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The secrets of synthetic drugs

A guide for nursing care

Smeltzer, Michelle D. MSN, RN

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doi: 10.1097/01.CCN.0000511825.04099.b5
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The ability of a nurse to assess and anticipate patient needs has always been crucial to effective plans of care and to meet the specialized needs of each patient and family. However, the rapid development of synthetic drugs (also known as designer drugs) and the ever-changing list of ingredients have added an additional layer of difficulty to assessing patients who may have taken them.

The use and abuse of these synthetic substances have dramatically increased over the last decade partly due to the misguided conception that they are a legal alternative to marijuana and amphetamines.1 Many synthetic drugs are mixed with other drugs, such as marijuana or synthetic marijuana, or contain fillers, which are usually toxic substances.2

The wide variance of dosages and the uncertainty of exactly what substances are in a given synthetic drug make rapid identification and treatment difficult. The majority of synthetic drugs are not detected on routine urine toxicology screens, resulting in the need for nurses to have strong assessment skills when caring for patients under the influence of these drugs. It has been suggested that the inability of a routine drug screen to identify synthetic drugs has contributed to an increase in use.3

Management of patients under the influence of synthetic drugs usually focuses on the physiologic and psychologic conditions the patient is experiencing. There are no specific antidotes for synthetic drugs; therefore, continuous monitoring of changes in patient status is critical to medical management.3

This article provides an overview of different synthetic drugs and related trends, as well as common adverse reactions, in order to help the critical care nurse more effectively care for patients who may have used them.

Scope of the problem

The Substance Abuse and Mental Health Services Administration states that bath salts accounted for over 22,904 ED visits in the United States in 2011.4 Approximately 33% of these patients were solely under the influence of bath salts, and over 15% used them in conjunction with other illegal substances.

These statistics, coupled with the inability to gather reliable prevalence data, help illuminate the challenge in providing care for these patients. The incidence and prevalence of synthetic drug use and abuse are unclear, because related overdoses can be difficult to diagnose; not all users require medical intervention; and most patients are not forthcoming about their use.2 Read on for a description of synthetic drugs that nurses are most likely to encounter.

Cathinones (bath salts)

Bath salts are a synthetic cathinone derived from naturally occurring plants in the East African and Arabian Peninsulas. The Catha edulis, or Khat plant, has leaves that contain a natural stimulant that results in hyperactivity and an increased sense of alertness when the leaves are chewed or ingested.2 Some of the main ingredients in synthetic cathinones are 4-methylmethcathinone; 3,4-methylenedioxypyrovalerone; 4-fluoromethcathinone; 3-fluoromethcathinone; and 4-methoxymethcathinone, which inhibit the reuptake of norepinephrine-dopamine and provide central nervous system stimulation.5

Originally, synthetic cathinone was developed for medicinal purposes. In the 1930s, methcathinone was used as an antidepressant. Then, in the 1950s, it was used as an appetite suppressant and later as a treatment for fatigue and weight loss in the 1960s. Once it became clear the drug caused physical dependence and resulted in abuse by patients, the medications were pulled from the market.6

Bath salts are increasingly popular as a cheap substitute for methamphetamine and cocaine.7 Bath salts were originally designed to evade existing laws in drug abuse; however, cathinone was added to the Schedule I controlled substance list in July 2011.2 Bath salts can be purchased at truck stops and other convenience stores, and may be called plant food, jewelry cleaner, phone screen cleaner, flakka, cloud 9, white lightning, or vanilla sky.7

Bath salts are easily altered by amateur drug makers and are available in a fine white or brown powder, which allows them to be easily taken by oral, rectal, or I.V. routes, or through smoking and insufflating.8

Adverse reactions. Tolerance to bath salts and related substances occurs relatively quickly, which results in patients requiring higher doses or the addition of another substance to feel the effects of the drug. The route of ingestion also affects the onset of effects.9

