Cardiovascular function depends on an adequate vascular tone facilitating appropriate blood flow to individual tissues according to their needs. The tone results from the interplay between vasodilatation and vasoconstriction. Its rapid and efficient regulation is secured by many interconnected physiological mechanisms, both at the level of the vascular smooth muscle and the endothelium. The purpose of this review is to provide an update of the current knowledge on the mechanisms of physiological vasodilatation. First, two principal intracellular signaling pathways linked to the activation of protein kinases PKA and PKG are introduced. Subsequently, the role of endothelium-derived relaxing factors together with the endothelium-dependent hyperpolarization is discussed. The roles of ion channels and gap junctions in the communication between endothelium and vascular smooth muscle cells are particularly discussed. Finally, principal vasodilatory stimuli (mechanical, thermal, chemical) and their mechanisms of action are briefly introduced.

• Keywords
• EDRF, NO, PKA, PKG, Vasodilatation,
• MeSH
• Endothelium, Vascular physiology   MeSH
• Ion Channels physiology   MeSH
• Humans MeSH
• Gap Junctions physiology   MeSH
• Cyclic AMP-Dependent Protein Kinases metabolism   MeSH
• Cyclic GMP-Dependent Protein Kinases metabolism   MeSH
• Signal Transduction physiology   MeSH
• Muscle, Smooth, Vascular physiology   MeSH
• Vasodilation * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Ion Channels MeSH
• Cyclic AMP-Dependent Protein Kinases MeSH
• Cyclic GMP-Dependent Protein Kinases MeSH

BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

• MeSH
• Androstenes MeSH
• Androgen Receptor Antagonists * adverse effects   therapeutic use   MeSH
• Benzamides adverse effects   MeSH
• Phenylthiohydantoin MeSH
• Cardiovascular Diseases * chemically induced   epidemiology   MeSH
• Humans MeSH
• Prostatic Neoplasms * drug therapy   pathology   MeSH
• Nitriles adverse effects   MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Network Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• abiraterone MeSH Browser
• Androstenes MeSH
• Androgen Receptor Antagonists * MeSH
• Benzamides MeSH
• enzalutamide MeSH Browser
• Phenylthiohydantoin MeSH
• Nitriles MeSH

Various medicinal plants find their use in cough treatment, based on traditions and long-term experience. Pharmacological principles of their action, however, are much less known. Herbal drugs usually contain a mixture of potentially active compounds, which can manifest diverse effects. Expectorant or antitussive effects, which can be accompanied by others, such as anti-inflammatory or antibacterial, are probably the most important in the treatment of coughs. The aim of this review is to summarize the current state of knowledge of the effects of medicinal plants or their constituents on cough, based on reliable pharmacological studies. First, a comprehensive description of each effect is provided in order to explain the possible mechanism of action in detail. Next, the results related to individual plants and substances are summarized and critically discussed based on pharmacological in vivo and in vitro investigation.

• Keywords
• Anti-inflammatory, Antibacterial, Antitussive, Antiviral, Cough, Expectorant, Herbal drugs, Mechanism of action, Medicinal plants, Phytotherapy,
• MeSH
• Antitussive Agents * pharmacology   MeSH
• Expectorants pharmacology   MeSH
• Phytotherapy MeSH
• Cough drug therapy   MeSH
• Plants, Medicinal * MeSH
• Humans MeSH
• Plant Extracts pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Antitussive Agents * MeSH
• Expectorants MeSH
• Plant Extracts MeSH

Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.

• Keywords
• adrenaline, cathinone, cocaine, ephedrine, trace amines,
• MeSH
• Amines MeSH
• Cocaine * pharmacology   MeSH
• Humans MeSH
• Norepinephrine MeSH
• Sympathomimetics * pharmacology   MeSH
• Tyramine pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Amines MeSH
• Cocaine * MeSH
• Norepinephrine MeSH
• Sympathomimetics * MeSH
• Tyramine MeSH

Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC50 values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects.

• Keywords
• antiplatelet, bleeding, bulbocapnine, drug, isoquinoline,
• MeSH
• Platelet Aggregation * MeSH
• Alkaloids * pharmacology   MeSH
• Platelet Aggregation Inhibitors pharmacology   MeSH
• Isoquinolines pharmacology   MeSH
• Humans MeSH
• Blood Platelets MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Alkaloids * MeSH
• Platelet Aggregation Inhibitors MeSH
• Isoquinolines MeSH

Khat (Catha edulis) is a recreational, chewed herbal drug that has been used as a psychostimulant for centuries in East Africa and the Arabian Peninsula, namely in Somalia, Ethiopia, and Yemen. However, the growing worldwide availability of khat has produced widespread concern. The plant comprises a large number of active substances, among which cathinone, cathine, and norephedrine are the main constituents, which can be included in the group of sympathomimetics of natural origin. In fact, these compounds are amphetamine analogues, and, as such, they have amphetamine-like nervous system stimulant effects. Chewing the leaves gives people a sensation of well-being and increases energy, alertness, and self-confidence. The chronic use of khat is, however, associated with severe cardiac, neurological, psychological, and gastrointestinal complications. The psychological dependence and withdrawal symptoms of khat are the reasons for its prolonged use. The aim of this paper is to review current knowledge on the khat plant with toxicokinetic and toxicodynamic perspectives. Namely, this review paper addresses in vitro, in vivo, and human studies. The models used, as well as the concentrations and doses with the respective biological effects, are discussed. Additionally, the main drug interactions involved with khat are described.

• Keywords
• amphetamine-like, cathine, cathinone, kinetics, norpseudoephedrine, toxicology,
• MeSH
• Catha toxicity   MeSH
• Humans MeSH
• Plant Leaves MeSH
• Toxicokinetics MeSH
• Mastication MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH