Penbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure. Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors, thus making it a non-selective β blocker. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors, it was approved by the FDA in 1987 and was withdrawn from the US market by January 2015. Penbutolol is used to treat mild to moderate high blood pressure. Like other beta blockers it is not a first line treatment for this indication, it should not be only used with caution in people with heart failure and people with asthma. It may mask signs of low blood sugar in people with diabetes and it may mask signs of hyperthyroidism. Animal studies showed some signs of potential trouble for women who are pregnant, it has not been tested in women who are pregnant, it is not known. Penbutolol has a low frequency of side effects; these side effects include dizziness, light headedness, nausea.
Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors, thus making it a non-selective β blocker. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors. Blocking β adrenergic receptors decreases the heart rate and cardiac output to lower arterial blood pressure. Β blockers decrease renin levels, which results in less water being reabsorbed by the kidneys and therefore a lower blood volume and blood pressure. Penbutolol acts on the β1 adrenergic receptors in the kidney; when β1 receptors are activated by a catecholamine, they stimulate a coupled G protein which activates adenylyl to convert adenosine triphosphate to cyclic adenosine monophosphate. The increase in cAMP alters the movement of calcium ions in heart muscle and increases heart rate. Penbutolol decreases heart rate, which lowers blood pressure; the ability of penbutolol to act as a partial agonist proves useful in the prevention of bradycardia as a result of decreasing the heart rate excessively.
Penbutolol binding β1 adrenergic receptors alters kidney functions. Under normal physiological conditions, the enzyme renin converts angiotensinogen to angiotensin I, which will be converted to angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal gland, causing a decrease in electrolyte and water retention increasing water excretion and decreasing blood volume and pressure. Like propanolol and pindolol, it is a serotonin 5-HT1B receptor antagonist. Penbutolol is absorbed from the gastrointestinal tract, has a bioavailability over 90%, has a rapid onset of effect. Penbutolol has a half life of five hours. Penbutolol was approved by the FDA in 1987. In January 2015 the FDA acknowledged that the penbutolol was no longer marketed in the US, determined that the drug was not withdrawn for safety reasons
This is a list of the counties of the United Kingdom. The history of local government in the United Kingdom differs between England, Northern Ireland and Wales, the subnational divisions within these which have been called counties have varied over time and by purpose; the county has formed the upper tier of local government over much of the United Kingdom at one time or another, has been used for a variety of other purposes, such as for Lord Lieutenants, land registration and postal delivery. This list is split by time period and purpose. Changes between the 1990s and 2009 subdivided the short-lived non-metropolitan counties of Cleveland and Humberside into unitary authorities, but the former county names continue for fire services and police forces; the short-lived county of Avon provides part of the area and name of Avon and Somerset Police and its area is that of the Avon Fire and Rescue Service. The historic counties of Yorkshire, Westmorland and Middlesex are the five defunct ceremonial counties which were counties.
With their abolition as ceremonial counties, Yorkshire is divided for that purpose into North Yorksire, East Yorkshire etc and Westmorland were combined with a former exclave of Lancashire to form Cumbria, Huntingdonshire merged into Cambridgeshire, the vast majority of Middlesex became part of Greater London. Contemporary reference to the Isle of Ely and nearby Soke of Peterborough is rare since the early 20th century and they have scant public resonance; the counties marked in italics below are neither historic. ♠ denotes a counter-intuitive pronunciation. See list of places in the United Kingdom and Ireland with counterintuitive pronunciations. ♠ denotes counter-intuitive pronunciation. Toponymical list of counties of the United Kingdom List of United Kingdom county nicknames Counties of Ireland Alias Data
The Theme of Sicily was a Byzantine province existing from the late 7th to the 10th century, encompassing the island of Sicily and the region of Calabria in the Italian mainland. Following the Muslim conquest of Sicily, from 902 the theme was limited to Calabria, but retained its original name until the middle of the 10th century. Since its reconquest from the Ostrogoths by Belisarius in 535–536, Sicily had formed a distinct province under a praetor, while the army was placed under a dux. A strategos is attested on the island in Arab sources between 687 and 695, it is at that time that the island was made into a theme; the theme was based in Syracuse, traditionally the chief city of Sicily. It comprised not only the island, divided into districts called tourmai, but the mainland duchy of Calabria, which extended up to the river Crati. In addition, the strategos of Sicily exercised some authority—varying according to the prevailing local political faction—over the autonomous duchies of Naples and Amalfi.
The Muslim conquest of the island began in 826. Following the fall of Syracuse in 878 and the conquest of Taormina in 902, the strategos moved to Rhegion, the capital of Calabria. During the first half of the 10th century, the Byzantines launched a number of failed expeditions to regain the island and maintained a few isolated strongholds near Messina until 965, when Rometta, the last Byzantine outpost, fell; the post of "strategos of Sicily" was thus retained as the official title until the mid-10th century, when the "strategos of Calabria" begins to appear in the lists. Note: Holders of the office known only from seals who can not be dated are not included. Uncertain or conjectural entries are denoted in italics. Exarchate of Ravenna History of Islam in southern Italy Brown, Thomas S.. "Byzantine Italy". In Sheppard, Jonathan; the Cambridge History of the Byzantine Empire c. 500–1492. Cambridge: Cambridge University Press. Pp. 433–464. ISBN 978-0-521-83231-1. Kazhdan, Alexander, ed.. The Oxford Dictionary of Byzantium.
Oxford and New York: Oxford University Press. ISBN 0-19-504652-8. Lilie, Ralph-Johannes. Prosopographie der mittelbyzantinischen Zeit Online. Berlin-Brandenburgische Akademie der Wissenschaften. Nach Vorarbeiten F. Winkelmanns erstellt. Berlin and Boston: De Gruyter. Nesbitt, John W.. Catalogue of Byzantine Seals at Dumbarton Oaks and in the Fogg Museum of Art, Volume 2: South of the Balkans, the Islands, South of Asia Minor. Washington, DC: Dumbarton Oaks Research Library and Collection. ISBN 0-88402-226-9. Oikonomides, Nicolas. Les listes de préséance byzantines des Xe siècles. Paris: Editions du Centre National de la Recherche Scientifique. Pertusi, A.. Constantino Porfirogenito: De Thematibus. Rome: Biblioteca Apostolica Vaticana. Prigent, Vivien. "Les stratèges de Sicile. De la naissance du thème au règne de Léon V". Revue des études byzantines. 61: 97–141. Doi:10.3406/rebyz.2003.2273