NUR 2047 Pharmacology Lecture 2 PDF

NUR 2047 Pharmacology Lecture 2 Drugs affecting the Urinary and the Immune System Urinary System  Learning Objectives After this lecture, students should be able to:- ❖Describe the function of the kidneys ❖Describe the process of reabsorption and secretion ❖Describe how renal fail...

NUR 2047 Pharmacology Lecture 2 Drugs affecting the Urinary and the Immune System Urinary System  Learning Objectives After this lecture, students should be able to:- ❖Describe the function of the kidneys ❖Describe the process of reabsorption and secretion ❖Describe how renal failure impacts pharmacotherapy ❖List the indications for diuretics ❖Understand the usage of diuretics ❖Understand the usage of other urinary tract medications The urinary system List some ways you can celebrate Asian Pacific Heritage Month. Here are a few examples: Discover Asian Pacific American artists Read Asian Pacific American authors Listen to Asian Pacific American Heritage musicians Learn important moments of Asian Pacific American Heritage history The nephron https://www.nottingham.ac.uk/helmopen/rlos/biological-sciences/genito-urinary-system/kidney- physiology/page_two.html#:~:text=The%20first%20process%20by%20which,capsular%20membrane%20into%20t he%20nephron.  Reabsorption ❖The composition of filtrate changes dramatically as a result of the processes of reabsorption and secretion ❖Reabsorption is the process by which some substances in the filtrate cross the walls of the nephron to re-enter the blood ❖Water is the most important molecule reabsorbed in the tubule ❖Glucose, amino acids and essential ions (sodium, chloride, calcium and bicarbonate) are also reabsorbed  Secretion ❖Certain ions and molecules that are too large to pass through the glomerulus can still enter the urine by crossing from the blood to the filtrate Potassium, phosphate, hydrogen and ammonium ions enter the filtrate through secretion ❖Drugs are secreted through the proximal tubule Penicillin G, Ampicillin, Non-steroidal anti-inflammatory drugs (NSAIDs), Furosemide, Epinephrine  Renal failure ❖Renal failure significantly impacts pharmacotherapy ❖Renal failure is the decrease in the kidney’s ability to maintain electrolyte and fluid balance and the excretion of waste products ❖Drugs will accumulate to high concentrations in the blood and tissues, resulting in toxicity ❖Can be classified as acute and chronic Pharmacotherapy includes Administer diuretics Administer medications for erythropoietin Administer cardiovascular drugs  Diuresis ❖Blocks sodium (Na+) reabsorption in the nephron ❖Sends more Na+ to the urine ❖Chloride (Cl-) follows Na+ ❖Water molecules travel with sodium ❖Prevent the reabsorption of Na+ will increase the volume of urine  Diseases treated by diuretics ❖Hypertension ❖Heart failure ❖Kidney failure ❖Pulmonary edema ❖Liver failure or cirrhosis Site of action of diuretics  Diuretics ❖Loop diuretics ❖Thiazides and thiazide-like diuretics ❖Potassium-sparing diuretics ❖Other diuretics  Loop diuretics ❖The most effective diuretics are those that act on the Loop of Henle ❖Blocks the reabsorption of sodium and chloride in the Loop of Henle ❖When given by IV route, they have the ability to cause large amounts of fluid to be excreted by the kidneys in a very short time https://www.youtube.com/watch?v=5k5btYZTKhQ  Loop diuretics Furosemide (Lasix) Dosage PO 20-80mg daily IV bolus 20-40mg IV slow injection over 1-2 minutes, can be up to 80mg IV infusion 250mg Action A potent diuretic Inhibits reabsorption of Na+ and Cl- in the ascending loop of Henle and in both the proximal and distal renal tubules Inhibit the co-transport of Cl- and K+ Onset PO 30-60 min, peak 1-2 hours, duration 6-8 hours IV 5 mins, peak 30 mins, duration 2 hours  Loop diuretics Furosemide (Lasix) Adverse reactions Fluid and electrolyte