DOCSLIB.ORG

Anaesthetic Implications of Calcium Channel Blockers

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Anaesthetic Implications of Calcium Channel Blockers 436 Anaesthetic implications of calcium channel Leonard C. Jenkins aA MD CM FRCPC blockers Peter J. Scoates a sc MD FRCPC CONTENTS The object of this review is to emphasize the anaesthetic implications of calcium channel block- Physiology - calcium/calcium channel blockers Uses of calcium channel blockers ers for the practising anaesthetist. These drugs have Traditional played an expanding role in therapeutics since their Angina pectoris introduction and thus anaesthetists can expect to see Arrhythmias increasing numbers of patients presenting for anaes- Hypertension thesia who are being treated with calcium channel Newer and investigational Cardiac blockers. Other reviews have emphasized the basic - Hypertrophic cardiomyopathy pharmacology of calcium channel blockers. 1-7 - Cold cardioplegia - Pulmonary hypertension Physiology - calcium/calcium channel blockers Actions on platelets Calcium plays an important role in many physio- Asthma Obstetrics logical processes, such as blood coagulation, en- - Premature labor zyme systems, muscle contraction, bone metabo- - Pre-eclampsia lism, synaptic transmission, and cell membrane Achalasia and oesophageal spasm excitability. Especially important is the role of Increased intraocular pressure therapy calcium in myocardial contractility and conduction Protective effect on kidney after radiocontrast Cerebral vasospasm as well as in vascular smooth muscle reactivity. 7 Induced hypotensive anaesthesia Thus, it can be anticipated that any drug interfering Drag interactions with calcium channel blockers with the action of calcium could have widespread With anaesthetic agents effects. Inhalation agents In order to understand the importance of calcium - Effect on haemodynamics - Effect on MAC in cellular excitation, it is necessary to review some Neuromuscular blockers membrane physiology. Cell membranes are pri- Effects on epinephrine-induced arrhythmias marily phospholipids arranged in a bilayer. Inter- With other drugs spersed throughout are macromolecular proteins Digoxin and glycoproteins traversing the membrane, form- Beta adrenergic blockers Quinidine ing channels. These channels are relatively specific Theophylline to certain ions. Recently, channels which regulate Dantrolene Pathophysiological alterations (other than cardio- vascular) with anaesthetic implications Decrease in lower oesophageal sphincter tone From the Department of Anaesthesia, Faculty of Effects on intracranial hypertension Medicine, University of British Columbia, Asthma Vancouver General Hospital and Royal Columbian Muscular dystrophy Hospital, Vancouver, British Columbia. Hypoxic pulmonary vasoconstriction Address correspondence to: Dr. Leonard C. Jenkins, Malignant hyperthermia Inhibition of platelet aggregation Department of Anaesthesia, University of Hyperkalemia British Columbia, Room 3200, 910 West 10th Avenue, Summary Vancouver, British Columbia V5Z 4E3. CAN ANAESTH SOC J 1985 / 32:4 / pp436-47 Jenkins and Scoates: CALCIUM CHANNEL BLOCKERS 437 flOW of sodium and calcium have been identified. 7 The sodium channels are also known as fast channels because influx of sodium via these chan- ~L_NO ~ ~ OCH nels is responsible for the rapid (phase 0) upstroke of the action potential seen in the myocardial cell. H)COOC COOCH) OCOCH 1 N The calcium channels are known as slow channels H~C CH I I O /CH 1 CH;.CH~N\ CH ~ because when fast channels are blocked, as with H " i lidocaine, the resulting action potential has a slowly Nifedipine niltiazem rising and falling pattern as seen in the normal SA node or AV node action potential. Calcium fluxes play an important role in altering CH30--~ C--I CH~-- CH,--C;H,--N--CH~ CH,~-- OCH ~ the membrane potential during cellular excitation in CH,O ~--4~ C~-N E~'-- OCH j most myocardial cells. Sodium influx produces the Verapamil phase 0 of the action potential and calcium influx (After I) during phase 1 and 2 of the action potential contributes to the formation of the plateau. 2'~ FIGURE However, in the SA node and AV node of the heart, calcium is the important ion responsible for phase 0 depolarization, not sodium. Under abnormal condi- about contraction. In smooth muscle, calmodulin, tions such as hypoxia and ischaemia, ventricular rather than troponin acts as the receptor protein. cells may also become dependent on calcium for Rapid reduction of calcium ion concentration in the production of phase 0 of the action potential. 2 sarcoplasma must occur for relaxation to take place. The flow of ions through the membrane channels In skeletal muscle the calcium needed for excita- have been shown to be regulated by a number of tion-contraction is stored in the sarcoplasmic reti- gates. This is most clearly demonstrated for the culum and energy dependent processes bring about sodium channels but is felt to be similar for calcium its re-uptake after release. Cardiac muscle contains channels. 