DIURETICS an overview

The amount of fluid (water) retained by the body is controlled primarily by the kidneys. This occurs due to the kidney's ability to control the retention and elimination of sodium and chloride, because the amounts of sodium, chloride, and water in the body are carefully balanced. Thus, if sodium and chloride are eliminated from the body, water also is eliminated. Conversely, if sodium and chloride are retained by the body, so is water.

The elimination of sodium, chloride, and water from the body is somewhat complex. In the kidneys, sodium, chloride, and other small molecules are filtered out of the blood and into the tubules of the kidney where urine is formed. Most of the sodium, chloride, and water are reabsorbed into the blood before the filtered fluid leaves the kidney in the form of urine. To make matters even more complex, there are different mechanisms that are active in different parts of the tubules that affect the reabsorption of sodium and chloride.

A diuretic is any substance that promotes the production of urine. This includes forced diuresis. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way. Alternatively, an antidiuretic such as vasopressin, or antidiuretic hormone, is an agent or drug which reduces the excretion of water in urine.

Uses of Diuretics

Diuretics are used with other types of medications (adjunctive therapy) in edema associated with congestive heart failure (CHF), cirrhosis of the liver, and corticosteroid and estrogen therapy. Also are useful in edema caused by renal dysfunction (for example, nephrotic syndrome, acute glomerulo nephritis, and chronic renal failure).

Diuretics are used to lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones and as the sole therapeutic agents to treat hypertension. Diuretics can also be used in combination with other antihypertensive drugs to treat more severe forms of hypertension. Diuretics (specifically the carbonic anhydrase inhibitors) are used as adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma

CLASSIFICATION
1.      Acting at proximal convoluted tubules

i. Osmotic diuretics - Osmotic diuretics are substances that increase osmolality but have limited tubular epithelial cell permeability. They work primarily by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney,particularly the peritubular capillaries.

·       Glycerin, Mannitole, Isosorbide and Urea

             ii. Carbonic anhydrase inhibitors - Carbonic anhydrase                                     inhibitors inhibit the enzyme carbonic anhydrase which is                        found in the proximal convoluted tubule. This results in                              several effects including bicarbonate accumulation in the                            urine and decreased sodium absorption.

·       Acetazolamide, Methazolamide

iii.    Acidifying drugs

·       Ammonium chloride

iv.  Others

like tea, coffee, Theophylline, etc.

       2.Acting at loop of Henle

i.    Loop diuretics - Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at the ascending loop in the nephron, which leads to an excretion of water in the urine, whereas water normally follows sodium back into the extracellular fluid.

·       Furosemide, Torsemide, Ethacrynic acid and Bumetanide

ii.   Mercurial agents

·       Mercaptomerin

          3.Acting at distal convoluted tubule

i. Thiazides diuretics - Thiazide diuretics such as hydrochlorothiazide act on the distal convoluted tubule and inhibit the sodium-chloride symporter leading to a retention of water in the urine, as water normally follows penetrating solutes.

· Chlorothiazide, Chlorothalidone, Hydrochlorothiazide, Methyclothiazide, Metolazone

ii.  Sulfonamides

·       Indapemide, Xipemide

           4. Acting at collecting duct system

i.    K- sparing diuretics - These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is retained and not lost as much as with other diuretics. The term "potassium-sparing" refers to an effect rather than a mechanism or location

      . Aldosterone antagonist - Spironolactone

      . Direct acting - Triamterene, Amiloride

ii.    ADH antagonists

·       Lithium salts, Demeclocycline

               
OTHERS

·    Na/K acetate

·    Na/K bicarbonate

·    Na/K Acetate

·    Albumin

·    Dextrose

ANTI-DIURETICS

An antidiuretic is an agent or drug that, when administered to an organism, helps control body water balance by reducing urination opposing diuresis.Antidiuretics are the drugs that reduce urine volume, particularly in diabetes insipidus (DI) which is their primary indication. 

