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Narcotic Analgesics Narcotics Analgesic/Opioids Narcotic analgesics are drugs that relieve pain, by binding to opioid receptors, which are present in the central and peripheral nervous system, can cause numbness and induce a state of unconsciousness. Classified into: Natural Compounds: Morphine, Cod...

Narcotic Analgesics Narcotics Analgesic/Opioids Narcotic analgesics are drugs that relieve pain, by binding to opioid receptors, which are present in the central and peripheral nervous system, can cause numbness and induce a state of unconsciousness. Classified into: Natural Compounds: Morphine, Codeine, Papaverine Semi-Synthetic: Diacetylmorphine (Heroin), benzylmorphine and ethylmorphine Synthetic Derivatives: Fentanyl, Pethidine, Methadone, Tramadol and Propoxyphene Loperamide, an opiate that does not enter the brain and therefore lacks analgesic activity. Opioid Receptors They are of 4 types: Ø μ receptor Ø Ø Ø σ receptor δ receptor Κ receptor μ-Receptors are thought to be responsible for most of the analgesic effects of opioids, and for some major unwanted effects. Most of the analgesic opioids are μ-receptor agonists. Ø κ-Receptors contribute to analgesia at the spinal level and may elicit sedation and dysphoria, but produce relatively few unwanted effects and do not contribute to dependence. Ø δ-Receptors are probably more important in the periphery and may also contribute to analgesia. Ø σ-Receptors are not true opioid receptors and it is unclear that what delta actually responsible for but may regulate mu receptor activity. Agonist and Antagonist Opiates vary not only in their receptor specificity but also in their efficacy at the different types of receptor. Thus some agents act as agonists on one type of receptor, and antagonists or partial agonists at another, producing a very complicated pharmacological picture. Pure Agonists This group includes most of the typical morphine-like drugs. They all have high affinity for μ receptors and generally lower affinity for δ and κ sites. Some drugs of this type, notably codeine, methadone are sometimes referred to as weak agonists because their maximal effects, both analgesic and unwanted, are less than those of morphine, and they do not cause dependence. Whether they are truly partial agonists is not established. Pure agonist drugs include Morphine, Heroin, Methadone, Fentanyl, Codeine. Morphine Morphine is the major analgesic drug contained in crude opium and is the prototype strong agonist. Morphine may be given by injection (intravenous or intramuscular) or by mouth, often as slow-release tablets. It is metabolized to morphine-6-glucuronide, which is more potent as an analgesic. Actions of Morphine: Ø Analgesia Ø Euphoria and sedation Ø Respiratory depression and suppression of cough Ø Nausea and vomiting Ø Reduced gastrointestinal motility, causing constipation Ø Histamine release, causing bronchoconstriction. Disadvantage: Ø Drug of addiction due to euphoric effect Ø Over dose causes poisoning i.e. Coma and Respiratory Depression. Ø Cause dryness of mouth, mental clouding, vomiting, headache, fatigue, constipation etc. Methadone Methadone is a synthetic, orally effective opioid that is approximately equal in potency to morphine but induces less euphoria and has somewhat longer duration of action. Methadone is readily absorbed following oral administration. The drug is biotransformed in the liver and is excreted in the urine, mainly as inactive metabolites. Adverse effects: Methadone can produce physical dependence like that of morphine. Fentanyl Fentanyl and sufentanil are highly potent phenylpiperidine derivatives, with actions similar to those of morphine but with a more rapid onset and shorter duration of action, particularly sufentanil. Their main use is in anesthesia, and they may be given intrathecally. They are also used in patient-controlled infusion systems, where a short duration of action is advantageous, and in severe chronic pain, when they are administered via patches applied to the skin. Partial Agonist and Mixed Agonist-Antagonists These drugs, nalorphine and pentazocine, combine a degree of agonist and antagonist activity on different receptors. Nalorphine Nalorphine is closely related in structure to morphine and has a more complicated action. In low doses, it is a competitive antagonist and blocks most actions of morphine in whole animals or isolated tissues. Higher doses, however, are analgesic and mimic the effects of morphine. These effects probably reflect an antagonist action on μ-receptors, coupled with a partial agonist action on δ and κ-receptors, the latter causing dysphoria, which makes it unsuitable for use as an analgesic. Ø Pentazocine is a mixed agonist-antagonist with analgesic properties similar to those of morphine. However, it causes marked dysphoria, with nightmares and hallucinations, rather than euphoria, and is now rarely used. Ø Buprenorphine is a partial agonist on μ receptors. It is less liable to cause dysphoria than pentazocine but more liable to cause respiratory depression. Antagonist The most important examples are: Ø Naloxone Ø Naltrexone Naloxone Naloxone was the first pure opioid antagonist, with affinity for all three opioid receptors. The main clinical uses of naloxone are to treat respiratory depression caused by opiate over dosage. It is usually given intravenously, and its effects are produced immediately. It is rapidly metabolized by the liver, and its effect lasts only 2-4 hours, which is considerably shorter than that of most morphine-like drugs. Therefore it may have to be given repeatedly. Naloxone has no important unwanted effects of its own but precipitates withdrawal symptoms in addicts. It can be used to detect opiate addiction. Naltrexone Naltrexone is very similar to naloxone but with the advantage of a much longer duration of action (half-life about 10 hours). Its use in conditions such as alcoholism and septic shock, is being investigated, although the role of opioid peptides in these conditions is controversial. Specific antagonists at μ, δ and κ-receptors are available for experimental use but not yet for clinical purposes. Drugs Uses Adverse Effects Morphine Widely used for acute and chronic pain Sedation Respiratory depression Tolerance and dependence Euphoria Methadone Chronic pain Maintenance of addicts As morphine but little euphoric effect Accumulation may occur because of long half-life Pethidine Acute pain As morphine, anticholinergic effects Risk of excitement and convulsions Pentazocine Mainly acute pain Irritation at injection site. May precipitate morphine withdrawal syndrome Fentanyl Acute pain Anesthesia As morphine Codeine Mild pain Mainly constipation No dependence liability Dextropropoxyphene Mild pain Respiratory depression May cause convulsions No longer recommended Tramadol Acute (mainly postoperative) and chronic pain Dizziness May cause convulsions