Hypocalcemic tetany associated with simultaneous administration of cimetidine and nifedipine: a case report.

BACKGROUND: Acute hypocalcemia is generally caused by a sudden drop in serum calcium ion and presents with a mild or severe form of tetany. Even though the occurrence of hypocalcemia is well documented with certain drugs such as calcium chelators, bisphosphonates, and cisplatin, it is a very unusual and poorly documented adverse event with cimetidine and nifedipine. Here, we present a case of severe hypocalcemic tetany during simultaneous administration of cimetidine and nifedipine in a hypertensive patient with dyspepsia. CASE PRESENTATION: A 46-year-old known human immunodeficiency virus patient from Ethiopia on antiretroviral therapy over the past 14 years presented to the emergency department with acute exacerbation of dyspepsia and hypertensive urgency. She was given intravenous cimetidine (400 mg) and oral nifedipine (30 mg) simultaneously. One hour after the administration of these two drugs, she developed severe hypocalcemic tetany with carpopedal spasm, involuntary plantar flexion, and muscle spasms. She also had severe retrosternal chest pain and shortness of breath. Her blood pressure was 160/110 mmHg during the attack and she had no skin changes, such as urticaria. She was immediately given 1 g of calcium gluconate intravenously over 30 minutes. The carpopedal spasm progressively decreased during calcium gluconate administration. An hour later, she completely regained voluntary movement of her fingers and feet. The chest pain persisted, but resolved over the next 12 hours. The patient was discharged home after 2 days of observation. This is an unusual adverse effect that needs caution during concomitant administration of these drugs. CONCLUSIONS: Severe hypocalcemic tetany can occur with concomitant administration of cimetidine and nifedipine. Immediate treatment with calcium gluconate quickly reverses this adverse event. Concomitant administration of these drugs should be done with caution or be avoided if possible.

Clinical data analysis of 22 cases with hypoparathyroidism misdiagnosed as epilepsy.

OBJECTIVE: Patients with hypoparathyroidism always present with recurrent tetany caused by hypocalcemia. These patients are usually misdiagnosed with epilepsy and incorrectly treated with anti-epileptic drugs. This research analyzed clinical data about 22 patients with hypoparathyroidism misdiagnosed as epilepsy and summarized the clinical experience for reducing misdiagnosis and incorrect therapy about hypoparathyroidism. METHOD: Totally 160 patients with hypoparathyroidism, administrated to the First Medical Center of Chinese PLA General Hospital from January 1st, 2008, to July 1st, 2021, were enrolled in this report. Clinical data about 22 patients initially misdiagnosed with epilepsy were analyzed. RESULTS: Of the 160 cases with hypoparathyroidism, 22 patients (12 males and 10 females) were misdiagnosed with epilepsy in local hospitals. The misdiagnosis rate was 13.75% and the median duration of misdiagnosis was 8.0 (2.0, 14.8) years. The clinical manifestations of the 22 patients misdiagnosed as epilepsy included tetany 81.8% (18/22), disturbance of consciousness 27.3% (6/22), limb numbness 13.6% (3/22), limb weakness 27.3% (6/22), mental and behavioral abnormality 9.1% (2/22), and memory impairment 13.6% (3/22), etc. Electroencephalogram (EEG) was performed in 9 cases, which presented as slow wave and spike-slow complex wave in 3 cases, slowing down of Î¸ and δ band background in 2 cases and normal EEG in 4 cases. Out of the 15 cases that underwent head computed tomography (CT) scan, in which 13 cases had intracranial calcification. Anti-epileptic drugs were used to treat 22 patients, of which 17 patients were treated with two kinds of drugs. With calcium and calcitriol supplement in all these 22 patients, the anti-epileptic drugs were gradually reduced and withdrawn in 17 cases. In the other 5 cases with secondary epilepsy, the type of anti-epileptic drugs was reduced to one and the clinical condition improved obviously. CONCLUSION: The clinical manifestations of hypoparathyroidism are complex and usually be misdiagnosed as primary epilepsy. Detection of serum calcium, phosphorus and parathyroid hormone is very important to avoid misdiagnosis and incorrect therapy about hypoparathyroidism.