Classification

1. Antidiuretic hormones - Vasopressin, also known as arginine vasopressin (AVP), antidiuretic hormone (ADH), or argipressin, is aneurohypophysial hormone found in most mammals. Its two primary functions are to retain water in the body and to constrict blood vessels. Vasopressin regulates the body's retention of water by acting to increase water reabsorption in the kidney's collecting ducts, the tubules which receive the very dilute urine produced by the functional unit of the kidney, the nephrons.
  --ADH/Vasopressin, Desmopressin, Lypressin, Terlipressin

2. Miscellaneous
  --Chlorpropamide, Carbamazepine

Sources

Dale, M. M., H. P. Rang, and Maureen M. Dale. 2007. Rang & Dale's pharmacology. [Edinburgh]: Churchill Livingstone.

Laurence L. Brunton (2011). Goodman & Gilman's pharmacological basis of therapeutics. (12th ed.). New York: McGraw-Hill.

http://www.rxlist.com/diuretics/drugs-condition.htm

https://en.wikipedia.org/wiki/Diuretic

https://en.wikipedia.org/wiki/Antidiuretic

Hypertension : An overview

Hypertension (HTN or HT), also known as high blood pressure or arterial hypertension, chronic abnormal increase in arterial blood pressure. Blood pressure (BP) is expressed by two measurements, the systolic and diastolic pressures, which are the maximum and minimum pressures, respectively, in the arterial system. The systolic pressure occurs when the left ventricle is most contracted; the diastolic pressure occurs when the left ventricle is most relaxed prior to the next contraction. Normal blood pressure at rest is within the range of 100–140 millimeters mercury (mmHg) systolic and 60–90 mmHg diastolic. Hypertension is present if the blood pressure is persistently at or above 140/90 mmHg for most adults; different numbers apply to children.

Increase in blood pressure can be seen during exercise, during endurance work or during heavy labored work but it gets normalized with time and is not harmful. But long term increase in BP can lead to  hypertensive heart disease, coronary artery disease, stroke, aortic aneurysm, peripheral artery disease, and chronic kidney disease. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.

Hypertension can be mainly of two types – primary hypertension (or essential) maximum cases are of such types of hypertension and in this no underlying cause of the disease is known. And the rest of the other causes are of secondary hypertension which is caused due to an identifiable cause such as renal disease or adrenal hyperfunction, or an endocrine disorder such as excess aldosterone, cortisol, or catecholamines.

                                                Systolic BP (mm hg)                Diastolic BP (mm hg)

                        Normal                     130-139                                          85-89

                        Mild                           140-159                                          90-99

                        Moderate                 160-179                                          100-110

                        Severe                       180-209                                          110-119

                        Very severe                >210                                               >120

Reno-vascular hypertension is mainly caused due to improper functioning of RAS (rennin-angiotensin system), which when functioning normally can regulate blood pressure and fluid balance. Angiotensinogen (in liver) is the starting inactive peptide which is converted to angiotensin-I (A-I) in presence of renin (kidney), which is then converted to angiotensin-II (A-II) by angiotensin converting enzyme (ACE) (thought to be found in lung capillary).

A-II is 100 times more biologically potent than A-I but has a very short t_1/2 (1 min) and its first degradation product is termed as angiotensin-III (A-III) which is 3-9times less potent that A-II, except when secreting aldosterone it is equipotent. Angiotensin-I may have some minor activity, but angiotensin-II is the major bio-active product. So, whenever there is problem in the RAS cycle there is abnormality in blood pressure and fluid balance in our body.

Angiotensin-II increases sympathetic activity causes tubular Na⁺ Cl^-, K⁺ excretion and water retention, arteriolar vasoconstriction and increase in BP, ADH (antidiuretic hormone secretion) secretion which causes water absorption in collecting duct, enhancing adrenaline/nor-adrenaline release from adrenal medulla/adrenergic nerve endings and by increasing central sympathetic outflow. In addition to secreting aldosterone, A-III promotes Na⁺/H⁺ exchange in proximal tubule causing increased Na⁺ Cl^- and bicarb reabsorption. Vasodilators and diuretics stimulate rennin release by lowering BP.

