Opioid cardiovascular effects

Am J Physiol Lung Cell Mol Physiol 291 L58-L65 Hassen AH, Eeuerstein G, Eaden Al (1982) X Receptors and opioid cardiovascular effects in the NTS of rat. Peptides 3 1031-1037... 

Abrahamsson C (2000) Neuropeptide Y1- and Y2-receptor-mediated cardiovascular effects in the anaesthetized guinea pig, rat, and rabbit. J Cardiovasc Pharmacol 36 451-8 Ackley MA, Hurley RW, Virnich DE et al (2001) A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist. Pain 91 377-88 Aimone LD, Yaksh TL (1989) Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo. Peptides 10 1127-31... 

Pharmacodynamic interactions. Many TCAs cause sedation and therefore co-prescription with other sedative agents such as opioid analgesics, antihistamines, anxiolytics, hypnotics and alcohol may lead to excessive drowsiness and daytime somnolence. The majority of TCAs can have undesirable cardiovascular effects, in particular prolongation of the QT interval. A similar risk of QT prolongation arises with many other cardiovascular drugs including amiodarone, disopyramide, procainamide, propa-... 

The conorfamides, isolated from Conus spurius, belong to the RFamide neuropeptide family and may act as an agonist of the FMRF-amide-gated ion channels. In invertebrates, this peptide family has many diverse functions, whereas in the mammalian system they moderate opioid function in the CNS, modulate epithelial Na" " channels, have important cardiovascular effects, and stimulate pancreatic somatostatin secretion. ... 

Endogenous opioids and their multiple receptors continue as the focus of vigorous research. The proceedings of the 1983 International Narcotic Research Conference were published, and reviews were recently provided on opioid peptides,opioid receptors and their functional roles,pharmacology and therapeutic implications of enkephalins and endorphins, " cardiovascular effects of endogenous opioids, opioids and the adrenal-pituitary axis, opioids and the hippocampus, substance P in nociception, potential therapeutic roles for opioid antagonists, roles of opioid peptides in appetite control,and autoradiography of opioid receptors. 

Robinson et al. [8] noted that oxymorphone injectable was less likely to release histamine in dogs than equivalent doses of morphine. Since cardiovascular effects associated with histamine release (vasodilatation, hypotension) are minimal with oxymorphone this opioid may offer safety advantages for patients presenting with cardio- and cerebrovascular disease. 

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... 

Opioids depress respiration via the ji2-receptor at the level of the medulla and thereby increase PCO2. Opioids reduce respiration, an effect that is fatal in the case of overdose, by a dual action. The opioids decrease both the sensitivity of the medulla to carbon dioxide concentrations and the respiratory rate. Cardiovascular function and the response to hypoxia are not compromised. By contrast, tolerance to the respiratory depressant effects of the opioids does not appear to occur, while tolerance to the emetic effects of the opioids occurs upon repeated administration. The area postrema chemoreceptor trigger zone of the medulla mediates opioid-induced vomiting. 

Nitrous oxide has both a direct depressant and sympthomimetic effect on the myocardium. In healthy patients these tend to counterbalance each other, the resultant effect being minimal cardiovascular depression. In patients with car-diovascular disease or who are taking conconcurrent medication with, e.g. 3 blockers, its depressant effect may be more obvious. Nitrous oxide supplementation of high-dose opioid-based anaesthesia may result in a reduction in cardiac output and heart rate although the mechanism of this is unclear. Nitrous oxide may have a venoconstrictor effect resulting in increased pulmonary vascular resistance, particularly in the presence of pulmonary hypertension. 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

Etomidate is a carboxylated imidazole that can be used for induction of anesthesia in patients with limited cardiovascular reserve. Its major advantage over other intravenous anesthetics is that it causes minimal cardiovascular and respiratory depression. Etomidate produces a rapid loss of consciousness, with minimal hypotension even in elderly patients with poor cardiovascular reserve. The heart rate is usually unchanged, and the incidence of apnea is low. The drug has no analgesic effects, and coadministration of opioid analgesics is required to decrease cardiac responses during tracheal intubation and to lessen spontaneous muscle movements. Following an induction dose, initial recovery from etomidate is less rapid (< 10 minutes) compared with recovery from propofol. 

Nearly all opioids induce bradycardia (Bowdle, 1998), most likely mediated via central stimulation of the vagus nerve. Cardiovascular depression associated with most opioids is moderate and only the stronger opioids of the fentanyl group induce a more severe effect. Morphine and some of its analogs induce a non-opioid receptor-mediated release of histamine, which can result in a decrease in blood pressure and compensatory... 

Side-effects Levomethadyl acetate induces opioid-type side-effects with respiratory depression, bradycardia and impairment of cardiac contractility (Wolven and Archer, 1976). The compound increases the QT-interval and may induce Torsade de pointes (Deamer et al., 2001). Because of the cardiovascular side effects (Q/T interval prolongation) Levomethadyl acetate was recently withdrawn from the market in most of the european countries. 

Fentanyl is primarily used alone, but sometimes it is combined with other opiates such as Licodaine, Bupiva-caine, or morphine in epidural administration or in some I Vs. However, one of the more appealing virtues of fentanyl is that, unlike other opioids, it has a very mild effect on the emetic trigger zone of the medulla. For this reason, patients have less nausea and no vomiting when fentanyl is used. With other drugs, such as morphine, this unwanted side effect can be intense. Fentanyl also does not cause the release of histamine, which makes it safer for the cardiovascular system than morphine. 

Patients with a history of cardiovascular, respiratory, or intestinal problems should use hydromorphone with great caution. One of the most serious and overlooked side effects that develops from the long-term use of opioids is the potential for serious dehydration. 

The NEP and APN levels are moderate on heart [74,75] while the concentration of both peptidases is higher in vascular endothelium or vagus nerve terminals [76-78]. However, the mechanisms and site of action (central or peripheral) involved in the cardioprotective effects of the endogenous opioid peptides remain unknown. Nevertheless, owing to their lack of narcotic effects, inhibition of endogenous enkephalin catabolism and subsequent stimulation of delta receptor could have interesting clinical applications in the cardiovascular domain. 

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