UNIT

2
Drugs used in
the Treatment
of Urinary
System
Disorders
 Functions of Kidney
❑Kidneys filter blood to excrete exogenous poisons (e.g.,
drugs) and endogenously created poisons (e.g., ammonia as
urea).
❑Regulate salt and water excretion and controls extracellular
volume.
❑Regulate blood pressure through volume and pressor.
❑Help regulate red cell mass as erythropoietin help in
formation of haemoglobin.
❑Regulate calcium metabolism (1,25-dihydroxy vitamin D).
RENIN ANGIOTENSIN SYSTEM
 DRUGS AFFECTING RENIN/ANGIOTENSIN/
• Direct renin inhibitor: Alliskiren (150-300 mg once daily).
• Angiotensin converting enzyme inhibitors (ACE inhibitors).
E.g., Enalapril prodrug (2.5-40 mg per day).
❑Lisinopril (5-40 mg per day).
❑Benazepril, fosinopril (10-40 mg per day).
❑Captopril (25-150 mg per day).
❑Ramipril (1.25-10 mg per day).
• Angiotensin receptor blocking agent

❑Losartan (50 mg once daily).

❑Andesartan (8 mg once daily).

❑Prosartan (600 mg once daily).

Alliskiren
Direct Renin Inhibitor.
Indications
❑Hypertension
❑CHF
❑ Prevention or delay of nephropathy in diabetics.
❑Myocardial infarction: reduce mortality.
❑Scleroderma crisis: ACE inhibitors.
Contra Indications
❑Patients with a known hypersensitivity.
❑Pediatric patients less than two years.
❑Patients with diabetes mellitus.
❑Who are taking an ACE inhibitor or an angiotensin receptor blocker.
Adverse Effects
❑Hypotension
❑Renal Insufficiency (if bilateral renal artery stenosis)
❑Hyperkalemia in Sodium restricted, on Potassium
❑sparing diuretic, COX inhibitors.
❑Cough
DIURETICS

Definitions

▪ Diuretic: Drugs that promote the excretion of urine are called

diuretics.

▪ Natriuretic: Substance that promotes the renal excretion of

sodium are called natriuretic.
Classification of Diuretics
Diuretics are classified as following:
❑Osmotic diuretics
❑Carbonic anhydrase inhibitors
❑Thiazide diuretics
❑Loop diuretics
❑Potassium (K+)-sparing diuretics
Osmotic Diuretics

Osmotic diuretics do not interact with receptors and its activity is

dependent on development of osmotic pressure.
Mechanism of Action
❑An osmotic diuretic increases osmotic pressure specifically in
the proximal tubule and loop of Henle.
❑Increases H2O and Na+ excretion from body.
❑ Increases osmotic force in nephrons which prevents passive
reabsorption of H2O.
❑Osmotic diuretics are not reabsorbed.
Therapeutic uses of Osmotic Diuretic
Mannitol
Indications
❖It is infused to lower intracranial pressure.
❖ It is administered prophylatically for acute renal failure secondary to trauma, CVS
disease, surgery or nephrotoxic drugs.
❖It is also used for the short-term treatment of acute glaucoma.
❖Anuria
❖Pulmonary edema
Dosage and Route

Cerebral Edema

❑Reduction of intracranial pressure and treatment of cerebral edema.

❑1.5-2 g/kg intravenously (IV) infused over 30-60 minutes.

Edema, Pediatric

0.25-1 g/kg intravenously (IV) initially; maintenance dose of 0.25-0.5 g/kg IV every 4-6 hours.

Intraocular Pressure

1.5-2 g/kg intravenously (IV) infused over 30-60 minutes.

Anuria/Oliguria

❑Test dose: 200 mg/kg intravenously (IV) infused over 3-5 minutes.

❑ Load: 500-1000 mg/kg IV for 1 dose.

❑Maintenance: 250-500 mg/kg IV every 4-6 hours.

❑ Pediatric: Test dose: 0.2 g/kg IV over 3-5 minutes; not to exceed 12.5 g.
❑Discontinue if no diuresis within 2 hours.
Drug Interactions

❑Serious interactions

❑Tobramycin

❑Moderate interactions

❑Dichlorphenamide

❑Lurasidone
Side Effects
❑Headache, nausea, vomiting.
❑Hyponatremia.
❑Increased extracellular fluid volume.
Toxicity
Mannitol has the potential to exacerbate intracranial hypertension in individuals,
particularly children with hyperemia, which can be fatal. Mannitol, when taken
frequently, can infiltrate into the brain and cause cerebral edoema in the long
term.
Urea and Glycerol
❑Used as an osmotic diuretics. They also promote osmotic dieresis and filtered freely
from glomerulus and its reabsorption is less.
Indications
❑These agents reduce increased intraocular pressure and intracranial pressure.
Contraindications
❑Diabetics
❑Administered with caution to patients with hypervolaemia, cardiac failure, renal
disease or dehydration.
Route
❑Urea (ureaphil) administered intravenous
❑Glycerol given orally.
Carbonic Anhydrase Inhibitors

These agents have limited use as diuretics. It is prototype carbonic anhydrase inhibitor.
This drug is developed from sulfanilamide (which causes metabolic acidosis and

alkaline urine).
Mechanism of Action

It inhibits carbonic anhydrase in renal proximal tubule cells which decreases [H+] in
tubule lumen.

