Hypotensive Agents

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Hypotensive Agents

• R1 ???

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Hypotensive Agents

• volatile anesthetics
• sympathetic antagonists and agonists
• calcium channel blockers
• and ACE-inhibitors
• Nitrates, Adenosine, Fenoldopam
• -gt dilating pph. vessels

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SODIUM NITROPRUSSIDE

• Mechanism of Action
• -relax both arteriolar and venous smooth
• muscle
• -?? nitrates (eg. hydalazine and
• nitroglycerine)? ??? ??
• -gt nitric oxide? release
• -gt activate guanylyl cyclase
• -gt cGMP ? ??
• -gt smooth m. contraction

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SODIUM NITROPRUSSIDE

• Nitric oxide
• endothelium-derived relaxing factor
• Inhaled nitric oxide
• -selective pulmonary vasodilator
• reversible pulmonary HTN? ??? ??
• -ARDS ?? ?? one-lung ventilation? ???
  oxygenation ? ??
• -antiinflammatory effect

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SODIUM NITROPRUSSIDE

• Clinical Uses
• -potent reliable antihypertensive
• -?? 100µg/ml? ???? 0.5-10 µg/kg/min
• ? continuous IV infusion
• -extremely rapid onset 1-2 min
• -bolus (1-2 µg/kg) laryngoscopy?? BP
• ??? ?????? ??, transient HoTN
• ?? ??
• -??? BP ??(intraarterial monitoring ??)

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SODIUM NITROPRUSSIDE

• Metabolism
• -Sodium nitroprusside(SNP)? RBC?? ???
  oxyhemoglobin?? Fe 2? ?? unstable nitroprusside
  radical(SNP?)? methemoglobin(Hgb Fe 3)?? ??
• -SNP?? 5?? cyanide???? ??
• (1)cyanmethemoglobin
• (2)thiocyanate
• (3)cyanide toxicity

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SODIUM NITROPRUSSIDE

• Acute cyanide toxicity
• -metabolic acidosis, cardiac arrhythmia,
• venous oxygen contents ??, tachyphlaxis
• -?? ??? 0.5mg/kg/h? ?? ??
• -??
• mechanical ventilation with 100 oxygen,
• sodium thiosulfate(150mg/kg over 15 min),
• 3 sodium nitrate(5mg/kg over 5min)

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SODIUM NITROPRUSSIDE

• Effects on organ systems
• Cardiovascular
• -venous and arterial beds? dilatation
• -gt preload? afterload ??
• -pph. vascular resistance ??
• -gt ABP? ??
• -?? preload ????? ??
• -gt myocardia work??, ischemia ?????
• ??

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SODIUM NITROPRUSSIDE

• Cerebral
• -cerebral vessels ?? autoregulation ??
• -cerebral blood flow ?? ?? ??
• -intracranial compliance? ???? ??
• (eg. brain tumor) ??? ??? intra-cranial
• pr.? ?? ??

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SODIUM NITROPRUSSIDE

• Respiratory
• pul. vasculature dilatation
• -gt pul. artery pr.?? -gt perfusion ?? -gt
• physiological dead space ??
• -gt hypoxia? ?? ?? pul. vasoconstrictive
• effect ??
• -gt pul. ventilation? perfusion? mismatch,
• arterial oxygenation??

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SODIUM NITROPRUSSIDE

• Renal
• -ABP? ??-gt rennin catecholamine ??,
• ? ?? ? pressure rebound? ??? ? ??
• Drug Interactions
• -NM blocking agent? ?? ????? ???
• -muscle blood flow? ??? ??
• -????? neuromuscular blockade?
• onset? ??? ????? ?????

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NITROGLYCERIN

• Mechanism of action
• -relax vascular smooth m.
• -venous dilation? a. ?? ??
• Clinical uses
• -?? 100µg/ml? ???? 0.5-10 µg/kg/min
• ? continuous IV infusion
• -sublingual (peak effect 4mL)
• -transdermal

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NITROGLYCERIN

• Metabolism
• reductive hydrolysis in liver and blood
• by glutathione-organic nitrates reductase
• Effect on organ systems
• Cardiovascular
• -venous return? preload??
• -arteriolar dilation?? ?? afterload ??
• -end-systolic pr.? ?????? ??
• -coronary blood flow? subendocardium?
• ischemic areas?? ???

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NITROGLYCERIN

• -coronary artery spasm? relieve
• -platelet aggregation ??? coronary vessel
• ? potency? ??
• Cerebral
• -sodium nitroprusside? ??
• -side effect? headache (cerebral vessel?
• dilation)
• Respiratory
• -bronchial smooth muscle? relax

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HYDRALAZINE

• Mechanism of Action
• -arteriolar smooth muscle? relax
• Clinical Uses
• -?? intraoperative HTN? control
• IV 5-20mg (15? ?? ??, 2-4?? ??)
• -continuous infusion? slow onset? prolong
• duration??? ? ???? ??

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HYDRALAZINE

• Effects on organ systems
• Cardiovascular
• -pph. vascular resistance? ?? -gt arterial
• blood pr. ??
• -gt HR, myocardial contractility, CO ??
• Cerebral
• -potent cerebral vasodilator cerebral blood
• flow autoregulation ??
• Renal
• -renal blood flow? ????? ??

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ADENOSINE

• Mechanism of Action
• -several vascular beds? AV node? ????
• specific adenosine receptors? ??
• -adenylate cyclase? activation ? action
• potential? depression
• -paroxysmal supraventricular tachycardia pt.
• ? ?? AV block ? sinus rate? slowing

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ADENOSINE

• Clinical Uses
• -potent vasodilator during anesthesia
• -arteriolar reistance vessel(afterload)? ???
• -preload? venous capacitance ?? ?? ??
• ? ??? ???
• -very short half-life ( lt10s )
• -continuous infusion(60-120µg/kg/min)
• -PSVT? WPW synd ? ?? IV bolus 6mg
• -gtatrial fibrillation? ??? ? ??

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ADENOSINE

• Effects on Organ Systems
• Cardiovascular
• -lowering systemic vascular resistance?
• ?? ABP??
• -cardiac index, HR, stroke vol.??
• -myocardial blood flow??
• -A-V conduction? ????? reentrant
• arrhythmias? ??

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ADENOSINE

• Pulmonary
• -pul. vascular resistance? ??
• ?? intrapul. shunt ??
• -gt arterial oxygen saturation ??
• Renal
• -Renal vasoconstriction-gt renal blood flow?
• ????

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FENOLDOPAM

• Mechanism of Action
• -rapid vasodilation
• Clinical Uses
• -systolic and diastolic blood pr. ??
• -side effect headache, flushing, nausea,
• tachycardia, hypokalemia,
  HTN
• -15? ?? ??, ????? rebound HTN??
• ??? reverse

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FENOLDOPAM

• Effects on Organ Systems
• Cardiovascular
• -systolic and diastolic pr.??
• -HR??
• Ophthalmic
• -Intraocular pr.??
• -glaucoma? intraocular pr.?? ? ??

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FENOLDOPAM

• Renal
• -Renal blood flow??
• -ABP? ???? ???? GFR? ??
• -Sodium nitroprusside? ????,
• uinary flow rate, urinary sodium extraction,
• creatinine clearance ??

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FENOLDOPAM

• Warnings
• -allergic reaction asthma?? sulfite
• sensitivity history?? ?? high risk