Notebook: Anesthesia

Injectable anesthetics: rapidly acting anesthetics (examples: thiopental, propofol, etomidate, ketamine); slow acting (examples: potent opioids, neuroleptanalgesics)

BARBITUATES
- mechanism of action: allosteric modulation of the GABA A receptor
- increase in average duration of GABA-activated Cl- ion channel openings

Other mechanisms of action -- keywords for CNS: interaction w/ central Ca2+ and Na+ channels, glutamate and nicotinic ACh receptors. Depression of autonomic ganglia. keywords for PNS: block ACh effects at nicotinic synapses, inhibition of transmembrane Ca2+ fluxes

What do barbituates do?
- gradually depress the CNS (anesthesia)
- (don't provide analgesia)
- decrease EEG activity
- decrease cerebral blood flow
- decrease intracranial pressure
- provide anticonvulsive activity

Undesired effects of barbituates?
- central respiratory depression (i.e. hypoventilation)
- cardiovascular depression
- decrease in cardiac output
- decrease in arterial blood pressure
- may cause tachyarrhythmias
- decrease in renal blood flow
- decrease in hematocrit
- decrease in white blood cells
- perivascular injection may cause thrombophlebitis

Pharmacokinetics: How are barbituates eliminated?
- metabolized in the liver; conjugated with glucuronic acid
- renal excretion

Case in point: thiopental (pentothal)
- indicated for brief surgeries/ exams, neurosurgical patients with increased intracranial pressure, induction of general anesthesia, immediate control of convulsions

PHENOLS
- unrelated to barbituates
- main mechanism of action:
- allosteric modulation of GABA A receptor

What do phenols do?
- gradually depress CNS
- intravenous deep sedation
- non-hypnotic CNS effects:
- decrease cerebral blood flow
- decrease intracranial pressure
- antiemetic effects
- can be used for general anesthesia
- decrease EEG activity
- no analgesia

Undesired effects of phenols?
- respiratory system
- central respiratory system depression
- bronchodilation
- inhibition of laryngeal reflexes
- cardiovascular system
- hypotension
- transient excitatory effects

IMIDAZOLE (ETOMIDATE)
- good for inducing anesthesia in high-risk patients
- mechanism of action: allosteric modulation of GABA A receptor
- no analgesic effects
- decrease in EEG activity
- decrease in cerebral blood flow
- decrease in intracranial pressure
- cons: occasional CNS excitatory effects, hemolysis, pain, inhibition of adrenal steroid genesis

CYCLOHEXANONES
- ketamine, tiletamine. "dissociative anesthesia"
- loss of consciousness
- catalepsy
- maintenance of protective reflexes
- skeletal muscle movements
- mechanism of action: blocks NMDA receptor
- decrease in central glutamatergic activity
- provides analgesia and anesthesia

INHALANT ANESTHETICS
- inhalant anesthetic dose required to maintain an appropriate surgical plane of anesthesia is lower in older animals than in younger animals
- the speed of upake of inhalant anesthetics into the blood is inversely related to blood solubility and cardiac output
- inhalant anesthetics commonly cause vasodilation and negative inotropic effects
- they suppress the effects of excitatory neurotransmitters such as glutamate and ACh within the CNS
- inhalant anesthetics: degree of hepatic metabolism (ranked highest to lowest) is sevoflurane > isoflurane > desflurane > nitrous oxide
- the minimal alveolar concentration (MAC) of an anesthetic agent prevents gross purposeful movement in 50% of subjects exposed to a supramaximal noxious stimulus.

Isoflurane
- causes more significant cardiovascular depression than sevoflurane.

Sevoflurane
- sevoflurane is less potent than isoflurane
- sevoflurane allows for more rapid adjustment of anesthetic depth during anesthesia than does isoflurane
- In general, renal toxicity is not a common problem with sevoflurane.
- sevoflurane is more lipid soluble than desflurane

Desflurane
- desflurane is a halogenated ether
- desflurane has a more pungent odor and irritates airways more than sevoflurane does
- recovery of anesthesia from desflurane is faster than from isoflurane