DOCSLIB.ORG

What Is the Best Sedative Agent for NIV Intolerance?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
What Is the Best Sedative Agent for NIV Intolerance? SECTION REPORT What Is the Best Sedative Agent for NIV CRITICAL CARE MEDICINE Intolerance? Yi Li, MD and Andrew W Phillips, MD MEd FAAEM respiratory distress. His SpO2 was 85% on 6L Ketamine NC so additional airway support was needed Summary: Limited evidence but theoretically a but he was unable to tolerate NRB or BiPAP good choice. Patients should mentally travel to due to agitation. He was given haloperidol their happy places. 5mg IV and lorazepam 2mg IV with minimal Ketamine, a phencyclidine derivative, acts as improvement. During shift change he removed Introduction a dissociative agent primarily by blocking the the mask, desaturated and suffered a hypoxic N-methyl-D-aspartate (NMDA) receptor. It pro- espiratory failure is a common cause of cardiac arrest. emergency department (ED) presenta- vides both analgesic and sedative effects and Rtion in both pediatric and adult patients. What went wrong? can provide amnesia depending on dosing. In Invasive ventilation is associated with multiple First, let us review the current sedative options contrast to opioids, ketamine preserves pharyn- hemodynamic, infectious, and respiratory and their evidence. geal and laryngeal protective reflexes, lowers complications that require sedation and ICU airway resistance, increases lung compliance, Opioids admission. Noninvasive ventilation (NIV) pro- and is less likely to produce respiratory depres- vides respiratory support by applying positive Summary: Opioid infusion seems to work but sion. Hemodynamically, ketamine results in pressure to conscious patients, often avoiding respiratory rate and mental status need to be increased heart rate and blood pressure due to intubation.1 However, one of the risk factors for carefully monitored. Buyer beware. its sympathomimetic effect which may provide NIV failure is intolerance. It was reported that Opioids remain the mainstay of pharmacologic additional advantage in managing respiratory about 5% of patients on NIV experienced intol- management of dyspnea that is refractory to failure patients with hypotension.10 Emergence erance which is associated with higher rate of disease-modifying treatment because of their reaction, however, may trigger anxiety if the pa- intubation and mortality.2 ability to suppress respiratory drive.5 Opioids tient is not mentally prepared when ketamine is are commonly used in mechanically ventilated administered. There are currently two available There are multiple factors that contribute to NIV patients in the ICU and are one of the most case reports discussing ketamine use during intolerance, including the type and severity of commonly used sedative/analgesic drugs NIV - one in asthma exacerbation and another respiratory failure, the underlying disease, inter- during NIV.4 The combined effects of analgesia in acute decompensated heart failure.11,12 face (mask) tolerance, hemodynamic instability, and sedation make it easier for physicians to Currently there are no studies comparing ket- neurological status deterioration, and poor pa- use them if the cause of NIV intolerance is un- amine with other sedatives. tient–ventilator synchrony.3 A prospective, inter- clear. However, respiratory depression and he- national, multicenter study showed that about modynamic effects are less desirable in NIV, a Dexmedetomidine 20% of patients received analgesic or sedative modality that is dependent on respiratory drive. Summary: Theoretically and in-practice a good drugs during NIV.4 Sedation and analgesia can Newer machines have backup ventilation, but choice if the heart rate and blood pressure can mitigate the effects of psychological stress and it is not a consistently reliable feature. Several tolerate it. pain thus potentially improving NIV tolerance. opioids were studied in the past to facilitate NIV But data on sedative or analgesic agent use in Dexmedetomidine acts as an α2 adreno- tolerance, including morphine, fentanyl, remi- NIV remains limited. Agent selection is really at receptor agonist with anxiolytic, sedative, fentanil, and sufentanil.4 Intravenous morphine the physician’s judgement. and some analgesic effects. Like ketamine, infusion was found to be effective in improving dexmedetomidine does not cause respiratory Neurocognitive disorders such as developmen- NIV compliance in acute pulmonary edema depression. The main adverse effects