Morphine concentrations plasma

Conversion from Avinza to other pain control therapies - It is important to remember that the persistence of Av/> za-derived plasma morphine concentrations may be in excess of 36 hours when making a conversion to other pain control therapies. 

M3G has no analgesic activity but may antagonise the analgesic effects of morphine. M6G is pharmacologically active with potency higher than morphine. The plasma concentration of M6G exceeds that of the parent drug by a factor of nine within 30 minutes of intravenous (IV) administration (Figure 7.4). Despite... 

Kronstand R, Jones AW. Concentration ratios of codeine-to-morphine in plasma after a single oral dose (100mg) of codeine phosphate. J Anal Toxicol 2001 25 486-7. 

With most opioids, including morphine, the effect of a given dose is less after oral than after parenteral administration because of variable but significant first-pass metabolism in the liver. The bioavailability of oral preparations of morphine is -25%. The shape of the time-effect curve also varies with the route of administration, so the duration of action often is somewhat longer with the oral route. If adjustment is made for variability of first-pass metabolism and clearance, adequate relief of pain can be achieved with oral administration of morphine. Satisfactory analgesia in cancer patients is associated with a very broad range of steady-state concentrations of morphine in plasma (16-364 ng/mL). 

Susceptibility factors Genetic Rapid metabolism of a dose of codeine within the recommended limits resulted in high plasma morphine concentrations, resulting in death in a 2-year-old boy who was given codeine syrup postoperatively following adenotonsillectomy [66 ]. The authors suggested that the ultrarapid metabolizer phenotype had been the main contributor to the occurrence of bronchopneumonia,... 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

The use of prodrugs with higher lipophrlicity compared to the parent molecule is realized in the classical example of heroin and morphine. Heroin, the di-acetyl derivative of morphine, penetrates the BBB by one log order better than morphine and is cleaved by tissue esterases to release the active parent drug. As follows from fhe pharmacokinetic principles shown in Section 2.3.2.1 (Eq. 2.3), brain concentration is a function of bofh BBB permeability, reflected by and plasma area under the curve ... 

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Since milk is more acidic (pH 6.5) than plasma, basic compounds (e.g., alkaloids, such as morphine and codeine) may be somewhat more concentrated in this fluid. In contrast, the levels of weak organic acids will probably be lower than those in plasma. In general, a high maternal plasma protein binding of drug will be associ-... 

Buprenorphine is a semi-synthetic derivative of thebaine, one of the opium alkaloids. It is approximately 30 times as potent as morphine. A dose of 0.3 mg intramuscularly has a duration of analgesic action of 6-18 h. Buprenorphine is also effective sublingually. The average bio-availability by this route is about 55%, but absorption is slow and the time to achieve peak plasma concentrations is variable, with a range of 90-360 min. The onset of action is rather slow (5-15 min) after both intramuscular and intravenous administration, possibly due to slow receptor association. Buprenorphine binds to and dissociates from the p receptor very slowly, which may account for its low potential for physical abuse. It also means that buprenorphine-induced respiratory depression is difficult to reverse with naloxone, even with very high doses. Doxapram may in these circumstances be useful. Drowsiness and dizziness are the most common side effects, although they rarely... 

M3G is the predominant metabolite in young children. The total body morphine clearance is 80% of an adult at 6 months of age.23 When the brains of experimental animals are directly injected with M3G, neuroexcitatory and anti-analgesic responses result, although this does not happen after system administration. Nonetheless, small amounts of M3G do cross the blood-brain barrier, and this may account for some reports of neuroexcitatory responses to morphine in humans. Attempts at correlating M3G plasma concentrations or M3G morphine or M3G M6G concentration ratios with the clinical activity of M3G have sometimes been successful, and sometimes not. To date, there are only two published studies describing the effects of injecting M3G directly into humans both studies yielded equivocal results.24... 

A patient is being treated with morphine by intravenous infusion. The steady state plasma concentration of the drug is to be maintained at 0.04 fig cm 3. Calculate the rate of infusion necessary assuming a first order elimination process (for morphine Vd is 4.0 dm3 and tU2 is 2.5 hours). 

Haskins JT, Gudelsky GA, Moss RL, Porter JC (1981) Iontophoresis of morphine into the arcuate nucleus effects on dopamine concentrations in hypophysial portal plasma and serum prolactin concentrations. 

FIGURE 17 Morphine plasma concentration after nasal administration of morphine formulations in sheep Mor Sol, morphine solution Mor Chi Sol, morphine solution containing chitosan Mor Chi PWD, morphine chitosan powder Mor SMS LPC, starch microspheres with lysophosphatidylcholine and morphine as a freeze-dried powder. (Reproduced from ref. 105 with permission of the American Society for Pharmacology and Experimental Therapeutics.)... 

Increased plasma concentrations of tricyclic drugs Potentiation of analgesic effect of morphine... 

In some cases, when the codeine-to-morphine ratio is higher than one, codeine abuse shall be considered as highly probable in association with heroin addiction whether 6-acetylmorphine has been detected or not. Finally, in all cases of chronic heroin abuse, 6-acetylmorphine, despite its very short plasma life, predominated over morphine and codeine in head and nonhead hair samples as well. The 6-acetylmorphine concentrations were approximately two- to threefold greater than metabolite morphine whatever the anatomical origin of the hair tested. 

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