CHARACTERISTICS OF FENTANYLS.- The fentanyls are most commonly taken by intravenous administration, but like heroin, they may be smoked or snorted. In fact, some users prefer the intranasal route and there are reports that the drugs are available in two forms-one for shooters and one for snorters. Illicit fentanyls are generally diluted (cut) with very large amounts of lactose or mannitol and occasionally are mixed with cocaine or heroin. Because street samples contain only a small amount of active drug, generally less than 1 percent, they do not usually have a distinctive color, odor, or taste. The color of fentanyl samples may range from pure white (in which case it may be sold as Persian white) to an off-white or light tan (sold as China white, synthetic heroin, or fentanyl), to light or dark brown (sold as Mexican brown). The brown color is thought to come from lactose that has been heated until it becomes slightly caramelized. Similarly, the texture of the samples may range from light and finely powdered to somewhat coarse, cakelike and crumbly, resembling powdered milk. Occasionally, fentanyl samples may have a medicinal or chemical odor, but this is not characteristic. There is nothing about the appearance of fentanyl samples that is unique, and it is impossible to distinguish them from heroin except by chemical analysis.

EFFECTS OF FENTANYLS.- Fentanyls produce all the effects and side effects of the classical narcotic analgesics. They are among the most potent respiratory depressants and analgesics discovered to date and can produce profound pain relief at remarkably low doses. Other effects include euphoria, pinpoint pupils, nausea, and an increase in muscle tone commonly called wooden chest or lead-pipe rigidity. A transient drop in heart rate and blood pressure, effects not usually found with heroin use, are observed in surgical patients receiving fentanyls. Respiratory depression and coma are the most serious adverse effects of the fentanyls. Fentanyl plasma levels above 2 to 3 rig/ml are associated with respiratory depression which may be life-threatening.

Chronic use of fentanyls does not typically produce any damage to organs or tissues. Bacterial and viral infections may develop from the use of infected needles. When used regularly, the fentanyls produce narcoticlike tolerance and physiological dependence. Experienced heroin users report that the effects of fentanyls are similar to, and are an acceptable substitute for, heroin. Fentanyls thus appear to have an abuse liability equivalent to heroin.

Respiratory depression is the most serious toxic effect of the fentanyls. This can be quickly and effectively reversed by naloxone (Narcan). Naloxone is a specific opiate antagonist and is the antidote of choice; however, because the fentanyls are so extraordinarily potent, higher doses than are normally used may be required (for example, milligrams rather than micrograms). Naloxon must be administered quickly, because life-threatening respiratory depression occurs within minutes after administration of the fentanyls. Repeated naloxon administration may be necessary when dealing with a long-acting fentanyl analogue.

DEPRESSANTS

Substances regulated under the FCSA as depressants have a high potential for abuse associated with both physical and psychological dependence.

Taken as prescribed by a physician, depressants may be beneficial for the relief of anxiety, irritability, and tension, and for the symptomatic treatment of insomnia. In excessive amounts, however, they produce a state of intoxication that is remarkably similar to that of alcohol.

As in the case of alcohol, these effects may vary not only from person to person but from time to time in the same individual. Low doses produce mild sedation. Higher doses, insofar as they relieve anxiety or stress, may produce a temporary sense of wellbeing. They may also produce mood depression and apathy. In marked contrast to the effects of narcotics, however, intoxicating doses invariably result in impaired judgment, slurred speech, and loss of motor coordination.

Tolerance to the intoxicating effects develops rapidly, leading to a progressive narrowing of the margin of safety between an intoxicating and lethal dose. The person who is unaware of the dangers of increasing dependence will often increase the daily dose up to 10 to 20 times the recommended therapeutic level. The source of supply maybe no further than the family medicine cabinet. Depressants are frequently obtained by theft, illegal prescription, or purchase on the illicit market.