of dex- tal delay and delirium can present additional caused by heart failure.6 Two European studies medetomidine are bradycardia and hypoten- challenges in managing NIV tolerance as well. found that remifentanil improved NIV tolerance sion, so it should be used cautiously in patients In this article, we discuss a hypothetical case of safely in patients with respiratory failure.7,8 One with hemodynamic instability. Multiple studies a patient with concomitant neurodevelopment study showed sufentanil helped induce awake have demonstrated that dexmedetomidine and respiratory distress requiring NIV, empha- sedation without significant adverse effects can be used safely in pediatric respiratory sizing pearls and pitfalls. but did not comment on whether it improved failure patients to facilitate NIV tolerance.13-16 In NIV tolerance.9 There is currently no evidence adults, there are reports of successful use of Case presentation suggesting fentanyl can improve NIV tolerance. dexmedetomidine to improve ventilator-patient A 24-year-old man with a history of autism None of the studies went into detail about ad- and morbid obesity presented to the ED in verse effects. >> COMMON SENSE JULY/AUGUST 2020 17 SECTION REPORT CRITICAL CARE MEDICINE Antipsychotics comorbidities, allergies, and the cause of NIV Summary: Theoretically helpful but no intolerance. The ideal agent should be able to synchronization among patients with acute evidence. improve NIV tolerance without further respira- respiratory failure.17-19 Compared to midazolam, tory deterioration. dexmedetomidine seems to be superior in Antipsychotics are usually dopamine antago- terms of maintaining sedation with fewer dose nists that are commonly used to treat agitation Case conclusion adjustments.20,21 In addition to common medical in the ICU and ED. Despite their potential Is there a better sedation option than the B-52? (and likely frequent off-label use for NIV), etiologies of respiratory failure, dexmedetomi- Probably ketamine or dexmedetomidine, but dine was also found to improve NIV tolerance currently there is no data evaluating whether in blunt chest trauma patients.22 One study failed to show improvement of NIV tolerance with dexmedetomidine, although the sample Sedation and analgesia can mitigate the size was small (n=33) and both arms could effects of psychological stress and pain thus receive midazolam and fentanyl, which prob- potentially improving NIV tolerance. ably negated the effects of dexmedetomidine.23 Overall, it seems that dexmedetomidine is safe and probably effective during NIV. Benzodiazepines Summary: Often used, barely studied. Get the endotracheal tube ready if adding to opioids. Benzodiazepines are anxiolytics that bind to GABA receptors. Despite being the most Several factors need to be considered in selecting the most used sedative/analgesic drugs during NIV (particularly midazolam),4 benzodiazepines appropriate sedative agent, including hemodynamic and do not have an analgesic effect and increase respiratory status, comorbidities, allergies, and the cause of the risk of delirium. There is very limited data NIV intolerance. on benzodiazepine use during NIV to facilitate tolerance. One case report showed suc- no matter which agent, an infusion rather than cessful use of lorazepam in severe asthma antipsychotics can improve NIV tolerance. 24 bolus injection. The combined use of haloperi- exacerbation requiring NIV. It is unclear if the Theoretically they would slow psychomotor ac- dol and lorazepam might be associated with benefit of benzodiazepines outweighs the risks. tivity without reducing respiratory drive. Of note, increased mortality and there are no data sup- Benzodiazepines such as midazolam might be antipsychotics can cause extrapyramidal effects porting antipsychotic use to facilitate NIV. Given a good choice if the cause of NIV intolerance which could potentially worsen NIV tolerance. is clearly identified as anxiety and the patient’s that the patient had been hemodynamically respiratory status can be closely monitored. Combination of sedatives and stable but with severe hypoxemia, efforts could analgesics have been made to achieve adequate sedation Propofol without compromising respiratory status. Summary: Not a good idea. Summary: Milk of amnesia is well known for Current available data suggest that single use hypotension and apnea; it requires very careful References of analgesic or sedative during NIV does not observation. 1. Masip, J., et al., Indications and practical have an apparent effect on outcome. However, approach to noninvasive ventilation in acute Propofol activates central GABA receptors in a study comparing analgesic only, sedative heart failure. European Heart Journal, 2017. and is an intravenous anesthetic that is com- only, and combined use during NIV, the com- 39(1): p. 17-25. monly used for sedation of agitated adult ICU bined had higher mortality.4 2. Liu, J., et al., Noninvasive Ventilation patients. Propofol is well known to cause hypo- Intolerance: Characteristics, Predictors, and tension and apnea. However, there are a few So, what is the best sedative agent? Outcomes. Respir Care, 2016. 61(3): p. 277- studies showing
