RENAL SYSTEM

GROUP 2
ABOGADO
TUNGAL
PENTOY
KIDNEY

 Plays a very important role in the day today functioning of the body.
 It filters out toxic waste products from the blood while simultaneously
conserving essential substance.
NEPHRON

■ Maintain delicate balance between elimination of toxins and retention of

essential chemical.
■ Main structural unit of the kidney, and each kidney contains approximately one
million of them.
■ It is in the nephron where diuretic drugs exert their effect.
GLOMERULUS

■ Where the initial filtering of the blood takes place.

■ A cluster of capillaries surrounded by the glomerular capsule.
■ The rate at which this filtering occurs is refer to as the glomerular
filtration rate/GFR.
DIURETIC DRUGS
 CLASSIFICATION OF DIURETICS
CLASS DRUGS
Carbonic anhydrase inhibitors Acetazolamide, dichlorphenamide,
methazolamide
Loop Diuretics Bumetanide, Ethacrynic acid, furosemide,
Torsemide
Osmotic Diuretics Mannitol
Potassium-sparing diuretics Amiloride, spironolactone, triamterene
Thiazide and thiazide-like diuretics bendroflumethiazide, benzthiazide
diuretics
chlorthalidone, chlorothiazide,
hydrochlorothiazide,
hydroflumethiazide,
indapamide, methyclothiazide,
metolazone, polythiazide, trichlormethiazide
CARBON ANHYDRASE INHIBITORS

■ Are chemical derivatives of sulfonamide antibiotics.

■ Inhibit the activity of the enzyme carbonic anhydrase, which is found in the
kidney, eyes, and other parts of the body.
■ The site of action of the CAIs is the location of carbonic anhydrase enzyme
system along the nephron, primarily in the proximal tubule.
■ Acetazolamide, acts principally in the proximal tubule, which as previously
described is directly distal to the glomerulus.
MECHANISM OF ACTION AND DRUG EFFECTS

■ A specific active transport systems operates that exchanges sodium for

hydrogen ions.
■ Helps to make the hydrogens ions available for this exchange, when its
action are inhibited by a CAI such as acetazolamide, little sodium and
water can be resorbed into the blood and they are eliminated with the
urine.
■ Reduce the formation of hydrogen and bicarbonate ions from carbon
dioxide and water by the noncompetitive, reversible inhibition of
carbonic anhydrase activity.
■ Is beneficial in the prevention of certain seizure conditions.
■ May increase oxygenation during hypoxia by increasing
ventilation, cerebral blood flow and the dissociation of oxygen
from oxyhemoglobin, all of which is usually beneficial to the
patient.
■ They elevate the blood glucose level and cause glycosuria in
diabetic patients.
■ Enhanced potassium loss through the urine.
INDICATIONS

■ Used in the treatment of glaucoma, edema, epilepsy and high

altitude sickness.
■ Used principally as adjunct drugs in the long term management
of open-angle glaucoma that cannot be controlled by topical
miotic drugs or epinephrine derivatives alone.
■ Used short term in conjunction with miotics to lower
intraocular pressure in preparation for ocular surgery in
patients with acute ocular disorders.
CONTRAINDICATIONS

■ Contraindication to the use of CAIs include known drug

allergy and may include hyponatremia, hypokalemia, severe
renal or hepatic dysfunction, adrenal gland insufficiency, and
cirrhosis.
ADVERSE EFFECT

■ The more common undesirable effects of CAIs are metabiloc

abnormalities such as acidosis and hypokalemia.
■ These drugs may also cause drowsiness, anorexia, paresthesias,
hematuria, urticarial, photosensitivity, and melena (blood in the
stool).
INTERACTIONS

■ Significant during interactions that occur with CAIs include an

increase in digitalis toxicity when CAIs and digitalis are given
together, stemming from the hypokalemia that CAIs may
induce.
■ The concomitant use of CAIs and corticosteroids may also
cause hypokalemia, and their use with oral hypoglycemic
drugs and quinidine may induce greater activity or toxicity of
the latter drugs.
DOSAGES

■ For information on the dosages of acetazolamide, see the

following drug profile
Drug Profiles

Acetazolamide
Use of acetazolamide (Diamox) is contraindicated in the patients who
have shown a hypersensitivity to it and to sulfonamides, as well as in
those with significant liver or kidney dysfunction, low serum
potassium or sodium levels, acidosis, or adrenal gland failure.
Acetazolamide is available in both oral and parenteral forms. A
recommended dosage for pediatric patients is oral administration of 5
mg/kg/day. A common oral dosage for adults is 250 to 375 mg/day
given on alternate days. Pregnancy category C.
LOOP DIURETICS

■ Loop diuretics (bumetanide, ethacrynic acid, furosemide, and

torsemide) are very potent diuretics. Bumetanide, furosemide,
and torsemide are chemically related to the sulfonamides
antibiotics.
MECHANISM OF ACTION AND DRUG EFFECTS
■ Loop diuretics have renal, cardiovascular, and metabolic effects.
■ Their renal effects are their major mechanism of action.These
drugs act primarily along the thick ascending limb of the loop of
Henle, blocking chloride and, secondarily, sodium resorption.
■ They are also believed to activate renal prostaglandins, which
result in dilation of the blood vessels of the kidney, the lungs, and
the rest of the body(i.e., reduction in renal, pulmonary, and
systemic vascular resistance).
■ The beneficial hemodynamics effects of loop diuretics are a
reduction in both the preload and central venous pressures, which
are the filling pressure of the ventricles.
INDICATIONS

