52. General anaesthetics: Difference between revisions

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= Inhaled anaesthetics =
= Inhaled anaesthetics =
{{#lst:Inhaled anaesthetics|pharmacology}}
{{#lst:Inhaled anaesthetics|pharmacology}}
== Intravenous anaesthetics ==
The important IV anaesthetics are:


* Propofol
= Intravenous anaesthetics =
* Etomidate
{{#lst:Intravenous anaesthetics|pharmacology}}
* Ketamine
* Barbiturates
** Thiopental
** Methohexital


While inhalational anaesthetics can be “fast-acting”, they’re still relatively slow and need a few minutes to kick in. Intravenous anaesthetics can cause anaesthesia in as little as 20 second.
IV anaesthetics can be given in doses or as continuous infusion via IV.
=== Mechanism of action ===
All intravenous anaesthetics (except ketamine) activate the GABAA receptor. They may also inhibit receptors like neuronal acetylcholine receptor and NMDA glutamate receptor.
Ketamine blocks NMDA glutamate receptors in the CNS.
=== Pharmacokinetics ===
IV anaesthetics are lipophilic drugs that distribute rapidly to well-perfused organs like the brain immediately after IV injection. This rapid distribution is what causes anaesthesia to kick in so quickly.
Later the anaesthetic will redistribute to poorly perfused organs like muscles, skin and adipose tissue. When this happens the level of anaesthetic in the CNS will drop, causing the patient to recover from anaesthesia. In people with decreased perfusion or muscle and adipose tissue mass, this redistribution will take longer, and the anaesthesia will last longer as well.
To reiterate: the anaesthetic action of IV anaesthetics is terminated by redistribution and not by elimination. Because all IV anaesthetics follow the same pattern of redistribution, they all cause similar duration of action, 5 – 10 minutes.
All IV anaesthetics are eliminated by biotransformation. All IV anaesthetics have similar half-life of around 1 – 4 hours, except thiopental, which has a half-life of 12 hours. Because thiopental has such a long elimination half-life it would accumulate in the body if given as a continuous infusion. Thiopental is instead given in doses. All other IV anaesthetics have short half-lives and will not accumulate in the body, so they can be given as continuous infusion.
=== Indications ===
All IV anaesthetics can be given in single IV doses for:
* Induction of anaesthesia, which is later maintained by an inhalation anaesthetic
* Induction of a short (5 – 10 minute) anaesthesia, for short surgeries or painful interventions
Some IV anaesthetics (especially propofol) can be given in continuous infusion for:
* Production of long-lasting anaesthesia (total intravenous anaesthesia (TIVA))
* Sedation of patients (in low doses)
=== Propofol ===
Propofol is the standard drug for inducing anaesthesia. It can also be used to maintain anaesthesia.
Advantages:
* Induces anaesthesia rapidly, within 20s
* Decreases cerebral blood flow and <abbr>ICP</abbr>
Disadvantages:
* Cardiodepressive effects
* Vasodilator effect
* Propofol infusion syndrome may occur
Propofol infusion syndrome (PRIS) is a rare but potentially lethal side effect of propofol. The drug can uncouple the oxidative phosphorylation in the mitochondria, which can cause lactic acidosis, rhabdomyolysis and acute renal failure.
=== Etomidate ===
Etomidate is also used for inducing anaesthesia. It cannot be used in prolonged infusion as it inhibits the synthesis of cortisol.
Indications:
Etomidate is preferred in patients with haemodynamic instability.
Advantages:
Etomidate preserves cardiovascular stability by not affecting vascular tone or the heart. This is especially useful for patients with impaired myocardial contractility.
=== Ketamine ===
Ketamine can also be used to induce anaesthesia.
Mechanism of action:
Unlike the other IV anaesthetics ketamine acts by blocking NMDA glutamate receptors in the CNS.
* Ketamine induces a state called ''dissociative anaesthesia'', a form of anesthesia characterized by catalepsy, catatonia, analgesia, and amnesia. The patient may remain conscious
Indications:
Ketamine is especially useful in emergency medicine due to its stimulatory effects on the cardiovascular system.
Advantages:
* Ketamine stimulates the cardiovascular system
Disadvantages:
* Ketamine causes unpleasant experiences like weird dreams and hallucinations when recovering from the anaesthesia
== Benzodiazepines in anaesthesia ==
Benzodiazepines can be used to induce a state of conscious sedation, which can be useful if the patient should be awake during the procedure. They can’t induce general anaesthesia alone.
Indications:
* Minor procedures like colonoscopy
== Barbiturates in anaesthesia ==
The important barbiturates used as IV anaesthetics are thiopental and methohexital.
Indications:
Barbiturates are especially useful in cases where there is increased intracranial pressure.
Advantages:
* Barbiturates decrease the intracranial pressure
== Opioids in anaesthesia ==
Certain opioids like fentanyl can be used in combination with benzodiazepines to induce general anaesthesia. This is especially useful in cardiac surgery as this combination does no affect cardiac function.
The combination of fentanyl and a certain antpsychotic called droperidol was previously used to induce ''neuroleptanalgesia'', a state where the patient is conscious but indifferent to pain. This is rarely used nowadays but has been asked on the exam.
[[Category:Pharmacology 2]]
[[Category:Pharmacology 2]]