Diuretics and HMG-CoA Reductase Inhibitor
Diuretics
Diuretic are drugs used to eliminate solutes, such as salts in the body, by removing a lot of water. They are used for treating various conditions, such as kidney problems, high blood pressure, glaucoma, and heart failure. There are different groups of diuretics: thiazide, loop, potassium-sparing, and osmotic diuretics.
Thiazine Drugs
Thiazine drugs impede the transportation of chloride and sodium irons in the distal convoluted tubules. The drugs block sodium and chloride ions from entering distal convoluted tubules, therefore, the concentration of sodium ions reduces in the internal cells (Sarafidis, Georgianos, & Lasaridis, 2010). Thiazine also promotes the removal of sodium and potassium ions from the body but impede the removal of calcium ions. Some thiazine drugs promote the removal of carbon anhydrase and, like other drugs that enhance removal of carbon anhydrase, thiazides have sulfonamide group which is not replaceable. Even though thiazine drugs do not lead to hypercalcemia because they are readily reabsorbed, they increase the likelihood of developing hypercalcemia. There are various thiazide drugs, including metolazone, chlorothalidone, benzthiazide, cyclothiazide, chlorothiazide, indapamide, hydrochlorothiazide, and chlorthalide.
Thiazide drugs are clinically indicated in hypertension, mild heart failure, idiopathic hypercalciuria, nephronic diabetes insipidus, and resistance edema, when combined with loop diuretics. Though all thiazide drugs can be administered orally, their mechanisms of action differ. For example, Chlorothazide is highly soluble in liquids but takes a lot of time to dissolve and act in the body; therefore, it should be administered in large quantities. The side effects of thiazide drugs include hyperlipidemia, allergic reactions, hyperglycemia, hyponatremia, weakness, fatigability, and paresthesias.
Loop Diuretics
Loop diuretics drugs include bumetanide, furosemide, and torasemide. They are used for treating heart failure by removing excess fluids in the body that results when the heart does not pump enough blood to the body. The symptoms of this kind of heart failure include swelling of the legs and ankles and inability to breath properly. Loop diuretics are also used to treat other conditions, such as kidney and liver disorders that lead to accumulation of fluids in the body. Loop diuretics function by allowing the kidneys to pass a lot of fluids by inhibiting the transportation of water and salt in the kidney’s intracellular cells (Sica, Carter, Cushman, & Hamm, 2011). As more fluids get out of the body, fewer fluids remain in the blood stream. Fluids that had accumulated in the tissues of various body components, such as the lungs get to blood stream to replace the water lost. Loop diuretics bind to plasma proteins and thus prevent their filtration.
The side effects of loop diuretics include the imbalance of salt levels in the body, leading to lower levels of sodium, potassium, and magnesium and higher levels of calcium which may lead to confusion, abnormal beat of the heart, and weakness of the body. The conditions become severe when patients are diagnosed of gout or diabetes. Patients under loop diuretics might also feel dizzy if they stand for long and can have upset stomach. Other side effects brought about by loop diuretics include metabolic alkalosis, imbalance of electrolyte, hypokalemia, and hypocalcemia. Metabolic alkalosis takes place either because of the transport of sodium ions in the distal tubule through the exchange of sodium ions for hydrogen ions or due to the production of bicarbonate because of loss of negatively charged ions.
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Potassium-Sparing Diuretics
Potassium-sparing diuretics are drugs that inhibit the discharge of potassium in urine. They are used in combination with other drugs to help in the maintenance of the levels of potassium in the body. They work by either competing with aldosterone for places that help in the production of proteins which are usually processed when they react with aldosterone or blocking canals for sodium (Epstein & Calhoun, 2011). Since the proteins are not formed, there are low chances that the sites for exchanging potassium and sodium might take place.
The drugs include triamterene, spironolactone, eplerenone, and amiloride, and are clinically indicated for heart failure, as they increase the chances of heart failure patients’ survival. Triamterene and amiloride cause side effects, such as stomach cramp or ache, stomach upset, dry mouth, skin rash, weakness, headache, and dizziness. Epelerenone and spironolactone drugs cause side effects, such as sexual problems, irregular menstruation, skin rash, and confusion.
Osmotic Diuretics
Osmotic diuretics are drugs that impede water and sodium reabsorption. They include isosorbide and mannitol. The drugs normally work at the parts that allow the passage of water in nephrons. They improve the flow of blood to the kidney, thus deter the loop of Henle from concentrating urine. Osmotic diuretics are used to prevent anuria by increasing the volume of urine passed out of the body. They are also used to remove water from inside the cells, thus enhance the reduction of water from the body. This leads to treatment of diseases, such as oedema. Mannitol is widely used to manage cerebral oedema because it acts both immediately by improving the flow of blood and in a delayed manner through osmosis (Shawkat, Weatwod, & Mortimer, 2012). Mannol is also used to protect the kidneys, especially in patients with high likelihood of renal failure because it is allowed to pass in the kidney but not absorbed back, thus improves the delivery of sodium to distal tubules leading to constant osmotic diuretics. The side effects of osmotic diuretics drugs include vomiting, head ache, dizziness, nausea, blurred vision, and dehydration, in case a lot of water is removed from the body and hypernatremia in case the lost fluids are not adequately replaced.
