Flashcards in Barbiturates Class (Dr. E's lecture) Deck (60)
How are barbs commercially prepared?
as sodium salts
How are barbs prepared with respect to pH? why?
HIGHLY Alkaline formulary (about pH >10)
At room temp, what is different about TPL?
prepared TPL is stable and sterile for at least 6 days
What types of isomers are in the Barbs?
Racemic Prep, BUT levo isomer is the potent one
What are barbiturates derived from? what constitutes this?
Urea + Malonic Acid = Barbituric Acid
What makes a barbiturate, chemically speaking with regards to structure? What effects does this cause?
Substitutions at Carbon 2 and 5; have sedative, hypnotic properties
What does it mean if there is a branched chain at C # 5 for the structure of Barbs?
-Branched Chain at #5 increases hypnotic activity
If there is an Oxygen at Carbon #2 what does this mean?
OXYbarbiturate (Phenobarbital, Pentobarbital, Methohexital)
If there is a Sulfur at Carbon #2 what does this mean?
What does it mean if there is a phenyl group at C # 5 for the structure of Barbs?
-Phenyl group at #5 increases ANTIconvulsant activity (phenobarbitol)
What does it mean if there is a methyl radical imparted in the structure of Barbiturates?
-Methyl radical imparts CONVULSANT activity (methohexital)
What does it mean if there is sulfuration in the structure of barbs?
-Sulfuration=fat soliuble, as lipid solubility increases: shorter duration, more rapid onset, increased potency
What is different regarding the long vs straight chain w/r/t the structure/activity relnships of Barbs?
-long branched chain is more potent than a straight chain
What are the relative potencies of TPL, Thiamylal, and Methohexital?
What is the MOA of Barbiturates?
-decreases the rate at which GABA dissociates from its receptor->increases duration of GABA activated Cl channel opening (enhances GABA)
-Mimics GABA at the receptor
-Decreases POST-synaptic membrane sensitivity to Ach-> some muscle relaxation- NOT surgical depth
-Also Directly decreases the transmission in the sympathetic ganglia-->hypotension
-interaction with GABA receptor produces functional inhibition of the postsynaptic neuron
What does Barbs mimic physiologically?
Depresses RAS-> SLEEP
What is the onset of barbs?
RAPID onset of action
What is important about the redistribution of Barbs?
Redistribution=Rapid termination of Effect
Is TPL protein bound?
70-85% protein bound
What is the fat: blood partition coefficient? what does this mean?
11= veryyyyy lipid soluble
what should you calculate your dosage of barbs based on?
If the patient is alkalotic, what does this do to the barbs?
alkalosis decreases the intensity of Barbs
If the patient is acidotic, what does this do to the barbs?
Are barbs acids or bases?
WEAK acids!!!!! remember they are ACIDS, although they are prepared in >10 pH alkaline soln
How are oxybarbiturates metabolized?
How are thiobarbiturates metabolized?
Hepatic and some extra hepatic
What terminates pharmacologic activity?
side chain oxidation at C#5 to Carboxylic Acid
Generally, how are the barbs metabolized?
desulfuration, hydrolysis, opens ring to water soluble combounds
How are barbs excreted?
renal primarily; < 1% excreted unchanged