The hallmark signs of bath salts intoxication are extreme agitation and life-threatening psychosis.3 Other symptoms include hyperthermia, hyponatremia, profound sweating, extreme hypertension, increased myocardial oxygen consumption, and pulmonary and cerebral edema.3

Treatment. There is currently no antidote for bath salts and treatment is supportive care directed at managing the signs and symptoms. Mild-to-moderate management begins with a dimly lit room to decrease stimulation, calm reassurance, and patients are often prescribed a benzodiazepine to decrease anxiety.10 Benzodiazepines can help combat agitation, which contributes to tachycardia and hypertension.10 Patients exhibiting extreme paranoia and/or violent, aggressive, or self-destructive behavior may need repeated doses of sedatives or antipsychotic medication and one-on-one observation.5

MDMA

MDMA is the pure form of 3,4-methylenedioxymethamphetamine, sold in pill or capsule form. It is a semisynthetic hallucinogenic amphetamine that is similar to endogenous catecholamines.11,12 MDMA is a “club drug,” an umbrella term that includes drugs that are popular with teens and young adults and frequently found at music concerts and dance clubs. These drugs may be in liquid form that can be placed (sometimes unknowingly) in a drink or on a piece of paper that can be licked.11,13

MDMA first appeared around 1914 as an appetite suppressant and regained popularity in the 1970s as an adjunct to psychotherapy. MDMA is a Schedule I controlled substance.12 Formulations can be found under a variety of names such as ecstasy, XTC, E, X, Adam, and clarity. MDMA and ecstasy are frequently found at concerts and music festivals.1

“Molly,” which is slang for molecular, is another common name for MDMA. Many users believe that molly does not contain additives such as caffeine that are found in other MDMA formulations, such as ecstasy. Although it may not contain caffeine, it may contain various other synthetic cathinones, such as methylene.7

Adverse reactions. An increase in the inappropriate release of antidiuretic hormone is a potentially fatal adverse reaction of MDMA. The rapid loss of sodium from profuse sweating at dance parties, combined with excessive water intake, can lead to a rapid development of cerebral edema that can also be potentially fatal.1 Other symptoms include hyperthermia, profound euphoria, hypertension, increased heart rate, and increase in sexual arousal.12

Treatment. The management of MDMA overdose is supportive care directed at managing the signs and symptoms much like that of synthetic cathinones. Benzodiazepines, I.V. fluids, and cooling measures may be required. Seizures and agitation may be treated with benzodiazepines.10

Synthetic cannabinoids

Synthetic cannabinoids, known as K2 or Spice, have become increasingly popular as a synthetic form of marijuana. Although its chemical structure is similar to marijuana, it is a misguided conception that it is “legal weed” or a safe alternative to marijuana.1,14 In 2011, Schedule I controlled substance status was given to several synthetic cannabinoids.10

These man-made cannabinoids are sprayed or mixed on dried plant material that can be smoked or made into liquids for inhalation.12,14 There is very little natural material in these substances, and they are primarily made of strong, man-made mind-altering compounds that are chemically similar to tetrahydrocannabinol (THC) but affect brain receptors differently.14 Synthetic cannabinoids contain high THC levels that can range from 40% to 80%, which is much stronger in THC content than high-grade marijuana, which normally has THC levels around 20%.12 Synthetic cannabinoids attach to the same receptor sites as THC; however, they bind more strongly and produce stronger effects.12,14

Adverse reactions. Since the exact chemical composition of synthetic cannabinoids is unknown and can change from source to source, patients may experience different signs and symptoms and varying degrees of intensity.14 Effects may include paranoia, anxiety, panic attacks, violent behavior, and hallucinations.12,14 In addition, the patient may experience an increase in heart rate and BP, vomiting, and suicidal ideation.12,13,15 Overdose may result in myocardial infarction (MI) or acute kidney injury.12