It reduces the formation of bicarbonate (HCO3-) from H2O and CO2.

Less H+ are available for Na+/H+ exchange for active transport system.
Indications

❑Used to treat chronic open-angle glaucoma.

❑ High aqueous Humor [HCO3-].

❑ Acute mountain sickness.

❑Prevention and treatment of metabolic alkalosis.

❑Sometimes in epilepsy treatment as adjunct to antiepileptics.

Side Effects and Adverse Effects

❑Increased HCO3 – excretion causes metabolic acidosis.

❑Drowsiness

❑Fatigue

❑CNS depression

❑Paresthesias (pins and needles under skin).

❑K+ wasting from body.

Toxicity

There have been reports of toxicity in a few cases in chronically receiving aspirin
therapy and patients undergoing hemodialysis. Symptoms of toxicity are lethargy,
confusion, fatigue, and incontinence.
Loop Diuretics

These loop diuretics are active in “loop” of Henle and also called high–ceiling agents.
This group of drugs causes more loss of fluid and electrolytes as compared to other
category of diuretics. These are very useful as their onset of action is rapid (diuresis
starts within 60 minutes and last for at least 2 hours).
Mechanism of Action
Dosage and Route

▪ Several loop diuretics come in IV and oral forms.

▪ Furosemide comes in oral tablet form in 20, 40, and 80 mg dosages. Injectable
solutions come in 10 mg/ mL doses. Oral solutions come in either 8 or 10 mg/ mL
doses.

▪ Torsemide comes in tablet form in 5, 10, 20, or 100 mg doses. Injectable solution is 10
mg/mL dosing.
Indications

❑Edema: cardiac, pulmonary or renal

❑Chronic renal failure or nephrosis

❑ Hypertension

❑ Hypercalcemia

❑Acute and chronic hyperkalemia

Contraindications
❑Anuria.
❑History of hypersensitivity to furosemide, bumetanide, or torsemide
(or sulfonamides).
❑Hepatic coma.
❑Severe states of electrolyte depletion.
Drug Interactions
Loop diuretics can interact with drugs such as amphotericin B, digoxin,
angiotensin-converting enzyme inhibitors (ACE inhibitors), antidiabetic
drugs, antifungal agents, dobutamine, gossypol and sotalol due to
diuretic associated hypokalemia.
Side Effects
❑Hypokalemia
❑Hyperuricemia
❑Metabolic alkalosis
❑ Hyponatremia
Toxicity

Diuretic toxicity can occur as electrolyte imbalances (hyponatremia,

hypokalemia, and hypocalcemia), acid/ base abnormalities
(hypochloremic alkalosis), and dehydration as a result of severe
diuresis.
Thiazide Diuretics

Thiazide diuretics are the class of drugs that inhibit reabsorption of 3% to

5% of luminal sodium in the distal convoluted tubule of the nephron. By
doing so, thiazide diuretics promote natriuresis and diuresis.

Three thiazide diuretics are as follow:

▪ Hydrochlorothiazide (HCTZ)

▪ Chlorthalidone

▪ Indapamide
Mechanism of action of thiazide
diuretics
Therapeutic Uses/Indications

❑Hypertension

❑Congestive heart failure

❑Hypercalciuria as they prevent excess Ca2+ excretion to form stones in

ducts.

❑Nephrogenic diabetes Insipidus.

❑Contraindication

❑Patients with anuria and sulfonamide allergies.

Drug interactions

❑Thiazide diuretics interact with corticosteroids and cause hypokalemia

and with digitalis it increase digitalis toxicity.

❑Cause lithium toxicity after interaction with lithium.

❑Decrease therapeutic effect of oral hypoglycemic agents.

Side Effects

• Hypokalemia: Most widely recognized, the first adverse effect of thiazide

diuretics is hypokalemia. Volume-contraction induced aldosterone release.

• Hyponatremia: It decreases sodium reabsorption and therefore decreased

fluid reabsorption; this directly causes decreased levels of circulating

sodium.
• Metabolic alkalosis

• Hyperuricemia

• Hypercalcemia

Toxicity
• Thiazides have a toxic effect on the pancreas and cause
• increased pancreatic secretions and pancreatic ischemia.
Potassium (K+) Sparing Diuretics

These drugs are called potassium sparing diuretics as they decrease

excretion of potassium and show modest increase in urine production.
They act by two mechanisms:

❑Aldosterone antagonists as they block aldosterone receptors.

