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Fractional Excretion of Sodium


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181. Nitisinone (Nityr) - Tyrosinemias

Page 4/42 CYP1A2 Cytochrome P450 1A2 CYP2C19 Cytochrome P450 2C19 CYP2D6 Cytochrome P450 2D6 CYP3A4 Cytochrome P450 3A4 D Dose EC50 Concentration of drug producing 50% of Emax Emax Maximum effect a drug produces Et or Ec Extent of effect a drug produces at time t or at concentration c EU European Union F Absolute bioavailability fe Fraction of the systemically available drug excreted into the urine Fr Relative bioavailability FT Fourrier Transform fu Unbound fraction of drug in plasma GC Gas (...) 38 2.6. Pharmacovigilance 40 2.7. Product information 40 2.7.1. User consultation 40 2.7.2. Labelling exemptions 40 3. Benefit-risk balance 40 4. Recommendation 41 Assessment report EMA/413721/2018 Page 3/42 List of abbreviations Ae,t Cumulative amount of unchanged drug excreted into the urine until time t Ae 8 Cumulative amount of unchanged drug excreted into the urine in infinite time Ae-INF Cumulative amount of unchanged drug excreted into the urine in infinite time AeT Cumulative amount

2018 European Medicines Agency - EPARs

182. Neratinib (Nerlynx) - Breast cancer, breast neoplasms

epidermal growth factor receptor HERA study HERceptin Adjuvant study HR hazard ratio HRc hormone receptor IC50 half-maximal inhibitory concentration iDFS invasive disease-free survival IDMC independent data monitoring committee I-SPY study Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and moLecular Analysis study ITT intent-to-treat IV intravenous LVEF left ventricular ejection fraction M3 pyridine N-oxide Assessment report EMA/CHMP/525204/2018 Page 5/169 M6 N

2018 European Medicines Agency - EPARs

183. Varicella Zoster Virus glycoprotein E antigen (Shingrix) - Herpes Zoster

Qualification PRNT Plaque Reduction Neutralization Test PS80 Polysorbate 80 QA Quality Attributes QC Quality Control QoL Quality of Life QS-21 Quillaja saponaria Molina fraction 21 RCT Randomized Controlled Trial RMP Risk Management Plan RR Relative Risk SAE Serious Adverse Event SC Subcutaneous SCR Seroconversion Rate SmPC Summary of Product Characteristics SPR Seroprotection Rate TNF-a Tumour Necrosis Factor alpha TSE Transmissible Spongiform Encephalopathy TTC threshold of toxicological concern TVC Total (...) ) adjuvanted with AS01 B (suspension). Varicella Zoster Virus (VZV). gE is produced by recombinant DNA technology in Chinese Hamster Ovarian (CHO) cells. The AS01 B adjuvant system is composed of 50 µg each of the immunoenhancers: plant extract Quillaja saponaria Molina, fraction 21 (QS-21, and 3-O-desacyl-4’-monophosphoryl lipid A (MPL) from Salmonella minnesota (50 micrograms). These are combined with liposomes, which consist of the excipients dioleoyl phosphatidylcholine (DOPC) and cholesterol

2018 European Medicines Agency - EPARs

184. Bictegravir / emtricitabine / tenofovir alafenamide / fumarate (Biktarvy) - HIV Infections

the concentration versus time curve over the dosing interval B/F/TAF bictegravir/emtricitabine/tenofovir alafenamide (coformulated) BCS Biopharmaceutics Classification System BIC bictegravir BIC Bictegravir sodium BLQ below the limit of quantitation BMD bone mineral density BMI body mass index CHB chronic hepatitis B CI confidence interval Clast last observed quantifiable concentration of the drug Cmax maximum observed concentration of drug CMH Cochran-Mantel-Haenszel COBI cobicistat (Tybost) CPK creatine (...) statistical analysis plan SBR stay on baseline regimen SD standard deviation SDS Sodium dodecyl sulfate SmPC Summary of Product Characteristics t1/2 estimate of the terminal elimination half-life of the drug TAF tenofovir alafenamide (Vemlidy) TAF Tenofovir alafenamide TDF tenofovir disoproxil fumarate (Viread) TFV tenofovir Tmax time (observed time point) of Cmax TSH thyroid-stimulating hormone UGT1A1 uridine diphosphate glucuronosyltransferase 1A1 ULN upper limit of normal UPLC Ultra performance liquid

