Morphine infarction

Relief of pain associated with a myocardial infarction (morphine)... 

Morphine produces venous and arteriolar dilation, which may result in orthostatic hypotension. Hypovolemic patients are more susceptible to morphine-induced hypotension. Morphine is often considered the opioid of choice to treat pain associated with myocardial infarction, as it decreases myocardial oxygen demand. 

Q87 Morph ine should not be used for pain relief in myocardial infarction. Morphine may induce hypotension as a side-effect. 

Opioids such as diamorphine, pethidine, and pentazocine strongly inhibit gastric emptying and greatly reduce the absorption rate of paracetamol. Codeine, however, has no significant effect on paracetamol absorption. Morphine and diamorphine have been shown to reduce the absorption of antiarrhyth-mics such as mexiletine in patients with myocardial infarction. 

Most of the contraindications specific to pentazocine stem from its excitatory effects. Other contraindications are similar to those for morphine. Pentazocine is contraindicated in patients with myocardial infarction because it increases heart rate and cardiac load. Similarly, it is contraindicated in epileptic patients because it decreases seizure threshold. In addition, in head trauma patients, it can increase intracranial pressure and brain injury. Pentazocine use in patients with psychoses is contraindicated because of its psychotomimetic side effects. 

Butorphanol tartrate is a weak partial p-receptor agonist, 3.5-5 times as potent as morphine. The incidence of psychotomimetic effects is relatively low. The recommended doses are 1-4 mg intramuscularly every 3-4 h or 0.5-2 mg intravenously. Respiratory depression produced by butorphanol 2 mg IV is similar to that of 10 mg morphine. However, there is a ceiling effect for respiratory depression, and near-maximum depression occurs after 4 mg in normal adults. In healthy volunteers, butorphanol 0.03-0.06 mg-kg-1 produces no significant cardiovascular changes. However, in patients with cardiac disease, progressive increases in cardiac index and pulmonary artery pressure occur, and butorphanol should be avoided in patients with recent myocardial infarction. Butorphanol is metabolised mainly in the liver to inactive metabolites. The terminal half-life is 2.5-3.5 h. 

On the other hand, a number of studies have shown that morphine and opioid peptides could have cardioprotective effects toward ischemic processes and may be able to reduce the size of infarct [72,73]. These effects seem to involve the activation of delta opioid receptors, the localization of which remains unknown. In addition, enkephalin-degrading enzyme inhibitors, such as acetorphan and, particularly, RB 101, have also been demonstrated to decrease the susceptibility to the arrhythmogenic action of epinephrine. Thus RB 101 completely prevented the ventricular tachycardia, fibrillation, and repetitive ventricular extrasystoles induced by epinephrine (Maslov et al., unpublished data). These effects were reversed by the selective delta antagonist ICI 174,864. 

Interestingly, morphine is primarily considered to have selective effects on the mu opioid receptor for its analgesic effects however, there is also evidence that it possesses effects on delta or kappa opioid receptors and that crosstalk can occur between mu and delta opioid receptors [44]. To test the hypothesis that the cardioprotective effects of IPC and morphine were acting via a delta opioid receptor, Schultz et al. [45] administered the selective delta receptor antagonist naltrindole to rats prior to IPC or morphine infusion. In both instances, the cardioprotective effects of morphine and IPC were completely abolished at a dose of naltrindole that had no effect by itself on infarct size in nonpreconditioned rat hearts. These data clearly suggest that both IPC and morphine are exerting their cardioprotective effects via the delta opioid receptor in the intact rat heart. 

To further address the signaling pathways involved in opioid-induced cardioprotection, Schultz et al. [55] determined the involvement of a Gi/o protein in mediating delta -induced cardioprotection produced by the selective nonpeptide delta opioid agonist, TAN-67. Pretreatment with pertussis toxin for 48 h prior to TAN-67 administration completely blocked its cardioprotective elfect as well as that to IPC, suggesting that a Gi/o protein is intimately involved in the cardioprotection produced by these two interventions. Subsequently, Miki et al. [56] found that morphine produced a cardioprotective elfect in isolated rabbit hearts which was blocked by pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor at a concentration that had no elfect on infarct size in the absence of morphine. More recently, Fryer et al. [57] extended these findings to the intact rat heart and showed that the protective elfect of TAN-67 to reduce infarct size was blocked by chelerythrine and GF 109203X, two selective PKC inhibitors with different binding sites, and that TAN-67 produced a selective translocation of the PKC-delta isoform to the mitochondria. 

Acute severe pain after trauma (accidents), myocardial infarction, etc. and life-threatening pulmonary edema requiring inhibition of the respiratory center. For these indications, administration of morphine (intravenously or subcutaneously) in suf cient amounts is appropriate. With short-term use, development of tolerance or dependence is of no concern. 

