ABSTRACT Hypokalaemia (defined as a plasma potassium concentration<3.5 mEq/L) is a common electrolyte abnormality in clinical practice. Drugs are a common cause of either asymptomatic or symptomatic hypokalaemia. Drug-induced hypokalaemia is an important problem particularly in the elderly and in patients with cardiovascular, renal or hepatic disease. Hypokalaemia can complicate the use of the drug in the therapeutic concentration range, and can also be precipitated with overdose or conditions leading to drug intoxication. Because the etiologies of hypokalaemia are numerous, the diagnosis of drug-induced hypokalaemia may be overlooked. Physicians should always pay close attention to this common side effect. Evaluation and management of a hypokalaemic patient should include a careful review of medications history to determine if a drug capable of causing or aggravating this electrolyte abnormality is present.
- SourceAvailable from: Shunsuke Yamada[Show abstract] [Hide abstract]
ABSTRACT: Yokukansan is a Chinese herbal medicine containing licorice that has been shown to alleviate the behavioral and psychological symptoms of Alzheimer’s disease, with few adverse effects. Increasing numbers of patients with Alzheimer’s disease in Japan are now being treated with this drug. However, yokukansan should be used with caution because of its potential to induce pseudoaldosteronism through the inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol into cortisone. We present the case of an 88-year-old woman with a history of Alzheimer’s disease who was transferred to our emergency department because of drowsiness, anorexia, and muscle weakness. Her blood pressure was 168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic alkalosis (pH 7.54; HCO 3−, 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140 mmol/l), and respiratory disorders (pCO2, 60.5 mmHg; pO2, 63.8 mmHg). Plasma renin activity and aldosterone concentration were suppressed, and urinary potassium excretion was 22 mmol/l (calculated transtubular potassium gradient 12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular premature contractions. Echocardiography denied volume depletion. Medical interview disclosed that she had been treated with a Chinese herbal medicine (yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and respiratory acidosis all subsided shortly after the discontinuation of yokukansan and initiation of intravenous potassium replacement. This case highlights the need for nephrologists to consider the possible involvement of Chinese herbal medicines, including yokukansan, when they encounter hypokalemia in elderly patients.CEN Case Reports. 05/2012; 2(1).
Article: Drug-Induced Hyperkalemia.[Show abstract] [Hide abstract]
ABSTRACT: 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.Drug Safety 07/2014; · 2.62 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The Wadi Onib mafic-ultramafic complex represents the best preserved, though tec-tonically dismembered, Neoproterozoic (Pan-African) ophiolite in the northern Red Sea Hills of the Sudan. Forming part of a regionally distinct, southwest to northeast trending ophiolite-decorated shear belt (Onib-Sol Hamed suture) it consists, from bottom to top, of a basal peridotite unit, an exceptionally thick (2–3 km) transitional zone (TZ) of in-terlayered cumulates, an isotropic gabbroic mass with plagiogranite bodies, and a sheeted basic dyke complex. The highest stratigraphic section of the ophiolitic sequence is rep-resented by pillowed basaltic lavas (containing fragmentary lenses of ribbon chert and/or graphitic to shaly carbonates) which are tectonically juxtaposed against the basal peri-dotite. Whereas the basal unit is strongly serpentinized and/or carbonatized, the transitional zone comprises abundant and well preserved pyroxenites, some of which are enriched in Cr relative to TiO 2 . The TZ also shows a polycyclic cumulate arrangement that possibly originated from multiple magma pulses rather than from tectonic interslicing. Moreover, mineral grading, gravity stratification and a spectrum of folds with varying geometrical dispositions and amplitudes within discrete layers as well as a vertical metamorphic zona-tion (suggesting seafloor hydrothermal processes) are evident within the Onib ophiolitic sequence. In particular, the volcanic component is Ti-rich, has a transitional IAT/MORB character and is indistinguishable from anomalous MORB and/or marginal basin basalts. Thus, the Onib is envisaged to be of arc/back-arc (marginal) basin affiliation, and it is clas-sified as a supra-subduction zone (SSZ) rather than normal MORB-type ophiolite. It was generated at 808 ± 14 Ma as documented by a plagiogranite single zircon Pb-Pb age. The ophiolitic sequence probably resulted from parental magma(s) generated through multi-stage partial fusion of mantle peridotite.Precambrian ophiolites, Developments in Precambrian geology, vol. 13 edited by TM Kusky, 01/2006: pages 163-206; Elsevier Science Publishers.
Current Drug Safety, 2009, 4, 55-61 55
1574-8863/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd.
Chaker Ben Salem*,1, Houssem Hmouda2 and Kamel Bouraoui1
1Department of Clinical Pharmacology, Faculty of Medicine of Sousse, Sousse, Tunisia
2Medical Intensive Care Unit, Sahloul University Hospital, Sousse, Tunisia
Abstract: Hypokalaemia (defined as a plasma potassium concentration <3.5 mEq/L) is a common electrolyte abnormality
in clinical practice. Drugs are a common cause of either asymptomatic or symptomatic hypokalaemia. Drug-induced hy-
pokalaemia is an important problem particularly in the elderly and in patients with cardiovascular, renal or hepatic dis-
ease. Hypokalaemia can complicate the use of the drug in the therapeutic concentration range, and can also be precipitated
with overdose or conditions leading to drug intoxication. Because the etiologies of hypokalaemia are numerous, the diag-
nosis of drug-induced hypokalaemia may be overlooked. Physicians should always pay close attention to this common
side effect. Evaluation and management of a hypokalaemic patient should include a careful review of medications history
to determine if a drug capable of causing or aggravating this electrolyte abnormality is present.