Treatment. There is no known antidote for synthetic cannabinoids. Treatment is symptomatic management to prevent further damage from the array of symptoms. Fluid administration of 0.9% sodium chloride solution can prevent dehydration from vomiting and help prevent the development of rhabdomyolysis and acute kidney injury.15 Withdrawal from synthetic cannabinoids can result in nausea, vomiting, and irritability.3 Withdrawal is not life-threatening and generally does not require pharmacologic management.3

Flunitrazepam

Flunitrazepam is a benzodiazepine that is sold in Europe and Latin America under the trade name Rohypnol.16 It is not sold or manufactured in the United States; however, it does have a strong street presence, and is commonly called Mexican valium, roach 2, rope, or roofies.12,13,16 The effects of flunitrazepam are similar to diazepam, although the effects are 7 to 10 times stronger and the half-life is around 20 hours.16 The onset is extremely rapid (less than 30 minutes) and it is associated with anterograde amnesia, lack of muscle control, and a loss of consciousness.13

Flunitrazepam is referred to as the date-rape drug because a pill can be dissolved into drinks and appear colorless, tasteless, and odorless.12 The manufacturers of brand-name Rohypnol changed the appearance of the pill to an oblong, olive green pill with blue speckles, which forms a blue dye when dissolved in liquid.12 Unfortunately, generic forms of the drug still come in a plain white tablet that can be difficult to detect.12 Flunitrazepam is a Schedule IV controlled substance and possession carries the same penalty as Schedule I controlled substances.12,16

Adverse reactions. Deep sedation, unconsciousness, slowed heart rate, and respiratory depression can occur, especially when flunitrazepam is taken in high doses or combined with alcohol or other drugs.12

Treatment. Flunitrazepam is a benzodiazepine, and chronic use can lead to physical dependence and tolerance.13 Treatment for dependence follows traditional benzodiazepine withdrawal treatment, including inpatient detoxification with 24-hour cardiac and respiratory monitoring, because withdrawal can be life-threatening.13

Gamma-hydroxybutyrate acid (GHB)

GHB is a short-chain fatty acid metabolite that is a central nervous system depressant, known for producing rapid eye movement within 15 minutes of ingestion.16 GHB is a Schedule I controlled substance that can be legally prescribed (as sodium oxybate) to treat narcolepsy.12 GHB increases dopamine, serotonin, and acetylcholine levels in the brain, and binds to the gamma-aminobutyric acid receptor site, resulting in euphoric sensations.16,17

GHB is available as a liquid or white powder, is easily absorbed orally, and quickly breaks down to carbon dioxide and water. This means that no metabolites are readily found on routine blood and urine toxicology screens.16,17 It is colorless and slightly salty in taste.1,12 Street names for GHB include georgia homeboy, grievous bodily harm, and liquid X.12

Adverse reactions. High doses of GHB can result in loss of consciousness, seizures, bradycardia, respiratory depression, hypothermia, and even death.12

Treatment. There is no current antidote for GHB overdose and treatment should focus on symptom management.

Ketamine

Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that has a very complex chemical structure; complete understanding of the mechanism of action is unclear.12 Ketamine is a schedule III controlled substance, FDA-approved rapid-acting anesthetic agent that is used in combination with other agents as a general anesthetic. It is also used for procedural sedation and analgesia. Ketamine is approved for use in humans and animals and is commonly used in veterinary medicine.13

Ketamine (when used illegally) is known as vitamin K or special K to the teenage and young adult population.13 Ketamine comes in a clear liquid or a white powder that can be injected, smoked in marijuana or tobacco, or snorted.12 Popularity of the drug has increased among teens and young adults who attend dance clubs or “rave” parties, where it is sometimes used as a date-rape drug.12

The onset of effects is very quick, occurring within minutes of ingestion, and the duration lasts approximately 30 to 60 minutes.12

