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Valproic Acid Toxicity

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81. Brivaraceta

treatment ? 1 to 3 AEDs in a stable dosage with or without VNS from = 4 weeks (phenobarbital and primidone for at least 3 months) before baseline period: carbamazepine, clobazam, clonazepam, diazepam, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, tiagabine, topiramate, valproic acid, zonisamide ? VNS was allowed and was not counted as AED VNS had to be in place = 9 months before study inclusion ? benzodiazepines were allowed (...) : Institute’s calculation: sodium valproate + valproic acid + magnesium valproate + valpromide. d: Institute’s calculation: phenytoin + phenytoin sodium. CBZ: carbamazepine; CLB: clobazam; CZP: clonazepam; FAS: full analysis set; GBP: gabapentin; ITT: intention to treat; LEV: levetiracetam; LTG: lamotrigine; OXC: oxcarbazepine; PB: phenobarbital; PGB: pregabalin; PHT: phenytoin; PRM: primidone; TPM: topiramate; VPA: valproate; ZNS: zonisamide The patient characteristics were balanced within the studies

2017 Institute for Quality and Efficiency in Healthcare (IQWiG)

82. Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients

be experiencing toxicity from them. Tier III tests can also be examined when they are clin- ically indicated, either by history of use, medication list, or very high probability of misuse/abuse, in a specific patient rather than for every patient. Frequency of laboratory testing CONSENSUS-BASED EXPERT OPINION #1: Based on level II evidence, baseline drug testing should be performed prior to initiation of acute or chronic controlled substance therapy. In addition, random drug testing should be performed (...) be enzymatic or chemi- cal. Enzymes used include ß-glucuronidase from abalone, ß-glu- curonidase type H-3 from Helix pomatia, ß-glucuronidase type L-II from Patella vulgata, and glusulase(23, 24). Recombinant ß-glucuronidase is also now available (IMCSzyme from IMCS). A common approach to chemical hydrolysis includes incubation with concentrated hydrochloric acid. Hydrolysis conditions, such as substrate concentrations, temperature, pH, and time, should be evaluated and optimized by the laboratory. One

2018 American Academy of Pain Medicine

83. Treatment for Bipolar Disorder in Adults: A Systematic Review

(placebo) Paliperidone Placebo Paliperidone Olanzapine Perphenazine plus Mood Stabilizers Mood Stabilizers alone (placebo) Quetiapine Placebo Quetiapine Lithium Quetiapine plus Mood Stabilizers Mood Stabilizers alone (placebo) Quetiapine and Personalize Treatment Lithium and Personalized Treatment Risperidone Placebo Risperidone Olanzapine Risperidone Long Acting Injectable and Treatment as Usual Placebo and Treatment as Usual ES-7 Category Drug Comparator Valproic Acid plus Aripiprazole Lithium plus

2018 Effective Health Care Program (AHRQ)

84. Evaluation and Treatment of Hirsutism in Premenopausal Women Full Text available with Trip Pro

by a partner ( ), exogenous androgens or anabolic steroids ( ), or valproic acid when evaluating patients with hirsutism. 1.0 Diagnosis of Hirsutism 1.1. We suggest testing for elevated androgen levels in all women with an abnormal hirsutism score (2 |⊕⊕OO). In those cases where serum total testosterone levels are normal, if sexual hair growth is moderate/severe or sexual hair growth is mild but there is clinical evidence of a hyperandrogenic endocrine disorder (such as menstrual disturbance or progression (...) in athletes, users of dietary supplements, patients with sexual dysfunction, or in patients with a partner who uses testosterone gel) and valproic acid (a consideration in patient with neurologic disorders). An accurate and specific assay, such as mass spectrometry, is the best choice for assessing serum total testosterone concentrations. Norms are standardized for early morning, when levels are the highest, and for days 4 to 10 of the menstrual cycle (see Section 5, Androgen Testing Remarks) when ovarian

2018 The Endocrine Society

85. Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU Full Text available with Trip Pro

randomized trial (R01HL132887) evaluating nutrition and exercise in acute respiratory failure and, related to this trial, is currently in receipt of an unrestricted research grant and donated amino acid product from Baxter Healthcare and an equipment loan from Reck Medical Devices to two of the participating study sites, external to his institution. Dr. Slooter has disclosed that he is involved in the development of an electroencephalogram-based delirium monitor, where any (future) profits from