tion <3.5 mEq/L) is one of the most common electrolyte
abnormality found in clinical practice. Mild hypokalaemia is
usually well tolerated in healthy people, but hypokalaemia
can be lifethreatening when severe. The risks of morbidity
and mortality are increased in the elderly, patients with car-
diovascular, hepatic or renal disease. Patients with underly-
ing cardiovascular disease including myocardial infarction
have an increased risk of ventricular dysrhythmias which is
almost linearly related to the degree of hypokalaemia. In
fact, the catecholamine surge that accompanies acute myo-
cardial infarction causes redistributional hypokalaemia and
hyperpolarizes non-ischemic myocardium, producing electri-
cal inhomogeneity and ventricular arrhythmias . Hy-
pokalaemia seems also to be an independent predictor of
mortality in heart failure. In a recent study serum potassium
<4 mEq/L was associated with increased mortality, with a
trend towards increased hospitalization in wide spectrum of
ambulatory patients with chronic, mild to moderate systolic
and diastolic heart failure . Potassium depletion can lead
to muscle cramps and other symptoms. However, the elderly
are less likely to have classic symptoms since they are less
active, and their symptoms may be confused with other
medical problems. In addition, they are predisposed to be-
coming potassium depleted because of possible inadequate
dietary intake of potassium, and greater number of medica-
tions that may lead to potassium depletion . Potassium
depletion causes a decrease in acetylcholine levels due to
diminished choline acetylase activity. This effect can depress
neuromuscular function causing decreased intestinal motility
and even paralytic ileus, contributing to the precipitation of
hepatic coma in patients with hepatic insufficiency. In addi-
tion, hypokalaemia can contribute to the development, or
aggravates the symptoms of hepatic encephabopathy by in-
creasing proximal tubule ammoniagenesis. In hepatic
Hypokalaemia (defined as a plasma potassium concentra-
*Address correspondence to this author at the Departement de Pharmacolo-
gie Clinique, Faculté de Médecine de Sousse, Avenue Mohamed Karoui,
4002 Sousse, Tunisia; Tel: 00 216 98 240 775; Fax: 00 216 73 224 899;
E-mail: email@example.com or firstname.lastname@example.org
insufficiency, the increased systemic burden of ammonia
resulting from increased renal ammoniagenesis can be suffi-
cient to cause the development or worsen the symptoms of
hepatic encephabopathy .
the diagnosis of drug-induced hypokalaemia may be over-
looked. Only systematic review of medications history al-
lows recognition and prompt treatment.
Below, we provide an exhaustive review of drug-induced
hypokalaemia, and discuss the underlying mechanisms and
consequent relevant issues for clinical practice.
Because the etiologies of hypokalaemia are numerous,
between January 1966 to June 2008, regardless of the lan-
guage. The approach used was: hypokalaemia and potassium
disorders as keywords with the subheading “drug-induced”,
and certain drugs were inserted as keywords.
Data were identified from MEDLINE from the period
describe the same topic, only English or French articles were
analysed. However, in our review, pertinent informations in
articles written in other languages (such as Danish or Chi-
nese) has been extracted from the abstract in MEDLINE.
Identified articles were evaluated to determine whether any
of their references contained additional relevant publications.
We excluded the articles with insufficient clinical or labora-
If there were relevant articles in many languages which
lyte abnormality [5,6], and can induce either mild and as-
ymptomatic disorder or severe, even lethal hypokalaemia.
Patients with mild hypokalaemia usually have no symptoms.
If serum potassium level decreases further, nerves and mus-
cles are predominantly affected, causing weakness, fatigue,
leg cramps, myalgias, fasiculations, constipation and ileus
. In severe cases, rhabdomyolysis, ascending paralysis and
respiratory failure may occur. Other manifestations may be
associated such as atrial flutter, paroxysmal atrial tachycar-
dia, ventricular tachycardia and fibrillation, metabolic alka-
losis, nephrogenic diabetes insipidus, and enhanced renal
Medications constitute a common cause of this electro-
56 Current Drug Safety, 2009, Vol. 4, No. 1 Ben Salem et al.
hypokalaemia in hospitalised patients. Hypokalaemia has
been reported in over 20% of hospitalised patients (potas-
sium level <3.6 mmol/l), and a level < 3 mmol/l was found
in almost 3.5 to 5% in these studies [6,8,9]. Profound hy-
pokalaemia, defined as a serum potassium level of less than
2.5 mmol/l, is rare and occurred in less than 1% of hospital-
ised patients [9,10]. Mortality in the hypokalaemic popula-
tion was 10-fold higher than the general hospitalised popula-
tion. Drugs accounted for a consequent proportion in the
pathogenesis of this electrolyte abnormality in these hospi-
talised patients. In a recent study, drug-induced hypokalae-
mia is found in 2.5% of a population of the very old elderly
(subjects aged ?75 years) . Hence, it is important to ap-
propriately detect and treat hypokalaemia.
Several studies have examined the incidence and cause of
two major mechanisms. Hypokalaemia may result from re-
distribution between extracellular and intracellular compart-
ments, or an increased potassium loss through the gastroin-
testinal tract or kidney.
TRANSCELLULAR POTASSIUM SHIFTS
Drugs can decrease serum potassium concentration by
extracellular compartment to cells but the total body potas-
sium remains usually normal. Consequently, hypokalaemia
may be sometimes apparently minor, but should not be un-
derestimated . Indeed, clinicians should be aware that the
extent and consequences of hypokalaemia may vary in clini-
cal practice depending on factors such as co-morbidity, co-
prescribed medications, self-medications, drug dosage or
Numerous drugs can cause a shift of potassium from the
the Na+-K+-ATPase pump, leading to a shift of extracellular
potassium to the intracellular space . Conventional intra-
venous or inhaled doses of selective ?2-agonists reduce se-
rum potassium by 0.4-1.2 mmol/l in a dose dependent man-
ner [13,14]. Indeed, profound hypokalaemia (less than 2.5
mmol l-1) has been described when ?2-agonists are used in
higher doses and in self poisoning . Patients with severe
asthma, taking also theophylline and corticosteroids that also
decrease potassium level, appear to be more likely to de-
velop severe hypokalaemia when treated with ?2-agonists
. Serum potassium levels should therefore be monitored.
More interestingly, the hypokalaemic effect of ?2-agonists is
used in some cases to treat hyperkalaemia. Indeed, albuterol
was prescribed as adjunctive therapy to insulin and glucose
to manage hyperkalaemia.
?2-agonists may precipitate hypokalaemia by activating
Inhibitors of Uterine Contraction
patients treated with intravenous ritodrine or terbulatine .
The stimulation of cellular potassium uptake by these drugs
underlies the decrease of serum potassium level with a
maximum decrease in plasma potassium occurring few hours
of drug infusion. Changes in plasma aldosterone, renal po-
tassium excretion or acid-base homeostasis do not contribute
to ritodrine-or terbutaline-induced hypokalaemia. Careful
Various degrees of hypokalaemia have been described in
monitoring of electrolytes and cardiac rhythm during toco-
lytic therapy with ritodrine or terbutaline are mandatory.
are potent stimulants of the Na+-K+-ATPase activity .
Intentional ingestion of large amounts of pseudoephedrine
and the abuse of ephedrine used in some cough mixture can
cause severe hypokalaemia . The association of corticos-
teroids with these decongestants can aggravate hypokalae-
mia. Physicians should be aware of the potential for these
drug-combinations to cause hypokalaemia.
