PHARMACOLOGY ASSIGNMENT

MODULE :URIsNARY SYSTEM

Q1.CLASSIFY THE VARIOUS DIURETICS ALONG WITH DRUG EXAMPLES
(ALL DRUGS IN EACH GROUP):

1. CARBONIC ANHYDRASE INHIBITORS:

 ACETAZOLAMIDE
 METHAZOLAMIDE
 EHOXZOLAMIDE
 BRINZOLAMIDE
 DORZOLAMIDE
 DICHLORPHENAMIDE
 LODOXAMIDE

2.LOOP DIURETICS :
 FUROSEMIDE
 TORSEMIDE
 ETHACRYNIC ACID
 BUMETANIDE

3.THIAZIDE DIURETICS :
 HYDROCHLOROTHIAZIDE
 B ENZTHIAZIDE
 BENDROFLUMETHAIZIDE
 HYDROFLUMETHIAZIDE

THIAZIDE LIKE DIURETICS :

 CLORTHALIDONE
 INDAPAMIDE
 CLOPAMIDE
 XIPAMIDE

4.POTASSIUM SPARRING DIURETICS :

ALDOSTERONE ANATOGNISTS :
 SPIRINOLACTONE
 EPLERENONE
ENaC BLOCKERS :
 TRIAMTERENE
 AMILORIDE

5.OSMOTIC DIURETICS :
 MANNITOL
 UREA
 ISOSORBIDE
 GLYCERINE

Q2.WHAT ARE THE SITES AND MECHANISM OF ACTION :

1.FUROSEMIDE :

SITE OF ACTION :
THICK ASCENDING LIMB OF LOOP OF HEENLE (NA_K_2Cl CHANNEL BLOCKER )

MECHANISM OF ACTION :
FUROSEMIDE BLOCKS THE SODIUM POTASSIUM TWO CHLORIDE CHANNEL IN THICK ASCENDING LIMB
OF LOOP OF HENLE INHIBITING THE REABSORPTION OF SODIUM ,POTASSIUM AND CHLORIDE BACK
INTO THE CELL.AS THE POTASSIUM DIFFUSION CEASES ,THE LUM INAL MEMBRANE WOULD NOT
BECOME POSITIVE THAT IS THE DRIVING FORCE FOR THE REABSORPTION OF DIVALENT CATIONS
.THUS ,FUROSEMIDE INCREASES THE EXCRETION OF SODIUM ,POTASSIUM,MAGNESIUM AND CALCIUM
IN THE URIINE .

 LOSS OF SODIUM AND WATER

 HYPOKALEMIC METABOLIC ALKALOSIS
 DIVALENT CATION LOSS
2,HYDROCHLOROTHIAZIDE:

SITE OF ACTION:
DISTAL CONVOLUTED TUBULE(NA Cl CHANNEL BLOCKER)

MECHANISM OF ACTION :
IT INHIBITS THE SODIUM CHLORIDE CHANEEL IN DISTAL CONVOLUTED TUBULE THUS PREVENTING THE
REABSORPTION OF SODIUM AND CHLORIDE .UNDER THE ACTION OF PARATHYROID HORMONE .TRPV5
CHANNEL REABSORBS THE CALCIUM ON THE LUMINAL MEMBRANE .AT THE BASOLATERAL
MEMBRANE ,SODIUM CALCIUM COUNTERTRASNPORT OCCURS .

 LOSS OF SODIUM AND WATER

 HYPOKALEMIC METABOLIC ALKALOSIS
 LOW SODIUM FACILITATES THE REABSORPTION OF CALCIUM BY SODIUM CALCIUM
EXCHANGER .
3.SPRINOLACTONE :

SITE OF ACTION :
ALDOSTERONE RECEPTORS

MECHANISM OF ACTION :
IT IS A STEROID DRUG .IT BINDS TO THE COMPETETIVELY BINDS TO THE ALDOSTERONE RECEPTOR
,HENCE DOWNREGULATION THE ENaC CHANNELS AND THE SODIUM POTASSIUM ATPASE PUMPS .

