Ex 1 Barbs Slides Flashcards
Sedative hypnotic effects of barbiturates result from what?
Substitutions at the 2 and 5 carbon atoms of barbaturic acid
A branched chain on 5 results in
Greater hypnotic activity than straight chain
Phenol group on 5 results in
Enhanced anticonvulsant activity
Methyl radical on barbituric acid
Pro-convulsive effects
***Methohexital
Oxygen on 2 of barbaturic acid
Oxybarbiturates
** Methohexital, Pentobarbital
Sulfur on 2 results in
Thiobarbiturates - greater lipid solubility, faster onset, greater potency, shorter DOA
**Thiopental
Barbiturates MOA
Sedative, hypnotic via GABA-A (increase affinity of GABA for its receptor)
Increased Cl- conductance (directly activates Cl- channel) and hyperpolarizes post-synaptic cell
Distribution is dependent on
Lipid solubility — MOST
Protein binding
Degree of ionization
Tissue blood flow
Metabolism of oxybarbiturates
** methohexital, pentobarbital
Only in hepatocytes
Metabolites inactive/H20 soluble
Metabolism of thiobarbs
** Thiopental
Hepatocytes & extraheptic (kidney, CNS)
Metabolites inactive/H2O soluble
Most important step in terminating pharmacological activity in barbiturates
Oxidation of 5 carbon to carboxylic acid
Prolonged DOA means what?
Extreme hepatic dysfunction
STP is primarily metabolized in ______
Liver by CYP
Cirrhosis does not alter clearance
_____ metabolism is more rapid than _____
Methohexital
STP
STP induction dose
3-5mg/kg IV
Dose decreased with age/pregnancy
Pediatric induction dose STP
5-6mg/kg IV
Methohexital IV induction dose
1-1.5 mg/kg
Methohexital pediatric induction IV
1-2 mg/kg
Awakening from barbs are dependent on
Redistribution not metabolism
CNS effects
Tx of increased ICP in combo w/ hyperventilation and diuresis
-decreased CBF/CMRO2
STP CV effects
Transient hypotension d/t decreased preload Increased HR (d/t baroreceptors)
STP additional CV effects
Histamine release - rapid IVP
Profound hypotension, bronchoconstriction
STP ventilation effects
Dose dependent depression of ventilation
Shifts CO2 curve to the right (decreased sensitivity)
Decreased RR, VT
What may occur if barb dose inadequate?
Laryngospasm/bronchospasm
STP Liver effects
Decreased hepatic blood flow (related to BP)
CYP induction after 2-7d
How long will CYP induction persist after d/c?
30 days
Which Rx is most potent CYP inducer?
Phenobarb
As a result of the CYP inducer effect, what may happen to other drugs?
Other drugs are cleared more quickly
AE of barbs
Acute intermittent porphyria
S/S of AE
AIP- abd pain, constipation, muscular weakness, seizures, severe N/V
