Group 7 - Pharmacology

DRUGS AFFECTING
THE RENAL SYSTEM
Abagat, Danna Jane Q.
Caracas, Lyra Dee S.
Laroya, Joebert E.
Sembrana, James Bond
THE RENAL SYSTEM
Also known as the urinary system, is a vital
physiological system that filters waste and
excess substances from the bloodstream,
regulates fluid and electrolyte balance, and
keeps blood pressure stable.

It functions to filter blood and urine. It is

composed of two kidneys, two ureters, a bladder,,
and a urethra.

The basic unit of the kidney is nephron. A

nephron has of a renal tubule and a renal
corpuscle. The renal corpuscle has glomerulus –
a tuft of capillaries, and an encompassing
Bowman's capsule.
THE RENAL SYSTEM
The glomerulus is the network (tuft) of filtering
capillaries located at the vascular pole of the
renal corpuscle in the Bowman's capsule. It
receives blood supply from an afferent arteriole
of the renal circulation.

Glomerular blood pressure causes water and

solutes to be filtered out of blood plasma to the
Bowman's space. The filtrate moves to the renal
tubule where excess waste and molecules are
removed or filtered. The renal tubule has a few
segments: thick and thin ascending limb, a thin
descending limb, loop of Henle, proximal
convoluted tubule, and a distal convoluted tubule
which empties to the collecting duct which
collects urine. The renal tubule secretes and
reabsorbs fluid and ions like sodium, potassium,
and chloride to maintain homeostasis.
 LOOP DIURETICS
Osmotic diuretics have major effect in the proximal
tubule and the descending limb of the loop of Henle.
Both are permeable to water. Osmotically active
agents filtered by the glomerulus but not reabsorbed
Loop diuretics are medications used in the management and treatment of fluid overload
causes water retention and promotes water diuresis.
conditions such as heart failure, nephrotic syndrome or cirrhosis, and hypertension, in
addition to edema.
MECHANISM OF ACTION
Loop diuretics induce its effect by competing with chloride
to bind to the Na-K-2Cl (NKCC2) cotransporter at the
apical membrane of the thick ascending limb of the loop of
Henle and blocking the cotransporter, which inhibits the
reabsorption of sodium and chloride. By inhibiting NaCl
reabsorption, tonicity in the interstitium decreases, and free
water excretion increases as a result. Blocking of the
NKCC2 cotransporter makes potassium unable to be
reabsorbed back into the lumen, which results in the loss of
calcium and magnesium ions.
ADMINISTRATION
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.
Bumetanide comes in oral tablets of 0.5, 1 and 2
mg doses. IV solution is 0.25 mg/mL.
Ethacrynic acid is available with oral tablets of 25
mg and in a powder form for injections at 50 mg.
ADVERSE EFFECT
hyponatremia
hypokalemia
metabolic alkalosis
dehydration
restlessness
headache
dizziness
vertigo
syncope.
interstitial nephritis
muscle soreness
CONTRAINDICATIONS
Contraindications to loop diuretics include:
Anuria
History of hypersensitivity to furosemide,
bumetanide, or torsemide (or sulfonamides)
Hepatic coma
Severe states of electrolyte depletion
FUROSEMIDE
BRAND NAME: LASIX
Furosemide reduces extra fluid in the body caused by
conditions such as heart failure, liver disease, and kidney
disease. This can lessen symptoms such as shortness of
breath and swelling in your arms, legs, and abdomen. This
drug is also used to treat high blood pressure. Furosemide is
a "water pill" (diuretic) that causes you to make more urine.
This helps your body get rid of extra water and salt.

Furosemide is indicated for the treatment of edema

associated with congestive heart failure, cirrhosis of the liver,
and renal disease, including the nephrotic syndrome, in adults
and pediatric patients.
INDICATIONS
Oral furosemide is indicated for the management of mild to moderate hypertension or
severe hypertension in combination with other antihypertensive medications.
Intravenous furosemide is indicated as adjunctive therapy in acute pulmonary edema
when a rapid onset of diuresis is desired.

PHARMACODYNAMICS
Furosemide manages hypertension and edema associated with congestive heart failure,
cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide is a potent loop
diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting
their reabsorption from the proximal and distal tubules, as well as the loop of Henle. It
works directly acts on the cells of the nephron and indirectly modifies the content of the
renal filtrate. Ultimately, furosemide increases the urine output by the kidney.
 MECHANISM OF ACTION
Furosemide promotes diuresis by blocking tubular reabsorption of sodium and chloride in the
proximal and distal tubules, as well as in the thick ascending loop of Henle. This inhibition
results in increased excretion of water along with sodium, chloride, magnesium, calcium,
hydrogen, and potassium ions. As with other loop diuretics, furosemide decreases the
excretion of uric acid.