Adverse reactions. Ketamine is a dissociative agent that distorts perceptions of sight and sound and makes the patient feel disconnected from his or her body and not in control.12 Ketamine may also cause hallucinations.12 Patients may experience involuntary rapid eye movements, increased salivation, stiffening of muscle, and an immediate increase in heart rate that subsequently decreases 10 to 20 minutes after ingestion.12 Elevation in BP also occurs after ingestion. Although the effects on mood and dissociative behavior are short term, some patients may experience psychotic episodes that can last for weeks to months after use.13

Ketamine may cause nausea and vomiting and can result in loss of consciousness, and overdose may cause severe respiratory depression, which all pose a threat to a patent airway and adequate oxygenation.13

Treatment. There is no specific treatment for ketamine overdose. Because of the dissociative effects of the drug, provide calm reassurance to the patient and maintain a quiet, dimly-lit environment to decrease stimulation. Management of overdose includes supportive care for acute symptoms; nurses should pay special attention to cardiac and respiratory function.13

Methamphetamines

Methamphetamines and other amphetamine stimulants are the second most abused group of substances in the United States, with approximately 1.2 million individuals reporting methamphetamine use in 2012.18,19

Methamphetamine is a Schedule II controlled substance that is used legally to treat disorders such as attention-deficit hyperactivity disorder and morbid obesity through a nonrefillable prescription.18,19 It is found illegally on the street in a crystal form, under names such as crystal, glass, ice, Tina, chalk, or chalk dust.18-20

Burn injuries related to methamphetamine labs have compounded the consequences of methamphetamine abuse.18,20 There are a variety of chemicals that are used to make it, including brake fluid, antifreeze, and paint thinners, to name a few, which can make treatment difficult if the formulation is unidentifiable.19,20

Adverse reactions. Patient assessment may reveal signs and symptoms similar to those of patients experiencing a stimulant overdose. Patients frequently present with chaotic, psychotic symptoms that resemble the symptoms of patients with schizophrenia. Common signs and symptoms include hallucinations and paranoid behavior, severe agitation, involuntary muscle movements, dilated pupils, tachycardia, hypertension, and/or panic attacks.1,19

Treatment. The treatment for methamphetamine intoxication depends on the patient presentation and severity of the symptoms.

Drug screening and diagnostic testing

Once the patient and staff are in a safe environment, testing can begin to identify and treat any physiologic problems. Although some patients may be able to self-report, ascertaining which drug is responsible for individual signs and symptoms can be difficult.2 Sometimes a patient, family member, friend, or first responder will bring the suspected drug of ingestion along with the patient to the facility, which makes diagnosis easier; however, even if it is packaged with an ingredients list, some ingredients may not be listed, and others may not provide exact amounts of individual components because of the ease of substance alteration.2

When there is suspicion of any synthetic drug use, the nurse should anticipate a full lab workup. Testing should include cardiac enzymes, troponin-I, and creatine kinase to rule out MI; electrolytes to identify abnormalities from dehydration and decreased nutrition; and urine function and alcohol level drug screening to identify any coingestants.10

The oral cavity should be thoroughly inspected for burns from inhalation, which could compromise respiratory function.3,17 Inspection of the oral cavity should include the condition of the teeth, especially in patients with suspected methamphetamine use.19 Methamphetamine abuse is strongly associated with severe tooth decay and tooth loss, frequently referred to as “meth mouth.”19

Traditional urine toxicology tests may fail to detect substances such as bath salts and other synthetic drugs in the acute treatment period. However, routine urine drug screens can identify substances such as phencyclidine, cocaine, amphetamines, and alcohol, which are commonly used in conjunction or formulated in combination with synthetic drugs.5

Gas or liquid chromatography is a highly sensitive technique used to physically separate chemical particles from a mass, so they can be detected and identified.10 Chromatography is expensive and if performed, will not provide diagnostic results within a typical critical care treatment time frame.5,10 Because all synthetic drugs have the potential for physiologic complications, routine chemistry and complete blood cell counts will identify anemia, electrolyte imbalances, and kidney and liver dysfunction.5 A finger-stick blood glucose level will quickly rule out hypoglycemia as a cause of psychologic behavior changes.21

