Essential Ions Lecture Notes PDF

University of Babylon Faculty of Pharmacy Lecture 2 Essential ions Lec. Ph.D Aamer Mousa Ali 1  Potassium Potassium has atomic number 19 and the chemical symbo...

University of Babylon Faculty of Pharmacy Lecture 2 Essential ions Lec. Ph.D Aamer Mousa Ali 1  Potassium Potassium has atomic number 19 and the chemical symbol K, which is derived from its Latin name ‘kalium’. Biological importance: Potassium ions are essential for the human body and are also present in plants, The so-called action potential occurs in a variety of excitable cells such as neurons, muscle cells and endocrine cells The Na+/K+-based action potential is short-lived (only 1 ms) and therefore mostly found in the brain and nerve cells The major use of K+ Fertilisers such as potassium chloride (KCl), potassium sulfate (K2SO4) and potassium nitrate (KNO3). oxidizing agent such as potassium bromate (KBrO3) food preservative such as Potassium bisulfite (KHSO3) in wine and beer. In the human body, 95% of the K+ can be found inside the cells, with the remaining 5% mainly circulating in the blood plasma 2  This balance is carefully maintained by the Na+/K+ pump, and imbalances, such as seen in hypo or hyperkalaemia, can have serious consequences. Hypokalemia. is a potentially serious condition where the patient has low levels of K+ in his/her blood Plasma Symptoms include weakness of the muscles or ECG (electrocardiogram) abnormalities hypokalemia can be a result of reduced K+ intake caused by GI disturbance , such as diarrhea and vomiting increased excretion of K+ caused by diuresis is often found in patients treated with diuretics such as thiazides Potassium ions are excreted via the kidneys. Within the kidneys, ∼150–180 of plasma is filtered every day through the glomerulus, which is part of the nephron a variety of ions are secreted and re-absorbed in order to regulate plasma imbalances and manage the urine volume K+ is passively secreted at the proximal tubule and also moves into the interstitial fluid via a counter-flow process to Na+ mainly at the distal tubule (Figure 2.1). 3 Figure 2.1: Illustration of a nephron showing areas of potassium transport 4 Oral supplementation Oral supplementation in form of potassium salts is especially necessary in patients patients who is take anti-arrhythmic drugs patients who is suffer from renal artery stenosis. patients who is suffer from severe heart failure. patients who is shown severe K+ losses due to  chronic diarrhea  abusive use of laxatives Regulation of the plasma K+ level may also be required in the care of elderly patients when the K+ intake is reduced as a result of changing dietary habits (special attention has to be given to patients with renal insufficiency because K+ excretion might be reduced) 5 Potassium salts and their clinical application: Potassium salts are preferably given as liquid preparations, and KCl is the preferred salt used. Other potassium-based salts can be used if the patient is at risk of developing hyperchloraemia – increased chloride plasma levels Typically potassium salts are dissolved in water, but the salty and bitter taste makes them difficult to formulate Oral bicarbonate solutions such as potassium bicarbonate are typically given orally for chronic acidosis states – low pH of the blood plasma This can be again due to impaired kidney function. The use of potassium bicarbonate for the treatment of acidosis has to be carefully evaluated Potassium citrate is used in the United Kingdom as an over-the-counter drug for the relief from discomfort experienced in mild urinary-tract infections by increasing the urinary pH(It should be not given to men if they experience pain in the kidney area (risk of kidney stones) or if blood or pus is present in the urine. Also, should avoid taking potassium citrate without consultation with their general practitioner (GP). Caution is generally advised to patients with renal impairment, cardiac problems and the elderly 6  Adverse effects and toxicity: hyperkalaemia The therapeutic window for K+ in the blood plasma is very small (3.5–5.0 mmol), and especially hyperkalemia, an increased level of K+ in the plasma, can lead to severe health problems Potassium salts can cause nausea and vomiting and in extreme cases can lead to small bowel ulcerations Acute severe hyperkalaemia is defined when the plasma potassium concentration exceeds 6.5 mmol/l or if ECG changes are seen This can lead to cardiac arrest, which needs immediate treatment Treatment options include  the use of calcium