PBSN 529 Pharmacology & Medicinal Chemistry II - Fall 2024 PDF
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2024
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Summary
These lecture notes cover electrolyte imbalances, including pathophysiology, definitions, classifications, and causes of acute kidney injury (AKI). The document describes kidney functions, acid-base imbalances, and frequently used terminologies in the field.
Full Transcript
PBSN: 529- Pharmacology & Medicinal Chemistry II PART- I ELECTROLYTE IMBLANACES Fall 2024 Time: Tue: 2:00 PM to 4:00 PM/ Thurs: 9:00 to 10:00 AM 1 LECTURE SPECIFIC OBJECTIVE...
PBSN: 529- Pharmacology & Medicinal Chemistry II PART- I ELECTROLYTE IMBLANACES Fall 2024 Time: Tue: 2:00 PM to 4:00 PM/ Thurs: 9:00 to 10:00 AM 1 LECTURE SPECIFIC OBJECTIVES * Describe Electrolyte imbalances in the body and its consequences; * Explain pathophysiology of Kidney diseases (AKI/ARF & CKI); * List definitions and classification of AKI (various forms of AKI); * List factors that cause AKI (ARF) and classify ARF; * Identify medication-related causes of the various types of acute kidney injury * Describe the epidemiology and clinical outcome of AKI; * Describe complications associated with acute kidney injury * Describe etiology and diagnosis of AKI; * Explain approach and management of AKI; * Analyze risk factors and preventive strategies of AKI; 2 Kidney’s Primary Functions 1. Regulating blood volume and blood pressure 1. Remove/Excretes wastes 2. Regulates extracellular fluid & osmolarity, 2. Secretes renin electrolyte concentrations, & acid-base balance 3. Produces erythropoietin for RBC 3. Stabilizing pH of blood/Medium for chemical production reactions 4. Converts vitamin D to active form 4. Conserving nutrients 5. Detoxifying poisons (with the liver) 6. Transport of waste to lung & kidneys 7. Maintain body temperature * See notes below for syndromes! Acid-Base Imbalances * Acidosis [arterial blood pH 7.45] can also be either respiratory or metabolic; * Recall that principal buffer in the plasma is between carbonic acid [H 2CO3 ] and bicarbonate [HCO3- ]~ HCO3- + H+ ↔ H2CO3 ↔ CO2 + H2O * The lungs regulate H2CO3 levels by excreting CO2; * The kidneys regulate HCO3- levels by making or wasting HCO3- ; * Read explanations below…………. Frequently Used Terminologies in this field Mix – Match Exercise before A. Frequent January 11,voiding- 2024 Excessive urination (4) 1. Urgency B. Strong desire to void (1) 2. Pyuria 3. Proteinuria C. Painful or difficult voiding (12) 4. Polyuria D. Delay, difficulty in initiating voiding (8) 5. Oliguria E. Excessive urination at night (6) 6. Nocturia F. Involuntary loss of urine (7) 7. Incontinence G. Involuntary voiding during sleep (11) 8. Hesitancy H. Increased volume of urine voided (10) 9. Hematuria I. Urine output less than 500 ml/day (5) 10. Frequency J. Urine output ‘zero’ or less than 50 ml/day (13) 11. Euresis K. Red blood cells in the urine (9) 12. Dysuria L. Abnormal amounts of protein in the urine (3) 13. Anuria M. Pus in the urine (2) 14. Azotemia 15. Uremia N. Elevation of nitrogenous wastes (14) 16. Sepsis O. Clinical syndrome which occurs due to azotemia (15) P. The systemic presence of bacteria, toxin etc. (16) Renal Panel: Normal Values 1. Medline plus: https://medlineplus.gov/kidneytests.html 2. Labcorp: https://testdirectory.questdiagnostics.com/test/results?q=Renal%20Function%20Panel Normal ranges: Albumin - 3.4 -5.4g/dL/ Serum Globulin: 2.0 to 3.5 g/dL BUN (Blood Urea Nitrogen) - 10 - 20 mg/dL BUN-to-Creatinine Ratio (calculated)- 5 - 18mg/dL Calcium - 8.5 - 10.5 mg/dL Phosphorus - 1 – 1.5 mEq/L. Sodium: 135 -147 