Complications

The physiologic and psychologic effects of synthetic drugs manifest differently among patients. Common complications include extreme hypertension and increased oxygen consumption, MI, pulmonary edema, hyperthermia, hyponatremia, life-threatening psychosis, and/or cerebral edema.22

Cardiovascular effects of synthetic drugs can be life-threatening. With the exception of GHB, synthetic drugs increase the cardiac workload. Patients may exhibit an increase in heart rate, systemic vascular resistance, and BP.2,5,16 If untreated, patients can experience MI and heart failure.16 Methamphetamine intoxication can result in a hypertensive crisis or MI.10,18

Neurologic effects can include irritation and agitation, and may be as severe as psychosis and seizures.2,5,16,23 If the patient's nervous system becomes overstimulated, the patient may lose touch with reality and a playful, excitable mood can turn quickly into abusive and self-destructive behavior.5,18-20

Respiratory depression may occur from an overdose of flunitrazepam, GHB, or ketamine.12 Benzodiazepines used to treat agitation and reduce anxiety from synthetic drugs such as cathinones, cannabinoids, or methamphetamine may also cause respiratory depression.5,12 Patients should be continually monitored for the need of rapid sequence intubation to protect their airway.21 Hypoventilation frequently occurs due to a decreased level of consciousness, so frequent monitoring of arterial blood gases, oxygen saturation via pulse oximetry, and end-tidal CO2 levels can ensure adequate continued oxygenation.10

Fluid and electrolyte imbalance. MDMA can cause an inappropriate release of antidiuretic hormone, resulting in the loss of sodium. This loss of sodium from diuresis and profound sweating, combined with large amounts of water intake, can result in cerebral edema and fatal hyponatremia.1 The fluid replacement that is needed for treatment may result in cerebral and/or pulmonary edema; therefore, strict intake and output monitoring is required.2,5,16 Patients that have an altered perception of reality may not be aware of the amount of fluid that they are or are not ingesting, which can also contribute to fluid overload and cerebral edema.2

Temperature changes. Synthetic cannabinoids, cathinones, and methamphetamine are associated with the development of hyperthermia.24 These drugs can effect thermoregulation and the effects are similar to malignant hyperthermia, where temperatures can rise as high as 107.5° F (42° C).2,16 Antipyretics are not effective in the treatment of this kind of hyperthermia because the temperature change is not a result of a change in hypothalamic temperature regulation but possibly hypermetabolism involving the skeletal muscle or induced by serotonin syndrome.5,15 If hyperthermia persists after the administration of sedation, active and/or passive cooling may be required.10

There is a link between hyperthermia and synthetic cathinones that is related to the effect on serotonin release and reuptake.2,5,16 Although bath salts are chemically similar to cocaine, amphetamines, and MDMA, the effects are 10 times more powerful.11 This may be explained by the ability of bath salts to stimulate the release of neurotransmitters.2,5

Kidney injury. Urine output and color needs to be closely monitored to detect acute kidney injury or rhabdomyolysis. Extreme agitation, seizures, and muscle spasms can cause the breakdown of skeletal muscle and result in rhabdomyolysis.2,15,16 If the condition is not identified early and promptly treated, the patient can develop acute kidney injury.

The exact etiology of synthetic drug-related acute kidney injury is unknown; it is potentially linked to hypovolemia and the heavy metals found in various synthetic substances.25 Reported cases of acute kidney injury have shown patients with peak creatinine levels of over 13.0 mg/dL. Creatinine levels should be monitored several weeks after discharge to prevent chronic injury.25

Nursing considerations

Patients under the influence of synthetic drugs usually do not present willingly to the ED and are frequently accompanied by police and EMS personnel. A state of excited delirium sometimes results in violent and self-destructive behavior, which makes safety a priority upon arrival; both safety of the patient and the safety of the staff involved in their care.5,11,18 Verbal de-escalation is often an important step toward an environment conducive for patient evaluation.22