2018 European Medicines Agency - EPARs

185. Renal tubular acidosis

immunoglobulins interstitial nephritis hyperparathyroidism Thai or southeast Asian ancestry outdated tetracycline cis-platinum therapy toluene, paraquat, lysol exposure Balkan heritage Dent's disease ibuprofen overdose lamivudine antiviral therapy (cidofovir, adefovir, or tenofovir) Diagnostic investigations serum bicarbonate serum chloride serum sodium serum potassium arterial blood pH serum anion gap urine pH serum aldosterone urine anion gap measurement of fractional bicarbonate excretion urine PCO2 (...) bicarbonate infusion furosemide test ammonium chloride loading test furosemide and fludrocortisone test urine glucose tubular maximum (Tm) reabsorption of phosphate fractional excretion of amino acids ultrasound CT/spiral CT nuclear renal scan Treatment algorithm ONGOING Contributors Authors Professor Emeritus Texas Tech University Health Sciences Center Lubbock TX Disclosures MEL declares that he has no competing interests. Dr Melvin E. Laski would like to gratefully acknowledge Dr Elizabeth Cobb, Dr

2017 BMJ Best Practice

186. Acute tubular necrosis

to nephrotoxins exposure to radiocontrast media muscle trauma haemolysis hyperuricaemia infection advanced age multiple myeloma sepsis pancreatitis Diagnostic investigations basic metabolic profile (including urea and creatinine) urea-to-creatinine ratio urine sodium concentration urine osmolality fractional excretion of sodium fractional excretion of chloride urinalysis for sediment FBC coagulation studies urinary myoglobin arterial blood gases (ABG) platelet aggregation studies ultrasound ECG central venous

2017 BMJ Best Practice

187. Asthma

include fractional exhaled nitric oxide (FeNO) testing, spirometry, bronchodilator reversibility (BDR), peak expiratory flow (PEF) readings, and direct bronchial challenge testing with histamine or methacholine. Combinations of signs and symptoms, and the results of these tests should be used to determine the likelihood of an asthma diagnosis. All people with asthma should be prescribed an occasional relief bronchodilator such as an inhaled short-acting beta- 2 agonist to be used as required. Further (...) a previous record of skin-prick tests, blood eosinophilia of 4% or more, or a raised allergen-specific IgE to corroborate atopic status, but do not offer these tests routinely to support an asthma diagnosis. The results of fractional exhaled nitric oxide (FeNO) testing — should be used where possible be used to confirm eosinophilic airway inflammation to support an asthma diagnosis in people aged 17 years and older. This test may be available in some primary care practices or may require referral

2017 Prodigy

188. Diagnosis and Treatment of Peripheral Arterial Diseases

in the case of CKD, with precautions in case of allergies. Nephrotoxicity can be limited by minimizing contrast agent volume and ensuring adequate hydration before and after imaging. The benefit of acetyl-cysteine to limit nephrotoxicity is uncertain. , Recent studies have suggested that statins or sodium bicarbonate could prevent contrast agent nephrotoxicity. , Further research is required. Magnetic resonance angiography MRA is used for peripheral artery imaging using contrast (i.e. gadolinium

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2017 European Society of Cardiology

189. Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure. (PubMed)

immunohistochemical analysis of RAS signalling proteins in the kidney confirm the immunoblotting results for both groups. The present investigation also showed a pronounced decrease in fractional urinary sodium excretion in maternal protein-restricted offspring, compared with the NP age-matched group. This occurred despite unchanged creatinine clearance.The current data led us to hypothesize that foetal undernutrition could be associated with decreased kidney expression of AT(R) resulting in the inability (...) Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure. Intrauterine growth restriction due to low maternal dietary protein during pregnancy is associated with retardation of foetal growth, renal alterations and adult hypertension. The renin-angiotensin system (RAS) is a coordinated hormonal cascade in the control of cardiovascular, renal and adrenal function that governs body fluid and electrolyte