mEq/L Potassium: 3.5 – 5 mmol/L Chloride - 96 - 106MEq/L. Creatinine - 0.9 to 1.5mg/dL for men and 0.6 to 1.1mg/dL for women. Estimated Glomerular Filtration Rate (calculated): 90 - 120mL/minute. Glucose - 145 mEq/L mmol/L; Severe HyperNatre: = 160 mEq/L or greater *common with fluid losses; *commonest non-drug cause-- is water deprivation; * The second most common non-drug cause is hyperglycemic osmotic diuresis in diabetic patients – - b/c glucose pulls water out of cells & glucose carries water out in the urine; * The most common drug-induced cause are corticosteroids, which inhibit ADH release; * Hypernatremia is accompanied by high plasma osmolality which pulls water out of cells, in the brain, this can lead to seizures, coma and death; TRX: IV 5% dextrose/ Half normal saline depending on pt condition! Loop diuretic, such as Furosemide IV ( 20-40mg) and 5% dextrose Na+ is the 2nd electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review Labs – Fractional excretion of sodium (FENa) FENa – percentage (%) of Na filtered by the kidney which is excreted in the urine, measure of renal clearance in the context of low urine output Low fractional excretion indicates sodium retention by the kidney High fractional excretion indicates sodium wasting due to acute tubular necrosis Formula - Fractional Excretion of Sodium (FENa), % = 100 × (SCr × UNa ) / (SNa × UCr) SCr, serum creatinine; UNa, urine sodium; SNa, serum sodium; UCr, urine creatinine. 3. Calcium imbalances Normal Range: 9 – 10.5 mg/dl Hypocalcemia * Total serum Ca2+ 10.5 mg/dL is most commonly observed with malignancies, * Symptoms are musculo-skeletal cramping and myeloma, breast, bone and lung cancers and tetany; benign tumors of the parathyroid gland (primary hyperparathyroidism); chronic granulomatous Acute pancreatitis, parathyroid hormone deficiency disease (genetic immune disorder of WBCs); after thyroidectomy, neck dissection, resistance to parathormone, hypomagnesemia, sepsis; * Hypercal is less common than sodium * It is uncommon overall; imbalances; [Remember: production of PTH at LOW serum calcium] Ca++ is the 3rd electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review Electrolyte and its connection to Hyperparathyroidism Linked to Calcium & Phosphorus metabolism Over-active parathyroid glands results in excess production of PTH; PTH regulates calcium and Pi levels; Primary HyperPTH – Over secretion of PTH due to adenoma, hyperplasia or carcinoma of parathyroid glands * HIGH PTH, serum calcium; LOW phosphates Secondary HyperPTH – production of PTH due to hypocalcemia. * Occurs in vitamin D deficiency and chronic renal failure * HIGH phosphates; Tertiary HyperPTH – long-term secondary hyperPTH which leads to hyperplasia of the parathyroid glands and loss of response to serum calcium levels. Seen in chronic renal fail (CKD) * HIGH PTH and serum calcium Hypocalcemia Meds Calcium citrate or Calcium carbonate Hypercalcemia Meds * Calcitonin (Miacalcin). A salmon derived hormone, helps calcium levels in the blood. * Calcimimetics. Help control overactive parathyroid glands. Cinacalcet (Sensipar) has been approved for managing hypercalcemia. * Bisphosphonates. IV osteoporosis drugs, which can quickly lower calcium levels, are often used to treat hypercalcemia due to cancer. Risks: are osteonecrosis of the jaw/ certain types of thigh fractures. * Denosumab (Prolia, Xgeva): This drug is often used to treat people with cancer-caused hypercalcemia who don't respond well to bisphosphonates. * Prednisone: In high levels of vitamin D, short-term use of prednisone is usually helpful. Ca++ is the 3rd electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review 23 4. Magnesium Imbalances (HYPO) * Bone contains approx. 