The use of activated charcoal is not recommended because many patients present with nausea and vomiting, and the risk of charcoal aspiration outweighs the benefit of administration.21

Regardless of the substance involved, every patient can present differently and require different amounts of sedation or different levels of monitoring.2 Patient disposition depends on the presenting symptoms. Patients with persistent hyperthermia, vital sign and psychiatric abnormalities, or the need for intubation will require ICU monitoring.10 All patients should be placed on telemetry monitoring and have frequent BP and temperature assessments in order to identify and manage any cardiovascular or respiratory conditions and hyperthermia that may occur.2,5 Pay special attention to patients intoxicated with GHB, as bradycardia is a common adverse event.17

Some patients may need care and assistance to meet basic needs.2,26 Depending on the drug, dosage, and effects, patients may have an altered perception of reality and may not eat, drink, or attend to other personal needs for an extended period of time.2

Nurses should complete a skin assessment on patients with acute intoxication. Needle marks from drug injection may become infected and result in sepsis.3

Many substances, especially methamphetamines, cause patients to feel as if insects are crawling on them, and they may scratch and pick at their skin.3,10,19 This picking results in open wounds and delayed healing time if the patient continues to pick or has poor nutrition.3,10,19

Club drugs can decrease inhibitions and cause impaired memory, and synthetic cathinones and cannabinoids increase sex drive and alter reality. Therefore, nurses should screen patients for sexual assault and sexually transmitted infections before discharge.2,11,16 If there is a suspected sexual assault, perform a forensic evidence exam (a sexual assault evidence collection kit, also known as a rape kit, is used to collect the evidence) according to local law and facility protocols. The exam can be performed by any healthcare provider who is qualified in the collection, documentation, and preservation of sexual assault evidence.27

Prior to discharge, patients should receive a comprehensive psychiatric evaluation and be assigned a social worker to assist with housing, rehabilitation, and other basic needs.5 If there are family members involved, social services should assist with the transition home.18

Prevention and follow-up

Mobile drug labs and the ability of amateur drug makers to create and alter illegal substances make it very difficult to create a specific prevention program. The National Drug Early Warning System (NDEWS), funded by the National Institute on Drug Abuse in 2014, monitors emerging drug trends to allow healthcare professionals and others to respond to new substances and growing trends with preventive efforts. Organizations such as NDEWS scan social medial and other sources for keywords, substances used, and other trends that are associated with illegal drug use.28 These data help identify substances, regions, and populations that may be effected, hopefully allowing for early interventions. Nurses and other healthcare providers need to remain up-to-date on new illegal and synthetic substances that are present in their region and what signs and symptoms they involve, as well as the latest interventions in case of abuse or overdose.5

Conclusion

Clearly, synthetic drugs are a growing problem for healthcare providers. Patients can present with a wide array of symptoms that can be the result of one drug or combined substances. The mechanism of action of many of these substances is not fully understood, and the lack of patient disclosure often makes a definitive treatment plan virtually impossible. The key to treatment is frequent assessment and monitoring until the patient returns to baseline functioning.

Further, when it comes to the long-term effects of synthetic or chemically altered drugs, there is a lot of uncharted territory. Patients may require ongoing medical evaluation and psychologic support to help identify and treat long-term problems. Nurses must continually update their knowledge of synthetic substances in order to solve these complex emergencies and effectively manage patients.

REFERENCES

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21. Arnold TC, Ryan ML. Acute amphetamine and synthetic cathinone (“bath salt”) intoxication. UpToDate. 2014. www.uptodate.com.
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28. University of Maryland National Drug Early Warning System. 2016. http://ndews.umd.edu.
Keywords:

amphetamines; bath salts; cannabinoids; cathinones; designer drugs; ecstasy; MDMA; methamphetamine; synthetic drugs

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