Furosemide exerts direct vasodilatory effects, which results in its therapeutic effectiveness in
the treatment of acute pulmonary edema. Vasodilation leads to reduced responsiveness to
vasoconstrictors, such as angiotensin II and noradrenaline. It also leads to increased
production of prostaglandins with vasodilating properties. Furosemide may also open
potassium channels in resistance arteries. The main mechanism of action is independent of its
inhibitory effect on carbonic anhydrase and aldosterone.
DO NOT TAKE WHEN:
You are unable to urinate.

Using more than your recommended dose will not make

this medicine more effective. High doses of furosemide
may cause irreversible hearing loss.

Before using furosemide, tell your doctor if you have

kidney disease, enlarged prostate, urination problems,
cirrhosis or other liver disease, an electrolyte imbalance,
high cholesterol, gout, lupus, diabetes, or an allergy to
sulfa drugs.
 ROUTE, PEAK, ONSET, DURATION
Route: Oral and IV

Onset of Action:
Oral tablets: 1 to 2 hours.
Intravenous (IV) injection: usually within 5 minutes.

Peak Effect:
Oral tablets: within 1 to 2 hours.
Intravenous (IV) injection: usually within 30 minutes.

Duration of Action:
Generally around 4 to 6 hours, but this can vary among individuals.
In some cases, especially in patients with kidney dysfunction or certain medical
conditions, the duration of action may be shorter.
 THIAZIDE DIURETICS
Thiazide diuretics are drugs that causes natriuresis and diuresis. It
is commonly used to treat high blood pressure and manage edema.
Their primary function is to increase the excretion of sodium and
water in the urine, leading to reduced fluid volume in the body and
decrease in blood pressure.
 PROPERTIES
Pharmacokinetic
Pharmaceutic Pharmacodynamic
Thiazide diuretics exert their Thiazide diuretics
actions from the luminal side; inhibit the reabsorption
All thiazide diuretics
therefore they must be in the of 3% to 5% of luminal
are administered orally
lumen of the tubule to sodium in the distal
except Chlorothiazide
achieve their effect. They convoluted tubule of
which is also available
primarily enter the renal the nephron. By doing
for IV use.
tubule through secretion in so, thiazide diuretics
the proximal tubule via the promote natriuresis
organic acid co-transporter and diuresis.
CHLOROTHIAZIDE
BRAND NAME: DIURIL
Chlorothiazide is a thiazide diuretic used to treat hypertension and
edema caused by a variety of medical disorders, including
congestive heart failure, hepatic cirrhosis, and when patients are on
corticosteroid or estrogen therapy.

INDICATIONS
Edema from right-sided HF, mild to moderate left-sided HF, or
nephrotic syndrome; edema and ascites caused by hepatic
cirrhosis, HTN; diabetes insipidus, particularly nephrogenic
diabetes insipidus.
CONTRAINDICATIONS
Contraindicated in patients hypersensitive to these drugs and
in those with anuria.

Use cautiously in patients with severe renal disease, impaired

hepatic function, or progressive liver disease.

Use cautiously in pregnant women. Drugs appear in human

milk; patient should either discontinue breastfeeding or
discontinue drug.
ACTION
Like other thiazide, chlorothiazide promotes water loss from the body. It inhibits
Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. It also results
to loss of potasium and increase in serum uric acid.

ADVERSE REACTION
Therapeutic doses cause electrolyte and metabolic disturbances, most commonly
potassium depletion. Other abnormalities include elevated cholesterol levels,
hypercalcemia, hyperglycemia, hyperuricemia, hypochloremic alkalosis,
hypomagnesemia, hyponatremia, and photosensitivity.
Route: Oral and IV
Peak Onset Duration

IV: 30 min Initial effect: 2 hour

6-12 hour
PO: 4 hr Max effect: 4 hour
POTASSIUM-SPARING DIURETICS

Potassium-sparing diuretics are medications that help the body eliminate excess
sodium and water while preventing significant potassium loss. They are commonly
prescribed for conditions like hypertension and edema to promote urine production
without disrupting the body's potassium balance.
 MECHANISM OF ACTION

Potassium-sparing diuretics work by interfering with the

reabsorption of sodium in the kidneys, leading to
increased excretion of sodium and water while sparing
potassium. They achieve this by blocking aldosterone to
aid in sodium reabsorption in the renal tubules, ultimately
promoting diuresis (increased urine production) without
causing significant potassium loss.
SPIRONOLACTONE
BRAND NAME: ALDACTONE
Aldactone is a potassium-sparing diuretic that prevents your
body from absorbing too much salt and keeps your potassium
levels from getting too low. Aldactone is used to treat heart
failure, high blood pressure, or hypokalemia.

