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| All anaesthetic agents can cause death at doses higher than those used to induce anaesthesia. These agents depress the heart and/or lungs, and at high doses death occurs by circulatory or respiratory failure. | | All anaesthetic agents can cause death at doses higher than those used to induce anaesthesia. These agents depress the heart and/or lungs, and at high doses death occurs by circulatory or respiratory failure. |
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| == Inhalation anaesthetics == | | = Inhaled anaesthetics = |
| The inhalation anaesthetics are lipophilic molecules to different degree. The lipophilicity of the inhalation anaesthetics determines several properties, like:
| | {{#lst:Inhaled anaesthetics|pharmacology}} |
| {| class="wikitable"
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| !Property
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| !More lipophilic anaesthetics
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| !Less lipophilic anaesthetics
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| |-
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| !Potency
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| |More potent
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| |Less potent
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| |-
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| !Induction of anaesthesia
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| |More slowly
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| |More rapidly
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| |-
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| !Recovery from anaesthesia
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| |More slowly
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| |More rapidly
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| |-
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| !Minimal alveolar concentration (MAC)
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| |Lower
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| |Higher
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| |} | |
| However, even the fastest-acting inhalation anaesthetics take a few minutes before anaesthesia is induced.
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| The important inhalation anaesthetics are:
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| * Halogenated hydrocarbons
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| ** Halothane
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| * Halogenated ethers
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| ** Sevoflurane
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| ** Desflurane
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| ** Isoflurane
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| * Gases
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| ** Nitrous oxide (N2O)
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| When talking about inhalation anaesthetics, the ''minimal alveolar concentration'' (MAC) is important. The MAC is the concentration of anaesthetic in the alveolar space that is enough to cause anaesthesia in 50% of patients. Each drug has a characteristic MAC value. Typically, concentrations of 1.3 times the MAC are used during surgical procedures.
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| A potent inhalation anaesthetic will have a low MAC while less potent one will have a higher MAC. Drugs that are more lipophilic are more potent (and therefore have lower MAC) than drugs that are less lipophilic.
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| === Pharmacokinetics ===
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| These drugs are rapidly absorbed by diffusion across the alveolar membrane.
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| More lipophilic drugs will immediately dissolve in lipids in the blood. This causes them to enter the brain more slowly, which is why more lipophilic inhalation anaesthetics induce anaesthesia more slowly and vice versa.
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| These drugs are mainly eliminated by exhalation. More lipophilic drugs are more retained in the CNS and adipose tissue and are therefore eliminated more slowly. More lipophilic drugs therefore cause the patient to recover from the general anaesthesia more slowly and vice versa.
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| === Adverse effects ===
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| Inhaled anaesthetics can cause cardiac depression and respiratory depression.
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| Halogenated inhaled anaesthetics can induce malignant hyperthermia in people who have a mutation in the ryanodine receptor. The ryanodine receptor is a calcium channel in the muscle, and in susceptible people halogenated inhaled anaesthetics or depolarizing muscle relaxants like succinylcholine will cause calcium to enter skeletal muscles. This causes hyperthermia and potentially rhabdomyolysis. Treatment is with dantrolene, which blocks the ryanodine receptor.
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| == Halogenated hydrocarbons ==
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| The only important drug in this class is halothane, and it isn’t widened used anymore in the developed world. Halothane induces a massive hepatic necrosis called ''halothane hepatitis'' in 1 out of 10 000 cases. It has a mortality rate of 80%. This development of halothane hepatitis was very unpredictable, so the use of halothane has been mostly discontinued where possible.
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| Halothane is metabolized into a compound called TFA in the liver. TFA acts as a hapten, so it binds to surface proteins on hepatocytes and make them immunogenic. The immune system will then attack the hepatocytes.
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| == Halogenated ethers ==
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| * Isoflurane
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| * Desflurane
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| * Sevoflurane
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| Enflurane also belongs to this category but isn’t used anymore due to being seizure-inducing and nephrotoxic.
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| These drugs are favourable because they don’t have significant cardiodepressive effect, nor do they cause hepatotoxicity or nephrotoxicity. They do cause respiratory depression, though.
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| Halogenated ethers also increase the cerebral blood flow, which increases the intracranial pressure. This is an undesirable effect, especially during brain surgery.
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| == Gases ==
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| The only important gas currently used in general anaesthesia is nitrous oxide, also known as laughing gas or N2O. Nitrous oxide is the least potent inhalation anaesthetic. It’s more useful for smaller procedures where complete loss of consciousness is not necessary, like dental procedures. It can also be combined with other anaesthetics.
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| It’s the only inhaled anaesthetics that doesn’t depress respiration, and it can’t cause malignant hyperthermia. It does not induce muscle relaxation, so it should be used with a muscle relaxant.
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| === Special considerations ===
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| After the surgical procedure is finished and the nitrous oxide anaesthetic is removed, N2O will rapidly diffuse back into the alveolar space. This causes it to displace oxygen, which causes so-called “diffusional hypoxia”. This effect is counteracted by giving the patient pure O2 for a few minutes after the procedure.
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| Repeated use of N2O causes vitamin B12 deficiency, because N2O can oxidize the vitamin. This is mostly only a problem in medical personnel who abuse the gas repeatedly.
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| == Intravenous anaesthetics == | | == Intravenous anaesthetics == |
| The important IV anaesthetics are: | | The important IV anaesthetics are: |
