Opioids physiological effects

The addictiveness of a given substance goes beyond the chemical structure of the addictive drug itself (i.e., morphine, cocaine, or nicotine). The effects are also related to the dose and speed of delivery, as well as to other substances that might be part of the formulation. For example, just as the oral consumption of opioids and cocaine produce substantially less pronounced behavioral and physiological effects than intravenous or smoked consumption, slow release forms of nicotine produce generally less pronounced effects than smoked forms (Henningfield and Keenan 1993). Similarly, the free base or unprotonated forms of cocaine and... 

Behavioral effects of opioids include euphoria, sedation and mental clouding. Physiological effects include respiratory depression, decreased heart rate, contraction of the pupil, constipation, nausea, and vomiting. Opioids can also release histamine from body stores, causing severe itching, hypotension, sweating, and flushing. 

Walker, D.J. et al., Subjective, psychomotor, and physiological effects of cumulative doses of mixed-action opioids in healthy volunteers, Psychopharmacology, 155, 362, 2001. 

Agonist occupancy of GPCRs, such as the delta opioid receptor, leads to physiological effects through interactions with heterotrimeric G proteins. Such G proteins consist of a Ga subunit and its Gpy dimeric partner. There are four major families of Ga proteins with different profiles of effector interaction 1) Gas, which activate adenylyl cyclase 2) Gai/o, so-called inhibitory G proteins named for their ability to inhibit adenylyl cyclase, but interact with many effectors 3) Gaq/11, which activate phospholipase C- 3 (PLC- 3) and 4) Gal2/13, which may regulate small GTP-binding proteins. Delta opioid receptors, like mu and kappa opioid receptors, couple to mem-... 

The idea that interactions between mu and delta contribute to behavioral and physiological effects of opioid agonists has been considered for over a decade. Evidence for mu/delta cooperativity has been obtained using molecular, cellular, and behavioral approaches [46-52]. However, models of mu/delta interaction have not yet been considered in detail from a circuit perspective. Thus, given that both mu and delta agonists can produce antinociception following focal application within the RVM, the question arises whether mu and delta actions in this system are coordinated or functionally independent. This issue has been addressed from two perspectives. 

OFQ/N and the ORLl receptor are also involved in a number of other physiological effects (see Refs. 87,891. One of the most significant effects is the anxiolytic activity of OFQ/N (1013), which has been postulated to be one of OFQ/N s most fundamental actions, and may help explain the effects of OFQ/N on other phenomena [e.g., locomotion, reward, and feeding (87)]. A small molecule ORLl agonist has also demonstrated anxiolytic activity (1014), demonstrating an important potential therapeutic application of these compounds. Like opioids, OFQ/N inhibits electrically induced contractions in the GPI and MVD smooth muscle preparations these effects are... 

Met-enkephalin and leu-enkephalin belong to a group of peptides called the opioid peptides, found predominantly in nerve tissue cells. Opioid peptides are molecules that relieve pain (a protective mechanism in animals that warns of tissue damage) and produce pleasant sensations. They were discovered after researchers suspected that the physiological effects of opiate drugs such as morphine resulted from their binding to nerve cell receptors for endogenous molecules. Leu-enkephalin and met-enkephalin are pentapeptides that differ only in their C-terminal amino acid residues. Substance P and bradykinin stimulate the perception of pain, an effect opposed by the opioid peptides. 

Rush CR. Pretreatment witii hydromorphone, a ja-opioid agonist, does not alter the acute behavioral and physiological effects of ethanol in humans. Alcohol Clin Exp Res (2001) 25, 9-17. 

More study and research is needed to evaluate parecoxib fully and the possible risks and benefits of its use. The benefits of opioid-sparing effects and decreased bleeding ride must be weighed against the cardiovascular ride in certain patient populations. The data available are still not definitive in the absolute risk profile of parecoxib. The possibiUties for use in non-cardiac patients, as well as the use of other agents in cardiac patients to temper the physiological mechanisms of 247... 

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