 LOSS OF SODIUM AND WATER

 HYPERKALEMIA
 ACIDOSIS
CARBONIC ANHYDRASE INHIBIRORS :

SITE OF ACTION :PROXIMAL CONVOLUTED TUBULE

MECHANISM OF ACTION :
IT INHIBITS THE CARBONIC ANHYDRASE INHIBITOR THUS HALTING THE CONVERSION OF CATBONIC ACID
INTO BICARBONATE AND HYDROGEN IONS .IT PREVENTS THE REABSORPTION OF SODIUM IONS AT
APICAL MEMBRANE AS HYDROGEN IONS ARE IMPORTANT FOR THE REABSORPTION OF SODIUM AT
APICAL MEMBRANE AND BICARBONATE IONS ARE IMPORTANT FOR THE REABSORPTION OF SODIUM AT
THE BASOLATERAL MEMBRANE .
OSMOTIC DIURETICS :

SITE OF ACTION :PROXIMAL CONVOLUTED TUBULES

MECHANISM OF ACTION :
OSMOTIC DIURETICS ARE PHARMACOLOGICALLY INERT SUSBSTANCES THAT ARE EXCRETED FROM THE
GLOMERULAR FILTRATION WITHIN 30 TO 60 MINUTES .WITHOUT ANY REABSORPTION OR SECRETION
.THEY CAUSE A HIGH OSMOLARITY IN PROXIMAL CONVOLUTED TUBULES THUS HAVE A AQUARETIC
EFFECT .

 LOSS OF WATER
 DECRASE EXTRACELLULAR VOLUME

HYPERNATREMIA
COMPARE THE CLINICAL USES AND ADVERSE EFFECTS OF VARIOUS DIURETICS
:
LOOP DIURTICS :

CLINICAL USES :
 EDEMA(RENAL,HEPATIC,CARDIAC)

 ACUTE PULMONARY EDEMA(AFTERLVF FOLLOWING MI)

 HYPERTENSION (HYPERTENSIVE EMERGENCIES 0
 HYPERCALCIMIA OF MALIGNANCY
 CEREBRAL EDEMA

ADVERSE EFFECTS ;
 HYPERURICEMIA(EXCEPT ETHACRYNIC ACID)
 OTOTOXICITY
 HYPOKALEMIC METABOLIC ALKALOSIS
 DEHYDRATION
 ALLERGIC MANIFESTATIONS
  HYPOCALCEMIA AND HYPOMAGNESEMIA
 DEHYDRATION

THIAZIDE DIURETICS :

CLINICAL USES:
 EDEMA(RENAL,HEPATIC,CARDIAC)
 HYPERTENSION
 NEPHROLITHIASIS(IDIOPHATIC CALCIURIA)
 HYPOCALCEMIA

ADVERSE EFFECTS :
 HYPERGLYCEMIA

HYPERURICEMIA
 DEHYDRATION
 HYPOKALEMIC METABOLIC ALKALOSIS
 HYPERLIPIDEMIA
 HYPONATREMIA
 ALLERGIC MANIFESTATIONS (DUE TO SULFONAMIDE RELATED DRUGS )

CARBONIC ANHYDRSE INHIBITORS :

CLINICAL USES :
 ACUTE MOUNTAIN SICKNESS
 EPILEPSY
 GLAUCOMA
 METABOLIC ALKALOSIS

ADVERSE EFFECTS :
 DROWSINESS AND PARERSTHESIA
 HYPOKALEMIC METABOLIC ACIDOSIS
 CROSS AllERGENECITY
 ALKALINIZATION OF URINE LEADS TO NEPHROLITHIASIS

OSMOTIC DIURETICS :

CLINICAL USES :
 PROPHYLAXIS FOR RENAL SHUTDOWN(TO INCREASE THE URINE VOLUME)
 TO REDUCE THE INTRACRANIAL AND INTRAOCULAR PRESSURE
ADVERSE EFFECTS :
 EXTRACELLULAR VOLUME EXPANSION ANF HYPONATREMIA
 DEHYDRATION AND HYPONATEMIA

