Hi my name is captain shellabarger and i’m a student at the united states army graduate program in anesthesia nursing and this is a presentation on the drug labetalol labetalol is formulated for iv injection with a concentration of 5 milligrams per milliliter it comes in a unit dose or multi-dose vial labetalol is classified as a beta adrenergic antagonist
It competitively inhibits beta 1 into adrenergic receptors and weakly inhibits alpha 1 receptors the ratio of binding beta receptors to alpha receptors is 7 to 1 it is primarily used to treat hypertension and tachycardia intraoperatively adrenergic receptors are transmembrane receptors that are coupled to an intracellular g-protein these g proteins have three
Subunits and alpha beta and gamma subunit these protein receptors are termed g coupled protein receptors the sympathetic nervous systems effects are mediated via two different types of g coupled protein receptors alpha and beta receptors these two classes are further broken down into alpha 1 and alpha 2 and beta 1 and beta 2 g cohort proprioceptors do not cause
Intracellular events by themselves but are linked to intracellular primary messengers which lead to a cascade of events in production of second messengers beta 1 and beta 2 receptors are linked with the enzyme adenylate cyclase a primary intracellular messenger g coupled protein receptors they’re linked to adenylate cyclase are termed gs coupled protein receptors
Binding of a lightened to a gs transmembrane receptor activates the intracellular g-protein the alpha subunit disassociates from the beta and gamma subunit and activates the intracellular enzyme adenylate cyclase adenylate cyclase facilitates the conversion of adenosine triphosphate or atp into cyclic adenosine monophosphate or cyclic gmp cyclic anp acts as a second
Messenger to dis inhibit protein kinase a which activates intracellular processes through phosphorylation alpha one receptors are linked to the primary messenger phospholipase sc the transmembrane enzyme g coupled protein receptors that are linked to this enzyme are termed gq coupled protein receptors ligand binding to a gq coupled protein receptor activates the
Intracellular g-protein the alpha subunit disassociates from the beta and gamma subunits and activates a phospholipase to see spots will type acc is an enzyme that cleaves a membrane phospholipid into two molecules inositol one four five triphosphate or ip3 and diacylglycerol or dag ip3 acts on endoplasmic reticulum and causes the release of stored calcium into
The intracellular space dag activates protein kinase c which phosphorylates many intracellular processes a generic receptors are found throughout the body but the preponderance of beta 1 receptors are found on the heart on the myocardium beta 2 receptors are primarily found on the respiratory uterine and vascular smooth muscle and afwan receptors are found on the
Vascular smooth muscle beta one activation in the heart under normal conditions causes protein kinase a to phosphorylate ion channels thereby speeding depolarization and repolarization of the heart increasing heart rate contractility and cardiac output when a patient is given labetalol it competitively antagonizes these beta 1 receptors which leads to a decrease
In heart rate and contractility beta 2 activation on the respiratory smooth muscle stimulates the activation of protein kinase a protein kinase a phosphorylates myosin light-chain kinase which inhibits the phosphorylation of respiratory smooth muscle causing bronchial dilation when a patient is given labetalol it competitively antagonizes these beta 2 receptors
Allowing myosin light-chain kinase to work on the smooth muscle in promoting bronchial constriction alpha-1 activation on the vascular smooth muscle causes the release of intracellular calcium from the endoplasmic reticulum when calcium is released it binds to the intracellular protein calmodulin which forms a calcium calmodulin complex this complex then activates
Myosin light-chain kinase which phosphorylates myosin enables its interaction with actin stimulating vascular smooth muscle contraction and raising blood pressure when a patient is given labetalol it competitively inhibits these alpha 1 receptors leading to a decrease in calcium release promoting vascular smooth muscle dilation labetalol is typically administered
5 to 10 milligrams at a time in 5-minute intervals until the desired blood pressure has been reached labetalol can also be administered as an infusion a mixture of 200 milligrams in 250 milliliters d5w is titrated to a desired response at a rate of 10 to 180 milligrams an hour prolonged infusions of labetalol are not recommended onset for iv labetalol is typically
2 to 5 minutes but it can take up to several minutes peak effects are typically reached within 5 minutes labetalol is elimination half-life or its t1f beta is 5.5 hours this long elimination half-life accounts for its prolonged a clinical effect total body elimination of a single dose of labetalol typically occurs within 22 to 27 hours the beta law is primarily
Metabolized in the liver through conjugation to glue karana metabolites and excreted by the kidney and in the stool impaired hepatic renal function does not significantly affect the metabolism of lib labetalol is commonly used as an antihypertensive during the perioperative period the f1 blockade decreases vascular resistance and drops blood pressure this normally
Triggers the baroreceptor reflex to increase heart rate and contractility however labayda loss blockade of beta 1 receptors on the heart inhibits this reflex thus labetalol is used to decrease blood pressure without causing a reflex tachycardia because reflex tachycardia increases the cardiac workload in myocardial oxygen demand labayda law is an excellent choice
To treat intraoperative hypertension in hypertensive patients with coronary artery disease labetalol antagonism of alpha one receptors will decrease blood pressure and should be avoided in patients with severe hypotension labetalol antagonism of beta 1 receptors may decrease heart rate and contractility and should be avoided in patients with significant cardiac
Failure second are third-degree heart blocks cardiac shock or severe bradycardia labetalol antagonism of beta 2 receptors can promote bronchial smooth muscle constriction increasing airway resistance it should be avoided in patients with copd or reactive airway disease
Transcribed from video
Labetalol By Michael Bentley
