Opiates half-lives

Dmgs, such as opiates, may undergo metabolism both in the intestinal wall and in the fiver (first-pass metabolism). The metabolism may be extensive and considerably reduce the amount of dmg reaching the systemic circulation. Alternatively, the metabolite may be metabofically active and contribute significantly to the action of the parent dmg. Some compounds undergo enterohepatic circulation in which they are secreted into the GI tract in the bile and are subsequently reabsorbed. Enterohepatic circulation prolongs the half-life of a dmg. 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

Mechanism of Action An opioid agonist that binds at opiate receptor sites in central nervous system (CNS). Therapeutic Effect Reduced intensity of pain stimuli incoming from sensory nerve endings, alteringpain perception and emotional response to pain. Pharmacokinetics Rapidly absorbed. Protein binding 40%-50%. Extensively distributed. Metabolized in liver. Excreted in urine. Half-life 11 hr. 

The most commonly used opiate substitute is methadone which has been available since the Second World War. It is a potent analgesic with a long half life, and thus once substituted for diamorphine can be reduced over a variable period of time. It is available in ampoules (for injection), tablets, linctus (2 mg in 5 ml), and mixture (1 mg in 1 ml). The use of ampoules and tablets is to be discouraged and many centres now are using the methadone mixture. This can be prescribed by any medical practitioner and requires no central licence. The use of ampoules and tablets has led to abuse, and these preparations have more of a black market value than the mixture. The amount of mixture used will depend on the amount of street heroin consumed and its potency, but it is usual to start at a safe dosage of between 30 and 50 mg daily for opiate dependents consuming half to one gramme... 

Friedrich, G., Braunstein, P., Friedrich, M., Vach, W. [Elimination half life of the opiate etorphine], Beitr. Gerichtl. Med. 1991, 49, 111-119. 

Cross-tolerance occurs between all opiates that act primarily via the mu receptors. This is the basis of the methadone substitution therapy which is commonly used to withdraw people who are dependent on heroin or morphine methadone is used because of its relatively long half-life (about 12 hours) and its ease of administration in an oral form. Cross-tolerance does not occur between the opiates and other classes of dependence-producing drugs such as the barbiturates, alcohol or the amphetamines, which act through different mechanisms. 

Indications Pain, migraine Category Opiate agonist-antagonist Half-life 2.5—4 hours... 

Indications Pain, cough suppressant Category Opiate agonist Half-life 2.5-4 hours... 

Trade name Heroin Indications Recreational drug Category Opiate agonist Half-life N/A... 

Category Analgesic Opiate agonist Half-life 1.3 7.0 hours... 

Indications Epidural and general anesthesia Category Anesthetic, general Opiate agonist Half-life 152 minutes... 

The enkephalins, H—Tyr—Gly—Gly—Phe—X—OH (X=Leu, Met), or so-called opioid peptides because they mimic the action of the opiates, morphine and heroin, have a very short half life in the body because all four peptide bonds are prone to undergoing proteolysis. The Tyr—Gly bond can be hydrolysed by amino-peptidases, the Gly—Gly bond by dipeptidylaminopeptidases, the Gly—Phe bond by enkephalinase and the Phe—Met and Phe—Leu bonds by carboxypeptidases. An enormous number of analogues have been synthesised, especially with the object of producing compounds that exert potent analgaesic action but are free from side effects. Protection of the susceptible bonds by changing the amino-acid sequence is the obvious way to achieve this. The analogue H—Tyr—d—Met—Gly—Phe—... 

Opiates Pupillary constriction, constipation, drowsiness, coma, slurred speech, respiratory depression, Flu-like muscle aches, nausea or vomiting, yawning, piloerection, [animation, rhinorrhea, fever, insomnia, pupillary dilation Opiates receptors, locus cereleus pathway (noradrenergic) Naloxone (short half-life), naltrexone (longer half-life), donidine (ease withdrawal), methadone, LAMM (Levo-ac-aretyl-methadol) substitute addictions,longer withdrawal period Males > Females 3 1 TB, AIDS, hepatitis, pulmonary hypertension, pneumonia... 

Naloxone and naltrexone are both competitive opiate antagonists. Naloxone has a very short half-life while the duration of action of naltrexone is several days. 

Naltrexone is particularly useful in outpatient therapy for withdrawal, as it has a long half-life (T /2 = 10 hours) and a single dose can block the euphoric effects of opiates up to 48 hours This helps to prevent the patient from procuring opiate drugs outside of the therapy milieu and getting high. ... 

As an oral drug, codeine is much less effective as an analgesic due to its large first-pass hepatic metabolism compared to morphine, hydrocodone and oxycodone. The plasma half-life of codeine is also shorter than many other orally available opiates such as morphine, hydromorphone, and oxymorphone. Like all opioids, continued use of codeine may result in tolerance development and physical dependence. However, when compared to potent mu agonists, codeine is less addictive and is associated with mild withdrawal symptoms. 

Naloxone s half life is shorter than most opiates, wearing off in 20-60 minutes... 

Heroin is rapidly metabolized to the active and specific metabolite 6-MAM and further to morphine and conjugated morphine. In turn, morphine is quickly converted to its principal metabolite M3G and, more slowly and in smaller amounts, to M6G. In general, the metabolism pathway of opiates is complex, because the taking place of several reactions of interconversion makes it difficult to certainly evaluate what a patient has consumed. For example, it is hard to understand if the patient, who has been prescribed diamorphine or morphine sulphate, has also consumed illicit heroin. The diagnosis cannot be done on the basis of morphine and 6-MAM contents, because their presence can be due to prescribed medications. Acetyl codeine would be a very useful marker for illicit heroin consumption, but unfortunately has a short half-life of only 237 min. Also through the determination of codeine and norcodeine, it is possible to evaluate whether the patient has taken illicit heroin as a source of morphine, but the interpretation is still difficult if codeine has been used in addition to diamorphine or illicit heroin. 

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