Pharmacological Management of Traumatic Brain Injury and Implications for Speech Language Pathology
ABSTRACT
This article provides an overview of the pharmacological management of traumatic brain injury (TBI). A basic introduction to key pharmacokinetic and pharmacodynamic principles is used to guide the reader. The goals of the pharmacological management of TBI are explained starting with mild TBI. The main medications used for each medical condition are described with a primary emphasis of effects that may interfere with the role of speech-language pathology (SLP). Some medications may interfere with cognitive, motor, and neuromuscular functions, and others may cause ototoxicity. A basic overview of the pharmacological management of moderate to severe TBI is included because the SLP practitioner may encounter patients with TBI during the recovery phase. The importance of assessment of swallowing evaluations is discussed because the oral route of administration of medications is preferred once the patient is stable. KEYWORDS: Pharmacology, pharmacokinetics, pharmacodynamics, traumatic brain injury
Learning Outcomes: As a result of this activity, the reader will be able to (1) discuss and contrast the difference between pharmacokinetic and pharmacodynamic effects; (2) select medications that can be used for the treatment of some of the conditions resulting from mild traumatic brain injury (TBI); (3) identify medications that can have an effect in cognition, motor, and neuromuscular functions in the management of mild TBI; (4) identify medications that can cause ototoxicity in the management of TBI.
1
University of Texas at El Paso College of Health Sciences and University of Texas at Austin College of Pharmacy, El Paso, Texas. Address for correspondence: Jose O. Rivera, Pharm.D., University of Texas at El Paso College of Health Sciences and University of Texas at Austin College of Pharmacy, 1101 N. Campbell, Suite 710, El Paso, TX 79902 (e-mail: [email protected]).
196
Concussion 101 for SLPs; Guest Editor, Anthony P. Salvatore, Ph.D., CCC-SLP Semin Speech Lang 2014;35:196–203. Copyright # 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 5844662. DOI: http://dx.doi.org/10.1055/s-0034-1384681. ISSN 0734-0478.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O. Rivera, Pharm.D.1 Jose
T
he pharmacological management of traumatic brain injury (TBI) is driven by the severity of the injury and can be quite complex. A wide range of pharmacological agents may be necessary depending on severity and considering comorbidities and complications. It is necessary to establish a basic understanding of the effects (both desired effects and side effects) of these agents when implementing speech-language interventions. This would include a basic understanding of pharmacokinetic and pharmacodynamic principles that explain drug effects. A brief overview of these concepts is presented here. BASIC PHARMACOKINETIC AND PHARMACODYNAMIC PRINCIPLES Pharmacokinetics is the science that studies the absorption, distribution, metabolism, and elimination of a drug in the body. The absorption phase depends on the route of administration and the formulation of the drug. As a general rule, the intravenous administration is the most rapid and complete method of administration of a drug. Parenteral routes of administration include intravenous (IV), intramuscular (IM), and subcutaneous (SQ). In most critical situations, the IV route will be the preferred method of administration. Once a drug is absorbed into the intravascular compartment, it is then distributed throughout the body. Several drugrelated factors will determine the extent of distribution. Some drugs will be metabolized by the liver to inactive, active, or even toxic metabolites. Other drugs are eliminated by the kidney or through the feces without being metabolized, and finally some drugs are partially metabolized and partially eliminated via the kidneys or feces. Onset of action (how quickly the intended effect is seen), peak (maximum effect), and duration of action (how long the effect lasts) are determined by several drugrelated factors, the route of administration, and the formulation. Frequently, the half-life (time required to eliminate 50% of the drug from the body) will determine the onset, peak, and duration of action of the drug. The longer the half-life, the more time is required for the drug to achieve a concentration at steady state where there is a balance between intake and elimina-
tion. For some drugs, the amount in the body that is effective and the amount in the body that is toxic are not very different. This is called a narrow therapeutic toxic ratio and may require monitoring the serum concentration of the drug (therapeutic drug monitoring). Examples of these types of drugs are phenytoin, gentamicin, and vancomycin. Pharmacodynamics is the science that studies the drug action primarily via a drugreceptor interaction. Usually the concentration of the drug at the receptor site and the affinity of the drug for a particular receptor will produce the therapeutic and adverse effects. Many types of receptor are distributed throughout the body. Pharmacokinetic principles often determine the pharmacodynamic properties of a given agent, although not always. A more extensive review of these concepts is available to the reader.1 SEVERITY OF TBI TBI can be classified as severe, moderate, or mild. Glasgow Coma Scale (GCS) is a common clinical tool that is used to quickly assess the severity of the injury. GCS scores range from 3T to 15, with lower scores indicating more severe injury.2 A score of 3T indicates the most severe head injury, and a 15 indicates normal. The letter T indicates intubation or tracheotomy in patients who require mechanical ventilation support. A score of 13 or higher is indicative of mild TBI, 9 to 12 is moderate, and 8 or less is severe. Other neurologic tests, computer tomography scans, magnetic resonance imaging, intracranial pressure (ICP) monitors, and other laboratory test are usually used for more precise determination of the severity of the head trauma. GOALS OF THERAPY The primary goal of therapy in TBI is to have a positive oxygen supply/consumption ratio. Cerebral perfusion pressure (CPP) is a clinical target that is used to achieve this goal, especially in cases of moderate to severe TBI. The CPP goal is more than 70 mm Hg in adults (more than 60 mm Hg in children) and is calculated from the following equation: CPP ¼ MAP
197
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
SEMINARS IN SPEECH AND LANGUAGE/VOLUME 35, NUMBER 3
ICP, where MAP is mean arterial pressure and ICP is intracranial pressure. The goals of pharmacotherapy in TBI are to use drugs that increase MAP and reduce ICP. Several IV fluids, blood products, and drugs are given to try to achieve this goal. TREATMENT AFTER MILD TBI There are no specific pharmacological agents used to treat mild TBI. Several psychoactive drugs have been suggested including methylphenidate, dextroamphetamine, amantadine, bromocriptine, and others, but none of these agents have become standard of care.3 However, several conditions that could occur with this diagnosis may require pharmacological interventions. These could involve long-term management.
