Severe Acquired Hypokalemic Paralysis in a Bodybuilder After Self-Medication With Triamterene/Hydrochlorothiazide.

BACKGROUND: Severe hypokalemia with severe neurological impairment and electrocardiogram (ECG) abnormalities due to the misuse of triamterene/hydrochlorothiazide (HCTZ) in a bodybuilder has not yet been reported. CASE REPORT: A 22-year-old bodybuilder developed acute generalized muscle cramps, sensory disturbance of the distal lower and upper limbs, quadriparesis, and urinary retention. These abnormalities were attributed to severe hypokalemia of 1.8 mmol/L (normal range 3.4-4.5 mmol/L) due to misuse of triamterene/HCTZ together with fluid restriction. He was cardiologically asymptomatic, but ECG revealed a corrected QT (QTc) interval of 625 ms. On intravenous application of fluids along with intravenous and oral substitution of potassium, his condition rapidly improved, such that the sensory disturbances, quadriparesis, and bladder dysfunction completely resolved within 2 days after admission. CONCLUSIONS: Self-medication with diuretics along with fluid restriction may result in severe hypokalemia, paralysis, and ECG abnormalities. Those responsible for the management of bodybuilding studios and competitions must be aware of the potential severe health threats caused by self-medication with diuretics and anabolic steroids. Although triamterene is potassium-sparing, it may enhance the potassium-lowering effect of HCTZ.

A Medical Review of Fatal High-G U.S. Aerobatic Accidents.

INTRODUCTION: Exposure to high G force is a known safety hazard in military aviation as well as civilian aerobatic flight. Tolerance to high G forces has been well studied in military pilots, but there is little research directed at civilian pilots who may have medications or medical conditions not permitted in military pilots.METHODS: In this case-control study, we identified 89 fatal high-G aerobatic accidents and 4000 fatal control accidents from 1995 through 2018 from the NTSB accident database and the FAA autopsy database. We retrieved medications and medical conditions from the FAA's pilot medical databases. Logistic regression models were used to explore the associations of drugs, medical conditions, height, and medical waivers with high-G accidents.RESULTS: Seven drugs (alprazolam, clonidine, ethanol, meclizine, phentermine, triamterene, and zolpidem) reached statistical significance in our models, but had such small case counts that we consider these findings to be uncertain, except for ethanol, which was found in seven cases. Of these, only triamterene was known to the FAA. Statistically significant medical predictors included only alcohol abuse (seven cases) and liver disease (only two cases).DISCUSSION: Our analysis found that the drug ethanol and the condition alcohol abuse are significantly associated with high-G accidents. Seven other factors were statistically significant, but should only be considered as hypothesis generating due to very low case counts. Our study does not suggest that restricting pilots with otherwise permissible medications or medical conditions from aerobatics is warranted.Mills WD, Greenhaw RM, Wang JMP. A medical review of fatal high-G U.S. aerobatic accidents. Aerosp Med Hum Perform. 2019; 90(11):959-965.

Systematic analysis and identification of unexpected interactions from the neuroprotein drug interactome in hydrocephalus pharmacological intervention.

Hydrocephalus is a neurological condition caused by an abnormal accumulation of cerebrospinal fluid; pharmacological intervention of the disease has been found to elicit a variety of adverse drug reactions (ADRs) in central nervous system (CNS) by unexpectedly targeting certain functional neuroproteins. Here, a systematic neuroprotein drug interactome (SNDI) is created for 11 hydrocephalus drugs/metabolites plus 20 control drugs across 518 druggable pockets on the surface of 472 CNS neuroproteins via a large-scale molecular docking approach. Heuristic clustering analysis of the SNDI profile divides the 31 investigated drug ligands into a distinct panel and a background panel; the former consists of two hydrocephalus drugs (Furosemide and Triamterene) and their respective metabolites (Furosemide glucuronide and Hydroxytriamterene) that are inferred to have generally high affinity towards the whole array of neuroprotein pockets. A total of 13 neuroproteins are enriched in gene ontology semantic mining as putative unexpected targets of the distinct panel, and their intermolecular interactions with hydrocephalus drugs/metabolites are investigated in detail using dynamics simulation and energetics analysis. We also perform kinase assay and viability test to substantiate the interactome analysis. It is found that the Furosemide and Triamterene have significant cytotoxic effects on normal human astrocytes, in which the Triamterene can inhibit the neurokinase ROCK2, a representative of putative unexpected targets, with a high activity, which is comparable with the sophisticated ROCK2 inhibitor Fasudil.

