Class – V Drugs:

Digoxin causes shortening of the atrial refractory period with small doses (vagal action) and a prolongation with the larger doses (direct action). It prolongs the effective refractory period of

1. node directly and through the vagus. This action is of major importance in slowing the rapid ventricular rate in patients with atrial fibrillation

Diuretics

Diuretics are drugs, which increase renal excretion of salt and water: are principally used to remove excessive extracellular fluid from the body.

In order to understand the action of diuretics it is important to have some knowledge of the basic processes that take place in the nephron (unit structure of kidney.

Approximately 180 liters of fluid is filtered from the glomerulus into the nephron per day. The normal urine out put is 1-5 liters per day. The remaining is reabsorbed in different areas of nephron. There are three mechanisms involved in urine formation

1. glomerular filtration
   1. tubular reabsorption
   2. Tubular secretion. These processes normally maintain the fluid volume, electrolyte concentration and PH of the body fluids.

Classification of diuretics:-

Most of the diuretics used therapeutically act by interfering with sodium reabsorption by the tubules. The major groups are:

1. Thiazides and related diuretics: e.g. Hydrochlorothiazide chlorthalidone, bendrofluazide, etc.
2. Loop diuretics: e.g. furosemide, ethacrynic acid, etc.
3. Potassium sparing diuretics e.g. triamterene, amiloride, spironolactone, etc.
4. Carbonic anhydrase inhibitors e.g. acetazolamide
5. Osmotic diuretics e.g. mannitol, glycerol

1. Thiazide diuretics act by inhibiting NaCl symport at the distal convoluted tubule. They are used in hypertension, edema of hepatic, renal and cardiac origin.

Adverse effects: epigastric distress, nausea, vomiting, weakness, fatigue, dizziness, impotence, jaundice, skin rash, hypokalemia, hyperuricemia, hyperglycaemia and visual disturbance.

1. Loop diuretics: Loop diuretics like frusemde inhibit Na⁺– K – 2Cl symporter in the ascending limb.

Adverse effects: Hypokalemia, nausea, anorexia, vomiting epigastric distress, fatigue weakness muscle cramps, drowsiness. Dizziness, hearing impairment and deafness are usually reversible. Therapeutic uses: acute pulmonary edema, edema of cardiac, hepatic and renal disease. Hypertension, cerebral edema, in drug overdose it can be used to produce forced diuresis to facilitate more rapid elimination of drug.

1.   Potassium sparing diuretics mechanism of action: Potassium sparing diuretics (spironolactone, triamterene, amiloride) are mild diuretics causing diuresis by increasing the excretion of sodium, calcium and bicarbonate but decrease the excretion of potassium.

Adverse effects: G.I. disturbances, dry mouth, rashes confusion, orthostatic hypotension, hyperkalaemia. Hyponatraemia

Therapeutic uses: used with conjunction with thiazides or loop diuretics in edema due to, cardiac failure nephrotic syndrome and hepatic disease.

1. Carbonic anhydrase inhibitors: these drugs like acetazolamide inhibit the enzyme carbonic anhydrase in renal tubular cells and lead to increased excretion of bicarbonate, sodium and potassium ions in urine. In eye it results in decrease information of aqueous humor. Therefore these are used in treatment of acute angle glaucoma. Main adverse effects of these agents are drowsiness, hypokalemia, metabolic acidosis and epigastric distress.
2. Osmotic diuretics: these drugs like mannitol and glycerine (glycerol) are freely filtered at the glomerulus and are relatively inert pharmacologically and undergo limited reabsorption by renal tubule. These are administered to increase significantly the osmolality of plasma and tubular fluid. Some times they produce nausea, vomiting, electrolyte imbalances. They are used in cerebral edema and management of poisoning.

Drugs used in hypotensive states and shock

Antihypotensive drugs or agents are used to elevate a low blood pressure and may be classified as follows:

1. Agents intended to increase the volume of blood in active circulation. These include intravenous fluids such as whole blood, plasma, plasma components, plasma substitutes and solution of crystalloids
2. Vasoconstrictor drugs these include:

• Peripherally acting vasoconstrictors which are further divided into sympathomimetic drugs and direct vasoconstrictors.

Sympathomimetics used to elevate the blood pressure include adrenaline, noradrenaline, methoxamine, phenylephrine, mephentermine and ephedrine.

Direct vasoconstrictors include vasopressin and angiotensin.

Treatment of shock

Shock is a clinical syndrome characterized by decreased blood supply to tissues. Common signs and symptoms include oliguria, heart failure, disorientation, mental confusion, seizures, cold extremities, and comma.

Most, but not all people in shock are hypotensive. The treatment varies with type of shock. The choice of drug depends primarily on the patho-physiology involved.

• For cardiogenic shock and decreased cardiac out put, dopamine or other cardiotonic drug is indicated. With severe CHF characterized by decreased CO and high PVR, vasodilator drugs (nitropruside, nitroglycerine) may be given along with the cardiotonic drug. Diuretics may also be indicated to treat pulmonary congestion if it occurs.
• For anaphylactic shock or neurogenic shock characterized by severe vasodilation and decreased PVR, a vasoconstrictor drug (e.g. levarterenol) is the first drug of choice
• For hypovolemic shock, intravenous fluids that replace the type of fluid lost should be given
• For septic shock, appropriate antibiotic therapy in addition to other treatment measures.