Substance Abuse: A History of the Opiods

Analgesic Effects: The primary reason for the use of opiods is for pain relief. These agents suppress the perception of pain without completely clouding the consciousness.

Each of the opiods relieves pain in dose-related increments, until they reach a plateau. This plateau is different for each of the opiods. Beyond this plateau, ever-greater doses will only produce greater side effects such as respiratory depression, sedation, seizures, and loss of motor control.

Among the most effective analgesics are parenterally administered heroin, morphine, and hydromorphone (Dilaudid) because of their rapid absorption and high threshold for side effects. Codeine and methadone have good oral absorption, but morphine and meperidine (Demerol) do not.

Antitussive Effects:
Opiods suppress the cough reflex by decreasing the sensitivity of the central respiratory center to rising carbon dioxide levels. Death from respiratory arrest can result.

Respiratory Effects: Respiratory arrest is the major cause of death from acute opiod overdose. The opiate antagonists (e.g. naltrexone) can dramatically reverse respiratory depression.

Gastrointestinal Effects: Nausea and emesis may be the initial reaction due to central stimulation, but as central depression occurs, emesis may not occur even with an emetic agent. Both the longitudinal and circular muscular layers of the intestine contract simultaneously, sharply reducing peristalsis action. This can be a helpful effect in patients with dysentery, minimizing loss of fluid and electrolytes. However, the effect can be unpleasant in people being treated for pain because these same effects on the gastric musculature lead to constipation.

Smooth Muscle Effects: The smooth muscle of the urinary bladder is stimulated by opiods. This can produce a troublesome feeling of constant urgency, however, most opiod abusers come to ignore this due to reduced central perception of this effect. The uterine muscle is mildly affected by opiods so that labor is frequently prolonged.

Peripheral Effects: Opiods induce a release of histamine which results in peripheral blood vessel dilation, and may cause reddened skin and itching. Another mechanism causes reflex vasoconstriction inhibition resulting in orthostatic hypotension.

Endocrine Effects: Opiods act on the pituitary gland to decrease thyroid activity and production of gonadotropins and adrenocorticotropic hormone. This leads to lessened sexual desire in both men and women.

CNS Effects: There are receptor sites in the central nervous system for endogenous, opiod-like substances called enkephalins, dynorphins, and endorphins. These substances, collectively called opiopeptins, attach to their receptor sites and act as neurotransmitters in the regulation of pain and other body functions.Apparently opiod drugs mimic the natural endogenous opiopeptins, attach to their receptor sites, and act in their place to regulate pain and certain other body functions.

Four receptor sites for opiopeptins have been identified. The mu receptors are believed to regulate euphoria, physical dependence, withdrawal, respiratory depression, and supraspinal analgesia. The kappa receptors have prominent actions on diuresis, sedation, sleep, and spinal analgesia. Stimulation of the sigma receptors can produce emotional unease, dysphoria, hallucinations, and vasomotor stimulation. Delta receptors appear to affect cardiovascular function, contribute to analgesia, and cause changes in affective behavior.

When an opiod drug is in the right shape to fit one of these receptors, it can attach and produce a response (agonist), produce a partial response (partial agonist) or prevent any response from occurring (antagonist). For example, mu receptors are usually occupied by the morphine-like opiods (agonists), but can be displaced by drugs such as naloxone (antagonist) so that their effects at the mu receptor cannot be felt.

All the opiods are addictive substances, but some are more rapidly addicting than others and more likely to be abused.

Tolerance: Tolerance results from the chronic use of opiods. This means that over time the user must increase the dose to feel the euphoric effects, and certain other less desired effects such as respiratory depression, nausea, emesis, and impairment of consciousness. Certain other effects such as orthostasis, myosis, constipation, and urinary urgency continue to be felt with no dose increase. Tolerance to most opiods, especially the more potent analgesics, develops rapidly. But, a period of abstinence reverses tolerance and their user can again experience the effects with a smaller dose. The intermittent use of small quantities of opiods does not appear to produce tolerance. It is estimated that about half of recreational opiod users, in certain settings, do not progress to chronic use.

