RENAL DRUGS  Major clinical use are in managing disorders involving:

Kidney Function in Disease o Abnormal fluid retention (edema)

1. Congestive Heart Failure o Elevated blood pressure (hypertension)
 decreased ability of failing heart to sustain adequate cardiac  Diuretics primarily prevent Na+ entry into the
output tubule cell.
 kidney responds as if there is hypovolemia - renal retention  Once a diuretic enters the tubule fluid, the nephron
of salt and water site at which it acts determines its effect.

2. Premenstrual edema
 result of imbalances in hormones such as estrogen excess
which facilitates loss of fluid in ECF

3. Hepatic Ascites
A. Blood flow in portal system often obstructed in cirrhosis 
elevates BP
 Colloid osmotic pressure of blood is decreased as result of
impaired plasma CHON synthesis by a diseased liver
 elevated BP + low osmolarity of blood  fluid escape
from portal system  abdomen
B. Secondary aldosteronism due to decreased ability of liver to
inactivate steroid hormone

4. Kidney disease
 damaged by disease, glomerular membranes allow plasma
CHONs to enter ultrafiltrate
 protein loss  edema
I. CARBONIC ANHYDRASE INHIBITORS (CAIs)
 low plasma volume  increased aldosterone  increased
retention of Na+ & fluid  aggravates edema  Mercurial Diuretics
 Prototype – Acetazolamide
Water & Diuretic Salts  Mechanism of action
 Water & various electrolytes/non-electrolytes act as diuretic o inhibits carbonic anhydrase  catalyzes dehydration of
agents when- in excess carbonic acid, H2CO3 , required for bicarbonate
 Water – true physiologic diuretic reabsorption
 blockade of carbonic anhydrase activity  induces
 High water intake permits excretion of drugs
a sodium bicarbonate diuresis, reducing body
Sodium salts
bicarbonate levels
 Restriction of salt intake – tx of edema
 Therapeutic uses:
 NaCl used primarily to tx deficits in ECF volume
o Glaucoma
 Decreases production of aqueous humor  reduces
Drugs Used in Renal Disorders
elevated intraocular pressure; most common use of
 Drugs that modify SALT excretion
Carbonic anhydrase inhibitors
o PCT  Carbonic Anhydrase Inhibitors
o Urinary alkalinization
o TAL  Loop Diuretics
 increasing urinary pH – enhances renal excretion of
o DCT  Thiazides
cystine and other weak acids - 2-3 day effect
o CD  K+ Sparing Diuretics
o Acute mountain sickness
 Drugs that modify WATER EXCRETION  used as prophylaxis - rapid ascent above 10,000 ft
o ADH Agonists – given nightly before ascent – cerebral and
o ADH Antagonists pulmonary edema
 Drugs that modify BOTH salt and water excretion o Metabolic alkalosis
o Osmotic Diuretics  alkalosis due to excessive use of diuretics in heart
failure
DIURETICS o Epilepsy
 Drugs inducing a state of increased urine flow  both grand mal & petit mal- reduces severity &
 Most diuretics act directly on the kidney with few magnitude of seizures- in conjunction with
exceptions on tubular antiepileptic medications to enhance action
 All diuretics except spironolactone exert their effects from o Hydrocephalus
the luminal side of the nephron  reduces the rate of CSF formation and decreases
 It is necessary for diuretics to get into the tubule fluid in cerebral spinal fluid pH
order to be effective
 Pharmacokinetics  Preparations Available
o well absorbed orally or topically o Bumetanide
o for glaucoma – applied topically 2-4x daily  oral: 0.5,1,2 mg tablets
 Adverse effects  parenteral: 0.5 mg/2ml ampule for IV/IM
o hyperchloremic metabolic acidosis - due to reduction of  oral dosage - 0.5-2 mg/daily dose
body bicarbonate stores o Ethacrynic acid
o potassium depletion, drowsiness and paresthesia; Hssn  oral: 25, 50 mg tablets
reaction  parenteral: 50 mg IV inj
 Preparations Available  oral dosage - 50-200 mg/daily dose
o Oral o Furosemide
 Acetazolamide (Diamox) tablet 250 mg 1-4x/d  oral: 20,40,80 mg tablets; 10 mg/ml sol
 Dichlorphenamide 50 mg 1-3x/d;  parenteral: 10 mg/ml for IM or IV inj; total daily
 Methazolamide 50-100 mg 2-3x/d dose – 20-80 mg
o Topical o Torsemide – total daily dose – 5-20 mg
 Dorzolamide ophthalmic drops 2%
 Brinzolamide ophthalmic drops B. Muzolomine
 New loop diuretic
II. LOOP DIURETICS  Longer half-life = 10-20 hours
 high ceiling diuretics  Effective in treatment of Advanced Renal Failure
 major action on Thick Ascending Limb of Loop of Henle  Withdrawn because of sever neurologic effects

