HYPERTENSION Emergencies & Urgencies,Stephen S. Levin, D.O.,Definitions,Emergencies Symptomatic Acute End-Organ Damage Diastolic B.P. usually 130 mmHg Urgencies Asymptomatic NO Acute End-Organ Damage Diastolic B.P. usually 110 mmHg; Systolic B.P. usually 180 mmHg,Begin Treatment! This is a Hypertensive Emergency Begin to look for other causes of symptoms,Principles of Therapy,Lower B.P. over hours Initial goal B.P. 160s/90s Too rapid lowering may cause dire consequences (CVA, MI) May take several days to get to reasonable levels Avoid medications that cannot be controlled (sublingual nifedipine),Hypertensive Emergencies: Treatment,For most patients the greatest risk of treating a hypertensive emergency is the risk of accompanying hypotension.Treat with short acting, easily titratable, I.V. drug.,Parenteral Drugs for Treatment of Hypertensive Emergencies,Parenteral Drugs for Treatment of Hypertensive Emergencies,Parenteral Drugs for Treatment of Hypertensive Emergencies,Parenteral Drugs for Treatment of Hypertensive Emergencies,Parenteral Drugs for Treatment of Hypertensive Emergencies,Parenteral Drugs for Treatment of Hypertensive Emergencies,Fenoldopam: Indications,In-hospital, short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end organ function. Transition to oral therapy with another agent can begin at any time after blood pressure is stable during fenoldopam infusion.,Physiologic Effects Fenoldopam,Systemic Vasodilation,Does not cross BBB,Coronary Vasodilationwithout “steal”(in animals)Reflex tachycardia,Metabolized by conjugationNo P450 interaction, RBF Na excretion H2O excretionMaintains GFR during BP lowering,Mesenteric vasodilation Mucosal PO2(in animals),Fenoldopam Receptor Activity,Selective peripheral dopamine-1 (DA1) receptor agonism Systemic vasodilation Regional vasodilation (especially renal) Renal proximal and distal tubular effects No binding to DA2 or beta-adrenergic receptors No alpha-adrenergic agonism, but is an alpha1 antagonist Does not cross blood brain barrier,Mechanism of Action of Fenoldopam,Fenoldopam infusion,Selective stimulation of D1-dopamine receptors,Adenylyl cyclase activation,Increase in intracellular concentration of cAMP,Vascular smooth muscle relaxation,Vasodilation of renal arteries,Vasodilation of coronary arteries,Vasodilation of mesenteric arteries,Vasodilation of systemic arteries,Maintenance of blood flow to vital organs,Decrease in systemic vascular resistance,Decrease in blood pressure,Direct increase in sodium excretion,Fenoldopam Metabolism,Metabolism via conjugation Metabolites pharmacologically inactive No cytochrome P450 interactions No known metabolic drug interactions 88% albumin bound Elimination: 90% urine, 10% feces No dose adjustment for renal or hepatic impairment, t ( 5 min) Small volume of distribution Rapid attainment of steady state ( 30 min) Plasma concentrations proportional to dose No alteration in pharmacokinetics over 48 hr infusion Rapid elimination upon discontinuation,Fenoldopam: Pharmacokinetics,Predictable hemodynamic effect Rapid onset of effect Predictable dose response for lowering BP No rebound hypertension,Fenoldopam: Pharmacodynamics, Rapid, predictable, dose-dependent blood pressure decrease (without overshoot) Short t, rapid attainment of steady state titration Linear pharmacokinetics No cytochrome P450 interactions Dose-response curves well defined No dosing adjustment for pre-existing renal or hepatic impairment Increases renal blood flow and maintains GFR Ease of use,Fenoldopam: Potential Benefits,Fenoldopam: Adverse Events,Headache Flushing Nausea Hypotension Hypokalemia,EKG Abnormalities Tachycardia Vomiting Dizziness Extrasystoles Dyspnea,Nicardipine: Characteristics,Dihydropyridine Reflex tachycardia Useful when -Blockers contraindicated Water soluble and light stable (allows for IV infusion),Slow onset and offset Arterial catheter not mandatory May accumulate Variable duration of hypertensive effect Good in patients with renal disease,Nitroprusside,Onset 1-4 min., half-life 1-2 min. Metabolized by RBC to cyanide then by liver to thiocyanate, cleared by kidneys Caution with hepatic &/or renal disease,Toxicity related to total dose S&S: met. acidosis, confusion, air hunger, hyper-reflexia, confusion, and seizures. Reversible by hydroxycobalamine, sodium nitrate, (?) methylene blue,Therapy Hypertensive Urgencies,Oral meds. Preferred Close monitoring Fast follow-up Start with short acting forms (not Ca+2 channel blockers),Drugs for Urgencies,Clonidine -Blockers, - Blockers Captopril, Enalapril Minoxidil (if already on -blocker & diuretic) Hydralazine,Drug Related Malignant Hypertension,MAO Inhibitors “Cold Preparations” Withdrawal Antihypertensive Meds Clonidine, -Blockers “Street Drugs” Cocaine, PCP,