IV Induction Agents

Thiopental: 4-7mg/kg, GABAa receptor positive allosteric  modulator (increase length that channels opens compared to benzos which increases frequency, aka efficiacy vs potency)

Special Properties:
- in subhypnotic dose, thiopental can be hyperalgesic (lowering pain threshold), can cause disinhibition and excitation

- acute tolerance: Early studies showed plasma thiopental concentration at awakening is proportional to the intubating dose rather than depth of anesthesia. The higher the induction dose, the higher the plasma levels at awakening. This was found to be not true in further studies and accounted for by studies that peripheral venous plasma thiopental concentrations poorly reflect brain (i.e., jugular venous) thiopental concentrations.
http://web.squ.edu.om/med-Lib/MED_CD/E_CDs/anesthesia/site/content/v02/020221r00.htm

- pH 10-11, long shelf life but precipitates NMBs, which come in acidic solutions

- Pain on arterial infection. DON'T DO IT because it extensive edema, gangrene, limb loss, and even death.

#Neuro
- See neuroprotection article. Basically thiopental is equal to etomidate and propofol.

#Resp
- decreases resp drive and airway reflexes. Airway responsiveness increases and this increased coughing and largynospasm more than other IV induction agents. Increases histamine circulation which can be bad for asthmatic.

#CV: unlike propofol, thiopental does not block sympathetic response and pts are more likely to become tachycardic with thiopental than propofol on inductoio

#Heme
- absolute contraindication in porphyrias. Thiopental induces CYP450 and delta-aminolevulinic acid (ALA) synthase, which builds up in pts with porphyria (downstream mutation). ALA is neurotoxic.

Propofol

Egg allergies to yolk (Lecithin) precludes its use.
Clearance is mostly hepatic but also extrahepatic, lungs play a role


#Neuro:
also acts on GABAa receptors. Also decreases CMRO2, CBP, ICP but may decrease CPP as propofol decreased MAP more than thiopental. (CPP=MAP-ICP). Does not produce hyperalgesia in sedative doses like thiopental. Has some amnestic qualities in sedative doses as well. Antiemetic effect as well.

#Resp:
Decreases vent drive, profound in COPD pts. Incidence of wheezing is lower with propofol than etomidate of barbituates.

#CV:
Profound hypotension from decreased preload (lower SVR), decreased afterload (cardiodepressant), and decrease baroreceptors and sympahtetic reflexes. More than thiopental

Fospropofol is a prodrug that is metabolized by alkaline phsophatase to form propofol, phosphate, and formaldehyde. Supposed to cause less pain in IV, less hyperlipidemia, and less risk of bacterial infection.

Etomidate
0.2-0.5mg/kg

- activates GABAa receptors and also some possible disinhibiting of extrapyramidal system causing myoclonus 40% of the time.
- dissolved in propylene glycol, which causes pain on injection

Ketamine
1-2mg/kg

#Neuro
- dissociates thalamus from limbic cortex causing dissociative anaesthesia
- elevates ICP, CMRO2, CBP but new research shows this may not be true when combined with benzos

#Resp:
Ketamine in USA is a bronchodilator and sialagogue. However, the S enantiomer found in Europe is the more potent version of ketamine and does not bronchodilate. Does not depress vent drive much

#CV
- cardiodepressant but potent stimulator of the sympathetic system. Increases HR, BP, and myocardial demand. Bad for CAD but may be good for shock.
- spinals or sympathectomies unmask the cardiodepression