A. Bumetanide, Furosemide, Torsemide(sulfonamide

derivative), Ethacrynic acid (non-sulfonamide)
 Mechanism of action
o inhibition of NaCl reabsorption in the thick ascending
limb of the loop of Henle à inhibit the Na/K/2Cl
transport system in the luminal membrane
o Most efficacious of diuretics, prompt onset
o increases Ca++ content of urine
o decreases renal vascular resistance
o increases renal blood flow
 Therapeutic Use:
o Edematous state
 drug of choice for reducing acute pulmonary
edema of Congestive Heart Failure; useful in
emergencies w/c calls for rapid intense diuresis
o Hypercalcemia
 stimulate tubular Ca++ excretion & therefore
useful in treating hypercalcemia
o Hyperkalemia
 enhance K+ excretion
o Acute renal failure
 increase urine flow and enhance K+ excretion
o Anion overdose
 in toxic ingestions of bromide, fluoride and iodide
 Pharmacology
o administered orally or IV; duration of action 1- 4 h;
eliminated unchanged by kidneys
 Adverse effects
o Hypokalemic metabolic alkalosis - K+ replacement and
correction of hypovolemia
o Ototoxicity - reversible
o Hyperuricemia – hypovolemia-associated enhancement
of uric acid reabsorption in Proximal tubule
o Hypomagnesemia- consequence of chronic use of loop
agents
o Allergic reactions – sulfonamides
III. THIAZIDE DIURETICS
 Most widely used; sulphonamide derivatives
A. Chlorothiazide - prototype
 Mechanism of Action
o Inhibition of NaCl reabsorption from the distal
convoluted tubule à increase Na+ & Cl- in tubular fluid
 Actions
o Increased excretion of Na+ & Cl-; loss of K+
o Decreased urinary Ca++ excretion
o Reduced peripheral vascular resistance
 Therapeutic Uses
o Hypertension; CHF; Nephrosis; Hypercalciuria;
Diabetes insipidus
 Pharmacology
o Orally given; Half-life = 40 h
o Excretion – kidney
 Adverse Effects:
o K depletion; hyperuricemia;hypercalcemia; volume
depletion; hyperglycemia, hypersensitivity reaction
B. Hydrochlorothiazide
 Thiazide derivative
 less ability to inhibit carbonic anhydrase
 more potent, less required dose, efficacy same
C. Chlorthalidone
 very long duration of action; used to treat HPN; given once
daily
D. Thiazide Analogues
 Metozalone
o more potent than thiazides; causes Na+ excretion in
advanced renal failure
 Indapamide
o nonthiazide diuretic; lipid soluble; shows significant
antihypertensive effect with minimal diuretic effect;
useful in patients with renal failure
 Toxicity: V. AGENTS THAT ALTER WATER EXCRETION
o Hypokalemic metabolic alkalosis and hyperuricemia A. OSMOTIC DIURETICS
o Impaired carbohydrate tolerance - hyperglycemia  Attributes
o Hyperlipidemia - 5-15% increase in total cholesterol o ability to carry water with them into the tubular fluid
and LDL o used to maintain urine flow following acute toxic
o Hyponatremia - due to combination of hypovolemia ingestion of substances
induced elevation of ADH, decreased diluting capacity  Mechanism of Action
of the kidney and increased thirst o osmotically inhibits Na & H2O reabsorption;
o Allergic reactions - hemolytic anemia, o reduction of pressure & volume of CSF
thrombocytopenia, acute necrotizing pancreatitis  Clinical Indications & Dosage
 Preparations Available o increase urine volume
o Chlorothiazide oral: 250, 500 mg tabs, parenteral:500  useful when Na+ retention limits response to
mg inj conventional agents
o Chlorthalidone (Hygroton) oral: 15,25,50,100 mg  mannitol 12.5 -25 g IV
tablets o reduction of intracranial and intraocular pressure
o Hydrochlorthiazide (Esidrix) 25,50,100 mg tabs  water leaves cells and decreases intracellular
o Indapamide (Lozol) oral: 1.25, 2.5 mg tablets volume
o Metozalone oral: 0.5, 2.5,5, 10 mg tabs  mannitol 1-2 g/ kg IV
 Undesirable effects
IV. POTASSIUM-SPARING DIURETICS o headache; nausea; vomiting; chills; dizziness;
A. Spirinolactone (Aldactone) polydipsia; lethargy; confusion; and chest pain
 Mechanism of Action  Pharmacokinetics
o synthetic aldosterone antagonist- competes with o given oral & IV
aldosterone for intracellular receptor sites  Contraindications
 Actions o Heart failure, hypertension
o elevated aldosterone levels – antagonized by o pulmonary edema