Classification of antihypertensive drugs

1.Adrenergic receptor antagonists

a.Beta blockers

                                 atenolol

                                 metoprolol

                                 nadolol

                                 oxprenolol

                                 pindolol

                                 propranolol

                                 timolol

      b.Alpha blockers:

                                 doxazosin

                                 phentolamine

                                 indoramin

                                 phenoxybenzamine

                                 prazosin

                                 terazosin

                                 tolazoline

          c.Mixed Alpha + Beta blockers:

                                 bucindolol

                                 carvedilol

                                 labetalol

2.Diuretics

Diuretics help the kidneys eliminate excess salt and water from the body's tissues and blood.

          a.Loop diuretics:

                                 bumetanide

                                 ethacrynic acid

                                 furosemide

                                 torsemide

           b.Thiazide diuretics:

                                 epitizide

                                 hydrochlorothiazide and chlorothiazide

                                 bendroflumethiazide

            c.Thiazide-like diuretics:

                                 indapamide

                                 chlorthalidone

                                 metolazone

             d.Potassium-sparing diuretics:

                                 amiloride

                                 triamterene

                                 spironolactone

3.Calcium channel blockers

Calcium channel blockers block the entry of calcium into muscle cells in artery walls.

       a.dihydropyridines:

                                 amlodipine

                                 felodipine

                                 isradipine

                                 lercanidipine

                                 nicardipine

                                 nifedipine

                                 nimodipine

                                 nitrendipine

          b.non-dihydropyridines:

                                 diltiazem

                                 verapamil

4.ACE inhibitors

ACE inhibitors inhibit the activity of Angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.

                     captopril

                     enalapril

                     fosinopril

                     lisinopril

                     perindopril

                     quinapril

                     ramipril

                     trandolapril

                     benazepril

      Indomethacin (and other NSAIDs) attenuates the hypotensive action of captopril.

5.Angiotensin II receptor antagonists

Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors.

                     candesartan

                     eprosartan

                     irbesartan

                     losartan

                     olmesartan

                     telmisartan

                     valsartan

      Losartan is 10,000 times more selective for A-I than A-II still is its competitive antagonist but has partial activity. It causes fall in BP in hypertensives which lasts for 24hours.

6.Aldosterone antagonists

Aldosterone receptor antagonists:

                     eplerenone

                     spironolactone

Aldosterone antagonists are not recommended as first-line agents for blood pressure, but spironolactone and eplerenone are both used in the treatment of heart failure.

7.Centrally acting adrenergic drugs

Central alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. Central alpha agonists, such as clonidine, are usually prescribed when all other anti-hypertensive medications have failed. For treating hypertension, these drugs are usually administered in combination with a diuretic.

                     Clonidine

                     Guanabenz

                     Methyldopa

                     Moxonidine

Adverse effects of this class of drugs include sedation, drying of the nasal mucosa and rebound hypertension.

Some adrenergic neuron blockers are used for the most resistant forms of hypertension:

                     Guanethidine

                     Reserpine

8.Vasodilators

Vasodilators act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them; they are only used in hypertensive emergencies or when other drugs have failed, and even so are rarely given alone.

Sodium nitroprusside, a very potent, short-acting vasodilator, is most commonly used for the quick, temporary reduction of blood pressure in emergencies (such as malignant hypertension or aortic dissection). Hydralazine and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies. They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety concerns, but hydralazine remains a drug of choice in gestational hypertension.

9.Adrenergic receptor agonists

              Alpha-2 agonists:

                                 clonidine

                                 methyldopa

                                 Guanfacine

Referred from:

https://en.wikipedia.org/wiki/Hypertension

https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system

https://en.wikipedia.org/wiki/Antihypertensive_drug

http://studenttopics.blogspot.in/2011/03/antihypertensive-drug-classification.html