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2009 Transplantation

190. CRACKCast E144 – High Altitude Medicine

in the gradual return of the resting heart rate to near sea-level values. Continued resting tachycardia is evidence of poor acclimatization. 1.3 Release of erythropoietin (in hours: but the response is delayed) Leading to new circulatory red blood cells in 4 or 5 days. During the next 2 months, red blood cell mass increases in proportion to the degree of hypoxemia. Delayed (days to weeks) Renal excretion of bicarbonate to adapt to the respiratory alkalotic state induced by the HVR, Maximum rate/amount by 6-8 (...) “backup” in the lungs. There is a wide variation in both individual HPVR due to epigenetic reasons as well as UNEVEN vasoconstriction leading to patchy pulmonary edema. Proposed reasons? decreased nitric oxide bioavailability at the pulmonary tissue level. Acute inflammatory mediators post lung injury Sodium channel-mediated alveolar fluid clearance changes (inhaled beta-adrenergic agonists, which have been proven to decrease risk of HAPE.) Sensitized lung due to ongoing pulmonary infection See Figure

2018 CandiEM

191. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy

consistent with the ESA, Scandinavian, and most recent German guidelines (all of which incorporate a pharmacologic approach to newer anticoagulants where data are sparse). Recommendations are frequently made with a time interval, rather than an exact time (eg, 4–6 hours), representing normal variation in pharmacologic activity. In patients without additional comorbidities that affect metabolism, excretion, and/or distribution, the shorter time may be observed. Significant renal insufficiency (...) (in a renally excreted medication) is not included in this time interval and will require longer periods. Also to be considered are a patient history of bruising/bleeding, the presence of multiple medications affecting hemostasis, and the proposed regional technique (deep vs superficial, continuous vs single injection). | Strength and Grade of Recommendations The recommendations presented are based on a thorough evaluation of the available information using a grading system based on level of evidence

2018 American Society of Regional Anesthesia and Pain Medicine

192. When and how to treat hyponatremia in the ED

- or hypervolemia. Edema, ascites, pulmonary effusion Investigations Urine sodium excretion (<20-30 mmol/L), fractional excretion of uric acid, trial of volume expansion Urine sodium excretion (>20-30 mmol/L), trial of volume expansion Urine sodium excretion (<20-30 mmol/L), Elevated BUN Notes on Treatment Correction of volume deficit, treatment of underlying disease, avoiding over-rapid correction. In case of cerebral salt wasting, do NOT restrict fluids See guidelines for recommended treatment by specific (...) ”. No further details are available. Her medications include L-thyroxine, a statin and a thiazide diuretic. Vitals are normal. On exam, Marjorie is weak and is unable to sit up without assistance. Strength testing reveals bilateral weakness in the arms and legs. A walk test is not attempted. No focal neurological deficits are noted. Cardiac, respiratory, and abdominal exams are normal. Investigations are ordered and results reviewed. Electrolytes : sodium 110 mmol/L , potassium 3.4 mmol/L, chloride 76 mmol

2018 CandiEM

193. QTc Prolongation and Psychotropic Medications

at a cellular level. Sodium (Na + ), calcium (Ca 2+ ), and potassium (K + ) ionic movements underlie the processes of depolarization and repolarization. A resting potential is maintained by sodium-potassium pump and other mechanisms resulting in uneven distribution of ions between the interstitium and interior of the cardiac myocyte (7). Cellular depolarization (QRS interval on the surface ECG; Figure 1) derives mostly from a net inward flux of sodium and then calcium ions. Cell repolarization (JT/QT (...) ? Advanced age ? Pharmacokinetic drug-drug interactions ? Congenital long QT syndrome ? Drug toxicity ? Personal history of drug-induced QTc interval prolongation ? Rapid intravenous infusion of QTc interval prolonging drugs ? Personal history of structural or functional cardiac disease (e.g. heart failure with reduced ejection fraction) ? Severe acute illness ? Metabolizer status ? Bradycardia © Copyright, American Psychiatric Association, all rights reserved. ? Family history of sudden cardiac death