Hypercalcaemia to hypocalcaemia: tetany as a side effect of intravenous bisphosphonate treatment.

A woman in her 40s with advanced bladder cancer was admitted to hospital with hypercalcaemia of malignancy. Initially, she presented with non-specific symptoms of malaise, fatigue and general deterioration. She was treated with intravenous fluids and zoledronic acid in order to bring her calcium levels down, but subsequently developed significant hypocalcaemia. This manifested as tetany in the hands in the form of bilateral carpopedal spasm. She also reported perioral paraesthesia. Bloods during her admission revealed deranged electrolytes, and her vitamin D level was on the lower scale of normal (25 nmol/L). The patient's symptoms improved with electrolyte replacement and oral baclofen for her symptomatically distressing wrist and hand muscle spasms. This case report is a reminder that bisphosphonates can cause significant hypocalcaemia with symptoms of tetany, even when they are given for initial hypercalcaemia. Baclofen worked well to improve symptoms.

A reconnaissance survey of farmers' awareness of hypomagnesaemic tetany in UK cattle and sheep farms.

Hypomagnesaemic tetany (HypoMgT) in ruminants is a physiological disorder caused by inadequate intake or impaired absorption of magnesium (Mg) in the gut. If it is not detected and treated in time, HypoMgT can cause the death of the affected animal. A semi-structured questionnaire survey was conducted from July 2016-2017 to assess farmers' awareness of HypoMgT in cattle and sheep in the UK. The questionnaire was distributed to farmers at farm business events and agricultural shows, and through a collaborative group of independent veterinary practices to their clients. Farmers were asked about (i) the incidence of presumed HypoMgT (PHT); (ii) their strategies to treat or prevent HypoMgT; (iii) mineral tests on animals, forage and soil, and (iv) farm enterprise type. A total of 285 responses were received from 82 cattle, 157 mixed cattle and sheep, and 46 sheep farmers, of whom 39% reported HypoMgT in their livestock, affecting 1-30 animals. Treatment and/or prevention against HypoMgT was reported by 96% respondents with PHT and 79% of those without. Mineral tests on animal, forage, and soil was conducted by 24%, 53%, and 66% of the respondents, respectively, regardless of PHT. There was a highly significant association between the use of interventions to tackle HypoMgT and the incidence of PHT (p < 0.01). The top three treatment/prevention strategies used were reported as being free access supplementation (149), in feed supplementation (59) and direct to animal treatments (drenches, boluses and injections) (45) although these did vary by farm type. Although some (9) reported using Mg-lime, no other pasture management interventions were reported (e.g., Mg-fertilisation or sward composition). Generally, the results indicate that UK farmers are aware of the risks of HypoMgT. A more integrated soil-forage-animal assessment may improve the effectiveness of tackling HypoMgT and help highlight the root causes of the problem.

[Tetany secondary to phosphate enema toxicity, case report]. / Tetania severa por uso de enemas fosfatados, reporte de caso.

Phosphate enemas are frequently used in the treatment of constipation. Errors in dosage and administration can lead to severe complications. OBJECTIVE: To report a case of severe toxicity of phosphate enemas in a child with no risk factors. CASE: 2 years old female, with functional constipation, was brought to emergency department because abdominal pain. She was diagnosed with fecal impaction and received half a bottle of Fleet Adult® (Laboratorio Synthon, Chile) two times, with no clinical resolution, deciding to start proctoclisis in pediatric ward. Soon after admission, she presented painful tetany, but alert and oriented. Patient was transferred to PICU where severe hyperphosphatemia and secondary hypocalcemia were confirmed. Her treatment included electrolyte correction; removal of residual phosphate enema and hyperhydration. Tetany resolved over 2 hours after admission and no other complications. Proctoclisis was performed and patient was discharged three days after admission with pharmacological management of constipation. CONCLUSION: Phosphate enemas may cause serious complications in children with no risk factors. Errors in dosage, administration and removal of the enema are causes of toxicity in this group. Pediatricians and health personnel must be aware of risks and signs of toxicity of phosphate enema.

