Morphine withdrawal symptoms

Trilobine Raised pain threshold in mice did not induce or relieve morphine withdrawal symptoms in rats or monkeys and hence is nonaddicting 533... 

The methanol-chloroform extract has been reported to alleviate morphine withdrawal symptoms induced in mice by naloxone. The essential oil, the hydroalcoholic and the methanohc extracts displayed a concentration-dependent spasmolytic activity on isolated rat ileum. Such activity was partially attributed to a- and P-pinene. ... 

Jasinski DR, PevnickJS, Griffith JD Human pharmacology and abuse potential of the analgesic buprenorphine. Arch Gen Psychiatry 35 501-516, 1978 Jasinski DR, Johnson RE, Kocher TR Clonidine in morphine withdrawal differential effects on signs and symptoms. Arch Gen Psychiatry 42 1063-1066, 1983... 

Tapering of opioids may be necessary once the painful situation has resolved in patients receiving doses greater than 160 mg/day of oral morphine (or the equivalent) or in those with prolonged opioid use. In these situations the dose should be reduced by 15% to 20% each day to avoid withdrawal symptoms. 

Matthes HWD, Maldonado R, Simonin et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the /i-opioid-receptor gene. Nature 1996 383 819-823. 

In 1976 Martin proposed the theory that there are three subtypes of opioid receptor on the basis of behavioural studies using a chronic spinal dog model which revealed that the opioids morphine (mu) (1), ketazocine (kappa) (2) and A-allylnormetazocine (SKF 10047) (4) (sigma) had different effects on respiration, heart rate and locomotor activity [13]. Furthermore, these ligands were unable to replace each other to prevent withdrawal symptoms in dogs that had been chronically treated with one of the compounds. 

Patients dependent on narcotics Patients dependent on narcotics may experience withdrawal symptoms upon the administration of nalbuphine. If unduly troublesome, control by slow IV administration of small increments of morphine until relief occurs. If the previous analgesic was morphine, meperidine, codeine or another narcotic... 

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

The answers are 264-c, 263-c. (Katzung, pp 519, 535-537.) Heroin and other opioids (such as morphine and meperidine) exhibit a high degree of tolerance and physical dependence. The tolerance rate magnitudes to all of the effects of opioids are not necessarily the same. The physical dependence is quite clear from the character and severity of withdrawal symptoms, which include vomiting spasms, abdominal cramps, diarrhea, and acid-base imbalances among others. 

Nalbuphine hydrochloride is structurally related to oxymorphone and naloxone. It is approximately equipotent with morphine. Nalbuphine is metabolised in the liver to inactive metabolites. The plasma terminal half-life is approximately 5 h. The onset of analgesia is within 2-3 min of intravenous administration and 15 min after intramuscular injection, and lasts 3-6 h with an adult dose of 10 mg. With equi-analgesic doses, similar degrees of respiratory depression to that of morphine occur up to a dose of approximately 0.45 mg-kg-1. With higher doses a ceiling effect occurs. Sedation, possibly mediated by K-receptor activation, occasionally occurs. The incidence of psychotomimetic side effects is lower than with pentazocine. The abuse potential is low, but is can cause withdrawal symptoms in opioid-dependent subjects. It has occasionally been used to reverse opioid-induced respiratory depression. 

Methadone Slow-acting agonist of M-opioid receptor Acute effects similar to morphine (see text) Substitution therapy for opioid addicts High oral bioavailability half-life highly variable among individuals (range 4-130 h) Toxicity Respiratory depression, constipation, miosis, tolerance, dependence, and withdrawal symptoms... 

This example, and the point it supports, come from Seeburger (1993, 46) "Hospital patients who are given morphine or other narcotics for relief from pain can develop tolerance and can show withdrawal symptoms, once the administration of the drug is discontinued. Nevertheless, they rarely become addicted. Most have no difficulty getting off the drug and are often grateful to be able to do so."... 

The next four drugs are what are referred to as "mixed agonists-antagonists". Although all can be abused, the potential is lower for the normal person because of the lowered potency. However, the addict will experience withdrawal symptoms either from the drug itself or if the drug is taken with heroin or morphine because of the competition for opiate receptors. 

Matthes, H.W., Maldonado, R., Simonin, F., Valverde, O., Slowe, S., Kitchen, I., Befort, K., Dierich, A., Le Meur, M., Dolle, P., Tzavara, E., Hanoune, J., Roques, B.P., Kieffer, B.L. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene, Nature 1996, 383, 819-823. 

In the tail flick assay -conotoxin GVIA in combination with morphine leads to an additive effect similar to the combination of morphine with SNX-111 in the formalin test. But when -conotoxin GVIA was applied 24 h before morphine, antinociception was greatly reduced. In morphine-dependent rats, w-conotoxin GVIA given i.c.v. 15 min before naloxone challenge (2 mg/kg i.p.), significantly attenuated the withdrawal symptoms (Table 4, Basilico et al., 1992). 

Ethanol. As with morphine addiction, tolerance to alcohol is developed, and a lack of ethanol produces withdrawal symptoms. Tire principal route of metabolism of ethanol (both ingested and the small amount of endogenous alcohol) is believed to be oxidation in the liver to the chemically reactive acetaldehyde (p. 774),874/875 which is further oxidized to acetate. Some theories of alcoholism assume that addiction, and possibly also the euphoric feeling experienced by some drinkers, results from a metabolite of ethanol in the brain. For example, acetaldehyde could form alkaloids (Eq. 30-5).876... 

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