Pentothal, Brevital, Etomidate, & Dexmedetomidine Flashcards
Define “intravenous anesthetic agent.”
Typically, a drug injected IV to induce unconsciousness at the beginning of general anesthesia, but allows rapid recovery after the end of its effect.
By which MOAs does an intravenous anesthetic agent typically work?
It changes level of consciousness by depressing the reticular activating system either by enhancing inhibition properties of GABA or inhibiting the NMDA excitatory synapses.
Which IV anesthetic agent is the “gold standard” to which all other agents are compared?
Thiopental (Sodium Pentothal)
What is the primary mechanism for terminating the central effect of IV induction agents?
Their redistribution from the central, highly-perfused compartment to the larger and less-well perfused “peripheral” compartments (skeletal muscles)
What is the alpha phase of pharmacokinetics?
Redistribution - plasma concentration declines so drug moves out of vessel-rich central group and to peripheral group
What is the beta phase of pharmacokinetics?
Elimination - metabolism and excretion
Describe the “ideal” IV anesthetic.
Water soluble/chemically stable/IV fluid compatible
Rapid onset w/o myoclonus or unpredictable CV or CNS SE
Anticonvulsant/antiemetic/analgesic/amnestic
Rapid onset (lipid soluble) and predictable recovery
No impairment of renal/hepatic function, steroid synthesis, or teratogenicity
No pain on injection
Low potential for histamine release/anaphylaxis
Rapidly metabolize to inactive substances/minimal accumulation
“Dialable”/rapidly responsive to titration
Cerebroprotective - dec metabolism in proportion to dec CBF, no inc in ICP
No hangover/HA
What drug class is thiopental?
Barbiturate - Thiobarbiturate (sulfur)
Describe the 2.5% preparation of thiopental
2.5% sodium salt (25 mg/ml) is water-soluble but highly alkaline pH 10.5 therefore bacteriostatic
How long will thiopental stay stable after reconstituted from a powder?
6 days at room temperature, 2 weeks in the refrigerator
What can occur when thiopental is mixed with opioids, catecholamines, NMB, and LR, which are more acidic? If injected intraarterially?
Precipitation!!
Is thiopental (2.5%) painful upon injection?
Minimally; irritating if extravascular but NOT necrotic
What is the MOA of thiopental?
Increases duration of GABA on its receptor (Cl- channels open longer –> hyperpolarization) AND mimics GABA on its receptor (directly causing Cl- channels to open)
Also activates glutamate, adenosine, and nACh receptors (SNS causes hemodynamic depression & desensitizes nACh receptors to depolarizing effects of ACh (large doses)
How do the hemodynamic effects of thiopental compare to propofol?
They are minimal in magnitude
What are the cardiovascular effects of thiopental?
Transient decrease in BP (arterial AND venous); increase in HR (carotid sinus baroreceptor - can be absent with beta blockade or hypovolemia); peripheral vasodilation (venous pooling, decreased venous return/CO) usually offset by sympathetic activation; HISTAMINE RELEASE.
Can you decrease CV effects of thiopental through SLOW administration?
No
How do myocardial depressant effects of thiopental compare with volatile agents?
Less; no direct myocardial depressant effect.
What are the respiratory effects of thiopental?
Decreases sensitivity of medullary ventilatory center to CO2 stimulation; respiration returns with small TV and slow RR; AW reflexes intact
Apnea potentiated with opioids, benzos, and other depressant drugs
Why might thiopental require concurrent administration of propofol for a general anesthetic?
Because airway reflexes remain intact, allowing the possibility of a laryngospasm
What are the CNS effects of thiopental?
Decreased ICP by cerebral vasoconstriction; decrease CMRO2 by 55%
Hypotension with large doses can decrease CPP below adequate
How much does thiopental decrease CMRO2?
55%
By what mechanism and under what conditions does thiopental provide cerebral protection?
Mechanism: reduction of CMRO2 is greater than decrease in CBF (demand less than supply)
Conditions: Successful in incomplete cerebral ischemia (CBP, hypotension, circ. arrest); NO protection for global ischemia (cardiac arrest)
Doses adequate to provide cerebral protection cause vasodilation/myocardial depression; hypothermia does same thing without these SE.
Does thiopental cause liver and kidney damage?
No; slight decrease in flow d/t reduction in BP, but no damage
What blood condition contraindicates use of methohexital and thiopental?
Porphyria; stimulates/increases production of heme
Does thiopental cross the placenta? If so, is it safe for the fetus?
Yes; maternal doses up to 4 mg/kg are safe for fetus
Dr. Cahoon knew of a resident who died in the call room from an overdose of which drug?
Thiopental; can cause tolerance and physical dependence
Thiopental can cause _________ and __________ reactions. (negative)
anaphylactoid; anaphylaxis
What is thiopental’s redistribution 1/2 life?
2-4 minutes
What is thiopental’s elimination 1/2 life?
10-12 hours (long beta phase!)
Thiopental (is/is not) highly lipid soluble and (non/ionized) at physiologic pH.
is lipid soluble; nonionized
Thiopental is __% protein bound.
85; protein binding effects the diffusion rate of the drug - the more bound, the slower the diffusion
What is the dose of thiopental?
3-5 mg/kg (less for elderly and early pregnancy)
What is the onset of thiopental?
30 seconds
What is the duration of thiopental?
5-10 minutes
How many redistribution 1/2 lives are required for termination of effect?
3-4
Summarize the properties of thiopental as an IV anesthetic.
“Gold standard,” minimal CV effects, good cerebral protection, minimal pain on injection, hangover, moderate emetic, precipitation
What is the drug class of methohexital?
Barbiturate - oxybarbiturate (less lipid soluble than thiopental)