Drugs that affect the Urinary System

Pharmacology

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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.

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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

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Objective 7: describe the actions of diuretics

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Diuretics act to

Deplete blood volume

Excrete sodium

Vasodilate peripheral arterioles (how is unknown)

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 itWorks 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 potassium–rich 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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Thiazides• 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 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)46

• 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 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.

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).

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. 15Nursing 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 client’s current drug therapy, monograph of

quinolone being used

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Methenamine mandelate (Mandelamine)

◦ 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

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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 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

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Phenazopyridine (Pyridium)

Produces local anesthetic effect in urinary tractActs about 30 min. after administrationUsed to relieve burning, pain, urgency, frequency

in UTIReduces bladder spasms

SE to expect◦ Reddish-orange urine color

SE to report◦ Yellow sclera or skin

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Tolterodine (Detrol)

Muscarinic receptor antagonists Inhibit muscarinic action of acetylcholine on bladder

smooth muscleUsed to treat overactive bladderDo 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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