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The Journal of Clinical Investigation Oct 2019Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP...
Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.
Topics: Adenosine Triphosphate; Aged; Aged, 80 and over; Animals; Brain; Disease Progression; Dopamine; Drosophila melanogaster; Female; Glycolysis; Humans; Induced Pluripotent Stem Cells; Male; Mice; Mice, Inbred C57BL; Nerve Degeneration; Parkinson Disease; Parkinsonian Disorders; Phosphoglycerate Kinase; Prazosin; Rats
PubMed: 31524631
DOI: 10.1172/JCI129987 -
Current Cardiology Reviews 2022Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These... (Review)
Review
Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These medications have diverse effects on the heart, vascular system, as well as other tissues and organ systems. The extra cardiovascular effects have been found to be of use in the treatment of non-cardiovascular diseases and pathologies. Minoxidil is used to manage systemic hypertension with its well-known side effect of hirsutism used to treat alopecia and baldness. Sildenafil was originally investigated as a treatment option for systemic hypertension; however, its side effect of penile erection led to it being widely used for erectile dysfunction. Alpha-1 blockers such as terazosin are indicated to treat systemic hypertension but are more commonly used for benign prostatic hyperplasia and post-traumatic stress disorder. Beta blockers are the mainstay treatment for congestive heart failure and systemic hypertension but have been found useful to help in patients with intention tremors as well as prophylaxis of migraines. Similarly, calcium channel blockers are indicated in medical expulsion therapy for ureteric calculi in addition to their cardiovascular indications. Thiazides are commonly used for treating systemic hypertension and as diuretics. Thiazides can cause hypocalciuria and hypercalcemia. This side effect has led to thiazides being used to treat idiopathic hypercalciuria and associated nephrolithiasis. Spironolactone is commonly utilized in treating heart failure and as a diuretic for edema. It's well described anti-androgen side effects have been used for acne vulgaris and hirsutism in polycystic ovarian syndrome. This review article discusses how the various extracardiovascular effects of commonly used cardiovascular medications are put to use in managing non-cardiovascular conditions.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Diuretics; Heart Failure; Hirsutism; Humans; Hypertension; Male; Thiazides
PubMed: 34779371
DOI: 10.2174/1573403X17666211015145132 -
Journal of Clinical Hypertension... Sep 2022There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood... (Review)
Review
There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.
Topics: Adrenergic alpha-Antagonists; Aged; Aldosterone; Antihypertensive Agents; Diuretics; Doxazosin; Humans; Hypertension; Renin
PubMed: 36196467
DOI: 10.1111/jch.14556 -
International Braz J Urol : Official... 2021To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. (Review)
Review
PURPOSE
To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice.
MATERIALS AND METHODS
A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors.
RESULTS
The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes.
CONCLUSIONS
Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.
Topics: Adrenergic alpha-Antagonists; Doxazosin; Humans; Male; Pharmaceutical Preparations; Prazosin; Prostatic Hyperplasia; Tadalafil; Tamsulosin
PubMed: 33566468
DOI: 10.1590/S1677-5538.IBJU.2021.99.06 -
Chemical Science Sep 2021A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150...
A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of an oxygen atom into the spirocyclic unit dramatically improved water solubility (by up to 40 times) and lowered lipophilicity. More potent oxa-spirocyclic analogues of antihypertensive drug terazosin were synthesized and studied .
PubMed: 34667540
DOI: 10.1039/d1sc03615g -
Drug Delivery Dec 2021This study aimed to construct a transdermal iontophoresis delivery system for terazosin hydrochloride (IDDS-TEH), which included a positive and negative electrode...
This study aimed to construct a transdermal iontophoresis delivery system for terazosin hydrochloride (IDDS-TEH), which included a positive and negative electrode hydrogel prescription. Intact guinea pig skin was used as a model for the skin barrier function, and the current intensity, terazosin hydrochloride (TEH) concentration, pH, competitive salt, and transdermal enhancer properties were studied. The blood drug concentration was determined in Sprague-Dawley (SD) rats using HPLC, and the antihypertensive effects of IDDS-TEH were evaluated in spontaneously hypertensive rats (SHRs). The results showed that the steady-state penetration rate of TEH increased (from 80.36 µg·cm·h to 304.93 µg·cm·h), followed by an increase in the current intensity (from 0.10 mA·cm to 0.49 mA·cm). The pH values also had a significant influence on percutaneous penetration. The blood concentration of IDDS-TEH was significantly higher ( < .05) than with passive diffusion, which could not be detected. The main pharmacokinetic parameters of the high current group (0.17 mA·cm) and the low current group (0.09 mA·cm) were AUC: 5873.0 ng·mL·h and 2493.7 ng·mL·h, respectively. Meanwhile, the pharmacodynamic results showed that IDDS-TEH significantly decreased the blood pressure of SHRs compared with the TEH hydrogel without loading current. Therefore, TEH could be successfully delivered by the transdermal iontophoresis system and , and further clinical studies should be explored to develop a therapeutically useful protocol.
Topics: Administration, Cutaneous; Adrenergic alpha-1 Receptor Antagonists; Animals; Antihypertensive Agents; Area Under Curve; Blood Pressure; Chromatography, High Pressure Liquid; Drug Delivery Systems; Female; Guinea Pigs; Hypertension; Iontophoresis; Male; Prazosin; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Skin Absorption
PubMed: 33620010
DOI: 10.1080/10717544.2021.1889719 -
European Journal of Hospital Pharmacy :... Jul 2022Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in...
OBJECTIVE
Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in reducing high blood pressure, clinical data on the potential role of valsartan in PCC are currently limited. Therefore, the aim of this study was to investigate the effects of pretreatment with terazosin and valsartan on patients with PCC.
METHODS
In this retrospective cohort study, 50 patients who underwent laparoscopic resection of PCC were enrolled. During preoperative preparation, the patients (n=25) in the control group were treated with terazosin, while those (n=25) in the combination treatment group were treated with terazosin and valsartan. The levels of catecholamine hormones before and after surgery were determined, and the intraoperative blood pressure and the incidence of complications were compared between the two groups.
RESULTS
The results showed no significant differences in baseline patient characteristics or surgical conditions between the two groups (p>0.05). However, on the third day after surgery, the levels of catecholamine hormones in the two groups were significantly lower than those before surgery (p<0.05), while the levels in the combination treatment group were notably lower than those in the control group (p<0.05). The patients in the combination treatment group showed lower intraoperative blood pressure fluctuations and incidence of perioperative complications compared with the control group (p<0.05).
CONCLUSIONS
Terazosin combined with valsartan can effectively improve perioperative haemodynamic instability and reduce postoperative complications in the preoperative management of PCC.
Topics: Adrenal Gland Neoplasms; Catecholamines; Hemodynamics; Hormones; Humans; Pheochromocytoma; Prazosin; Retrospective Studies; Valsartan
PubMed: 32895230
DOI: 10.1136/ejhpharm-2020-002375 -
International Journal of Molecular... Dec 2021Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them,...
Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.
Topics: Apoptosis; Caco-2 Cells; Cell Survival; Colitis; Cytokines; Deoxyglucose; Dextran Sulfate; Gastric Mucosa; Gastrointestinal Diseases; Glucose; Humans; Hydrogen Peroxide; Inflammation Mediators; Lactic Acid; Malondialdehyde; Models, Biological; Peroxidase; Phosphoglycerate Kinase; Prazosin; Pyroptosis; Stomach Ulcer; Superoxide Dismutase
PubMed: 35008842
DOI: 10.3390/ijms23010416