2018 Society of Critical Care Medicine

86. CRACKCast E175 – Neurologic Disorders

) Second line: Fosphenytoin/phenytoin Dose: 20 mg/kg Interval: IV over 5-10 minutes (in NS or D5W) Phenobarbital Dose: 20 mg/kg Interval: 1 mg/kg/min over 20 minutes Valproic acid Note: probably has a role, but not as fully researched in kids How does it differ if you are unable to obtain IV or IO access? Remember: Effectiveness (compared to IV) in descending order: IN >>> Buccal >> PR IN route Midazolam Dose: 2 mg/kg (max 5 mg/nostril) IM route Midazolam Dose: 2 mg/kg Fosphenytoin Dose: 20 mg/kg IM (...) Overview Causes of altered mental status in children are broad. Use a comprehensive approach! (e.g. DIMES) Includes vascular events (e.g., stroke, arteriovenous malformation with bleed), infection (e.g., meningitis, sepsis, encephalitis), trauma, toxic ingestion, anatomic or structural abnormality (e.g., intracranial mass or tumor), metabolic derangements, intussusception, or seizures, which may be subclinical. Altered mental status in children has a varied spectrum of clinical presentations and may

2018 CandiEM

87. Treatment of cerebellar motor dysfunction and ataxia

ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study). For patients with Friedreich ataxia or spinocerebellar ataxia (SCA), riluzole probably improves ataxia signs at 12 months (1 Class I study). For patients with SCA type 3, valproic acid 1,200 mg/d possibly improves ataxia at 12 weeks. For patients with spinocerebellar (...) direct current stimulation ; TMS = transcranial magnetic stimulation ; TRH = thyrotropin-releasing hormone ; VPA = valproic acid The cerebellum is composed of the vermis, the hemispheres, and 3 cerebellar peduncles on each side, and contributes largely to balance and motor coordination. The causes of cerebellar dysfunction are numerous and include vitamin deficiencies, structural lesions (caused by tumors or trauma), infection, inflammation, toxins, neurodegeneration, genetics, stroke, multiple

2018 American Academy of Neurology

88. CRACKCast Episode 148 – Acetaminophen

testing Give the antidote = NAC when appropriate. Its all about the nomogram! Don’t forget about the differential diagnosis! In patients with elevated Liver enzymes / abnormal liver function and with or without Renal failure, think: acute tubular necrosis Rhabdomyolysis ischemic hepatitis alcoholic hepatic disease cyclopeptide-containing mushroom toxicity (eg Amanita Phalloides) viral hepatitis Wilson disease, other hepatic toxicities (eg, valproic acid, isoniazid [INH], statins, herbal medications (...) that doesn’t have a bottle or two around. The issue is its relatively a silent clinical syndrome until overt hepatocellular toxicity has ensued! NAC saves lives! Increased glutathione availability Direct binding of NAPQI Provision of inorganic sulfate Reduction of NAPQI back to paracetamol 18% of all unexplained liver failure ends up being attributed to APAP overdose As with all tox, don’t forget the basics (see episode 147) But with APAP overdoses there are 3 goals: Determine the patient’s risk Diagnostic

2018 CandiEM

89. CRACKCast E147 – General Approach to the Poisoned Patient

Emulsion Local Anesthetics, Systemic Toxicity, Fat Soluble Medications [4] List 10 T oxins T hat C ause D elirium Ten toxins that cause delirium (As per UptoDate) are as follows: Prescription medications (e.g., opioids, sedative-hypnotics, antipsychotics, etc…) Non-prescription medications (e.g., OTC antihistamines) Drugs of abuse (e.g., ethanol, heroin, hallucinogens, etc…) Withdrawal states (e.g., ethanol, benzodiazepines) Medication side effects (e.g., hyperammonemia from valproic acid, serotonin (...) ialyzable D rug P roperties Low molecular weight Low protein binding or easily saturable protein binding in a toxicological context Low volume of distribution Low plasma clearance Low dialysate drug concentrations High water solubility For more information, check out the following link: [11] List 8 D ialyzable D rugs Here’s the list: STUMBLED Salicylates Theophylline Uremia Metformin / methanol Barbituates Lithium Ethylene glycol Depakote – valproic acid Or IV STUMBLE ( add Isoniazid and Valproic Acid