Seizures Seizures can also result from mild TBI. Early posttraumatic seizures (within 1 week) are usually managed acutely and do not require long-term management. Late seizures represent epilepsy. In such cases, long-term use of antiseizure medications may be necessary. Depending on the diagnosis of the seizure type, many antiepileptic drugs (AEDs) are available as single agents or as part of a combination regimen. Treatment guidelines are available from the International League against Epilepsy.4,5 As a general rule, many AEDs are known to cause central nervous system (CNS) depression and have effects on cognitive functions. Examples of older AEDs are phenytoin (Dilantin; Pfizer, New York, NY), phenobarbital, carbamazepine (Tegretol; Novartis, East Hanover, NJ), and sodium valproate. Examples of newer agents that generally have fewer side effects are gabapentin (Neurotin; Pfizer, New York, NY), lamotrigine (Lamictal; GlaxoSmithKline, Abbotsford, Victoria, Australia), levetiracetam (Keppra; UCB, Inc., Smyrna, GA), and zonisamide (Zonegran; Elan Pharma International Ltd., Teaneck, NJ). In some patients with TBI, chronic anticonvulsant therapy is indicated. When phenytoin and valproic acid are used, we must consider
2014
that both agents have suppressive effects on the CNS, especially in high doses. Because both agents having a narrow therapeutic toxic ratio, it is necessary to monitor serum concentration to maximize efficacy and reduce side effects. High levels of phenytoin can cause nystagmus, ataxia, and CNS depression. Valproic acid causes minimal cognitive impairment, but monitoring of serum concentrations is recommended to reduce the possibility of other side effects. If levetiracetam is used as a chronic antiseizure medication, the effects on the CNS are minimal (somnolence, and dizziness most commonly).
Depression There are two classes of antidepressant agents that are commonly used to treat depression. The older agents are called tricyclic antidepressants (TCAs). Examples of these include amitriptyline and nortriptyline, and their use is limited by their side effect profile. Amitriptyline is sometimes used for neurologically mediated pain. Common side effects for these agents include dry mouth, blurred vision, constipation, urinary retention, drowsiness. They can precipitate seizures in patients with epilepsy. The other major classes are the selective serotonin reuptake inhibitors (SSRIs) and the serotonin norepinephrine reuptake inhibitors (SNRIs). Examples of SSRIs are fluoxetine and sertraline; SNRIs include duloxetine and venlafaxine. Clinicians should be aware that these types of drugs have a slow onset of action (4 to 6 weeks for TCAs and 2 to 3 weeks for SSRIs and SNRIs) and that suicidal tendencies are well documented especially in adolescents. Both TCAs and the newer agents have been reported to cause extrapyramidal symptoms, such as dystonia and dyskinesia.6,7
Dizziness The most common medications used to treat dizziness are two antihistamines, meclizine (Antivert [Pfizer, New York, NY] and others) and dimenhydrinate (Dramamine Medtech Products, Inc., Irvington, NY). These drugs are relatively safe but can cause drowsiness and dry mouth.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
198
Headaches and Pain Long-term oral narcotic pain treatment should be avoided unless absolutely necessary. Prescription opiates are becoming the number one drug of abuse in the United States, especially hydrocodone-containing products.8 Alternatives to oral narcotics are acetaminophen and ibuprofen, although longer-term use of these agents also presents some risks. Concerns include a potential for acetaminophen-induced liver toxicity with higher than recommended doses or coadministration of alcohol. With long-term use of ibuprofen, there is potential for gastrointestinal bleeding and risk for cardiac-related events. Neurologically mediated pain may be treated with amitriptyline and gabapentin. Amitriptyline is a tricyclic antidepressant that needs careful monitoring because of its side effects profile, which includes anticholinergic activity and dyskinesia. Gabapentin is an anticonvulsant that has a good safety profile.
Sleep Diphenhydramine (Benadryl; Parkedale Pharmaceuticals, Inc., Rochester, MI) is an antihistamine that is used to treat some drug reactions. Diphenhydramine-containing overthe-counter products can induce sleepiness. Routine use can increase anticholinergic side effects like dry month, urinary retention, pupillary constriction, and constipation. Trazodone is a tetracyclic antidepressant that could be used for depression-related insomnia. This agent has side effects similar to those of TCAs. Melatonin is a neurohormone produced by the brain and it is promoted as a natural remedy for the treatment of sleep disorders. Commercially available, melatonin is either isolated from the pineal gland of cows or is chemically synthesized. The 1994 Dietary Supplement Health and Education Act provide requirements for good manufacturing standards, although these standards are typically not held to.9 In addition, most supplements are easily accessible through the Internet, could come from anywhere in the world, and may not meet U.S. standards. Consumers must be aware that many concerns exist with these products including mislabeling, adulterations, and con-
tamination.10 If melatonin is used to treat sleep disorders, it should be obtained from a reliable source. Benzodiazepines (estazolam and temazepam) and benzodiazepine-like products (zolpidem and zaleplon) are effective hypnotics. They should only be used for short-term treatment of sleep disorders or sporadically because they are addicting and can cause tolerance and lifethreatening withdrawal reactions. Lifestyle and behavioral treatments (i.e., relaxation training, cognitive therapy, stimulus control, sleep restriction therapy, sleep hygiene) may be a better long-term solution to sleep disorders in general. THERAPEUTIC AGENTS FOR MODERATE TO SEVERE HEAD TRAUMA Guidelines for the management of both adults11 and infants/children12 have been published providing recommendations for the treatment of TBI. These recommendations are based on evidence from available studies, many of which are not large randomized, double-blinded placebo-controlled clinical trials, which would be considered the ideal. Studies of this type would be extremely difficult to conduct with this population.
Fluid and Electrolyte Management Intravenous fluid and electrolyte management in TBI is directed toward achieving homeostasis or a state of hypernatremia and hyperosmolarity. Perhaps the most important aspect to replacing fluids and electrolytes in TBI is to use isotonic (0.9% sodium chloride or lactated Ringers) or hypertonic (3% sodium chloride) solutions and not a hypotonic solution (5% dextrose in water) because free water could increase ICP, which is counter to the goal. Other electrolytes like potassium, calcium, magnesium, and phosphate are replaced as needed by adding them to a large volume parenteral solution or to a small volume as piggyback. Crystalloids, which are aqueous solutions with soluble molecules, are used as the first option for volume expansion. Occasionally, the
199
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
SEMINARS IN SPEECH AND LANGUAGE/VOLUME 35, NUMBER 3
use of colloids is necessary when blood pressure or MAP goals are not achieved. Colloids contain larger insoluble molecules. Examples of colloids are blood, albumin, and hetastarch. Albumin is extracted from blood, and hetastarch is a synthetic compound derived from the corn molecule. Theoretically when colloids are administered to a patient they draw water into the intravascular compartment, thereby increasing blood pressure. Similarly, sympathomimetic amines or adrenergic agents may be used if the blood pressure or MAP goal is not achieved. The two most commonly used agents of this type are phenylephrine and norepinephrine. These two agents are preferred because phenylephrine is a pure vasoconstrictor (a-adrenergic effect) and norepinephrine is considered the most potent vasoconstrictor (a-adrenergic effect), although it also has the effect of increasing cardiac output (b-adrenergic effect). Both of these agents have a quick onset of action and short duration, thus requiring constant intravenous infusion to maintain their effects.