❑Direct Na+ channel blockers and block ion exchange mechanism.

MECHANISM OF ACTION OF K+ SPARING
DIURETICS
Indications

❑ Primary hyperaldosteronism (adrenal adenoma, bilateral adrenal hyperplasia).

❑Congestive heart failure

❑Cirrhosis

❑ Nephrotic syndrome

❑ In conjunction with K+ wasting diuretics.

Contraindications

❑Anuria

❑Acute renal insufficiency

❑Marked renal impairment, and hyperkalemia.

Side/Adverse Effects

❑Hyperkalemia: monitor plasma [K+] level.

❑Spironolactone cause gynaecomastia.

❑Triamterene cause megaloblastic anemia in cirrhosis patients.

❑ Amiloride cause increase in blood urea nitrogen, glucose intolerance in

diabetes mellitus.

Drug Interactions

These drugs cause hyperkalemia after interacting with ACE inhibitors and
potassium supplements and increase lithium toxicity with lithium interaction.
 ANTIDIURETICS

Antidiuretic hormone (ADH) is secreted by posterior pituitary gland and acts on

kidneys. ADH is also called vasopressin. Two preparations of ADH are available

-vasopressin and desmopressin. Desmopressin is more effective as it has

prolonged action and is easy to administer and have less side affects especially
vasoconstriction.
Examples
❑Desmopressin (DDAVP) used intravenous.
❑Intranasal and SC, 10 microgram (0.1 mL)
❑Intranasal twice a day or 0.25- 0.5 ml Sc or IV twice daily.
❑Vasopressin (Pitressin)- 5-10 units IM /SC, 3-4 times daily for diabetes
insipidus.
❑For abdominal distension after surgery -5 units and followed by 10 units IM
every 3-4 hours for abdominal X-ray-10 units 2 hours before X-ray and again
30 min before the procedure.
Mechanism of Action
It acts on collecting tubules of kidneys and increase permeability to water and
increase water reabsorption and cause diuretic effect. ADH also stimulates
contraction of vascular smooth muscle and smooth muscles of GI tract and cause

vasoconstriction.
Indications
❑Diabetes insipidus (neurogenic).
❑Postoperative abdominal distension.
❑ Preparartion of abdominal X-ray.
❑Nocturnal enuresis- to reduce urine production.
❑Hemophilia A to increase production of clotting factor VIII.
❑Von Willebrand's disease- to increase production of clotting factor VIII.
Contraindications
❑ Known hypersensitivity
Drug Interaction

When used with carbamazepine, chlorpropamide, clofibrate,

fludrocortisone, TCAs, and urea, the antidiuretic action may be improved.

Drug Interaction

When used with carbamazepine, chlorpropamide, clofibrate,

fludrocortisone, TCAs, and urea, the antidiuretic action may be improved.
DRUGS TOXIC TO KIDNEY
Drugs which harm the kidneys are called nephrotoxic drugs. To avoid this,
following precautions should be
taken:
❑Always prescribe medicine carefully and count the days for administration of
medicine.
❑Renal function tests (RFT) should be done periodically.
❑ Monitor proteinuria.
❑Check urine output carefully.
 URINARY ANTISEPTICS

Urinary antiseptics are substances capable of killing agents causing urinary

tract infections or preventing them from spreading. While administering oral
doses, antibacterial concentration attained only in urinary tract. They are
infrequently used as other better drugs available.
Example

Nitrofurantoin (50 mg 304 times a day).

Indications

❑Urinary tract infection (UTI) acidifiers and alkalinizers.

❑ Choice of drug and length of treatment depends on the patient’s history

and the urine tests that identify the offending bacteria and drug sensitivity
test.
Contraindications

❑ Hypersensitivity to drug

❑ Person having oliguria, anuria, renal function disorder( decreased

creatinine clearance)

❑Pregnancy women during labor or near delivery date

❑ Neonates

❑Liver dysfunction
Other Drugs used in UTI

❑Quinolones: Norfloxacin and Ciprofloxacin are most popular drugs.

❑Sulfonamides

❑Cotrimoxazole

❑Piperacillin/Carbenicillin (serious UTI, Pseudomonas)

❑Gentamycin
 Role of a Nurse While Administrating Urinary Antiseptics

❑Teach the patient regarding measures for Urinary Tract Infection

(UTI).

❑Drink plenty of water every day.

❑Urinate when you feel the need, don’t resist the urge to urinate.

❑ Wipe from front to back to prevent bacteria around the anus from
entering the vagina or urethra.