4 The external surface of the membrane relatively small amounts of stored calcium and has gates which open and close in response to vascular smooth muscle even less. These latter voltage changes in the membrane (voltage depen- tissues depend to a greater extent on transmembrane dent gates). The intemal surface has gates which influx of calcium for contraction to occur. It appears depend on phosphorylation of ATP to control ion that the calcium entering the cell during the plateau flows (phosphorylation dependent gate). For exam- phase plays an important role in inducing calcium ple, histamine or beta-adrenergic drugs may induce release from the sarcoplasmic reticulum, thus the formation of cyclic AMP thus modifying chan- bringing about contraction. L2,4.7,s nel proteins and altering calcium influx 7 The drugs currently used as specific calcium Calcium also plays a major role in bringing about channel blockers are verapamil, nifedipine and excitation-contraction coupling. In striated and diltiazem. These drugs are but a few of the myriad cardiac muscle, calcium ions in the cell inhibit the drugs that possess calcium blocking activity (Table binding of troponin and tropomyosin and thus bring I). A review of the structure of these drugs shows that they vary greatly. The figure depicts the TABLE 1 Drugsthat interfere with calcium actions structures of verapamil, nifedipine and diltiazem, t Ions: Various di- and trivalent cations This variability implies that there is no one receptor Calcium entry blockers: verapamil, nifedipine, that mediates the effects of the calcium channel diltiazem, lidoflazinetiapamil and others Papavarine blockers. Procaine, procainamide Calcium channel blockers function by altering Phenytoin calcium uptake across the cellular membrane and Diazoxide, nitroprusside, nitroglycerine also by affecting intracellular uptake and release Inhalational anaesthetics: halothane, enflurane mechanism. 2'8 Verapamil, which exists in a D & L and isoflurune isomer form in commercial preparations, acts pri- 438 CANADIAN ANAESTHETISTS' SOCIETY JOURNAL TABLE II Summaryof clinical effects of calcium channel blockers on the cardiovascular system (in viva) Vasodilation Heart rate and A V Cardiac conduction depression systemic coronary Verpamil + + + + + + + + + Nifedipine 0 0 + + + + + + Diltiazem + + + + + + + AV- atrioventrlcular marily at the inner phosphorylation dependent gate making it very useful for terminating supraventricu- of the membrane. It has also been shown that the D lar arrhythmias, whereas nifedipine has no activity isomer of verapamil acts almost exclusively as a fast in this regard. channel blocker and is almost devoid of slow It is interesting that both nifedipine and isoflurane channel inhibition. Diltiazem also has some fast have little (but are not devoid of) influence on channel inhibition. Nifedipine is believed to act contractility and conduction, but markedly reduce primarily at the voltage dependent (outer) gate of systemic vascular resistance. Patients exposed to the calcium channel. 2.3.7 Diltiazem appears to act at both drugs may be expected to exhibit additive the inner phosphorylation dependent gate, like effects, which may be significant, on systemic verapamil.S vascular resistance and blood pressure, but little Most cardiovascular effects of calcium channel disturbance of myocardial contractility or conduc- blockers can be explained on the basis of selective tion. However, verapamil, in a dose which causes inhibition of transmembrane influx of Ca + § Inhibi- the same reduction in arterial pressure as nifedipine, tion of Ca ++ dependent membrane excitation ac- significantly impairs cardiac conduction and con- counts for the depressive effect of calcium channel tractility. 2 Similarly, the blood pressure decrease blockers on sinus automaticity and atrioventricular which accompanies halothane anaesthesia is princi- conductivity. Interference with the excitation-con- pally due to reduced myocardial contractility - and traction coupling process is the reason for their halothane appears to depress conduction more than negative inotropic effect. The effects of calcium isoflurane. 2 Thus, a patient exposed to verapamil channel blockers on the vascular smooth muscle and halothane may be expected to exhibit additive may result from either inhibition of excitation effects on contractitlity and AV nodal conduction. contraction coupling or from suppression of Ca ++ dependent smooth muscle spike activity. Uses of calcium channel blockers Table II is a summary of the clinical effects of calcium channel blockers on the cardiovascular Traditional system. Verapamil and nifedipine
Load more

Recommended publications
  • Once-Daily Skeletal Muscle Relaxant in SA