2018 CandiEM

90. CRACKCast E162 – Opioids

, guanfacine, valproic acid, gamma-hydroxybutyrate (GHB), ethanol, sedative hypnotics, and atypical antipsychotics. Nontox: pontine stroke or hemorrhage, hypoglycemia. 2) What opioids don’t cause miosis? Meperidine (Demerol) causes mydriasis. 3) Risk factors for opioid overdose? Using alone. IVDU. Co-ingestions. Using shortly after detox. Any drugs acquired on the street. Fentanyl use. 4) What is NAPE? Narcan induced pulmonary edema. Similar to negative-pressure associated pulmonary edema – while patient (...) , miosis, and most importantly, respiratory depression – but presentations may be variable. A negative urine screen is unreliable, and absence of detection should not deter a diagnosis of opioid intoxication when clinical findings support it. Airway protection, oxygenation, ventilation, and early administration of naloxone are the cornerstones for management of patients with opioid toxicity. The duration of action of many opioids, especially after overdose, is significantly longer than that of naloxone

2018 CandiEM

91. Practice Guideline Update Summary: Efficacy and Tolerability of the New Antiepileptic Drugs I: Treatment of New-onset Epilepsy

epilepsy or generalized-onset GTC seizures (1 Class II study), no recommendations can be made regarding TPM use at the studied doses, particularly in new-onset epilepsy and pediatric patients.AAN.com ©2018 American Academy of Neurology Monotherapy in adults and children with new-onset GE or unclassified GTC seizures Level Recommendation No Recommendation Evidence is insufficient to compare efficacy of LTG and TPM with that of valproic acid (VPA) in children and adults with new-onset or relapsing GE (1 (...) Recommendation Level B LTG use should be considered to decrease seizure frequency. Levels B and Level C LTG use should be considered (Level B) and GBP use may be considered (Level C) to decrease seizure frequency in patients aged =60 years. Level C LEV use may be considered to decrease seizure frequency. Level C ZNS use may be considered to decrease seizure frequency. Level C VGB use appears to be less efficacious than immediate-release carbamazepine (CBZ) use and may not be offered; furthermore, toxicity

2018 American Academy of Neurology

92. Compensate victims!

the manufacturers to court, to gain media coverage, and to get politicians' attention. In France, the brand names Mediator° (benfluorex) and Depakine° (valproic acid) are associated with two notorious public health disasters that generated numerous legal proceedings, intense media coverage, and indignant political reactions. The victims of these two very different scandals were recognised as such because they were able to get media coverage and thus capture politicians' attention. They were subsequently (...) the individuals concerned a considerable amount of money and mental energy. Fewer in number, but no less noteworthy, are the victims of severe drug reactions such as toxic epidermal necrolysis. Why not simply recognise, once and for all, that every year thousands of patients are victims of drug toxicity and set up a collective fund for compensating all such individuals? The fund would be paid for by drug companies or their insurers. The first step is to recognise that accidents due to medicinal drugs

2017 Prescrire

93. Palliative Care for the Patient with Incurable Cancer or Advanced Disease: Part 2: Pain and Symptom Management

cases. • See Palliative Care Part 2: Pain and Symptom Management – Constipation. Nausea • Resolves after ~ 1 week. Consider metoclopramide * first line; avoid dimenhydrinat e (Gravol®). Sedation • Stimulants may be helpful if sedation persists, e.g., methylphenidate, dextroamphetamine, or modafanil. Myoclonus • May respond to benzodiazepines, but may be a sign of opioid toxicity requiring hydration, opioid dose reduction or rotation. Delirium • Assess for other causes, e.g., hypercalcemia, UTI

