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BMJ Case Reports Apr 2024We present a case involving a male patient in his 30s who was admitted to hospital due to recurrent episodes of hypokalaemia over the past 5 years. His medical history...
We present a case involving a male patient in his 30s who was admitted to hospital due to recurrent episodes of hypokalaemia over the past 5 years. His medical history revealed hypertension, attention deficit hyperactivity disorder (ADHD), autism, and paranoia. He was taking citalopram, ramipril, amlodipine, and pramipexole. Tests indicated normal levels of aldosterone/renin ratio and plasma metanephrines. On reviewing his dietary history, it was noted that he consumed 3 to 3.5 L of cola-flavoured drinks on a daily basis. Normal potassium levels were achieved after a significant reduction in cola-flavoured drinks intake and potassium replacement. Subsequent outpatient clinic follow-up revealed that normal potassium levels were maintained even after the patient ceased taking potassium replacement tablets. Given the rarity of hypokalaemia associated with fizzy drinks, the underlying mechanism for this association remains unclear. In this case report, we attempt to provide a possible explanation for the involved mechanisms.
Topics: Humans; Male; Hypokalemia; Adult; Carbonated Beverages; Attention Deficit Disorder with Hyperactivity; Hypertension
PubMed: 38649244
DOI: 10.1136/bcr-2023-258873 -
Functional & Integrative Genomics Apr 2024Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the...
BACKGROUND
Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies.
PURPOSE
This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC.
METHODS
We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity.
RESULTS
SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine.
CONCLUSION
SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies.
Topics: Humans; Amlodipine; Calcium; Calcium Signaling; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Stomach Neoplasms; Synaptotagmins; Calcium Channel Blockers
PubMed: 38632140
DOI: 10.1007/s10142-024-01345-8 -
Malaysian Family Physician : the... 2024Buccal lichenoid lesions (BLLs) are characterised by a unique, linear whitish striation in the buccal region and can be accompanied by ulcers, plaques, erythemas,...
Buccal lichenoid lesions (BLLs) are characterised by a unique, linear whitish striation in the buccal region and can be accompanied by ulcers, plaques, erythemas, atrophies and blisters. They are distinguished from oral lichen planus (OLP) by the association of the administration of a drug or contact with a metal. Herein, we present the case of a 42-year-old woman with underlying hypertension with amlodipine-induced BLLs. She complained of a 1-month history of right buccal whitish streaks and oral ulcers 2 months after taking amlodipine. She visited a private otorhinolaryngology clinic, and a biopsy for the right buccal ulcer was conducted. The biopsy result showed features suggestive of OLP. The patient was then diagnosed with OLP. Her symptoms were persistent despite treatment, so a dental referral was made. Amlodipine was suspected as the cause of her condition and was therefore stopped. Her condition gradually resolved after amlodipine withdrawal. Hence, primary care physicians should be aware of BLLs as one of the adverse drug reactions of amlodipine so that prompt management can be taken to avoid further debilitating impacts on patients.
PubMed: 38623417
DOI: 10.51866/cr.531 -
Georgian Medical News Feb 2024The Nitrosogenesis of skin cancer is a modern newly introduced concept in medicine, mainly concerning melanoma, but also keratinocytic cancers such as basal cell...
PERIOCULAR HIGH RISK BCCS AFTER ADDITIONAL/PARALLEL INTAKE OF TORASEMIDE, MOXONIDINE AND MIRABEGRON: IMPORTANT LINKS TO SKIN CANCER RELATED (PHOTO-) NITROSOGENESIS IN THE CONTEXT OF PHARMACO-ONCOGENESIS.
The Nitrosogenesis of skin cancer is a modern newly introduced concept in medicine, mainly concerning melanoma, but also keratinocytic cancers such as basal cell carcinoma. The nitroso-contamination of more than 300 drugs worldwide and the permanent (relatively short-term) intake of mutagen-contaminated drugs could create serious prerequisites for the development of skin cancer. Retrospective but also prospective analyses following potentially contaminated polymedication with a heterogeneous type of nitrosamines in real patients are indicative of a causal connection rather than a sporadic association between 1) intake of a possibly nitrosamine-contaminated drug and 2) generation of keratinocytic skin cancer. The pathogenesis of high-risk periocular localized basal cell carcinomas was until recently shrouded in mystery as it was mainly and until now associated with 1) intake of phototoxic drugs and 2) intense exposure to UV radiation (without intake of drugs), 3) congenital or acquired immunodeficiencies, and 4) Goltz Gorlin syndrome or 5) Xeroderma pigmentosum. Nitrosamines/ NDSRIs within the framework of polycotaminated drug intake appear to be one reasonable additional explanation for the association between carcinogen intake and subsequent skin cancer development and progression, and a relatively short-term one at that. Recently published scientific data provide information on a new ability of some of the nitrosamines - namely that some of them are photocarcinogenic or genotoxic after activation with UVA radiation. We present 4 patients who developed high-risk periocular localized basal cell carcinomas of the skin after/within the intake of potentially nitrosamine-contaminated drugs. The presented data are confirmatory with respect to previously published scientific observations on the carcinogenic effects of valsartan, candesartan, bisoprolol, metoprolol, perindopril, lisinopril and amlodipine. The contribution of newly validated data concerning potential/actual carcinogenic/genotoxic activity in the article is also due to the following newly announced nitroso preparations: torasemide, moxonidine and mirabegron. The expansion of the ˝bases of the pyramid˝ determining the stability of drug related (Photo) Nitrosogenesis/ Carcinogenesis (in terms of skin cancer generation) is growing daily. Exogenously/drug-induced