Load more

Recommended publications
  • 22 Psychiatric Medications for Monitoring in Primary Care
    22 Psychiatric Medications for Monitoring in Primary Care Medication Warnings, Precautions, and Adverse Events Comments Class: SSRI Fluvoxamine Boxed Warnings: Suicidality Used much less than SSRIs in the group of eight Indications: Warnings and Precautions: Similar to other SSRIs medications for prescribing, probably because it has no Adult: OCD Adverse Events: Similar to other SSRIs FDA indication for MDD or any anxiety disorder. Still Child/Adolescent: OCD (10-17 years) somewhat popular as a medication for OCD. Uses: Anxiety, OCD Monitoring: Same as other SSRIs Citalopram Boxed Warning: Suicidality. Escitalopram, one of the SSRIs in the group of Indications: Warnings and Precautions: Similar to other SSRIs medications for prescribing, is an active metabolite of Adult: MDD Adverse Events: Similar to other SSRIs citalopram. Escitalopram reportedly has fewer AEs and Child/Adolescent: None less interaction with hepatic metabolic enzymes than Uses: Anxiety, MDD, OCD citalopram but is otherwise essentially identical. Citalopram offers no advantage other than price, as Monitoring: Same as other SSRIs escitalopram is branded until 2012. Paroxetine Boxed Warnings: Suicidality. Paroxetine used much less than the SSRIs for Indications: Warnings and Precautions: Similar to other SSRIs prescribing, probably because of its nonlinear kinetics. Adult: MDD, OCD, Panic Disorder, Generalized Anxiety Adverse Events: Similar to other SSRIs A study of children and adolescents showed doubling Disorder, Social Anxiety Disorder, Posttraumatic Stress Disorder the dose of paroxetine from 10 mg/day to 20 mg/day Child/Adolescent: None resulted in a 7-fold increase in blood levels (Findling et Uses: Anxiety, MDD, OCD al, 1999). Thus, once metabolic enzymes are saturated, paroxetine levels can increase dramatically with dose Monitoring: Same as other SSRIs increases and decrease dramatically with dose decreases, sometimes leading to adverse events.
    [Show full text]
  • Benzodiazepine Anti-Anxiety Agents: Prevalence and Correlates of Use in a Southern Community
    Benzodiazepine Anti-anxiety Agents: Prevalence and Correlates of Use in a Southern Community rn- rn Marvin Swartz, MD, Richard Landerman, PhD, Linda K George, PhD, Mary Lou Melville, MD, Dan Blazer, MD, PhD, and Karen Smith, PhD Introduction alence and patterns of benzodiazepine antianxiolytic drug use in the Piedmont re- Benzodiazepine anti-anxiety agents gion of North Carolina during 1982-83, uti- are the most widely prescribed psycho- lizing logistic regression analysis, which al- therapeutic drugs in the United States to- lows prediction of benzodiazepine use day.' First introduced in 1960, these drugs while introducing controls for potential rapidly achieved a lead position in the pre- confounding and mediating variables. scription drug market,2 stimulating public and professional debate over appropriate Method psychotropic drug use.3 Recent evidence, however, suggests that the prevalence and The present paper reports results patterns of psychotropic use, especially from Wave 1 of the Piedmont Health Sur- those of benzodiazepine anxiolytics, may vey, one site of the five-site National In- be changing and resulting in decreased stitute of Mental Health Epidemiologic use.4,5 The first detailed population survey Catchment Area program (NIMH- of psychotropic drug use, the National ECA).'1 The sampling frame for the Pied- Household Sample in 1970-71,6-9 found mont Health Survey (PHS) was a five- that 22 percent of American adults had county area in north central North used prescription psychotropic medica- Carolina, consisting of one urban county tion during the year 1969-70, with higher and four contiguous rural counties. The use among women and the elderly.