depletion, Hypovolemia, hypotension, dehydration, hypokalemia Metabolic alkalosis -> increase Na+ in the collecting tubule and increase K+ in the urine Ototoxicity -> dose related hearing loss that is usually reversible Absorption Rapid (47-64% bioavailability) for PO Metabolism Minimal hepatic metabolism Excretion Mainly via urine (80%) within 24 hours, the rest via faeces Half-life: 0.5 – 2 hours  Loop diuretics Furosemide (Lasix) Nursing considerations Keep accurate I&O (Intake and Output) and BW (Body weight) Monitor BP for postural hypotension in supine and standing positions Monitor serum electrolytes for early detection of electrolytes imbalance Assess for tinnitus and hearing loss Assess odema, lung sounds Assess skin turgor and mucous membranes Stand up slowly from a supine or sitting position to avoid postural hypotension, and to avoid falls Beware of patients taking digoxin and presenting hypokalemia – cause digoxin toxicity Take in the morning and/or early afternoon to prevent disruption of sleep Storage: protect from light (IV)  Thiazides and thiazide-like diuretics ❖Largest and one of the most frequently prescribed class of diuretics ❖Acts on the distal tubule to block Na+ reabsorption and increase water excretion ❖Primary use is for the treatment of mild to moderate hypertension  Thiazides and thiazide-like diuretics Indapamide Indications HT (Hypertension) Dosage PO 1.25-2.5mg daily PO SR 1.5mg daily Action Enhance excretion of Na+, Cl- and water by interfering with the transport of sodium ions across the renal tubules  Thiazides and thiazide-like diuretics Indapamide Adverse reactions Fluid and electrolyte imbalance Hypokalemia, hyponatremia Dehydration, low BP Absorption Rapid (93% bioavailability) Metabolism Extensively metabolized in the liver Excretion Mainly via urine (70%) within 24 hours, the rest via faeces Half-life: 14 hours  Thiazides and thiazide-like diuretics Indapamide Nursing considerations Monitor BP Monitor serum electrolytes for early detection of electrolytes imbalance Keep accurate I&O and BW Take in the morning May cause photosensitivity, avoid exposure to direct sunlight. Use protective measures  Thiazides and thiazide-like diuretics Hydrochlorothiazide (Microzide) Indications HT (Hypertension) Dosage PO 12.5-100mg daily Action Enhance excretion of Na+, Cl- and water by interfering with the transport of sodium ions across the distal convoluted tubules Onset PO 2 hours, peak 4 hours, duration 6-12 hours  Thiazides and thiazide-like diuretics Hydrochlorothiazide (Microzide) Adverse reactions Fluid and electrolyte imbalance Hypokalemia, hyponatremia Dehydration, low BP Transient myopia, acute glaucoma Contraindications Patients with anuria Absorption Rapid (65-75% bioavailability) Metabolism Not metabolized by liver Excretion Mainly via urine unchanged Half-life: 6-15 hours  Thiazides and thiazide-like diuretics Hydrochlorothiazide (microzide) Nursing considerations Monitor BP Monitor serum electrolytes for early detection of electrolytes imbalance Keep accurate I&O and BW Take in the morning Monitor vision May cause photosensitivity, avoid exposure to direct sunlight. Use protective measures  Thiazides and thiazide-like diuretics Other examples Chlorothiazide (Diuril) Metolazone Bendroflumathiazide and Nadolol (Corzide)  Combination preparations CoAprovel Angiotensin II antagonist (irbesartan)/diuretic (hydrochlorothiazide) Co-Diovan Angiotensin II antagonist(valsartan)/diuretic (hydrochlorothiazide) Hyzaar Angiotensin II antagonist (losartan)/diuretic (hydrochlorothiazide) Micardis Plus Angiotensin II antagonist (telmisartan)/diuretic (hydrochlorothiazide)  Potassium-sparing diuretics ❖Increase diuresis without adversely affecting blood potassium levels ❖Cause Na+ to stay in the tubule and leave through the urine (prevents reabsorption of Na+) ❖Blocks the exchange of K+ and Na+ ❖As a