NURS 1950: Pharmacology 1

Renal Regulation: Obj 1  Kidneys regulate ◦ Fluid volume, electrolytes, acid-base balance  Kidneys secrete ◦ Renin- for blood-pressure regulation ◦ Erythropoietin – to stimulate blood-cell production ◦ Calcitrol –active form of vitamin D for bone hemeostasis

Kidney Structure  Urinary system consists of ◦ Two kidneys ◦ Two ureters ◦ One bladder ◦ One urethra

 Objective 2: List the four processes carried out by the nephron.  Objective 3: Name the part of the nephron responsible for each process. 4

Nephron  Nephron is functional unit of kidney  Blood enters nephron and is filtered through Bowman’s capsule  Fluid is called filtrate  Water and small molecules pass into proximal tubule

Nephron (continued)  Filtrate passes through loop of Henle, then distal tubule  Filtrate empties into collecting ducts and leaves nephron as urine

Reabsorption  Filtrate in Bowman’s capsule is same composition as plasma minus large proteins  Some substances in filtrate cross wall of nephron and reenter blood  Most of water in filtrate is reabsorbed  Glucose, amino acids, sodium, chloride, calcium, and bicarbonate are reabsorbed

Secretion  Some substances pass from blood through walls of nephron and become part of filtrate  Potassium, phosphate, hydrogen, ammonium ion, and some acid drugs are secreted into filtrate  Reabsorption and secretion are critical to pharmacokinetics of many drugs

Figure 30.1 The nephron

Renal Failure  Decrease in kidney’s ability to function ◦ Drugs can accumulate to high levels ◦ Medication dosages need to be adjusted ◦ Administering average dose to person in renal failure can be fatal

Diagnosis of Renal Failure  Urinalysis  Serum creatinine  Diagnostic imaging  Renal biopsy

Diagnosis of Renal Failure (continued)  Glomerular filtration rate (GFR) ◦ Best marker for estimating renal function ◦ Measure volume of water filtered per minute

Acute Renal Failure  Requires immediate treatment  Accumulation of waste products can be fatal  Most common cause is hypoperfusion

Acute Renal Failure (continued)  Cause must be rapidly identified ◦ Heart failure ◦ Dysrhythmias ◦ Hemorrhage ◦ Dehydration

Chronic Renal Failure  Occurs over months or years  Usually history of diabetes mellitus or hypertension  May be undiagnosed for a long time  Nephrotoxic drugs can cause acute or chronic renal failure ◦ See Table 30-1

Pharmacotherapy  Attempts to cure cause of dysfunction ◦ Diuretics to increase urine output ◦ Cardiovascular drugs to treat hypertension or heart failure ◦ Dietary management  Restriction of protein, reduction of sodium, potassium, phosphorus, magnesium

 Objective 4: pituitary hormone that influences urine volume: ◦ ADH (Posterior pituitary)  Objective 5: adrenocortical hormone that influences urine volume: ◦ Aldosterone (increases Na+ reabsorption in the distal tubule)  Objective 6: four ways fluid is lost from the body ◦ Urine, perspiration, lungs, stool 19

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Diuretics  Increase rate of urine flow  Excretion of excess fluid used to treat ◦ Hypertension, heart failure, kidney failure ◦ Liver failure or cirrhosis, pulmonary edema

Side Effects of Diuretic Therapy  Fluid and electrolytes disturbances ◦ Dehydration ◦ Orthostatic hypotension ◦ Potassium and sodium imbalances

 Diuretics work in the kidney at various sites of the nephron  Can interfere with the action of aldosterone causing loss of sodium ◦ Where goes sodium, so goes water 24

 What happens with diuretics ◦ Decrease excess water ◦ Loop diuretics + 0.9% NaCl = loss of calcium ◦ Decrease excess NaCl ◦ Decrease cerebral edema (Mannitol) ◦ Decrease increased IOP (Diamox) 25

 Mannitol is an osmotic diuretic (a sugar); ◦ in the brain, its presence causes water to be drawn to it  Works the same way in the eye: ◦ the excess intraocular fluid is drawn to the mannitol in the hyperosmotic plasma 26

