To classify opioid analgesics we need to analyse the activity of the drug and decide whether it activates or inhibits the function of the opioid receptors. We are going to look at two different opioid analgesics – Agonists and Antagonists.Pure AgonistsAn agonist is a drug that has an affinity for cell receptors to induce changes in the cell characteristic of the natural ligand.
3 Morphine, the prototype of methadone, is a long-lasting opioid which is used to treat heroin dependency. Fentanyl is a short-acting opioid with clinical use in anaesthesia and has a very high potential for abuse.Pure AntagonistsHave an affinity for a receptor, but after attaching they elicit no change in cellular functioning. However, they block access of either endogenous ligands or an exogenous drug e.g. morphine.Structure and UseMorphineIs used as an analgesic which has tranquillising actions. Water-soluble opioid penetrates the blood-brain barrier more slowly than the more fat-soluble opioids.
Only small amount of morphine ever penetrates the brain. When metabolized morphine has many different forms; one of them (morphine-6-glucuronide) is even more potent as an analgesic than morphine. The half-life of both opioids is about 3 to 4 hours. Study of morphine led to the discovery of substances which could act as full or partial agonists or competitive antagonistsProduction3 – the harvested opium is mixed with lime in boiling water. When the organic waste sinks to the bottom and morphine can be drawn off the top. It is then reheated with the addition of ammonia, filtered and boiled down to form a brown paste – the morphine base.Although both morphine and methadone are classified as opioids, methadone is a synthetic drug which is not an opiate.Methadone & LAAMAlso known as Dolophine is synthetic opioid that has similar activity to Morphine.
The key properties are effective analgesic activity, pressing withdrawal symptoms in physically dependent individuals and its extended duration of action. LAAM is similar to methadone but has a longer duration of action. It has been approved for the clinical management of opioid dependence in heroin addicts.HeroinAlso known as diacetylmorphine, or diamorphine, is produced from morphine by a slight modification of chemical structure.
(include chem. Formula for the reaction) is a structural variant of morphine. Heroin is three times more potent than morphine because it is much more fat-soluble due to its modified chemical structure. When injected it produces an intense rush due to its high lipid solubility which leads to faster penetration of the blood-brain barrier. It is metabolized to monoacetylmorphine and morphine. Morphine is eventually metabolized and excreted. Include chem.
Formula for reactionProduction3- the morphine base must be further boiled, after the addition of acetic anhydride, to form diacetylmorphine. This is then purified with chloroform and water and precipitated out with sodium carbonate. Include chem. Reaction CodeineCodeine occurs naturally in opium. It is almost identical to morphine apart, the molecule of codeine is short of one carbon and two hydrogen atoms. It is nowhere as strong as morphine – only one-tenth as potent.
It is partially demethylated in the body to morphine. Usually taken orally. Used for the management of mild to moderate pain, and is often combined with aspirin in oral tablets. The plasma half-life and duration of action is about 3 to 4 hours.