The term narcotic is derived from the Greek narke, 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. However, the term is not used in pharmacological context.
Drug potency is a quantitative measure of the binding of a drug to its receptor, and therefore of its pharmacological effect.3
Opioids are substances that act on opioid receptors to produce morphine-like effects. These include legal drugs like morphine, codeine, methadone, endorphin and fentanyl, and the illegal drug heroin.
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.1
Endorphins are opioids that occur naturally in the 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.
Opioids attach to receptors in the brain. Normally these opioids are the endogenous variety created naturally in the body. Once attached, they send signals to the brain of the “opioid effect” which blocks pain, slows breathing, and has a general calming and anti-depressing effect. The body cannot produce enough natural opioids to stop severe or chronic pain nor can it produce enough to cause an overdose.
An opioid is any agent that binds to opioid receptors (protein molecules located on the membranes of some nerve cells) found principally in the central nervous system and gastrointestinal tract and elicits a response. There are four broad classes of opioids:
· Endogenous opioid, naturally produced in the body, endorphins
· Opium alkaloids, such as morphine and codeine
· Semi-synthetic opioids such as heroin, oxycodone, and Buprenorphine
· Fully synthetic opioids, such as methadone, that have structures unrelated to the opium alkaloids
Classification of Opioid Analgesics
To do that we need to analyse the activity of each drug at each type of receptor and indicate whether it activates or inhibits the function of any of the three opioid receptors.
An agonist is a drug that has an affinity for cell receptors to induce changes in the cell characteristic of the natural ligand e.g. endorphin for that receptor.
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.
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.
Is 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 antagonists
Production3 – 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 & LAAM
Also 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.
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.
Production3- 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.
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.