    [Show full text]
  • (Orion) 5 Mg Tablets Buspirone (Orion) 10 Mg Tablets
    NEW ZEALAND DATA SHEET 1. PRODUCT NAME Buspirone (Orion) 5 mg tablets Buspirone (Orion) 10 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 5 mg buspirone hydrochloride. Each tablet contains 10 mg buspirone hydrochloride. Excipient with known effect: 5 mg tablet: Each tablet contains 59.5 mg lactose (as monohydrate) 10 mg tablet: Each tablet contains 118.9 mg lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet. 5 mg tablet: White or almost white, oval tablets debossed with ‘ORN 30’ on one side and a score on the other side. The tablet can be divided into equal doses. 10 mg tablet: White or almost white, oval tablets debossed with ‘ORN 31’ on one side and a score on the other side. The tablet can be divided into equal doses. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Buspirone hydrochloride is indicated for the management of anxiety with or without accompanying depression in adults. Buspirone hydrochloride is indicated for the management of anxiety disorders or the short- term relief of symptoms of anxiety with or without accompanying depression. 4.2 Posology and method of administration The usual starting dose is 5 mg given three times daily. This may be titrated according to the needs of the patient and the daily dose increased by 5 mg increments every two or three days depending upon the therapeutic response to a maximum daily dose of 60 mg. After dosage titration the usual daily dose will be 20 to 30 mg per day in divided doses.
    [Show full text]
  • Calcium Channel Blockers in Mental Health and Neuro Sciences
    Article NIMHANS Journal Editorial : Calcium Channel Blockers in Mental Health and Neuro Sciences Volume: 15 Issue: 01 January 1997 Page: 3-5 S M Channabasavanna, - Vice-Chancellor, NIMHANS, (Deemed University), Bangalore Calcium is a familiar ion; first year medical students learn of its physiological importance in a host of situations, such as in nutrition, in enzymatic reactions, in muscle contraction, and in the structure of bone. Calcium has long been known to also play an important role in the physiology of the nervous system, for example, it is well recognised that calcium is a co-factor in several enzymatic processes in the central nervous system (CNS), that release of neurotransmitters from synaptic vesicles is calcium-dependent, that the stability of the neuronal membrane is partly regulated by calcium, that calcium is involved in neurotoxic processes etc. [1]. Several cognitive functions have been associated with calcium mechanisms. For example, the involvement of calcium is learning and memory processes is widely documented [2], [3]; most of the work to-date concerns calcium influx through receptors for excitatory amino acids [4]; compounds that block inonotropic glutamate receptors and inhibit calcium inflow, such as MK 801, are reported to impair memory [5], [6]. Voltage-dependent calcium channels, of which the best characterized are those that contain dihydropyridine binding sites, form a second mechanism controlling calcium inflow into the cells [7]. In recent years, these calcium channels in the neuron have assumed substantial importance; treatments affecting these channels have been shown to affect a number of functions related to the CNS. For example, repeated electroconvulsive shocks upregulate voltage dependent calcium channels, which effect appears to increase sensitivity to pain, enhance responsiveness to dopaminergic agonists etc [8], [9], [10].