gluconate intravenous injections, which minimises the effects of hyperkalaemia on the heart  The intravenous injection of soluble insulin promotes the shift of potassium ions into the cells  Diuretics can also be used to increase the secretion of K+ in the kidneys  and dialysis can be a good option if urgent treatment is required Potassium salts are also available in the form of tablets or capsules for oral application especially as nonprescription very high concentrations of K+ are known to be toxic to tissue cells and can cause injury to the gastric mucosa. Therefore, nonprescription potassium supplement pills are usually restricted to < 100 mg K+ 7 Magnesium The element magnesium (Mg) is a silvery-white and lightweight metal Mg2+ is an essential ion in the human body and the imbalance should be corrected Most magnesium salts are soluble in water, and given in large amounts they work as a laxative in the human body Aqueous magnesium ions are sour in taste Magnesium hydroxide (MgOH2) has only limited solubility in water and the resulting suspension is called milk of magnesia , which is commonly used as an antacid and is known to be a mild base the most magnesium salts are water soluble and therefore processed vegetables, mainly cooked in water, are low in magnesium ion content. 8 Biological importance: Mg2+ is an essential ion in the human body  Mg2+ is a crucial constituent in numerous enzymatic processes  Mg2+ is essential to most living cells as a signaling molecule and is involved in nucleic acid biochemistry dealing with the manipulation of ATP (adenosine triphosphate), DNA, RNA and related processes. For example, ATP has to be coordinated to a magnesium ion in order to become biologically active. Mg2+ also stabilizes DNA and RNA structures, which can be seen in their increased melting points. Mg2+ ions form the redox-active center in chlorophyll In the human body, Mg2+ is the fourth most abundant cation and the second most abundant ion in the interstitial fluid Mg2+ is an essential co-factor dealing with more than 300 cellular enzymatic processes Clinical features the human body contains about 24 g of magnesium ions, with half of it being incorporated into bones and the other half being present in muscles and soft tissue The majority of Mg2+ is absorbed in the ilium and colon, and the kidneys are the major excretory organ Mg2+ is filtered at the glomerulus 9  The kidneys regulate the magnesium ion levels in plasma. Magnesium ion imbalances can manifest in a variety of conditions such as hypo- and hypermagnesaemia. Hypermagnesia  as a result high levels of Mg2+ are retained when the patient has renal failure  hypermagnesia can cause muscle weakness and arrhythmia, but it is a rare condition Hypomagnesia  defined as low magnesium levels in the blood plasma,  can be the result of losses in the GI tract, for example, excessive diarrhea , alcoholism  Hypomagnesia is often followed by hypocalcaemia (low calcium ion plasma levels) as well as hypokalaemia and hyponatraemia 10  Oral supplementation and preparations Magnesium ion preparations are also used  antacids mostly in combination with aluminium-based salts aluminium hydroxide [Al(OH)3] Magnesium hydroxide [Mg(OH)2] Magnesium trisilicate (Mg2Si3O8)  magnesium salts are involved in the treatment of arrhythmia  treatment of eclampsia (threatening hypertensive disorder in pregnant women)`  Laxative(stimulates intestinal movement, as the magnesium ions increases the water content in the intestines through its osmotic effect and as a result softens any faeces present.  threatening hypertensive disorder in pregnant women. Symptomatic hypomagnesaemia is associated with plasma serum Mg2+ levels of < 0.5- 1 mmol/ kg for a period of 5 days or more Mg2+ ions are initially given as intravenous (i.v.) or intramuscular (i.m) injection; the latter is fairly painful and consisting of magnesium sulfate (MgSO4) MgSO4 can also be used as emergency treatment for very serious arrhythmias, a disorder of the heart rate (pulse). In an emergency treatment, it is usually given intravenously as one single dose or with one repeat orally taken magnesium salts can show interactions with other drugs taken simultaneously.  