Morphine dosage forms

Rectal Administration. The administration of drugs by a solid rectal dosage form (i.e., suppositories) results in a wide variability in the rate and extent of absorption in children [79]. This fact, coupled with the inflexibility of a fixed dose, makes this a route that should not be promoted for pediatric patients. At least one death involving a 7-month-old infant can be directly attributed to the use of solid rectal dosage form of a therapeutic dose of morphine [80]. 

Despite an intensive research effort over the past two decades involving many innovative approaches in the global academic community and by the pharmaceutical industry, the latter representing an aggregate investment in excess of 2.5 billion, the only new opioid-based pain medications either in clinical development or on the market are alternative dosage forms of the classical opioids, morphine, loperamide, and fentanyl, or compounds such as tramadol. ... 

Hallucinations have been described after the use of morphine in various dosage forms in one series, patients experienced adequate pain relief and no further hallucinations or nightmares when changed to oxycodone (540). Delusions and hallucinations have been reported in a patient who was also taking dosulepin (541). Restlessness, vomiting, and disorientation were described in two male patients over 60 years of age taking modified-release morphine for relief of pain in advanced cancer (542). 

HPLC has found considerable application within the pharmaceutical laboratory. For example, Roos [248] described a HPLC method for the separation, identification and quantitative determination of barbiturates in pharmaceutical dosage forms. The separation of 16 barbiturates was described and the effects of varying experimental parameters discussed. The successful separation of two cinchona alkaloids, four opium alkaloids, and heroin-related narcotics with measurements at nanogram to microgram levels has been achieved [249]. Quantitation and identification of morphine in opium in three samples was described by Wittwer [250]. 

Hydromorphone Hydrochloride, U5P. Hydromor-phone hydrochloride, dibydromurphinonc hydrochloride (Dilaudid). (K-curs as a light-sensitive, while cry.sialline powder that is freely soluble in water (l .1).. sparingly soluble in alcohol, and practically insoluble in ether. It is used in about one-fifth die dose of morphine for any of the indications of morphine. It is available in tablet, liquid, parenteral, and suppository dosage forms. The dose is I to 8 mg. 

A dosage interval of 12 h appears to be appropriate to use in dogs for oral sustained-release anhydrous theophylline tablets (Koritz et al, 1986) and oral sustained-release morphine sulphate tablets (Dohoo et al, 1994). Following oral administration of these sustained-release dosage forms, the average systemic availability of theophylline is 76% and of morphine is 21%. Gastro-... 

Coc,benzoylecgoni ne.morphine, he roi n, OAc-mo rph i ne, benzoic acid Stability coc and heroin in pharmaceutical dosage form pBondapak C18 300x4 ACN-0.015M Na2HP04(pH 3.0)(1 3) 51... 

Substitution of tetrazol-5-one for the thiophene ring in sufentanil results in a decrease in potency ( 25 times that of morphine) and a decrease in the pKa of the resultant compound, alfentanil (Table 24.4). The lower pKa of alfentanil results in a lower percentage of the drug existing in the ionized form at physiological pH. Being more un-ionized, alfentanil penetrates the blood-brain barrier faster than other fentanyl derivatives and has a faster onset and shorter duration of action. Alfentanil is 99% metabolized in the liver and has a half-life of only 1.3 hours. Alfentanil is available as an intravenous dosage form for use in ultrashort anesthetic procedures. 

Some additives can suppress dissociation of CyD complexes. Morphine occurs naturally in the opium poppy. It is a potent narcotic analgesic, and its primary clinical use is in the suppression of moderately severe pain. In patients with vomiting, a rectal dosage form such as a suppository should be usefiil, especially a prolonged-release-type suppository. We have demonstrated that a combination of a-CyD and xanthan gum, a polysaccharide-type polymer with high swelling capacity, enhanced rectal absorption of morphine in rabbits, when administered to rabbit s rectum in the form of Witepsol H-15 [81] hollow-type suppositories. The combination of CyDs and viscous polymers may be useful for optimizing the trans-mucosal delivery of morphine [81]. 

In clinical practice various oral dosage forms are also used for rectal administration. There is often little scientific support for such use, nevertheless it may be effective. Evidence exists for rectal administration of an oral controlled release morphine tablet (MS-Contin ) [2, 3]. Rectal use of temazepam oral capsules is not effective. There is a broad variation in time to reach the maximum plasma concentration and in the biological availability. Better outcomes are obtained with temazepam dissolved in glycofuroFethanol water = 5 1 4 and given rectally as an enema [4]. 

When the occurrence of flip-flop kinetics is not recognised it may compromise the interpretation of results from studies on the pharmacokinetic behaviour of slow release dosage forms. Flip-flop pharmacokinetics may occur with any extravascularly administered parenteral slow release dosage form. Intramuscular depot injectimis of antipsychotics such as fluphenazine decanoate, haloperidol decanoate or flupenthixol decanoate show this behaviour. It also occurs after the administration of oral slow release products of active substances such as isoxuptine, carbamazepine, diclofenac, valproic acid, morphine and theophylline. 

Morphine, distinction from codeine by ultraviolet Local anesthetics, ultraviolet as one of the techniques by which they can be identified in their dosage form Narcotics, 56 ultraviolet spectra... 

Causes of adverse effects over-dosage (A). The drug is administered in a higher dose than is required for the principal effect this directly or indirectly affects other body functions. For instances, morphine (p. 210), given in the appropriate dose, affords excellent pain relief by influencing nociceptive pathways in the CNS. In excessive doses, it inhibits the respiratory center and makes apnea imminent The dose dependence of both effects can be graphed in the form of dose-response curves (DRC). The distance between both DRCs indicates the difference between the therapeutic and toxic doses. This margin of safety indicates the risk of toxicity when standard doses are exceeded. 

Dosages and routes of administration Morphine is available in different salt forms but the hydrochloride and sulfate (Vermeire and Remon, 1999) are used preferentially. The compound can be administered by the oral, parenteral or intraspinal route. Oral application is preferred for chronic pain treatment and various slow release forms have been developed to reduce the administration frequency to 2-3 times per day (Bourke et al., 2000). Parenteral morphine is used in intravenous or intramuscular doses of 10 mg, mostly for postoperative pain and self-administration devices are available for patient-controlled analgesia (PCA). Morphine is additionally used for intraspinal (epidural or intrathecal) administration. Morphine is absorbed reasonably well in the lower gastrointestinal tract and can be given as suppositories. 

The time taken for diffusion of poorly lipid-soluble opioids, such as morphine, from the lumbar subarachnoid space to the fourth ventricle is the most likely explanation for the delayed onset of respiratory depression. It has been suggested that the frequency of respiratory depression can be influenced by the position of the patient and the form of administration, as well as by the dosage of the opioid and the volume of the solution (112). 

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