Gender differences in morphine pharmacokinetics and dynamics.

Abstract

The opioid system, composed of a family of structurally related endogenous peptides acting at µ-, δ- and κ-opioid receptors, (µOR, δOR and κOR, is involved in responses to pain, stress, reward and emotion and has a modulatory influence on physiological functions such as the control of breathing, thermoregulation, nociception and the immune response. 1 The opioid system displays marked differences among individuals with respect to its pharmacological and physiological effects. Evidently, this is the cause of the large variable effects of opioids in the delivery of adequate analgesia in patients with acute and chronic pain. Animal studies, particularly those using inbred strains of mice and rats, show that this variability is related, in part, to genetic differences in pain sensitivity, in the analgesic potency of exogenously administrated opioids, and in the response of the endogenous opioid system to pain and stress. 2–4 Recent studies revealed the importance of sex-related differences in the analgesic/antinociceptive responses of opioids. For example, male rats are more sensitive to the antinociceptive properties of morphine compared to female animals. 5 Strain-and sex-differences are not restricted to the analgesic properties of opioids, but also involve other opioid-mediated behaviour, such as locomotor activity, respiration, learning, memory, and addiction. Prospective human studies on the interaction of sex and opioid effect are scarce. An overview of studies investigating gender and opioid effect is given in Table 1. Here we describe the effects of gender on morphine’s pharmacokinetics and pharmacodynamics. The emphasis of this chapter will be on prospective placebo-controlled analgesic and respiratory studies. Tabele 1 Effect of µ- and κ-opioids and placebo in men versus womenFull size table KeywordsAnalgesic EffectRespiratory DepressionBolus DoseVentilatory ResponseMorphine AnalgesiaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.