HMG-CoA Reductase Inhibitor
Drugs that fall under HMG-CoA Inhibitor
HGM-CoA reductase drugs include simvastatin, rosuvastatin, atorvastatin, patavastatin, lovastatin, and fluvastatin. The extract from red yeast rice also contains natural molecules that lower the level of cholesterol.
Mechanism of Action of HMG-CoA Inhibitor
HMG-CoA reductase inhibitor works by replacing the HMG-CoA that is found in the liver thus lowering the level of cholesterol produced (Jasmine & Vanaja, 2013). This leads to the development of a protein referred to as LDL receptors. LDL moves to the cell membrane of the liver combine with LDL that passes the cell membrane. The LDL then passes to the liver and gets digested. In case the number of agents that receive cholesterol increases in the liver, the demand for cholesterol in the liver increases. This normally takes place in order to regulate the number of LDL. This means that the regulation of LDL depends on the movement of cholesterol in the body. In case the liver realizes high levels of cholesterol in the body, it increases the number of LDL receptors in the membrane of its cells. This improves the catabolism of LDL thus its removal from the cells. HMG-CoA reductase also works by inhibiting the production of VLDL (very low density lipoprotein). Statins are also effective at stabilizing plagues and reducing inflammation.
When HMG-CoA reductase is inhibited, the level of mevalonate comes down which consequently reduces the regulatory sterol pool that stimulates the regulation of HGM-CoA reductase, other coenzymes, and the LDL receptor. HGM-CoA reductase is able to deter the process that lead to conversion of HGM-CoA to L-mevolonate and manufacture of isoprenoid geranylgeranylpyrophosphate (Puttananjaiah et al., 2011). In addition to reducing the level of cholesterol, HGM-CoA reductase drugs have been clinically indicated in the myocardial infarction and stroke.
Effect of HMG-CoA reductase inhibitor on LDL and cholesterol level
HMG CoA reductase inhibitors are drugs that reduce the level of LDL (low density lipoprotein) cholesterol by stopping the biosynthesis of CoQ10 coenzyme and cholesterol. CoQ10 coenzyme is responsible for the production of cellular ATP. Though cholesterol is important for the working of the cells of the body, they contribute to the formation of atherosclerosis, a condition that facilitates blockage of arteries thus slowing the flow of blood in arteries. The reduction of the flow of blood in arteries normally causes chest pains and heart attack. If the reduction of blood flow occurs in arteries in the brain, stroke may occur. Statins are also capable of reducing the chances of developing Alzheimer’s disease and many forms of dementias (Padala et al., 2012).
Side Effects of HMG-CoA reductase and drug interactions
The side effects of HMG-CoA include pain in the abdomen, headache, diarrhea, bloating, chest pain, stomach pain, problems when urinating, pale stools, yellowness of skin or eyes, and rashes. Major side effects include damage of skeleton muscles and liver failure. The damage of muscles is a serious kind of myopathy that usually starts as muscle pain and can lead to loss of cells of muscles, a situation known as rhabdomyolysis. The situation is normally evident when HMG-CoA reductase inhibitor drugs are combined with other drugs that enhance the level of statin in the body. Rhabdomyolysis are probably as a result of lowering of levels of cholesterol in the membranes of skeleton muscles, lowering of the level of ubiquinone, and lowering of the level of farnesyl pyrophosphate. The drugs should therefore not be combined with drugs such as verapamil, diltiazem, itraconazole, clarithromycin, or protease inhibitors. Loss of memory and fusion are also associated with statins; some patients report cognitive weakening especially those suffering from Alzheimer’s disease because of the abnormal production of energy and metabolism of cholesterol in the brain (Padala et al., 2012). Statins can also cause loss in memory to patients with dementia. The loss of memory is because statins normally depend on their rate of solubility in water or lipids in order to move from the blood to brain. Statins that highly dissolve in lipids including lovastatin and simvastatin cross to the brain and reduce the level of cholesterol in the brain to a dangerous level causing problems to the neural system. Cognition problem brought about by statins that dissolve in lipids are also caused by the level of dosage of statins. High dosage levels worsen the problem of cognition than low or moderate dosage levels.
Patients with signs and symptoms of aching muscles, weakness of the body, or dark or brown urine should report their conditions immediately. Such patients should have their levels of creatine kinase assessed, and administration of HMG-CoA reductase drug stopped in case the level of creatine kinase is more than ten times the normal level. In case the level of creatine kinase resumes to normalcy, the administration of the statin drug can be resumed. Patients with small levels of creatine kinase may not be discontinued from statin administration.
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While many HMG-CoA reductase drugs have been administered to children, Food and Drug Administration recommends only lovastatin drug to be administered to pediatric patients. FDA also approved lovastatin for use by adolescents with heterozygous to lessen the levels of cholesterol, apolipoprotein B, and LDL-C. Pediatric patients should be given a dosage of less than 189 mg/dl irrespective of the therapy they take for diet or less than 160 mg/dl for patients whose family history indicates that they are more prevalent to contacting cardiovascular disease. Dosage less than 160 mg/dl should also be administered to patients who are twice as much likely to contact cardiovascular disease. HMG-CoA reductase are also capable of treating children with high levels of serum lipids, and managing patients after they have undergone cardiac transplantation and patients with Smith-Lemli-Opitz syndrome.