    NEWS Once-daily skeletal muscle relaxant in SA Myprocam (cyclobenzaprine with spine-related disorders and other 8. What are the classes of muscle a protective coating, and a polymer extended release [ER] sports injuries are excellent candidates relaxants? membrane that controls the rate of hydrochloride) is the most widely for Myprocam. Skeletal muscle relaxants (SMRs) are drug release. prescribed skeletal muscle a group of structurally unrelated drugs, The formulation of the drug relaxant in the US, is now available 4. What are the common as shown in Figure 1. These are divided ensures early systemic exposure in SA. Myprocam’s safety and efficacy indications for which Myprocam into two categories: to cyclobenzaprine, with a plasma has been shown in more than 20 clinical is used, and what are the common • Antispasticity agents: Used to concentration at four hours that trials. It was recently launched by causes of these ailments? treat muscle spasticity caused by is similar to that observed with Adcock Ingram nationally, making SA Low back pain, neck pain, sports traumatic neurologic injury, multiple cyclobenzaprine IR. the second country (only to the US) to injuries, muscle sprains and strains. sclerosis, and other conditions. However, in contrast to the bring the product to market. Common causes of these conditions • Antispasmodic agents: Used fluctuating peaks and troughs in Myprocam, indicated for the relief of include sports injuries, car accidents, to treat muscular pain or spasm plasma cyclobenzaprine concentration muscle spasm associated with acute work-related injuries, and everyday associated with acute, nonspecific after administration of the IR and painful musculoskeletal conditions, activities, which account for acute musculoskeletal conditions.
    [Show full text]
  • Neurontin (Gabapentin)
    Texas Prior Authorization Program Clinical Criteria Drug/Drug Class Gabapentin Clinical Criteria Information Included in this Document Neurontin (gabapentin) • Drugs requiring prior authorization: the list of drugs requiring prior authorization for this clinical criteria • Prior authorization criteria logic: a description of how the prior authorization request will be evaluated against the clinical criteria rules • Logic diagram: a visual depiction of the clinical criteria logic • Supporting tables: a collection of information associated with the steps within the criteria (diagnosis codes, procedure codes, and therapy codes); provided when applicable • References: clinical publications and sources relevant to this clinical criteria Note: Click the hyperlink to navigate directly to that section. Gralise (gabapentin Extended Release) • Drugs requiring prior authorization: the list of drugs requiring prior authorization for this clinical criteria • Prior authorization criteria logic: a description of how the prior authorization request will be evaluated against the clinical criteria rules • Logic diagram: a visual depiction of the clinical criteria logic • Supporting tables: a collection of information associated with the steps within the criteria (diagnosis codes, procedure codes, and therapy codes); provided when applicable • References: clinical publications and sources relevant to this clinical criteria Note: Click the hyperlink to navigate directly to that section. March 29, 2019 Copyright © 2019 Health Information Designs, LLC 1 Horizant
    [Show full text]
  • Pharmacokinetic Interactions of Drugs with St John's Wort
    http://www.paper.edu.cn Pharmacokinetic interactions of Journal of Psychopharmacology 18(2) (2004) 262–276 © 2004 British Association drugs with St John’s wort for Psychopharmacology ISSN 0269-8811 SAGE Publications Ltd, London, Thousand Oaks, CA and New Delhi 10.1177/0269881104042632 Shufeng Zhou Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore. Eli Chan Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore. Shen-Quan Pan Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore. Min Huang Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510089, PR China. Edmund Jon Deoon Lee Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore. Abstract There is a worldwide increasing use of herbs which are often cancer patients receiving irinotecan treatment. St John’s wort did not administered in combination with therapeutic drugs, raising the alter the pharmacokinetics of tolbutamide, but increased the incidence potential for herb–drug interactions. St John’s wort (Hypericum of hypoglycaemia. Several cases have been reported that St John’s wort perforatum) is one of the most commonly used herbal antidepressants. A decreased cyclosporine blood concentration leading to organ rejection. literature search was performed using Medline (via Pubmed), Biological St John’s wort caused breakthrough bleeding and unplanned pregnancies Abstracts, Cochrane Library, AMED, PsycINFO and Embase (all from their when used concomitantly with oral contraceptives. It also caused inception to September 2003) to identify known drug interaction with serotonin syndrome when coadministered with selective serotonin- St John’s wort. The available data indicate that St John’s wort is a reuptake inhibitors (e.g.