Tetania severa por uso de enemas fosfatados, reporte de caso / Tetany secondary to phosphate enema toxicity, case report

Los enemas fosfatados son utilizados frecuentemente en el tratamiento de la constipación. Errores en la posología pueden producir complicaciones graves. Objetivo: Reportar un caso de toxicidad grave por enema fosfatado en un pre escolar sin factores de riesgo. Caso clínico: Paciente de 2 años con constipación funcional, evaluada en servicio de urgencia por dolor abdominal a quién se le diagnosticó un fecaloma impactado. Recibió 2 dosis de enema de fosfato, “medio frasco” de Fleet® adulto (Synthon, Chile) por vez, sin resolución de su fecaloma, decidiéndose hospitalización para proctoclisis. Posterior al ingreso presentó un cuadro clínico de tetania. Ingresó a la Unidad de Paciente Crítico donde se confirmó una hiperfosfemia e hipocalcemia secundaria. Se realizó corrección electrolítica progresiva, retiro de enema fosfatado residual del recto e hiperhidratación forzando diuresis. La tetania cedió 2 horas después del ingreso sin otras complicaciones. Se realizó proctoclisis y fue dada de alta a los 3 días. Conclusión: Los enemas fosfatados pueden presentar complicaciones graves en niños sin factores de riesgo. Errores en la posología son la causa más frecuente de toxicidad en este grupo, pero esta puede estar favorecida también por una administración y eliminación inadecuadas. Pediatras y personal de salud que atiende a niños deben conocer factores de riesgo, signos y síntomas de intoxicación por enemas fosfatados.

Phosphate enemas are frequently used in the treatment of constipation. Errors in dosage and administration can lead to severe complications. Objective: To report a case of severe toxicity of phosphate enemas in a child with no risk factors. Case: 2 years old female, with functional constipation, was brought to emergency department because abdominal pain. She was diagnosed with fecal impaction and received half a bottle of Fleet Adult® (Laboratorio Synthon, Chile) two times, with no clinical resolution, deciding to start proctoclisis in pediatric ward. Soon after admission, she presented painful tetany, but alert and oriented. Patient was transferred to PICU where severe hyperphosphatemia and secondary hypocalcemia were confirmed. Her treatment included electrolyte correction; removal of residual phosphate enema and hyperhydration. Tetany resolved over 2 hours after admission and no other complications. Proctoclisis was performed and patient was discharged three days after admission with pharmacological management of constipation. Conclusion: Phosphate enemas may cause serious complications in children with no risk factors. Errors in dosage, administration and removal of the enema are causes of toxicity in this group. Pediatricians and health personnel must be aware of risks and signs of toxicity of phosphate enema.

"Ghosts in my body": Seizure-like presentation of hypocalcemic tetany secondary to hypomagnesemia in a patient receiving cetuximab therapy for metastatic medulloblastoma.

Cetuximab, a monoclonal antibody specific for epidermal growth factor receptor, is increasingly used off-label and in early-phase trials for pediatric malignancies. Here, we report a patient with metastatic medulloblastoma receiving therapy with cyclophosphamide, vinblastine, and cetuximab. During evaluation for possible seizures, he was noted to be severely hypocalcemic, hypokalemic, and hypomagnesemic, a consequence of the blockade of renal epidermal growth factor receptor expression. His symptoms rapidly abated with intravenous electrolyte repletion. This case highlights the clinical heterogeneity of tetany and the importance of careful laboratory screening for known adverse effects of chemotherapy, particularly when newer biological agents are used off-study in combination chemotherapeutic regimens.

Stavudine induced acute necrotizing pancreatitis with tetany in a pediatric patient.

A nine year old female patient presented with complaints of severe colicky abdominal pain, vomiting, and tingling with numbness for 3 days. Acute necrotizing pancreatitis associated with tetany due to anti-retroviral therapy was diagnosed. Stavudine was the probable causal agent. Unfortunately, the patient died due to severity of the reaction. High index of suspicion and early withdrawal of the offending drug may prevent further harm in such cases.