In experimental studies, pseudoephedrine and ephedrine
pamine and dobutamine can cause hypokalaemia [20,21]. At
dosages of epinephrine > 80 ng/kg/min, hypokalaemia is
common . Catecholamines shift the potassium of ex-
tracellular space to the intracellular space via stimulation of
the ?2-adrenoceptors and enhancement of insulin secretion.
They may lead to arrhythmias and rhabdomayolysis in se-
vere cases . Therefore, potassium levels must be moni-
tored during and after high doses infusion of epinephrine
particularly during cardiac arrest .
Catecholamines such as adrenaline, noradrenaline, do-
toxication but it can also be seen with therapeutic doses .
A linear concentration-response relationship was docu-
mented between serum theophylline concentration and hy-
pokalaemia . Theophylline increases Na+-K+-ATPase
activity by inhibiting cellular phosphodisesterase with a re-
sultant trans-cellular shift of potassium which may aggravate
the theophylline-induced arrhythmia. Consumption of large
quantities of caffeine, present in some drinks, can lead to
severe hypokalaemia by stimulating cell membrane Na+-K+-
Severe hypokalaemia was noted with theophylline in-
pathogenesis of hypokalaemia remains equivocal . Cal-
cium-channel blockers alter potassium transport to cells .
Their possible hypokalaemic effect may be due in a part to
the enhancement of the adrenaline-induced intracellular
transfer of potassium from the extracellular space . Long
term treatment with nifedipine and nitrendipine may reduce
serum potassium concentrations in hypertensive patients
. Verapamil does not usually lead to hypokalaemia when
serum verapamil levels are therapeutic; however, intentional
ingestion of excess amounts of verapamil, can significantly
reduce plasma potassium levels .
The implication of calcium-channel blockers in the
can lead to hypokalaemia. Exogenous insulin always causes
a transient reduction in serum potassium but severe hy-
pokalaemia can occur during the treatment of diabetic ke-
toacidosis or in intentional overdose of insulin . Insulin
tolerance test may also be responsible for severe hypokalae-
mia with cardiac arrhythmias . Insulin increases cellular
potassium uptake in the liver, muscle, and adipose tissue by
activating the cellular Na+-K+-ATPase pump. The fall in
Insulin promotes transfer of potassium to the cells and
Drug-Induced Hypokalaemia Current Drug Safety, 2009, Vol. 4, No. 1 57
potassium level is independent of plasma aldosterone and
epinephrine levels .
large amounts of chloroquine . It seems due to a potas-
sium shift from extracellular space to cells. The decrease of
potassium serum is closely correlated with chloroquine con-
centration. Profound hypokalaemia (< 2mmol/l) has been
reported in 11% of cases after acute chloroquine intoxica-
tion. Patients who died from chloroquine overdose had sig-
nificantly lower serum potassium than survivors, but this
disorder could not be directly considered as the cause of
death in most cases . Potassium supplementation can be
used for the treatment of severe chlorquine-induced hy-
pokalaemia; however aggressive replacement can lead to
hyperkalaemia which potentially could contribute to the car-
diotoxic effects of this drug .
Hypokalaemia was frequently noted after ingestion of
lowing anaesthesia. The cause of this decrease is uncertain. It
may be due to the adrenergic stimulation or hyperventilation
during surgery. Thiopental sodium may induce severe hy-
pokalaemia . The exact mechanism of thiopental-induced
hypokalaemia is not elucidated, but seems secondary to the
movement of potassium between the extracellular and intra-
cellular compartments . Hypokalaemia was also noted
with supra-normal levels of lidocaine .
A decrease in serum potassium levels has occurred fol-
Increased Loss of Potassium
Loss from Gastrointestinal Tract
In addition, sodium wasting in diarrhoeal stool can aggravate
potassium loss from both gut and kidney by secondary aldos-
teronism. Laxatives abuse causes excessive potassium loss in
the stool and may result in hypokalaemia, sometimes severe
resulting in rhabdomayolysis . Phenolphthalein and
docusate sodium has been found empirically to cause more
potassium loss than other laxatives such as sorbitol or so-
dium sulphate . In all cases of hypokalaemia, a laxative
abuse must be looked for in the patient history. Phosphate
enemas, used in bowel clearance before radiology, endo-
scopy and surgery, are associated with significant hy-
pokalaemia , and should be used cautiously in children
Drug-induced chronic diarrhoea can cause hypokalaemia.
with severe diarrhoea leading to hypokalaemia . Chemo-
therapy which induces diarrhoea and vomiting can also lead
to hypokalaemia . Diarrhea is the most common cause of
hypokalaemia in patients treated by capecitabine . Cyclo
3 fort, used in the treatment of chronic venous insufficiency,
can cause chronic diarrhoea with hypokalaemia . Diace-
tylrhein, a chondroprotective agent, can also cause severe
diarrhoea with hypokalaemia.
Persistent vomiting complicating drug therapy could lead
to hypokalaemia which is generally due to metabolic alkalo-
sis and hyperaldosteronism. For example, recreational drug-
induced vomiting can lead to severe hypokalaemia and
metabolic alkalosis . Vomiting-induced by quinine in-
toxication can cause severe hypokalaemia, potentiating the
Some antibiotics can cause pseudomembranous colitis
risk of quinine-induced arrhythmias . Vomiting due to
digitalis toxicity can aggravate an existing lack of potassium.
Even, at therapeutic dose, digitalis-induced arrhythmias can
be observed when hypokalaemia is present. Potassium deple-
tion must be corrected in patients taking digoxin.
Loss from Kidney
of potassium by various mechanisms. The main mechanisms
include renal tubular damage, increased delivery of sodium
or an excessive anion load to the distal tubule, and an inap-
propriate increase of sodium potassium exchange in the
Many classes of drugs may cause excessive kidney loss
of drug-induced hypokalaemia . Loop diuretics seem to
produce less average fall of potassium concentration com-
pared with thiazides . However, the potassium depletion
is usually mild and severe hypokalaemia (less than
3.0mmol/l) is uncommon with diuretics. The prevalence of
diuretic-induced hypokalaemia varies from a study to an-
other and with the used dosage. A recent study found that
diuretic-induced hypokalaemia was the most prevalent ad-
verse drug reaction in an elderly hospitalised population both
during hospitalisation and at the time of admission . In a
retrospective study, 33% of elderly patients taking fu-
rosemide alone were hypokalaemic as compared to 4% of
those receiving furosemide in combination with potassium
supplementation . In a recent observational study, hy-
pokalaemia occured in 8.5% of patients treated with low
doses of thiazide diuretics but in only about 1% did the po-
tassium level fall to less than 3 mmol/l . The risk of hy-
pokalaemia with thiazide is dose dependent and is greater
when dietary sodium intake is higher . There was no
significant association with age and no association with gen-
der. Diuretics affect the potassium serum levels by a variety
of mechanisms. Loop and thiazide diuretics block chloride-
associated sodium reabsorption in the loop of Henle and in
the early distal tubule respectively, resulting in an increased
sodium delivery to the distal tubule channel. Sodium is se-
lectively reabsorbed via the amiloride-sensitive sodium
channel creating a favourable gradient for potassium secre-
tion via potassium channels leading to hypokalaemia.
