Local anaesthetics now have many clinical uses and can be applied in a number of ways; they vary in their pharmacological properties, and as such are used in various techniques of anesthesia. Infiltration anesthesia sees the direct injection of local anesthetic into tissues to reach nerve branches and nerve terminals, and is mainly used in minor surgeries. In Intravenous regional anaesthesia, the local anaesthesia is injected distal to a pressure cuff, and remains effective until circulation is restored, this process is used for limb surgery. In nerve block anesthesia local anesthetic is injected close to nerve trunks to produce a loss of sensation peripheral, and is used in surgery and dentistry. In spinal anesthesia, local anaesthesia is injected into the subarachnoid space to act on the spinal roots and spinal cord, this is used for surgery to the abdomen, pelvis, or leg, mainly when general anesthesia cannot be used. In epidural anesthesia, local anesthetic is injected into the epidural space, blocking spinal roots, and is used for a painless child birth.
Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. They consist of an aromatic part linked by an ester or amide bond to a basic side chain. Thus they contain hydrophobic region and a basic region, accounting for their weak basic nature. They have pka values mainly in the range 8-9, so that the majority, but not all, are ionised at physiological pH. This is important in the local anesthetic mechanism of action as they need to remain non-ionized when outside the cell to remain effective. Thus the majority of local anesthetics are tertiary amines, as quaternary amines are fully ionized irrespective of pH and as such are ineffective as local anesthetics.
[...] Single anaesthetics are rarely used on their own, it is more common for a mixture of drugs to be used throughout the anaesthetic process to increase control over the anaesthetic, and to remove the unwanted effects. The patient may be given pre-medication drugs before the operation, such as opioids like fentanyl or sedatives such as the benzodiazepine midazolam, to induce drowsiness of relaxation. Commonly, unconsciousness is produced rapidly with an initial dose of intravenous anaesthetic, such as propofol, and unconsciousness and analgesia is often maintained throughout the surgery by supplying one or more inhalation agents, such as nitrous oxide and halothane. [...]
[...] Sodium and hydrogen ions are constantly moving into and out of the sodium channel, even when it is closed and they do not pass through to the cytosol, and as such a passing hydrogen ion protonates the local anaesthetic at the binding site, creating the hydrostatic repulsion needed to block the channel. Thus it can be seen that local anaesthetic activity is strongly pH dependant, being increased at alkaline pH when there are less protonated molecules outside the cell and so more can diffuse into the cell, and being decreased at an acid pH when there is a high majority of protonated molecules outside the cell that cannot diffuse in. [...]
[...] There are generally four stages associated with the onset of action of general anaesthetics as their concentration increases in the blood. Stage one is considered the analgesic stage, where the response to painful stimuli is reduced in a drowsy state. Stage two is considered the excitement stage, where the patient loses consciousness, and no longer responds to non-painful stimuli, but will respond to painful stimuli in a reflex fashion. Other reflexes may be exacerbated, such as the cough or gag reflex. [...]
[...] They are normally used for the induction of anaesthesia, though are unsatisfactory for producing maintained anaesthesia as their elimination from the body is relatively slow compared with that of inhalation agents. The most commonly used intravenous agents are thiopental, etomidate, and propofol. Thiopental is a barbiturate with very high lipid solubility. It has a rapid action due to its rapid transfer across the blood brain barrier, though a short duration of action due to its redistribution, mainly to the muscles. [...]
[...] High levels of local anaesthetic may also cause atrioventricular block with sever bradycardia, leading to coma and death. Yet there are reports that intralipid, an intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose. General anaesthesia is a state of total unconsciousness, in which the patient is unaware of, and unresponsive to, painful stimuli, resulting from the giving of general anaesthetic drugs. A variety of drugs that have different effects, along with the general anaesthesia, are given to the patient to ensure total unconsciousness, amnesia disturbance of memory), and analgesia (the relief of pain). [...]
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