result, the body retains more K+ https://www.youtube.com/watch?v=j4S8bg1J-wc  Potassium-sparing diuretics Spironolactone (Aldactone) Indications HT, nephrotic syndrome, ascites, heart failure, oedema, Dosage PO 50-100mg daily Action Inhibits aldosterone receptors in the late distal convoluted tubules Increase excretion of NaCl and water but conserve K+ and H+ ions Onset PO 30-60 min, peak 2-4 hours, duration 6-8 hours  Potassium-sparing diuretics Spironolactone (Aldactone) Adverse reactions Dizziness, Headache Fluid and electrolyte imbalance, Hypovolemia, hypotension, dehydration, hyperkalemia Breast tenderness and enlargement in men Irregular menstrual cycle Contraindications Patients with anuria Absorption Rapid (60-90% bioavailability) Metabolism Rapidly and extensively metabolized in the liver to several active metabolites Excretion Mainly via urine as metabolites, minimal amounts are handled by biliary excretion Half-life: 1.4 hours  Potassium-sparing diuretics Spironolactone (Aldactone) Nursing considerations Monitor BP for hypotension Monitor serum electrolytes for early detection of electrolytes imbalance (hyperkalemia) Monitor renal function (eGFR) Keep accurate I&O and BW Monitor for dizziness, drowsiness and somnolence Take in the morning and or early afternoon to prevent sleep disruption Avoid high potassium foods to prevent hyperkalemia  Potassium-sparing diuretics Other examples ❖Amiloride (Midamor) ❖Eplerenone (Inspra) ❖Triamterene (Dyrenium) Combinations ❖Moduretic (Amiloride + Hydrochlorothiazide) Other diuretics ❖Osmotic agents - Mannitol (Osmitrol) ❖Major action at the proximal tubule and descending limb of Loop of Henle ❖Remain in the lumen and hold water by osmotic effect hence, promote water diuresis ❖Used to reduce swelling in the brain ❖Used to lower intraocular pressure in certain types of glaucoma ❖IV only  Other diuretics ❖Carbonic anhydrous inhibitor – acetazolamide (Diamox), methazolamide (Neptazane) ❖Used to treat glaucoma – decrease intraocular pressure ❖Used to reduce swelling in the brain – idiopathic intracranial hypertension ❖PO and IV  Antispasmodics Oxybutinin (Ditropan) Indications Overactive bladder, neurogenic bladder disorders Dosage PO 2.5-5mg BD-QID Action Exerts direct and potent antispasmodic effect on the smooth muscles of the urinary bladder by inhibiting the muscarinic action of acetylcholine Relaxes the muscles in the urinary bladder and reduce urgency and frequent urination Onset PO 60 min, peak 4-6 hours, duration 6-8 hours  Antispasmodics Oxybutinin (Ditropan) Adverse reactions Dry mouth Urinary retention Dizziness, drowsiness Blurred vision, dry eyes Reduced sweating Nausea, stomach upset, abdominal pain, constipation Absorption Rapid (6% bioavailability) Metabolism In liver Excretion Only 0.1% as metabolites Half-life: 2-3 hours  Antispasmodics Oxybutinin (Ditropan) Nursing considerations Monitor for urinary retention – I&O, distended and painful suprapubic area, difficultly in urination Assess for dizziness/drowsiness that may affect gait and precipitate falls Monitor anticholinergic effects – agitation, confusion, somnolence Be alert for increased body temperature and reduced sweating during exercise Increase fibre and fluid in diet to offset the anticholinergic side effects (constipation)  Urinary tract analgesics Phenazopyridine (Pyridium) Indications Relief of burning pain, urgency and other discomforts associated with irritation, infection, surgery or injury to the urinary tract Dosage PO 200mg TDS Action Exerts a local anesthetic effect on the mucosa lining of the urinary tract  Urinary tract analgesics Phenazopyridine (Pyridium) Adverse reactions Produces a color change in the urine to dark orange to reddish Also leaves a permanent discoloration orange-yellow stain on surfaces, clothing Headache, stomach upset Metabolism In liver (40%) Excretion