Moreover, Volume depletion caused by diuretics activates
renin-angiotensin-aldosterone pathway. Therefore, increased
production of aldosterone stimulates the reabsorbtion of so-
dium and water and promotes excretion of potassium via the
secretory potassium channels in the collecting ducts leading
to hypokalaemia . In addition, aldosterone can cause
metabolic alkalosis which can worsen the diuretic-induced
hypokalaemia by increasing potassium shift into cells. Hy-
pokalaemia can also contribute to the maintenance of a
metabolic alkalosis by enhancing bicarbonate absorption and
increasing chloride excretion in the kidney. Aldosterone also
has an extrarenal activity by stimulating cellular Na+-K +-
ATPase pump activity. Loop and, occasionally, thiazide diu-
retics may cause hypomagnesemia. The coexistent hyomag-
nesemia can promote renal potassium wasting and increase
the potential for arrhythmias. In fact, any magnesium deficit
should be detected and corrected with magnesium supple-
mentation. Magnesium is important for potassium uptake
Loop and thiazide diuretics are the most common cause
58 Current Drug Safety, 2009, Vol. 4, No. 1 Ben Salem et al.
and for the maintenance of intracellular potassium levels,
particularly in the myocardium. Combined deficiency may
potentiate the risk of cardiac arrhythmias .
tolerance. It has been also implicated as a cause of new onset
diabetes and in theory in a possible reduction in benefice of
diuretic therapy. However, the new onset diabetes that oc-
curs during diuretic treatment has not been shown to increase
cardiovascular disease, either in clinical trials, or during
longer observational studies . The exact mechanism by
which hypokalaemia may cause glucose intolerance is still
unclear. It seems related to the inhibition of insulin secretion
by the beta cells, and reductions in extracellular fluid volume
and cardiac output. In addition, the evidence linking ar-
rhythmias or cardiac death to the diuretic-induced hy-
pokalaemia remains an area of controversy. Some studies
suggest that hypokalaemia-induced arrhythmias, torsades de
pointes and cardiac arrest have been involved as a cause of
the deleterious effect of diuretics on cardiovascular risk, es-
pecially in patients at greatest risk such as history of left ven-
tricular hypertrophy, heart failure or myocardial infarction
[58-60]. However, several studies have shown no increase in
the cardiac arrhythmias or in the mortality [61,62]. Even
though the evidence linking arrhythmias and cardiac death to
the diuretic-induced hypokalaemia remains an area of con-
troversy; this latter is undoubtedly associated with a risk of
serious arrythmias when diuretics are co-administrated with
drugs that prolong the QT interval. Therefore, caution should
be taken when diuretics are co-administrated with drug-
inducing QT interval prolongation.
Diuretic-induced hypokalaemia may lead to glucose in-
increase of the delivery of sodium and bicarbonate to the
distal nephrons leading to potassium excretion. During long-
term therapy with this drug, hypokalaemia is not common
due to a compensatory potassium retention secondary to aci-
Acetazolamide can causes hypokalaemia. It causes an
sium excretion by increasing sodium delivery to the distal
nephron and by acting as nonreabsorbable anions in the dis-
tal renal tubule, which enhances the secretion of potassium
and hydrogen ion and results in hypokalaemia and metabolic
alkalosis . In a series of 16 patients treated with ticarcil-
lin, the risk of hypokalaemia appeared greatest among pa-
tients who received higher doses (>18g/day) . Oxacillin,
dicloxacillin, flucloxacillin and piperacillin can also cause
severe hypokalaemia . Meropenem , outdated tetra-
cycline, neomycin, polymyxin B, colistin and bacitracin have
also been reported to cause hypokalaemia .
Large doses of penicillins may promote urinary potas-
tassium wasting by inducing depletion of magnesium. These
drugs can cause Bartter-like syndrome, which associated
hypokalaemic metabolic alkalosis, hypomagnesemia, and
hypocalcemia. NSAIDs are beneficial in some situations;
however, in one of the cases, electrolyte abnormalities were
unaffected by indomethacin treatment but were partially cor-
rected by large doses of spironolactone . In a more recent
case, gentamicin therapy induced a marked hypokalaemia
and hypomagnesaemia associated with excessive kaliuresis
and magnesiuria. Hypokalaemia was corrected with potas-
Aminoglycosides and capreomycin can induce renal po-
sium and magnesium supplements and the use of diclofenac
. The frequency of hypokalaemia ranges from 4 to 15%
of patients receiving capreomycin therapy for 6 to 26
months. In a cohort study, among 44 patients taking capreo-
mycin, 30 (68.2%) developed hypokalaemia (defined as se-
rum potassium below 3.3 meq/l) . Capreomycin-induced
hypokalaemia seems to be more common in patients with
low initial body weight or malnutrition. The exact mecha-
nism of the urinary loss of potassium and magnesium due to
aminoglycoside is not entirely elucidated. It may be due to
aminoglycoside-induced hyperaldosteronism and tubular
toxicity. Chou and colleagues  hypothesize that gentami-
cin, stimulates calcium-sensing receptors on the thick as-
cending loop of Henle and distal tubule leading to renal
wasting of potassium, sodium and magnesium. Close moni-
toring of serum potassium in patients who receive aminogly-
coside especially capreomycin and/or high doses of penicil-
lins is mandatory.
effect on the renal tubule. It causes inhibition of hydrogen
ions secretion by collecting-duct cells as well as magnesium
depletion . Amphotericin-induced hypokalaemia is dose
dependent and generally occurs before renal failure. In com-
parison with amphotericin, the lipid formulation of ampho-
tericin causes less hypokalaemia . Hypokalaemia is sig-
nificantly less common with caspofungin than with ampho-
tericin . Amiloride may be beneficial in amphotericin-
induced hypokalaemia . Spironolactone may also pre-
vent amphotericin-related hypokalaemia in neutropenic pa-
tients . Itraconazole can induce severe hypokalaemia by
excessive urinary loss of potassium . In a recent study,
hypokalaemia represents the most common adverse effect of
itraconazole therapy . Hypokalaemia is also seen with
oral fluconazole . Patients who are treated with these
antifungal drugs should have their serum potassium level
Amphotericin promotes renal potassium wasting by toxic
Drugs Associated with Mineralocorticoid Effects
serum potassium and is occasionally accompanied by hy-
pokalaemia and severe metabolic abnormalities. Only a few
case reports about severe hypokalaemia have been described.