[Apparent life-threatening event in infants: think about star anise intoxication!]. / Malaise du nourrisson pensez à une intoxication à l'anis étoilé

UNLABELLED: In previous years, several publications have reported cases of infants presenting neurological and gastrointestinal symptoms after ingestion of star anise tea. Such teas are sometimes given in various cultures for the treatment of infant colic pains. In most cases, the cause of intoxication was contamination of Chinese star anise (Illicium verum) by Japanese star anise (Illicium anisatum). Indeed, the toxicity of Illicium anisatum, also known as Shikimi, is caused by its content in potent neurotoxins (anisatin, neoanisatin, and pseudoanisatin), due to their activity as non-competitive antagonists of GABA receptors. The main reasons explaining the frequent contaminations are the strong macroscopic resemblance of the 2 substances, as well as the fact that the fruits are often sold partially broken or in ground form. Therefore, in most cases, chemical analysis is required to determine the possible adulterations. CASE REPORT: A 2-month-old infant, in good general health, was brought to the emergency unit after 3 consecutive episodes of central cyanosis and tetany of the limbs with spontaneous recovery the same afternoon. The child was also very irritable, regurgitated a lot, and positioned himself in opisthotonos. Between these episodes, the neurological exam showed some perturbations (horizontal nystagmus and Bell's phenomenon, hypertony of the extensor muscles, and mild hypotony of the axial flexor muscles) with slow improvement over the following hours. The remaining clinical exam, the laboratory work (complete blood count, renal, hepatic, and muscular tests, capillary blood gas, plasmatic amino acids, and urinary organic acids), and the electroencephalogram findings were all normal. In the course of a detailed interview, the parents reported having given 3 bottles to their child, each one containing 200 mL of an infusion with 4 to 5 fruits of star anise, in the hours preceding the symptoms to relieve colic pains. The last seizure-like event took place approximately 8h after the last ingestion. We could prove the ingestion of anisatin, the toxic substance found in Japanese star anise, and the contamination of Chinese star anise by the Japanese species. Indeed, the anisatin analysis by liquid chromatography and mass spectroscopy (LC-MS) in a urine sample taken 22 h after the last infusion ingestion showed trace amounts of the substance. In another urine sample taken 33 h after ingestion, no anisatin could be detected. Furthermore, the analysis of the fruit sample gave an anisatin concentration of 7800 µg/kg while the maximum tolerance value in Switzerland is 1000 µg/kg. CONCLUSION: The evaluation of ALTE in infants should always include the possibility of intoxication. Star anise is generally considered a harmless medicine. Nevertheless, it can sometimes cause a severe intoxication resulting in various neurological and gastrointestinal symptoms. To prevent such events, not only the parents, but also the care personnel and pharmacists must be informed about the possible adverse effects caused either by the overdose of Chinese star anise or by the eventual contamination of herbal teas with Japanese star anise. A better control of the substances by the health authorities is also necessary.

Characterization of diffusion and duration of action of a new botulinum toxin type A formulation.

RT002, an injectable form of botulinum neurotoxin type A (BoNTA), comprised of a purified 150 kDa neurotoxin formulated in a novel formulation, is designed to limit the extent of diffusion and permit safe administration of longer acting doses. The aim of this study was to evaluate the degree of diffusion of RT002 in comparison to another commercially available BoNTA product, Botox® Cosmetic (OnabotulinumtoxinA, Allergan, Inc., Irvine, CA, USA), and establish the relative duration of effect for diffusion matched doses of the two BoNTA formulations using quantitative measurements in mice. Measurement of muscle paralysis by muscle force generation (MFG) in mice at the injected gastrocnemius muscles indicated that RT002 and Botox are equipotent. Measurements of MFG inhibition in an adjacent muscle, the tibialis anterior muscle, indicated significantly less diffusion for RT002 as compared to Botox. When RT002 and Botox were dosed using the established diffusion matched doses, RT002 treatment resulted in an extended duration of drug effect as compared to Botox by 58-100% as assessed by either partial or complete recovery endpoints. Use of a daily voluntary running activity model provided confirmation that the two BoNTA formulations are equipotent by daily running distance and further confirmed the diffusion matched dose ratio assessed by degree of drug effect on body weight gain. Using these diffusion matched doses, RT002 treatment resulted in an extended duration of drug effect as compared to Botox (100-126% increase in duration) as assessed by either partial or complete recovery endpoints. Use of this model provides further evidence that the RT002 formulation limits diffusion with equipotency and thereby may permit safe administration of higher and more efficacious doses. In summary, data from two murine models suggest that RT002 may represent a next generation of BoNTA drug formulation offering superior degree and duration of effect at the intended target while controlling the unwanted diffusion and accompanying adverse effects of BoNTA at neighboring muscles and distal systemic targets.