❑Take showers instead of tub baths.

 TREATMENT OF UTI—ACIDIFIERS AND ALKALINIZERS

Some drugs alter the pH of urine and effect the excretion of acid and
bases. Agents that increase pH of urine (make the urine alkali) are called
alkalinizers and they promoteexcretion of acids from the body. Drugs
that decrease pH of urine (make the urine acidic)are called acidifiers and
they promote excretion of basesfrom the body.
Examples with mechanism of action

Acidifiers: Ammonium chloride and ascorbic acid acts as acidifier and

increase excretion of bases like amphetamines, phencyclidine. They are also
used to treat severe metabolic alkalosis.

Alkalinizers: Sodium bicarbonate make the urine more alkaline and reduce
the passive reabsorption of acids like aspirin, phenobarbital and increase their

excretion. Citralka (disodium hydrogen citrate) is a sodium salt of citric acid.

Acidifiers: Ammonium Chloride

Introduction

Ammonium chloride is an inorganic compound with the formula

NH4Cl. It is highly soluble in water producing mildly acidic solutions.

Mechanism of Action

Ammonium chloride increases acidity by increasing the amount of

hydrogen ion concentrations.
Indications

▪ Urinary acidifier in case of UTI.

▪ Metabolic alkalosis.

▪ Hypochloremic states.

Contradictions

▪ Severe impairment of renal or hepatic function.

▪ Metabolic alkalosis due to vomiting of hydrochloric acid is

accompanied by loss of sodium.
Adverse Effects

❑Pain or irritation at the site of injection or along the venous route.

❑ Fever, infection at the site of injection, venous thrombosis or phlebitis.

Toxicity

❑Overdosage can cause serious degree of metabolic acidosis, disorientation,

confusion and coma.
Acidifiers: Ascorbic Acid

Ascorbic acid, also known as vitamin C, is necessary for various metabolic

reactions.

Indications

Neutralization of alkali excess to reduce the pH value to its normal values.

Mechanism of Action

❑Absorption is through two mechanisms: simple diffusion and active

transport.

❑Two transporters are involved: SVCTs (sodium-dependent vitamin C

transporters) and hexose transporters.

❑The site for absorption is the distal small intestine and is regulated by renal
excretion. Usual dietary doses of up to 100 mg/day are almost completely
absorbed.
Contraindications

❑Blood disorders like thalassemia, G6PD deficiency sickle cell disease, and
hemochromatosis.

❑Avoid taking supplements immediately before or following angioplasty.

❑Diabetic patients should take vitamin C supplements with care as it raises

blood sugar levels.
Alkalinizer: Sodium Bicarbonate
Alkalinizers are the drugs used to neutralize pH of blood as pH decrease
due to metabolic acidosis. It is a chemical compound made of sodium
(Na+) and bicarbonate (HCO3-).
Indications
❑It controls acid base disorders by increase of serum bicarbonate ions.
It is used in patients with metabolic acidosis and chronic kidney
disease (CKD).
❑ To increase pH of urine up to 8 in order to increase the excretion of
salicylates or lithium and toxic substances from kidneys.
Contraindications

❑Patients with signs/symptoms or laboratory values indicating

underlying metabolic or respiratory alkalosis due to the potential for
exacerbation of symptoms.

❑Hypocalcemia.
Mechanism of Action

The main therapeutic effect of sodium bicarbonate administration is

increasing plasma bicarbonate levels, which are known to buffer excess
hydrogen ion concentration, thereby raising solution pH to combat

clinical manifestations of acidosis. Bicarbonate ions reach the renal

tubules intact, they will cause increases in urinary pH.
Adverse Effects

❑Metabolic alkalosis

❑Headache

❑Muscle pain and twitching

❑Nausea or vomiting

❑Bradypnea

❑Nervousness or restlessness

❑Unpleasant taste
Alkalinizers: Potassium Citrate and Citric Acid Oral Suspension

It is used to prevent formation of uric acid and cystine

kidney stones.

Mechanism of Action

After absorption, it metabolized to potassium bicarbonate and act as systemic alkalizer.

Indications

❑Burning micturation.

❑Urinary calculi wih cystinuria.

❑To make urine more alkaline.

Toxicity

If administered with ACE inhibitors, potassium sparing

diuretics and cardiac glycosides lead to toxicity.

Adverse Effects

❑Well tolerated if patient have normal kidney function.

❑In case of Potassium intoxication- weakness, mental confusion, tingling of

extremities, ECG changes.
Role of Nurse

❑Nurses should monitor serum electrolytes, including calcium, urinary pH,

and when indicated, arterial blood gases.

❑Observe any toxicity or side effects from its administration.

❑Administer the drug if the patient is inpatient or give instructions for

home administration for outpatient use and counsel regarding potential
adverse events.