The maximum decrease in potassium serum levels is reached
in the first week of corticosteroids treatment . High
doses of hydrocortisone (> 100 mg/day) can induce severe
hypokalaemia by causing sodium retention and excessive
renal potassium loss secondary to their significant mineralo-
corticoid effect . Dexamethasone, methylprednisolone,
cortisol and prednisolone seem to be less likely to induce
hypokalaemia . Severe potassium depletion can occur
when these drugs are prescribed with concomitant diuretics
. Fludrocortisone, used in the treatment of Addison's
disease and orthostatic hypotension, can cause potassium
wasting and severe hypokalaemia especially in the elderly
population . It is proposed in the treatment of hy-
perkalaemia in patients undergoing hemodialysis.
Long-term therapy with corticosteroids slightly reduces
dependent hypokalaemia in 1% of users . Some patients
were reported to have chronic persistent hypokalaemia long
after cessation of gossypol treatment. Gossypol-induced hy-
Gossypol, a male contraceptive agent, can cause dose
Drug-Induced Hypokalaemia Current Drug Safety, 2009, Vol. 4, No. 1 59
pokalaemia is related, in part, to the inhibition of 11 ?-
hydroxysteroid dehydrogenase that causes an apparent min-
eralocorticoid excess leading to excessive potassium excre-
tion and sodium resorption. Carbenoxolone can cause also
hypokalaemia by inhibiting the renal enzyme ?11-
hydroxysteroid dehydrogenase. Hypokalaemia appears most
frequently in those receiving excessive doses of carbenox-
olone . Mifepristone, an antiprogestogenic steroid, has
also been incriminated as a possible cause of severe hy-
pokalaemia which is related to excessive cortisol activation
of the mineralocorticoid receptor .
Chemotherapy and Other Nephrotoxic Drugs
bolic alkalosis, hypomagnesaemia, and hypocalciuria resem-
bling Gitelman’s syndrome . The exact mechanism of
this drug’s nephrotoxicity is not elucidated, but it seems to
be due to a tubular necrosis, predominantly in the distal con-
voluted tubule and the collecting ducts, which may result in
salt wasting and stimulation of the renin-angiotensin-
aldosterone system, with consequent hypokalaemic meta-
Cisplatin has been associated with hypokalaemic meta-
secondary to proximal renal tubular dysfunction . The
lower weight, the concomitant association of ritonavir or
didanosine and the long duration of tenofovir use appear to
be risk factors for tenofovir-induced renal tubular disease
. Foscarnet may cause hypokalaemia by renal potassium
wasting probably by magnesium depletion .
Tenofovir can lead to nephrotoxicity and hypokalaemia
act mechanism is still unknown, but seems to be secondary
to a dysfunction of ion channels on skeletomuscular mem-
branes . Sirolimus has been shown to cause hypokalae-
mia by excessive urinary excretion of potassium, probably
secondary to tubular dysfunction. Potassium deficit is mild
and seems to be dose dependent and it can disappear when
doses are reduced. It can occur without associated metabolic
acidosis, hyperaldosteronism or Fanconi syndrome. Patients
with sirolimus-induced hypokalaemia respond well to potas-
sium supplements .
Methotrexate may induce severe hypokalaemia. The ex-
vere hypokalaemia and metabolic alkalosis, especially in
patients with impaired renal function . Hypokalaemia is
due to an excessive delivery of acid, sodium or bicarbonate
to distal tubule which stimulates distal tubular hydrogen ions
secretion and potassium secretion leading to hypokalaemia.
Sodium bicarbonate is also proposed in treatment of hy-
perkalaemia with metabolic acidosis . Salicylate intoxi-
cation can cause hypokalaemia, which may be aggravated
with forced alkaline diuresis used in this situation. Hpoka-
lemia may complicate poisoning with papaverine when there
is a lactic acidosis. The biochemical features of papaverine-
induced acid-base disturbance closely resemble those caused
by salicylates . Paracetamol overdose is associated with
dose-related hypokalaemia, and kaliuresis of short duration
(<24 h). A specific renal effect of paracetamol in overdose
possibly linked to cyclo-oxygenase inhibition, distinct from
any nephrotoxic effect of paracetamol, irrespective of N-
Excessive administration of bicarbonate may lead to se-
acetylcysteine administration and independent of whether
vomiting occurred has been suggested [98,99]. Vitamin D
intoxication induces potassium and water depletion and hy-
pernatraemia probably because of renal tubular damage
. The abuse of thyroxine can cause severe hypokalae-
mia . Indeed, animal studies show that the thyroid-
hormones stimulate the synthesis of Na+-K+-ATPase pump
. Overdose of risperidone and quetiapine, has also been
associated wih hypokalaemia . Symptomatic hy-
pokalaemia has also been reported with infliximab ,
ibuprofen , ondansetron , and meglumine antimo-
DRUGS INDUCING CELLULAR PROLIFERATION
during initial treatment. The presumed mechanism was an
increase in cellular proliferation with sudden production of
millions of new cells leading to a shift of potassium to cells
. In addition, such patients are probably chronically
hypoxic and predisposed to total body potassium depletion.
Massive leukocytosis after Granulocyte–macrophage colony-
stimulating factor therapy has also been associated with se-
vere hypokalaemia due to potassium shift to cells recently
Hydroxocobalamin may rarely precipitate hypokalaemia
and the presence of symptoms and ECG abnormalities. Cor-
rection of drug-induced hypokalaemia is generally not indi-
cated especially in the case of transcellular potassium shift.
This situation may not have significant total body potassium
deficit and when corrected rebound hyperkalaemia can occur
and should be kept in mind by the clinician. Withdrawal of
the offending drug is usually sufficient to restore a normal
level of serum potassium. However, severe hypokalaemia
should be corrected by intravenous infusion of potassium. In
moderate hypokalaemia, and in the absence of digoxin toxic-
ity or severe heart disease, oral administration of potassium
salts may be useful, but can cause gastrointestinal adverse
effects and contact irritation. The daily dose should be di-
vided into three to four doses to prevent these side effects.
When drug-induced hypokalaemia is predictable e.g with
prescription of diuretics, concomitant potassium supplements
should be provided to patients. In case of co-existent magne-
sium depletion, its correction will facilitate more rapid cor-
rection of hypokalaemia.
