Department of Pharmacology, DSMA. Analgesics. 1. Opioid Analgesics. 2. Nonopioid Analgesics. Department of Pharmacology, DSMA. Opioid Analgesics. " Thou has the keys of Paradise, oh just, subtle and mighty opium" Thomas de Quincy Confessions of an English Opium-Eater.
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"Thou has the keys of Paradise,
oh just, subtle and mighty opium"Thomas de QuincyConfessions of an English Opium-Eater
Nociceptive and antinociceptive systems:
Nociceptive system -
is the system of pain reception and it's psychical appreciation with launching of some defensive conditional and inconditional reflexes.
Antinociceptive system -
is the system of excessive pain receptionsupression. If feeling of pain reaches excessive level, pain from the distress signal turns to source of distress and may cause shock.
μ-(mju)-receptors: analgesia, euphoria, physical dependence, inhibition of breathing, decrease of digestive tract's motility, bradycardia, myosys.
K-(kappa)-receptors: analgesia, sedative effect, disphoria, psychosomymetic effect.
ε-(epsylon)-receptors: are insufficiently discovered.
σ-(sigma)-receptors: are insufficiently discovered.
Opiates are drugs derived from opium and include morphine, codeine, and a wide variety of semisynthetic congeners derived from them and from thebaine, another component of opium. The term opioid is more inclusive, applying to all agonists and antagonists with morphine-like activity as well as to naturally occurring and synthetic opioid peptides. Endorphin is a generic term referring to the three families of endogenous opioid peptides: the enkephalins, the dynorphins, and b- endorphins
Source and Composition of Opium. Because the laboratory synthesis of morphine is difficult, the drug is still obtained from opium or extracted from poppy straw. Opium is obtained from the unripe seed capsules of the poppy plant, Papaver somniferum. The milky juice is dried and powdered to make powdered opium, which contains a number of alkaloids. Only a fewѕmorphine, codeine, and papaverineѕhave clinical usefulness. These alkaloids can be divided into two distinct chemical classes, phenanthrenes and benzylisoquinolines. The principal phenanthrenes are morphine (10% of opium), codeine (0.5%), and thebaine (0.2%). The principal benzylisoquinolines are papaverine (1.0%), which is a smooth muscle relaxant, and noscapine (6.0%).
History. Although the psychological effects of opium may have been known to the ancient Sumerians, the first undisputed reference to poppy juice is found in the writings of Theophrastus in the third century B.C. The word opium itself is derived from the Greek name for juice, the drug being obtained from the juice of the poppy, Papaver somniferum. Arabian physicians were well versed in the uses of opium. Paracelsus (1493-1541) is credited with repopularizing the use of opium in Europe after it had fallen into disfavor because of its toxicity. By the middle of the sixteenth century, many of the uses of opium were appreciated. In 1680, Sydenham wrote, "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium."
Opium contains more than 20 distinct alkaloids. In 1806, Serturner reported the isolation of a pure substance in opium that he named morphine, after Morpheus, the Greek god of dreams. The discovery of other alkaloids in opium quickly followed that of morphine (codeine by Robiquet in 1832, papaverine by Merck in 1848). By the middle of the nineteenth century, the use of pure alkaloids rather than crude opium preparations began to spread throughout the medical world.
- Analgesic - opression of pain of any origin.
- Sedative - decrease of emotional exitability.
- Effects upon hypothalamus:
- Exitation of centre of Nervus oculomotorius - myosis.
- Inhibition of breathing centre.
- Opression of coughing centre.
- Inhibition of vomiting centre (but exitation of chemoceptors of the trigger-zone).
- Exitation of centres of Nervus vagus.
2. Peripheral effects:
- Increase of smooth muscle tonus and sphincters' tonicity of GIT organs -
- Increase of tonicity of bronchial smooth muscles
- Increase of hystamine release.
- Dilation of peripheral veins.
The development of tolerance and physical dependence with repeated use is a characteristic feature of all the opioid drugs. Tolerance and dependence are physiological responses seen in all patients and are not predictors of abuse. For example, cancer pain often requires prolonged treatment with high doses of opioids, leading to tolerance and dependence. Yet, abuse in this setting is very unusual. Neither the presence of tolerance and dependence nor the fear that it may develop should interfere with the appropriate use of opioids. Opioids can be discontinued in dependent patients without subjecting them to withdrawal. Suppression of withdrawal requires only minimal doses. Clinically, the dose can be decreased by 50% every several days and eventally stopped without signs and symptoms of withdrawal. However, decreases in dosage may lead to a reduction in the degree of pain control.
The patient who has taken an overdose of an opioid is usually stuporous or, if a large overdose has been taken, may be in a profound coma. The respiratory rate will be very low (sometimes only 2 to 4 breaths per minute), and cyanosis may be present. As respiratory exchange decreases, blood pressure, at first likely to be near normal, will fall progressively. If adequate oxygenation is restored early, the blood pressure will improve; if hypoxia persists untreated, there may be capillary damage, and measures to combat shock may be required. The pupils will be symmetrical and pinpoint in size; however, if hypoxia is severe, they may be dilated. Urine formation is depressed. Body temperature falls, and the skin becomes cold and clammy. The skeletal muscles are flaccid. Frank convulsions occasionally may be noted in infants and children. When death occurs, it is nearly always due to respiratory failure. Even if respiration is restored, death still may occur as a result of complications that develop during the period of coma, such as pneumonia or shock.
The first step is to establish a patent airway and ventilate the patient. Opioid antagonists can produce dramatic reversal of the severe respiratory depression, and the antagonist naloxone is the treatment of choice. However, care should be taken to avoid precipitating withdrawal in dependent patients, who may be extremely sensitive to antagonists. The safest approach is to dilute the standard naloxone dose (0.4 mg) and slowly administer it intravenously, monitoring arousal and respiratory function.