Opioid analgesic drugs pharmacokinetics

Numerous applications of pharmacokinetic-dynamic models incorporating a biophase (or effect) compartment for a variety of drugs that belong to miscellaneous pharmacological classes, e.g., anesthetic agents [419], opioid analgesics [420-422], barbiturates [423,424], benzodiazepines [425], antiarrhyth-mics [426], have been published. The reader can refer to a handbook [427] or recent reviews [405] for a complete list of the applications of the biophase distribution model. 

The pharmacokinetics, pharmacodynamics and adverse effect profile of opioid analgesics are all relevant when considering the risks involved in using these drugs in patients with liver disease. There are also small variations between drugs in relation to pharmacokinetics and side effects, which may affect choice in certain circumstances. The decision to use opioids, the choice of opioid and the dose will therefore depend... 

While drug interactions based on pharmacokinetics do occur with sedative-hypnotics, the most common drug interaction is additive CNS depression. Additive effects can be predicted with concomitant use of alcoholic beverages, anticonvulsants, opioid analgesics and phenothiazines. Less obvious but equally important is enhanced CNS depression with many antihistamines, antihypertensives, and antidepressants of the tricyclic class. The answer is (A). 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

Pharmacokinetic/pharmacodynamic modeling can also assist in identification of the appropriate animal model in which to evaluate the mechanism of action. " Cox and his colleagues have developed a tooth pulp evoked potential (TPEP) rat model in order to investigate the analgesic effects of opioid drugs. The authors utilized a population sigmoidal pharmacody-... 

A placebo-controlled, crossover study in 26 healthy subjects found that both intravenous granisetron 3 mg and tropisetron 5 mg blocked the analgesic effect of a single 1 oral dose of paracetamol given 90 minutes later. The pharmacokinetics of paracetamol were unaffected by the two drugs. The interaction was thought to involve the serotonergic system, see Mechanism, in Opioids + Antiemetics Ondansetron , p.l61. 

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