Morphine respiratory effects

Bourke DL, Allen PD, Rosenberg M, Mendes RW, Karabelas AN. Dextroamphetamine with morphine respiratory effects. JC/mP/tanMaco/( 1983) 23, 65-70. 

Respiratory effects - A therapeutic dose of 0.3 mg buprenorphine can decrease respiratory rate similarly to an equianalgesic dose of morphine (10 mg). 

The most common side effect of pentazocine is sedation resulting from an interaction with the K-receptor. Also observed are sweating, dizziness, psychotomimetic effects, anxiety, nightmares, and headache. Nausea and vomiting are less frequent than with morphine. Respiratory depression and increased heart rate, body temperature, and blood pressure accompany overdose. Naloxone is effective in reducing the respiratory depression but requires the use of higher doses than for morphine overdose. 

Tolerance develops to the narcotic and analgesic actions of morphine, so that increasingly larger doses are needed to render patients pain free. Tolerance develops to many effects of morphine such as analgesia, euphoria, narcosis, respiratory depression, hypotension, and antidiuresis. Morphine-induced bradycardia may be experienced. However, no tolerance develops to morphine-induced miosis or constipation. If the administration of morphine is discontinued, the tolerance is lost and the preaddiction analgesic doses of morphine become effective once more. 

Interactions. Morphine (also pethidine and possibly other opioids) is potentiated by monoamine oxidase inhibitors. Any central nervous system depressant (including alcohol) will have additive effects. Patients recently exposed to neuromuscular blocking agents (unless this is adequately reversed, e.g. by neostigmine) are particularly at risk from the respiratory depressant effects of morphine. The effect of diuretic drugs may be reduced by release of antidiuretic hormone by morphine. Useful interactions include the potientating effect on pain relief of tricyclic antidepressants and of dexamfetamine. 

Cole PJ, Craske DA, Wheatley RG. Efficacy and respiratory effects of low-dose spinal morphine for postoperative analgesia following knee arthroplasty. Br J Anaesth 2000 85(2) 233-7. 

Nalbuphine was approximately equianalgesic with morphine (1) and its hemodynamic and respiratory effects were not statistically significantly different from those of morphine (SEDA-14, 69). Other studies have shown that this also apphes to other organ systems. However, unlike morphine, nalbuphine has a ceiling effect on respiratory depression, a low incidence of dysphoric effects, and a low addiction potential. Ten patients with a history of cardiac or orthopedic problems who received intravenous nalbuphine (6-20 mg) required additional doses of morphine (15-70 mg) to relieve pain (2). However, this report was not supported by objective physiological measures or recognized pain scores. 

Von Pahtzsch J. Respiratory effects of epidural morphine analgesia. Anaesthesiol Reanim 1982 7 335. 

Muir W V /, Skarda R T, Sheehan W C 1979 Hemodynamic and respiratory effects of xylazine-morphine sulfate in horses. American Journal of Veterinary Research 40 1417-1420... 

Tile general pharmacological action of codeine is similar 10 that of morphine, but as indicated above, it does not possess the same analgesic potency. Studies indicate that a dose uf. fO to 120 mg of ctxleinc is considerably less efficient uninterally than 10 mg of morphine, and the usual side effects of morphine—respiratory depression, constipation, nausea, and such—occur. Codeine is less effective orally lhan pareiitemlly, and Houde and Wallenstein stated that a do.se of. 52 mg of codeine is about as effective as 650 mg nf aspirin in relieving terminal cancer pain. Combinations... 

Children are generally more sensitive than adults (codeine should not be given to children less than Vi year old). The main risk of poisoning is the CNS-effect and respiratory depression, which can come late (especially for ethyl-morphine). An effective antidote is Naloxone (Narcan) ... 

Peak respiratory depression is observed within 1 hour of intramuscular administration, and there is a return toward normal starting in about 2 hours. Like other opioids, meperidine causes pupillary constriction, increases the sensitivity of the labyrinthine apparatus, and has effects on the secretion of pituitary hormones similar to those of morphine. Meperidine sometimes causes CNS excitation, characterized by tremors, muscle twitches, and seizures these effects are due largely to accumulation of a metabolite, normeperidine. As with morphine, respiratory depression is responsible for an accumulation of CO2 which, in turn, leads to cerebrovascular dilation, increased cerebral blood flow, and elevation of cerebrospinal fluid pressure. 

Amitriptyline, clomipramine, desipramine, and doxepin can enhance the analgesic and respiratory effects of morphine (mediated by serotonergic stimulation). 

The effects of a drug upon circulation and respiration are of prime importance in determining their safety in clinical use. If one follows published opinion one must come to the conclusion that morphine depresses the respiratory center. If one analyzes the published data, it is difficult to substantiate such a decision. Extensive data on the respiratory effects of morphine in the rabbit, dog, and cat are available and have been discussed in detail elsewhere (1). The concept of a depression of the respiratory center by morphine was initiated by the ex cathedra statement of van Bezold (22). Fluorens paper (23) on the location of the vital node or the first motor point of the respiratory mechanism had been published a few years earlier, and this probably served to focus attention on the respiratory center and led to the very logical explanation of decreased respiratory movements on the basis that morphine depressed the respiratory center. 

The researches of van Heerswynghels (198) on the analeptic respiratory action of theophylline-ethylenediamine follow the clinical observations of amelioration of respiratory conditions under the influence of this substance. The intravenous injection of theophylline-ethylenediamine (48 mg./kg.) provokes a prolonged and intense respiratory stimulation. It also abolishes the depression caused by morphine or Evipan by acting on the respiratory center in the medulla. This respiratory stimulation is seen in dogs whose carotid sinuses have been denervated. Theophylline alone provokes a respiratory stimulation ethylenediamine acts similarly, but its effects are very transitory. There is a synergistic activity of the respiratory effects of these two substances. 

The effect of metoclopramide on oral morphine absorption is an established interaction that can be usefully exploited in anaesthetic practice, but the increased sedation may also represent a problem if the morphine is being given long-term. The morphine-sparing effect of droperidol is also a useful interaction, but the increased sedation and possible respiratory depression and hypotension should be borne in mind. One manufacturer of fentanyl specifically warns that concurrent use with droperidol can result in a higher incidence of hypotension. ... 

Moren J, Francois T, Blanloeil Y, Pinaud M. The effects of a nonsteroidal antiinflammatory drug (ketoprofen) on morphine respiratory depression a double-blind, randomized study in volunteers. Anesth Analg (1997) 85, 400-5. 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

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