Pharmacology for Anaesthesia and Intensive Care

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9 Analgesics

Table 9.6.Clinical and kinetic data for some NSAIDs.

Drug

Maximum

daily dose

Elimination

half-life (h)

Plasma

protein-

binding

(%)

Analgesic and

antipyretic

activity

Anti-

inflammatory

activity

Aspirin 4 g variable* 85 +++ ++

Paracetamol 4 g 2 10 +++ ++

Diclofenac 150 mg 1–2 99 + +++

Ketorolac 40 mg 5 99 ++ +

Indomethacin 200 mg 6 95 + +++

Phenylbutazone 300 mg 50–100 98 + ++++

Tenoxicam 20 mg 72 99 +++

Meloxicam 15 mg 20 99 +++

Ibuprofen 1.8 g 2–3 99 ++

*When obeying first-order kinetics the t 1 / 2 elimination of aspirin is short (15–30 min). However, this is

significantly prolonged when enzyme systems become saturated and its kinetics become zero-order.

Ketorolac

Ketorolac is an acetic acid derivative with potent analgesic activity but limited anti-

inflammatory activity. It is also a potent antipyretic. It may be given orally or par-

enterally and has a duration of action of up to 6 hours. It shares the side-effect profile

common to all NSAIDs.

Indomethacin

Indomethacin is a potent anti-inflammatory agent but is a less effective analgesic.

Rectal use has been associated not only with a reduced peri-operative opioid require-

ment, but also with reduced platelet function resulting in wound haematoma and

increased blood loss. It is used to promote closure of the ductus arteriosus in the

premature infant by inhibiting prostaglandin synthesis. It shares the other effects

common to NSAIDs but has been particularly linked with headache. It may also

impair hepatic function and antagonize the effects of diuretics and angiotensin-

converting enzyme inhibitors.

Kinetics

Indomethacin is well absorbed from the gut with an oral bioavailability of 80%. It is

more than 99% bound by plasma proteins and is metabolized to inactive metabolites

that are excreted in the urine and bile. Five percent is excreted unchanged.

Pyrazolones

Phenylbutazone

Phenylbutazone is a potent anti-inflammatory agent. Its use has been limited to

hospital patients with ankylosing spondylitis due to serious haematological side