◦ Diamox very weak diuretic  Useful in treating glaucoma 27

◦ Aminophylline ◦ Theophylline ◦ Caffeine ◦ Theobromine  Diuretic effect from improved blood flow to kidney  Generally not used for diuretic effect 28

 Drugs that affect the loop of Henle ◦ Bumetanide (Bumex) ◦ Ethacrynic acid (Edecrin) ◦ Furosemide (Lasix) ◦ Torsemide (Demadex) 29

 Act in the loop of Henle in the kidney ◦ Inhibits Na and Cl reabsorption  Some increase blood flow to glomeruli  Inhibits electrolyte absorption in proximal tubule ◦ Lose sodium, chloride, potassium, magnesium, sodium bicarbonate 30

 Onset of diuretic effect varies, but is within 1-2 hours. IV, drugs work within 5-10 minutes  Peak effect within 1-2 hours  Duration approximately 6 hours 31

 Maximum mg/day ◦ Bumex 10 mg per 24 hours ◦ Edecrin 400 mg per 24 hours ◦ Lasix 1000 mg/24 hours  Cross sensitivities ◦ Sulfonamides and Lasix, Demadex  SE to expect ◦ Oral irritation ◦ Dry mouth ◦ Orthostatic hypotension 32

 SE to report with loop diuretics ◦ GI irritation, abdominal pain ◦ Electrolyte imbalance, dehydration ◦ Hives, pruritus, rash ◦ Some can cause loss of hearing and hyperglycemia (interfere with hypoglycemic agents) 33

 Drug interactions ◦ Alcohol, barbiturates, narcotics ◦ Aminoglycosides ◦ Cisplatin ◦ NSAIDs ◦ Corticosteroids ◦ Probenecid ◦ Digoxin 34

 Loop diuretics include ◦ Bumetanide (Bumex) ◦ Ethacrynic acid (Edecrin) ◦ Furosemide (Lasix) ◦ Torsemide (Demadex) 35

Loop Diuretics  Loop or high-ceiling are most effective diuretics  Mechanism of action: to block reabsorption of sodium and chloride in loop of Henle  Primary use: to reduce edema associated with heart, hepatic, or renal failure  Furosemide and torsemide also approved for hypertension

Loop (High-Ceiling) Diuretics  Obtain baseline and monitor periodically lab values, weight, current level of urine output  Monitor electrolytes, especially potassium, sodium, and chloride

Loop (High-Ceiling) Diuretics (continued)  Monitor blood urea nitrogen (BUN), serum creatinine, uric acid, and blood-glucose levels  Assess for circulatory collapse, dysrhythmias, hearing loss, renal failure, and anemia

Loop (High-Ceiling) Diuretics (continued)  Monitor for side effects orthostatic hypotension, hypokalemia, hyponatremia, polyuria  Observe for rash or pruritis  Teach clients to take diuretics in the morning, change position slowly, monitor weight

Loop (High-Ceiling) Diuretics (continued)  Clients should take potassium supplements, if ordered, and consume potassium–rich foods

 Action of the thiazides ◦ Act on the distal tubules of the kidney  Block reabsorption of sodium and chloride ions from the tubule  The unreabsorbed Na and Cl ions pass into the collecting ducts, taking water with them  Thiazides have antihypertensive properties because of direct vasodilation effect on peripheral arterioles ◦ Expected outcomes from treatment  Decreased edema and improvement of symptoms RT excess fluid accumulation  Reduction in BP 42

 Assessments ◦ Mental status ◦ Diabetics require baseline blood glucose ◦ Assess hearing ◦ Assess for symptoms of acute gout  SE to expect: orthostatic hypotension ◦ Usually in initial stages of treatment ◦ Teach client safety measures 43

 SE to report ◦ GI irritation, N/V, constipation ◦ Electrolyte imbalance, dehydration ◦ Hyperuricemia ◦ Hyperglycemia ◦ Hives, rash  Thiazides can interact with ◦ Digoxin, corticosteroids ◦ Lithium, NSAIDs ◦ Oral hypoglycemic agents 44

