Antihypertensives Flashcards
Agents that lower BP & BP formula
volatile anesthetics, sympathetic antagonists, Ca channel blockers, B blockers & ACE inhibitors
BP= CO x SVR
Nitric Oxide Mechanism of Antihypertensives
the release of NO activates guanylyl cyclase, the enzyme need to synthesize, cGMP. cGMP controls the phosphorylation of several proteins including some involved in the control of free intracellular calcium (decreases) and smooth muscle contraction.
- NO is a naturally occurring potent vasodilator released by endothelial ells
- Ultra short half life < 5s
Perioperative HTN causes
Pain/anxiety, hypoxemia/hypercapnia, distended bladder or failure to continue baseline antihypertensive medications
Sodium Nitroprusside
Relaxes BOTH arterial & venous smooth muscle via NO pathway.
Inf: 0.3-10mcg/kg/min
O:1 min
DOA: 3 min
must be protected from light - photodegredation
CV: decreased after load, preload, MAP
-intracoronary steal
- May cause headache, reflex tachycardia and bronchodilation
- caution in its that cannot tolerate increased O2 demand and in ICP its
Cerebral: dilates cerebral vessels and abolished auto regulation = increased ICP
Pulm: vasculature dilates = decreased pressure = decreased perfusion of some alveoli = increased physiologic dead space
- dilation may prevent normal vasoconstrictive response to hypoxia = V/Q mismatch
Sodium Nitroprusside Metabolism
- enters RBC’s receives free e- from the iron of oxyhemoglobin = unstable nitroprusside radical & methemoglobin
- Radical decomposes to 5 cyanide ions & active N=O group, the cyanide ions have 3 reaction options
1. Bind to methemoglobin = cyanmethemoglobin
- Reaction in kidney & liver catalyzed by enzyme rhondanase into thiocyanate
- Cleared slowly by kidneys, can build up and cause thyroid dysfunction, muscle weakness, nausea, hypoxia, acute toxic psychosis - Bind to tissue cytochrome oxidase which interferes with normal O2 utilization leading to cyanide toxicity.
S/S: Metabolic acidosis, arrhythmia, increased venous O2 content (as an inability to use it)
- Early sign: resistance to increased doses sodium nitroprusside (tachyphylaxis)
-Risk Factors: Cumulative daily dose >500mcg/kg or infusion >2mcg/kg/min for >2 hrs
Treatment:
• Mechanical ventilation
• Sodium thiosulfate 150 mg/kg over 15 min
• Or 3% sodium nitrate 5mg/kg over 5 min
• Oxidizes hgb to methemoglobin, want a conc of 10-20%
• Large doses can lead to methemeglobinemia – tx methylene blue
Nitroglycerin
Relaxes vascular smooth muscle. Peripheral vasodilation. Venous > arterial. NO pathway isn’t activated in arterial space. Relieves myocardial ischemia, HTN & ventricular failure.
Inf: 0.5-5 mcg/kg/min
5-100 mcg/min
SL: 0.4mg
O: 2 min
DOA: 5 min
M: rapid reductive hydrolysis in liver & blood by glutathione-organic nitrate reductase
nitrite metabolite = hgb to methemoglobin
E: renal
Nitroglycerin Organ Effects
Reduction in myocardial O2 demand & increased supply:
- Pooling of blood in large capacitance vessels = decreased circulating BV & preload
-reduced preload
o Redistributes coronary blood flow to ischemic areas of subendocardium
o May relieve coronary artery spasm
CV: minimal HR effect
Cerebral: vessel dilation = increased ICP = HA
Pulm: dilates vasculature and bronchodilates
Uterine Relaxant
Hydralazine
Relaxes arteriolar smooth muscle. Activates guanylate cyclase to increase cGMP = decreased intracellular Ca++ = vasodilation.
IV: 2.5-20 mg O: 15 min DOA: 2-4 hrs M: hepatic E: renal
Decreases PVR and arterial BP. Reflex tachycardia, increased contractility and CO can occur. Increases cerebral BF and ICP.
Caution with heart disease who cannot tolerate increased myocardial O2 demands. Admin with concurrent beta blocker can mitigate risk.
Fendolopam
Rapid vasodilation via activation of D1 dopamine receptors. Decreases systolic & diastolic BP. HR increases.
Inf: 0.01-1.6mcg/kg/min
O: 15 min
M: hepatic
Increases IOP and renal blood flow increasing UOP.
Side Effects: HA, flushing, nausea, tachycardia, hypokalemia, hypotension
Clevidipine
dihydropyridine Ca++ channel blocker
Arterial selective vasodilator. Bind to L type calcium channels & impair Ca2+ entry into vasc smooth muscle.
IV: 1-2 mg/hr up to 16 mg/hr
M: blood esterase’s.
Lipid emulsion
Minimal effect on cardiac conduction & ventricular contractility
Pentolamine
Nonselective competitive antagonism of alpha 1 & 2 receptors.
IV: 1-5 mg bolus
Inf: 1-10 mcg/kg/min
SubQ: 5*-10 mg diluted in 10 ml of NS
O: 1 min
DOA: 10 min
M: hepatic
E: renal
Can cause reflex tachycardia
Labetalol
Non-selective beta antagonist and some alpha. Ratio 7:1 B:A
IV: 15-20 mg
O: 5 min
DOA: 3 hrs
E: hepatic & renal
Caution in asthma & COPD
May cause L ventricular failure, orthostatic hypotension, bronchospasm
Propranolol
Non-selective beta antagonist. Competitive antagonism of B1 & B2.
IV: 0.5mg bolus O: 5 min DOA: 4 hrs M: hepatic E: renal
- extensive first pass effect, 90% highly protein bound**
- bronchospasm risk, bradycardia
Esmolol
Selective B1 antagonist.
IV: 0.5mg/kg or 10mg Inf: 50 mcg/kg/min O: 1 min DOA: 5 min M: rapid hydrolysis via plasma esterases E: renal
- prevent or minimize tachycardia & HTN in response to periop stimulation
- emerging evidence suggest intraop infusion may decrease post-op opioid requirements.
Nicardipine
dihydropyridine Ca2+ channel blocker. Binds L-type decrease calcium in cardiac and smooth muscle. Depresses electrical impulses in the SA & AV node. Negative chronotropic & inotropic effects. coronary & systemic vasodilation.
IV: 5 mg/hr, increase by 2.5 mg/hr q 15 min up to 15 mg/hr O: 1 min DOA: 3 hrs M: hepatic E: renal
tx of angina, htn, arrhythmias, peripheral vascular disease, esophageal spasm, cerebral vasospasm, and controlled hypotension
- may cause reflex tachycardia
- caution in pts getting dantrolene.
