Drug Dosing and Renal Function Estimation PDF

Therapeutic Renal Part Drug-induced renal issues, and strategies for prevention and management. Learning Outcomes Identify Drugs Manage Disorders Adjust Dosing Understand the relationship Apply the knowledge of drug-...

Therapeutic Renal Part Drug-induced renal issues, and strategies for prevention and management. Learning Outcomes Identify Drugs Manage Disorders Adjust Dosing Understand the relationship Apply the knowledge of drug- Learn how to adjust drug dosing between certain drugs and renal induced renal disorders to effectively based on evaluations of a patient's disorders. Be able to recognize drugs manage and mitigate these issues. renal function. Ensure appropriate that can potentially cause or Develop strategies to address and medication management for contribute to kidney problems. prevent drug-related kidney individuals with impaired kidney problems. function. Drugs Induced Renal Disorders Certain medications can have adverse effects on the kidneys, leading to drug-induced renal disorders. These disorders can range from acute kidney injury to chronic kidney disease, and can be caused by various mechanisms such as direct toxicity, inflammation, or altered hemodynamics. Recognizing and managing drug-induced renal disorders is crucial to prevent further kidney damage and ensure patient safety. Careful monitoring of renal function, dose adjustments, and timely intervention are essential in managing these conditions.  In Class Activity Each student should write one medication from the list below on a sticky note 1. Gentamicine 2. Vancomycin 3. Acetaminophen 4. Multivitamines 5. Ibuprofen 6. Lisinopril 7. Ranitidine 8. Ceftriaxone 9. Insulin 10.Amlodipine 4  Drugs Induced Renal Disorders Serious Clinical Syndromes Nephrotoxicity can result in serious clinical syndromes, including acute kidney injury (AKI), which is associated with high hospitalization rates, morbidity, and mortality. Diverse Drug Classes Drug-induced renal impairment involves many classes of drugs, including prescription agents and commonly encountered over-the-counter drugs. High Incidence The incidence of drug-related acute kidney injury (AKI) may be as high as 60%, making knowledge of typical nephrotoxic agents essential.  Drugs Induced Renal Disorders Aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), contrast agents, and angiotensin converting enzyme inhibitors (ACEIs) are the most common cause of AKI in hospitalized patients The risk of contrast-induced nephropathy is highest in diabetics and chronic kidney disease  In Class Small Case Scenario 1 Case Overview A.A is a 45-year-old male admitted to the ICU after a car accident. He is currently receiving resuscitation fluids for hemorrhagic shock, and the neurosurgeon is requesting a CT head with contrast. Why A.A is considered at risk for AKI? A. The contrast B. Hemorrhagic shock C. Age D. A and B What is the best strategy to prevent A.A from having AKI? In Class Small Case Scenario Why is A.A. at risk for AKI? A.A. is at risk for AKI due to the combination of hemorrhagic shock and the planned administration of contrast for the CT head scan. Hemorrhagic shock can lead to decreased renal perfusion and contrast media can cause direct kidney injury. Best strategy to prevent AKI The best strategy to prevent AKI in A.A.'s case is to ensure adequate hydration and renal perfusion prior to the contrast administration. This may involve delaying the CT scan until the patient's hemodynamic status is stabilized. Monitoring and Intervention Close monitoring of A.A.'s renal function, including serum creatinine and urine output, will be crucial. If AKI develops, prompt intervention with fluid resuscitation, avoidance of further nephrotoxic agents, and potential renal replacement therapy may be necessary. Risk Factors 1 Drug and Kidney Specific Factors Certain drugs and their interactions with the kidneys can increase the risk of drug-induced renal disorders. Factors like drug potency, route of administration, and duration of use play a role. 2 Patient Specific Risk Factors Individual patient characteristics such as age, underlying kidney disease, dehydration, and concomitant medications