PHENCYCLIDINE Dana Bartlett, RN, BSN, MSN, MA, CSPI Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU and ER experience and over 20 years of as a poison control center information specialist. Dana has published numerous CE and journal articles, written NCLEX material, written textbook chapters, and done editing and reviewing for publishers such as Elsevier, Lippincott, and Thieme. He has written widely on the subject of toxicology and was a contributing editor, toxicology section, for Critical Care Nurse journal. He is currently employed at the Rocky Mountain Poison Control Center. ABSTRACT Phencyclidine (PCP) is a dissociative anesthetic. Animal and human studies showed that PCP was an effective anesthetic and analgesic. There are multiple mechanisms of action of PCP that are responsible for its clinical effects. Phencyclidine mainly works as an NMDA receptor antagonist. Phencyclidine can also inhibit the reuptake of the biogenic amines dopamine, norepinephrine, and serotonin. Phencyclidine causes significant adverse effects, delirium, depersonalization, dysphoria and hallucinations. As a consequence, PCP is no longer used in humans as an anesthetic. Phencyclidine continues to be used as an illicit drug. Although PCP is far less popular now than it was, its use continues. Phencyclidine intoxication can lead to PCP substance use disorder and it can cause serious, long-lasting morbidities. 1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 2.5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content is 2.5 hours. Statement of Learning Need Phencyclidine causes significant adverse effects, and phencyclidine intoxication can lead to PCP substance use disorder and it can cause serious, long-lasting morbidities. Clinicians need to know how to identify PCP substance use disorder, and how to treat PCP intoxication. Course Purpose To inform health clinicians of PCP substance use disorder, and how to treat PCP intoxication. 2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Planning Team Conflict of Interest Disclosures Dana Bartlett, RN, BSN, MSN, MA, CSPI, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – All have no disclosures. Acknowledgement of Commercial Support There is no commercial support for this course. Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. 3 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. Phencyclidine is a/an _____________________ that has hallucinogenic and stimulant properties. a. dissociative anesthetic b. anticonvulsant c. barbitutuate d. opiate 2. Phencyclidine mainly works as an NMDA receptor antagonist, a type of _____________ receptor. a. histamine b. adrenergic c. glutamate d. GABA 3. Phencyclidine is primarily metabolized and excreted by the a. kidneys. b. liver. c. lungs. d. spleen. 4. ____________ is defined as a prolonged period of fixed, rigid posture. a. Myoclonus b. Catalepsy c. Ataxia d. Catatonia 5. Phencyclidine is highly lipophilic, so it a. is primarily excreted by the kidneys. b. requires active transport in order to cross the blood-brain barrier. c. cannot be smoked but must be ingested. d. easily crosses the blood-brain barrier. 4 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Introduction Phencyclidine (PCP) is a dissociative anesthetic that was discovered in the 1920s and first used clinically in the late 1950s. It is marketed by the trade name Sernyl. Animal and human studies showed that PCP was an effective anesthetic and analgesic but it caused significant adverse effects, such as delirium, depersonalization, dysphoria and hallucinations. Because of the adverse effects, the application of PCP as an anesthetic for humans was quickly abandoned. By 1967, its use was officially restricted to animals. The illicit use of PCP, however, followed soon after. Although PCP is far less popular now than previously, the use of the drug continues, and PCP intoxication can lead to substance use disorder and cause serious and long- lasting morbidities. Pharmacological Profile Phencyclidine is a dissociative anesthetic that also has hallucinogenic and stimulant properties. An anesthetic prevents the patient from feeling pain and a dissociative drug produces a state of dissociation; the patient is awake but is not aware of and cannot respond to environmental stimulation. Phencyclidine is no longer used as an anesthetic in humans. It is categorized by the Drug enforcement Agency (DEA) to be a Schedule II drug, and considered dangerous with a high potential for a severe substance use disorder. N-methyl-D-aspartate (NMDA) Receptor Antagonist There are multiple mechanisms of action of PCP that are responsible for its clinical effects.1-3 Phencyclidine mainly works as an NMDA receptor antagonist. An NMDA receptor is a type of glutamate receptor. Glutamate is the primary excitatory neurotransmitter of the central nervous system 5 nursece4less.com nursece4less.com nursece4less.com nursece4less.com (CNS), and activation of the NMDA receptor causes inward movement of calcium and sodium ions and depolarization of the neuron. As an antagonist of an NMDA receptor, PCP would then have an inhibitory effect on the CNS. Paradoxically, PCP can also increase the release of glutamate, which may explain in part the intense excitation seen in PCP intoxication. Biogenic Amine Reuptake Phencyclidine can inhibit the reuptake of the biogenic amines dopamine, norepinephrine, and serotonin. Binding to the Sigma Receptor The sigma receptor is a protein that is found in the membranes of neurons in certain parts of the central nervous system. Its function is not completely understood but ligand binding to the sigma receptor allows for ion movement, e.g., calcium and potassium, across cell membranes. It is thought that binding of PCP to sigma receptors is responsible for some of the behavioral, motor, physical, and psychological effects that are characteristic of PCP intoxication.1 Phencyclidine is usually found in powder form but PCP liquid and tablets are also manufactured. It is most often smoked by mixing the liquid or the powder with marijuana or tobacco but PCP is also ingested, injected, or insufflated (snorted). The drug is highly lipophilic, so it easily crosses the blood-brain barrier. The onset of effects depends on the route of administration (IV and smoking being the fastest), and the duration of intoxication is quite variable, ranging from ~ three hours to several days.1,4 Phencyclidine is primarily metabolized and excreted by the liver but a small amount is excreted by the kidneys, and this latter fact has some implications 6 nursece4less.com nursece4less.com nursece4less.com nursece4less.com for the detection and diagnosis of PCP intoxication. (Note: this topic will be discussed later in the module.) Epidemiology Accurate statistics on PCP use are not available. It is commonly stated that the popularity of PCP has decreased considerably since its peak in the 1970s,1 and a review of the medical database PubMed would seem to confirm this: using the search terms PCP overdose, PCP intoxication, phencyclidine intoxication, and phencyclidine overdose the first reports of PCP overdose were published in 1975 and the last (a review article) in 1990. There are countless numbers of drug overdoses and intoxications that are not written about or reported, and the most current statistics this author located indicate that although PCP has been much less popular as a drug of abuse than cocaine, heroin, prescription opioids, or marijuana, the numbers are not insignificant. A study published in 2013 using information gathered by the Drug Abuse Warning Network (DAWN) noted that the estimated number of PCP-related visits to emergency departments (EDs) from 2005 to 2011 had increased 400%, from 14,825 to 75,538,5 and the National Survey on Drug Use and Health found that 2.4% of Americans 12 years of age or older had used PCP at least once.6 In contrast, the Centers for Disease Control and Prevention (CDC) reported that from July 2016 to September 2017, there were 142, 557 ED visits related to suspected opioid overdose.6 Common names for PCP are angel dust, hog, horse tranquilizer, and elephant. Phencyclidine Intoxication The clinical presentation of PCP intoxication is quite variable. The most pronounced and dramatic signs of PCP intoxication are neurologic: confusion, 7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com delirium, inattention to environmental stimulation, inability to