15 Hypotensive Agents Flashcards
“Vascular age” & pulse pressre
Pulse wave generated by ventricular contraction, propagated through arterial system - at branch points, wave reflected back towards heart - reflected wave augments diastole, improving diastolic pressure
“Older” vasculature - wave arrives sooner, conducted back by non-compliant vasculature during late systole, causes increase in cardiac workload and decrease diastolic pressure –> increased systolic pressure and decreased diastolic pressure (widened pulse pressure)
Diastolic dysfunction
Acute diastolic heart failure can develop in perioperative period 2/2 hypertensive crisis
Occurs due to inability of heart to relax effectively
Failure to actively sequester Ca2+ into sarcoplasmic reticulum (energy-dependent process) impedes relaxation
Can lead to elevated L ventricular end-diastolic pressure, myocardia ischemia, pulmonary edema
Nitrovasodilators - NO mechanism of action
Relaxes arteriolar & venous smooth muscle
Releases nitric oxide (NO) as metabolized
NO activates guanylyl cyclase - enzyme synthesizes cyclic guanosine 3’,5’-monophosphate (cGMP) - controls phosphorylation
NO - naturally occurring vasodilator released by endothelial cells
Ultrashort t1/2 (< 5s)
Inhaled - selective pulmonary vasodilator
Nitroprusside
Bolus: 1-2 mcg/kg - e.g. at time of laryngoscopy
IV infusion: 0.5-10 mcg/kg/min
Rapid onset (1-2 min)
Metabolism: enters RBC, receives e- from Fe2+, results in unstable nitroprusside radial and methemoglobin (Hgb-Fe3+)
- Nitroprusside radical decomposes to 5 CN- & nitroso (N=O)
- Three rxn of CN-
1) CN- + methhemoglobin –> cyanmethemoglobin
2) CN- + thiosulfate –> thiocyanate (in liver and kidney, catalyzed by enzyme rhodanase)
3) CN- + cytochrome oxidase –> cyanide toxicity - Acute CN toxicity characterized by metabolic acidosis, cardiac arrhythmia, increased venous O2 content (b/c inability to utilize O2) & tachyphylaxis to nitroprusside
- Most likely at cumulative dose of 500 mcg/kg infused fater than 2 mcg/kg/min
- Treatment: Sodium thiosulfate or 3% sodium nitrate
Rx effect:
- Decrease preload & afterload
- Cardiac output usually unchanged b/c tachycardia and increased myocardic contracility - may be decreased in Pts with CHF, mitral/aortic regurg
- Intracoronary steal - general coronary dilation steals blood flow from ischemic areas that are already maximally dilated
- Dilated cerbral vessels & abolishes cerebral autoregulation
- Increases ICP
- Dilate pulmonary vasculature - may decrease perfusion of some normally ventilate alveoli, increase physiologic dead space - prevents normal vasoconstrictive response to hypoxia
- Decreased arterial BP releases renin & catecholamines
Nitroglycerin
Releases vascular smooth muscle
Relieves myocardial ischemia, hypertension, and ventricular failure
IV infusion: 0.5-10 mcg/kg/min
Glass containers & special IV tubing b/c adsorption to polyvinylchoride
Tolerance due to depletion of reactants necessary for NO formulation, compensatory vasoconstriction, volume expansion
Rapid reductive hydrolysis in liver and blood by gluathione-organic-nitrate reductase
Metabolic product is nitrite - can convert Hb to Hb-Fe3+
Reduces myocardia O2 demand and increases myocardia O2 supply by:
a) Pooling of blod in large capacitance vessels reduces venous return and preload - decrease in ventricular end-diastolic pressure reduces myocardial O2 demand and increases endocardial perfusion
b) afterload reduction from arteriolar dilation decrease end-systolic pressure and oxygen demand
c) Redistributes coronary blood flow to ischemic areas - no coronary steal
d) Relieves coronary artery spasm
Cerebral blood increased and abolishes autoregulation - headache side effect from cerebral vessel dilation
Pulmonary vessel dilation - releases bronchial smooth muscle
Effective but transient uterine relaxant
Hydralazine
Relaxes arteriolar smooth muscle
Dilation of precapillary resistance vessels via increase cGMP
IV bolus dose: 5-20 mg - onset within 15 min - effects last 2-4 hr
Acetylation and hydroxylation at liver
Reflex tachycardia, increase myocardial contractility, and CO - effects minimized with concurrent B-blocker
Cerebral vasodilator and inhibits autoregulation
Fenodopam
Activates D1 receptor & moderate affinity for a2 receptors
Reduces systolic and diastolic BP
Side effects: HA, flushing, nausea, tachycardia, hypokalemia
Studies conflicted if actually provide renal “protection”
Conjugation without P-450 enzymes - but inactive metabolites - no dose changes for renal/hepatic failure
Calcium Antagonists
Dihydropyridine (nicardipine, clevidipine) are arterial selective vasodilators
Unlike non-DHP (verapamil, diltiazem), have minimal effect on cardiac conduction and ventricular contractility
Ca2+ channel blockers bind to L-type Ca channel, impair Ca entry into vascular smooth muscle
L-type more prevalent on arterial than venous