can also contribute to the development of drug-induced renal problems. Drug And Kidney Specific Factors Inherent Toxicity The toxicity of therapeutic and diagnostic agents may be inherent to the pharmacological compound itself. The potential for toxicity may be heightened in the kidney microenvironment. Chemotherapy Impact The aim of chemotherapy is to kill malignant cells. Since the cell cycle operates normally, healthy tissues, including renal parenchymal cells, are also affected. Genetic Factors Genetic polymorphisms that affect the function of the renal tubular system may explain differences in susceptibility to nephrotoxicity of drugs such as cisplatin. Patient Specific Risk Factors Older Age and Female Sex Comorbid Conditions Volume Depletion Older age and female sex are Patients with CKD, CHF, or hepatic Patients on diuretics or experiencing associated with reduced muscle mass failure are more vulnerable to toxic vomiting/diarrhea are at risk of true and lower total body water, which can drug effects and more likely to be on volume depletion, which can lead to increase the concentration of drugs in multiple nephrotoxic medications. prerenal AKI and toxic drug effects. the serum. Prevention Strategies Maintain Hydration Therapeutic Monitoring Dosage Optimization Ensure adequate hydration and avoid Maintain drug levels within the Administer drugs orally and use the the use of nephrotoxic drugs recommended therapeutic range to lowest effective dose and shortest whenever possible to prevent drug- minimize the risk of toxicity and duration of therapy whenever possible induced kidney injury. kidney damage. to reduce the impact on the kidneys. Prevention Strategies 1 Adjust Medication Dosages 2 Assess Baseline Renal Function Use the Cockcroft-Gault formula (in adults) or Schwartz Evaluate the patient's baseline renal function consider their formula (in children) to adjust medication dosages based on renal status when prescribing new medications. the patient's renal function. 3 Avoid Nephrotoxic Combinations 4 Correct Risk Factors Avoid using multiple medications that can potentially cause Address any underlying risk factors for nephrotoxicity before nephrotoxicity when possible. initiating drug therapy. Lists Of Drugs Causing AKI Prerenal Drugs that can cause prerenal acute kidney injury (AKI) include ACEIs/ARBs, calcineurin inhibitors, COX-2 inhibitors, diuretics, and NSAIDs. Glomerular Injury Drugs that can cause glomerular injury and AKI include interferon and pamidronate. Acute Interstitial Nephritis Drugs that can cause acute interstitial nephritis and AKI include allopurinol, azathioprine, certain Chinese herbs, cimetidine, diuretics, NSAIDs, phenytoin, proton pump inhibitors, quinolones, rifampin, semisynthetic penicillins, sulfonamides, and vancomycin. Lists Of Drugs Causing AKI. Lists Of Drugs Causing AKI. Recognition And Early Intervention Reversible Impairment Monitoring Renal Function Most episodes of drug-induced renal impairment are A decrease in renal function, as evidenced by a rise in reversible, provided the impairment is recognized early serum creatinine levels following the initiation of a drug, and the offending medication is discontinued. signals the possibility of drug-induced renal injury. Recognition And Early Intervention Criteria for Drug-induced AKI A 50% rise from baseline in serum creatinine, an increase of 0.5 mg/dL or more when baseline is less than 2 mg/dL, or an increase of 1 mg/dL or more if baseline is greater than 2 mg/dL.. is 33'1 ;92 Medication Review The patient's medication list should be reviewed to identify any offending agents that may be causing acute kidney injury (AKI). Kidney Labs Monitoring kidney function through lab tests like serum creatinine is crucial for early detection and intervention of drug-induced AKI. Blood Urea Nitrogen (BUN) Urea Nitrogen ( 8-25 mg/dl) BUN is the concentration of urea nitrogen, an end product of protein metabolism, in the blood. & Liver Production Urea is produced in the liver and then filtered by the kidneys. Kidney Filtration Elevations in BUN can indicate acute or chronic renal failure, dehydration, GI bleeding, or a high protein diet.  