    [Show full text]
  • Drugs Used to Treat Joint and Muscle Disease
    PHARMACOLOGY Drugs used to treat joint and Learning objectives muscle disease After reading this article, you should be able to: David G Lambert C list the main joint and muscle diseases and their treatments C describe the treatment options for arthritic disease, myasthenia gravis and muscle spasticity Abstract Joint disease: Arthritis can be simply broken into osteoarthritis and rheumatoid arthritis (RA). Osteoarthritis is treated with symptomatic pain relief and surgery. RA is a chronic autoimmune disease that causes 1. Osteoarthritis: this is the most common joint disease and is inflammation of joints (leading to their destruction), tissues around joints often described as a disease of wear and tear. This disease affects and other organ systems. Treatment (for pain) of RA in the first instance is around 8.5 million people in the UK alone, is more common in with non-steroidal anti-inflammatory drugs, with second-line treatment women and those who are overweight and affects a range of using disease-modifying antirheumatic drugs (DMARDs). DMARDs are a joints (knees, hips, hands and neck). There are important disparate group and include methotrexate, D-penicillamine, sulphasala- anaesthetic consequences relating to a reduced range of move- zine, gold salts, antimalarial drugs and immunosuppressant drugs. The ment when the neck is affected. Typical degenerative changes newer class of ‘biological’ DMARDs includes etanercept (tumour necrosis include a thinning of joint cartilage, growth of osteophytes and factor a (TNF-a) receptoreimmunoglobulin G chimera), infliximab (mono- increased synovial fluid production. Typical presenting symp- clonal anti-TNF-a antibody), anakinra (interleukin 1 receptor antagonist) toms are pain, joint stiffness, swelling and a reduced range of and rituximab (an anti-CD20 antibody that depletes B cells).
    [Show full text]
  • Analysis of the Modern Pharmaceutical Market of Anxiolytic Drugs in Ukraine
    Int. J. Pharm. Sci. Rev. Res., 43(1), March - April 2017; Article No. 32, Pages: 169-172 ISSN 0976 – 044X Research Article Analysis of the Modern Pharmaceutical Market of Anxiolytic Drugs in Ukraine Liana Unhurian1*, Oksana Bielyaieva1, Nataliia Burenkova1, 2 1Department of organization and economics of pharmacy, Faculty of Pharmacy, Odessa National Medical University, Odessa, Ukraine. 2A.V. Bogatsky Physico - Chemical Institute of NAU, Odessa, Ukraine. *Corresponding author’s E-mail: [email protected] Received: 15-01-2017; Revised: 23-02-2017; Accepted: 11-03-2017. ABSTRACT The results of the marketing analysis of domestic selection of anxiolytic drugs registered in Ukraine are presented. There were analyzed the preparations for the following characteristics: the country - manufacturer, the firm - manufacturer, the active substance. It is established that the Ukrainian market is formed mainly by imported products. There were identified subgroups that were promising for further comprehensive market study for the purpose of expediency of local anxiolytic drugs. Keywords: Medicines, anxiolytics, selection, diseases of the nervous system, marketing study. INTRODUCTION of anxiolytic drugs. In this regard topical study of the domestic pharmaceutical market of anxiolytic drugs he tempo of modern life, the rapid development of becomes exceptionally important. The study aimed at information technology in various fields of activity, assessment of this group of drugs is also conditioned by unfavorable social situation have a strong impact on T relatively high volumes of industrial production of this the human nervous system, and his mental health. At pharmacotherapeutic group of drugs in the world, which present, one of the leading medical and social problems is in turn allows us to determine the need to expand the neurotic disorders.