Triamterene crystalline nephropathy.

Medications can cause a tubulointerstitial insult leading to acute kidney injury through multiple mechanisms. Acute tubular injury, a dose-dependent process, occurs due to direct toxicity on tubular cells. Acute interstitial nephritis characterized by interstitial inflammation and tubulitis develops from drugs that incite an allergic reaction. Other less common mechanisms include osmotic nephrosis and crystalline nephropathy. The latter complication is rare but has been associated with several drugs, such as sulfadiazine, indinavir, methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been reported only rarely, and its histologic characteristics are not well characterized. We report 2 cases of triamterene crystalline nephropathy, one of which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy.

[Clinical strategies for prevention of drug-induced urinary calculi].

Drug-induced urinary calculi, although they account for only 1-2% of urinary calculi, deserve consideration because most of them are preventable. In the drug-containing calculi resulting from the crystallization of a certain drug and its metabolites in the urine, stone analysis can identify the responsible drug. While, in the drug-induced metabolic calculi caused by interference with calcium, oxalate and purine metabolism, careful clinical inquiry is necessary to reveal involvement of a certain drug in stone formation. Better awareness of the possible drugs with lithogenic potential and close surveillance of patients on long-term treatment with these drugs are necessary. Especially, in patients with a history of urolithiaisis, prescription of lithogenic drugs deserve careful consideration.

Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China.

BACKGROUND: A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although HTDR has been used in China for more than 30 years, there have been few comprehensive evaluations of this treatment. OBJECTIVE: The aim of this study was to investigate the long-term efficacy and tolerability of HTDR in Chinese patients with essential hypertension. METHODS: This was a 36-month, community-based, open-label surveillance study, conducted in the Huangpu District (Shanghai, China). The study was based in local primary healthcare settings. Subjects were recruited if they had essential hypertension, were aged ≥35 years at the time of enrolment, were expected to remain in the area for 3 years, and were able to provide informed consent. Patients who had secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional hydrochlorothiazide was added. Blood pressure (BP) was measured at baseline and throughout the 36-month surveillance period every 3 months. Biochemical indicators (e.g. fasting blood glucose, plasma lipid parameters, plasma sodium and potassium, plasma uric acid and serum creatinine) were also measured, and adverse events were noted. BP reductions and the rate at which patients achieved BP targets (systolic BP [SBP] <140 mmHg and diastolic BP [DBP] <90 mmHg) throughout the period were determined. Subgroup analyses by sex and age were also conducted. RESULTS: A total of 1529 patients (550 male, 979 female; mean age 65.7 years) entered the study. After the 36-month treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipid profiles were improved after 24 months of treatment. In addition, a significant increase in plasma potassium and a significant reduction in plasma uric acid were seen. CONCLUSION: HTDR was found to have good long-term efficacy and tolerability in Chinese patients with essential hypertension.

[Differential diagnosis of a macrocytic, hyperchromic anemia following alcohol abuse and simultaneous therapy with triamterene and cotrimoxazole]. / Differentialdiagnose einer makrozytären, hyperchromen Anämie bei Alkoholabusus und gleichzeitiger Triamteren- und Cotrimoxazoltherapie.