    [Show full text]
  • CYP3A4 Mediated Pharmacokinetics Drug Interaction Potential of Maha
    www.nature.com/scientificreports OPEN CYP3A4 mediated pharmacokinetics drug interaction potential of Maha‑Yogaraj Gugglu and E, Z guggulsterone Sarvesh Sabarathinam1, Satish Kumar Rajappan Chandra2 & Vijayakumar Thangavel Mahalingam1* Maha yogaraja guggulu (MYG) is a classical herbomineral polyherbal formulation being widely used since centuries. The aim of this study was to investigate the efect of MYG formulation and its major constituents E & Z guggulsterone on CYP3A4 mediated metabolism. In vitro inhibition of MYG and Guggulsterone isomers on CYP3A4 was evaluated by high throughput fuorometric assay. Eighteen Adult male Sprague–Dawley rats (200 ± 25 g body weight) were randomly divided into three groups. Group A, Group B and Group C were treated with placebo, MYG and Standard E & Z guggulsterone for 14 days respectively by oral route. On 15th day, midazolam (5 mg/kg) was administered orally to all rats in each group. Blood samples (0.3 mL) were collected from the retro orbital vein at 0.25, 0.5, 0.75, 1, 2, 4, 6, 12 and 24 h of each rat were collected. The fndings from the in vitro & in vivo study proposed that the MYG tablets and its guggulsterone isomers have drug interaction potential when consumed along with conventional drugs which are CYP3A4 substrates. In vivo pharmacokinetic drug interaction study of midazolam pointed out that the MYG tablets and guggulsterone isomers showed an inhibitory activity towards CYP3A4 which may have leads to clinically signifcant interactions. Te use of alternative medicine such as herbal medicines, phytonutrients, ayurvedic products and nutraceuticals used widely by the majority of the patients for their primary healthcare needs.
    [Show full text]
  • Topical Therapy As a Treatmentfor Brachioradial
    Journal of Case Reports: Open Access Case report Open Access Topical Therapy as a Treatmentfor Brachioradial Pruritis: a Case Report Brianna De Souza M.D, Amy McMichael M.D* Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina *Corresponding author: Amy McMichael, MD Department of Dermatology, Wake Forest Baptist Medical Center,1 Medical Center Blvd, Winston-Salem, NC 27157, Phone: 336-716-7882, Email: [email protected] Received Date: April 12, 2019 Accepted Date: May 06, 2019 Published Date: May 08, 2019 Citation: Brianna De Souza (2019) Topical Therapy as a Treatmentfor Brachioradial Pruritis: a Case Report. Case Reports: Open Access 4: 1-5. Abstract Management of brachioradial pruritus (BRP) presents a formidable challenge to dermatologists and neurologists. BRP is a rare, neurocutaneous condition characterized by sharply localized, chronic pain with associated itching, burning, stinging, and or tingling sensation. Effective care of this patient population is confounded by limitations within the litera- ture, comprised of case series and case reports. We present a case of one middle-aged female with a chronic history of BRP recalcitrant to the following oral therapies: pregabalin, gabapentin, mirtazapine, prednisone, and amitriptyline, as well as topical triamcinolone. After being evaluated in the clinic, the patient was started on combination therapy withKetamine 10%, Amitriptyline 5%, and Lidocaine 5% topical cream to which she responded. Keywords: Brachioradial pruritus, Brachioradial, Pruritus, Neurocutaneous ©2019 The Authors. Published by the JScholar under the terms of the Crea- tive Commons Attribution License http://creativecommons.org/licenses/ by/3.0/, which permits unrestricted use, provided the original author and source are credited.