    [Show full text]
  • CENTRAL NERVOUS SYSTEM DEPRESSANTS Opioid Pain Relievers Anxiolytics (Also Belong to Psychiatric Medication Category) • Codeine (In 222® Tablets, Tylenol® No
    CENTRAL NERVOUS SYSTEM DEPRESSANTS Opioid Pain Relievers Anxiolytics (also belong to psychiatric medication category) • codeine (in 222® Tablets, Tylenol® No. 1/2/3/4, Fiorinal® C, Benzodiazepines Codeine Contin, etc.) • heroin • alprazolam (Xanax®) • hydrocodone (Hycodan®, etc.) • chlordiazepoxide (Librium®) • hydromorphone (Dilaudid®) • clonazepam (Rivotril®) • methadone • diazepam (Valium®) • morphine (MS Contin®, M-Eslon®, Kadian®, Statex®, etc.) • flurazepam (Dalmane®) • oxycodone (in Oxycocet®, Percocet®, Percodan®, OxyContin®, etc.) • lorazepam (Ativan®) • pentazocine (Talwin®) • nitrazepam (Mogadon®) • oxazepam ( Serax®) Alcohol • temazepam (Restoril®) Inhalants Barbiturates • gases (e.g. nitrous oxide, “laughing gas”, chloroform, halothane, • butalbital (in Fiorinal®) ether) • secobarbital (Seconal®) • volatile solvents (benzene, toluene, xylene, acetone, naptha and hexane) Buspirone (Buspar®) • nitrites (amyl nitrite, butyl nitrite and cyclohexyl nitrite – also known as “poppers”) Non-Benzodiazepine Hypnotics (also belong to psychiatric medication category) • chloral hydrate • zopiclone (Imovane®) Other • GHB (gamma-hydroxybutyrate) • Rohypnol (flunitrazepam) CENTRAL NERVOUS SYSTEM STIMULANTS Amphetamines Caffeine • dextroamphetamine (Dexadrine®) Methelynedioxyamphetamine (MDA) • methamphetamine (“Crystal meth”) (also has hallucinogenic actions) • methylphenidate (Biphentin®, Concerta®, Ritalin®) • mixed amphetamine salts (Adderall XR®) 3,4-Methelynedioxymethamphetamine (MDMA, Ecstasy) (also has hallucinogenic actions) Cocaine/Crack
    [Show full text]
  • Anxiolytic Activity of an Aqueous Extract of Alchornea Cordifolia (Euphorbiaceae) Leaves
    Vol. 7(16), pp. 816-821, 29 April, 2013 DOI 10.5897/AJPP12.115 African Journal of Pharmacy and ISSN 1996-0816 © 2013 Academic Journals http://www.academicjournals.org/AJPP Pharmacology Full Length Research Paper Anxiolytic activity of an aqueous extract of Alchornea cordifolia (Euphorbiaceae) leaves A. Kamenan1, G. Kouakou-Siransy1*, Irié-Nguessan1, I. Dally2 and J. Kablan Brou1 1Laboratoire de Pharmacologie et de Physiologie, UFR Sciences Pharmaceutiques et Biologiques, Université Félix Houphouët Boigny, Abidjan, Ivory Coast. 2Laboratoire de Galénique, UFR Sciences Pharmaceutiques et Biologiques, Université Félix Houphouët Boigny, Abidjan, Ivory Coast. Accepted 4 April, 2013 Alchornea cordifolia, a half way growing shrub from Africa is very valued by traditional doctors in treating numerous ailments including psychical and nervous troubles. The aim of our study was to investigate the anxiolytic activity of A. cordifolia leaves by estimating the effect of an aqueous extract of this plant upon the spontaneous movements and the exploratory behaviour of laboratory mouse. Study of spontaneous movements (moving, straightening-up, activity duration) was done using an activemeter. To assess the exploratory behaviour, a hole-board test was used. The results showed that all spontaneous movements as rapid moving, rapid straightening-up as well as activity duration of mouse decreased after administration of A. cordifolia in the dose of 2500 mg/kg body weight, p.o. A reduction of exploratory behavior in A. cordifolia 2500 mg/kg body weight p.o-treated mice could also be noticed. Thus, the present findings suggest that A. cordifolia might be a potential candidate for use as an anxiolytic drug in the treatment of neuro-psychical troubles.
