Ketamine: Reinventing Chronic Pain Management | Page...
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Login | Register | Subscription PRACTICE SETTING Ketamine: Reinventing Chronic Pain Management | Page 1 Jeannette Y. Wick, RPh, MBA, FASCP Published Online: Friday, August 8, 2014 For patients who respond poorly or incompletely to opioids, ketamine may be the answer. In the middle of the past century, phencyclidine hydrochloride—called PCP or angel dust on the street—was developed to be a safe, effective anesthetic that did not cause cardiovascular and respiratory depression. However, its propensity to cause convulsions at high doses and long-lasting psychoactive side effects during emergence from anesthesia destroyed its potential. Ketamine—a PCP derivative—was synthesized in 1963 and was tested on 20 prison volunteers in 1965. One-tenth as potent as PCP, ketamine was intended to induce anesthesia like PCP, but with greater specificity and fewer side effects. 1 The FDA approved it in 1970, and its widespread use in the Vietnam conflict theater catapulted its popularity. 2 Today, ketamine is used less and less in the operating suite.3 Although ketamine’s psychomimetic side effects are milder than those of PCP, they can be problematic (Table 1 2-10 ). Recreational abuse has dogged ketamine since its approval. Abusers have injected, inhaled, and smoked ketamine, revealing characteristics of the drug that would otherwise remain unknown. Researchers hypothesize that abusers may develop tolerance because ketamine induces liver enzymes. 11 Abusers rarely experience withdrawal, instead reporting a sensation called the K-hole—a constellation of visual hallucinations, dissociation, and out-of-body, and sometimes, near-death experiences. Heavy, prolonged ketamine use can cause cognitive and psychological impairment. 4,12-15 Up to one-third of chronic ketamine abusers develop dose-dependent urinary tract symptoms within weeks to years: lower urinary tract irritation (vesicopathy), hydroureter, and hemorrhagic or ulcerative cystitis. 13,16,17 The symptom etiology remains unclear, but may be direct toxic damage, immune system activation, or the effect of unknown bacteria. 16,18 Long-term complications include hepatotoxicity (jaundice, itching, or elevated liver enzyme levels, especially in alcoholic patients) and/or cholangiopathy. 19,20 Some long-term abusers develop corneal edema. 21 These complications reverse after cessation of ketamine use. 17,20,21 Clinically, the most common side effects of ketamine are inebriation, mental alteration, headache, hypertension, and altered liver enzymes. 22 Newer, cleaner drugs or biologics are replacing ketamine in the operative suite. Yet ketamine is finding a new place in clinical therapy. Ketamine, an N-methyl-D-aspartate (NMDA)–receptor antagonist, is becoming an option for perioperative pain management among patients with opioid tolerance, acute hyperalgesia, and chronic neuropathic pain. 1 NMDA Receptors NMDA receptors are 1 of 3 glutamategated ion receptors. Gated by a magnesium ion, they normally open only briefly to allow calcium ions and other cations to enter the cell. Calcium activates second- messenger systems, causing neuronal hyperactivity. 1,22-24 NMDA receptors may be involved in neuronal survival and maturation, synaptic plasticity, and memory. Abnormal NMDA function may cause neurologic disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, depression, epilepsy, multiple sclerosis, Parkinson’s disease, and schizophrenia. 25 Unrelenting NMDA receptor excitation allows continuous calcium influx into the cell and creates hyperexcitability. This presents clinically as opioid tolerance, hyperalgesia, and allodynia. 22,26,27 MORE ARTICLES >> Pharmacist Threatened with Explosives During Robbery A Delaware man warned a Walgreens pharmacist that he would blow himself up with explosives if she did not comply with his demands for prescription pills. Graft Device Now Approved for Diabetic Foot Ulcers Patients with certain diabetic foot ulcers now have a new treatment option. Pharmacy Week in Review: January 8, 2016 This weekly video program highlights the latest in pharmacy news, product news, and more. Retail Pharmacist MTM Roles Supported by US House More than 40 members of the US House of Representatives have expressed support for greater pharmacist roles in improvements made to Medicare Part D’s medication therapy management (MTM) program. News Videos Resource Centers Continuing Education Community Publications Latest Articles Ketamine: Reinventing Chronic Pain Management | Page 1 http://www.pharmacytimes.com/publications/issue/2014/august201... 1 of 2 1/10/16, 3:06 PM
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PRACTICE SETTING
Ketamine: Reinventing Chronic Pain Management | Page 1Jeannette Y. Wick, RPh, MBA, FASCPPublished Online: Friday, August 8, 2014
For patients who respond poorly or incompletely to opioids, ketamine may be the answer.
