Antihypertensive Vasodilators Flashcards
Review nitric oxide (NO) pathway.
What is a side effect of inhaled NO?
- NO Toxicity
- Inhaled NO increases methemoglobin levels (usually modest)
What can occur with d/c of inhaled NO therapy?
Rebound hypoxemia or pulmonary HTN may occur with sudden discontinuing inhaled therapy (must wean inhaled NO slowly)
What can happen when given NO in patients with LV dysfunction/failure?
Can precipitate acute left heart failure and pulmonary edema when given in presence of LV dysfunction/failure
What is NO toxicity?
- NO oxidized to NO2 especially with high oxygen concentrations
- NO2 is a pulmonary toxin
Why is it important to continuously monitor inspired NO and NO2 concentrations?
NO Toxicity
Important to continuously monitor inspired NO and NO2 concentrations during inhaled therapy (inhaled NO delivery system should have this)
What are examples of nitrodilators?
- Sodium Nitroprusside
- Nitroglycerin
What is the target of Sodium Nitroprusside (SNP)?
Direct-acting nonselective peripheral vasodilator
What is the effect of Sodium Nitroprusside (SNP)?
- venous and arterial smooth muscle
- lacks effect on nonvascular smooth muscle or cardiac muscle
What is the onset of Sodium Nitroprusside (SNP)?
Immediate onset & administered by continuous IV infusion
What is the MOA of Sodium Nitroprusside (SNP)?
IV SNP infusion interacts w/oxyhemoglobin and dissociates immediately to form methemoglobin while releasing cyanide & NO
What does released NO from Sodium Nitroprusside (SNP) cause?
- released NO activates GC in vascular smooth muscle
- increased cGMP
- inhibits calcium entry into vascular smooth muscle cells
- vasodilation
What is the metabolism of Sodium Nitroprusside (SNP)?
SNP interacts with the Fe in oxyhemoglobin to yield methemoglobin and an unstable SNP radical
What does an unstable SNP radical from Sodium Nitroprusside (SNP) metabolism breakdown into?
which breaks down into 5 cyanide ions; 1 ion forms cyanomethemoglobin (non-toxic)
What happens to the remaining CN molecules from Sodium Nitroprusside (SNP) metabolism?
- The remaining CN molecules are converted to thiocyanate by way of rhodanese enzyme
What can be used to treat cyanide toxicity?
Rhodanese also uses exogenous thiosulfate as a sulfur donor to treat cyanide toxicity
Sodium Nitroprusside (SNP) metabolism: When is Thiocyanate eliminated from the body?
Thiocyanate is eliminated in the urine (3-7 days)
What is the dose of Sodium Nitroprusside (SNP)?
O.3 mcg/kg/min IV infusion titrated
What is the max dose of Sodium Nitroprusside (SNP)?
a max of 10 mcg/kg/min (not to infuse max rate longer than 10 min)
What needs to be present Sodium Nitroprusside (SNP) infusion?
Need arterial line
What occurs with Sodium Nitroprusside (SNP) doses over 2 mcg/kg/min?
place patient at risk for cyanide toxicity
What HR change can occur with Sodium Nitroprusside (SNP)?
Baroreceptor mediated tachycardia with increased myocardial contractility can oppose vasodilatory effect
What effect does Sodium Nitroprusside (SNP) have on venous return and CO?
Decreased venous return but increase in CO may result due to reflex sympathetic activity and afterload reduction
What effects occur with Sodium Nitroprusside (SNP) administration in LV failure?
SNP decreases SVR, pulmonary vascular resistance, & right atrial pressure
Why must caution with Sodium Nitroprusside (SNP) be used in the presence of myocardial ischemia?
- Implicated in “coronary steal” phenomenon
- SNP can also decrease diastolic BP
- decrease coronary perfusion pressure & decrease coronary blood flow
What effect does Sodium Nitroprusside (SNP) have on renal function?
- May result in decreased renal function (from low BP)
- Increase renin (blood pressure overshoot when D/C’d)
What effect does Sodium Nitroprusside (SNP) have on liver?
Does not effect hepatic blood flow changes or hepatic injury
What impact can occur with Sodium Nitroprusside (SNP) and cerebral system?