POTASSIUM SPARRING DIURETICS :

CLINICAL USES :
 NEPHROTIC SYNDROME
 CIRRHOSIS
 CHF
 CONDITIONS IN WHICH EXCESSIVE ALDOSTERONE SECRETION OCCURS

ADVERSE EFFECTS :
 HYPERKALEMIA
 ACIDOSIS
 GYNECOMASTIA
 IMPOTENCE

4. Compare the effects of above mentioned diuretics on serum and urinary

electrolytes and PH changes.

1.LOOP DIURETICS:
THESE DRUGS INCREASES THE EXCRETION OF SODIUM ,POTASSIUM ,CALCIUM AND MAGNESIUM
,HENCE THEY CAUSE HIGH LEVELS OF THSE ELECTROLYTES IN URINE AND CAUSES THE
HYPONATREMIA,HYPOMAGNESEMIA AND HYPOCALCEMIA AS WELL AS DEHYDRATION .THE PH OF
BLOOD RAISES DUE TO HYPOKALEMIC MRTABOLIC ALKALOSIS .

2,THIAZIDE DIURETICS :
THESE DRUGS ALSO INCREASES THE EXCRETION OF SODIUM ,CHLORIDE ,HENCE INCREASING THESE
ELECTROLYTES IN URINE AND CAUSING HYPONATREMIA IN SERYM .IT CAUSES DIFFUSION OF CALCIUM
THROUGH TRPV5 ,HENCE CAUSING HYPERCALCEMIA IN SERUM .IT ALSO CVAUSES HYPOKALEMIC
ALKALOSIS .

3.CARBONIC ANHYDRASE INHIBITORS :

THEY INCREASES THE CONCENTARION OF SODIUM AND POTASSIUM IN THE URINE .

THEY CAUSE HYPOKALEMIC METABOLIC ACIDOSIS .

4.OSMOTIC DIURETICS :
IT INCREASES THE OSMOLARITY OF LUMEN FLUID AND CAUSES LOSS OF WATER AND HYPERNATREMIA .

5.POTASSIUM SPARRING DFIURETICS :

IT CAUSES SODIUM AND WATER LOSS .IT CAN CAUSE HYPERKALEMIAS AS WELL AS ACIDOSIS ,HENCE
DECREASING THE SERUMS PH .
Q5.DESCRIBE THE DRUG DRUG INTERACTION AND THE CONTRAINDICATIONS
OF FUROSEMIDE .

FUROSEMIDE INTERACTIONS :

1.LITHIUM TOXICITY :
FUROSEMIDE INTERFERE THE RENAL CLEARANCE OF LITHIUM CAUSING LITHIUM TOXICITY .

2.AMINOGLYCOSIDES AND CEPHALOSPORIN ANTIBIOTICS :

FUROSEMIDE SHOULDN’T BE PRESCRIBED WITH AMINOGLYCOSIDES AND CEPHALOSPORIN ANTIBIOTICS
AS IT ENHANCES THE OTOTOXIC POTENTIAL OF THESE DRUGS .

3.NSAIDS:
NSAIDS INTERFERES WITH THE ACTION OF LOOP DIURETICS AS THEY INHIBITS THE PROSTAGLANDIN
SYNTHESIS .

CONTRAINDICATION OF FUROSEMIDE :
TETRATOGENIC(CONTAINDICATED IN PREGNANCY)

Q6.LIST THE VARIOUS DRUGS USED IN THE TREATMENT OF OVERACTIVE BLADDER .