    [Show full text]
  • Treatment of Anxiety Prior to a Medical Procedure Using an Atenolol
    essio epr n D an f d Thomas and Dooley, J Depress Anxiety 2018, 7:2 o A l a n n x r DOI: 10.4172/2167-1044.1000303 i e u t y o J Journal of Depression and Anxiety ISSN: 2167-1044 ResearchReview Article Article OpenOpen Access Access Treatment of Anxiety Prior to a Medical Procedure using an Atenolol - Scopolamine Combination Drug Ty Thomas1 and Thomas P Dooley2* 1National Centers for Pain Management and Research, 2868 Acton Road, Vestavia Hills, Alabama, USA 2Trends in Pharma Development LLC, 7100 Cabin Lane, Pinson, Alabama, USA Abstract Objective: Patients often experience anxiety in anticipation of medical procedures. A new class of anti-anxiety medications, PanX®, has been developed as alternatives to benzodiazepines, and is combinations of beta blockers and antimuscarinic motion sickness agents. An atenolol - scopolamine HBr drug combination was tested in an open label physician-sponsored study in patients experiencing anxiety in anticipation of a medical procedure. Methods: Eight patients were assessed in a pain management clinic. They experienced anxiety prior to an electromyography procedure and consented to a physician-sponsored study using a compounded medication of atenolol - scopolamine HBr delivered by the oral mucosal route. A pair of questionnaires assessed their overall level of anxiety and their individual symptoms of anxiety prior to the anxiolytic treatment and then during the procedure that commenced ca. 10 - 20 minutes after drug administration. Results: All eight patients remained clear minded and none reported any side effects. Seven of eight patients perceived a calming effect from the drug treatment. Six of eight patients were responders to the treatment and experienced a reduction in anxiety on a 10-point scale from an average of 6.3 points prior to the procedure to 2.7 points during the procedure.
    [Show full text]
  • Interaction of Calcium Channel Blockers with Non-Neuronal Benzodiazepine Binding Sites* (Nitrendipine/Nifedipine/Ro5-4864) E
    Proc. Nati. Acad. Sci. USA Vol. 81, pp. 1549-1552, March 1984 Medical Sciences Interaction of calcium channel blockers with non-neuronal benzodiazepine binding sites* (nitrendipine/nifedipine/Ro5-4864) E. H. CANTOR, A. KENESSEY, G. SEMENUK, AND S. SPECTOR Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110 Communicated by John J. Burns, November 18, 1983 ABSTRACT The ability of calcium channel blockers to displace the binding of benzodiazepine ligands was investigat- ed in rat heart, kidney, and brain. The dihydropyridine calci- um channel blockers nifedipine and nitrendipine displaced the H3-CH2ZO-C C-O-CH3 binding of the non-neuronal-site ligand [3H]Ro5-4864, but not that of the neuronal-site ligands [3H]flurazepam or [3H]clona- CH3 N CH3 zepam. The inhibition was competitive, with K1 values in the H micromolar range. Other calcium channel blockers-i.e., ver- NITRENDIPINE apamil and diltiazem-were inactive at both sites. Thus, non- neuronal benzodiazepines bind to a class of sites that also binds dihydropyridines. This implies a role for benzodiazepines in 0-CH3 the mediation of calcium-dependent phenomena. 0 s 01 Binding sites for benzodiazepines can be divided into two 101 O-C-CH3 major categories. Those on neuronal membranes are gener- 0 ally influenced by y-aminobutyric acid (1-3), are linked to a I ,CH3 chloride channel (4), and are probably responsible for the CH2-CH2-N,CH anxiolytic and anticonvulsant activities of the benzodiaze- pines (4). Benzodiazepines also bind to membranes from a DI LTIAZEM variety of other tissues including kidney (5, 6), heart (6, 7), lung (5, 6), liver (5, 6), mast cells (6), platelets (8), intestinal smooth muscle (9), several cell lines (10, 11), and central ner- vous system non-neuronal elements (12-15).
