Pharmacology for Anaesthesia and Intensive Care

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8 General anaesthetic agents

N

N

H

HS C

O

O

C

C

R 1

R 2

—

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——

——

—

—

—

—

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N ——

N

Na

N

N

H

−S C

O

O

C

C

R 1

R 2

—

——

——

——

—

—

—

—

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——

Na+

H

S C

KETO FORM ENOL FORM

Alkaline

environment

O

O

C

C

R 1

R 2

——

— ——

——

—

—

—

—

—

——

——

Figure 8.4.Keto-enol transformation of barbiturates – tautomerism. Alkaline solutions favour

the water-soluble enol form.

Effects


Cardiovascular – there is a dose-dependent reduction in cardiac output, stroke

volume and systemic vascular resistance that may provoke a compensatory tachy-

cardia. These effects are more common in patients that are hypovolaemic, acidotic

and have reduced protein binding.


Respiratory – respiratory depression is dose-dependent. It may produce a degree

of laryngospasm and bronchospasm.


Central nervous system – a single dose will rapidly induce general anaesthesia

with a duration of about 5 to 10 minutes. There is a reduction in cerebral oxygen

consumption, blood flow, blood volume and cerebrospinal fluid pressure. When

used in very low doses it is antanalgesic.


Renal – urine output may fall not only as a result of increased anti-diuretic hormone

release secondary to central nervous system depression, but also as a result of a

reduced cardiac output.


Severe anaphylactic reactions – these are seen in approximately 1 in 20 000 admin-

istrations of thiopental.


Porphyria – it may precipitate an acute porphyric crisis and is therefore absolutely

contraindicated in patients with porphyria. The following drugs may also precipi-

tate an acute porphyric crisis:


Other barbiturates


Etomidate


Enflurane