Diuretic

High ceiling loop diuretic

High ceiling diuretics are diuretics that may cause a substantial diuresis – up to 20% of the filtered load of NaCl and water. This is huge when compared to normal renal sodium reabsorption which leaves only ~0.4% of filtered sodium in the urine.

Loop diuretics have this ability, and are therefore often synonymous with high ceiling diuretics. Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at the ascending loop in the nephron which leads to a retention of water in the urine as water normally follows sodium back into the extracellular fluid (ECF). Other examples of high ceiling loop diuretics include ethacrynic acid,torsemide and bumetanide.

Thiazides

Thiazide-type 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. Frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. On the other hand the long-term effect is due to an unknown vasodilator effect that decreases blood pressure by decreasing resistance.

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 retention in the urine, potassium retention in urine and decreased sodium absorption. Drugs in this class include acetazolamide and methazolamide.

Digitalis

Digitalis increases output of urine by increasing cardiac output and increasing circulation through the kidneys. Digitalis has a diuretic effect on heart failure patients due to cardiac edema.

Potassium-sparing diuretics

These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is spared and not lost as much as in other diuretics. The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations:

• Aldosterone antagonists: spironolactone, which is a competitive antagonist of aldosterone. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. A similar agent is potassium canreonate.

• Epithelial sodium channel blockers: amiloride and triamterene.

Calcium-sparing diuretics

The term "calcium-sparing diuretic" is sometimes used to identify agents that result in a relatively low rate of excretion of calcium.

The reduced concentration of calcium in the urine can lead to an increased rate of calcium in serum. The sparing effect on calcium can be beneficial in hypocalcemia, or unwanted in hypercalcemia.

The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics.

• The thiazides cause a net decrease in calcium lost in urine.
• The potassium-sparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than the increase associated with other diuretic classes.

By contrast, loop diuretics promote a significant increase calcium excretion. This can increase risk of reduced bone density.

Osmotic diuretics

Compounds such as mannitol are filtered in the glomerulus, but cannot be reabsorbed. Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.

Glucose, like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike mannitol, glucose is commonly found in the blood. However, in certain conditions such as diabetes mellitus, the concentration of glucose in the blood (hyperglycemia) exceeds the maximum reabsorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Glucosuria causes a loss of hypotonic water and Na⁺ leading to a hypertonic state with signs of volume depletion such as: dry mucosa, hypotension, tachycardia, and decreased turgor of the skin. Use of some drugs, especially stimulants may also increase blood glucose and thus increase urination.

Low ceiling diuretics

The term "low ceiling diuretic" is used to indicate that a diuretic has a rapidly flattening dose effect curve (in contrast to "high ceiling", where the relationship is close to linear). It refers to a pharmacological profile, not a chemical structure. However, there are certain classes of diuretic which usually fall into this category, such as the thiazides.

Mast cell stabilizer

Mast cell stabilizers are cromone medications used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmacodynamic mechanism is the blocking of IgE-regulated calcium channels. Without intracellular calcium, the histamine vesicles cannot fuse to the cell membrane and degranulate.

As inhalers they are used to treat asthma, as nasal sprays to treat hay fever (allergic rhinitis) and as eye drops for allergic conjunctivitis. Finally in oral form they are used to treat the rare condition of mastocytosis.

Leukotriene antagonists

Inhibition of the 5-lipoxygenase pathway

Drugs such as zileuton block 9998 lipo protein oxydatenase 5-lipoxygenase, inhibiting the synthetic pathway of leukotriene metabolism, whereas drugs such as MK-886 block the 5-lipoxygenase activating protein (FLAP) and may help in treating atherosclerosis

Antagonism of cysteinyl-leukotriene type 1 receptors

Agents such as montelukast and zafirlukast block the actions of cysteinyl leukotrienes at the CysLT1 receptor on target cells such as bronchial smooth muscle.

