Morphine injectable forms

B. Benzomorphans - Clinical trials of the d 1 isomers of pentazocine (k) have shown "16 th both analgesic activity and side effects reside in the levo-isomer. Other trials, double-blind in many patients, confirm" 7,18 the activity of the compound at about one-third that of morphine, while measurements of respiratory depression in treated patients suggest" 9,20 this to be less than morphine at equianalgesic doses. The oral absorption has been determined2 1 and metabolic breakdown found22 to occur predominantly at the terminal methyl groups of the side chain. Reports of addiction to the injected form of pentazocine have been published ,24,25 including one to the oral form. 

A). Mice react to morphine with excitation, evident in the form of an abnormal posture of the tail and limbs. The dose dependence of this phenomenon is observed in groups of animals (e.g., 10 mice per group) injected with increasing doses of morphine. At the low dose, only the most sensitive, at increasing doses a growing proportion, at the highest dose all of the animals are affected... 

While heroin can be smoked and inhaled in its powder form, the primary method of administration is through intravenous injection. To inject heroin, the user mixes the powder with water, heats it, suctions it into a hypodermic needle, and injects it into a muscle or directly into a vein. Once in the body, heroin acts much more rapidly than morphine, crossing the... 

Heroin is diucetylmorphine idiamorphine hydrochloride I and is prepared hy (he action of acetic anhydride on morphine, possessing four times the analgesic affect of morphine, but having a considerably less depressant effect. Addiction is common, the drug being taken in the form of snuff, or by injection,... 

Anileridine, ethyl l-(4-amino phenethyl)-4 phenylisonipecotate is available in the form of its dihydrochloride for oral administration and as the phosphate for injection (Leritine ). Its analgesic potency is intermediate between that of meperidine and morphine. Similar to meperidine, it exerts mild antihistaminic and spasmolytic effects, but it is devoid of the constipating effect of opiates. Sedative and direct hypnotic effects are similar to those of meperidine but less than those of morphine. 

OFFICIAL NAMES Morphine sulfate or morphine hydrochloride (solutions for injection), Duramorph (for spinal use), MS Contin and Oramorph SR (long-acting, controlled release oral form), Kadian (oral, sustained release), MSIR (instant release), Roxanol (liquid concentrate)... 

Morphine is available by prescription in many forms. It can be taken orally as a liquid or as pills, and by injection under the skin, into the veins, or into the space surrounding the spinal cord. Rectal suppositories for pain control provide longer-lasting relief with less potential for nausea. As an abused drug, morphine can be smoked and sniffed as well as swallowed. 

In Figure 2.4 the serum concentrations of three tablet forms of a drug are compared with its IV form. As you can see, tablets A and B have approximately the same bioavailability (AUC). Tablet C, on the other hand, has significantly less. Poor oral bioavailability can obviously influence a drug s ideal mode of delivery. It is because of poor oral bioavailability (approximately 25 percent) of heavily charged weak bases, such as the opiates (pKa values in the range of 8.0-9.0), that heroin and morphine abusers resort to injection of the drugs to maximize their effects. 

Impurities in illicit morphine or heroin samples are important in establishing the manufacturing source of the drug. A16,17-Dehydroheroinium chloride (208) has been found(32l) in trace amounts in illicit heroin and may also be formed as a post-injection artefact during GC analysis of heroin samples. A synthesis from morphine-N-oxide by treatment with excess of hot acetyl chloride has been effected and 208 converted to 16-cyanoheroin (209) with aqueous KCN. 

Disposition in the Body. Readily absorbed after oral administration or by injection. Rapidly hydrolysed to 6-monoacetylmorphine in blood and then more slowly metabolised to morphine which is the major active metabolite normorphine is also formed to a minor extent small quantities of codeine are occasionally seen in the urine of addicts, but this is thought to arise from the presence of acetylcodeine as an impurity in illicit heroin samples. All metabolites may be conjugated with glucuronic acid. Up to 80% of a dose is excreted in the urine in 24 hours, mainly as morphine-3-glucuronide with about 5 to 7% of the dose as free morphine, 1% as 6-monoacetylmorphine, 0.1 % as unchanged drug, and trace amounts of other metabolites after inhalation, 14 to 20% of the dose appears in the urine morphine metabolites are excreted in the bile. 

Uethadone Hydrochloride, USP, Methadone hydrochloride. 6-(Dimethylamino)-4.4-diphenyl-3-heptanone hy-dnK hloride (Dolophine Hydrochloride), occurs as a bitter, white crystalline powder. It is soluble in water, freely soluble in alcohol and chloroform, and insoluble in ether. Methadone IS synthesized in several ways. The method of Easton et al. is noteworthy, in that it avoids the formation of the troublesome i.someric intermediate aminonitriles. The analgesic effect and other morphine-iike properties are exhibited chiefly by the (-) form. Aqueous solutions are stable and may be sterilized by heat for intramuscular and intrave-noas use. Like all amine salts, it is incompatible with alkali and salts of heavy metals. It is. somewhat irritating when injected subcutaneously. 

Edlund described a method for simultaneous determination of morphine, 6-0-acetyl morphine and codeine in human plasma or blood. The samples were buffered to pH 9 and extracted on silica columns, cleaned by extraction and finally acylated with pentafluoropropionic anhydride. The derivatives formed were separated on a glass capillary column (25 m by 0.36 mm I.D., coated with OV-1) at 220°C. The falling needle injection and electron capture detection were used. Although degradation of the solutes was observed, the degradation observed was very reproducible, so that quantitative analyses could be carried out in spite of the degradation. The author recommended regular control and calibration in order to obtain reliable results. 

Oberst (317) found that heroin (3,6-diacetylmorphine) (LXX) is de-acetylated to morphine which is then excreted in the free and conjugated forms by man. Morphine addicts excrete some 40 to 50 per cent of injected heroin hydrochloride as conjugated morphine and an additional 7 per cent as free morphine. A morphine addict was found to require only half as much heroin as morphine to satisfy physical dependence. When heroin and morphine were administered in doses having equal satisfying power (i.e., 1 2) 7 per cent of either drug was excreted as free morphine, and about 50 per cent as conjugated morphine. 

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