 Thiazides can interact with ◦ Digoxin, corticosteroids ◦ Lithium, NSAIDs ◦ Oral hypoglycemic agents 45

 Thiazide diuretics include ◦ Bendroflumethiazide (Naturetin) ◦ Chlorothiazide (Diuril) ◦ Hydrochlorothiazide (HCTZ) {Esidrix, HydroDiuril} ◦ Polythiazide (Renese) ◦ Trichlomethiazide (Naqua, Metahydrin, Diurese) 46

 Thiazide-like drugs include ◦ Chlorthalidone (Hygroton) ◦ Indapamide (Lozol) ◦ Metolazone (Zaroxolyn) 47

Thiazide Diuretics  Largest, most commonly prescribed class of diuretics  Mechanism of action: to block Na + reabsorption and increase potassium and water excretion  Primary use: to treat mild to moderate hypertension ◦ Also indicated to reduce edema associated with heart, hepatic, and renal failure

Thiazide Diuretics (continued)  Less efficacious than loop diuretics ◦ Not effective in clients with severe renal failure

 Why is there concern about the electrolyte balance? 51

 Weak antihypertensives  Mechanism of action unknown  Do work in distal renal tubule ◦ Retains potassium ◦ Excretes sodium ◦ Some have anti-aldosterone activity 52

 Maximum dosing per 24 hrs ◦ drug dependent  SE to expect with Midamor: ◦ anorexia, N/V, flatulence and HA  SE to report: ◦ electrolyte imbalance, dehydration, 53

 SE to expect and report with Aldactone and Dyrenium: ◦ mental confusion, HA, diarrhea, electrolyte imbalance, dehydration, gynecomastia, reduced libido, breast tenderness  Dyrenium can also cause allergic reaction (hives, pruritus, rash) 54

 Generally, drug interactions for the K+ sparing agents ◦ Lithium, ACE inhibitors, salt substitutes, K+ replacement ◦ NSAIDs,  Potassium-sparing drugs include ◦ Amiloride (Midamor) ◦ Spironolactone (Aldactone) ◦ Triamterene (Dyrenium) 55

 Potassium-sparing drugs include ◦ Amiloride (Midamor) ◦ Spironolactone (Aldactone) ◦ Triamterene (Dyrenium) 56

Potassium-Sparing Diuretics  Advantage: diuresis without affecting blood potassium levels  Mechanism of action: either by blocking sodium or by blocking aldosterone  Potassium-sparing diuretics shown in Table 30.5

 Why is an adequate fluid intake important with diuretic therapy?  If the client has to get up during the night to void, what will they probably do? 58

Miscellaneous Diuretics  Cannot be classified as loop, thiazide, or potassium-sparing agents  Three of these drugs inhibit carbonic anhydrase  Primary use: to maintain urine flow in times of hypoperfusion ◦ For clients with acute renal failure or during prolonged surgery

Role of the Nurse  Pharmacological management of renal failure and diuretic therapy ◦ Careful monitoring of client’s condition ◦ Providing education relating to prescribed drug management

Role of the Nurse (continued)  Obtaining medical, drug, dietary, and lifestyle history  Assessment of client’s weight, intake/output, skin turgor/moisture, vital signs, breath sounds, and presence of edema

Thiazide and Thiazide-like Diuretics  Obtain baseline and monitor periodically lab values, weight, current level of urine output  Measure electrolytes, especially potassium, sodium, and chloride, prior to loop-diuretic therapy  Monitor blood urea nitrogen (BUN), serum creatinine, uric acid, blood-glucose levels

Thiazide and Thiazide-like Diuretics (continued)  Increased potassium loss may occur when used with digoxin  Increased risk of lithium toxicity when taking thiazide diuretics  Allergies to sulfa-based medications can indicate hypersensitivity  Use with caution in pregnant women  DO not administer to lactating women

