Morphine drug metabolism studies

Chemical studies on drug metabolism. IV. Synthesis and analgesic activity of morphine-7,8-oxide and heroin-7,8-oxide... 

In addition to studying hemodynamic changes caused by liberated histamine, plasma epinephrine and norepinephrine levels have been investigated following injection of morphine. In a study of a patient who experienced an anaphylactoid response following the intravenous injection of morphine 0.3 mg/kg, plasma catecholamines were increased and this was accompanied by decreases in systemic vascular resistance and arterial blood pressure. In another study, intravenous morphine increased cardiac output, histamine, and epinephrine plasma concentrations and decreased arterial blood pressure and systemic vasculature resistance in adult subjects with no history of drug allergy or clinical evidence of cardiovascular, pulmonary, or metabolic disease. 

Pentazocine has been successfully used to relieve labour pain [201] and its obstetric use in place of pethidine is favoured by,its apparent inferior ability to pass the placental barrier [206]. A clinical trial of (+)- and (-)-pentazocine adds to the rare number of examples in which optical enantiomorphs have been evaluated [207]. In post-operative patients, response to 60 mg of the dextro isomer was less than that to 5 mg of morphine, while 25—29 mg of (-)-pentazocine was as effective as 10 mg of morphine. Hence most of the activity of the race-mate resides in the laevo isomer, as anticipated from results in animals [208]. Several studies of the distribution, excretion and metabolism of pentazocine have been made. Peak levels of the tritium-labelled drug (and its c/s-3-chloroallyl analogue) were present in the C.N.S. of a cat within 40 minutes of intramuscular administration [209], the comparable figure for morphine being 2 hours [210]. 

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. 

Alkaloids are mainly plant-derived compounds that have been used as drugs such as morphine. Alkaloids are produced by simple extraction from plants. Studies show that alkaloids can be synthesized from amino acids by metabolic engineering in E. colt and S. cerevisiae. 

Ecstasy, cocaine and heroin are illegal in most countries. Although morphine and codeine are prescription rather than illicit drugs, they were included in the study by Agarwal et al. because they are major components of opium. Morphine is more generally used as an analgesic to relieve severe pain, while codeine is an antitussive (cough suppressant) and is partly metabolized to morphine in the body. 

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