Osmotic Diuretic Mannitol is an osmotic diuretic that is used intravenously to reduce ICP rapidly. Usually it is dosed by weight and is only used in extreme cases when ICP is very high. It is a large molecule, unable to pass through the blood– brain barrier, so it does not penetrate the CNS. Initially, it produces a colloid-like effect, increasing blood pressure. Once distributed, it draws water from extravascular spaces (including the brain) into the intravascular space and is eliminated by the kidneys, drawing water with it. Fluid and electrolyte imbalance may result. It is necessary to monitor and replace fluids as needed.
Pain Control and Sedation Analgesics and anxiolytics are often used to treat pain and anxiety, conditions that can both increase blood pressure. Most clinicians are likely to treat aggressively, although the direct benefits of these treatments in terms of reducing morbidity and mortality in patients with TBI are not proven.
2014
Analgesic Agents Another important element in the management of TBI is pain control. Patients that are experiencing pain can also have increased ICP. Pain assessment tools (e.g., numeric scales) and clinical signs of pain are used to adjust the dose and frequency of administration of the analgesic agent. For the management of moderate to severe pain, intravenous narcotic or opioid agents are usually preferred. Examples of the most powerful narcotic agents include fentanyl and morphine. The selection of the agent depends on many factors including drug allergies, the presence of hypotension, the level of renal function, among other factors. In addition to causing hypotension, these agents can cause CNS depression, respiratory depression, constipation, addiction, tolerance, and drug withdraw upon discontinuation. Careful management is essential to minimize the side effects. We must be mindful that the combination of anesthetic and sedative agents can enhance hypotension, CNS depression, and respiratory depression. This combination is also likely to affect cognition. Acetaminophen or ibuprofen can be used as alternatives to narcotics or as a step-down therapy from narcotic therapy. The use of oral narcotics is reserved for mild TBI and usually is a combination of hydrocodone or codeine with acetaminophen.
Anesthetic and Sedative Agents Several anesthetic and sedative agents are used in the treatment of TBI with the goal of controlling anxiety or agitation with the theoretical benefits of reducing oxygen consumption and ICP. Sedation assessment tools (e.g., Ramsey Sedation Scale)13 and clinical signs are used to adjust the dose and frequency of administration of the anesthetic or sedative agent. Propofol is an anesthetic agent that is used in some of the most severe cases of TBI. It is used as an IV infusion because it has a quick onset of action and short duration. Propofol is usually not used for more than a few days. If sedation is still indicated after that period of time, another agent may be used. In infants and children, the infusion should be limited to prevent lifethreatening complications. Perhaps the two most common sedative agents used are
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
200
lorazepam (adults) and midazolam (children), both of which are benzodiazepines. Physical tolerance and addiction may occur with prolonged therapy and may require tapering off the dose over time to prevent withdrawal reactions. Longer-acting benzodiazepines (e.g., diazepam) frequently cause residual effect the day after administration. Benzodiazepines are also known to impair mental and motor functions and can cause anterograde amnesia (loss of memory). Dexmedetomidine is another alternative. This drug is considered to be safer than benzodiazepines in that it causes less respiratory depression and does not have addictive properties. Although preferable for these reasons, its effectiveness in terms of sedation is not as well established as the others.
Pentobarbital Coma One of the goals in the treatment of moderate to severe TBI is to increase oxygen supply while reducing oxygen consumption. Optimal oxygen supply is delivered through manipulations of mechanical ventilation, and decreasing oxygen demands can be achieved by using drug-induced coma. Pentobarbital is a potent barbiturate that acts as an anesthetic agent thus suppressing the oxygen demand of the brain. Although pentobarbital has a long pharmacokinetic half-life, the pharmacodynamics effect is shorter, meaning that the patient may continue to experience sedation effects but not remain in coma. This agent is given as a loading dose followed by a constant intravenous infusion to maintain the coma state. The goal of pentobarbital therapy is to suppress bursts of brain electrical activity. This goal is monitored by use of electroencephalogram or bispectral index.
Antiepileptic Drugs One of the potential sequelae of TBI is seizure activity. Although the type of seizure activity may vary and may not be clinically obvious, the presence of tonic-clonic generalized seizures must be treated. Usually benzodiazepines are the treatment of choice in the acute phase. The most common agents used are diazepam and lorazepam. Diazepam and lorazepam have a
quick onset of action but short duration. Although both agents have long pharmacokinetic half-lives, the pharmacodynamic effect for seizure control is of short duration due to redistribution from the brain to other parts of the body. The sedative effects of these agents last much longer than their antiseizure effects. Rapid intravenous administration is preferred followed by a longer-acting anticonvulsant like phenytoin. Oftentimes, fosphenytoin (which the body converts to phenytoin) is the agent that is used.
Posttraumatic Seizure Prophylaxis Current guidelines indicate the use of early (7 days) posttraumatic seizure prophylaxis in patients with TBI. Although phenytoin and valproic acid (or valproate) are recommended, more recently the use of levetiracetam has become more prevalent, primarily because levetiracetam offers easier dosing and fewer side effects. Although preferable for these reasons, studies demonstrating that levetiracetam is safe and effective in reducing the incidence of early posttraumatic seizures are limited.
Neuromuscular Blocking Agents The use of neuromuscular blocking agents is sometimes indicated in patients with TBI for the purpose of maximizing benefits of mechanical ventilation and in patients with intractable high ICPs. These agents will block muscular activity, temporarily paralyzing the patient. Due to their relatively short duration, they are usually given as an intravenous infusion. Ideally, these agents are only used for a short time, but occasionally they are continued for longer periods. With all of these agents, the patient can sometimes remain paralyzed beyond the period in which this effect would be expected. Although we must consider differences in half-life, active metabolites, renal elimination, and renal function, when selecting these agents, we still recommend a “drug holiday” (stopping for short periods of time) to prevent unexpected prolonged neuromuscular blockage. Some of the agents in this class include succinylcholine, vecuronium, and cisatracurium.