Tetany: possible adverse effect of bevacizumab.

BACKGROUND: Bevacizumab a recombinant humanized monoclonal antibody was approved in 2004 by US FDA for metastatic colorectal cancer. It is reported to cause potentially serious toxicities including severe hypertension, proteinuria, and congestive heart failure. AIM: To correlate adverse event tetany with the use of bevacizumab. MATERIALS AND METHODS: World Health Organization's Uppsala Monitoring Centre, Sweden, for reporting of adverse drug reactions from all over the world, identified 7 cases with tetany-related symptoms to bevacizumab from four different countries. These 7 patients reported to UMC database developed adverse events described as musculoskeletal stiffness (1), muscle spasm (1), muscle cramps (1), lock jaw or jaw stiffness (4), and hypertonia (1), with hypocalcaemia. RESULTS: After detailed study of the possible mechanism of actions of bevacizumab and factors causing tetany, it is proposed that there is a possibility of tetany by bevacizumab, which may occur by interfering with calcium metabolism. Resorption of bone through osteoclasts by affecting VEGF may interfere with calcium metabolism. Another possibility of tetany may be due to associated hypomagnesaemia, hypokalemia, or hyponatremia. CONCLUSIONS: Tetany should be considered as a one of the signs. Patient on bevacizumab should carefully watch for tetany-related symptoms and calcium and magnesium levels for their safety.

[Serious adverse effects of blood collection]. / Effets indésirables donneurs et leur prise en charge.

The notification of serious adverse events occurring resulting from the collection of blood or blood components is a statutory requirement. The value of this set of surveillance procedures is the use of data collected. This article focuses on the organization of the French notification system, and the management of the main side effects known and reported.

Tetany in kala azar patients treated with paromomycin.

Paromomycin, an aminoglycoside, is known to cause several side effects like nephrotoxicity and ototoxicity like other aminoglycosides but tetany has not been reported. Three cases of tetany were detected in the patients of kala-azar treated with paromomycin. They were promptly treated with intravenous 10 per cent calcium gluconate and tetany was relieved immediately and treatment with paromomycin continued with oral calcium supplement. After completion of 21 days treatment with paromomycin patients' splenic aspirates were free of parasites. Paromomycin may cause temporary tubular damage leading to calcium wasting in urine and hypocalcaemia resulting in tetany. Prompt detection of symptoms and intravenous calcium gluconate treatment promptly reverse the situation.

When EGF is offside, magnesium is wasted.

Our understanding of magnesium (Mg(2+)) regulation has recently been catapulted forward by the discovery of several disease loci for monogenic disorders of Mg(2+) homeostasis. In this issue of the JCI, Groenestege et al. report that their study of a rare inherited Mg(2+) wasting disorder in consanguineous kindred shows that EGF acts as an autocrine/paracrine magnesiotropic hormone (see the related article beginning on page 2260). EGF stimulates Mg(2+) reabsorption in the renal distal convoluted tubule (DCT) via engagement of its receptor on the basolateral membrane of DCT cells and activation of the Mg(2+) channel TRPM6 (transient receptor potential cation channel, subfamily M, member 6) in the apical membrane. These authors show that a point mutation in pro-EGF retains EGF secretion to the apical but not the basolateral membrane, disrupting this cascade and causing renal Mg(2+) wasting. This work is another seminal example of the power of the study of monogenic disorders in the quest to understand human physiology.