Serum Creatinine (0.7-1.5 mg/dl) Srcr Product of Muscle Breakdown Serum creatinine is a byproduct of normal muscle breakdown and is filtered and secreted by the kidneys, but not reabsorbed. Limitations as a Predictor Serum creatinine levels can be influenced by factors such as age and muscle mass, limiting its accuracy as a sole indicator of kidney function. j Interpretation of Levels Elevated serum creatinine can indicate medication effects or renal jraou disease, while decreased levels may suggest low muscle mass. Interpretation requires considering baseline, hydration status, and trends. 9 Estimate Of Renal Function Cockcroft-Gault Formula 24-Hour Creatinine Clearance Monitoring Renal Function The Cockcroft-Gault formula is a simple A 24-hour creatinine clearance (Clcr) is Close monitoring of renal function is and widely used method to estimate another practical and useful method to essential during the course of therapy glomerular filtration rate (GFR) when a approximate GFR, especially in patients with potentially nephrotoxic medications. new drug is prescribed. It provides an with stable renal dysfunction. This test Baseline renal function should be approximation of renal function before provides a more accurate assessment of evaluated before initiating these drugs, initiating potentially nephrotoxic renal function compared to the Cockcroft- and regular monitoring should continue medications. Gault formula. throughout the treatment period. Estimate Of Renal Function Cockcroft-Gault Formula The Cockcroft-Gault formula is used to estimate creatinine clearance (eCrCl) based on age, ideal body weight, and serum creatinine. It is a widely used method to adjust medication dosages for patients with renal impairment. Estimate Of Renal Function  2 65)x82.. nat 140- In Class Case ~ Time= 5 min 175. u , B.M is 65 Y old Male patient under your care, wt 80 kg and Ht 175 cm. his baseline SrCr is 0.7mg/dl. Please calculate his estimated CrCl ml/min? 1 inch= 2.54 cm 1 feet= 30.48 cm 1 feet= 12 inches= 30.48 cm 5 feet= 60 inches= 152.4 cm Males: IBW = 50 kg + 2.3 kg for each inch over (5 feet or 60 inches) Females: IBW = 45.5 kg + 2.3 kg for each inch over (5 feet or 60 inches) 2 3.. 24X 50 "s 2. 2 Drug Dosing In AKI Concepts Cockcroft-Gault Formula Dosage Adjustments Pharmacokinetic Alterations The preferred formula for estimating Most drugs eliminated renally do not Acute kidney injury can significantly renal function is the Cockcroft-Gault require dosage adjustment until the impact the pharmacokinetics of drugs, equation, which tends to overestimate creatinine clearance falls below 50 requiring close monitoring and the GFR compared to the MDRD ml/min, at which point careful potential dose adjustments to ensure formula. monitoring and dose titration is safe and effective therapy. required. Pharmacokinetic Alterations Absorption AKI may reduce drug absorption, believed to be due to decreased gastrointestinal motility and blood flow. Distribution AKI can alter the volume of distribution (Vd) of drugs, as well as reduce plasma protein binding. Metabolism AKI may decrease nonrenal clearance and lead to accumulation of active drug metabolites. Elimination D * AKI can reduce renal clearance, leading to increased drug accumulation and potential toxicity. General Principles For Drug Dosing Alterations Loading Dose Maintenance Dose The loading dose does not require adjustment in acute The maintenance dose depends on clearance and kidney injury (AKI). However, some drugs with decreased consequently requires dose adjustment. This can be done O tissue binding in renal failure, such as digoxin, may require by reducing the dose, extending the interval, or using a = aO taper in the loading dose. combination of dose and interval modification. -  In Class Case Time= 5 min B.M is 65 Y old M patient under your care, wt 80 kg and Ht 175 cm. his baseline SrCr is 0.7mg/dl. One day ago his baseline CrCl was ml/min? Today his SrCr is 1.8mg/dl, so what is his estimated CrCl today? Your team would like to start him on oral Ciprofloxacin for UTI, what is the recommended dose? 1 inch= 2.54 cm 1 feet= 30.48 cm 1 feet= 12 inches= 30.48 cm 5 feet= 60 inches= 152.4 cm Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.