201
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
SEMINARS IN SPEECH AND LANGUAGE/VOLUME 35, NUMBER 3
Antithrombotic Agents Patients with moderate to severe TBI are likely to be immobilized, either as a result of their injury or as part of their treatment. Once a patient is immobilized, there is an increased risk of thromboembolism and the use of prophylactic antithrombotic agents may be indicated. The development of pulmonary embolism is a potentially fatal complication. Heparin and lowmolecular-weight heparins (e.g., enoxaparin) are the most common agents used for the prophylaxis or treatment of this complication. Low doses of these agents are used for prophylaxis, and higher doses are used for the treatment of a thromboembolic event. The main concern with these therapies is bleeding, so careful monitoring is necessary to reduce the risk of this drug-related complication.
Antimicrobial Agents Several classes of antibiotics that could be used to treat severe to life-threatening infections are associated with ototoxicity. The aminoglycosides are used primarily to treat gram-negative infections, especially Pseudomonas aeruginosa. They can also be used for specific gram-positive infections. The most common agents in this class are gentamicin, tobramycin, and amikacin. Persistent high tissue concentrations are associated with vestibular (gentamicin) or cochlear (tobramycin, amikacin) permanent damage.14 Current dosing practices are intended to minimize these persistent high concentrations and may decrease the incidence of this side effect. The other class of antibiotics associated with ototoxicity is glycopeptides, of which only vancomycin is currently available in the United States. Vancomycin is used to treat gram-positive infections especially methicillin-resistant Staphylococcus aureus. Similar to the aminoglycosides, persistent high tissue concentration is associated with tinnitus, although there exists some controversy with regard to current dosing practices and the incidence of this side effect.15,16 The use of these two types of antibiotics together may increase the possibility of this side effect. Another antibiotic class associated with ototoxicity is the macrolides. Erythromycin is a macrolide that is sometimes used in TBI patients, although it is typically used for the purpose of
2014
increasing gastrointestinal motility and not as an antibiotic. Although not an antibiotic, loop diuretics (e.g., furosemide) may also induced ototoxicity in some patients and potentiate the antibiotic-induced ototoxicity.
Stress Ulcer Prophylaxis Another possible complication of some patients with TBI is stress ulcers and gastrointestinal bleeding. Two well-established indications for stress ulcer prophylaxis are patients on mechanical ventilation for more than 48 hours and patients with preexisting coagulopathies. The most common agents used for this purpose are histamine 2 antagonist (e.g., famotidine) and proton pump inhibitors (e.g., pantoprazole). These drugs will reduce acid secretion in the stomach but there are questions as to whether they may increase the incidence of certain types of infections.
IV to Oral Switch One of the goals of most medication regimens is to switch parenteral medications (IV, IM, SQ) to the oral route whenever possible. The oral route of administration is ideal for multiple reasons, including it is more physiological, has fewer complications, and costs less. Many pharmacy departments have programs in place to initiate and carry out this transition. A typical case is when the medication is first given via a nasogastric tube in liquid form and subsequently as an oral liquid, tablet, or capsule. In transitioning a patient to an oral route of administration, an assessment of their ability to swallow is essential to prevent complications like aspiration pneumonia.
Role of Progesterone in TBI Progesterone is a naturally occurring hormone that appears to have beneficial effect as a neuroprotective agent when given to patients with TBI. A 2012 Cochrane review concluded that progesterone may improve the neurologic outcome of patients suffering from TBI, but further studies are needed to better understand how progesterone may benefit this population.17
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
202
CONCLUSION A wide range of pharmacological interventions are used in the treatment of TBI, and the type of intervention is related to the severity of the injury, comorbidities, and complications. Since interventions by SLP practitioners can be seen in all types of head injuries, a basic understanding of these drugs is important. Some of the drugs can affect cognitive, motor, and neuromuscular functions, and others may cause ototoxicity. Finally, after the acute phase of the head trauma, the prefer route of administration of most drugs is oral, and swallowing evaluation is necessary. REFERENCES 1. Spruill WJ, Wade WE, DiPiro JT, Blouin RA, Pruemer JM, eds. Concepts in Clinical Pharmacokinetics. 6th ed. Bethesda, MD: American Society of Health-Systems Pharmacists; 2014 2. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2(7872):81–84 3. Arciniegas DB, Anderson CA, Topkoff J, McAllister TW. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat 2005;1(4): 311–327 4. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006;47(7): 1094–1120 5. Glauser T, Ben-Menachem E, Bourgeois B, et al; ILAE Subcommission on AED Guidelines. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013; 54(3):551–563
6. Vandel P, Bonin B, Leveque E, Sechter D, Bizouard P. Tricyclic antidepressant-induced extrapyramidal side effects. Eur Neuropsychopharmacol 1997;7(3):207–212 7. Madhusoodanan S, Alexeenko L, Sanders R, Brenner R. Extrapyramidal symptoms associated with antidepressants—a review of the literature and an analysis of spontaneous reports. Ann Clin Psychiatry 2010;22(3):148–156 8. Dietary Supplement Health and Education Act of 1994. Available at: http://ods.od.nih.gov/About/ DSHEA_Wording.aspx. Accessed May 21, 2014 9. National Institute on Drug Abuse. Prescription Drugs: Abuse and Addiction. DHHS Publication No. 11–4881. Washington, DC: U.S. Government Printing Office; 2011 10. Rivera JO, Loya AM, Ceballos R. Use of herbal medicines and implications for conventional drug therapy medical sciences. Altern Integ Med 2013; 2(6):1–6 11. Guidelines for the Management of Severe Traumatic Brain Injury J Neurotrauma 2007;24(Suppl 1):1–106 12. Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents-Second Edition. Pediatr Crit Care Med 2012;13(Suppl 1):1–82 13. Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadolone. BMJ 1974;2(5920):656–659 14. Selimoglu E. Aminoglycoside-induced ototoxicity. Curr Pharm Des 2007;13(1):119–126 15. Forouzesh A, Moise PA, Sakoulas G. Vancomycin ototoxicity: a reevaluation in an era of increasing doses. Antimicrob Agents Chemother 2009;53(2): 483–486 16. Shields RK, Martello JL, Potoski BA. Is vancomycin ototoxicity a significant risk? Antimicrob Agents Chemother 2009;53(10):4572–4573, author reply 4572–4573 17. Ma J, Huang S, Qin S, You C. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2012;10(10):CD008409
203
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
Copyright of Seminars in Speech & Language is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
ABSTRACT
This article provides an overview of the pharmacological management of traumatic brain injury (TBI). A basic introduction to key pharmacokinetic and pharmacodynamic principles is used to guide the reader. The goals of the pharmacological management of TBI are explained starting with mild TBI. The main medications used for each medical condition are described with a primary emphasis of effects that may interfere with the role of speech-language pathology (SLP). Some medications may interfere with cognitive, motor, and neuromuscular functions, and others may cause ototoxicity. A basic overview of the pharmacological management of moderate to severe TBI is included because the SLP practitioner may encounter patients with TBI during the recovery phase. The importance of assessment of swallowing evaluations is discussed because the oral route of administration of medications is preferred once the patient is stable. KEYWORDS: Pharmacology, pharmacokinetics, pharmacodynamics, traumatic brain injury
Learning Outcomes: As a result of this activity, the reader will be able to (1) discuss and contrast the difference between pharmacokinetic and pharmacodynamic effects; (2) select medications that can be used for the treatment of some of the conditions resulting from mild traumatic brain injury (TBI); (3) identify medications that can have an effect in cognition, motor, and neuromuscular functions in the management of mild TBI; (4) identify medications that can cause ototoxicity in the management of TBI.