50% of the body’s magnesium; blood contains very little. * Mg is necessary for the formation of bone and teeth and for normal nerve and muscle function; * Many enzymes in the body depend on magnesium to function normally; * Magnesium is also related to the calcium metabolism; Hypomagnesemia may cause- nausea, vomiting, sleepiness, weakness, personality changes, muscle spasms, tremors, and loss of appetite. If severe, hypomagnesemia can cause seizures, especially in children. Causes of hypo: See in the text below (U R responsible) Mg is the 4th electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review 24 4. Magnesium Imbalances (HYPER) * Bone contains approx. 50% of the body’s magnesium; blood contains very little. * Mg is necessary for the formation of bone and teeth and for normal nerve and muscle function; * Many enzymes in the body depend on magnesium to function normally; * Magnesium is also related to the calcium metabolism; Hypermagnesemia is uncommon; Develops only when people with kidney failure are given Mg salts or take drugs that contain Mg (such as some antacids or laxatives). Hypermagnesemia can cause- * Muscle weakness * Low blood pressure * Impaired breathing * In severe hypermagnesemia, heart can stop beating Trx: Calcium gluconate; Diuretics Mg is the 4th electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review 25 5. HYPO - Phosphate imbalances 1 – 1.5 mEq/L or 2.5– 4.5 mmol/dl Hypophosphatemia * Total serum PO4- < 1.0 mg/dL is most commonly observed with chronic alcoholism, chronic ingestion of Mg/Al antacids and I.V. hyperalimentation without adequate phosphate; * Symptoms (myalgia, weakness, decreased myocardial contractility, neurologic confusion, seizures) relate to low ATP stores and tissue hypoxia; *Rx I.V. phosphate in saline or oral potassium or sodium phosphate for mild cases; Ergocalciferol, Vit -D2 [HIGH PTH, high serum calcium; LOW phosphates] Phosphorus is the 5th electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review 5. HYPER -Phosphate imbalances 1 – 1.5 mEq/L or 3 – 4.5 mmol/dl Hyperphosphatemia * When Total serum PO4 > 4.5 mg/dL is most commonly observed in renal failure pts; * Low GFR leads to inadequate phosphate excretion, causing plasma phosphorus complexing with Ca2+ & precipitating in soft tissues: joints, blood vessels, heart & kidney; * Rx: Calcium salt infusion; For non-emergency cases, oral phosphate-binding calcium carbonate or acetate or others can be used; * The primary adverse effect is constipation; Phosphorus is the 5th electrolyte: https://www.osmosis.org/learn/Electrolyte_disturbances:_Pathology_review Expectations: 100% of the slide 1.Top box: All the features 2.Features associated with Pre-renal, Intrinsic and postrenal AKI HPI= History of the Present illness; PMH= Past Medical History; HUS: Hemolytic uremic syndrome; TTP: Thrombotic thrombocytopenic purpura; Ref: McGraw Hill- Access Pharmacy Acute Kidney Injury (AKI) – Definitions and Risk Factors * Abrupt decline in renal function resulting in inability to properly excrete waste (BUN & SCr) and maintain acid-base balance; * An acute decrease in kidney function or glomerular filtration rate (GFR) over hours, days, or even weeks and associated with an accumulation of waste products and (usually) volume; * Renal insufficiency + abnormal biochemical values and altered homeostasis; (i) Fluid overload; (ii) Persistent acid-base abnormalities can lead to Electrolyte imbalances which was the focus of this presentation! (iii) Increased SCr and/or BUN + several other parameters. Conclusion