This article provides an overview of hyperkalaemia and hypokalaemia, two common electrolyte disturbances encountered in clinical practice. It explores their definitions, severity classification, underlying causes, and evidence-based management strategies. Particular emphasis is placed on pharmacological treatments, including mechanisms of action, adverse effects, and clinically significant drug interactions. Read more about the physiology of the external balance of potassium here. Hyperkalaemia Hyperkalaemia is defined as a serum potassium level over the reference range (typically >5.5 mmol/L). Hyperkalaemia primarily affects cardiac, neuromuscular, and metabolic function, and can be life-threatening. Elevated extracellular potassium reduces the resting membrane potential, impairing cardiac conduction. Severity Classification Severity Potassium serum level Mild 5.5-5.9mmol/l Moderate 6-6.4mmol/l Severe ≥6.5 mmol/l Treatment of hyperkalaemia depends on the serum level and the causative factor(s). Causative Factors of Hyperkalaemia Causative factors for hyperkalaemia include Chronic kidney disease or acute kidney injury Heart failure Uncontrolled diabetes Medications: ACE inhibitors Angiotensin-II receptor antagonists Potassium-sparing diuretics NSAIDs Trimethoprim Ciclosporin Tacrolimus Potassium salts Heparins Treatment of Hyperkalaemia The main aims of treatment for hyperkalaemia are 1. Protect the heart Intravenous calcium chloride or calcium gluconate is used when there are ECG changes, in order to protect the heart against myocardial excitability. 2. Redistribution of potassium into cells Rapid acting insulin can be administered intravenously to shift potassium back into cells thus reducing serum potassium levels via stimulation of the Na+/K+-ATPase. Insulin is often administered alongside glucose to avoid hypoglycaemia. Salbutamol is a β₂ adrenergic agonist usually used in the treatment of asthma, but can be used to treat hyperkalaemia via activation of the Na+/K+-ATPase. It is usually given via nebulisation for this indication. 3. Remove potassium from the body Potassium binders are used including sodium-zirconium-cyclosilicate, patiromer calcium and calcium resonium, the mechanism of action, pharmacokinetic parameters, side effects and clinically significant interactions are described below. Adobe stock Fig 1: Sodium potassium pump. Three sodium ions go outward and two potassium ions go inward, via an active transport mechanism Potassium Binding Agents Sodium zirconium cyclosilicate Sodium zirconium cyclosilicate (brand name Lokelma) is a cation exchange compound which can be given orally to treat hyperkalaemia. sodium zirconium is not absorbed or metabolised. The mechanism of action involves a uniform micropore structure that selectively captures potassium throughout the GI tract in exchange for hydrogen and sodium cations. This leads to a reduction in serum potassium levels and increases faecal excretion of potassium. Its’ onset of action is about an hour and normokalaemia is usually achieved within 24-48 hours. Patients who have a higher initial serum potassium level are likely to see greater reductions in serum potassium. Cautions Sodium zirconium should be used cautiously in patients undergoing abdominal x-ray as it can appear opaque. Furthermore, is high in sodium so should be used cautiously in patients with cardiovascular disease Adverse Effects Common side effects include oedema and hypokalaemia, sodium zirconium can also cause constipation. Interactions Sodium zirconium can transiently increase gastric pH by absorbing hydrogen ions which can lead to changes in solubility of drugs with pH dependent release profiles therefore administration should be at least 2 hours before or after these drugs e.g. ketoconazole, posaconazole, anti-HIV agents and tyrosine kinase inhibitors. Tacrolimus should also be administered at least 2 hours before or after sodium zirconium. Patiromer calcium Patiromer calcium (brand name Veltassa) is a cation exchange polymer which contains calcium-sorbitol complex as a counterion, which binds potassium in the GI tract, leading to a reduction in serum potassium and increase in faecal potassium excretion The onset of action is 4-7 hours and patiromer calcium is excreted in 24-48 hours. Cautions Patiromer calcium should be used cautiously in hypomagnesaemia and gastrointestinal disorders such as a history of bowel obstruction or major gastrointestinal surgery Adverse Effects Patients’ magnesium levels should be monitored, hypomagnesemia can occur (~5% of patients). Other common side effects include constipation, diarrhoea, abdominal pain and flatulence. Patiromer calcium also contains calcium, which may be absorbed, monitor calcium levels in patients at risk of hypercalcaemia. Interactions Patiromer calcium is not absorbed or metabolised by the body but may bind to co administered medicinal products, therefore administration should be separated by 3 hours from other medicinal products Calcium Resonium Calcium resonium is a polystyrene cation exchange resin which acts to remove excess potassium from the body by exchanging it for the cation ion (Ca2+). The onset of action is slow (>4 hours). The powder can be administered rectally as a retention enema (which is required to be retained for 9 hours) which is of use in vomiting or conditions such as ileus. Cautions Calcium resonium should not be used in obstructive bowel disease, conditions associated with hypercalcaemia, and should not be given orally to neonates. Adverse Effects Side effects include constipation, however magnesium based laxatives should not be used as this may cause systemic alkalosis. Interactions Intestinal obstruction due to concretions of aluminium hydroxide has been reported when aluminium hydroxide has been combined with the resin, therefore concomitant use should be avoided. Calcium Resonium should be administered at least 3 hours before or 3 hours after other oral medications as calcium resonium may bind to other orally administered medications that as lithium and levothyroxine Avoid administration with sorbitol or in patients with compromised gastrointestinal mobility as this may increase risk of GI stenosis, intestinal ischaemia, necrosis and perforation. Hypokalaemia Hypokalaemia is defined as a serum potassium level of <3.5mmol/L. Low potassium can lead to muscle weakness, cramps and cardiac arrhythmias. Causative Factors of Hypokalaemia Common causes of hypokalaemia include low potassium intake, excess losses e.g. in diarrhoea and vomiting, re-feeding syndrome and medications. Medications that can cause hypokalaemia include the following Loop diuretics Thiazide and thiazide-like diuretics Theophylline Laxatives Corticosteroids Amphotericin B Insulin Treatment of Hypokalaemia Treatment for hypokalaemia includes treating the root cause when possible. Potassium supplements may also be required, which may be provided IV or oral depending on the severity and patient condition. In patients taking digoxin or anti-arrhythmic drugs, potassium depletion may induce arrhythmias therefore treatment is required. References https://bnf.nice.org.uk/drugs/sodium-zirconium-cyclosilicate/ accessed 12.1.25 https://www.medicines.org.uk/emc/product/10059/smpc#gref accessed 12.1.25 https://www.medicines.org.uk/emc/product/10417/smpc accessed 12.1.25 https://bnf.nice.org.uk/treatment-summaries/hyperkalaemia/ accessed 12.1.25 Tingting Li, Anitha Vijayan, Insulin for the treatment of hyperkalemia: a double-edged sword?, Clinical Kidney Journal, Volume 7, Issue 3, June 2014, Pages 239–241, https://doi.org/10.1093/ckj/sfu049 https://www.medicines.org.uk/emc/product/1439/smpc#gref accessed 15.1.25 Do you think you’re ready? Take the quiz below Pro Feature - Quiz Hyperkalaemia and Hypokalaemia Question 1 of 3 Submitting... 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