1
University of Texas at El Paso College of Health Sciences and University of Texas at Austin College of Pharmacy, El Paso, Texas. Address for correspondence: Jose O. Rivera, Pharm.D., University of Texas at El Paso College of Health Sciences and University of Texas at Austin College of Pharmacy, 1101 N. Campbell, Suite 710, El Paso, TX 79902 (e-mail: [email protected]).
196
Concussion 101 for SLPs; Guest Editor, Anthony P. Salvatore, Ph.D., CCC-SLP Semin Speech Lang 2014;35:196–203. Copyright # 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 5844662. DOI: http://dx.doi.org/10.1055/s-0034-1384681. ISSN 0734-0478.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O. Rivera, Pharm.D.1 Jose
T
he pharmacological management of traumatic brain injury (TBI) is driven by the severity of the injury and can be quite complex. A wide range of pharmacological agents may be necessary depending on severity and considering comorbidities and complications. It is necessary to establish a basic understanding of the effects (both desired effects and side effects) of these agents when implementing speech-language interventions. This would include a basic understanding of pharmacokinetic and pharmacodynamic principles that explain drug effects. A brief overview of these concepts is presented here. BASIC PHARMACOKINETIC AND PHARMACODYNAMIC PRINCIPLES Pharmacokinetics is the science that studies the absorption, distribution, metabolism, and elimination of a drug in the body. The absorption phase depends on the route of administration and the formulation of the drug. As a general rule, the intravenous administration is the most rapid and complete method of administration of a drug. Parenteral routes of administration include intravenous (IV), intramuscular (IM), and subcutaneous (SQ). In most critical situations, the IV route will be the preferred method of administration. Once a drug is absorbed into the intravascular compartment, it is then distributed throughout the body. Several drugrelated factors will determine the extent of distribution. Some drugs will be metabolized by the liver to inactive, active, or even toxic metabolites. Other drugs are eliminated by the kidney or through the feces without being metabolized, and finally some drugs are partially metabolized and partially eliminated via the kidneys or feces. Onset of action (how quickly the intended effect is seen), peak (maximum effect), and duration of action (how long the effect lasts) are determined by several drugrelated factors, the route of administration, and the formulation. Frequently, the half-life (time required to eliminate 50% of the drug from the body) will determine the onset, peak, and duration of action of the drug. The longer the half-life, the more time is required for the drug to achieve a concentration at steady state where there is a balance between intake and elimina-
tion. For some drugs, the amount in the body that is effective and the amount in the body that is toxic are not very different. This is called a narrow therapeutic toxic ratio and may require monitoring the serum concentration of the drug (therapeutic drug monitoring). Examples of these types of drugs are phenytoin, gentamicin, and vancomycin. Pharmacodynamics is the science that studies the drug action primarily via a drugreceptor interaction. Usually the concentration of the drug at the receptor site and the affinity of the drug for a particular receptor will produce the therapeutic and adverse effects. Many types of receptor are distributed throughout the body. Pharmacokinetic principles often determine the pharmacodynamic properties of a given agent, although not always. A more extensive review of these concepts is available to the reader.1 SEVERITY OF TBI TBI can be classified as severe, moderate, or mild. Glasgow Coma Scale (GCS) is a common clinical tool that is used to quickly assess the severity of the injury. GCS scores range from 3T to 15, with lower scores indicating more severe injury.2 A score of 3T indicates the most severe head injury, and a 15 indicates normal. The letter T indicates intubation or tracheotomy in patients who require mechanical ventilation support. A score of 13 or higher is indicative of mild TBI, 9 to 12 is moderate, and 8 or less is severe. Other neurologic tests, computer tomography scans, magnetic resonance imaging, intracranial pressure (ICP) monitors, and other laboratory test are usually used for more precise determination of the severity of the head trauma. GOALS OF THERAPY The primary goal of therapy in TBI is to have a positive oxygen supply/consumption ratio. Cerebral perfusion pressure (CPP) is a clinical target that is used to achieve this goal, especially in cases of moderate to severe TBI. The CPP goal is more than 70 mm Hg in adults (more than 60 mm Hg in children) and is calculated from the following equation: CPP ¼ MAP
197
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
SEMINARS IN SPEECH AND LANGUAGE/VOLUME 35, NUMBER 3
ICP, where MAP is mean arterial pressure and ICP is intracranial pressure. The goals of pharmacotherapy in TBI are to use drugs that increase MAP and reduce ICP. Several IV fluids, blood products, and drugs are given to try to achieve this goal. TREATMENT AFTER MILD TBI There are no specific pharmacological agents used to treat mild TBI. Several psychoactive drugs have been suggested including methylphenidate, dextroamphetamine, amantadine, bromocriptine, and others, but none of these agents have become standard of care.3 However, several conditions that could occur with this diagnosis may require pharmacological interventions. These could involve long-term management.