Spirinolactone  retention of K+ & excretion of Na+  Preparations
 Therapeutic Use o Mannitol, urea, glycerine
o Diuretic
 often in conjunction with a thiazide or loop diuretic B. ADH ANTAGONISTS
to prevent K+ excretion  Produces water diuresis in patients with water intoxication
o Conn's syndrome /2° hyperaldosteronism due to SIADH
 routinely used alone to induce net negative salt  Treatment of SIADH
balance o Restores concentration of Na in plasma to normal
 Pharmacokinetics within 5-14 days
o given orally; strongly bound to proteins converted to  Available as
active metabolite Canrenone o Conivaptan – 5 mg/ml IV
o has mineralocorticoid blocking activity o Demeclocycline at 600 – 1200 mg daily preparations:
 Adverse effects 150 mg tabs and capsules; 300 mg tabs
o gynecomastia – males
o menstrual irregularities – females C. ADH AGONISTS
o nausea; lethargy; hyperkalemia; mental confusion  Vasopressin and Desmopressin
o hyperchloremic metabolic acidosis o used in treatment of Central or pituitary diabetes
insipidus
B. Amiloride/Triamterene o peptide hormone released in response to increasing
 Inhibits Na+ influx through ion channels in the luminal plasma tonicity or falling blood pressure
membrane  Administered IV or IM, SQ & intranasally/orally
 Have diuretic activity even in Addison’s disease (desmopressin)
 frequently used in combination with other diuretics  Toxicity
 Adverse effects o headache, nausea, abd cramps, seizures
o leg cramps; increase BUN & uric acid; K+ retention
 Availability
o Amiloride (Midamor)
 oral: 5 mg tab
o Spirinolactone (Aldactone)
 25, 50,100 mg tab
o Triamterene (Dyrenium)
 50,100 mg tabs
VI. URICOSURIC AGENTS  Contraindications
 Drugs w/c Alter Excretion of Organic Molecules o known hypersensitivity, pregnancy and lactation -
containing Sulfamethizole
A. Probenecid o Methenamine – hepatic impairment
 lipid soluble derivative of benzoic acid o Nitrofurantoin – renal impairment
 inhibits reabsorption of urate in the proximal convoluted o Nalidixic acid – convulsive disorders
tubule  Interactions
 effect on Penicillin – inhibits its excretion thus increasing o Methenamine – decreased effect with antacids
plasma concentration o Nalidixic acid – increase effects with anticoagulants
 given orally, well absorbed in GIT, peak concentration – 3 h  Examples include Nalidixic acid, fosfomycin and
 90% bound to protein methenamine mandelate, nitrofurantoin,
 Actions:
B. Sulphinpyrazone o Nalidixic acid interfere with bacterial multiplication by
 congener of Phenylbutazone interfering with replication of DNA
 powerful inhibitory effects on uric acid reabsorption in PCT o Fosfomycin – inhibit bacterial cell wall synthesis
 absorbed in GIT o Nitrofurantoin maybe bacteriostatic or bactericidal
 highly protein bound depending on the concentration
*Indacrinone o Methenamine breakdown and form ammonia and
formaldehyde - bactericidal
 diuretic with uricosuric properties

VII. DRUGS WHICH ALTER pH of URINE

A. AGENTS WHICH INCREASE URINARY pH
 Na bicarbonate; Na or K citrate or other salts(acetate or
lactate)
o metabolized & cations are excreted with bicarbonate to
give an alkaline urine  alkalinization:
 Prevent certain drugs (e.g. sulfonamides) from
crystallizing out
 Decreases formation of uric acid & cystine stones
 Increases excretion of drugs w/c are weak
acids(salicylates & barbiturates)
 antibacterial effect
 decreases irritation or inflammation of urinary
tract
B. AGENTS WHICH DECREASE URINARY pH
 Ammonium chloride
o rarely used clinically except in specialized test for
Renal Tubular Acidosis
o metabolized to urea in liver leaving chloride/hydrogen
ion
o chloride displaces bicarbonate  Hyperchloremic
acidosis
o base-conserving mechanism
 H+ ion excreted in exchange for Na+, ammonia is
generated  acid urine

VIII. URINARY ANTI-INFECTIVES

 used in the treatment of UTIs, have effect on bacteria of the
urinary tract
 No significant levels and are of no value in treatment of
systemic infections
 Primarily excreted by the kidneys and exert major
antibacterial effects in the urine
 Use: for urinary tract infections