Exam 1: General Barbiturates Flashcards
Barbiturates are commercially prepared as:
Highly alkaline sodium salts
Racemic mixture
Once prepared, barbs are:
Stable and sterile at room temp for 6 days
Isomers:
Levo and dextro; levo isomer is the potent one
Derived from:
Barbituric acid (urea + malonic acid)
Addition that ↑ hypnotic activity:
Branched chain at #5
Brain BRANCHES off into sleep
Addition that ↑ anticonvulsant activity:
Phenyl group at #5
PHENobarb is anticonvulsant
Addition that ↑ convulsant activity:
Methyl radical at #5
METHohexital used in ECT as it doesn’t dampen EEG
Effect of sulfuration:
More lipid soluble and thus more potent, more rapid onset, shorter duration
More potent: long branched chain or straight chain?
Long branched chain
Two classes of barbs based on carbon #2:
Oxygen at #2: oxybarbiturate
Sulfur at #2: thiobarbiturate
Relative potencies of three main barbiturates:
Thiopental: 1
Thiamylal/Surital: 1.1
Methohexital/Brevital: 2.5
MoA (5):
↓ rate of GABA dissociation
Mimics GABA
↓ transmission in SNS ganglia (hypotension)
↓ postsynaptic membrane ACh sensitivity (sub-surgical depth muscle relaxation)
Functional inhibition of RAS neurons (sleep)
General PK:
Rapid onset and short duration
Moderately high protein binding (70-85%)
Weak acids at physiologic pH (pK 7.6)
Metabolism of oxybarbiturates:
Hepatic
Metabolism of thiobarbiturates:
Hepatic + extrahepatic (renal, CNS)
Biotransformation that terminates pharmacologic activity:
Carbon #5 side chain oxidized to carboxylic acid
CNS effects:
↓ LOC Cerebral vasoconstriction and ↓ CBF, ICP, IOP, CMRO₂ Isoelectric EEG at high doses No effect on SSEPs Small doses: "anti-analgesic" effect
CV effects:
↓ SVR, preload, SBP
↑ HR
If SNS not intact: ↓ BP, myocardial depression
Histamine release with rapid IV admin
Reason for peripheral vasodilation:
Depression of medullary vasomotor center and ↓ SNS outflow
Respiratory effects:
Depression of pontine and medullary ventilatory centers
↓ response to hypoxia, hypercapnia
Incomplete depression of laryngeal reflexes
Complication with too-small dosing:
“Stage 2”-like response to airway manipulation
↑ risk of spasm
Metabolic effects:
Chronic use induces hepatic enzymes
Accelerates heme production
Other system effects:
N/V potential higher than midaz/prop (less than etomidate)
Allergy (1:30,000, high mortality)
Induction dosing of thiopental:
3 - 5 mg/kg IV
↓ for elderly, 1st trimester
↑ for kids (5-6mg/kg) and infants (7-8mg/kg)