Members of the drug subculture often resort to the use of depressants as self-medication to soothe jangled nerves brought on by the use of stimulants, to quell the anxiety of "flashbacks" resulting from prior use to hallucinogens, or to ease their withdrawal from heroin. The dangers are compounded when depressants are used in combination with alcohol or other drugs. Chronic intoxication, though it affects every age group, is most common in middle age.

Depressants vary with respect to their potential for overdose. Moderate depressant poisoning closely resembles alcoholic inebriation. The symptoms of severe depressant poisoning are coma, cold clammy skin, a weak and rapid pulse, and slow or rapid, but shallow, respiration. Death will follow if the reduced respiration and low blood pressure are not counteracted by proper medical treatment.

Among the depressants that give rise to the general conditions described are a broad array of barbiturates, glutethimide, meprobamate, and the benzodiazepines. Barbiturates

Among the drugs most frequently prescribed by both physicians and veterinarians to induce sedation and sleep are the barbiturates. About 2,500 derivatives of barbituric acid have been synthesized, but of these only about 15 remain in medical use. Small therapeutic doses tend to calm nervous conditions, and larger doses cause sleep 20 to 60 minutes after oral administration. As in the case of alcohol, some individuals may experience a sense of excitement before sedation takes effect. If dosage is increased, however, the effects of the barbiturates may progress through successive stages of sedation, sleep, and coma to death.

Barbiturates are often referred to as "sleepers" or "downers" because of their depressant and sleepproducing effects on the central nervous system. The effects and symptoms of barbiturate use resemble intoxication associated with alcohol except that there is no odor on the breath.

Barbiturates are classified as ultrashort, short, intermediate, and long-acting. The ultrashort-acting barbiturates produce anesthesia within 1 minute after intravenous administration. The rapid onset and brief duration of action make them undesirable for purposes of abuse.

Among the short-acting and intermediate-acting barbiturates are pentobarbital (Nembutal), secobarbital (Seconal), and amobarbital (Amytal)-three of the drugs in the depressant category most sought after by abusers. The group also includes butabarbital (Butisol), butalbital (Lotusate), allobarbital (Dial), aprobarbital (Alurate), and vinbarbital (Delvinal). After oral administration, the onset time of action is from 15 to 40 minutes and duration of action is up to 6 hours.

Long-acting barbiturates, which include barbital (Veronal), phenobarbital (Luminal), mephobarbital or methylphenobarbital (Mebaral), and metharbital (Gemonil), have onset times of up to 1 hour and durations of action up to 16 hours. Their slow onset of action discourages their use for episodic intoxication, and they are not ordinarily distributed on the illicit market except when sold as something else.

Barbiturates are capable of depressing or inhibiting the normal activity of nerves and muscles. Under medical supervision, barbiturates are safe and effective, but when they are abused in large amounts, they can be very dangerous because tolerance and physical and mental dependence develop.

Barbiturates appear as tablets, powders, capsules, and in injection and liquid form; but are most often taken orally in tablets or capsules. Barbiturates appear in a variety of colors due to the manner in which they are packaged and marketed. The more popular tablets and capsules are usually called by their slang names referring to their color; for example:

Pentobarbital and Nembutal are called "yellow jackets."

Seconal and secobarbital are referred to as "reds," "red devils," "red birds," or "pinks."

Amobarbital tablets and capsules are called "blue birds," "blue devils," or "blue heavens."

Tuinal, a mixture of amobarbital and secobarbital, is called "rainbows," "double trouble," or "red and blues."

Most barbiturates are manufactured legitimately in massive quantities by pharmaceutical firms. They reach the illicit market by diversion and theft, by bogus prescriptions, or by poor control by the manufacturer. Some barbiturates are manufactured by clandestine laboratories for distribution on the illicit market.

Glutethimide

When glutethimide (Doriden) was introduced in 1954, it was said to be a safe barbiturate substitute without an addiction potential. But experience has shown that glutethimide has no particular advantage over the barbiturates and has several important disadvantages. Because the effects of this drug are of long duration, it is exceptionally difficult to reverse overdoses that often result in death.