Nitrosogenesis and the subsequently triggered carcinogenesis are a completely new explanatory concepts concerning the pathogenesis of skin tumors that remained unanalyzed and hidden for decades. Until now. The official lack of 1) availability, and of 2) precise concentrations regarding nitrosamines in medicinal preparations, are some of the most unexplained acts of irresponsibility to end-users and remain for the moment without a definitive answer from either regulators and manufacturers respectively. Polycontamination of polymedication in polymorbid patients remains highly problematic, at least as a cofactor in the development and progression of keratinocytic cancers, and this in the short term. Recently published data but also data from the past are suggestive that nitrosamines in tobacco are pivotal in the development of acquired mutations in p53 and RAS oncogenes in humans and rodents. The same genes are also affected by mutations in keratinocytic cancer patients. The overlapping mutation patterns of UV radiation-induced mutations in target genes such as p53 and RAS with those caused by some nitrosamines is indicative of a synergism available in terms of gene toxicity or possibly photocarcinogenicity of the latter. What leads the scientific community to believe that the nitrosamines in drugs, similar in composition and carcinogenic potency, act differently, is unclear. The link between drug intake, nitrosamine contamination, generation of some acquired mutations and subsequent cancer development becomes more than obvious and logically conditioned. The thesis of the controlled spread of cancer sounds more than logical today because: whoever controls and regulates the spread of carcinogens/mutagens/nitrosamines is also able to control the occurrence and spread of skin cancer. The Pharmaco-oncogenesis of skin cancer is determined by exogenously mediated Nitrosogenesis or the permissive availability for certain nitrosamines in drugs worldwide.
Topics: Humans; Torsemide; Prospective Studies; Retrospective Studies; Tumor Suppressor Protein p53; Carcinogenesis; Cell Transformation, Neoplastic; Skin Neoplasms; Carcinoma, Basal Cell; Nitrosamines; Acetanilides; Imidazoles; Thiazoles
PubMed: 38609117
DOI: No ID Found -
Frontiers in Pharmacology 2024Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and...
Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine . The novel conjugates were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound was refluxed with various aldehydes and ketones for 5-8 h in methanol at 60°C-90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands were established based on spectral and analytical data. The synthesized compounds were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds have good inhibition potential against the enzyme tyrosinase. Compounds , , , and depicted excellent antityrosinase activity. Compound , with an IC value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC 6.04 ± 0.11 µM), standing out among all synthesized compounds . The studies of the conjugates were evaluated via . Compound showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of -219.66 kcal/mol. The structure-activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables.
PubMed: 38595924
DOI: 10.3389/fphar.2024.1332184 -
Hypertension Research : Official... Jun 2024New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP... (Randomized Controlled Trial)
Randomized Controlled Trial
New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.
Topics: Humans; Female; Male; Hypertension; Middle Aged; Biphenyl Compounds; Antihypertensive Agents; Double-Blind Method; Benzimidazoles; Amlodipine; Tetrazoles; Blood Pressure; Aged; Treatment Outcome; Bisoprolol; Indapamide; Adult; Drug Therapy, Combination
PubMed: 38584159
DOI: 10.1038/s41440-024-01658-y -
European Heart Journal. Case Reports Apr 2024Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers...
BACKGROUND
Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis.
CASE SUMMARY
A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable.
DISCUSSION
Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear.
PubMed: 38576465
DOI: 10.1093/ehjcr/ytae161 -
The Journal of Veterinary Medical... May 2024An increase in systemic blood pressure causes bleeding and ischemia owing to peripheral vascular breakdown, leading to various forms of organ damage. The brain, eyes,...
An increase in systemic blood pressure causes bleeding and ischemia owing to peripheral vascular breakdown, leading to various forms of organ damage. The brain, eyes, kidneys, and cardiovascular system are known target organs for hypertension. To our knowledge, no reports in Japan describe, in detail, the types of antihypertensive drugs used to treat hypertension in cats or its underlying causes. Therefore, we aimed to investigate the use of antihypertensive drugs in domestic cats with hypertension in Japan, the causes of hypertension, and the vital prognosis of these patients. In the present survey, we found that amlodipine was used alone (60/80 cats) or concomitantly (20/80 cats) in all cat patients with hypertension in Japan. We also determined that blood pressure measurements were not yet routinely performed on cats at veterinary clinics in Japan. Furthermore, we have new information suggesting that amlodipine administration in cats with hypertension, which lowers systolic arterial pressure levels to within the normal range (<140 mmHg), may have a negative impact on their survival. Routine blood pressure measurements for cats during their regular health checkups can help identify hypertension, and proper interpretation of blood pressure readings can facilitate suitable treatment measures.
Topics: Animals; Amlodipine; Cats; Hypertension; Japan; Cat Diseases; Antihypertensive Agents; Male; Female; Blood Pressure
PubMed: 38569838
DOI: 10.1292/jvms.23-0444 -
BMJ Case Reports Apr 2024This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman...
This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.
Topics: Middle Aged; Female; Humans; Olmesartan Medoxomil; Telmisartan; Vildagliptin; Polypharmacy; Amlodipine; Drug Overdose; Angioedema; Tetrazoles; Antihypertensive Agents; Hypertension
PubMed: 38569737
DOI: 10.1136/bcr-2023-259485