These modifiers have been shown to improve asthma symptoms, reduce asthma exacerbations and limit markers of inflammation such as eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid. This demonstrates that they have anti-inflammatory properties.

Antiasthmatic drugs

Bronchodilator

A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be endogenous (originating naturally within the body), or they may be medications administered for the treatment of breathing difficulties. They are most useful in obstructive lung diseases, of which asthma and chronic obstructive pulmonary disease are the most common conditions. Although this remains somewhat controversial, they might be useful in bronchiolitis. They are often prescribed but of unproven significance in restrictive lung diseases.

Bronchodilators are either short-acting or long-acting. Short-acting medications provide quick or "rescue" relief from acute bronchoconstriction. Long-acting bronchodilators help to control and prevent symptoms. The three types of prescription bronchodilating drugs are β2-agonists (short- and long-acting), anticholinergics (short-acting), and theophylline (long-acting).

Short-acting β2-agonists

These are quick-relief or "rescue" medications that provide quick fast, temporary relief from asthma symptoms or flare-ups. These medications usually take effect within 20 minutes or less, and can last from four to six hours. These inhaled medications are best for treating sudden and severe or new asthma symptoms. Taken 15 to 20 minutes ahead of time, these medications can also prevent asthma symptoms triggered by exercise or exposure to cold air. Some short-acting β-agonists (for example salbutamol) are specific to the lungs; they are called β2-agonists and can relieve bronchospasms without unwanted cardiac (β1) side effects of nonspecific β-agonists (for example, ephedrine or epinephrine). Patients who regularly or frequently need to take short-acting β-agonists should consult their doctor, as such usage indicates uncontrolled asthma, and their routine medications may need adjustment.

Salbutamol is an example of a Short-acting β2-agonists

Long-acting β2-agonists

These are long-term medications taken routinely in order to control and prevent bronchoconstriction. They are not intended for fast relief. These medications take longer to begin working, but relieve airway constriction for up to 12 hours. Commonly taken twice a day with an anti-inflammatory medication, they maintain open airways and prevent asthma symptoms, particularly at night.

Salmeterol and Formoterol are examples of these.

Anticholinergics

Main article: Anticholinergics

Some examples of anticolinergics are tiotropium (Spiriva) and ipratropium bromide.

Tiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD).

Only available as an inhalant, ipratropium bromide is used in the treatment of asthma and COPD. It relieves acute or new asthma symptoms. Because it has no effect on asthma symptoms when used alone, it is most often paired with a short-acting β2-agonist. While it is considered a relief or rescue medication, it can take a full hour to begin working. For this reason, it plays a minor role in asthma treatment. Dry throat is the most common side effect. If the medication gets in contact with the eyes, it may cause blurred vision for a brief time.

Other

Available in oral and injectable form, theophylline is a long-acting bronchodilator that prevents asthma episodes. It belongs to the chemical class methyl xanthines (along with caffeine). It is prescribed in severe cases of asthma or those that are difficult to control. It must be taken 1–4 times daily, and doses cannot be missed. Blood tests are required to monitor therapy and to indicate when dosage adjustment is necessary. Side effects can include nausea, vomiting, diarrhea, stomach or headache, rapid or irregular heart beat, muscle cramps, nervous or jittery feelings, and hyperactivity. These symptoms may signal the need for an adjustment in medication. It may promote acid reflux, also known as GERD, by relaxing the lower esophageal sphincter muscle. Some medications, such as seizure and ulcer medications and antibiotics containing erythromycin, can interfere with the way theophylline works. Coffee, tea, colas, cigarette-smoking, and viral illnesses can all affect the action of theophylline and change its effectiveness. A physician should monitor dosage levels to meet each patient's profile and needs.

Additionally some psychostimulant drugs that have an amphetamine like mode of action, such as amphetamine, methamphetamine, and cocaine, have bronchodilating effects and were used often for asthma due to the lack of effective β2-agonists for use as bronchdilators, but are now rarely, if ever, used medically for their bronchodilation effect.