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1 PHARMACOLOGY FOR THE RENAL & CARDIOVASCULAR SYSTEMS N402 Lipids are essential… and can be problematic 2 Triglycerides—fat storage and energy source Phospholipids—plasma membrane component Steroids—plasma membrane component Excessive levels contribute to cardiovascular disease Triglycerides Phospholipids Steroids Desirable lipid levels 3 Lipid Desirable High Risk Total < 200 mg/dl Cholesterol LDL Cholesterol < 100 mg/dl > 240 mg/dl HDL Cholesterol Triglycerides > 60 mg/dl < 35 mg/dl < 149 mg/dl > 200 mg/dl > 160 mg/dl Lifestyle modifications 4 Monitor No smoking Weight Lipid control Increase fiber Exercise ↓ Saturated fats Major lipid lowering agents 5 Statins Cholesterol absorbing Fibric acid agents Bile acid sequestrants Niacin Statins—Mechanism of action 6 HMG-CoA reductase Regulates cholesterol biosynthesis Statins inhibit HMG-CoA Liver makes less cholesterol, more LDL receptors Increased removal of LDL→lower LDL and cholesterol Statins—Precautions 7 Minor side effects Headache Fatigue Muscle, joint pain heartburn Serious adverse effects Severe myopathy Rhabdomyolysis Bile acid sequestrants—Mechanism of action 8 Sequestrant binds with bile acid Bile acid contains large amounts cholesterol Acids and cholesterol eliminated in feces Liver makes less cholesterol, more LDL receptors Increased removal of LDL→lower LDL and cholesterol Bile acid sequestrants—Precautions 9 Bloating Constipation Can bind with other drugs (e.g., digoxin, warfarin) Bind with some vitamins and minerals Niacin—Mechanism of action 10 Inhibits the peripheral mobilization of free fatty acids Less FFA available for hepatic synthesis of triglycerides and very low-density lipoprotein (VLDL) particles Reduces hepatic conversion of VLDL particles to LDL particles Interferes with conversion of VLDL-C to LDL-C Niacin—Precautions 11 Flushing and hot flashes almost always Nausea, gas, diarrhea Hepatotoxicity Gout Can raise BG levels Fibric acid agents— Mechanism of action 12 Activate lipase Lipase increases TG breakdown TG eliminated from plasma Fibric acid agents—Precautions 13 Does not reduce mortality from CV disease May increase mortality Reduces triglycerides only May be useful in combination with statins Cholesterol absorption inhibitors— Mechanism of action 14 Cholesterol absorbed by small intestine ⇩ Ezetimibe (Zetia) blocks absorption ⇩ Less cholesterol enters bloodstream ⇩ Body responds by producing more cholesterol Therefore requires use of statin at same time! Cholesterol absorption inhibitors— Precautions 15 Nasopharyngitis Myalgia URI Arthralgia Diarrhea Anatomy of the nephron 16 Classification of renal failure 17 What diuretics do…. 18 Remember…“water follows salt!” Osmotic—pulls water into nephron Thiazide—blocks reabsorption of Na+, Cl-, H20 in distal tubule Loop—blocks reabsorption of Na+, Cl-, H20 in loop of Henle Potassium-sparing—blocks reabsorption of Na+, reduce secretion of potassium Mechanism of action of various diuretics 19 Loop diuretics 20 Work directly on loop of Henle Rapid acting when given IV Reduce edema from multiple causes Increases urine output even when renal blood flow is diminished Can produce: Dehydration Electrolyte Otoxicity imbalance Thiazide diuretics 21 Most frequently prescribed Mild-moderate hypertension Moderate heart, liver, renal failure Similar adverse effects to loop diuretics Can raise BG levels Potassium-sparing diuretics 22 Do not affect potassium levels Produces a weaker diuresis Reduces mortality in patients with heart failure Should not be encouraged in increase potassium in diet! Examples of major groups of diuretics 23 Loop •??? Thiazide •??? + K •??? Sparing Single-tablet combination diuretics 24 Can reduce adverse effects Desired effects may be enhanced Enhanced patient convenience Promotes compliance Monitoring the patient on diuretic therapy (Quality & Safety Education for Nurses—QSEN) 25 Parameter Intake/output Daily weight Laboratory values Vital signs: Pulse, BP Level of consciousness Hypersensitivity Hearing and vision Sensitivity to light exposure Inadequate? Excessive? Roles of major electrolytes 26 Electrolyte Primary roles Sodium Muscle contraction Nerve transmission Chloride Peak muscle function Potassium Muscle contraction Nerve transmission Glycogen formation Magnesium Muscle relaxation ATP (energy production Calcium Bone health Nerve transmission Muscle contraction Symptoms of deficiency or excess??? Causes of electrolyte imbalance 27 Principles of the movement of body fluids 28 Osmolality—measure of the number of dissolved particles in 1 L of water Osmosis—movement of water from areas of low concentration (low osmolality) to higher concentration (high osmolality) Tonicity—ability of a solution to cause a change in water movement across a membrane due to osmotic forces Tonicity 29 Potential results 30 Hypotonic solution—water moves from plasma to interstitial fluid and cells, i.e., out of vascular system…may result in hypotension Hypertonic solution—water moves from cells and interstitial fluid to plasma, i.e, into the vascular system…more water than sodium is lost from the body…causes cell shrinkage and possible brain shrinkage Isotonic solution—water moves freely between plasma and interstitial fluid and cells Types of fluid replacement agents 31 Crystalloids Colloids ∙Contain electrolytes and