Diuretics

Introduction

Diuretics are chemicals that remove excess water salt toxins and metabolites such as urea from the body[1]. Typically they inhibit electrolyte reabsorption from the lumen of the nephron increasing osmolarity and increasing water excretion.

Indications

Diuresis is necessary for non-edematous and edematous conditions that require the removal of excess fluid as the body abnormally stores fluid in the third space in the form of edema (Third spacing is fluid accumulating abnormally into the extracellular and extravascular space). [2] .

The quintessential of edematous conditions is heart failure (HF) where the inefficiency of the heart’s pumping ability results in:

1. Decreased renal perfusion activation of the renin-angiotensin-aldosterone-system (RAAS) and
2. Long-standing venous stasis leading to extravasation of fluid into the interstitial space both of which lead to intravascular volume expansion and result in signs of congestion such as weight gain dyspnea and generalized edema.

Diuretics are used to treat a variety of diseases. These include:

• Chronic heart failure (see the aldosterone receptor antagonist diuretics to treat congestive heart failure)
• High blood pressure (see Diuretic Drugs for the Treatment of Coronary Arteries also) .
• Glaucoma
• Liver disease
• Kidney disease
• Hyperaldosteronism
• Edema
• Hypokalemia[3]

Types

The main difference between diuretic types is the level of potency. This difference in potency is due to the different sites of action of diuretics on renal structures. Different types include:

1. The most potent loop diuretics (eg, furosemide bumetanide torasemide) enhance sodium and chloride elimination by primarily inhibiting sodium and chloride reabsorption. Loop diuretics are commonly used to treat heartburn. The effectiveness of loop diuretics is because a unique functional area involving the loop of Henle (part of the renal tubule). Loop Diuretics are very powerful so if a less potent diuretic can be used they should be used. Symptoms:

• Presence of pulmonary edema and patient history of congestive heart failure (CHF)
• The edema around the heart of the liver, heart or kidney and other diuretic is useless
• Blood pressure and other diuretics are useless

2. Thiazides are the most commonly prescribed diuretics. It is often used to treat high blood pressure. These drugs not only reduce fluids but also relax blood vessels.[4] Thiazides act on the distal convoluted tubule. They are not as effective as Loop Diuretics. They’re not, either excretes sodium chloride potassium and water but raises uric acid and glucose (if the patient has normal kidney function these drugs are used only when the kidney function is impaired). After their development in the late 1950s, thiadiazides replaced most of the others already available diuretics. They are more convenient than some other diuretics in that they can be taken orally in the form of pills[1]. Therapeutic Uses:

• Hypertension
• Edema (that’s mild/moderate)
• Diabetes Insipidus (can decrease urine production by 30-50%)

3. Potassium-sparing diuretics reduce sodium reabsorption at the distal tubule thus decreasing potassium secretion. In the distal tubule potassium is excreted into the forming urine coupled with the reabsorption of sodium. Therapeutic uses: These drugs are most likely being used because a loop or they are using a thiazide diuretic and do not want the patient to become hypokalemic.

• Heart Failure
• Primary Hyperaldosteronism
• Premenstrual Syndrome
• Polycystic Ovary Syndrome

4. Carbonic anhydrase inhibitors work by increasing sodium potassium bicarbonate and renal secretion. Carbonic anhydrase inhibitors (acetazolamide) are used to prevent mountain sickness (meaning off-licence) and migraine.[5]

5. An osmotic diuretic (mannitol) is used in the hospital setting to treat cerebral edema [5]. They act on the lumen of the nephron by generating osmotic forces. No significant effect on electrolyte excretion. Therapeutic use:

• Primary medical treatment for elevated intracranial pressure (ICP) after traumatic brain injury and brain tumor.
• Mannitol also promotes diuresis in acute renal failure and excretes toxic metabolites and substances.
• Hypertonic saline is not considered a diuretic, although it is also used to treat high ICP and has sometimes been shown to be more effective than mannitol [6][3][7][2]

Natural Diuretics

Heart failure, hypertension, cirrhosis, and nephritic syndrome are among the conditions that alter fluid volume and composition and are modulated by diuretics. Natural products are a great source of diuretics and are considered significant alternatives with greater efficacy and less side effect. However, many plants used in traditional medicine must be scientifically evaluated for their efficacy and toxicity. Despite numerous published articles claiming that plants or plant-derived ingredients can act as diuretics, few studies have addressed Mechanism of action of medicinal plants [8]

Examples of natural diuretics include:

