Drugs that affect the Urinary System

Pharmacology

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.

Nephron
Nephron is functional unit of kidney Blood enters nephron and is filtered through Bowmans 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 Bowmans 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 kidneys 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

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Objective 7: describe the actions of diuretics

Diuretics act to
Deplete

blood volume

Excrete

sodium

Vasodilate

peripheral arterioles (how is unknown)

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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

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 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)

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 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

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Carbonic anhydrase inhibitor

Diamox very weak diuretic Useful in treating glaucoma

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Methylxanthines
Aminophylline Theophylline Caffeine Theobromine Diuretic effect from improved blood flow to kidney Generally not used for diuretic effect
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Objective 8: describe the uses, actions, and adverse effects of the thiazide and thiazide-like diuretics

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

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Loop Diuretics
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
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Loop Diuretics
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

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Loop Diuretics
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
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Loop Diuretics
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)

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Loop Diuretics
Drug interactions Alcohol, barbiturates, narcotics Aminoglycosides Cisplatin NSAIDs Corticosteroids Probenecid Digoxin
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Loop Diuretics
Loop diuretics include Bumetanide (Bumex) Ethacrynic acid (Edecrin) Furosemide (Lasix) Torsemide (Demadex)

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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 potassiumrich foods

Obj. 9 Thiazides
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
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Thiazides
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

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 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
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Thiazides

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

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Thiazide and Thiazide-like Drugs

Thiazide diuretics include Bendroflumethiazide (Naturetin) Chlorothiazide (Diuril) Hydrochlorothiazide (HCTZ) {Esidrix, HydroDiuril} Polythiazide (Renese) Trichlomethiazide (Naqua, Metahydrin, Diurese)
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 Thiazide-like drugs include Chlorthalidone (Hygroton) Indapamide (Lozol) Metolazone (Zaroxolyn)

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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

Objective 11: list the electrolyte imbalance that most commonly occurs as a result of diuretic therapy

Why is there concern about the electrolyte balance?

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Obj. 12 Potassium-Sparing Diuretics

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

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Potassium Sparing diuretics

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

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Potassium Sparing diuretics

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)

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Potassium Sparing diuretics

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)
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Potassium Sparing diuretics

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

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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

Objective 13: explain how increased fluid intake enhances the action of diuretics

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?
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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 clients condition Providing education relating to prescribed drug management

Role of the Nurse (continued)

Obtaining medical, drug, dietary, and lifestyle history Assessment of clients 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; oncea- 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.

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 drugs use, adverse effects and required precautions Demonstrates proper self-administration of the medication (e.g., dose, timing, when to notify provider).

Objective 14: list good dietary sources of potassium

What are some good dietary sources of potassium?

If a client is on Aldactone, what would you tell them about high potassium foods?

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Obj. 15 Nursing Implications: Diuretics

Assessments to make

Teaching to include:

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Obj. 16 Drugs for UTI

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

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Quinolones
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 clients current drug therapy, monograph of quinolone being used
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 Converts to ammonia and formaldehyde in acidic urine Used in clients susceptible to chronic, recurrent UTIs Preexisting infections treated with antibiotics

Methenamine mandelate (Mandelamine)

Implementation

DO NOT crush the tablets pH testing of urine: report over 5.5 N/V, belching Hives, pruritus, rash Bladder irritation, dysuria, frequency Acetazolamide, sodium bicarbonate Sulfamethizole
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SE to expect
SE to report

Drug interactions

Nitrofurantoin (Furadantin, Macrodantin)

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
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Obj. 17 Bladder Active Drugs

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

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Urecholine
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
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Neostigmine (Prostigmin)
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
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Oxybutynin (Ditropan)
Antispasmodic agentacts 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
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Phenazopyridine (Pyridium)
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 Yellow sclera or skin
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SE to report

Tolterodine (Detrol)
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
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 Objective 18: Discuss patient education guidelines for drugs that affect the urinary system

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

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