other substances that are similar to body’s ECF ∙Replace depleted fluids ∙Promote urine output ∙Sodium is most common crystalloid added to solutions ∙Dextrose can be added ∙Increases total fluid volume in the body ∙May be isotonic, hypertonic, or hypotonic ∙Proteins, starches, etc. ∙Remain in blood for long time ∙Molecules are too large to cross capillary membranes ∙Same effect as hypertonic solution ∙AKA plasma volume expanders ∙Used in hypovolemic shock ∙Burns, hemorrhage, surgery When imbalances occur… 32 Patient can present with: Irregular heartbeat Fatigue, lethargy Convulsions or seizures Nausea and/or vomiting Diarrhea, constipation, abdominal cramping Muscle weakness or pain Cognitive changes (mood, confusion) Headache Sodium imbalance 33 Hypernatremia Most common cause is renal disease Mild cases—low sodium diet Severe cases—hypotonic fluids if hypovolemic, diuretics if hypervolemic Hyponatremia Caused by ↑ ADH or other disorders Treated with NaCl, IV NS, or IV LR Potassium imbalance 34 Hyperkalemia Due to diet, renal disease Mild cases—restrict potassium intake Severe cases—Glucose & insulin (1 amp D50 and 10 U insulin) Kayexalate Hypokalemia Can be due to excessive use of laxatives Mild—increase potassium containing foods, oral preps Severe—parenteral KCl pH: acidosis and alkalosis 35 Acidosis = ↓pH Too much acid Too little base Alkalosis = ↑pH Too little acid Too much base Maintaining body pH 36 Lungs • Release CO2 • pH increases, acidity decreases Kidneys • Excrete excess acid or base • Make changes slower than lungs Buffer system • Body’s natural weak acids & bases • Work chemically to minimize pH changes Treatment of pH imbalance 37 Acidosis (pH < 7.35) Is cause respiratory, metabolic (renal) or both? Rapid infusion of NaHCo3 must be done carefully! Alkalosis (pH > 7.45) Correct underlying condition Infuse NaCl and KCl to promote excretion of NaHCO3 Treatment of hypertension based on its classification 38 Classification Blood pressure Without Compelling Indication With Compelling indication Normal 119/79 or less No medication Healthy lifestyle promotion No medication Healthy lifestyle promotion Prehypertension 120-139/80-89 Lifestyle modification Lifestyle modification Stage I 140-159/90-99 Thiazide diuretic Other antihypertensives as needed Stage 2 ≥160/≥100 Two drug combination Other antihypertensives as needed Incidence of hypertension 39 African Americans have higher incidence of stroke and ESRD Caucasians and Asians have higher incidence of CAD ACEI works best as 1st medication for Caucasians, CCB more effective for African Americans Hypertension rates vary Race of by race and ethnicity: Women Ethnic Group (CDC 07/07/2014) Men (%) (%) African Americans 43.0 45.7 Mexican Americans 27.8 28.9 Whites 33.9 31.3 All 34.1 32.7 Lifestyle modifications for hypertension management 40 Treatment with CCBs 41 Helpful in patients who are not as responsive to other medications: African Americans, elderly Can be either selective (blood vessels), e.g., Nifedipine, or nonselective (affect both blood vessels and heart), e.g., Diltiazem (add) Adverse effects are related to vasodilation Immediate-acting preparations can cause reflex tachycardia Treatment with β-adrenergic antagonists (β-blockers) 42 First-line drugs for treatment of HTN Reduce heart rate and contractility Can reduce angina because CO decreased Can treat certain dysrhythmias: Also useful in treating heart failure, MI, and migraines Treatment with β-adrenergic antagonists (β-blockers) 43 First-line drugs for treatment of HTN Reduce heart rate and contractility Can reduce angina because CO decreased Also useful in treating heart failure, MI, and migraines Adverse effects due to mechanism of action: Fatigue, activity intolerance Heart less responsive to exertion Male sexual dysfunction Treatment with Alpha1-Adrenergic Blockers 44 Block sympathetic receptors in arterioles causing vasodilation Used in conjunction with other medications, not firstline Also used in treatment of BPH, so be sure to ask patient why he is taking the drug! Summary of heart failure 45 Heart’s ability to pump becomes weaker Can be right-sided or both right- and left-sided Right-sided failure—heart cannot pump enough blood to lungs for oxygenation Causes fluid build up in LEs, abdomen and liver, NVD Left-sided failure—heart unable to pump enough blood to systemic circulation Fluid build up plus SOB and fatigue Symptoms of heart failure 46 Treatment with ACE-inhibitors 47 Angiotensin II increases blood pressure by stimulating smooth muscle cells: ACE-inhibitors lower peripheral resistance, inhibit aldosterone secretion, and dilate veins Treatment with diuretics 48 Produce few side effects Increase urine flow: Reduce blood volume Less peripheral edema Less pulmonary congestion Cardiac workload reduced, output increased Treatment with cardiac glycosides 49 Digoxin is only cardiac glycoside available in US Oldest of cardiac medications Can cause bradycardia Monitor potassium Check serum dig levels Digoxin toxicity 50 Can progress to… Treatment with vasodilators 51 Act directly on blood vessels Hydralazine (Apresoline) works on arterioles Isosorbide dinitrate (Isordil) works on veins Combination form available (BiDil) BiDil highly effective in African Americans Labs to monitor for CV disease 52 Renal function Drug levels Liver function K+ EKG Cholesterol Na