Seizures Seizures can also result from mild TBI. Early posttraumatic seizures (within 1 week) are usually managed acutely and do not require long-term management. Late seizures represent epilepsy. In such cases, long-term use of antiseizure medications may be necessary. Depending on the diagnosis of the seizure type, many antiepileptic drugs (AEDs) are available as single agents or as part of a combination regimen. Treatment guidelines are available from the International League against Epilepsy.4,5 As a general rule, many AEDs are known to cause central nervous system (CNS) depression and have effects on cognitive functions. Examples of older AEDs are phenytoin (Dilantin; Pfizer, New York, NY), phenobarbital, carbamazepine (Tegretol; Novartis, East Hanover, NJ), and sodium valproate. Examples of newer agents that generally have fewer side effects are gabapentin (Neurotin; Pfizer, New York, NY), lamotrigine (Lamictal; GlaxoSmithKline, Abbotsford, Victoria, Australia), levetiracetam (Keppra; UCB, Inc., Smyrna, GA), and zonisamide (Zonegran; Elan Pharma International Ltd., Teaneck, NJ). In some patients with TBI, chronic anticonvulsant therapy is indicated. When phenytoin and valproic acid are used, we must consider
2014
that both agents have suppressive effects on the CNS, especially in high doses. Because both agents having a narrow therapeutic toxic ratio, it is necessary to monitor serum concentration to maximize efficacy and reduce side effects. High levels of phenytoin can cause nystagmus, ataxia, and CNS depression. Valproic acid causes minimal cognitive impairment, but monitoring of serum concentrations is recommended to reduce the possibility of other side effects. If levetiracetam is used as a chronic antiseizure medication, the effects on the CNS are minimal (somnolence, and dizziness most commonly).
Depression There are two classes of antidepressant agents that are commonly used to treat depression. The older agents are called tricyclic antidepressants (TCAs). Examples of these include amitriptyline and nortriptyline, and their use is limited by their side effect profile. Amitriptyline is sometimes used for neurologically mediated pain. Common side effects for these agents include dry mouth, blurred vision, constipation, urinary retention, drowsiness. They can precipitate seizures in patients with epilepsy. The other major classes are the selective serotonin reuptake inhibitors (SSRIs) and the serotonin norepinephrine reuptake inhibitors (SNRIs). Examples of SSRIs are fluoxetine and sertraline; SNRIs include duloxetine and venlafaxine. Clinicians should be aware that these types of drugs have a slow onset of action (4 to 6 weeks for TCAs and 2 to 3 weeks for SSRIs and SNRIs) and that suicidal tendencies are well documented especially in adolescents. Both TCAs and the newer agents have been reported to cause extrapyramidal symptoms, such as dystonia and dyskinesia.6,7
Dizziness The most common medications used to treat dizziness are two antihistamines, meclizine (Antivert [Pfizer, New York, NY] and others) and dimenhydrinate (Dramamine Medtech Products, Inc., Irvington, NY). These drugs are relatively safe but can cause drowsiness and dry mouth.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
198
Headaches and Pain Long-term oral narcotic pain treatment should be avoided unless absolutely necessary. Prescription opiates are becoming the number one drug of abuse in the United States, especially hydrocodone-containing products.8 Alternatives to oral narcotics are acetaminophen and ibuprofen, although longer-term use of these agents also presents some risks. Concerns include a potential for acetaminophen-induced liver toxicity with higher than recommended doses or coadministration of alcohol. With long-term use of ibuprofen, there is potential for gastrointestinal bleeding and risk for cardiac-related events. Neurologically mediated pain may be treated with amitriptyline and gabapentin. Amitriptyline is a tricyclic antidepressant that needs careful monitoring because of its side effects profile, which includes anticholinergic activity and dyskinesia. Gabapentin is an anticonvulsant that has a good safety profile.
Sleep Diphenhydramine (Benadryl; Parkedale Pharmaceuticals, Inc., Rochester, MI) is an antihistamine that is used to treat some drug reactions. Diphenhydramine-containing overthe-counter products can induce sleepiness. Routine use can increase anticholinergic side effects like dry month, urinary retention, pupillary constriction, and constipation. Trazodone is a tetracyclic antidepressant that could be used for depression-related insomnia. This agent has side effects similar to those of TCAs. Melatonin is a neurohormone produced by the brain and it is promoted as a natural remedy for the treatment of sleep disorders. Commercially available, melatonin is either isolated from the pineal gland of cows or is chemically synthesized. The 1994 Dietary Supplement Health and Education Act provide requirements for good manufacturing standards, although these standards are typically not held to.9 In addition, most supplements are easily accessible through the Internet, could come from anywhere in the world, and may not meet U.S. standards. Consumers must be aware that many concerns exist with these products including mislabeling, adulterations, and con-
tamination.10 If melatonin is used to treat sleep disorders, it should be obtained from a reliable source. Benzodiazepines (estazolam and temazepam) and benzodiazepine-like products (zolpidem and zaleplon) are effective hypnotics. They should only be used for short-term treatment of sleep disorders or sporadically because they are addicting and can cause tolerance and lifethreatening withdrawal reactions. Lifestyle and behavioral treatments (i.e., relaxation training, cognitive therapy, stimulus control, sleep restriction therapy, sleep hygiene) may be a better long-term solution to sleep disorders in general. THERAPEUTIC AGENTS FOR MODERATE TO SEVERE HEAD TRAUMA Guidelines for the management of both adults11 and infants/children12 have been published providing recommendations for the treatment of TBI. These recommendations are based on evidence from available studies, many of which are not large randomized, double-blinded placebo-controlled clinical trials, which would be considered the ideal. Studies of this type would be extremely difficult to conduct with this population.
Fluid and Electrolyte Management Intravenous fluid and electrolyte management in TBI is directed toward achieving homeostasis or a state of hypernatremia and hyperosmolarity. Perhaps the most important aspect to replacing fluids and electrolytes in TBI is to use isotonic (0.9% sodium chloride or lactated Ringers) or hypertonic (3% sodium chloride) solutions and not a hypotonic solution (5% dextrose in water) because free water could increase ICP, which is counter to the goal. Other electrolytes like potassium, calcium, magnesium, and phosphate are replaced as needed by adding them to a large volume parenteral solution or to a small volume as piggyback. Crystalloids, which are aqueous solutions with soluble molecules, are used as the first option for volume expansion. Occasionally, the
199
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
SEMINARS IN SPEECH AND LANGUAGE/VOLUME 35, NUMBER 3
use of colloids is necessary when blood pressure or MAP goals are not achieved. Colloids contain larger insoluble molecules. Examples of colloids are blood, albumin, and hetastarch. Albumin is extracted from blood, and hetastarch is a synthetic compound derived from the corn molecule. Theoretically when colloids are administered to a patient they draw water into the intravascular compartment, thereby increasing blood pressure. Similarly, sympathomimetic amines or adrenergic agents may be used if the blood pressure or MAP goal is not achieved. The two most commonly used agents of this type are phenylephrine and norepinephrine. These two agents are preferred because phenylephrine is a pure vasoconstrictor (a-adrenergic effect) and norepinephrine is considered the most potent vasoconstrictor (a-adrenergic effect), although it also has the effect of increasing cardiac output (b-adrenergic effect). Both of these agents have a quick onset of action and short duration, thus requiring constant intravenous infusion to maintain their effects.