INDICATIONS
Edema due to HF, hepatic cirrhosis, or nephrotic syndrome; HTN; Diuretic-induced
hypokalemia; Detect and manage primary hyperaldosteronism; Severe HF (class III or
IV); NYHA HF (Class III or IV); Edema from hepatic cirrhosis.
Route: PO
Peak Onset Duration

3 - 4 hrs.
Unknown 2 - 3 days
2 1/2 - 5 hrs
 ADVERSE REACTIONS
CNS: headache, drowsiness, lethargy, confusion, ataxia.

GI: diarrhea, gastric bleeding, ulceration, cramping, gastritis, vomiting.

GU: renal failure, inability to maintain erection, menstrual disturbances, postmenopausal

bleeding.

Hematologic: agranulocytosis.

Metabolic: hyperkalemia, dehydration, hyponatremia, mild acidosis.

Skin: urticaria, hirsutism, maculopapular eruptions.

Other: anaphylaxis, gynecomastia, breast soreness, drug fever.

 CONTRAINDICATIONS
• Use only for conditions for which it's indicated. Drug has been shown to be tumorigenic in
long-term toxicity studies in rats. Avoid unnecessary use.

• Contraindicated in patients hypersensitive to drug and in those with anuria, Addison disease,
or hyperkalemia.

• Use cautiously in patients with fluid or electrolyte imbalances and in those with impaired renal
or hepatic function.

• Spironolactone should be initiated in a hospital setting for patients with hepatic disease with
cirrhosis and ascites. It can cause fluid and electrolyte disturbances, and impair neurologic
function.
 NURSING CONSIDERATIONS
• Monitor electrolyte levels, fluid intake and output, weight, and BP closely.
• Monitor elderly patients closely, who are more susceptible to excessive diuresis.
• Inform laboratory that patient is taking spironolactone because drug may interfere with
tests that measure digoxin level.
• Drug is less potent than thiazide and loop diuretics and is useful as an adjunct to other
diuretic therapy. Diuretic effect is delayed 2 to 3 days when used alone.
• Maximum antihypertensive response may be delayed for up to 2 weeks.
• Watch for hyperchloremic metabolic acidosis, especially in patients with hepatic cirrhosis.
• Look alike–sound alike: Don't confuse Aldactone with Aldactazide.
 OSMOTIC DIURETICS
Osmotic diuretics have major effect in the proximal tubule and the descending limb of
the loop of Henle. Both are permeable to water. This diuretic inhibits sodium and water
reabsorption, and increases urine production.

A nonreabsorbable solute like Mannitol prevents normal water absorption by causing a

countervailing osmotic force which results to increase in urine volume. This decreases
sodium and water reabsorption. The resulting natriuresis (excretion of sodium in urine)
is of lesser magnitude than water diuresis leading to excessive water loss and
hypernatremia, hence mannitol is considered as an aquaretic diuretic.
 PROPERTIES
Pharmacokinetic
Pharmaceutic Osmotic diuretics
Pharmacodynamic
inhibit water
reabsorption in the
Osmotic diuretics help
proximal convoluted
Osmotic diuretics are lower swelling in the
tubule and the thin
mainly administered brain or eye and
descending loop of
intravenously. increases the urine
Henle and collecting
output.
duct, regions of the
kidney that are highly
permeable to water.
 MANNITOL
BRAND NAME: OSMITROL

Mannitol is an osmotic diuretic that is metabolically inert in

humans and occurs naturally, as a sugar or sugar alcohol, in fruits
and vegetables. Mannitol elevates blood plasma osmolality, resulting in
enhanced flow of water from tissues, including the brain and cerebrospinal fluid,
into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial
pressure, and cerebrospinal fluid volume and pressure may be reduced. Mannitol
may also be used for the promotion of diuresis before irreversible renal failure
becomes established; the promotion of urinary excretion of toxic substances; as an
Antiglaucoma agent; and as a renal function diagnostic aid.
Route: IV
Peak Onset Duration

