IV Anesthesia Flashcards
What are the current IV anesthetic agents?
Induction agents (thiopental, propofol, and etomidate)
Ketamine, diazpam, lorazepam, modazolam, opiates (longer DOA)
All of the IV anesthetics are highly lipid soluble. Why is this bad?
Because they are different to formulate for liquid formulations (not very liquid soluble)- this is overcome by adjusting pH and adding surfactants like propylene glycol or glycerol, or even use of a pro-drug
Although adding surfactants is useful for liquid formulations, they can cause AEs such asL
thrombophlebitis (conc and speed senstive so dilute and give slow)
What happens to the brain metabolic (glucose) activity in an anesthetized pt?
While drugs like ketamine do lower the activity via reduced neuronal activity, barbiturates like thiopental tend to be much less selective and induce much more brain depression
So… just because two drugs can both anesthetize a pt, it does not mean the unconscious state is produced in precisely the same manner in each
The effects of IV and inhalational drugs on targets. Notice how impacted (potentiated) GABA and glycine signaling are in resposne to these drugs, and how propofol and ketamine also affect the NMDA receptor for glutamate
How do barbiturates, benzodiazepines, etomidate, and propofol act?
all act to reinforce the inhibitory effects produced by endogenous GABA binding to its receptor. Propofol, at high conc, can even act like GABA itself.
NOTE that ketamine and propofol have glutamate inhibiting action as well (but act at different points)
How does propofol affect NMDA receptors?
it blocks the binding of glutamate to its receptor, whereas ketamine works to physically occlude the channel
What pathways contribute to the ascending arousal system (maintaing the waking state)?
1) Cholinergic (Ach) cell groups in the upper pons, the pedunculopontine (PPT) and laterodorsal tegmental nuclei (LDT) activate the thalamus
2) A second pathway activates the cerebral cortex to facilitate the processing of inputs from the thalamus. This arises from neurons in the monoaminergic cell groups, including the tuberomammillary nucleus (TMN) containing histamine, the A10 cell group containing dopamine (DA), the dorsal and median raphe nuclei containing serotonin, and the locus coeruleus (LC) containing nor. this pathway also receives contributions from peptidergic neurons in the lateral hypothalamus (LHA) containing orexin or melanin-concentrating hormone, and from basal forebrain neurons containing GABA or ACh
Both barbiturates and benzodiazepines act pon the GABA receptor to reinforce actions of GABA in the CNS. How do they do this?
Barbiturates prolong the binding of GABA to the receptor (and at high conc are capable of opening the Cl- GABA channel in the absence of GABA)
benzodiazepines produce only an allosteric change in receptor activity
Why are the potential AEs of OD of barabiturates worse than that of benzodiazepines?
Because barbiturates maintain continued action while benzodiazepines experience a ‘ceiling effect’ in the extent to which they produce CNS depression (cant OD on the benzos)
When compared to the osnet of inhaled anesthesia, the effects of IV induction are almost instantaneous. Drug rapidly distributes out of plasma into high flow organs like the brain, heart, and kidneys, and over time (fast in, fast out) to the muscle and skin and lastly adipose with its poor blood supply.
Remember, one effect of IV anesthetics being so lipophilic is that even though they have a rapid onset, they also have:
a short DOA (remember awakening of the pt is due to redistribution of the drug from the brain, not total metabolism)
What is propofol infusion syndrome?
These pts have diminished responsiveness to cardioactive drug support