The treatment of hypokalaemia depends on its severity
 Macdonald JE, Struthers AD. What is the optimal serum potassium
level in cardiovascular patients? J Am Coll Cardiol 2004; 43: 155-
Ahmed A, Zannad F, Love TE, et al. A propensity-matched study
of the association of low serum potassium levels and mortality in
chronic heart failure. Eur Heart J 2007; 28: 1334-43.
Isaac G, Holland OB. Drug-induced hypokalaemia. A cause for
concern. Drugs Aging 1992; 2: 35-41.
Weiner ID, Wingo CS. Hypokalaemia--consequences, causes, and
correction. J Am Soc Nephrol 1997; 8(7): 1179-88.
Gennari FJ. Hypokalaemia. N Engl J Med 1998; 339: 451-8.
Paice BJ, Paterson KR, Onyanga-Omara F, Donnelly T, Gray JM,
Lawson DH. Record linkage study of hypokalaemia in hospitalised
patients. Postgrad Med J 1986; 62: 187-91.
Riggs JE. Neurologic manifestations of electrolyte disturbances.
Neurol Clin 2002; 20: 227-39.
60 Current Drug Safety, 2009, Vol. 4, No. 1 Ben Salem et al.
 Sørensen IJ, Matzen LE. Serum electrolytes and drug therapy of
patients admitted to a geriatric department. Ugeskr Laeger 1993;
Janko O, Seier J, Zazgornik J. Hypokalaemia--incidence and sever-
ity in a general hospital. Wien Med Wochenschr 1992; 142: 78-81.
Halevy J, Gunsherowitz M, Rosenfeld JB. Life-threatening
hypokalaemia in hospitalized patients. Miner Electrolyte Metab
1988; 14: 163-6.
Passare G, Viitanen M, Törring O, Winblad B, Fastbom J. Sodium
and potassium disturbances in the elderly : prevalence and associa-
tion with drug use. Clin Drug Investig 2004; 24: 535-44.
Clausen T, Flatman JA. The effect of catecholamines on Na–K
transport and membrane potential in rat soleus muscle. J Physiol
1977; 270: 383-414.
Udezue E, D'Souza L, Mahajan M. Hypokalaemia after normal
doses of nebulized albuterol (salbutamol). Am J Emerg Med 1995;
Scheinin M, Koulu M, Laurikainen E, Allonen H. Hypokalaemia
and other non-bronchial effects of inhaled fenoterol and salbuta-
mol: a placebo-controlled dose-response study in healthy volun-
teers. Br J Clin Pharmacol 1987; 24: 645-53.
Lewis LD, Essex E, Volans GN, Cochrane GM. A study of self
poisoning with oral salbutamol--laboratory and clinical features.
Hum Exp Toxicol 1993; 12: 397-401.
Whyte KF, Reid C, Addis GJ, Whitesmith R, Reid JL. Salbutamol
induced hypokalaemia: the effect of theophylline alone and in
combination with adrenaline. Br J Clin Pharmacol 1988; 25: 571-8.
Braden GL, von Oeyen PT, Germain MJ, Watson DJ, Haag BL.
Ritodrine- and terbutaline-induced hypokalaemia in preterm labor:
mechanisms and consequences. Kidney Int 1997; 51: 1867-75.
Gutman Y, Boonyaviroj P. Inhibition of catecholamine release by
alpha-adrenergic activation: interaction with Na, K-ATPase. J Neu-
ral Transm 1977; 40: 245-52.
Wong KM, Chak WL, Cheung CY, et al. Hypokalaemic metabolic
acidosis attributed to cough mixture abuse. Am J Kidney Dis 2001;
Brown MJ. Hypokalaemia from ?2-receptor stimulation by circu-
lating epinephrine. Am J Cardiol 1985; 56: 3D-9D.
Seck M, Bruder N, Courtinat C, Pellissier D, François G. Transfer
hypokalaemia induced by norepinephrine infusion. Ann Fr Anesth
Reanim 1996; 15: 204-6.
Darbar D, Smith M, Morike K, Roden D. Epinephrine-induced
changes in serum potassium and cardiac repolarization and effects
of pretreatment with propranolol and diltiazem. Am J Cardiol 1996;
Fang W, Chen J-Y, Fang Y, Huang J-L. Epinephrine overdose-
associated hypokalaemia and rhabdomyolysis in a newborn. Phar-
macotherapy 2005; 25: 1266-70.
Thangathurai D, Mikhail M, Shoemaker W. Implication of epi-
nephrine-induced hypokalaemia during cardiac arrest. Resuscita-
tion 2003; 58: 231.
Koh YI, Choi IS. Lactic acidosis associated with the usual theo-
phylline dose in a patient with asthma. Korean J Intern Med 2002;
Flack JM, Ryder KW, Strickland D, Whang R. Metabolic corre-
lates of theophylline therapy: a concentration-related phenomenon.
Ann Pharmacother 1994; 28: 175-9.
Appel CC, Myles TD. Caffeine-induced hypokalaemic paralysis in
pregnancy. Obstet Gynecol 2001; 97: 805-7.
Freed MI, Rastegar A, Bia MJ. Effects of calcium channel blockers
on potassium homeostasis. Yale J Biol Med 1991; 64: 177-86.
Sugarman A, Kahn T. Calcium channel blockers enhance extrare-
nal potassium disposal in the rat. Am J Physiol 1986; 250: F695-
Mimran A, Ribstein J, Sissmann J. Effects of calcium antagonists
on adrenaline-induced hypokalaemia. Drugs 1993; 46 (Suppl 2):
Tishler M, Armon S. Nifedipine-induced hypokalaemia. Drug Intell
Clin Pharm 1986; 20: 370-1.
Oe H, Taniura T, Ohgitani N. A case of severe verapamil overdose.
Jpn Circ J 1998; 62: 72-6.
Burghen GA, Etteldorf JN, Fisher JN, Kitabchi AQ. Comparison of
high-dose and low-dose insulin by continuous intravenous infusion
in the treatment of diabetic ketoacidosis in children. Diabetes Care
1980; 3: 15-20.
 Binder G, Bosk A, Gass M, Ranke MB, Heidemann PH. Insulin
tolerance test causes hypokalaemia and can provoke cardiac ar-
rhythmias. Horm Res 2004; 62: 84-7.
Muto S, Sebata K, Watanabe H, et al. Effect of oral glucose ad-
ministration on serum potassium concentration in hemodialysis pa-
tients. Am J Kidney Dis 2005; 46: 697-705.
Clemessy JL, Favier C, Borron SW, Hantson PE, Vicaut E, Baud
FJ. Hypokalaemia related to acute chloroquine ingestion. Lancet
1995; 346: 877-80.
Marquardt K, Albertson TE. Treatment of hydroxychloroquine
overdose. Am J Emerg Med 2001; 19: 420-4.
