Lecture 4: Barbiturates Flashcards
What are the two main barbiturates?
1) Thiopental
2) Methohexital
What is the common name of Methohexital?
1) Brevital
Which barbiturate is often used for ECT?
Methohexital
What is the pH of Thiopental and what are the implications of that?
Thiopental has a pH of 10.5, which means that bacteria cannot grow in it. However, it also means it burns upon injection when it comes into contact with the lower pH of blood.
Why do crystals form when you mix fentanyl and thiopental?
Fentanyl is an acid, and thiopental is a base. Acid + base = salt
How is thiopental supplied (in what form)? What is its expiration time in that form?
It is supplied as an anhydrous powder, and its shelf life is indefinite.
When thiopental is reconstituted and refrigerated, what is its shelf life?
Two weeks
When thiopental is reconstituted and left at room temperature, what is its shelf life?
24 hours
What is the mechanism of thiopental? How does it have a sedative/hypnotic effect on the brain?
It decreases dissociation of GABA to its receptor–makes GABA bind much stronger and much more long lasting. When GABA binds, Cl- channels open to hyperpolarize the cell and prevent neurotransmission.
How does the barbiturate mechanism of action differ from the benzodiazepine mechanism of action?
Barbiturates cause Cl- channels to remain open longer d/t an increase in strength in GABA bound to its receptor, whereas benzodiazepines affect the frequency at which Cl- channels open.
What is the pK of barbiturates? Does it favor the ionized or nonionized form?
pK= 7.6, so non-ionized form is favored
Of every dose you give, what percentage of barbiturates is bound to protein?
80%
Maximum uptake of barbiturates in the brain occurs in what time frame?
Within 1 minute of initial dose
Redistribution to the plasma results in barbiturate levels in the brain dropping to 10% in what time frame?
At what time point does the patient wake up? What sensation does this cause?
20-30 minutes, but patient wakes up after 5-10 minutes, leaving them with a hangover sensation
Barbiturates are metabolized in the:
liver
If you run an infusion of thiopental, it eventually redistributes to what type of tissue over every other type?
Fatty tissues
When you inject thiopental into the blood, what is its course of redistribution from that point?
From blood > brain and viscera > lean tissues > fat
Why do people often feel hung over after being put to sleep with thiopental?
The elimination phase of thiopental is long-lasting, and higher concentrations of thiopental stick around for longer amounts of time.
Onset, peak, and duration of thiopental?
Onset: 30-40 sec
Peak: 1 minute
Duration: 5-8 minutes
Are the metabolites of barbiturates active or inactive? How are they excreted?
Inactive
Excreted via kidneys
How does the half-life of thiopental compare to that of methohexital?
Thiopental’s half-life is over twice that of methohexital.
Thiopental is considered the gold standard treatment for what?
Cerebral protection
In what way does thiopental provide cerebral protection?
Provides circumstance in which brain is comatose to the point where it is not requiring any more O2 than that which necessary for basic cellular function–good for when you must reduce blood flow to the brain in neurosurgery.
What type of matter requires more O2 in the brain? What are the two CBFs of those two matters?
Gray matter: 75-80 mL/ 100 g/ min
White matter: 20 mL / 100g/ min
Therefore, gray matter requires more oxygen.
What is normal cerebral perfusion pressure? How do we calculate it?
80-100 mmHg
CPP = MAP - ICP
What is normal ICP?
8-12 mmHg
What is a normal value for global cerebral blood pressure?
45-55 mL/ 100 g/ min
What is normal CMRO2?
3-3.5 ml/ 100 g/ min
What percentage of cardiac output does the brain receive?
15%
60% of the brain’s energy consumption is used to support what?
Electrophysiologic function
What percentage of the brain’s energy consumption is used to support electrophysiologic function?
60%
What kind of effect do barbiturates have on CMRO2 and CBF?
Decreases them both (dose-dependent)
At what point will addition of barbiturate have no further effect on CMRO2 and CBF?
Point of EEG suppression–EEG is zero
For what type of ischemia is the concept of cerebral protection detrimental?
Global ischemia
Name three surgeries that would require focal ischemia:
1) CEA (carotid endarterectomy)
2) Thoracic aneurysm resection
3) Cerebral aneurysm clipping
Cardiovascular side effects of barbiturates?
Decrease SBP due to vasodilation, compensatory increase in HR
Which barbiturate causes histamine release?
Thiopental
By what means do barbiturates cause heat loss?
Vasodilatory effects
Describe the laryngeal response in patients induced with thiopental.
Patients retain their laryngeal response
By what degree does thiopental decrease CMRO2?
55%
As compared to benzos, why might barbiturates be a poor choice?
They have a lower therapeutic index, a less specific site of action, they result in tolerance much more frequently, and they have a high rate of abuse.
Under what circumstances might barbiturates cause a paradoxical effect?
1) In presence of uncontrolled pain
2) In children
3) In elderly
Rank these in terms of half-life, shortest to longest:
Diazepam, Midazolam, Remifentanil, Fentanyl, Thiopental, Propofol, Dexmedetomindine, Ketamine, Etomidate
1) Remifentanil
2) Etomidate
3) Propofol/Ketamine
4) Dexmedetomidine
5) Thiopental
6) Fentanyl
7) Diazepam
What is Acute Intermittent Porphyria?
A genetic metabolic disorder that affects heme production; deficiency in porphobilogen deaminase
What is porphobilogen deaminase?
The enzyme involved in heme synthesis
Why should you not administer barbiturates to patients with Acute Intermittent Porphyria?
Barbiturates exacerbate neurological episodes, use benzos instead
Which is more lipid soluble, thiopental or methohexital?
Methohexital
IV induction dose of methohexital?
1-1.5 mg/kg
Rectal dose of methohexital?
20-30 mg/kg
What is a common symptom of methohexital?
Hiccups
