Morphine VOLUME

The hasubanan alkaloids had been discussed as a subgroup of morphine alkaloids in Volume 13 of this treatise (/) until the succeeding review was published in 1977 (2) the two reviews cover the literature up to 1976. Since the... 

Hydromorphone is more soluble than morphine and approximately eight times more active upon parenteral administration. High solubility permits a lower volume of injected fluid, which is important if multiple injections are needed. It begins to work faster than morphine, but lasts for a shorter amount of time. It has a high sedative effect and a lessened capability of causing euphoria. Hydromorphone is used the same way as morphine. Side effects are analogous. Synonyms for this drug are dilaudid and others. 

In retrospect, the reason for this is not all that obscure. Most of the soldiers were in hypo-volaemic shock with low blood pressure, low blood volume, and as part of the shock syndrome, systemic circulation was minimal with intense vasoconstriction - hence the poor therapeutic effect. The repeated doses of morphine were usually given intramuscularly into the buttock or thigh but their clearance into the systemic circulation was minimal until resuscitation occurred and the peripheral circulation was restored. Blood flow to the muscle increased and all the morphine injected became available - all at once. This was the reason for the morphine overdoses and the occasional death. Thereafter it has become standard practice to give morphine in emergency directly into the veins and not into poorly perfused muscles. 

Morphine depresses all phases of respiration (respiratory rate, tidal volume, and minute volume) when given in subhypnotic and subanalgesic doses (Figure 47.6). In humans, a morphine overdose causes respiratory arrest and death. Therefore, morphine and other narcotic analgesics should be used with extreme caution in patients with asthma, emphysema, and cor pulmonale, and in disorders that may involve hypoxia, such as chest wound, pneumothorax, or bulbar poliomyelitis. 

Rasmussen [540] applied on-column silylation to the quantitative determination of morphine. A 1-jul volume of a morphine solution in ethyl acetate (containing ca. 1 /ig of the drug) and 2 jul of TMSIM were injected with temperatures of the injection port and of the column of 275 and 250°C, respectively, using 3% of Dexsil 300 as the stationary phase. It was stated that in this arrangement no free bases could be detected, i.e., the conversion was complete and the method provided reproducible results (the coefficient of variation was 1.3%). It was recommended preferrably for the rapid checking of pharmaceutical preparations. 

Respiratory depression is one of the most prominent adverse effects of p opioid agonists (e.g., morphine). The frequency of breathing and the inspiratory volume can be affected differently by drugs and have to be measured. 

Three animals are used for the test compound and the standard. Dose-response curves of the effect on respiratory frequency and volume are compared. While p, opioid agonists decrease respiratory function, k opioid agonist either increase or have no effect on respiratory function. The magnitude of respiratory depression produced by p, opioid agonists is related to their efficacy at opioid receptors with low efficacy agonists such as nalbuphine having much less effect on respiration as compared to morphine. 

The remaining two chapters provide fascinating insights into the alkaloids of mammals and of amphibians. As a follow-up to a chapter published in Volume 21 of this series, Arnold Brossi offers a critical review of the current status of the knowledge of mammalian alkaloids, such as those derived from tryptophan and from phenylalanine, and in particular he reviews the literature regarding the fascinating subject of whether morphine-like alkaloids are indeed mammalian metabolites. 

In order to extract the morphine, the opium resin must first be prepared. This is achieved by adding the raw opium to boiling water, in which the alkaloids dissolve, while the insoluble material can be removed while it floats, or is filtered from the solution. To extract the morphine from the processed opium, the latter is placed in a large volume of boiling water and calcium hydroxide added. The water is cooled and the unwanted alkaloids precipitate, while the morphine and some codeine remain in solution. The solution is then re-heated and ammonium chloride (and sometimes ethanol and diethyl ether) added. When the pH reaches 8-9, the... 

Morphine depresses respiration, principally by reducing sensitivity of the respiratory centre to increases in blood PaCOj. With therapeutic doses there is a reduced minute volume first due to diminished rate and then tidal volume. With higher doses carbon dioxide narcosis may develop. In overdose the patient may present with a respiratory rate as low as 2/min. 

Morphine and disease. When intense peripheral vasoconstriction accompanies, e.g. trauma, morphine administered s.c. or i.m. may appear to be ineffective because it fails quickly to enter the systemic circulation repeating the dose before the first has been absorbed may lead to poisoning when the vasoconstriction passes off. In such circumstances morphine should be given slowly i.v. (2.5 mg every 2-3 min). If the blood volume is low, morphine may cause serious hypotension. 

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