Barbiturate mechanism of action
- GABA receptor agonist (increases the receptors affinity for GABA)
- depression of the reticular activating system (suppress excitatory neurotransmitters [acetylcholine] and enhance inhibitory neurotransmitters [GABA])
(when GABA receptors are activated, transmembrane chloride conductance increases, resulting in hyperpolarization)
The duration of action of highly lipid-soluble barbiturates is determined by what?
redistribution
The duration of action of barbiturates is determined by what, after repeated administration?
elimination (redistribution cannot occur with repetitive doses)
Induction doses of barbiturates can affect the cardiovascular system by a fall in what and an elevation in what?
a fall in blood pressure and an elevation in heart rate
After barbiturate administration, cardiac output is often maintained by…
a rise in heart rate and increased myocardial contractility from compensatory baroreceptor reflexes
Which patients would have an inadequate baroreceptor response?
hypovolemic, congestive heart failure, beta-adrenergic blockade
What would happen if you gave a barbiturate and there was an inadequate baroreceptor response?
cardiac output and arterial blood pressure might fall dramatically due to uncompensated peripheral pooling and unmasked direct myocardial depression
The cardiovascular effects of barbiturates depend on….
volume status, baseline autonomic tone, and preexisting cardiovascular disease
Barbiturates increase or decrease ICP?
decrease
Barbiturates increase or decrease cerebral oxygen consumption?
decrease (up to 50% of normal)
Methohexital lowers what?
the seizure threshold
What solution do you use to mix sodium thiopental?
sterile water
Thiopental induction dose, onset, peak, duration?
dose: 3 - 6 mg/kg IV
onset: < 30 seconds
peak: 30 - 60 seconds
duration: 5 - 15 minutes
Methohexital induction dose, onset, peak, duration?
dose: 1 - 2 mg/kg IV
onset: 30 seconds
peak: 30 seconds
duration: 5 - 10 minutes
What will happen if you mix barbiturates with opioids, catecholamines, or muscle relaxants?
precipitation, due to the acids mixing with bases
Barbiturates undergo maximal brain uptake within…
30 seconds
Barbiturate equilibration with skeletal muscle is reached in….
about 15 minutes (decreased doses are needed when skeletal muscle perfusion is decreased [shock] or when skeletal muscle mass is decreased [elderly])
Metabolism of thiopental takes place where?
in the liver (almost 99% metabolized).
(hepatic clearance is characterized by a low hepatic extraction ratio - influenced by hepatic enzyme activity, not hepatic blood flow)
Thiopental decreases the sensitivity of the medullary ventilatory center to stimulation of what?
carbon dioxide
Do barbiturates stimulate enzyme induction in the liver?
yes, after 2-7 days of sustained administration
Intraarterial injection of thiopental usually results in what?
immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery
What chemical are all barbiturates derived from?
barbituric acid (it is a cyclic compound formed from the condensation of urea and malonic acid)
Substitution at the number 5 carbon (C5) determines what about a barbiturate?
hypnotic potency and anticonvulsant activity (longer side chains result in higher potency. adding a phenyl group, as in phenylbarbital, makes it an anticonvulsive)
Replacing the oxygen on the number 2 carbon on barbituric acid with a sulfur atom increases what?
lipid solubility (thiobarbiturates are more lipid soluble than oxybarbiturates)
Does an induction dose of thiopental adequately abtund laryngeal reflexes or produce analgesia?
no, thiopental does not produce analgesia. it is considered an antianalgesic.
What types of patients should not receive barbiturate hypnotic agents?
- barbiturate allergy
- undergoing painful procedures
- patients with seizures
- patients with decreased ICP
- asthmatics
Name three medications (or types) that can be affected by the induction of liver enzymes by barbiturates.
anticoagulants, phenytoin, and tricyclic antidepressants
Is thiopental a weak acid or base?
weak acid
Does thiopental cause a histamine release?
yes
What is the standard thiopental dose for an RSI in an emergency cesarean section?
250mg