2018 American Psychiatric Association

196. ANP Mediated Inhibition of Distal Nephron Fractional Sodium Reabsorption in Wild-Type and Mice Overexpressing Natriuretic Peptide Receptor. (PubMed)

. In contrast, the higher dose (0.2 ng x g body wt(-1) x min(-1), n = 6) increased DSD (2.8 +/- 0.3 mueq/min, P < 0.01) and also decreased fractional reabsorption of DSD (67.4 +/- 4.5%, P < 0.01), which markedly augmented the natriuresis. In Npr1 gene-duplicated four-copy mice (n = 6), the lower dose of ANP increased urinary sodium excretion (0.6 +/- 0.1 vs. 0.3 +/- 0.1 mueq/min, P < 0.05) and decreased fractional reabsorption of DSD compared with control (72.2 +/- 3.4%, P < 0.05) at similar mean arterial (...) pressures (91 +/- 6 vs. 92 +/- 3 mmHg, P > 0.05). These results provide in vivo evidence that ANP-mediated increases in DSD alone exert modest effects on sodium excretion and that inhibition of fractional reabsorption of distal sodium delivery is requisite for the augmented natriuresis in response to the higher dose of ANP or in Npr1 gene-duplicated mice.

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2009 American Journal of Physiology. Renal physiology

197. CRACKCast E081 – Heart Failure

to the brain and heart – but away from skin, muscles, kidneys Forces the heart to do extra work Neurohormonal changes – counterproductive on a chronic basis Renal neurohormonal response RAAS activation – ADH activation Neurochemicals and enhanced ANS activation Elevations in vasopressin Inhibition of parasympathetic tone Chronically elevated catecholamines Natriuretic peptides From the heart and brain: promote water and sodium excretion, increase vasodilation and inhibit RAAS Endothelin Disease (...) the systemic demands (despite a reduced ejection fraction) by adjusting other factors that contribute to stroke volume. “The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction (the end diastolic volume), when all other factors remain constant.” – Wikipedia By Huckfinne – Own work, Public Domain, Pousseils Law and LaPlaces Law Poiseuilles law: Flow is directly proportional to the fourth power of the vessel radius

2017 CandiEM

198. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

KD are often evaluated for incomplete KD ( ). If coronary artery abnormalities are detected, the diagnosis of KD is considered confirmed in most cases. Laboratory tests typically reveal normal or elevated white blood cell count with neutrophil predominance and elevated acute phase reactants such as C-reactive protein and erythrocyte sedimentation rate during the acute phase. Low serum sodium and albumin levels, elevated serum liver enzymes, and sterile pyuria can be present. In the second week

2017 American Heart Association

199. Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents

, particularly in girls and adolescents. – Physical activity measured by accelerometry shows less than half of school-aged boys and only one-third of school-aged girls meet the goal for ideal physical activity levels. More than 80% of youth 12 to 19 years of age have a poor diet (as defined by AHA metrics for ideal CV health); only ∼10% eat adequate fruits and vegetables, and only ∼15% consume <1500 mg per day of sodium, both of which are key dietary determinants of HTN. Finally, measuring BP at routine well

2017 American Academy of Pediatrics

200. Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association

or severe morbidity risk. Pregnancy is contraindicated. In the event of pregnancy, termination should be discussed. If pregnancy continues, care should follow class III recommendations. Pulmonary arterial hypertension (of any cause) Severe systemic ventricular dysfunction (LV ejection fraction <30%, NYHA class III-IV) Previous peripartum cardiomyopathy with any residual impairment of LV function Severe mitral stenosis, severe symptomatic aortic stenosis Aortic dilation >45 mm in Marfan syndrome Aortic (...) to the hypervolemia, with respective increases of ≈45% to 55% and 20% to 30%. Estrogen has a key role in plasma volume expansion and promotes sodium and water retention by upregulating the production of angiotensinogen, renin, and aldosterone. The disproportionate expansion of plasma volume relative to red cell mass contributes to the physiological anemia of pregnancy, with mean±SD hemoglobin concentrations of 10.9±0.6 and 12.4±1.0 g/dL for the second and third trimesters, respectively. Figure 1. Pregnancy

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2017 American Heart Association

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