- Increases cerebral blood flow/cerebral blood volume
- Can raise ICP with those with decreased intracranial compliance
What are increases in ICP from Sodium Nitroprusside (SNP) offset with?
Offset with hypocarbia and hyperoxia
When can maximum increases in ICP from Sodium Nitroprusside (SNP) be seen?
Maximal increases in ICP when SBP < 30%
When should Sodium Nitroprusside (SNP) be used cautiously?
Caution with carotid stenosis, patients with inadequate cerebral blood flow
What respiratory and ventilatory effects can be seen with Sodium Nitroprusside (SNP)?
Decreases in PaO2 by attenuating the homeostatic process of hypoxic pulmonary vasoconstriction (HPV) and resulting in shunting (VQ mismatch)
What can bee added to reverse the respiratory effects from Sodium Nitroprusside (SNP)?
Adding PEEP may reverse vasodilator-induced decrease in PaO2
What coagulation effects can be seen with Sodium Nitroprusside (SNP)?
Increase intracellular cGMP inhibits platelet aggregation and may increase bleeding bleeding time with infusion rates > 3 mcg/kg/min (reversible)
When does cyanide toxicity occur?
Cyanide toxicity may occur when the IV Sodium Nitroprusside (SNP) infusion rate is >2mcg/kg/min
How does cyanide toxicity occur?
- Prolonged or high infusion rates can cause cyanide radical accumulation which bind to tissue cytochrome oxidase and prevents oxidative phosphorylation (part of the cellular respiration process)
- Occurs with Sodium Nitroprusside (SNP)
What can cyanide toxicity lead to (3)?
Leads to tissue anoxia, anaerobic metabolism and lactic acidosis
When is cyanide toxicity is seen?
Suspect when tachyphylaxis is seen and with rates > 2 mcg/kg/min along with lactic acidosis and increase in mixed venous O2 (tissues aren’t able to use O2) d/t paralysis of cytochrome oxidase activity
What acid base disturbance can occur with cyanide toxicity?
Metabolic acidosis d/t anaerobic metabolism in the tissues
What are side effects of awake patients with cyanide toxicity?
Awake patients: CNS dysfunction (mental status changes, seizures)
What is the treatment of cyanide toxicity?
D/C Sodium Nitroprusside (SNP) and administer 100% O2
What medications should be adminsitered for cyanide toxicity?
- Sodium bicarbonate
- Hydroxocobalamin (vitamin B12a)
- For severe toxicity: Sodium nitrate
Cyanide toxicity: Why is sodium bicarbonate administered?
Sodium bicarbonate administered to correct metabolic acidosis
Cyanide toxicity: What is the components of Sodium thiosulfate administration?
- 150 mg/kg IV over 15 min: first-line tx
- acts as a sulfur donor to convert cyanide to thiocyanate which is non-toxic
What is the first line treatment for cyanide toxicity?
- Sodium thiosulfate 150 mg/kg IV over 15 min
- Hydroxocobalamin (vitamin B12a)
Cyanide toxicity: What is the components of Hydroxocobalamin (vitamin B12a) administration?
- 5gm initial dose; also first-line tx
- 2nd dose depends on clinical response
- binds cyanide to form cyanocobalamin (vitamin B12)
- expensive drug
- may produce reddish discoloration of skin & mucous membranes, and interfere with co-oximetry blood gas analysis
What is the treatment of severe cyanide toxicity treatment?
- Sodium nitrate 5mg/kg slow IV
- converts Hb to methemoglobin which cyanide reacts with to form cyanomethemoglobin (non-toxic)
What is cyanide toxicity associated with?
Sodium Nitroprusside (SNP)
What is the clearance of Thiocyanate?
Slowly cleared by the kidneys (elimination 1/2 time 3-7 days)
What is the components of Thiocyanate toxicity?
Rare, less toxic than free CN
When is Thiocyanate toxicity seen?
- Seen with prolonged infusions 2-5mcg/kg/min
- 7-14 days with normal renal function
- 3-6 with reduced function
What is the symptoms of thiocyanate toxicity?
fatigue, tinnitus, N/V
What is the neurotoxicity symptoms of thiocyanate toxicity?
hyperreflexia, confusion, psychosis, miosis, seizures, coma
Where does Nitroglycerin (NTG) act?
