General Principles:Pharmacokinetics continued
Pharmacokinetics and Barbiturates: Introduction and
- Barbiturates: Although barbituric acid
was the first barbiturate synthesized over hundred years ago,
thiopental (Pentothal) has been clinical use for about 70 years in
its use mark the beginning of IV anesthesia. Barbiturate acid is
composed of urea and melonic acid (cyclic ureide of malonic acid)
- Rapidity of onset and duration of action (that is more rapid
onset with a shorter duration) is significantly affected by a
substitution at position 2: Thiopental (Pentothal) and
thioamylal exhibit a shorter duration of action and a rapid
onset compared to secobarbital (Seconal) and pentobarbital
Side Chain Differences between Barbituric
- 5Barbiturates as
anesthetic agents: Thiopental
- Major factors that determine to the characteristic uptake
for thiopental (Pentothal) include not only its intrinsic
lipid solubility but also the concentration gradient between
blood and tissue and importantly the extent of perfusion.
- For example, the brain received a significant percentage
of cardiac output and is also relatively lipophilic.
As a result, there is a rapid rise in thiopental (Pentothal)
brain concentration and as a result a short time to onset of
- On the other hand, there will also be a relatively rapid
decrease in brain thiopental (Pentothal) concentration as a
thiopental (Pentothal) equilibrates with other compartments,
such as muscle initially and ultimately with other large but
increasingly poorly perfused compartments.
- An understanding of thiopental (Pentothal) pharmacology
begins with the recognition that the rapid time to onset is
largely due to the lipophilic characteristic of the drug and
the significant percentage of cardiac output that goes to
the brain. The second important aspect is the
recognition that the short duration is due not to metabolism
but to redistribution from the brain to other compartments.
pharmacology-- a summary of organ system and other effects:
- Barbiturates may increase the patient's sensitivity to
pain. Administration of barbiturates the patient
in pain may result in agitation as opposed to
sedation. This observation suggests that other
drugs, for example opioids, might be appropriate to
manage pain and then subsequently an assessment made
concerning the need to sedate.
- Cerebral metabolism is depressed by barbiturates and
barbiturate administration is associated with decreased
cerebral blood flow and intracranial pressure. Changes
in these parameters are of sufficient size to be
important in neurosurgical cases.
- Slight myocardial depression is associated with some
tachycardia (increased myocardial oxygen consumption)
- Peripheral vasodilation (venodilation) is a principal
effect that, because of reduced preload, results in
reduced cardiac output.
- These cardiovascular effects should be considered as
important for the subgroup of patients who may be
particularly sensitive to these hemodynamic
effects. For instance patients with ischemic heart
disease might be adversely affected by the increased
myocardial oxygen requirement secondary to tachycardia.
Similarly, a hypovolemic patient may be more sensitive
to reduced preload due to increase peripheral
capacitance. The peripheral vasodilation results
in a hypotensive state which appears more pronounced in
patients who were initially hypertensive compared to
those who were normotensive.
- Barbiturates are respiratory depressants; Depressed
respiration can lead to apnea during induction
- Also, respiratory system responses to hypoxia and
hypercarbia will be diminished following barbiturate
- Laryngospasm may still occur because laryngeal
reflexes are relatively less affected by the drug.
- Reduced urine output may occur secondary to reduced
renal blood flow (presumably due to depressed cardiac
- Vasodilation may increase heat loss to an extent that
postoperative shivering may be worsened.
- As discussed earlier, barbiturate are absolutely
contraindicated in patients who have abnormalities in
porphyrin metabolism. Episodes of acute
intermittent porphyria may be induced by barbiturates
because of their effect in increasing aminolevulinic
acid synthetase, which is the enzyme that catalyzes the
rate-determining step in the porphyrin biosynthetic
- Although barbiturate are properly classified as
sedative-hypnotic agents, they lack certain characteristics
which are important for anesthesia -- including analgesia
and amnesia. Other drug groups, such as the opioids,
represent effective approaches to analgesia, whereas
certain benzodiazepines are very effective amnestic and
- Thiopental (Pentothal), however, is an effective
anesthetic induction drug although other agents, such as
propofol (Diprivan) are increasingly commonly used.
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3Correia, M.A., Drug
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and Inhaled Drugs", in Pharmacology and Physiology
in Anesthetic Practice, Lippincott-Raven Publishers,
5Dolin, S. J. "Drugs and
pharmacology" in Total Intravenous Anesthesia, pp. 13-35 (Nicholas L.
Padfield, ed), Butterworth Heinemann, Oxford, 2000