Morphine is a phenanthrene derivative. The effects are mediated by μ receptors. It is more effective for visceral pain and pain arising from deep structures and is less useful for superficial pain. It suppresses REM sleep and produces dysphoria and euphoria. Bradycardia and hypotension may be seen due to histamine release. It causes contraction of most sphincters except for the lower oesophageal sphincter which it relaxes. It has low lipid solubility and thus takes more time for its peak effect when given by the intramuscular route. It has a first-pass metabolism of 10–30 % via the oral route. Its half-life is 3–4 h. Dosage should be administered cautiously both in neonates (poor liver conjugating mechanisms) and elderly (decreased volume of distribution). It should be given cautiously in patients with liver and renal disease. It is metabolised by the gut wall and liver and morphine-3-glucuronide is the main metabolite. Another metabolite morphine-6-glucuronide is more potent than the drug itself.

It is a methylated product of morphine. Its oral bioavailability is better than morphine because of the presence of methylated compound (resists degradation). Metabolism is by CYP2D6; poor activity of which may not give adequate pain relief. It is metabolised in the liver and excreted in urine. Analgesia is due to conversion to morphine. Its half-life is 2–4 h (codeine 60 mg – NNT 16.7).

Tramadol is a synthetic racemic mixture which is a weak agonist at μ receptors. It also inhibits uptake of serotonin and norepinephrine. It has a bioavailability of 69 % after oral intake. Its protein binding is 20 % with a volume of distribution of 3.0–4.4 l/kg. The metabolite (O-demethylate) is four times potent than the parent drug. Racemic mixture is more potent than either of the enantiomer. It is metabolised in the liver and excreted by the kidneys. It causes less respiratory depression and constipation but more of nausea, vomiting and headache (tramadol 100 mg – NNT 4.8).