Thiazide and Thiazide-like Diuretics (continued)  Teach client to ◦ Use sunscreen to decrease photosensitivity ◦ Take potassium supplements, if ordered ◦ Consume potassium-rich foods ◦ Report any tenderness or pain in joints

Potassium-Sparing Diuretics  Advantage: client will not experience hypokalemia  Critical to assess electrolytes (potassium and sodium), blood urea nitrogen (BUN), serum creatinine  Adverse effects : hyperkalemia, and GI bleeding, confusion, dizziness, muscle weakness, blurred vision, impotence, amenorrhea, gynecomastia

Potassium-Sparing Diuretics (continued)  Spironolactone may decrease effectiveness of anticoagulants  Clients taking lithium or digoxin may be at increased risk for toxicity  Triamterene contraindicated for lactating women  Report signs and symptoms of hyperkalemia

Potassium-Sparing Diuretics (Client Teaching)  Avoid use of potassium-based salt substitutes  When in direct sunlight use sunscreen  Avoid performing tasks that require mental alertness  Do not eat excess amount of foods high in potassium

Loop Diuretics  Prototype drug: furesomide (Lasix); increases urine output even when blood flow to kidney is diminished  Mechanism of action : to block reabsorption of sodium in Loop of Henle  Primary use: to treat hypertension and reduce edema associated with heart failure, hepatic cirrhosis, and renal failure

Loop Diuretics (continued) Adverse effects: rapid excretion of large amounts of water, dehydration and electrolyte imbalances ototoxicity  Other examples ◦ Torsemide: longer half life than furosemide; once- a- day dosing ◦ Bumetanide (Bumex): 40 times potency of furosemide; shorter duration of action

Thiazide Diuretics  Prototype drug: chlorothiazide (Diuril)  Mechanism of action: to block sodium absorption in distal tubule of nephron

Diuril

Thiazide Diuretics (continued)  Primary use: to treat mild to moderate hypertension ◦ To treat severe hypertension, in combination with other drugs ◦ To treat fluid retention from heart failure, liver disease, corticosteroid or estrogen therapy  Adverse effects: dehydration, orthostatic hypotension, hypokalemia

Potassium-Sparing Diuretics  Less effective than loop diuretics but help prevent hypokalemia  Prototype drug : spironolactone (Aldactone)  Mechanism of action: to block action of aldosterone  Primary use: to significantly reduce mortality in heart failure  Adverse effects: hyperkalemia

Aldactone

Spironolactone Animation Click here to view an animation on the topic of spironolactone.here

Miscellaneous Diuretics – Carbonic Anhydrase Inhibitors  Example: acetazolamide (Diamox)  Mechanism of action: to inhibit formation of carbonic acid  Primary use: to decrease intraocular fluid pressure in clients with glaucoma  Adverse effects: allergic reaction (contain sulfa), fluid and electrolyte imbalances

Miscellaneous Diuretics – Osmotic Diuretics  Example : mannitol  Mechanism of action: to quickly reduce plasma volume  Primary use: to reduce intracranial pressure due to cerebral edema  Also used to maintain urine flow in prolonged surgery, acute renal failure, or severe renal hypoperfusion

Miscellaneous Diuretics – Osmotic Diuretics (continued)  Adverse effects: ◦ Headache, dizziness, tremors, dry mouth ◦ Fluid and electrolyte imbalances, thrombophlebitis

Drug Therapy for Renal Failure  Evaluation the patient ◦ Experiences a decrease in blood pressure. ◦ Is free from, or experiences minimal adverse effects. ◦ Verbalizes an understanding of the drug’s use, adverse effects and required precautions ◦ Demonstrates proper self-administration of the medication (e.g., dose, timing, when to notify provider).