HISTORY AND ADMISSION FINDINGS: A 50-year-old woman was admitted to our emergency room because of progressive weakness. She collapsed the night before admission. Skin and mucosa were pale, she denied major infections or bleedings. An alcohol abuse was known for many years. Because of edema she received a therapy with triamteren, an infection of the urinary tract was treated with cotrimoxacol. INVESTIGATIONS: In addition to thrombocytopenia (50 Gpt/l) and leukocytopenia (1,51 10 (9)/l) we diagnosed a hyperchromic and macrocytic anemia (Hb 3,6 mmol/l [5,8 g/dl], Hk 0,17, MCH 2.52 fmol, 116,8 fl). Folic acid was decreased to 0.677 ng/ml, whereas levels of cobalamin, ferritin and iron were normal. Examination of bone marrow showed a hypercellular marrow with typical megaloblastic features of erythropoiesis and granulopoiesis. A systemic hematological disorder could be ruled out. The folic acid deficiency in our patient was the result of a long time alcohol abuse and a simultaneous therapy with mild folate antagonists (triamteren and cotrimoxacol). CLINICAL COURSE: The patient received folic acid (5 mg/d orally). Within one week the peripheral blood counts increased to normal, the follow up bone marrow examination showed a hyperplastic marrow with normal hematopoietic maturation. CONCLUSIONS: Folic acid deficiency can be aggravated because of simultaneous therapy with mild folate antagonists. In addition to megaloblastic anemia this can lead to thrombocytopenia and/or leukocytopenia. Therefore in patients with pancytopenia a deficiency of folic acid should be ruled out.

Drug-induced myopia.

(1) Acute myopia can be drug-induced. (2) Cholinergic drugs cause accommodative spasm responsible for myopia. (3) Many other drugs, such as sulphonamides, and diuretics, can cause myopia without accommodative spasm. (4) Early withdrawal of the responsible drug leads to rapid recovery.

Thiazide-induced lichenoid photosensitivity.

We report the case of a 77-year-old male who developed a florid photosensitive eruption while taking thiazide diuretics for heart failure. The lesions were lichenoid in appearance and this was confirmed histologically. The eruption cleared on withdrawal of the drug. Although thiazide-induced photosensitivity is a well-documented phenomenon, there have been no histologically proven cases of a lichenoid eruption in light exposed areas in the recent literature.

Antihypertensive therapy in renal patients - benefits and difficulties.

High blood pressure values, diastolic and systolic, are associated with decreased renal function. This is particularly true when the diastolic blood pressure is higher than 90 mm Hg. Several studies showed that lowering of the blood pressure within the range of normotension according to the WHO causes a reduction in the rate of progression to terminal renal failure. These studies have led to recommendations to aim at a target blood pressure of approximately 125/75 mm Hg in the treatment of patients with glomerular diseases and particularly diabetic nephropathy with proteinuria >1 g/day. In contrast to these results, blood pressure values corresponding to the recommendation (

Crystal-induced acute renal failure.

Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in human urine. Intratubular precipitation of these crystals can lead to acute renal insufficiency. Many patients who require treatment with these medications have additional risk factors, such as true or effective intravascular volume depletion and underlying renal insufficiency, that increase the likelihood of drug-induced intrarenal crystal deposition. Acute renal failure in this setting may be preventable if it is anticipated by appropriate drug dosing, volume expansion with high urinary flow, and alkalinization of the urine when appropriate. Renal failure may be reversible if the drug is discontinued, and by volume repletion and alkalinization of the urine when appropriate. Management of established renal insufficiency includes volume repletion, dialytic support if necessary, adjustment of drug doses, and avoidance of further exposure to nephrotoxins.

Hyperkalaemia and diarrhoea in a patient with surreptitious ingestion of potassium sparing diuretics.

We report a patient who presented with the unusual combination of chronic diarrhoea and hyperkalaemia. The patient was admitted to our hospital after repeated negative evaluations elsewhere including exploratory laparotomy. The patient had a long history of diarrhoea with hypokalaemia which was documented on several occasions in the past. Several months before admission to our hospital for evaluation of diarrhoea the patient developed hyperkalaemia. Her daily stool output reached 1200 g and her serum potassium was as high as 6.0 mmol/l. Extensive evaluation revealed surreptitious ingestion of the diuretics triamterene, hydrochlorothiazide and spironolactone as the cause of hyperkalaemia and diarrhoea. In addition, she had melanosis coli which was interpreted to be the consequence of surreptitious ingestion of anthraquinone-containing laxatives in the past although no current laxative intake could be proven. We postulate that diarrhoea in our patient was mainly due to the decreased sodium absorption in the small intestine and colon caused by diuretics. Serum aldosterone levels were more than eight times the upper limit of normal. Increased aldosterone levels presumably arose secondary to volume contraction and sodium chloride depletion, but presumably were not able to affect renal and colonic electrolyte transport because of blockage of mineralocorticoid receptors by spironolactone. Thus, the unusual combination of diarrhoea and hyperkalaemia resulted.

