Hyperuricaemia is a common clinical condition that can be defined as a serum uric acid level >6.8 mg/dl (404 µmol/l). Gout, a recognized complication of hyperuricaemia, is the most common inflammatory arthritis in adults. Drug-induced hyperuricaemia and gout present an emergent and increasingly prevalent problem in clinical practice. Diuretics are one of the most important causes of secondary hyperuricaemia. Drugs raise serum uric acid level by an increase of uric acid reabsorption and/or decrease in uric acid secretion. Several drugs may also increase uric acid production. In this review, drugs leading to hyperuricaemia are summarized with regard to their mechanism of action and clinical significance. Increased awareness of drugs that can induce hyperuricaemia and gout, and monitoring and prevention are key elements for reducing the morbidity related to drug-induced hyperuricaemia and gout.

Drug-induced hyperglycaemia and diabetes is a global issue. It may be a serious problem, as it increases the risk of microvascular and macrovascular complications, infections, metabolic coma and even death. Drugs may induce hyperglycaemia through a variety of mechanisms, including alterations in insulin secretion and sensitivity, direct cytotoxic effects on pancreatic cells and increases in glucose production. Antihypertensive drugs are not equally implicated in increasing serum glucose levels. Glycaemic adverse events occur more frequently with thiazide diuretics and with certain beta-blocking agents than with calcium-channel blockers and inhibitors of the renin-angiotensin system. Lipid-modifying agents may also induce hyperglycaemia, and the diabetogenic effect seems to differ between the different types and daily doses of statins. Nicotinic acid may also alter glycaemic control. Among the anti-infectives, severe life-threatening events have been reported with fluoroquinolones, especially when high doses are used. Protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors have been reported to induce alterations in glucose metabolism. Pentamidine-induced hyperglycaemia seems to be related to direct dysfunction in pancreatic cells. Phenytoin and valproic acid may also induce hyperglycaemia. The mechanisms of second-generation antipsychotic-associated hyperglycaemia, diabetes mellitus and ketoacidosis are complex and are mainly due to insulin resistance. Antidepressant agents with high daily doses seem to be more frequently associated with an increased risk of diabetes. Ketoacidosis may occur in patients receiving beta-adrenergic stimulants, and theophylline may also induce hyperglycaemia. Steroid diabetes is more frequently associated with high doses of glucocorticoids. Some chemotherapeutic agents carry a higher risk of hyperglycaemia, and calcineurin inhibitor-induced hyperglycaemia is mainly due to a decrease in insulin secretion. Hyperglycaemia has been associated with oral contraceptives containing high doses of oestrogen. Growth hormone therapy and somatostatin analogues may also induce hyperglycaemia. Clinicians should be aware of medications that may alter glycaemia. Efforts should be made to identify and closely monitor patients receiving drugs that are known to induce hyperglycaemia.

Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

Drugs are the most frequent cause of hypoglycaemia in adults. Although hypoglycaemia is a well known adverse effect of antidiabetic agents, it may occasionally develop in the course of treatment with drugs used in everyday clinical practice, including NSAIDs, analgesics, antibacterials, antimalarials, antiarrhythmics, antidepressants and other miscellaneous agents. They induce hypoglycaemia by stimulating insulin release, reducing insulin clearance or interfering with glucose metabolism. Several drugs may also potentiate the hypoglycaemic effect of antidiabetic agents. Administration of these agents to individuals with diabetes mellitus is of most concern. Many of these drugs, and depending on clinical setting, may also induce hyperglycaemia. Drug-induced hepatotoxicity and nephrotoxicity may lead in certain circumstances to hypoglycaemia. Some drugs may also induce hypoglycaemia by causing pancreatitis. Drug-induced hypoglycaemia is usually mild but may be severe. Effective clinical management can be handled through awareness of this drug-induced adverse effect on blood glucose levels. Herein, we review pertinent clinical information on the incidence of drug-induced hypoglycaemia and discuss the underlying pathophysiological mechanisms, and prevention and management.

Clinicians should be aware of the ability of metformin to induce cutaneous LV.