Osmotic Diuretic Mannitol is an osmotic diuretic that is used intravenously to reduce ICP rapidly. Usually it is dosed by weight and is only used in extreme cases when ICP is very high. It is a large molecule, unable to pass through the blood– brain barrier, so it does not penetrate the CNS. Initially, it produces a colloid-like effect, increasing blood pressure. Once distributed, it draws water from extravascular spaces (including the brain) into the intravascular space and is eliminated by the kidneys, drawing water with it. Fluid and electrolyte imbalance may result. It is necessary to monitor and replace fluids as needed.
Pain Control and Sedation Analgesics and anxiolytics are often used to treat pain and anxiety, conditions that can both increase blood pressure. Most clinicians are likely to treat aggressively, although the direct benefits of these treatments in terms of reducing morbidity and mortality in patients with TBI are not proven.
2014
Analgesic Agents Another important element in the management of TBI is pain control. Patients that are experiencing pain can also have increased ICP. Pain assessment tools (e.g., numeric scales) and clinical signs of pain are used to adjust the dose and frequency of administration of the analgesic agent. For the management of moderate to severe pain, intravenous narcotic or opioid agents are usually preferred. Examples of the most powerful narcotic agents include fentanyl and morphine. The selection of the agent depends on many factors including drug allergies, the presence of hypotension, the level of renal function, among other factors. In addition to causing hypotension, these agents can cause CNS depression, respiratory depression, constipation, addiction, tolerance, and drug withdraw upon discontinuation. Careful management is essential to minimize the side effects. We must be mindful that the combination of anesthetic and sedative agents can enhance hypotension, CNS depression, and respiratory depression. This combination is also likely to affect cognition. Acetaminophen or ibuprofen can be used as alternatives to narcotics or as a step-down therapy from narcotic therapy. The use of oral narcotics is reserved for mild TBI and usually is a combination of hydrocodone or codeine with acetaminophen.
Anesthetic and Sedative Agents Several anesthetic and sedative agents are used in the treatment of TBI with the goal of controlling anxiety or agitation with the theoretical benefits of reducing oxygen consumption and ICP. Sedation assessment tools (e.g., Ramsey Sedation Scale)13 and clinical signs are used to adjust the dose and frequency of administration of the anesthetic or sedative agent. Propofol is an anesthetic agent that is used in some of the most severe cases of TBI. It is used as an IV infusion because it has a quick onset of action and short duration. Propofol is usually not used for more than a few days. If sedation is still indicated after that period of time, another agent may be used. In infants and children, the infusion should be limited to prevent lifethreatening complications. Perhaps the two most common sedative agents used are
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
200
lorazepam (adults) and midazolam (children), both of which are benzodiazepines. Physical tolerance and addiction may occur with prolonged therapy and may require tapering off the dose over time to prevent withdrawal reactions. Longer-acting benzodiazepines (e.g., diazepam) frequently cause residual effect the day after administration. Benzodiazepines are also known to impair mental and motor functions and can cause anterograde amnesia (loss of memory). Dexmedetomidine is another alternative. This drug is considered to be safer than benzodiazepines in that it causes less respiratory depression and does not have addictive properties. Although preferable for these reasons, its effectiveness in terms of sedation is not as well established as the others.
Pentobarbital Coma One of the goals in the treatment of moderate to severe TBI is to increase oxygen supply while reducing oxygen consumption. Optimal oxygen supply is delivered through manipulations of mechanical ventilation, and decreasing oxygen demands can be achieved by using drug-induced coma. Pentobarbital is a potent barbiturate that acts as an anesthetic agent thus suppressing the oxygen demand of the brain. Although pentobarbital has a long pharmacokinetic half-life, the pharmacodynamics effect is shorter, meaning that the patient may continue to experience sedation effects but not remain in coma. This agent is given as a loading dose followed by a constant intravenous infusion to maintain the coma state. The goal of pentobarbital therapy is to suppress bursts of brain electrical activity. This goal is monitored by use of electroencephalogram or bispectral index.
Antiepileptic Drugs One of the potential sequelae of TBI is seizure activity. Although the type of seizure activity may vary and may not be clinically obvious, the presence of tonic-clonic generalized seizures must be treated. Usually benzodiazepines are the treatment of choice in the acute phase. The most common agents used are diazepam and lorazepam. Diazepam and lorazepam have a
quick onset of action but short duration. Although both agents have long pharmacokinetic half-lives, the pharmacodynamic effect for seizure control is of short duration due to redistribution from the brain to other parts of the body. The sedative effects of these agents last much longer than their antiseizure effects. Rapid intravenous administration is preferred followed by a longer-acting anticonvulsant like phenytoin. Oftentimes, fosphenytoin (which the body converts to phenytoin) is the agent that is used.
Posttraumatic Seizure Prophylaxis Current guidelines indicate the use of early (7 days) posttraumatic seizure prophylaxis in patients with TBI. Although phenytoin and valproic acid (or valproate) are recommended, more recently the use of levetiracetam has become more prevalent, primarily because levetiracetam offers easier dosing and fewer side effects. Although preferable for these reasons, studies demonstrating that levetiracetam is safe and effective in reducing the incidence of early posttraumatic seizures are limited.
Neuromuscular Blocking Agents The use of neuromuscular blocking agents is sometimes indicated in patients with TBI for the purpose of maximizing benefits of mechanical ventilation and in patients with intractable high ICPs. These agents will block muscular activity, temporarily paralyzing the patient. Due to their relatively short duration, they are usually given as an intravenous infusion. Ideally, these agents are only used for a short time, but occasionally they are continued for longer periods. With all of these agents, the patient can sometimes remain paralyzed beyond the period in which this effect would be expected. Although we must consider differences in half-life, active metabolites, renal elimination, and renal function, when selecting these agents, we still recommend a “drug holiday” (stopping for short periods of time) to prevent unexpected prolonged neuromuscular blockage. Some of the agents in this class include succinylcholine, vecuronium, and cisatracurium.