    [Show full text]
  • Gamma Hydroxybutyrate (GHB)
    If you have issues viewing or accessing this file, please contact us at NCJRS.gov. PROPERTY OF Executive Office of the President National CriminalJustice Reference Service (NOJRS) ~.~1~<~ ~ )~ Office of National Drug Control Policy Box 6000 \~~/ Rockvilte, MD 20849-6000 L lohn P. Waiters, Director www.whitchousedrugpolicy.gov 1-800-666-333~ Gamma Hydroxybutyrate (GHB) / Backgrou nd liquid packaged in vials or sma.ll bottles. In liquid form, Gamma hydroxybutyrate (GHB) is a powerful, rapidly it is clear, odorless, tasteless, and almost undetectable acting central nervous system depressant. It was first when mixed in a drink. GHB is typically consumed by synthesized in the 1920s and was under development as the capful or teaspoonful at a cost of $5 to $10 per dose. an anesthetic agent in the 1960s. GHB is produced nat- The average dose is I to 5 grams and takes effect in 15 urally by the body in small amounts but its physiologi- to 30 minutes, depending on the dosage and purity of cal function is unclear. the drug. Its effects last from 3 to 6 hours. GHB was sold in health food stores as a performance- Consumption of less than l gram of GHB acts as a enhancing additive in bodybuilding formulas until the relaxant, causing a loss of muscle tone and reduced Food and Drug Administration (FDA) banned it in inhibitions. Consumption of I to 2 grams causes a 1990. It is currently marketed in some European coun- strong feeling of relaxation and slows the heart rate tries as an adjunct to anesthesia. GHB is abused for its and respiration.
    [Show full text]
  • Sedative / Hypnotics
    Sedative / Hypnotics Robert Althoff, MD, PhD www.mghcme.org Disclosures I have the following relevant financial relationship with a commercial interest to disclose: ▪ I receive or have received research support from NIMH, NIDA, and the Klingenstein Third Generation Foundation ▪I have ownership equity in WISER Systems, LLC as a partner. www.mghcme.org www.mghcme.org • Sedative / Hypnotics are a general class of agents • Frequently refer to benzodiazepines (and like compounds) and barbiturates • Many similarities in mechanisms of action, medical indications, behavioral effects, withdrawal considerations, and treatment www.mghcme.org Benzodiazepine Mechanism of Action Benzodiazepines are a class of agents that work on the central nervous system, acting selectively on gamma-aminobutyric acid-A (GABA-A) receptors in the brain. It enhances response to the inhibitory neurotransmitter GABA, by opening GABA-activated chloride channels and allowing chloride ions to enter the neuron, making the neuron negatively charged and resistant to excitation www.mghcme.org • Traditional benzodiazepines – Diazepam (Valium) – Clonazepam (Klonopin) – Others • “Z” Drugs – Zaleplon (trade: Sonata) – Zolpidem (trade: Ambien, Edluar, Intermezzo) – Zopiclone (trade: Zimovane) www.mghcme.org Benzodiazepine: General Info • C IV DEA classification • Although more than 2,000 different benzodiazepines have been produced worldwide, only about 15 are currently FDA-approved in the United States. • Types of benzodiazepines therefore include those the following – Ultra-short acting: midazolam (Versed), triazolam (Halcion) – Short-acting: alprazolam (Xanax), lorazepam (Ativan) – Long-acting: chlordiazepoxide (Librium), diazepam (Valium) • The use of benzodiazepines during pregnancy is a risk factor for cleft lip or palate, lower muscle tone, and withdrawal symptoms in the developing fetus Bachhuber, et al.
    [Show full text]