[Potassium-sparing diuretics (spironolactone, triamterene, amylorid)]. / Káliummegtakarító diureticumok (spironolacton, triamteren, amilorid).

The group of drugs, so-called "potassium sparing diuretics" represent an important part of our modern therapeutic arsenal. Their "weak diuretic" properties are especially beneficial in cirrhotic patients with ascites, when highly effective loop diuretics may be hazardous. Potassium sparing diuretics have not only the advantage of avoiding potassium loss, but can potentiate the effects of diuretics acting in distal tubules and Henle's loop also. They may be combined by each other or ACE inhibitors too, taking the necessary precautions and laboratory monitoring. Their indications include the hypertension and special diseases as Conn's, Bartter's, Liddle syndromes and hirsutism. The broad clinical usefulness justifies the drug inventory ambition to develop new, more effective potassium sparing compounds without side effects. Authors overview their main clinicofarmacological properties, therapeutical indications alone or in combinations and their potential side effects.

Felodipine or hydrochlorothiazide/triamterene for treatment of hypertension in the elderly: effects on blood pressure, hypertensive heart disease, metabolic and hormonal parameters.

The aim of the study was to compare the antihypertensive efficacy of either felodipine or the diuretic combination hydrochlorothiazide/triamterene in a group (n = 65) of elderly (> or = 70 years) hypertensives (office blood pressure > or = 160/95 mmHg) with special regard to ambulatory blood pressure monitoring, hypertensive heart disease and metabolic parameters. This was a randomized, double-blind study with a treatment period of 6 months. Reduction of office and 24-hr ambulatory blood pressure was comparable with both treatment regimens; after 6 months. 18 of 29 patients in the felodipine group (62%) and 20 of 27 patients in the diuretic group (74%; p = 0.4) were controlled. While episodes of ischemic type ST-segment depression were significantly reduced in the felodipine group (from 49 to 9 episodes), there was no significant change in the diuretic group (from 24 to 21 episodes). Both regimens decreased left ventricular wall thickness, but the decline in left ventricular muscle mass index was significant only for felodipine. Felodipine did not induce any change in metabolic or hormonal parameters; the diuretic combination significantly increased serum creatinine, uric acid, plasma renin activity, and plasma prorenin. Thus, the antihypertensive efficacy of felodipine and the diuretic combination was comparable in elderly hypertensives; only felodipine, however, improved parameters of hypertensive heart disease and showed a neutral metabolic and hormonal profile.

Choroidal effusion as a mechanism for transient myopia induced by hydrochlorothiazide and triamterene.

PURPOSE: We treated a case of transient myopia in a patient being treated with hydrochlorothiazide and triamterene for tinnitus. METHODS: The patient underwent gonioscopic, ophthalmoscopic, and echographic examinations. RESULTS: Examination showed anterior chamber flattening and echography disclosed bilateral 360-degree shallow choroidal detachments. CONCLUSION: All of the patient's symptoms and signs resolved after the cessation of drug therapy.

Exercise-induced acute renal failure associated with ibuprofen, hydrochlorothiazide, and triamterene.

Nonsteroidal anti-inflammatory drugs predispose to acute renal failure in conditions associated with decreased RBF. Such conditions include advanced age, hypertension, chronic renal insufficiency, diuretic use, and any condition decreasing effective circulating volume. Strenuous exercise also causes marked reductions in RBF. The patient discussed developed severe acute renal failure after strenuous exercise and therapeutic doses of ibuprofen and hydrochlorothiazide-triamterene. Urinalysis showed a nephritic sediment with red blood cell casts. Renal biopsy showed acute tubular necrosis and arteriolar nephrosclerosis. Although exercise-associated acute renal failure is uncommon, susceptible patients with exercise-induced renal ischemia and prostaglandin inhibition may develop this complication.