2017 Clinical Practice Guidelines and Protocols in British Columbia

94. CRACKCast E103 – Headache Disorders

: Acetaminophen or NSAIDs First line agents for moderate-severe attacks: 1. DHE 2. Triptans 2.1. Sumatriptan 3. Prochlorperazine 4. Metoclopramide 5. Droperidol 6. Ketorolac Second line agents: 1. Morphine 1.1. Hydromorphone less effective 2. Magnesium 3. Valproic Acid More details: MILD TO MODERATE Acetaminophen 500–1000 mg PO Ibuprofen 600–800 mg PO Gastrointestinal upset Naproxen sodium 275–550 mg PO Gastrointestinal upset MODERATE TO SEVERE First-Line Agents: Dihydroergotamine (DHE) 1 mg IV or IM; may (...) IV or 30 to 60 mg IM Gastrointestinal upset; avoid this medication in elderly and in patients with renal insufficiency Second Line Agents: Morphine 4 to 8 mg IM or IV Opioids less efficacious than other treatment modalities Magnesium 2 g IV More efficacious in migraine with aura Valproic acid 1 g IV Contraindicated in pregnancy 5) List four migraine variants. Neuroimaging should be considered for older or immunocompromised patients with new-onset headaches, headaches associated with unexplained

2017 CandiEM

95. CRACKCast E102 – Seizures

Patient older than 65 years old Seizure duration more than 15 minutes [5] Describe the 1st, 2nd and third line management options for seizure See table 15.1 in 9 th Edition of Rosens – Seizure chapter In summary, they discuss abortive options for seizure, with dosing and precautions, particularly: Initial therapy of either: Diazepam Lorazepam Midazolam Second tier treatments of either: Phenytoin Fosphenytoin Valproic acid Levetiracetam Third-tier treatments Pentobarbital Phenobarbital Midazolam (...) epilepticus can mimic Hypoglycemia CNS infection CNS vascular event Drug toxicity Psychiatric disorder Metabolic encephalopathy Migraine Transient global amnesia [4] What factors predict abnormal CT findings in seizure patients? See Box 92.3 – Differential Diagnosis of AMS in Patient Who Has Seized Focal abnormality on neurological examination Malignancy Closed head injury Neurocutaneous disorder Focal onset of seizure Absence of a history of alcohol abuse History of cysticercosis Altered mental status

2017 CandiEM

96. CRACKCast E115 – Suicide

· Thyroid-stimulating hormone (TSH) (for suspected thyrotoxicosis or thyroid abnormality) Toxicologic Labs · Urine screen for drugs of abuse (to explain acutely altered mental status; to assist ongoing psychiatric care) · Ethanol level (to explain acutely altered mental status; to assist ongoing psychiatric care) · Testing for potential toxic ingestion (eg, aspirin, acetaminophen, serum osmolar gap) · Serum levels of measurable drugs (eg, lithium, valproic acid, phenytoin) Imaging · Electrocardiogram (...) diagnostic tests, which may be ordered based on your history and physical. Table 105.3 (9 th Edition) – Potential Targeted Diagnostic Testing in ED Patients Presenting with Suicidality General Labs · Pregnancy test (in females of childbearing age) · Complete blood count (for suspected anemia) · Serum chemistries (for suspected electrolyte abnormalities) · Urinalysis (for suspected infection) · Liver function tests (LFTs), ammonia (for suspected liver disease or valproic acid use) · Coagulation studies

2017 CandiEM

97. Interventions Targeting Sensory Challenges in Children with Autism Spectrum Disorder - An Update

, Tornatore LA, Brancazio L, et al. Can children with autism spectrum disorders "hear" a speaking face? Child Dev. 2011 Sep-Oct;82(5):1397-403. doi: 10.1111/j.1467-8624.2011.01619.x. PMID: 21790542.X-1 682. Ishikawa T, Takahashi K, Ikeda N, et al. Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)- Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors. Pharmaceutics. 2011;3(3):615-35. doi: 10.3390/pharmaceutics3030615. PMID: 24310600.X-1 (...) -5 688. Kaluzna-Czaplinska J, Michalska M, Rynkowski J. Vitamin supplementation reduces the level of homocysteine in the urine of autistic children. Nutr Res. 2011 Apr;31(4):318-21. doi: 10.1016/j.nutres.2011.03.009. PMID: 21530806. X-3 689. Kaluzna-Czaplinska J, Socha E, Rynkowski J. B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children. Nutr Res. 2011 Jul;31(7):497-502. doi: 10.1016/j.nutres.2011.06.002. PMID: 21840465.X-1, X-3 690. Kamp-Becker I

2017 Effective Health Care Program (AHRQ)

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