Onset varies but is

Generally reached
relatively quick upon Typically short-lived
within 15-30 minutes.
administration.
 OSMOTIC DIURETICS
CARBONIC ANHYDRASE INHIBITORS
Osmotic diuretics have major effect in the proximal
Carbonic anhydrase inhibitors (CAIs) treat excessive fluid buildup or alterations in
tubule and the descending limb of the loop of Henle.
pH balance within the body. Carbonic anhydrase is an enzyme found in multiple
Both are
tissues, including permeable
the kidneys, eyes,to
andwater. Osmoticallytract.
the gastrointestinal active
Inhibiting this
agents
enzyme filtered
leads by the
to reduction glomerulus
in the production but not reabsorbed
of bicarbonate ions, which
subsequently
causes affects theand
water retention body's pH and fluid
promotes regulation.
water diuresis.
 PROPERTIES
Pharmaceutic
Carbonic anhydrase inhibitors can be administered via oral tablets,
ophthalmic solutions, and intravenous preparations, depending on the
specific medical condition being treated. For instance, oral tablets are
commonly used to manage conditions like glaucoma and altitude sickness,
while intravenous preparations may be used in cases of metabolic acidosis.

Those administered orally are available in slow-release forms to provide

sustained therapeutic effects and minimize side effects. For ophthalmic
use, carbonic anhydrase inhibitors are formulated as eye drops to reduce
intraocular pressure.
 PROPERTIES
Pharmacokinetic
Most oral CAIs are well-absorbed by the gastrointestinal tract.
Carbonic anhydrase inhibitors are distributed throughout the body,
with different agents having varying tissue penetrance. Some CAIs, like
dorzolamide (used in eye drops), have specific tissue distribution
primarily targeting the eye. Many CAIs undergo minimal metabolism in
the liver. Instead, they are excreted primarily unchanged in the urine.
Renal elimination is a major route of excretion for CAIs.
 PROPERTIES
Pharmacodynamic
Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase,
particularly the isoform CA-II. This inhibition leads to the hindering of
conversion of carbon dioxide and water to bicarbonate ions. This
reduces the amount of bicarbonate available in the body causing in a
decrease in hydrogen ion secretion, affecting pH balance. In addition,
when CAI is used in glaucoma, reduces intraocular pressure by
decreasing aqueous humor production.
ACETAZOLAMIDE
BRAND NAME : DIAMOX

Indications: For treatment of edema due to congestive heart failure;

drug-induced edema; centrencephalic epilepsies; and glaucoma.

Pharmacodynamics: Acetazolamide is a potent carbonic anhydrase

inhibitor, effective in the control of fluid secretion, in the treatment of
certain convulsive disorders and in the promotion of diuresis in
instances of abnormal fluid retention. Acetazolamide is not a
mercurial diuretic. Rather, it is a non-bacteriostatic sulfonamide
possessing a chemical structure and pharmacological activity
distinctly different from the bacteriostatic sulfonamides.
Route: PO
Peak Onset Duration
Depends on the
specific condition
Generally reached being treated. For
within 2 to 4 hours glaucoma, a reduction
8-12 hours
after oral in intraocular pressure
administration. (IOP) may begin within
1-2 hours after oral
administration.
ACETAZOLAMIDE
BRAND NAME : DIAMOX

Contraindications:
1. Severe Liver or Kidney Dysfunction:
Patients with severe liver or kidney dysfunction may be at an increased risk of
adverse effects, and acetazolamide should be used cautiously or avoided.
2. Adrenal Gland Dysfunction:
Individuals with adrenal gland dysfunction may experience an exacerbation of
their condition with the use of acetazolamide.
3. Electrolyte Imbalance:
Acetazolamide can affect electrolyte levels, and its use may not be
recommended in individuals with certain electrolyte imbalances.
ACETAZOLAMIDE
BRAND NAME : DIAMOX
Adverse Effects:
1. Common Adverse Effects:
These may include fatigue, dizziness, lightheadedness, increased urination, and changes in
taste.
2. Gastrointestinal Issues:
Nausea, vomiting, and diarrhea have been reported in some individuals.
3. Metabolic Acidosis:
Acetazolamide can lead to an increase in the acidity of the blood (metabolic acidosis), which
may cause symptoms such as rapid breathing, confusion, and lethargy.
4. Electrolyte Imbalances:
This medication may lead to disturbances in electrolyte levels, including low potassium levels
(hypokalemia) or sodium levels (hyponatremia).
5. Hematologic Effects:
Rarely, blood disorders such as agranulocytosis and aplastic anemia have been reported.
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