PHARMACOLOGY

PART 9 Drugs Acting on the Renal System

1. Introduction to the Renal System
➢ The renal system is composed of the kidneys and the structures of the urinary tract: the ureters, the
urinary bladder, and the urethra. This system has four major functions in the body:
o Maintaining the volume and composition of body fluids within normal ranges, including the
following functions:
▪ clearing nitrogenous wastes from protein metabolism
▪ maintaining acid–base balance and electrolyte levels
▪ excreting various drugs and drug metabolites
o Regulating vitamin D activation, which helps to maintain and regulate calcium levels
o Regulating blood pressure through the renin– angiotensin–aldosterone system
o Regulating red blood cell production through the production and secretion of erythropoietin
➢ The functional unit of the kidneys is called the nephron; it is composed of Bowman’s capsule, the
proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct.
➢ The blood flow to the nephron is unique, allowing autoregulation of blood flow through the
glomerulus.
➢ Sodium levels are regulated throughout the tubule by active and passive movement and are fi ne
tuned by the presence of aldosterone in the distal tubule.
➢ The countercurrent mechanism in the medullary nephrons allows for the concentration or dilution of
urine under the influence of ADH secreted by the hypothalamus.
➢ Potassium concentration is regulated throughout the tubule, with aldosterone being the strongest
influence for potassium loss.
➢ The kidneys play a key role in the regulation of calcium by activating vitamin D to allow GI calcium
reabsorption and by reabsorbing or excreting calcium from the tubule under the influence of PTH.
➢ The kidneys influence blood pressure control, releasing renin to activate the renin–angiotensin
system, which leads to increased blood pressure and volume and a resultant increased blood flow to
the kidney. The balance of this reflex system can lead to water retention or excretion and has an
impact on drug therapy that promotes water or sodium loss.
➢ The ureters, urinary bladder, and urethra make up the rest of the urinary tract. The longer male
urethra passes through the prostate gland, which may enlarge or become infected, a problem often
associated with advancing age.

2. Diuretic Agents
➢ Diuretics—drugs that increase the excretion of sodium, and therefore water, from the kidneys—are
used in the treatment of edema associated with HF and pulmonary edema, liver failure and cirrhosis,
and various types of renal disease, and as adjuncts in the treatment of hypertension.
➢ Classes of diuretics differ in their site of action and intensity of effects. Thiazide diuretics work to block
the chloride pump in the distal convoluted tubule. This effect leads to a loss of sodium and potassium
 and a minor loss of water. Thiazides are frequently used alone or in combination with other drugs to
treat hypertension. They are considered to be mild diuretics.
➢ Loop diuretics work in the loop of Henle and have a powerful diuretic effect, leading to the loss of
water, sodium, and potassium. These drugs are the most potent diuretics and are used in acute
situations, as well as in chronic conditions not responsive to milder diuretics.
➢ Carbonic anhydrase inhibitors work to block the formation of carbonic acid and bicarbonate in the
renal tubule. These drugs can cause an alkaline urine and loss of the bicarbonate buffer. Carbonic
anhydrase inhibitors are used in combination with other diuretics when a stronger diuresis is needed,
and they are frequently used to treat glaucoma because they decrease the amount of aqueous humor
produced in the eye.
➢ Potassium-sparing diuretics are mild diuretics that act to spare potassium in exchange for the loss of
sodium and water in the urine. These diuretics are preferable if potassium loss could be detrimental
to a patient’s cardiac or neuromuscular condition. Patients must be careful not to become
hyperkalemic while taking these drugs.
➢ The osmotic diuretic mannitol uses hypertonic pull to remove fluid from the intravascular spaces and
to deliver large amounts of water into the renal tubule. There is a danger of sudden change of fluid
volume and massive fluid loss with this drug. This drug is used to decrease intracranial pressure, to
treat glaucoma, and to help push toxic substances through the kidney.
 3. Drugs Affecting the Urinary Tract and Bladder
➢ Urinary tract anti-infectives include two groups of drugs: antibiotics that are particularly effective
against gram-negative bacteria, and drugs that work to acidify the urine, ultimately killing the bacteria
that might be in the bladder.
➢ Many activities are necessary to help decrease the bacteria in the urinary tract (e.g., hygiene
measures, proper diet, forcing fluids) to facilitate the treatment of UTIs and help the urinary tract anti-
infectives be more effective.
➢ Inflammation and irritation of the urinary tract can cause smooth muscle spasms along the urinary
tract. These spasms lead to the uncomfortable effects of dysuria, urgency, incontinence, nocturia, and
suprapubic pain.
➢ The urinary tract antispasmodics act to relieve spasms of the urinary tract muscles by blocking
parasympathetic activity and relaxing the detrusor and other urinary tract muscles. The urinary tract
analgesic phenazopyridine is used to provide relief of symptoms (burning, urgency, frequency, pain,
discomfort) related to urinary tract irritation resulting from infection, trauma, or surgery.
➢ Pentosan polysulfate sodium is a heparin-like compound that has anticoagulant and fibrinolytic
effects and adheres to the bladder wall mucosal membrane to act as a buffer to control cell
permeability. This action prevents irritating solutes in the urine from reaching the cells of the bladder
wall. It is used specifically to decrease the pain and discomfort associated with interstitial cystitis.
➢ BPH is a common enlargement of the prostate gland in older men.
➢ Drugs frequently used to relieve the signs and symptoms of prostate enlargement include alpha-
adrenergic blockers, which relax the sympathetic effects on the bladder and sphincters, and
finasteride and dutasteride, which block the body’s production of a powerful androgen. The prostate
is dependent on testosterone for its maintenance and development; blocking the androgen leads to
shrinkage of the gland and relief of symptoms.
Reference:
Karch, A. M. (2013). Focus on nursing pharmacology. Sixth edition. Philadelphia: Wolters Kluwer.