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Comparative analgetic activity of opioids in equianalgetic doses (in accordance with E. Hurford et al., 2001 with some changes)

Depending on the dose opioids exert analgetic and sedative effect, often — euphoria (particularly, in repeated administration), in high doses — a moderate amnesia and even a loss of consciousness. They decrease MAC of inhalation and noninhalation anesthetics.

Side effects lie in the inhibition of respiratory center, deepness and rate of respiration are diminished, ventilation is decreased hypercapnea develops with the greater inhibition of respiratory center by the type of "carbon dioxide narcosis". A release of histamine under the action of opioids, particularly morphine and meperidine, increases a threat of bronchospasm development in the patients, predisposed to it, but remove a bronchospasm caused by manipulation on the respiratory tracts. Opioids, particularly of fentanyl family, increase the rigidity of respiratory musculature with a threat of hypoventilation.

Meperidine, the structure of which resembles atropine, increases HR, but inhibits myocardial contractility, and other opioids cause, in high doses, a bradycardia because of vagal tonus rise, having no effect on contractility of cardiac muscle. AP decreases as a result of bradycardia, vasodilatation and vagal tonus rise, and under the action of morphine and meperidine — and under the influence of histamine release. A slow administration of preparations, elimination of hypovolemia and antihistaminic agents impede histaminic response. A dose-dependent myosis is noted.

Independent opioid anesthesia is insufficient for an adequate anesthesia that is manifested by AP elevation and requires an additional administration of vasodilating agents and combination of opioids with inhalation anesthetics in the course of operations. A combination with noninhalation anesthetics significantly inhibits myocardial contractility.

Opioids on the background of normoventilation decrease an oxygen demand of the brain, cerebral blood flow and ICP, though not so actively as barbiturates and diazepam. Insignificant deepness of opioid anesthesia may be the reason of the sharp rise of ICP during tracheal intubation. High doses of fentanyl may cause convulsions.

Opioids often cause nausea and vomiting, they do not ensure sufficient amnesia even in high doses. A repeated application of opioids produces addiction and development of narcomania, inhibits a motility of gastrointestinal tract, causes a sphincter Oddi spasm and biliferous tracts up to the development of hepatic colic.

Opioids block up an activation of stress hormones that is, particularly, characteristic of the family of fentanyls.

In the interaction with MAO inhibitors, opioids may cause a respiratory standstill, sharp fluctuations in AP and hypotension.

Noninhalation and inhalation anesthetics intensify the opioids' effect upon CNS, respiration and blood circulation.

Erythromycin slows down alfentanyl biotransformation.

Agonists are used both for premedication and maintenance of anesthesia and for anesthesia in the perioperative period.

Agonists-antagonists are used, mainly, in pain syndromes not associated with operative interventions, as well as for anesthesia in the postoperative period, and only from time to time — in the complex of agents to maintain anesthesia.

Antagonist naloxone is applied to eliminate unexpected, undesirable effects caused by agonists or agonists-antagonists. It is a universal blocker of opioid receptors (i.e. receptors of various types, in particular m-, d- and c-receptors), deprived of properties of their agonist (a small agonistic activity it shows only in high doses). It is metabolized in the liver (95%), the products are excreted by the kidneys. Eliminating an anesthetizing effect of opioid analgetics, it may cause AP increase, pulmonary edema (rarely), delirium, abstinence syndrome in addicts. After a termination of naloxone action, the effect of opioid analgetics may repeat.

Naloxone (narcan) is administered intravenosly as a bolus every 2-3 min up to achieving a desirable effect — for adults by 0.04-0.4 mg (0.57-5.7 mg/kg), for children — 1-10 mg/kg (a total dose for children must not exceed 0.4 mg). The onset of dose action is in 1-2 min., its duration is 20-60 min depending on the dose.

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