ANTIMUSCARINIC RECEPTOR ANATAGONISTS :

TERTIARY AMINES :
 OXYBUTYNIN
 TRANSDERMAL OXYBYTYNIN
 FLAVOXATE
 DAREFENACIN
 SOLEFENACIN
 TOLTERODINE
 HYOSYCAMINE
 PROPIVERINE HYDROCHOLRIDE

QUATERNARY AMINES :
 TROSPIUM
 PROPANTELINE
B 3 ADRENERGIC RECEPTOR AGONISTS :
 MIRABEGRON

7. Describe the mechanisms (along with the description of receptors) of

various drugs used to control urinary symptoms.
ANTIMUSCARINIC RECEPTOR ANATAGONIST:
THESE DRUGS COMPETETIVELY INHBIT THE MUSCARNIC RECEPTOR OF THE DETRUSOR MUSCLE ,HENCE
RELAXING THE OVERACTIVE DETRUSOR MUSCLE .

B 3 ADRENERGIC RECEPTOR AGONIST :

THESE DRUGS STIMULATE THE B 3 ADRENERGIC RECEPTOR OF THE DETRUSOR MUSCLE HENCE CAUSING
THE RELAXATION OF THE OVERACTIVE BLADDER .

8. Describe the adverse effects of the drugs used in the treatment of over-
active bladder.?

ADVERSE EFFECTS OF ANTIMUSCARINIC ANTAGONISTS:

 BLURRED VISION
 DRY MOUTH AND CONSTIPATION
 TACHYCARDIA
 IMPAIRS COGNITION AND MEMORY (MORE WITH TERTIARY AMINES)

THESE ADVERSE EFFECTS OCCURS DUE TO THE STIMULATION OF M 3 RECEPTORS PRESENT IN OTHER
ORGANS APART FROM BLADDER .

ADVERSE EFFECTS OF B 3 ADRENERGIC RECEPTORS :

 HYPERTENSION
 RETENSION OF URINE
 HEADACHES
 TACHYCARDIA
 DRY MOUTH AND CONSTIPATION (LESS COMMON)

9. Enlist the agents used as uricosuric drugs.

1.URATE LOWERING FRUGS :

 SULFINPYRAZONE
 BENZBROMARONE
 PROBENECID
 LOASARTAN
 FENOFIBRATE
2.XANTHINE OXIDASE INHIBITORS :
 ALLUPURINOL
 XANTHINE OXIDASE

3.PEGLOCTICASE (BIOTECHNOLOGICALLY SYNTHESIZED URATE OXIDASE OR

URICASE )

10. Describe the mode of action (with target sites) and adverse effects of
uricosuric drugs.
1.URATE LOWERING DRUGS :

MECHANISM OF ACTION :
THESE DRUGS COMPETE FOR THE REABSORPTION FROM THE PROXIMAL CONVOLUTED TUBULAR
LUMEN BACK INTO THE TUBULAR CELLS ,HENCE DECREASING THE REABSORPTION OF THE URIC ACID
AS WELL AS INCREASES THE SECRETION OF URIC ACID INTO THE TUBULES .

ADVERSE EFFECTS :
 LEADS TO FORMATION OF STONES IF ADEQUATE URINE VOLUME IS NOT MAINTAINED
 GASTROINTESTINAL DUSTURBANCES
 VOMITING
 ANEMIA
 ANAPHYLACTIC REACTIONS
 INHIBITS THE SECRETION OF WEAK ACIDS SUCH AS METHOTREXATE AND PENICILLIN
 ALLERGIC DERMATITIS
 NEPHROTIC SYNDROME
XANTHINE OXIDASE INHIBITORS :

MECHANISM OF ACTION :

ADVERSE EFFECTS :
 NEURITIS
 VASCULITIS
 GI UPSET
 RASH
 FEBUXOSAT IS CONTRAINDICATED IN PATIENTS WITH HEART DISEASES AND STROKE .

URATE OXIDASE (PEGLOCTICASE)

PEGLOCTICASR IS A BIOTECHNOLOGICALLY SYNTHESIZED URATE OXIDASE ENZYME WHICH CONVERTS
THE URIC ACID INTO ALLANTOIN ,WHICH IS A WATER SOLUBLE PRODRUG .

ADVERSE REACTION :
INFUSION RELATED REACTIONS
.