In the middle of the past century, phencyclidine hydrochloride—called PCP or angel dust on the street—wasdeveloped to be a safe, effective anesthetic that did not cause cardiovascular and respiratory depression.However, its propensity to cause convulsions at high doses and long-lasting psychoactive side effectsduring emergence from anesthesia destroyed its potential.
Ketamine—a PCP derivative—was synthesized in 1963 and was tested on 20 prison volunteers in 1965.One-tenth as potent as PCP, ketamine was intended to induce anesthesia like PCP, but with greaterspecificity and fewer side effects.1 The FDA approved it in 1970, and its widespread use in the Vietnamconflict theater catapulted its popularity.2 Today, ketamine is used less and less in the operating suite.3Although ketamine’s psychomimetic side effects are milder than those of PCP, they can be problematic
(Table 12-10).
Recreational abuse has dogged ketamine since its approval.Abusers have injected, inhaled, and smoked ketamine, revealingcharacteristics of the drug that would otherwise remain unknown.Researchers hypothesize that abusers may develop tolerancebecause ketamine induces liver enzymes.11 Abusers rarelyexperience withdrawal, instead reporting a sensation called theK-hole—a constellation of visual hallucinations, dissociation, andout-of-body, and sometimes, near-death experiences. Heavy,prolonged ketamine use can cause cognitive and psychologicalimpairment.4,12-15
Up to one-third of chronic ketamine abusers developdose-dependent urinary tract symptoms within weeks to years:lower urinary tract irritation (vesicopathy), hydroureter, andhemorrhagic or ulcerative cystitis.13,16,17 The symptom etiologyremains unclear, but may be direct toxic damage, immunesystem activation, or the effect of unknown bacteria.16,18
Long-term complications include hepatotoxicity (jaundice, itching,or elevated liver enzyme levels, especially in alcoholic patients) and/or cholangiopathy.19,20 Some long-termabusers develop corneal edema.21 These complications reverse after cessation of ketamine use.17,20,21
Clinically, the most common side effects of ketamine are inebriation, mental alteration, headache,hypertension, and altered liver enzymes.22
Newer, cleaner drugs or biologics are replacing ketamine in the operative suite. Yet ketamine is finding anew place in clinical therapy. Ketamine, an N-methyl-D-aspartate (NMDA)–receptor antagonist, is becomingan option for perioperative pain management among patients with opioid tolerance, acute hyperalgesia, andchronic neuropathic pain.1
NMDA ReceptorsNMDA receptors are 1 of 3 glutamategated ion receptors. Gated by a magnesium ion, they normally openonly briefly to allow calcium ions and other cations to enter the cell. Calcium activates second- messengersystems, causing neuronal hyperactivity.1,22-24 NMDA receptors may be involved in neuronal survival andmaturation, synaptic plasticity, and memory. Abnormal NMDA function may cause neurologic disordersincluding Alzheimer’s disease, amyotrophic lateral sclerosis, depression, epilepsy, multiple sclerosis,Parkinson’s disease, and schizophrenia.25 Unrelenting NMDA receptor excitation allows continuous calciuminflux into the cell and creates hyperexcitability. This presents clinically as opioid tolerance, hyperalgesia,and allodynia.22,26,27
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Latest Articles
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Ketamine is the most potent clinically available, uncompetitive, open-channel NMDA-receptor blocker (itonly works if the receptor is activated and the channel is open). Ketamine depresses the thalamus andlimbic systems, preventing central nervous system centers from receiving or processing sensory input. Thiscreates anesthesia, analgesia, and amnesia, and sometimes unpleasant psychomimetic effects oremergence phenomena.23,28,29
Sympathetic cardiovascular stimulation caused by ketamine is unique among intravenous anesthetics: itinhibits neuronal catecholamine reuptake, thereby increasing heart rate, cardiac output, and systemic andpulmonary blood pressure.30,31 Theoretically, ketamine use should be avoided in patients with prolongedQT syndrome.32 Ketamine inhibits neuronal serotonin reuptake, causing an emesis that is reversed by5-HT–receptor blockers.33,34
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