Ok SH, Chung YW, Sohn JT, Jung JM, Chung YK. Severe
hypokalaemia occurring during barbiturate coma therapy in a
patient with severe acute head injury. Acta Anaesthesiol Scand
2005; 49: 883-4.
Hall RJ, Cameron IR. The effect of pentobarbitone on plasma and
intracellular sodium, potassium and pH in rabbit cardiac and skele-
tal muscle. Clin Sci (Lond) 1979; 57: 549-51.
van Heerden PV, Chew G. Severe hypokalaemia due to lignocaine
toxicity. Anaesth Intensive Care 1996; 24: 128-9.
Kallmeyer JC, Macleod IN, Bhagwan B. Marked hypokalaemic
rhabdomyolysis due to purgative abuse. South Afr Med J 1994; 84:
Chin RL. Laxative-induced hypokalaemia. Ann Emerg Med 1998;
Hill AG, Parry BR. Hypokalaemia following bowel cleansing with
sodium phosphate. N Z Med J 1996; 109: 347.
Craig JC, Hodson EM, Martin HC. Phosphate enema poisoning in
children. Med J Aust 1994; 160: 347-51.
Andrejak M, Lafon B, Decocq G, et al. Antibiotic-associated pseu-
domembranous colitis: retrospective study of 48 cases diagnosed
by colonoscopy. Therapie 1996; 51: 81-6.
Katerinis I, Fumeaux Z. Hypokalaemia: diagnosis and treatment.
Rev Med Suisse 2007; 3: 579-82.
Saif MW, Fekrazad MH, Ledbetter L, Diasio RB. Hypokalaemia
secondary to capecitabine: a hidden toxicity? Ther Clin Risk Man-
age 2007; 3: 177-80.
Thomas-Anterion C, Guy C, Vial F, et al. Unexplained chronic
diarrhea, apropos of 4 new cases under Cyclo 3 fort and review of
the literature. Rev Med Intern 1993; 14: 215-7.
Simons P, Nadra I, McNally PG. Metabolic alkalosis and myo-
clonus. Postgrad Med J 2003; 79: 414-5.
Gunawan CA, Harijanto PN, Nugroho A. Quinine-induced Ar-
rhytmia in a Patient with Severe Malaria. Acta Med Indones 2007;
Morgan DB, Davidson C. Hypokalaemia and diuretics: an analysis
of publications. Br Med J 1980; 280: 905-8.
Passarelli MC, Jacob-Filho W, Figueras A. Adverse drug reactions
in an elderly hospitalised population: inappropriate prescription is a
leading cause. Drugs Aging 2005; 22: 767-77.
Hamdy RC, Tovey J, Perera N. Hypokalaemia and diuretics. BMJ
1980; 280: 1187.
Clayton JA, Rodgers S, Blakey J, Avery A, Hall IP. Thiazide diu-
retic prescription and electrolyte abnormalities in primary care. Br J
Clin Pharmacol 2006; 61: 87-95.
Rose BD. Diuretics. Kidney Int 1991; 39: 336-52.
Alfonzo AV, Isles C, Geddes C, Deighan C. Potassium disorders--
clinical spectrum and emergency management. Resuscitation 2006;
Alderman MH. New onset diabetes during antihypertensive ther-
apy. Am J Hypertens 2008; 21: 493-9.
Grobbee DE, Hoes AW. Non-potassium-sparing diuretics and risk
of sudden cardiac death. J Hypertens 1995; 13: 1539-45.
Hoes AW, Grobbee DE, Lubsen J. Sudden cardiac death in patients
with hypertension. An association with diuretics and beta-blockers?
Drug Saf 1997; 16: 233-41.
Cohen JD, Neaton JD, Prineas RJ, Daniels KA. Diuretics, serum
potassium and ventricular arrhythmias in the Multiple Risk Factor
Intervention Trial. Am J Cardiol 1987; 60: 548-54.
The Hypertension Detection and Follow-up Program Cooperative
Research Group. The effect of antihypertensive drug treatment on
mortality in the presence of resting electrocardiographic abnormali-
ties at baseline: the HDFP experience. Circulation 1984; 70: 996-
Drug-Induced Hypokalaemia Current Drug Safety, 2009, Vol. 4, No. 1 61
 Papademetriou V. Diuretics, hypokalaemia and cardiac arrhythmia:
a 20-year controversy. J Clin Hypertens (Greenwich) 2006; 8: 86-
Critchlow AS, Freeborn SN, Roddie RA. Potassium supplements
during treatment of glaucoma with acetazolamide. BMJ (Clin Res
Ed) 1984; 289: 21.
Lipner HI, Ruzany F, Dasgupta M, Lief PD, Bank N. The behavior
of carbenicillin as a nonreabsorbable anion. J Lab Clin Med 1975;
Nanji AA, Lindsay J. Ticarcillin associated hypokalaemia. Clin
Biochem 1982; 15: 118-9.
Brunner FP, Frick PG. Hypokalaemia, metabolic alkalosis and
hypernatraemia due to massive sodium penicillin therapy. BMJ
1986; 4: 550-2.
Margolin L. Impaired rehabilitation secondary to muscle weakness
induced by meropenem. Clin Drug Investig 2004; 24: 61-2.
Brass EP, Thompson WL. Drug-induced electrolyte abnormalities.
Drugs 1982; 24: 207-28.
Steiner RW, Omachi AS. A Bartter's-like syndrome from capreo-
mycin, and a similar gentamicin tubulopathy. Am J Kidney Dis
1986; 7: 245-9.
Shiah CJ, Tsai DM, Liao ST, Siauw CP, Lee LS. Acute muscular
paralysis in an adult with subclinical Bartter's syndrome associated
with gentamicin administration. Am J Kidney Dis 1994; 24: 932-5.
Shin S, Furin J, Alcántara F, et al. Hypokalaemia among patients
receiving treatment for multidrug-resistant tuberculosis. Chest
2004; 125: 974-80.
Chou CL, Chen YH, Chau T, Lin SH. Acquired bartter-like syn-
drome associated with gentamicin administration. Am J Med Sci
2005; 329: 144-9.
Barton CH, Pahl M, Vaziri ND, Cesario T. Renal magnesium wast-
ing associated with amphotericin B therapy. Am J Med 1984; 77:
Subirà M, Martino R, Gómez L, Martí JM, Estany C, Sierra J.
Low-dose amphotericin B lipid complex vs conventional ampho-
tericin B for empirical antifungal therapy of neutropenic fever in
patients with hematologic malignancies--a randomized, controlled
trial. Eur J Haematol 2004; 72: 342-7.
