Barbiturates Class (Dr. E's lecture) Flashcards
Please note that the drug card information is for Educational Use ONLY, and the source is from Carrie Bowman's glossary of drug cards permitted by use of Georgetown NAP students. No permission is given to use these cards for anything other than as a study resource for our program.
How are barbs commercially prepared?
as sodium salts
How are barbs prepared with respect to pH? why?
HIGHLY Alkaline formulary (about pH >10)
they’re unstable
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?
Barbituric Acid
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?
THIObarbiturate (Thiopental)
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?
TPL: 1
Thiamylal: 1.1
Methohexital: 2.5
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?
IBW
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?
intensifies effect
Are barbs acids or bases?
WEAK acids!!!!! remember they are ACIDS, although they are prepared in >10 pH alkaline soln
How are oxybarbiturates metabolized?
Hepatic ONLY
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
Do barbs have active metabolites?
NO active metabolites
What is the E 1/2 time of TPL?
11.6 hours
What is the E 1/2 time of Methohexital?
3.9 hours
Why are the barbs prolonged in pregnancy?
due to increased protein binding
Which barb has greater hepatic clearance?
Methohexital
What is different between pediatric patients with TPL and the E 1/2 time
In pedi patients, TPL t 1/2 time is shorter than in adults, higher rate of HBF
What are the CNS effects of Barbs?
- Depresses level of consciousness
- Cerebrovasoconstriction, Reduced CBF, Decreased ICP and CMRO2
- Can produce isoelectric EEG (flatline the brain=cerebral protection)
- Paradoxical excitement
- Small doses decrease the pain threshold, “anti-analgesic”
- NO skeletal muscle relaxation
- Also decreases IOP
- Does NOT preclude SSEP monitoring
What is unique about Methohexital its CNS effects?
- excitatory skeletal muscle movements (myoclonus) and hiccups
- Cerebral protection
Do barbs produce skeletal muscle relaxation?
NO
What are the cardiovascular effects of Barbs?
- depression of medullary vasomotor center and decreased SNS outflow from CNS->peripheral vasodilation->preload decreases->SBP decreases, Compensatory HR INCREASE in normovolemic pts (activation of SNS peripherally!!!!)
- MINIMAL myocardial depression
- If SNS not intact (like in elderly), OR hypovolemic OR large doses given to decrease ICP, will see significant decreases in BP and myocardial depression
- Histamine release with rapid IV administration
- oral barbs produce minimal CV effects
What do barbs cause a release of ?
HISTAMINE release
What are the resp effects of Barbs?
- Dose dependent depression of medullary and pontine ventilatory centers
- Decreased ventilatory response to hypoxia and hypercapnia
- Apnea
- Depression of laryngeal and cough reflexes incomplete
What is important to note about subdoses of barbs? What does this increase the risk of?
if dose is not large enough can actually see a “Stage 2” like response to a/w manipulation-increased risk of laryngospasm, bronchospasm
What do barbs do to hepatic enzymes?
Hepatic enzyme induction with chronic use!
Which barb is the most potent inducer of hepatic enzymes?
Phenobarbital
What drugs are metabolized more quickly due to barbs?
Oral anticoags Phenytoin TCAs Corticosteroids Vit. K
What pathphysiologic condition is contraindicated with barbiturates? why?
Porphyrias!!!
barbs accelerate the production of heme by stimulation of the enzyme: D-aminolevulinic acid synthetase!!!
what can barbs cause vascularly?
venous thrombosis
What is a side effect of barbs that is greater than Midazolam and Propfol, but lower than Etomidate, Ketamine and volatiles?
N/V!
What can barbs do to metabolism?
can enhance their own metabolism-tolerance builds
What can happen if there is an allergic reaction to barbiturates?
Allergy 1:30,000 high mortality
presents as anaphylaxis
Allergy usually atopic patient-multiple allergies, with prior TPL exposure
What should you consider with dosing and age?
Decrease dosing in elderly
Increase dosing in peds
What is the induction dose of TPL?
3 -5 mg/kg IV
increase in peds (5-6mg/kg and infants 7-8mg/kg
What is the induction dose of Methohexital?
1-2 mg/kg IV or 20-30mg/kg PR in peds
What is the duration of a single IV induction dose of barbs? Why?
5 - 8 minutes
b/c of redistribution!
What medications should Not be in a mixture with barbs?
Dont mix with opioids, catechols, NMBs, midazolam, b/c they are acidic; and Pancuronium, Vecuronium, Atracurium Alfentanil, Sufentanil Midazolam LR is too acidic->precipitates
What solution should you use to reconstitute powder?
sterile H2O or NSS
What can occur if barbs are injected intra-arterially? What is the treatment?
- Immediate, intense vasoconstriction and pain
- mechanism-> crystalline precipitation inarterial vessel, inflammatory response, vasoconstriction, microembolization
Treatment:
- dilute with NS
- Phenoxybenzamine (alpha blockers!)
- Prevent thrombosis: heparin, urokinase
- Brachial plexus or stellate ganglion block
- Papaverine 40-80mg in 10-20ml saline or 5-10ml Lidocaine 1%
What are the S/S of a Porphyria attack?
- Severe abdominal pain with diarrhea and vomiting
- ANS instability-tachycardia, HTN
- Electrolyte disturbances
- skeletal muscle weakness, respiratory failure
- Seizure
- Neuropsychiatric disturbances
What specific drugs should you avoid giving with Porphyrias?
Thiopental Thamylal Methohexital Etomidate Pentazocine
In general, what is characteristic of the porphyrias?
- accumulation of porphyrins, the heme precursors (toxic to tissue in high concentrations)
- any increase in heme requirement (accumulation of the precursors immediately preceding the area of enzyme block