Cross-Tolerance: Cross-tolerance occurs among the opiods, thus an addict, experiencing withdrawal from one of the opiods, can suppress the withdrawal symptoms by substituting another opiod. When the substituted opiod is stopped, he/she will experience the withdrawal syndrome characteristic for that opiod. This procedure may be followed in the detoxification process.

Fetus: Opiods cross the placenta to affect the fetus. Newborns may have symptoms of intoxication or overdose and experience a withdrawal syndrome similar to that in the adult.

Opiods today are severely regulated in the United States. However, street demand continues to support a black market characterized by crime and poverty.

Overall, there are three groups of opiod users in the U.S.:

1. Street Abuser. The average street abuser tends to be a young male, black or Latino with a history of antisocial problems. Typically, he was introduced to heroin by another heroin user and he in turn introduces it to others. Drug abuse usually starts in mid-teens, first with marijuana, then harder drugs, like heroin by age 18. By age 20, the heroin addict is usually arrested for the first time.
2. Medical Abuser. The "medical" abusers of prescription opiods are predominantly middle-class individuals, women, the elderly, health-care professionals, and people with pain syndrome. The histories of these individuals may be more similar to that of alcoholics than to street abusers, although street opiod abusers also tend to rely on legal prescriptions from physicians as they get older.

   In the 1960's and 1970's propoxyphene HCL (Darvon) was the most abused prescribed opiod in the U.S. with 500 deaths reported in 1979. Many propoxyphene HCL dependents abused prescriptions given them by physicians for pain relief, taking the drug indiscriminately. Commonly abused opiods include such drugs as meperidine (Demerol), morphine, and pentazocine HCL (Talwin). Healthcare professionals are especially at risk to abuse opiods because of their accessibility.

3. Methadone Abuser. The methadone abuser, while being administered methadone at a clinic, may supplement his maintenance dose with black market methadone, alcohol, or other drugs. Or he may ask to go on methadone maintenance only because he is temporarily unable to obtain opiods, or because he wants to decrease his tolerance to an amount he can afford.

The cessation of chronic, moderate, or heavy use of an opiod, or a reduction in the amount used, or the administration of an opiod antagonist will produce acute withdrawal symptoms. The severity of the withdrawal symptoms depends up many factors such as the amount used, the length of addiction and how abruptly the drug is withdrawn; among other factors. The following table of withdrawal is a guide to the withdrawal symptoms you might expect.

Table of Opiod Withdrawal Symptoms
(adapted from Frances & Miller)

Stage I--begins within hours of last dose and peaks at 36-72 hours

• craving for the drug
• tearing (lacrimation)
• rhinorrhea (running nose)
• yawning
• diaphoresis (excessive sweating)

Stage II--begins at 12 hours and peaks at 72 hours

• mild to moderate sleep disturbance
• mydriasis (dilated pupils)
• anorexia (loss of appetite)
• piloerection (goose flesh, goose bumps)
• irritability
• tremors

Stage III--begins at 24-36 hours and peaks at 72 hours

• severe insomnia
• violent yawning
• weakness
• nausea, vomiting, diarrhea
• chills, fever
• muscle spasms (may be severe)
• flushing
• spontaneous ejaculation
• abdominal pain

Always remember that persons using opiods for short periods of time and for medical purposes, will probably have few and mild withdrawal symptoms. These may include slight restlessness or temporary insomnia. Those who have been "recreationally" addicted to high doses of opiods for long periods of time, may have severe withdrawal symptoms. These may include fever, chills, severe abdominal pain, seizures, coma, and even death. Deaths are rare today from withdrawal due to modern medical management of withdrawal.

Neonatal withdrawal:

Neonatal acute withdrawal symptoms include high-pitched crying, fever, sleep disturbances, frantic fist sucking, yawning, sneezing, nasal stuffiness, increased respirations, tremors, convulsions, vomiting, diarrhea, and dehydration. These symptoms may not be seen until several days to several weeks after birth, since drugs are retained longer in neonates. A protracted withdrawal of up to eighteen months is characterized by increased susceptibility to colds, flu, ear infections, viruses, and other conditions related to a deficient immune system.