201
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
SEMINARS IN SPEECH AND LANGUAGE/VOLUME 35, NUMBER 3
Antithrombotic Agents Patients with moderate to severe TBI are likely to be immobilized, either as a result of their injury or as part of their treatment. Once a patient is immobilized, there is an increased risk of thromboembolism and the use of prophylactic antithrombotic agents may be indicated. The development of pulmonary embolism is a potentially fatal complication. Heparin and lowmolecular-weight heparins (e.g., enoxaparin) are the most common agents used for the prophylaxis or treatment of this complication. Low doses of these agents are used for prophylaxis, and higher doses are used for the treatment of a thromboembolic event. The main concern with these therapies is bleeding, so careful monitoring is necessary to reduce the risk of this drug-related complication.
Antimicrobial Agents Several classes of antibiotics that could be used to treat severe to life-threatening infections are associated with ototoxicity. The aminoglycosides are used primarily to treat gram-negative infections, especially Pseudomonas aeruginosa. They can also be used for specific gram-positive infections. The most common agents in this class are gentamicin, tobramycin, and amikacin. Persistent high tissue concentrations are associated with vestibular (gentamicin) or cochlear (tobramycin, amikacin) permanent damage.14 Current dosing practices are intended to minimize these persistent high concentrations and may decrease the incidence of this side effect. The other class of antibiotics associated with ototoxicity is glycopeptides, of which only vancomycin is currently available in the United States. Vancomycin is used to treat gram-positive infections especially methicillin-resistant Staphylococcus aureus. Similar to the aminoglycosides, persistent high tissue concentration is associated with tinnitus, although there exists some controversy with regard to current dosing practices and the incidence of this side effect.15,16 The use of these two types of antibiotics together may increase the possibility of this side effect. Another antibiotic class associated with ototoxicity is the macrolides. Erythromycin is a macrolide that is sometimes used in TBI patients, although it is typically used for the purpose of
2014
increasing gastrointestinal motility and not as an antibiotic. Although not an antibiotic, loop diuretics (e.g., furosemide) may also induced ototoxicity in some patients and potentiate the antibiotic-induced ototoxicity.
Stress Ulcer Prophylaxis Another possible complication of some patients with TBI is stress ulcers and gastrointestinal bleeding. Two well-established indications for stress ulcer prophylaxis are patients on mechanical ventilation for more than 48 hours and patients with preexisting coagulopathies. The most common agents used for this purpose are histamine 2 antagonist (e.g., famotidine) and proton pump inhibitors (e.g., pantoprazole). These drugs will reduce acid secretion in the stomach but there are questions as to whether they may increase the incidence of certain types of infections.
IV to Oral Switch One of the goals of most medication regimens is to switch parenteral medications (IV, IM, SQ) to the oral route whenever possible. The oral route of administration is ideal for multiple reasons, including it is more physiological, has fewer complications, and costs less. Many pharmacy departments have programs in place to initiate and carry out this transition. A typical case is when the medication is first given via a nasogastric tube in liquid form and subsequently as an oral liquid, tablet, or capsule. In transitioning a patient to an oral route of administration, an assessment of their ability to swallow is essential to prevent complications like aspiration pneumonia.
Role of Progesterone in TBI Progesterone is a naturally occurring hormone that appears to have beneficial effect as a neuroprotective agent when given to patients with TBI. A 2012 Cochrane review concluded that progesterone may improve the neurologic outcome of patients suffering from TBI, but further studies are needed to better understand how progesterone may benefit this population.17
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
202
CONCLUSION A wide range of pharmacological interventions are used in the treatment of TBI, and the type of intervention is related to the severity of the injury, comorbidities, and complications. Since interventions by SLP practitioners can be seen in all types of head injuries, a basic understanding of these drugs is important. Some of the drugs can affect cognitive, motor, and neuromuscular functions, and others may cause ototoxicity. Finally, after the acute phase of the head trauma, the prefer route of administration of most drugs is oral, and swallowing evaluation is necessary. REFERENCES 1. Spruill WJ, Wade WE, DiPiro JT, Blouin RA, Pruemer JM, eds. Concepts in Clinical Pharmacokinetics. 6th ed. Bethesda, MD: American Society of Health-Systems Pharmacists; 2014 2. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2(7872):81–84 3. Arciniegas DB, Anderson CA, Topkoff J, McAllister TW. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat 2005;1(4): 311–327 4. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006;47(7): 1094–1120 5. Glauser T, Ben-Menachem E, Bourgeois B, et al; ILAE Subcommission on AED Guidelines. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013; 54(3):551–563
6. Vandel P, Bonin B, Leveque E, Sechter D, Bizouard P. Tricyclic antidepressant-induced extrapyramidal side effects. Eur Neuropsychopharmacol 1997;7(3):207–212 7. Madhusoodanan S, Alexeenko L, Sanders R, Brenner R. Extrapyramidal symptoms associated with antidepressants—a review of the literature and an analysis of spontaneous reports. Ann Clin Psychiatry 2010;22(3):148–156 8. Dietary Supplement Health and Education Act of 1994. Available at: http://ods.od.nih.gov/About/ DSHEA_Wording.aspx. Accessed May 21, 2014 9. National Institute on Drug Abuse. Prescription Drugs: Abuse and Addiction. DHHS Publication No. 11–4881. Washington, DC: U.S. Government Printing Office; 2011 10. Rivera JO, Loya AM, Ceballos R. Use of herbal medicines and implications for conventional drug therapy medical sciences. Altern Integ Med 2013; 2(6):1–6 11. Guidelines for the Management of Severe Traumatic Brain Injury J Neurotrauma 2007;24(Suppl 1):1–106 12. Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents-Second Edition. Pediatr Crit Care Med 2012;13(Suppl 1):1–82 13. Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadolone. BMJ 1974;2(5920):656–659 14. Selimoglu E. Aminoglycoside-induced ototoxicity. Curr Pharm Des 2007;13(1):119–126 15. Forouzesh A, Moise PA, Sakoulas G. Vancomycin ototoxicity: a reevaluation in an era of increasing doses. Antimicrob Agents Chemother 2009;53(2): 483–486 16. Shields RK, Martello JL, Potoski BA. Is vancomycin ototoxicity a significant risk? Antimicrob Agents Chemother 2009;53(10):4572–4573, author reply 4572–4573 17. Ma J, Huang S, Qin S, You C. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2012;10(10):CD008409
203
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
PHARMACOLOGY OF TRAUMATIC BRAIN INJURY/RIVERA
Copyright of Seminars in Speech & Language is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