■ Used to manage the edema associated with heart failure and

hepatic or renal disease, to control hypertension, and to
increase the renal excretion of calcium in patients with
hypercalcemia.
■ As with certain other classes of diuretics, they may also be
indicated in cases of heart failure resulting from diastolic
dysfunction.
CONTRAINDICATIONS

■ Used of loop diuretics include known drug allergy and may

include allergy to sulfonamide antibiotics, hepatic coma, or
severe electrolyte loss.
 Loop Diuretics: Common Adverse Effects

Body System Adverse Effects

Central Nervous Dizziness, Headache, tinnitus, blurred

vision

Gastrointestinal Nausea, vomiting, diarrhea

Hematologic Agranulocytosis, Thrombocytopenia,

Neutropenia

Metabolic Hypokalemia, hypoglycemia,

hyperuricemia
 Loop Diuretics: Common Drug Interactions

Interacting Drug Mechanism Results

Aminoglycosides Additive Effect Increased neurotoxicity, specially

capreomycin auto toxicity.
Chloroqune
Vancomycin

Corticosteroids Hypokalemia Additive hypokalemia increased

sDigoxin digoxin toxicity

Lithium Decrease in renal excretion. Increased lithium toxicity

NSAID’S Inhibition of renal prostaglandins Decreased diuretic activity

Sulfonylureas Decreased in glucose tolerance Hyperglycemia.

 DOSAGES
Selected Loop Diuretics and Osmotic Diuretics
Drug Pharmacologic Class Usual dosage range Indications
Bumetanide Adult Edema
(Bumex) PO: 0.5-2 mg/day as a single
dose
IM/IV: 0.5-1 mg; may be
repeated at intervals of 2-3 hr
but do not exceed to a total
dose of 10mg/day
Ethacrynic acid Pediatric Iv: 1mg/kg/dose;
(Edecrin) max 3 mg/kg/day
PO: Initial dose 25 mg/day; 3
mg/kd.day
Adult IV: 0.5-1 mg/kg; max
200 mg/day
Furosemide (Lasix) Loop Diuretics Pediatric IM/IV: 1 mg/kg/dose; do not Heart Failure,
exceed 6 mg/kg/day Hypertension,
PO: 2mg/kg as a single dose; do not exceed 6 Renal failure,
mg/kg/day Pulmonary
Adult IM/IV 20-40 mg//dose; max 600 edema,
mg/day; administer high dose IV therapy as a cirrhosis
controlled infusion at a rate of 4 mg/mL or
less.
PO: 20-80 mg/day as a single dose.

Mannitol Osmotic Diuretic Adult IV infusion: 50-200 g/day 1.5-2 g/kg Renal failure,
(Resectisol, over 30-60 min Suggested loading dose of 25 abnormally high
Osmitrol) g, followed by an infusion rate to produce a intraoccular or
urine flow of at least 100 ml/hr intracranial
pressure. Drug
Intoxication (to
induce diuresis)

Torsemide Loop Diuretic Adult PO/IV: 20-200 mg once daily Edema

(Demadex)
OSMOTIC DIURETICS

■ The osmotic diuretics include mannitol, urrea, organic acids and glucose.
Mannitol, a nonabsorbable solute, is the most commonly used of these
drugs.
MECHANISM OF ACTION AND DRUG EFFECTS
■ Mannitol works along the entire nephron.
■ Because it is nonabsorbable, it produces osmotic pressure in the
glomerular filtrate, which in turn pulls fluid, primarily water, into the renal
tubules from the surrounding tissues.
■ Mannitol may induce vasodilation and in doing so increase both
glomerular filtration and renal plasma flow. This makes it an excellent
drug for preventing kidney damage during acute renal failure.
■ Often used to reduce intracranial pressure and cerebral edema resulting
from head trauma.
■ Mannitol may be tried when elevated intraocular pressure is unresponsive
to other drug therapies.
INDICATION
■ Used in the treatment of patients in the early, oliguric phase of acute renal
failure. For it to be effective in this setting however, enough renal blood
flow and glomerular filtration must still remain to enable the drug to reach
the renal tubules.
■ It can also be used to promote the excretion of toxic substances, reduce
intracranial pressure, and treat cerebral edema.
■ Can be used as a genitourinary irrigant in the preparation of patients for
transurethral surgical procedures and as supportive treatment to patients
with edema induced by other conditions.
CONTRAINDICATIONS
■ Known drug allergy
■ Severe Renal Disease
■ Pulmonary edema (loop diuretics are used instead)
■ Active intracranial bleeding
ADVERSE EFFECTS
■ Convulsions
■ Thrombophlebitis
■ Pulmonary Congestion

Less Significant Effects

■ Headaches
■ Chest Pains
■ Tachycardia
■ Blurred vision
■ Chills
■ Fever
INTERACTIONS

There are no drugs that interact significantly with mannitol.

DOSAGE
Drug Pharmacologic Usual Dosage Indications
Class Range
Mannitol (Resectisol, Osmotic Diuretic Adult IV infusion: 50- Renal failure,
Osmitrol) 200 g/day 1.5-2 g/kg abnormally high
over 30-60 min intraoccular or
Suggested loading dose intracranial pressure.
of 25 g, followed by an Drug Intoxication (to
infusion rate to produce induce diuresis)
a urine flow of at least
100 ml/hr