PART-I-DIURETICS AND THEIR USAGES

TECHNIQUES OF DIURESIS

Diuresis is the technique by which the body increases the formation of urine, by volume, solutes, and water. In diuresis, more water and its solutes by volume and density are excreted. Excretion of urine is increased disregarding its concentration. Urine may or may not be diluted depending upon the methods of diuresis by which the urine is formulated by the kidneys. This is the difference between Diuresis and Diabetes Insipidus.

In general, diuresis happened when more sodium ion is excreted along with water.

Diuretics are generally targeting Proximal Convoluted Tubules(PCT), thick ascending Loop of Henle, the Distal Convoluted Tubule(DCT)and the Collecting Duct. Knowledge of the sites of action is important to predict the power and pattern of the diuretics, their side effects, and the way of electrolyte losses.

Techniques Of Diuresis

1.Osmotic

Osmotic diuretics are targeting the Bowman's Capsule PCT and Collectin Duct.

In osmotic diuresis, the concentration of the solute is higher in the glomerular filtrate(high osmolality)than the solution to be filtered and thereby increase more solvent to be filtered and decrease the solvent reabsorption and the result is more urine formation.

Mannitol and urea are the best examples of osmotic diuretics. These substances are inert, polar, and hydrophilic and are freely filtered through the glomerulus. This increases the filtrate osmolality.

Osmotic diuretics by limiting tubular reabsorption they increase the excretion of water, sodium, chloride, and bicarbonate excretion, and cause urine more alkaline.

Therapeutic Uses

1. To decrease cerebral edema and intracranial pressure.

2. To relieve Intra Ocular Pressure.

3.Treatments of oliguria, and anurea.

4.Treatment of acute kidney failure.

Osmotic diuretics can be given as intravenous injections.  

Side Effects

1.Headache

2.Blurred vision.

3. Hypovolemia or decreased blood volume, as a result, hypotension, and CHF.

4.Pulmonary edema by increasing the extracellular osmolality and thereby pulling more solvent into it.

2.Carbonic Anhydrase Inhibitors

The best prototype example is Acetazolamide.

Carbonic anhydrase is the enzyme that hydrolyzes carbon dioxide to form carbonic acid which ionizes into hydrogen ion and carbonium ion as follows

      H2O +CO2 >< H2CO3><H+ + HCO3-
The release hydrogen ion(H+) is exchanged for sodium ion from the lumen to inside the cells causes sodium and water reabsorption from the glomerular filtrate into the blood through the PCT into the blood.
By inhibiting this enzyme no carbon dioxide hydrolysis, no carbonic acid formation, and no hydrogen ion and thereby no sodium and water reabsorption and results in diuresis.
This is a weak diuretic agent as it acts only on PCT but when the filtrate moves further in the tube they later site such as the ascending and descending LH and DCT can compensate the sodium load by reabsorption.
These diuretics produce alkaline urine by excreting sodium, potassium, water, and bicarbonate ions. 
It can be given by the I.V. route or by the oral route.

Therapeutic Use

1. Acetazolamide can inhibit the production of aqueous humor in the eyes. Hence it is used in glaucoma.

2. In mountain sickness, it alleviates normal respiration by decreasing the carbonic acidosis in the blood.

3.Epilepsy.It normalizes the convulsions in epilepsy, and absence seizures, paroxysmal chorea, dystonia, ataxia, and tremor

4.Edema

5.Enhance the excretion of acidic drugs by alkalinizing urine

Side Effects

1.Hyperchloremia by excreting more bicarbonate ions

2. Hypokalemia due to exchange for sodium at the DCT leads to cardiovascular disturbances.

3.Renal stones

4.CNS effects such as depression, drowsiness and sedation, and paraesthesia

5.Nausea, vomiting, and constipation

6.Bone marrow depression,thrombocytopenia(Blood clotting delayed),hemolytic anemia,leukopenia,and agranulocytosis.

4. Sulpha allergy as acetazolamide is a sulpha drug.