OPIOIDS NIRALI PATEL (2009) Medical University of Sofia, Faculty of Medicine Department of Pharmacology and Toxicology

OPIOIDS DEFINITION Any natural or synthetic compound that imitates properties of natural narcotics Is an analgesic that works by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. The receptors mediate both the beneficial effects, and the undesirable side effects.

CLASSIFICATION  N atural opiates Alkaloids contained in the resin of the opium poppy (morphine, codeine, thebaine)‏  Semi-synthetic opiates Created from the natural opioids (hydromorphone, hydrocodone, oxycodone,oxymorphone, desomorphine, diacetylmorphine (Heroin)‏  Fully synthetic opioids Created from chemical compounds (fentanyl, pethidine, methadone, tramadol and propoxyphene)‏  Endogenous opioid peptides Produced naturally in the body (endorphins, enkephalins, dynorphins, and endomorphins)‏

PHARMACOKINETICS Distribution - Widely distributed throughout body tissue; concentration in kidney, liver and spleen is higher than that in plasma. Only a small fraction enters brain rather slowly. Morphine crosses placenta. Metabolism - Extensively in the liver. Metabolic- breakdown is the primary method of opioid duration Excretion - Metabolites are excreted by the kidneys. A small fraction is excreted in stool through the biliary tract. Routes of administration - Oral, Transmucosal, I.V (most rapid acting), I.M and S.C

PHARMACODYNAMICS They reduce pain by binding to receptor sites (mainly mu- receptors) in the central and peripheral nervous system. After stimulation of receptors they mimic the effects of naturally occurring opiates that are apart of the body's own pain relief system. Processing of pain information is inhibited by a direct spinal effect at the dorsal horn, which involves presynaptic inhibition of the release of tachykinins like substance P. Emotional response to pain altered by opioid actions on the limbic cortex Act presynaptically to block Ca 2+ uptake and consequently inhibit neurotransmitter release. Opioids have been shown to inhibit the release of many neurotransmitters, including substance P, acetylcholine, norepinephrine, glutamate, and serotonin.

PHARMACOTHERAPUTICS  Opioids are prescribed to relieve severe pain in acute, chronic and terminal illnesses. They are also used to reduce anxiety, control diarrhea and suppress coughing. ADVERSE EFFECTS ACUTE  Miosis, Respiratory Depression, Nausea and vomiting, Sedation, Skeletal muscle hypertonus, Euphoria, Constipation, Vasodilatation, Urinary retention, Bradycardia, Biliary Spasm, Morphine poisoning. CHRONIC  Tolerance, Physical Dependence and Apnea (in newborns)

DRUG INTERACTIONS Drugs that may effect opioid analgesic activity include amitriptyline, diazepam, phenytoin, protease inhibitors and rifampin. Drugs that may be affected by opioid analgesics include carbamazepine, warfarin, beta-adrenergic blockers and calcium channel blockers. Use of opioid agonists with other drugs that decrease respiration, such as alcohol, sedatives, hypnotic and anesthetics, increase the risk of severe respiratory depression. Taking tricyclic antidepressants, phenothiazines, or anticholinergics with opioid agonists may cause sever constipation and urine retention.