Morphine, conjugation

Figure 16. Effect of adding morphine antibodies to an external lysozyme-morphine conjugate on the release of glucose oxidase from a glutaraldehyde-crosslinked, partially deacetylated chitin. Amount of glucose oxidase in gel 1.5 mg/14.8 mg gel.

C morphine to correct for extractive losses. Morphine conjugates were hydrolyzed by B-gluc-uronidase and morphine extracted with ether. Nalorphine was used as an internal standard and... 

Livers of the mice receiving morphine alone had twice the amount of found in the W-allyl normorphine treated mice. Thus it seems that there is a lower rate of morphine conjugation in the livers of the mice treated with nalline. 

Morphin Albumine-morphine conjugate + fluoresceine marked antibody/ quartz fibre Competitive fluorescence, fibre optics... 

The analysis of codeine, morphine, 6-monoacetylmorphine (6-MAM, a metabohte of heroin), and cocaine is important for many toxicology labs to determine illicit drug use. When analyzing opiates in urine samples, frequently the matrix chosen for drug screening, the conjugated metabolites must be hydrolyzed however, this process can break down 6-MAM (Christophersen et al., 1987). These compounds can be derivatized to increase sensitivity, and both BCD and NPD are used for these assays. Derivatizations used include reaction with N-methyl-N-trimethylsilyltrifluoroacetamide followed by GC-FID (Lin et al., 1994) or with N,0-bis(trimethylsilyl)trifluoroacetamide (Christophersen et al., 1987 Lee and Lee, 1991), PFPA (Christophersen et al., 1987), or heptafluorobutyric anhydride (HFBA) followed by GC-ECD. All these methods show good sensitivity and selectivity. 

Other drugs are metabolised by Phase II synthetic reactions, catalysed typically by non-microsomal enzymes. Processes include acetylation, sulphation, glycine conjugation and methylation. Phase II reactions may be affected less frequently by ageing. Thus according to some studies, the elimination of isoniazid, rifampicin (rifampin), paracetamol (acetaminophen), valproic acid, salicylate, indomethacin, lorazepam, oxazepam, and temazepam is not altered with age. However, other studies have demonstrated a reduction in metabolism of lorazepam, paracetamol (acetaminophen), ketoprofen, naproxen, morphine, free valproic acid, and salicylate, indicating that the effect of age on conjugation reactions is variable. 

Meperidine readily passes the placenta into the fetus. However, respiratory depression in the newborn has not been observed, and meperidine clearance in the newborn is rapid in that it does not rely upon conjugation to glucuronides. Meperidine, unlike morphine, has not been associated with prolongation of labor conversely, it increases uterine contractions. 

Morphine orally is less effective and absorption is very slow. It has variable and high first pass metabolism when given by subcutaneous route, its analgesic effect starts within 10 minutes which persists for 4 to 5 hours and by IV route, it produces immediate action. In plasma, it binds to plasma proteins (approx. 30%). In liver it is metabolized by conjugation to glucuronic acid to form active and inactive products, which are excreted in urine. It is also excreted though bile and in the faeces. 

In neonates, and especially in premature infants, the mechanism for glucuronide conjugation is poorly developed. Renal function is also very inefficient. The pharmacokinetics of morphine in neonates is thus markedly different from that in older children and adults. This, together with age-related differences in the development of opioid receptors, may explain their increased sensitivity to morphine. 

Codeine, one of the principal alkaloids of opium, has an analgesic efficacy much lower than other opioids, due to an extremely low affinity for opioid receptors. It is approximately one-sixth as potent as morphine. It has a low abuse potential. In contrast to other opioids, with the exception of oxycodone, codeine is relatively more effective when administered orally than parenterally. This is due to methylation at the C3 site on the phenyl ring (Figure 7.3), which may protect it from conjugating enzymes. It is used in the management of mild-to-moderate pain, often in combination with non-opioid analgesics, such as aspirin or paracetamol. It is valuable as an antitussive and for the treatment of diarrhoea. Side effects are uncommon and respiratory depression, even with large doses, is seldom a problem. 

Esters (eg, heroin, remifentanil) are rapidly hydrolyzed by common tissue esterases. Heroin (diacetylmorphine) is hydrolyzed to monoacetylmorphine and finally to morphine, which is then conjugated with glucuronic acid. 

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