NURS 1950: Pharmacology

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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

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 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

Filtrate passes through loop of Henle, then distal tubule

Filtrate empties into collecting ducts and leaves nephron as urine

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

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

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

Urinalysis Serum creatinine Diagnostic imaging Renal biopsy

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

Requires immediate treatment Accumulation of waste products can be fatal Most common cause is hypoperfusion

Cause must be rapidly identified◦ Heart failure ◦ Dysrhythmias◦ Hemorrhage◦ Dehydration

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

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)

Increase rate of urine flow Excretion of excess fluid used to treat

◦ Hypertension, heart failure, kidney failure◦ Liver failure or cirrhosis, pulmonary edema

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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◦Diamox very weak diuretic Useful in treating glaucoma

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◦Aminophylline◦Theophylline◦Caffeine◦Theobromine Diuretic effect from improved blood flow to kidney

Generally not used for diuretic effect

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

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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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Onset of diuretic effect varies, but is within 1-2 hours. IV, drugs work within 5-10 minutes

Peak effect within 1-2 hoursDuration approximately 6 hours

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

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

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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

Obtain baseline and monitor periodically lab values, weight, current level of urine output

Monitor electrolytes, especially potassium, sodium, and chloride

Monitor blood urea nitrogen (BUN), serum creatinine, uric acid, and blood-glucose levels

Assess for circulatory collapse, dysrhythmias, hearing loss, renal failure, and anemia

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

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

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

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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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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

Less efficacious than loop diuretics◦ Not effective in clients with severe renal failure

Why is there concern about the electrolyte balance?

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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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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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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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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 drugs include◦Amiloride (Midamor)◦Spironolactone (Aldactone)◦Triamterene (Dyrenium)

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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?

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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

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

management

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

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

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

Teach client to◦ Use sunscreen to decrease photosensitivity◦ Take potassium supplements, if ordered◦ Consume potassium-rich foods◦ Report any tenderness or pain in joints

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

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

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

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

• 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

Prototype drug: chlorothiazide (Diuril) Mechanism of action: to block sodium

absorption in distal tubule of nephron

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

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

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

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

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

Adverse effects:◦ Headache, dizziness, tremors, dry mouth◦ Fluid and electrolyte imbalances,

thrombophlebitis

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?

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Assessments to make

Teaching to include:

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

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◦ 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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◦ 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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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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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

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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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