    [Show full text]
  • Effect of Amlodipine and Indomethacin in Electrical and Picrotoxin Induced Convulsions in Mice
    DOI: 10.5958/2319-5886.2014.00402.0 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 3 Coden: IJMRHS Copyright @2014 ISSN: 2319-5886 Received: 9th Apr 2014 Revised: 3rd Jun 2014 Accepted: 14th Jun 2014 Research Article EFFECT OF AMLODIPINE AND INDOMETHACIN IN ELECTRICAL AND PICROTOXIN INDUCED CONVULSIONS IN MICE *Jagathi Devi N1, Prasanna V2 1Assistant Professor, 2Professor and Head, Department of Pharmacology, Osmania Medical College, Hyderabad *Corresponding author email: [email protected] ABSTRACT Background and Objectives: Antiepileptic drugs (AEDs) are the drugs used in the treatment of epilepsy. Many AEDs have been developed, but the ideal AED which can not only prevent but also abolish seizures by correcting the underlying pathophysiology is still not in sight. Calcium channel blockers (CCBs) may form such a group, as the initiation of epileptogenic activity in the neuron is connected with a phenomenon known as “intrinsic burst firing” which is activated by inward calcium current. In this study, Amlodipine, a CCB of the dihydropyridine class was evaluated for its anticonvulsant activity in mice. It was compared with Phenytoin sodium, one of the oldest anti epileptic drugs. Amlodipine was also combined with Indomethacin, a conventional NSAID, to look for any potentiating effect of this prostaglandin-synthesis inhibitor. Materials and Methods: A total of 48 adult Swiss albino mice of either sex weighing 20-30 G were used for this study; 48 were divided into 8 groups, each group containing 6 mice. Group 1-4 MES (50 m Amp for 0.1 secs) induced convulsion method, Group 5-8 evaluated by using the chemo-convulsant, picrotoxin (0.7 mg / kg).
    [Show full text]
  • Grapefruit Juice and Psychotropics: How to Avoid Potential Interactions
    Savvy Psychopharmacology Grapefruit juice and psychotropics: How to avoid potential interactions Danielle L. Bishop, PharmD, BCPP s. H, age 42, was given a diagnosis she reports feeling much better during a fol- of bipolar disorder 10 years ago and low-up call and she makes an appointment Mhas been taking carbamazepine, to have her carbamazepine level rechecked 1,200 mg/d, and olanzapine, 10 mg/d, for the in a week. past 2 years. She has not experienced a mood episode while on this regimen, and her car- Although grapefruit products are high in bamazepine level was 9.2 μg/mL 6 months vitamins and low in calories, they can be Vicki L. Ellingrod, ago. The only adverse effect she experienced associated with potentially serious drug PharmD, FCCP was weight gain of approximately 10 lb. interactions. The interaction between Department Editor Ms. H takes a calcium supplement, but no grapefruit juice and the calcium channel other medications. blocker felodipine was discovered inad- Ms. H reports to her psychiatrist that, for vertently >20 years ago; since that time, the past few days, she has been feeling nau- possible interactions with >85 medica- seated, fatigued, and dizzy, but has contin- tions have been identified.1 Interactions ued taking her medications as prescribed. with grapefruit products are complicated Her carbamazepine level is found to be 13.1 μg/mL. Ms. H states she has not started Practice Points any new medications or supplements; her • In general, an entire grapefruit or 8 oz serum creatinine and liver function test of juice is enough to alter a susceptible results are within normal limits.
