General Anesthetics -- KEY POINTS ONLY

(1) analgesia
(2) excitement
(3) surgical anesthesia
(4) medullary depression

(1) loss of consciousness smoothly + rapidly (want to overcome 2nd stage of excitement)

(2) prompt recovery

(3) wide margin of safety

(1) sevoflurane
(2) desflurane
(3) isoflurane
(4) nitrous oxide
(5) halothane

(1) etomidate
(2) fentanyl
(3) ketamine
(4) midazolam
(5) propofol
(6) thiopental

--there is a linear relationship between potency and lipid solubility
--appears at different levels of CNS integration
(no longer accepted universally)

--"The NUMBER of anesthetic molecules dissolved at the site of anesthetic action, not the types of molecules present, cause anesthesia." = Meyer-Overton Rule

(1) GABA
(2) NMDA
(3) ACh

located in cerebral cortex, thalamus & reticular formation

(1) nitrous oxide
(2) age
(3) premedication
(4) alcohol intoxication
(5) sympathetic decrease
(6) hypotension
(7) hypothermia

(1) Age
(2) chronic alcohol abuse
(3) sympathetic increase from ephedrine, amphetamines, cocaine,etc

Implicit: recalled unconsciously; target of anesthesia

Explicit: recalled consciously


--anesthetics inhibit ACh receptors in hippocampus, amygdala & prefrontal cortex to produce amnesia

"anesthetic potency best described by MAC at 1atm of an agent that produces immobility in 50% of subjects exposed to a noxious stimulus"

Nitrous oxide decreases MAC!

(1) solubility
(2) cardiac output
(3) alveolar-to-venous partial pressure difference

FA=alveolar anesthetic concentration

FI=inspired concentration

If an anesthetic has a blood-gas partition coefficient of 1.4....

At equilibrium (meaning there is no shifting of the anesthetic through biolayers), the plasma concentration of the drug is 1.4 times higher than in gas.

In the presence of nitrous oxide...

(1) alveolar volume is reduced
(2) potency of 2nd gas is increased
(3) less of the 2nd gas is needed

All these factors increase the FA/FI rate of rise

...nitrous oxide concentration will increase in the alveoli and hypoxia could result.

cardiodepressive: halothane, enflurane

reduce SVR: sevoflurane, desflurane, isoflurane

they reduce myocardial oxygen consumptoin and act against myocardial reperfusion injury

If you give isoflurane to both a healthy and unhealthy vessel, the healthy one will react and steal blood flow from the unhealthy vessel.

(1) respiration: inc apneic threshold; depress mucociliary function; creates risk of atelectasis

(2) renal BF: reduces blood flow and GFR

(3) liver: reduces blood flow

(4) brain: reduce metabolic rate but increases cerebral blood flow; enflurane can cause spike-and-wave pattern; muscle twitching at high doses

Blood flow to the brain increases with addition of volatile anesthetic.

This is important in the case of increased intracranial pressure, as the volatile anesthetic can exacerabate the increased pressure in the brain.

(1) nephrotoxicity
(2) hepatotoxicity
(3) carbon monoxide intoxication

P-450 metabolism of halothane produces a reactive metabolite, which forms TFAA.

TFAA, then, binds to hepatocytes, acting as an antigen and producing an inflammatory response.

REDISTRIBUTION!!!

thiopental activates inhibitory GABA receptors and inhibits excitatory AMPA receptors

(1) ketamine
(2) etomidate

any kind of porphyria

d) midazolam

Midazolam is a benzodiazepine and is used in balanced anesthesia and conscious sedation.

recovery

(1) inhibit response to painful stimuli

(2) produce sedative effects

adrenal insufficiency

Ketamine does not interact with

c) GABA receptors.

Ketamine (analgesic properties attributed to its interaction with opiod receptors)

Benzodiazepines modulate the affinity of the GABA receptors for GABA.

Propofol infusion at 5 mg/kg/hr or greater for 48 hrs or more can lead to

--cardiomyopathy
--acute cardiac failure
--metabolic acidosis
--skeletal myopathy
--hyperkalemia
--hepatomegaly
--lipemia

(1) outpatient
(2) neurosurgery
(3) pediatric patients
(4) pollution issues
(5) costs & benefits in non-short term procedures

(1) use combo of propofol and remifentanil
(2) avoid long administrations
(3) IV access necessary
(4) rapid recovery even after long surgery time must be feasible
(5) PONV (post-op nausea & vomiting)

look at it..seriously

FA/FI rises more rapidly with less soluble anesthetics (nitrous oxide, desflurane)

see pg. 304 of the notes

(1) uptake -- thus the ratio of delivered to alveolar conc is greatest with more soluble drugs

(2) rebreathing -- thus, the ratio of delivered to alveolar conc decreases with increasing flow rates

..in other words, a higher fresh gas flow means that the equilibrium wil be reached quicker

(1) solubility of anesthetic
(2) duration of anesthesia

It is the time for the plasma level of the drug to drop 50% after cessation of infusion.

It is directly related to the time of infusion.

ketamine, propofol, etomidate have shorter half-times compared to thiopental & diazepam...thus, the 3 former drugs are more suitable for prolonged infusion

propofol

etomidate

distribution

TRUE

FALSE

This is the true statement:
Volatile anesthetics with LOW blood solubilities are associated with a rapid rise in FA/FI ratio.

Quicker

The less blood soluble a volatile anesthetic, the quicker anesthesia will be induced and the quicker the patient will recover.

ketamine or etomidate

1) thiopental: redistribution
2) etomidate: redistribution
3) ketamine: metabolized
4) propofol: metabolized