In urine, unchanged Half-life: 7.35 hours  Urinary tract analgesics Phenazopyridine (Pyridium) Nursing considerations Should be avoided in patients with G6PD deficiency (cause hemolysis of RBC) Inform patient that the urine color will change Will also stain objects/materials/clothes Avoid wearing contact lenses when taking Pyridium To take with meals to reduce stomach upset Immune System  Learning Objectives After this lecture, students should be able to:- ❖Understand what inflammation is ❖Describe the treatment for inflammation ❖Understand the use of steroids ❖Understand what pathogens are ❖Understand how anti-infective drugs work  The immune system ❖Immune system is a large network of organs, WBCs, proteins (antibodies) and chemicals. ❖Immune system works together to protect you from foreign invaders (bacteria, viruses, parasites and fungi) that cause illness and diseases ❖Immune system can differentiate between foreign and non- foreign substances ❖It activates, mobilizes, attacks and kills foreign invaders ❖It learns about these invaders after the body has been exposed to them and builds up antibodies to foreign cells. In this way, it can remember these foreign cells and destroy them if exposed in the future ❖When the immune system cannot mount a winning attack against an invader, infection develops. ❖When the immune system mounts an attack even in the absence of an invader, these result in autoimmune diseases The immune system  Inflammation ❖Inflammation is a body defense that limits the spread of invading microorganisms and injury ❖Occurs in response to many different stimuli (Physical injury, exposure to toxic chemicals, extreme heat, invading microorganisms, death of cells) Purpose of inflammation ❖Contain the injury or destroy the microorganism ❖By removing the cellular debris and dead cells, repair of the injured area can move at a faster pace Signs of inflammation ❖Swelling, pain, warmth, redness of the affected area ❖Can be acute or chronic https://www.youtube.com/watch?v=XS30Rnpka8M Steps in acute inflammation Source #1 Source #2 Source #3  Chemical mediators ❖Mediators are the substances that initiate and regulate inflammatory reactions ❖The body reacts to injury by releasing chemical mediators that cause inflammation ❖Damaged tissues release chemical mediators that act as “alarm” to notify the surrounding areas of the injury  Treatment of inflammation ❖Inflammation may be treated with non- pharmacological and pharmacological therapies ❖Cause of inflammation is identified and treated ❖For mild symptoms, non-pharmacological therapies e.g. ice pack, rest, elevation of affected extremities is used ❖Topical drugs for relieve of symptoms Diseases that benefit from anti-inflammatory drugs Two primary classes Non-steroidal anti-inflammatory drugs (NSAIDs) Glucocorticoids (Corticosteroids) ❖Allergic rhinitis ❖Anaphylaxis ❖Ankylosing spondylitis (AS) ❖Contact dermatitis ❖Crohn’s disease ❖Glomerulonephritis ❖Rheumatoid arthritis (RA) ❖Systemic lupus erythematosus (SLE)  NSAIDs Non-steroidal anti-inflammatory drugs (NSAIDs) ❖NSAIDS block the production of certain chemicals (cyclooxygenase (COX))that is used to make prostaglandins ❖By reducing prostaglandins, pain, fever and inflammation is reduced Diclofenac Ibuprofen Naproxen Mefenamic acid Indomethacin Celecoxib Arcoxia  NSAID Celecoxib (Celebrex) Class NSAID, COX-2 inhibitor Action Selective inhibition of COX 2 (which is responsible for prostaglandin synthesis), an integral part of pain and inflammation pathway Indications Pain, conditions that cause tissue injury and inflammation Has antipyretic, anti-inflammatory and pain reduction properties Dosage PO 200mg BD Peak effect 3 hours, Effect lasts for 12 hours  NSAIDs Celecoxib (Celebrex) Absorption Rapid (22-40% bioavailability) Metabolism Extensively metabolized in the liver Excretion Very little (