Anesthetics are depressant drugs that produce a partial or total loss of the sense of pain. In the case of general anesthetics, this is accompanied by a loss of consciousness. The first demonstration of such a drug was conducted in 1844 by Samuel Cooley, who demonstrated the effects of nitrous oxide on a Pharmacy student. During the demo, the student fell and injured his leg (but he didn't feel it until later).
Stage I - analgesia results from an increase in circulating endorphins, and there is a mild depression of cortical centers. This is the type of anesthesia referred to as twilight sleep.
Stage II - this stage is characterized by a loss of consciousness. It is also a critical period, since delerium and increased involuntary activity, as well as hypersecretion, can occur. Secretions can be managed with an anticholinergic agent, but it is best to get through Stage II as quickly as possible. Stage I and Stage II together are referred to as induction.
Stage III - this is the stage of anesthesia known as surgical anesthesia, and most surgical procedures are performed during this stage. There is a general loss of spinal reflexes and muscle tone.
Stage IV - this undesirable stage is characterized by respiratory depression, and other manifestations of overdose.
Most general anesthetics are non-specific agents, in that their activity depends on their lipid solubility rather than their structure. Inhaled and exhaled gas containing the agent equilibrates with the lung tissue, and then with the blood. In the brain, which has a great deal of vasculature, the agent equilibrates between the blood and neural tissue, depressing neurons and causing the pharmacological effect.
1. Ether and chloroform - these agents are the anesthetics from hell, because they have all of the negative traits of this class of drug. Ethyl ether is potent, and has a good margin of safety, but it is flammable, explosive, it forms peroxides, it produces an unpleasant induction phase, is irritating, and produces nausea and vomiting during recovery. Chloroform is also potent, and produces good skeletal muscle relaxation, but has a narrow margin of safety, produces liver and kidney toxicity, cardiac arrest and arrhythmias, and it can produce severe hypotension. The ideal general anesthetic is non-flammable, gives good muscle relaxation, has an uncomplicated induction and recovery, is non-toxic, and is easy to administer.
2. Non-halogenated hydrocarbons - all of these will work, and the longer the chain, the higher the potency. However, they have a tendency to produce cardiovascular toxicity. Cyclopropane (U.S.P.) is the only one still in use, and it is explosive.
3. Ethers - Like hydrocarbons, the longer the chain, the more potent the anesthetic. However, increasing chain length also increases toxicity and reduces induction time. Ethyl ether is seldom used, and divinyl ether is explosive and produces deep anesthesia too quickly.
4. Halogenated hydrocarbons - Addition of a halogen can reduce or eliminate flammability, and can also increase potency. Depending on the halogen, some of these compounds can cause arrhythmias and/or renal or hepatic toxicity. Compounds containing only bromine are generally not useful. Compounds containing only chlorine are subject to limited use, are toxic, and can cause arrhythmias. The best of the chlorinated agents are ethyl chloride and trichloroethylene, shown below.
Fluorinated hydrocarbons are the most useful of the general anesthetics, and were first discovered as offshoots of the nuclear weapons program. Addition of a fluorine decreases flammability, boiling point and the incidence of catechol-induced arrhythmias (these increase as the size of the halogen increases, and F is the smallest halogen). The structures of a few representative fluorinated hydrocarbon general anesthetics are shown in the figure above.
5. Nitrous oxide - This is the least toxic anesthetic, but is also the least potent. It causes good analgesia, but is a poor muscle relaxant.
6. Propofol and ketamine hydrochloride - Propofol, shown above, is the most commonly used intravenous anesthetic in the United States. It appears to act by enhancing GABAergic neurotransmission in the CNS. It has a very short duration of action, does not relax skeletal muscle and can only be used for short outpatient procedures unless supplemented by a volatile anesthetic. Ketamine, shown above, is a derivative of phencyclidine, and acts like a volatile anasthetic agent. When administered IV, it is potent, rapid acting and has a short duration. Patients older than 16 will often (27%) have wild dreams and hallucinations during emergence, and so it is only indicated for children less than 16 years old.
What do you see when you are experiencing the excitement phase of general anesthesia? Click here to find out!
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