 What are some good dietary sources of potassium?  If a client is on Aldactone, what would you tell them about high potassium foods? 82

 Assessments to make  Teaching to include: 83

 Drugs include ◦ Antibiotics  Fosfomycin (Monurol)  Quinolones : cinoxacin, nalidixic acid, norfloxacin  Methenamine madelate  Nitrofurantoin 84

 Fosfomycin (Monurol) ◦ Inhibits bacterial cell wall synthesis ◦ Reduces adherence of bacteria to epithelial cells of urinary tract ◦ Single dose therapy  SE to expect: ◦ nausea, diarrhea, abdominal cramps, flatulence  SE to report: ◦ perineal burning, dysuria  Indicates UTI is not responding to treatment  Drug interactions ◦ Drugs such as metoclopramide that increase GI motility 85

Norfloxacin (Noroxin) has wide range of activity against gram negative and gram positive bacteria  Expensive  Reserve for resistant/recurrent infections  SE to report ◦ Hematuria as crystals can form in urinary tract ◦ HA, tinnitus, dizziness, tingling sensations, photophobia  Various drug interactions can occur ◦ Assess client’s current drug therapy, monograph of quinolone being used 86

◦ Converts to ammonia and formaldehyde in acidic urine ◦ Used in clients susceptible to chronic, recurrent UTIs ◦ Preexisting infections treated with antibiotics  Implementation ◦ DO NOT crush the tablets ◦ pH testing of urine: report over 5.5  SE to expect ◦ N/V, belching  SE to report ◦ Hives, pruritus, rash ◦ Bladder irritation, dysuria, frequency  Drug interactions ◦ Acetazolamide, sodium bicarbonate ◦ Sulfamethizole 87

◦ Interferes with several bacterial enzyme systems ◦ Effective only in the urinary tract  SE to expect: ◦ N/V, anorexia, urine discoloration  SE to report: ◦ Dyspnea, chills, fever, erythematous rash, pruritus ◦ Peripheral neuropathies ◦ Second infection  Drug interactions ◦ Magnesium containing products can decrease absorption 88

 Bethanecole chloride (Urecholine)  Neostigmine (Prostigmin)  Oxybutynin chloride (Ditropan)  Phenazopyridine (Pyridium)  Tolterodine (Detrol) 89

◦ Parasympathetic nerve stimulant ◦ Causes contraction of detrusor urinae muscle  Results in urination  May also stimulate gastric motility  Can increase gastric tone  Can restore impaired rhythmic peristalsis  SE to expect ◦ Flushing of skin, HA  SE to report ◦ N/V, sweating, colicky pain, abdominal cramps ◦ Diarrhea, belching, involuntary defecation 90

◦ Anticholinesterase agent ◦ Binds to cholinesterase  Prevents destruction of acetylcholine  Effects are: miosis; increased tone of intestinal, skeletal, and bladder muscles  Bradycardia; stimulation of secretions of salivary and sweat glands  Constriction of bronchi and ureters  Neostigmine used to prevent and treat postoperative distension and urinary retention ◦ Assess for pregnancy, intestinal or urinary obstruction, peritonitis ◦ Assess coronary status 91

 Antispasmodic agent—acts directly on smooth muscle of the bladder ◦ Delays initial urge to void ◦ Do not use if glaucoma, myasthenia gravis, ulcerative colitis, obstructive uropathy  SE to expect ◦ Dry mouth, urinary hesitance, retention ◦ Constipation, bloating ◦ Blurred vision  Report any SE that are intensified 92

 Produces local anesthetic effect in urinary tract  Acts about 30 min. after administration  Used to relieve burning, pain, urgency, frequency in UTI  Reduces bladder spasms  SE to expect ◦ Reddish-orange urine color  SE to report ◦ Yellow sclera or skin 93

 Muscarinic receptor antagonists  Inhibit muscarinic action of acetylcholine on bladder smooth muscle  Used to treat overactive bladder  Do not use if glaucoma, ulcerative colitis, obstructive uropathy  S/E to expect ◦ Dry mouth ◦ Urinary hesitance, retention ◦ Constipation, bloating ◦ Blurred vision ◦ Report if the effects intensified 94

 Objective 18: Discuss patient education guidelines for drugs that affect the urinary system 95

 Objective 19: identify at least one nursing diagnosis that may be applicable for clients receiving diuretic therapy under the guidance of the instructor 96