Magnesium trisilicate reduces the absorption of iron products, certain antibiotics (such as Nitrofurantoin) or antimalarial drugs (such as Proguanil) 11  Magnesium salt preparations, which form part of antacids, are not recommended to be taken at the same time as a variety of drugs such as ACE inhibitors, aspirin and penicillamine. Calcium Calcium (Ca) Calcium has the symbol Ca and atomic number 20 and is a soft grey alkaline earth metal Ca is the most abundant inorganic element in the human body Ca2+ has numerous intra and extracellular physiological roles Calcium carbonate CaCO3 can be found in clinical applications such as antacids Ca2+ play important roles in the human body Biological importance Calcium ions play important roles in the human body in a variety of neurological and endocrinological processes Ca is known as a cellular messenger It has a large intra- versus extracellular gradient (1 : 10 000), which is highly regulated by hormones This gradient is necessary to maintain the cellular responsiveness to diverse extracellular stimuli Ca2+ are also involved in the formation of bones and teeth, which act also as a reservoir for Ca2+ 12 A normal adult body contains ~1000 g of Ca Most of which is stored in bones and teeth The remaining can be found in the extracellular space The intra and extracellular Ca2+ concentration is rigorously controlled Modified hydroxylapatite, also frequently called hydroxyapatite and better known as bone mineral, makes up ~50% of our bones Hydroxylapatite is a natural form of the mineral calcium apatite, whose formula is Ca10(PO4)6(OH)2 Modifications of hydroxylapatite can also be found in the teeth A chemically identical substance is often used as filler It is believed that an optimal dietary calcium intake can prevent chronic diseases In the Stone Age, the average calcium intake was 2000-3000 mg Ca2+/day per adult Now-a-days it has decreased to an average of 600 mg/day It is believed that there are linkages to various chronic diseases, such as bone fragility, high blood pressure and colon cancer Ca2+ is an essential nutrient Three stages of life identified when the human body needs an increased level of Ca2+: Childhood and adolescence Pregnancy and lactation 13 Old age Osteoporosis is most commonly associated with Ca deficiency 99% of Ca2+ is found in the bones Ca uptake and plasma concentrations are closely regulated by hormones PTH (parathyroid hormone) Studies support the hypothesis that Ca supplementation can reduce blood pressure It has been hypothesised that there exists a link between dietary Ca and weight management in humans Renal osteodystrophy, also called renal bone disease, is a bone mineralisation deficiency seen in patients with chronic or end-stage renal failure Vitamin D is activated in the liver to calcidiol and then in the kidney to calcitriol In patients with renal failure, the activation to calcitriol is depressed Results in a decreased concentration of Ca2+ in the blood plasma, This reduces the amount of free Ca2+ in the blood even more The pituitary gland senses the low levels of plasma Ca2+ and releases PTH This leads to a weakening of the bone structure Around 20-40% of all kidney stones are associated with elevated Ca2+ level in the urine, The conclusion is that kidney stone formation in healthy individuals is not associated with Ca supplementation 14  Ca supplements are usually required only if the dietary Ca2+ intake is insufficient A slow i.v. injection of a 10% calcium gluconate has been recommended In severe acute hypocalcaemia, Clinical application A variety of calcium salts are used for clinical application Ca carbonate, Ca chloride, Ca phosphate , Ca lactate ,Ca aspartate, Ca gluconate Ca carbonate is the most common and least expensive calcium supplement Ca carbonate consists of 40% Ca2+ Ca citrate is more easily absorbed (bioavailability is 2.5 times higher than Ca carbonate) It is believed that it contributes less to the formation of kidney stones The properties of Ca lactate are similar to those of Ca carbonate Ca gluconate is prescribed as a Ca supplement It is also used in the urgent treatment of hyperkalaemia Side effects have been observed only at relatively high doses Manifested in GI disturbances such as constipation and bloating and, in extreme cases, arrhythmia It is important to note that calcium ions can interfere with the absorption of some drugs, such as antibiotics 15  It has been suggested that low dietary Ca intake would be the best method to prevent the recurrence of kidney stones More recent studies showed that a low Ca diet did not prevent the formation of kidney stones It was actually found that a higher Ca intake resulted in a significant reduction of the recurrence of kidney stones by around 50% It is believed that the restriction of Ca leads to an increase in absorption and excretion of oxalate in the urine. 16 17 Thank you 18