Opioids drug interactions

The balance between hydrophobicity and hydrophilicity also determines the clinical characteristics of opioid analgesics, compounds that reduce pain without reducing consciousness (much). Dozens of opioids are in routine clinical use, and one reason so many are available is that they have different onset times and durations of action. This allows clinicians to choose the right one for a given circumstance. Most opioid drugs interact with a single type of receptor, the p-opiate receptor, which, like most cellular components, is lipophilic. Consequently, the primary determinant of onset time is lipophilicity, just as it is for local anesthetics and nonsteroidal anti-inflammatory drugs. 

The mu, kappa, and delta opioid receptors have been found to interact with endogenous peptide ligands that share certain pharmacologic properties with opioid drugs. These peptide ligands are derived from at least three different prohormones located in both... 

Managing Opioid Side Effects and Drug Interactions... 

Because seriously ill or hospitalized patients may require a large number of drugs, there is always a possibility of drug interactions when the opioid analgesics are administered. Table 31-5 lists some of these drug interactions and the reasons for not combining the named drugs with opioids. 

Portenoy and Payne (1997) observe that physical dependency as a result of prolonged use of opiates in programs of pain management does not reliably lead to addiction. "A reasonable hypothesis is that addiction results from the interaction between the reinforcing properties of opioid drugs and any number of characteristics... specific to the individual... such as the capacity for euphoria from an opioid and psychopathy" (582). 

Opioids basically exert their analgesic effects by inhibiting synaptic transmission in key pain pathways in the spinal cord and brain. This inhibitory effect is mediated by opioid receptors that are located on both presynaptic and postsynaptic membranes of pain-mediating synapses (Fig. 14—2). In the spinal cord, for example, receptors are located on the presynaptic terminals of primary (first-order) nociceptive afferents, and when bound by opioids, they directly decrease the release of pain-mediating transmitters such as substance P.35,38 Opioid drug-receptor interactions also take place on the postsynaptic membrane of the secondary afferent neuron—that is, the second-order nociceptive afferent neuron in the spinal cord.19,33 When stimulated, these receptors also inhibit pain transmission by hyperpolarizing the postsynaptic neuron.19... 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

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