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The term narcotic is derived from the Greek market, meaning numbness or stupor. Today the term became associated with opioids and is increasingly used today in a legal context to refer to a wide variety of abused substances. Drug potency is a quantitative measure of the binding of a drug to its receptor, and therefore of its pharmacological effect. Opioids are substances that act on opioid receptors to produce morphine-like effects. These include the illegal drug heroin and legal drugs like morphine, codeine and many more. Opioids occur in nature in two places: in the juice of the opium poppy Papaver somniferum and within the human body e.g. the endorphins. The opium contains more than a dozen alkaloids (naturally occurring organic nitrogen-containing bases.)4, of which the most important are codeine and morphine. Endorphin is a generic, all-inclusive term that applies to any “endogenous substance” i.e. one naturally formed in the living organism.These opioids occur naturally in the body and attach to receptors in the brain where they pass signals to the brain of the “opioid effect” – to block the pain, slow breathing or generally calm the body.
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Overall it has an anti-depressing effect on the human body. When humans experience feelings of joy, endogenous opioids are released which cause feelings of happiness and reduce pain. In a healthy human, the amounts of endogenous opioids are regulated so that the person never becomes too euphoric or is in too much pain. When external opioids are introduced, the same feelings are experienced at a greater level than can be experienced naturally. Even though endogenous substances are capable of controlling the body to the greatest extent, they cannot stop the severe or chronic pain.
There are four broad classes of opioids:
To classify opioid analgesics we need to analyze 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 Agonists An agonist is a drug that has an affinity for cell receptors to induce changes in the cell characteristic of the natural ligand. Morphine, the prototype of methadone, is a long-lasting opioid which is used to treat heroin dependency.
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Fentanyl is a short-acting opioid with clinical use in anesthesia and has a very high potential for abuse. The agonist binds using its phenol, aromatic, and amine, functional groups. The aromatic ring is far from the amine group o it overlaps more effectively with the more hydrophobic region, causing the equilibrium to shift to the active site.7 Pure Antagonists Have 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 Use Morphine Morphine is a water-soluble opioid that penetrates the blood-brain barrier more slowly than the more fat-soluble opioids. Only a 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 antagonists.
Morphine is one of the most effective painkillers available in medicine and is currently used as an analgesic which has tranquilizing actions. Morphine in action: The amine nitrogen is protonated and charged – it can form an ionic bond with a negatively charged region of the binding site. The phenol acts as a hydrogen bond donor and forms a hydrogen bond to a hydrogen bond acceptor in the binding site. Its aromatic ring has a defined orientation with respect to the rest of the molecule, allowing van der Waals interactions with a hydrophobic location in the binding site Production – 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.
Morphine is relatively polar. Although both morphine and methadone are classified as opioids, methadone is a synthetic drug which is not an opiate. Methadone & LAAM Also known as Dolophine is a 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.
Heroin Also known as diacetylmorphine, or diamorphine is produced from morphine by a slight modification of chemical structure. 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 reaction Production – 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.
Codeine 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.
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