    [Show full text]
  • Sharon R. Roseman, MD, FACP Practice Limited to Gastroenterology
    Sharon R. Roseman, MD, FACP Practice Limited to Gastroenterology 701 Broad Street, Suite 411 Sewickley, PA 15143 (412) 749-7160 Fax: (412) 749-7388 http://www.heritagevalley.org/sharonrosemanmd Patient Drug Education for Diltiazem / Nifedipine Ointment Diltiazem/Nifedipine ointment is used to help heal anal fissures. The ointment relaxes the smooth muscle around the anus and promotes blood flow which helps heal the fissure (tear). The ointment reduces anal canal pressure, which diminishes pain and spasm. We use a diluted concentration of Diltiazem/Nifedipine compared to what is typically used for heart patients, and this is why you need to obtain the medication from a pharmacy which will compound your prescription. It is also prescribed to treat anal sphincter spasm, painful hemorrhoids and pelvic floor spasm. The Diltiazem/Nifedipine ointment should be applied 3 times per day, or as directed. A pea-sized drop should be placed on the tip of your finger and then gently placed inside the anus. The finger should be inserted 1/3 – 1/2 its length and may be covered with a plastic glove or finger cot. You may use Vaseline ® to help coat the finger or dilute the ointment. (If you are unable or hesitant to use your finger to administer the ointment TELL U S and we will order you a suppository to use as an “applicator”.) If you are advised to mix the Diltiazem/Nifedipine with steroid ointment, limit the steroids to one to two weeks. The first few applications should be taken lying down, as mild light- headedness or a brief headache may occur.
    [Show full text]
  • Drug Interactions: What You Should Know
    DRUG INTERACTIONS: WHAT YOU SHOULD KNOW Council on Family Health Drug Interactions here are more opportunities today than ever before to learn about your health and to take Tbetter care of yourself. It is also more important than ever to know about the medicines you take. If you take several different medicines, see more than one doctor or have certain health conditions, you and your doctors need to be aware of all the medicines you take to avoid potential problems, such as drug interactions. Drug interactions may make your drug less effec- tive, cause unexpected side effects or increase the action of a particular drug. Some drug interactions can even be harmful to you. Reading the label every time you use a nonprescription or prescription drug and taking the time to learn about drug interactions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug interactions fall into three broad categories: ■ Drug-drug interactions occur when two or more drugs react with each other. This drug- drug interaction may cause you to experience an unexpected side effect. For example, mixing a drug you take to help you sleep (a sedative) and a drug you take for allergies (an antihistamine) can slow your reactions and make driving a car or operating machinery dangerous. ■ Drug-food/beverage interactions result from drugs reacting with foods or beverages. For example, mixing alcohol with some drugs may cause you to feel tired or slow your reactions.
    [Show full text]
  • Case Report Carbamazepine Toxicity Following Oxybutynin And
    Spinal Cord (2005) 43, 252–255 & 2005 International Spinal Cord Society All rights reserved 1362-4393/05 $30.00 www.nature.com/sc Case Report Carbamazepine toxicity following Oxybutynin and Dantrolene administration: a case report T Vander*,1, H Odi1, V Bluvstein1, J Ronen1,2 and A Catz1,2 1Department of Spinal Rehabilitation, Loewenstein Rehabilitation Hospital, Raanana, Israel; 2Tel-Aviv University, Tel-Aviv, Israel Objective: To report a case of Carbamazepine toxicity following the administration of Oxybutynin and Dantrolene. Study design: A case report. Setting: The Spinal Rehabilitation Department, Loewenstein Hospital, Raanana, Israel. Methods: A patient with C6D tetraplegia who sustained intoxication because of drug interaction is presented. She had been treated by Carbamazepine 1000 mg/day for neuropathic pain for 2 years without clinical or laboratory signs of toxicity. After administration of Oxybutynin concomitantly with an increase in the dose of Dantrolene, she presented the clinical symptoms and laboratory finding of Carbamazepine intoxication. Trying to adjust the treatment to the patient’s requirements, Carbamazepine together with Oxybutynin and Dantrolene was readministrated in lower doses. Results: The combination of these drugs, even small doses, caused toxicity. Adding Dantrolene and Oxybutynin elevated the blood level of Carbamazepine, possibly by inhibition of cytochrome P450. Conclusion: A possible pharmacokinetic interaction between Dantrolene and Oxybutynin should be borne in mind when considering Carbamazepine medication for a patient with a spinal cord lesion. Spinal Cord (2005) 43, 252–255. doi:10.1038/sj.sc.3101689; Published online 1 February 2005 Keywords: Carbamazepine; Oxybutynin; Dantrolene; drug interaction; cytochrome P450 Introduction Both Oxybutynin chloride and Dantrolene sodium are be required when patients have concomitant post- widely used in patients with spinal cord lesion (SCL).
