Hypotensive Agents

Hypotensive Agents R1 이송이

Hypotensive Agents • Hypotensive Agents • Volatile anesthetics • Sympathetic antagonists and agonists • Calcium channel blockers and ACE-inhibitors • Nitrates, Adenosine, Fenoldopam  dilating pph. vessels

SODIUM NITROPRUSSIDE • Mechanism of Action • Relax both arteriolar and venous smooth muscle • Its primary mechanism of action is shared with other nitrates (eg. hydalazine and nitroglycerine)  Release of nitric oxide  activate guanylyl cyclase  synthesis of cGMP  smooth m. contraction

SODIUM NITROPRUSSIDE • Nitric oxide • Potent vasodilater released by endothelial cells (endothelium-derived relaxing factor) • Inhaled nitric oxide • Selective pulmonary vasodilator : beneficial in the treatment of reversible pulmonary HTN • Improves oxygenation in ARDS pts or during one-lung ventilation • Anti-inflammatory effect

SODIUM NITROPRUSSIDE • Clinical Uses • Potent & reliable antihypertensive • Diluted to 100μg/ml • Continuous IV infusion : 0.5-10 μg/kg/min • Extremely rapid onset : 1-2 min • Bolus (1-2 μg/kg) : minimizes BP elevation during laryngoscopy, but can cause transient Hypotension • Requires frequent BP monitoring (intraarterial monitoring)

SODIUM NITROPRUSSIDE • Metabolism • Sodium nitroprusside(SNP) enters red blood cells  receives Fe 2+ from oxyhemoglobin  results in an unstable nitroprusside radical(SNP‾) and methemoglobin(Hgb Fe 3+) • SNP‾ decomposes in to5cyanide ions and the active nitroso group • Cyanide ions (1)bind to methemoglobin  cyanmethemoglobin (2)bind to thisulfate  thiocyanate (3)bind to tissue cytochrome oxidase cyanide toxicity

SODIUM NITROPRUSSIDE • Acute cyanide toxicity • Metabolic acidosis, cardiac arrhythmia, increased venous oxygen contents • Can be avoided if the cumulative dose is less than 0.5mg/kg/h • Treatment : mechanical ventilation with 100% oxygen, sodium thiosulfate(150mg/kg over 15 min), 3% sodium nitrate(5mg/kg over 5min)

SODIUM NITROPRUSSIDE <Effects on organ systems> • Cardiovascular • Dilation of venous and arterial beds  ↓ preload & afterload • ↓ pph. vascular resistance  ↓ ABP • ↓ preload  ↓ myocardia work, ↓ risk of ischemia • Cerebral • cerebral vessels dilation & abolish autoregulation • cerebral blood flow is maintained or increased • Pts with decreased intracranial compliance (eg. brain tumor)  increaseintracranial pr.

SODIUM NITROPRUSSIDE <Effects on organ systems> • Respiratory • Pul. vasculature dilatation • ↓ pul. artery pr. ↓ perfusion  ↑ physiological dead space • Prevent pul. vasoconstrictive response to hypoxia • Mismatch pul. Ventilation toperfusion & decrease arterial oxygenation • Renal • ↓ ABP  rennin & catecholamine release • Can cause pressure rebound after discontinuation • Renal function is fairly well maintained

SODIUM NITROPRUSSIDE • Drug Interactions • Does not directly interact with NM blocking agent • ↓ muscle blood flow indirectly prolong NM blockade

NITROGLYCERIN • Mechanism of action • Relax vascular smooth m. • venous dilation predominating over arterial dilation • Clinical uses • Diluted to 100μg/ml • Continuous Infusion : 0.5-10 μg/kg/min • Sublingual (peak effect 4min) • Transdermal

NITROGLYCERIN • Metabolism • reductive hydrolysis in liver and blood by glutathione-organic nitrates reductase <Effects on organ systems> • Cardiovascular • ↓ venous return&preload • ↓ afterload d/t arteriolar dilation • ↓ end-systolic pr. & O2 demand • Redistribution of coronary blood flow ischemic areas of subendocardium • Relief of coronary artery spasm • ↓ platelet aggregation & ↑coronary vesselpotency

NITROGLYCERIN <Effects on organ systems> • Cerebral • Similar to sodium nitroprusside • side effect :headache (cerebral vessel dilation) • Respiratory • bronchial smooth musclerelaxation

HYDRALAZINE • Mechanism of Action • Arteriolar smooth muscle relaxation • Clinical Use • Control of intraoperative HTN : IV 5-20mg (onset within15 min, duration 2-4 hr) • Continuous infusion is less frequently used d/t their slow onset and long duration

HYDRALAZINE <Effects on organ systems> • Cardiovascular • ↓ pph. vascular resistance  ↓ arterial BP • ↑ HR, myocardial contractility, CO • Cerebral • Potent cerebral vasodilator & inhibit cerebral blood flow autoregulation • Renal • Renal blood flow is maintained or increased

ADENOSINE • Mechanism of Action • Acts on specific adenosine Rc located in several vascular beds and on theAV node • Activates adenylate cyclase and Depresses action potential • Slows sinus rates in PSVT pts.

ADENOSINE • Clinical Uses • Potent vasodilator during anesthesia • Affects arteriolar reistance vessels(afterload) without affecting venous capacitance(preload) • Very short half-life : <10 seconds • Continuous Infusion : 60-120μg/kg/min • Tx of PSVT &WPW synd.: IV bolus 6mg  can cause atrial fibrillation

ADENOSINE <Effects on organ systems> • Cardiovascular • ↓ systemic vascular resistance  ↓ ABP • ↑ cardiac index, HR, stroke vol. • ↑ myocardial blood flow • ↓ A-V conduction  inhibitreentrant arrhythmias • Pulmonary • ↓ pul. vascular resistance↑ intrapulmonary shunt  ↓ arterial oxygen saturation • Renal • Renal vasoconstriction  renal blood flow를 떨어뜨림

FENOLDOPAM • Mechanism of Action • Rapid vasodilation • Clinical Uses • ↓ systolic and diastolic blood pr. • side effect : headache, flushing, nausea, tachycardia, hypokalemia, HTN • Onset within 15 min • No rebound HTN

FENOLDOPAM <Effects on organ systems> • Cardiovascular • ↓ systolic and diastolic pr. • ↑ HR • Ophthalmic • ↑ Intraocular pr. • Caution in glaucoma pts and ↑intraocular pr. • Renal • ↑ Renal blood flow • ↓ ABP but GFR is maintained • Compared to sodium nitroprusside • ↑ urinary flow rate, ↑ urinary sodium extraction, ↑ creatinine clearance

FENOLDOPAM • Warnings • allergic reaction : high risk in pts with a Hx of asthma or sulfite sensitivity history

Hypotensive Agents