MI usually develops after rupture or erosion of an atherosclerotic plaque within a coronary blood vessel. At this site, the clotting cascade is activated and the resultant thrombus occludes the lumen. In all patients under suspicion of MI, immediate therapy has to be initiated by the emergency physician. To relieve the patient from severe pain and anxiety, morphine and a benzodiazepine need to be given. Antiplatelet drugs and heparin are necessary for preventing further formation of thrombi. Nitroglycerin can be used to reduce cardiac load. When blood pressure and heart rate have stabilized, a p-blocker can be administered to lower cardiac 02 consumption and the risk of arrhythmias. Infusion of lidocaine is required to counter the threat of arrhythmias. The chance of survival of the MI patient depends on the interval between the onset of infarction and the start of therapy. 

Intrabiliaiy pressure may rise substantially after morphine (as much as 10 times in 10 minutes), due to spasm of the sphincter of Oddi. Sometimes biliary colic is made worse by morphine, presumably in a patient in whom the dose happens to be adequate to increase intrabiliary pressvue, but insufficient to produce more than slight analgesia. In patients who have had a cholecystectomy this can produce a syndrome sufficiently like a myocardial infarction to cause diagnostic confusion. Naloxone may give dramatic symptomatic relief, as may glyceryl trinitrate. Another result of this action of morphine is to dam back the pancreatic juice and so cause a rise in the serum amylase concentration. Morphine is therefore best avoided in pancreatitis but buprenorphine has less of this effect. 

Adverse cardiac effects due to morphine are rare. They comprise inappropriate heart rate responses to hypotension, rather than conduction defects. They are not especially associated with inferior myocardial infarction, as was previously thought (SED-11,142) (14). 

Intravenous patient-controlled administration of morphine (total 56 mg in 9 hours) was associated with down-beat nystagmus in a 61-year-old man with a Grade 3 adenocarcinoma of the gastro-esophageal junction and a previous small cerebellar infarct (18). Withdrawal of the analgesia led to complete resolution of aU signs and symptoms within 12 hours. 

Morphine hydrochloride Use in palliative care, pain relief in respect of suspected myocardial infarction or for relief of acute or severe pain after trauma, including in either case postoperative pain relief Rectal... 

Endogenous opioid peptides are increased in myocardial ischemia. Their effect is mediated through presynaptic and postsynaptic mechanisms. Opioids limit the release of stimulating catecholamines by its presynaptic action while opioid receptor agonists act via Gi -linked pathways postsynaptically and alter myocardial channel activity and intracellular activities of protein kinases. Table 1. Figure 10. Blockade of 5 and x-opioid receptors reduced the tolerance of the isolated rabbit heart to ischemia and reperfusion.105 Furthermore, blockade of 8-opioid receptor abrogated the ischemic preconditioning mediated cardioprotective effect while activation of 8-opioid receptor by morphine decreased infarct size and apoptosis in a rabbit model of coronary occlusion and reperfusion.106... 

S. Okubo, Y. Tanabe, K. Takeda, M. Kitayama, S. Kancmitsu, R.C. Kukreja and N. Takekoshi, Ischemic preconditioning and morphine attenuate apoptosis and infarction after ischemia-reperfusion in rabbits role of delta-opioid receptor, Am. J. Physiol. 287(4), H1786-H1791 (2004). 

Little information exists about how a patient s drug therapy influences the informed consent process. For example, can a patient who has had several doses of intravenous morphine give consent to participate in an acute myocardial infarction protocol Sedated patients may not understand adequately what they are being told therefore, they cannot make up their minds freely. As another example, how informed can patients be who are experiencing blurred vision from atropine Does drug exposure influence continued participation or future consent If there are any doubts, a family member, guardian, or patient advocate should be involved in the informed consent process. 

Therapeutic doses of morphine have minimal effects on blood pressure, cardiac rate, or cardiac rhythm when patients are supine however, morphine does produce venous and arteriolar vessel dilatation, and orthostatic hypotension may result. Hypovolemic patients are more susceptible to morphine-induced cardiovascular changes (e.g., decreases in blood pressure). Because morphine prompts a decrease in myocardial oxygen demand in ischemic cardiac patients, it is often considered the drug of choice when using opioids to treat pain associated with myocardial infarction. 

Enzyme changes occur in several gastrointestinal conditions, such as intestinal infarction or obstruction, parasitic infections, obstruction of the biliary system, and contraction of the sphincter of Oddi by drugs such as morphine, withdrawal of food, and age-related changes. 

Effects on the myocardium are not significant in normal individuals. In patients with coronary artery disease but no acute medical problems, 8-15 mg morphine administered intravenously produces a decrease in oxygen consumption, left ventricular end-diastolic pressure, and cardiac work effects on cardiac index usually are slight. In patients with acute myocardial infarction, the cardiovascular responses to morphine may be more variable than in normal subjects, and hypotension may be more pronounced. 

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