Inhalation (IH) The administration of volatile gases and vapours, followed by drug absorption in the lungs or nasal mucosa. Examples include general anaesthetics like nitrous oxide, nicotine from the tar droplets in tobacco smoke, cannabinoids from cannabis leaf smoke and various opiates from burning opium resin. 

Chemical synthesis did not seem, at first, a likely source of useful remedies. However, after Wohler s synthesis of urea, in 1828, a whole range of synthetic organic chemicals was introduced into medical practice. After several false starts, some relatively simple substances were adopted as inhalation anaesthetics, namely nitrous oxide, ether, and chloroform (1844-7) which, by giving the surgeon adequate time for his task, initiated a tremendous refinement and extension of the possibilities of surgery. 

Two methods of anaesthesia are currently in use, the application of inhaled gaseous or volatile anaesthetics such as halothane, sevoflurane and isoflurane to maintain a level of anaesthesia. Older compounds in this category include nitrous oxide and chloroform. 

Baden JM, Kelley M, Mazze Rl, et al. 1979. Mutagenicity of inhalation anaesthetics Trichloroethylene, divinyl ether, nitrous oxide, and cyclopropane. Br J Anaesth 51 417-421. 

Today we have sophisticated lab equipment to help us analyze the products of reactions. In the past, when such equipment was not available, chemists sometimes jeopardized their safety and health to determine the products of the reactions they studied. Sir Humphry Davy (1778-1829), a contributor to many areas of chemistry, thought nothing of inhaling the gaseous products of the chemical reactions that he carried out. He tried to breathe pure C02, then known as fixed air. He nearly suffocated himself by breathing hydrogen. In 1800, Davy inhaled dinitrogen monoxide, N20, otherwise known as nitrous oxide, and discovered its anaesthetic properties. What is nitrous oxide used for today ... 

Drug interactions. Addition of 50% nitrous oxide/ oxygen mixture to another inhalational anaesthetic... 

A small-scale but important use of ammonium nitrate is for the preparation of inhalation grade nitrous oxide for use as an anaesthetic. This is achieved by heating pure ammonium nitrate to about 200-250°C (Eq. 11.53), which gives nitrous oxide virtually free of nitric oxide or... 

Humphrey Davey first suggested the use of nitrous oxide as an inhalation anaesthetic in 1800. This gas was used for many years as laughing gas for entertainment. Around this time, an American dentist, Horace Wells, used it medicinally during the extraction of one of his own teeth. 

Inhalation anaesthetics are either gases or volatile liquids. Apart from nitrous oxide, which is still widely used, earlier inhalation anaesthetics are no longer used. Ether is not suitable because it is explosive and irritant to the respiratory tract. Chloroform cannot be used because it is toxic to the liver. Inhalation anaesthetics currently in use are the volatile liquids halothane (since 1956) and more recently isoflurane, desflurane and sevoflurane and nitrous oxide gas. 

Nitrous oxide has a low potency and must be used in combination with other inhalation anaesthetics for general anaesthesia. Nitrous oxide provides rapid induction and recovery. It also has an analgesic action and is used as a 50% mixture with oxygen to provide analgesia without loss of consciousness during labour and manipulations of injured body parts. 

Inhalation anaesthetics are gases or volatile liquids. Nitrous oxide and isoflurane are commonly used. 

Gases of interest are nitrous oxide and the inhalation vapours (or volatile halogenated anaesthetics) such as halothane (CF3CHBrCl), isoflurane (CHF2OCHCICF3) and enflurane (CHCIFCF2OCHF2). In this section electrochemical studies on nitrous oxide, halothane and isoflurane will be discussed. 

In a double-blind study in 11 healthy subjects there were several instances when alcohol 0.25 to 5 g/kg (equivalent to 1 to 3 drinks) enhanced the effects of nitrous oxide 30% in oxygen, inhaled for 35 minutes. Some effects were seen with the drug combination, which were not seen with either drug alone these included subjective effects and delayed free recall. For mention of the effect of alcohol following anaesthesia, see Anaesthetics, general -I- Alcohol , p.92. 

The dose requirement of inhalational anaesthetics and barbiturate anaesthetics is reduced by nitrous oxide, and the effect of ketamine may be prolonged by barbiturate anaesthetics. 

Nitrous oxide usually reduces the MAC of inhalational anaesthetics in a simple additive manner an inspired concentration of 60 to 70% nitrous oxide is commonly used with volatile anaesthetics. Similarly, the concurrent use of nitrons oxide reduces the dose of intravenous barbiturate anaesthetics and sevoflurane required for anaesthesia. 

The inhalational anaesthetics increase the effects of the neuromuscular blockers to differing extents, but nitrous oxide appears not to interact significantly. Ketamine has been reported to potentiate the effects of atracurium. Propofol does not appear to interact with mivacurium or vecuronium. Xenon is reported not to interact with mivacurium or rocuronium, and has less effect than sevoflurane on vecuronium neuromuscular blockade. Bradycardia has been seen in patients given vecuronium with eto-midate or thiopental. Propofol can cause serious bradycardia if it is given with suxamethonium (succinylcholine) without adequate antimuscarinic premedication, and asystole has been seen when fentanyl, propofol and suxamethonium were given sequentially. 

The effects of neuromuscular blockers are increased by inhalational anaesthetics, the greater the dosage of the anaesthetic the greater the increase in blockade. In broad terms desflurane, ether, enflurane, isoflurane, methoxyllurane and sevoflurane have a greater effect than halothane, which is more potent than cyclopropane, whereas nitrous oxide appears not to interact significantly with competitive blockers. " ... 

Pulmonary hypertension. In a study of the combined use of intravenous sildenafil and inhaled nitric oxide in the management of pulmonary hypertension in 15 infants, significant hypotension occurred, which, along with a decrease in oxygenation, was considered sufficiently detrimental for the study to be stopped early. Conversely, beneficial combined use has been described in one adult patient with severe hypoxemia caused by pulmonary hypotension. Note that nitric oxide is not to be confused with the anaesthetic nitrous oxide, which is not a nitric oxide donor and therefore poses no risk, see Mechanism below. 

At Bristol, Davy continued to experiment on nitrous oxide and began Inhaling It himself, and hence discovered Its curious effect on human sensations and behaviour. He also discovered its anaesthetic properties. This work made his name, and his hasty and unfortunate conclusions about phosoxygen, which had been published by Beddoes, were soon forgotten. 

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