DIURETICS
Diuretics are substances which help to increase the urination & remove excessive fluid & salts from the body.
Diuretics also help to lower the blood pressure & are used in medical conditions which are due to excessive fluid.Diuretics are also known as water pills.
In simple words diuretics are the Drugs/medications that produce a state of high urine flow.
OVERVIEW
Normally, diuretics tend to secrete a high amount of Sodium and ions alongside water through urination. Due to this capability, they are named among the First Line of Treatment of Hypertension.
Besides this, they are used in the treatment of Cardiovascular Events (CVEs) and Edema.
In this article we will discuss following,
Normal Physiology of Nephron
MOA of Diuretics
Classification Of Diuretics
Drugs MOA, Therapeutic Uses & Side Effects
Diuretic Resistance
Prevalence
Case study
Combination Therapy
Overall Side Effects
Important Points
NORMAL PHYSIOLOGY OF NEPHRON
Bowman's capsule performs the filtration of blood plasma (16%-20%) through capillaries. Filtrate buildup of glucose, electrolytes (k+, Na+, Cl-), sodium bicarbonate, and amino acids reabsorbed into the blood from the lumen.So
Regulation of
urine volume
&
iconic composition
is held by five zones of the nephron in the kidney.
These functional zones are as follow,
Proximal convoluted tubule (PCT)(67% reabsorption of Na)
Descending loop of Henle
Ascending loop of Henle (25% reabsorption of Na)
Distal Convoluted Tubule (DCT)(5% reabsorption of Na)
Collecting Tubule and Duct (1% reabsorption of Na)
PCT and DCT are present in the cortex part of the nephron while other zones are present in the medulla.
MOA OF DIURETIC
Diuretics mechanism of action is simply prescribed as ‘the inhibition of Na and water reabsorption from the lumen to blood’
Note
All diuretics act differently according to their mechanism.
CLASSIFICATION Of Diuretics
Diuretics are divided into five categories according to different nomenclature. These drugs are more defined to act at different sites of a nephron.
Loop Diuretics
Thiazide Diuretic
Potassium Sparing Diuretic
Carbonic Anhydrase Inhibitor
Osmotic Diuretics
LOOP DIURETICS
Normal Physiology of Nephron
In normal physiology of nephrons at the Ascending loop of Henle 25% of Na, Cl & k are reabsorbed from lumen to blood through Na & cl ion co-transporter.
Mechanism Of Action Of Loop Diuretics
Loop diuretic act as to inhibit the Na, Cl & K Co transporter pump and reabsorption of these ions does not take place.
As a result, these ions are excreted within water in large volumes of urine.
Drugs of Loop of Henle
It includes following drugs,
Bumetanide
Furosemide
Torsemide
Ethacrynic acid
Therapeutic Uses
Following are therapeutic uses
Edema
Hypercalcemia
Hyperkalemia
Side effects
It includes
Ototoxicity
Hypotension
Hypokalemia
THIAZIDE DIURETIC
Normal Physiology of Nephron
In normal physiology at distal convoluted tubules Na & Cl go into blood and Calcium into urine.
Mechanism Of Action Of THIAZIDE Dietetics
Thiazide controls the reabsorption of Na and Cl 5% by inhibiting the pump thus increased excretion of Na & Cl occurred.These drugs also have a vasodilation effect.Calcium reabsorbed occurred by thiazide diuretics.
Drugs of Thiazide
It includes
1.Chlorothiazide 2.Hydrochlorothizide 3.Indapamide
4.Metolazone
5.Chlorthalidone
Therapeutic Uses
It includes
Hypertension
Heart failure
Hypercalciuria
Side effects
It includes
Hypokalemia
Hypomagnesemia
Hypovolemia
CARBONIC ANHYDRASE INHIBITORS:
Normal Physiology of Nephron
In normal physiology, the carbonic anhydrase enzyme is responsible for the reabsorption of bicarbonate.These Act on the proximal convoluted tubules.
Mechanism Of Action OF Carbonic Anhydrase Inhibitors
In a drug situation, bicarbonate is not reabsorbed and is lost in the form of sodium bicarbonate from blood to urine.Hence large amounts of urine excrete.
Drugs of CAI
It includes
Acetazolamide
Therapeutic uses Of CAI
It includes
Glaucoma
Altitude Sickness
Side effects
It includes
Drowsiness
Metabolic acidosis
Renal stone formation
POTASIUM SPARING DIURETICS
Normal Physiology of Nephron
In normal physiology at collecting tubule, the reabsorption of Na along with excretion of K+ ions occurred.
MOA Of Potassium Sparing Diuretics
Potassium-sparing diuretics act on the collecting tubule, having a strong property of antagonizing the aldosterone receptor. Thus, Na+ moves outside the body in the form of urine and K+ moves backward to blood to retain in the body.
Drugs Of Potassium Sparing Diuretics
It includes
Spironolactone
Eplerenone
Therapeutic uses
It includes
1.Resistance Hypertension 2.Polycystic Ovary Syndrome
3.Heart failure
Side effects
It includes :
Drowsiness
Metabolic acidosis
Renal stone formation
OSMOTIC DIURETICS
Normal Physiology of Nephron
In normal physiology, the descending loop of Henle reabsorbs the amount of Na as well as Ca+ and Mg due to high blood concentration.
Mechanism Of Action Of Osmotic Diuretics
Osmotic diuretics act on the descending loop of Henle and prevent the reabsorption of water. Thus reduce the plasma volume also and conduct the elevated excretion of Na, K+, Mg, Ca+. Precisely, these drugs enhance the solute concentrations in the tubular lumen to retain the water in tubules.
Drugs Of Osmotic Diuretics
It includes
Mannitol
Urea
Therapeutic uses
It includes
Acute Glaucoma
It helps patients with increased intracranial pressure
Side effects
It includes
Dehydration
Hyponatremia
DIURETIC RESISTANCE
Diuretic resistance is defined as the inability to reduce edema even if the dose is provided to its maximal or therapeutic level. The main causes of resistance to diuretics are
Poor adherence to drug
Elevated level of Na+ Reabsorption
Pharmacokinetic problems
PREVALENCE
It is estimated that between 20% and 30% of HF patients have diuretic resistance (DR).
CASE STUDY
A case study results showed that increased usage of antihypertensive drugs with diuretics causes the arousal of renal cell cancer in white people. Added to more conclusions, the elevated duration of usage of Diuretics leads to an increased risk of renal cancer cells.
COMBINATION THERAPY
Practitioners prescribed diuretics as combination therapy for treating diseases such as Hypertension and Heart Failure patients.
OVERALL SIDE EFFECTS
Side effects of diuretics may count as
Stomach upset known as Indigestion
Hair Loss
Dizziness
Nausea
Headache
Muscle Cramps
Dehydration
Breast Enlargement
IMPORTANT POINTS
In a short way, some important points must be remembered related to diuretics,
All diuretics result in excretion of K+ except Potassium Sparring Diuretic
Potassium Sparring Diuretics may induce Gynecomastia
Furosemide (Loop Diuretic) is used only in an Emergency situation
Calcium Reabsorption results in the action of Thiazide Diuretics.
Weakest Diuretic action performed by the Carbonic Anhydrase Inhibitors
The most powerful action of diuretics is shown by the Loop Diuretics.
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