Physical dependence usually does not occur to a clinically significant degree until after several weeks of continued narcotic usage. Tolerance in which increasingly large doses are required in order to produce the same degree of analgesia, is initially manifested by a shortened duration of analgesic effect, and subsequently by decreases in the intensity of analgesia. This may be similar to the abstinence syndrome noted in patients who withdraw from heroin. These symptoms may increase in severity and over the next 72 hours may be accompanied by increasing irritability, anxiety, weakness, twitching and spasms of muscles, kicking movements, severe backache, abdominal and leg pains, abdominal and muscle cramps, hot and cold flashes, insomnia, nausea anorexia, vomiting, intestinal spasm, diarrhea, coryza and repetitive sneezing, increase in body temperature, blood pressure, respiratory rate and heart rate. Because of excessive loss of fluids through sweating, or vomiting and diarrhea, there is usually marked weight loss, dehydration, ketosis,and disturbances in acid-base balance.
Cardiovascular collapse can occur.
If abstinence symptoms become severe, the patient may be given methadone. Temporary administration of tranquilizers and sedatives may aid in reducing patient anxiety. Gastrointestinal disturbances or dehydration should be treated accordingly. The concomitant use of other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers and alcohol may produce additive depressant effects. Respiratory depression, hypotension and profound sedation or coma may occur.