    [Show full text]
  • Neurochemical Mechanisms Underlying Alcohol Withdrawal
    Neurochemical Mechanisms Underlying Alcohol Withdrawal John Littleton, MD, Ph.D. More than 50 years ago, C.K. Himmelsbach first suggested that physiological mechanisms responsible for maintaining a stable state of equilibrium (i.e., homeostasis) in the patient’s body and brain are responsible for drug tolerance and the drug withdrawal syndrome. In the latter case, he suggested that the absence of the drug leaves these same homeostatic mechanisms exposed, leading to the withdrawal syndrome. This theory provides the framework for a majority of neurochemical investigations of the adaptations that occur in alcohol dependence and how these adaptations may precipitate withdrawal. This article examines the Himmelsbach theory and its application to alcohol withdrawal; reviews the animal models being used to study withdrawal; and looks at the postulated neuroadaptations in three systems—the gamma-aminobutyric acid (GABA) neurotransmitter system, the glutamate neurotransmitter system, and the calcium channel system that regulates various processes inside neurons. The role of these neuroadaptations in withdrawal and the clinical implications of this research also are considered. KEY WORDS: AOD withdrawal syndrome; neurochemistry; biochemical mechanism; AOD tolerance; brain; homeostasis; biological AOD dependence; biological AOD use; disorder theory; biological adaptation; animal model; GABA receptors; glutamate receptors; calcium channel; proteins; detoxification; brain damage; disease severity; AODD (alcohol and other drug dependence) relapse; literature review uring the past 25 years research- science models used to study with- of the reasons why advances in basic ers have made rapid progress drawal neurochemistry as well as a research have not yet been translated Din understanding the chemi- reluctance on the part of clinicians to into therapeutic gains and suggests cal activities that occur in the nervous consider new treatments.
    [Show full text]
  • Cocaine Intoxication and Hypertension
    THE EMCREG-INTERNATIONAL CONSENSUS PANEL RECOMMENDATIONS Cocaine Intoxication and Hypertension Judd E. Hollander, MD From the Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA. 0196-0644/$-see front matter Copyright © 2008 by the American College of Emergency Physicians. doi:10.1016/j.annemergmed.2007.11.008 [Ann Emerg Med. 2008;51:S18-S20.] with cocaine intoxication is analogous to that of the patient with hypertension: the treatment should be geared toward the Cocaine toxicity has been reported in virtually all organ patient’s presenting complaint. systems. Many of the adverse effects of cocaine are similar to When the medical history is clear and symptoms are mild, adverse events that can result from either acute hypertensive laboratory evaluation is usually unnecessary. In contrast, if the crisis or chronic effects of hypertension. Recognizing when the patient has severe toxicity, evaluation should be geared toward specific disease requires treatment separate from cocaine toxicity the presenting complaint. Laboratory evaluation may include a is paramount to the treatment of patients with cocaine CBC count; determination of electrolyte, glucose, blood urea intoxication. nitrogen, creatine kinase, and creatinine levels; arterial blood The initial physiologic effect of cocaine on the cardiovascular gas analysis; urinalysis; and cardiac marker determinations. system is a transient bradycardia as a result of stimulation of the Increased creatine kinase level occurs with rhabdomyolysis. vagal nuclei. Tachycardia typically ensues, predominantly from Cardiac markers are increased in myocardial infarction. Cardiac increased central sympathetic stimulation. Cocaine has a troponin I is preferred to identify acute myocardial13 infarction. cardiostimulatory effect through sensitization to epinephrine A chest radiograph should be obtained in patients with and norepinephrine.
    [Show full text]