Acts on venous capacitance vessels and large coronary arteries
What does Nitroglycerin (NTG) produce?
- produce peripheral pooling of blood
- decreases cardiac ventricular wall tension
- larger doses relax arterial vascular smooth muscle
What is the clinical indications for Nitroglycerin (NTG)?
SL or IV in tx of myocardial ischemia or vasospasm, volume overload/HF, controlled hypotension
How does Nitroglycerin (NTG) help with HF?
Decreases preload
What is the MOA Nitroglycerin (NTG)?
Administration generates NO which stimulates production of cGMP to cause peripheral vasodilation
What does Nitroglycerin (NTG) require?
NTG requires a glutathione-dependent pathway involving glutathione and glutathione S-transferase to biotransform nitrate group in NTG into NO
When is Nitroglycerin (NTG) not recommended?
severe aortic stenosis or hypertrophic obstructive cardiomyopathy
What is characteristics of Nitroglycerin (NTG) SL route?
- limited hepatic first-pass
- peak plasma concentration achieved in 4 min
What is the elimination half time of Nitroglycerin (NTG)?
half-time 1.5 min
What is the dose of Nitroglycerin (NTG) for controlling BP?
10-200 mcg/min (approximately 0.1 to 3 mcg/kg per minute)
What is a side effect of Nitroglycerin (NTG)?
- Risk of methemoglobinemia at high doses
What is the nitrate metabolite of NTG capable of?
oxidizing ferrous ion in hemoglobin to the ferric state with production of methemoglobinemia
What is the tolerance to Nitroglycerin (NTG)?
- dose-dependent & duration dependent
- usually seen within 24 hrs of sustained treatment
What is recommendation to reversing Nitroglycerin (NTG) tolerance?
a drug-free interval of 12-14 hours recommended to reverse tolerance (NTG or other nitrates)
What is hydralazine?
Direct systemic arterial vasodilator
What is the MOA of Hydralazine?
Hyperpolarizes smooth muscles cells, activates guanylate cyclase to produce vasorelaxation
What is the side effect of Hydralazine?
Can result in reflex tachycardia
What population should hydralazine be used carefully?
careful with CAD/ischemia, lupus syndrome w/ long term use
What is the anesthesia use of Hydralazine?
Tx of elevated BP with low HR
What is the dose of Hydralazine?
Administered as bolus doses (eg, 2.5 mg), which may be repeated every 5 minutes up to 20 mg
What are disadvantage of Hydralazine?
include relatively slow onset compared with other IV antihypertensive agents, with a less predictable antihypertensive response
What is the onset of Hydralazine?
5–20 min
What is the peak of Hydralazine?
15–30 min
What is the duration of Hydralazine?
2–6 hr
What is the MOA of Fenoldopam?
Dopamine type-1 agonist resulting in systemic arterial dilation by increasing cAMP
What is the effects of Fenoldopam?
- Increases renal and splanchnic blood flow & increases UOP
When is Fenoldopam indicated?
It is indicated for patients undergoing cardiac surgery and aortic aneurysm repair because of its antihypertensive and renal-sparing properties
What is the side effects of Fenoldopam?
Reflex tachycardia and increased IOP
What is the dose of Fenoldopam?
0.05–0.3 mcg/kg/min
What is the first line oral agent for Diuretics?
First-line oral agents used for essential HTN
What diuretics are the first line choice?
Thiazide drugs first-line
When are loop diuretics are used for HTN?
loop diuretics reserved for patients w/renal insufficiency or HF
What are examples of loop diuretics?
furosemide, bumetanide
What is the side effect of loop diuretics?
Both result in K+ loss – monitor serum K+ & magnesium, may require supplementation
Diuretics: ___________ with IV furosemide
Venodilating effects
What are the properities of Diuretics?
Aldosterone antagonists “K+ sparing” used with ACE inhibitors
What is an example of Aldosterone antagonists diuretics?
Example: Spironolactone
What is the MOA of Aldosterone antagonists?
Blocks the effects of aldosterone which block the reabsorption of Na+ & excretion of K+ which leads to decrease in BP and fluid overload