Falagas ME, Ntziora F, Betsi GI, Samonis G. Caspofungin for the
treatment of fungal infections: a systematic review of randomized
controlled trials. Int J Antimicrob Agents 2007; 29: 136-43.
Bearden DT, Muncey LA. The effect of amiloride on amphotericin
B-induced hypokalaemia. J Antimicrob Chemother 2001; 48: 109-
Ural AU, Avcu F, Cetin T, et al. Spironolactone: is it a novel drug
for the prevention of amphotericin B-related hypokalaemia in can-
cer patients? Eur J Clin Pharmacol 2002; 57: 7713.
Ruiz-Contreras J, Rodriguez R, Gómez de Quero P, González
Tomé MI, Sánchez Díaz JI. Severe hypokalaemia and rhabdomy-
olysis associated with itraconazole therapy. Pediatr Infect Dis J
Wang A, Zhang Y, He L, et al. Clinical study on the efficacy and
safety of intravenous itraconazole infusion for the treatment of in-
vasive fungal infection in china. Jpn J Infect Dis 2006; 59: 370-6.
Kidd D, Ranaghan EA, Morris TC. Hypokalaemia in patients with
acute myeloid leukaemia after treatment with fluconazole. Lancet
1989; 1: 1017.
Li N, Wang GF, Wu YF, et al. Side effects of glucocorticosteroids
in the management of 1291 patients of SARS. Beijing Da Xue Xue
Bao 2004; 36: 519-24.
Tsai WS, Wu CP, Hsu YJ, Lin SH. Life-threatening hypokalaemia
in an asthmatic patient treated with high-dose hydrocortisone. Am J
Med Sci 2004; 327: 152-5.
Ramsahoye BH, Davies SV, el-Gaylani N, Sandeman D, Scanlon
MF. The mineralocorticoid effects of high dose hydrocortisone.
BMJ 1995; 310: 656-7.
Thorn GW. Clinical considerations in the use of corticosteroids. N
Engl J Med 1966; 274: 775-81.
 Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone
in the treatment of hypotensive disorders in the elderly. Heart 1996;
Qian SZ. Gossypol-hypokalaemia interrelationships. Int J Androl
1985; 8: 313-24.
Metcalfe MJ, Entrican JH. Carbenoxolone and hypokalaemia.
Lancet 1987; 2: 1525-6.
Hoffman AR, Feldman D. Successful long-term treatment of re-
fractory Cushing’s disease with high-dose mifepristone (RU 486). J
Clin Endocrinol Metab 2001; 86: 3568-73.
Mohammadianpanah M, Omidvari S, Mosalaei A, Ahmadloo N.
Cisplatin-induced hypokalaemic paralysis. Clin Ther 2004; 26:
Shepp DH, Curtis S, Rooney JF. Causes and consequences of hy-
pokalaemia in patients on tenofovir disoproxil fumarate. AIDS
2007; 21: 1479-81.
Cirino CM, Kan VL. Hypokalaemia in HIV patients on tenofovir.
AIDS 2006; 20: 1671-3.
Gearhart MO, Sorg TB. Foscarnet-induced severe hypomagne-
semia and other electrolyte disorders. Ann Pharmacother 1993; 27:
Thuss-Patience PC, Peters U, Jurkat-Rott K, et al. Acute hy-
pokalaemic tetraparesis induced by intravenous methotrexate. J
Clin Oncol 2003; 21: 1896-7.
Morales JM, Andrés A, Dominguez-Gil B, et al. Tubular function
in patients with hypokalaemia induced by sirolimus after renal
transplantation. Transplant Proc 2003; 35: 154S-156S.
Lin CJ, Chen YC, Chen HH, Liu CC, Wu CJ. Life-threatening
ventricular arrhythmia induced by hypokalaemia during sodium bi-
carbonate infusion. South Afr Med J 2008; 101: 215-6.
Carvalhana V, Burry L, Lapinsky SE. Management of severe
hyperkalemia without hemodialysis: case report and literature
review. J Crit Care 2006; 21: 316-21.
Vaziri ND, Stokes J, Treadwell TR. Lactic acidosis, a complication
of papaverine overdose. Clin Toxicol 1981; 18: 417-23.
Pakravan N, Bateman DN, Goddard J. Effect of acute paracetamol
overdose on changes in serum and urine electrolytes. Br J Clin
Pharmacol 2007; 64: 824-32.
Waring WS, Stephen AF, Malkowska AM, Robinson OD. Acute
acetaminophen overdose is associated with dose-dependent hy-
pokalaemia: a prospective study of 331 patients. Basic Clin Phar-
macol Toxicol 2008; 102: 325-8.
Anderson DC, Cooper AF, Naylor GJ. Vitamin D intoxication,
with hypernatraemia, potassium and water depletion, and mental
depression. Br Med J 1968; 4:744-6.
Chen YC, Fang JT, Chang CT, Chou HH. Thyrotoxic periodic
paralysis in a patient abusing thyroxine for weight reduction. Ren
Fail 2001; 23: 139-42.
Clausen T. Clinical and therapeutic significance of the Na+,K+
pump*. Clin Sci (Lond) 1998; 95: 3-17.
Malik AR, Wolf PK, Ravasia S. Hypokalaemia from risperidone
and quetiapine overdose. Can J Psychiatry 2005; 50: 76.
Karamanolis G, Tzathas C, Triantafyllou K, Tsiamoulos Z, Ladas
S. Symptomatic hypokalaemia associated with infliximab in a pa-
tient with Crohn's disease. Inflamm Bowel Dis 2006; 12 :1010-1.
Gaul C, Heckmann JG, Druschky A, Schöcklmann H, Neundörfer
B, Erbguth F. Renal tubular acidosis with severe hypokalaemic
tetraparesis after ibuprofen intake. Dtsch Med Wochenschr 1999;
Turner SR, Pinsk M. Ondansetron-associated Hypokalaemia in a 2-
year-old With Pre-B-cell ALL. J Pediatr Hematol Oncol 2008; 30:
Bouvresse S, Matichard E, Mahé E, et al. Symptomatic hy-
pokalaemia caused by meglumine antimoniate. Ann Dermatol
Venereol 2007; 134: 387-8.
Lawson DH, Murray RM, Parker JL, Hay G. Hypokalaemia in
megaloblastic anaemias. Lancet 1970; 2: 588-90.
Viens P, Thyss A, Garnier G, Ayela P, Lagrange M, Schneider M.
GM-CSF treatment and hypokalaemia. Ann Intern Med 1989; 111:
Received: August 22, 2008
Revised: September 20, 2008 Accepted: September 30, 2008