• Nigella sativa black cumin black seed or black caraway is a natural diuretic that may be as effective as a popular prescription drug. Nigella sativa increases water production and in turn reduces sodium and potassium levels.
• Hibiscus: The Hibiscus sabdariffa plant acts as a natural diuretic and also prevents the body from excreting potassium. Hibiscus sabdariffa is also known as roselle or red sorrel. It is often used as a supplement or made into a tea. Hibiscus tea is made by steeping the dried flowers of hibiscus flowers in warm water.
• Alcohol is a well-known diuretic, which works by increasing urine output. However, alcohol has many adverse health effects and should always be consumed in moderation.
• Nasturtium leaves: its main compound, isoquercitrin (ISQ), has a pronounced diuretic effect, supporting the ethnopharmacological use of the plant[9]
• Dandelion: A wildflower common in many parts of the Northern Hemisphere.
• Ginger: Both dandelion and ginger are commonly used in drinks and teas purportedly for their detoxifying properties due to their diuretic properties. However, there are no adequate human studies showing an effect.
• Cleakn: A study found that the amount of diuretic seeds for rats increased its urine volume significantly. Over the years, Celeba has been used as home therapy urine. The mechanism of the role of Pan sunscreen seems to be mediated by suppressing the NA+ -k+ pump, which will lead to a reduction In Na+and K+heavy absorption, the infiltration water flows into the lumen and diuretic. [10]
• Caffeine may have a mild short -term diuretic effect. Caffeine is found in coffee soda and energy drinks. People who often drink caffeine drinks can tolerate caffeine and do not see any differences [11].

General Adverse Effects

The most common adverse effect of any diuretic is mild hypovolemia, which can lead to transient dehydration and increased thirst.

• If diuretic is overtreated this can lead to severe hypertension leading to hypotension and depression.
• Persistent side effects of diuretics include headache urinary frequency breathing weakness fatigue and tiredness. GI side effects such as constipation diarrhea diarrhea anorexia and abdominal pain are more likely to occur with loop diuretics and PSDs than with any other diuretic class.
• Electrolyte abnormalities are generally associated with all diuretics. Acid-base disturbances are often accompanied by electrolyte disturbances because they are closely related to reabsorption in the renal tubules. Metabolic disturbances can lead to glucosuric acid or lipid disturbances Levels of certain diuretics are discussed separately.
• In general, side effects are dose-dependent and are higher with loop diuretics because they have the most pronounced diuretic effect. Side effects have been greatly reduced with controlled low-dose formulations, especially thiazide diuretics. [2]
• Diuretic-induced hypokalemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies have shown a prevalence of hypokalemia in 7%–56% of patients taking thiazide diuretics. Diuretic dose reduction and potassium supplementation Immediate effective therapy for hypokalemia. Coadministration with potassium-sparing diuretics or renin-angiotensin system blockers may also reduce the risk of hypokalemia. Lowering salt intake and increasing vegetable and fruit intake can help lower blood pressure and prevent Hypokalemia [12]

Diuretic Abuse

Diuretics are not highly regulated drugs and as such are likely to be abused, especially by athletes who may abuse them to lose weight rapidly or to mask the presence of other illicit drugs.

• The use of diuretics is prohibited in athletes. (Athletes require prior medical clearance in athletes) and are regularly inspected by the world anti-doping agency.
• This abuse, if sustained in the long term, can adversely affect CV and thermoregulatory function and, if combined with the excessive physical activity experienced by athletes, can lead to death [2].

Diuretics do not contribute to weight loss. Anyone who wants to lose weight should follow a healthy balanced diet and exercise regularly. Any weight loss will be restored as the body rehydrates.[11]

Patient Education

Patient education plays an important role along with adequate knowledge about the side effects of dietary and lifestyle changes required when using diuretics. Patients (especially in an outpatient clinic) need to understand that any changes in their compliance policies or any adverse events will be reported effect of consequences. Adherence to a strict treatment regimen and timely consumption of the drug and avoidance of any overdose as patients lose dose will greatly improve the clinical course and dialysis

Examples of education include:

• Diet – especially with loop diuretics, you must ensure that the patient’s diet is high in potassium. Loop diuretics are potassium-excreting diuretics, which means they use up potassium in the body and into the potty. Therefore, it is critical to instruct your patients Consume foods high in potassium, such as: bananas; oranges; spinach; green leafy vegetables. A low-salt diet should be promoted.
• The dose at night is taboos: never provide diuretics at night. You don’t want patients to fall or trip when they go to the toilet.
• Take in the morning: To prevent the risk of falls, diuretics are taken only in the morning [13].