Antihypertensives & Diuretics Flashcards
Adrenergic antagonists bind but do not ____.
activate adrenoceptors, thus preventing adrenergic agonist activity
Nonselective alpha antagonist
Phentolamine
Mixed antagonists
Labetalol
Nonselective beta antagonist
Propranolol
Selective beta 1 antagonists
Esmolol
Class and Clinical Use of Phentolamine
Class: Nonselective alpha antagonists
Clinical Use
- Treatment of hypertension (especially related to excessive alpha antagonism: pheochromocytoma, clonidine withdrawal)
- Minimize extravasation r/t norepinephrine infiltration
Mechanism of Action of Phentolamine & Route
Competitive antagonist of α1- and α2-receptors
Route: IV, SQ
Dosing of Phentolamine
IV: intermittent boluses (1-5 mg), followed by an infusion at 1-10 mcg/kg/min
SQ: 5 – 10 mg diluted in 10 mL of NS locally infiltrated
Onset and DOA of Phentolamine
Onset: 1 minute
Duration: 10 minutes
Metabolism and Excretion of Phentolamine
Metabolism: Hepatically metabolized
Elimination: Renally excreted
Phentolamine can cause ___.
reflex tachycardia for 2 – 15 minutes (until endogenous NE presence in the synaptic cleft is depleted from alpha 2 blockade)
Caution using phentolamine in patients with __.
CAD, MI
Class, Clinical Use and Route of Labetalol
Class: Non-selective beta antagonist
Clinical Use: Used to treat tachycardia and hypertension
Route: IV
Mechanism of Action of Labetalol
Competitive antagonist of β1, β2 and α1 receptors
β-blockade: α-blockade ratio is 7:1
Dosing of Labetalol
Intermittent boluses: 5 – 20 mg
Onset and DOA of Labetalol
Onset: 5 minutes
DOA: 3 - 6 hours
Metabolism and Excretion of Labetalol
Metabolism: Hepatically metabolized
Elimination: Hepatically and renally excreted
Caution use of Labetalol in patients with ___.
bradycardia, hypotension, CHF, asthma and COPD
Labetalol may cause ___.
left ventricular failure, orthostatic hypotension, and bronchospasm
Class, Clinical Use and Route of Propranolol
Class: Nonselective beta antagonist
Clinical Use: Used for tachycardia and hypertension by decreasing CO, HR, renin release and AV node conduction
Route: IV
Mechanism of Action of Propranolol
Competitive antagonist of β1 and β2 receptors
Dosing of Propranolol
Intermittent boluses: 0.5 mg
Onset and DOA of Propranolol
Onset: 5 minutes
DOA: 4 hours
Metabolism and Excretion of Propranolol
Metabolism
- Hepatically metabolized
- Extensive first pass effect (90%)
- Highly protein bound (90%)
Elimination: Renally excreted
Side effects of propranolol include _____.
bronchospasm, acute congestive heart failure, and bradycardia
Class, Clinical Use and Route of Esmolol
Class: Selective β1 antagonist
Clinical Use
- Used to prevent or minimize tachycardia and hypertension in response to perioperative stimuli, such as intubation, surgical stimulation, and emergence
- Emerging evidence suggests intraoperative esmolol infusions may decrease post operative opioid requirements
Route: IV
Mechanism of Action of Esmolol
Competitive antagonist of β1 receptors (inhibit β2 receptors at higher doses)
Dosing of Esmolol
Bolus: 0.5 mg/kg or 10 mg
Infusion: 50 mcg/kg/min (if desired, titrate up q 5 minutes to a max dose of 200 mcg/kg/min)
Onset and DOA of Esmolol
Onset: 1 - 2 minutes
DOA: 5 - 10 minutes
Metabolism and Excretion of Esmolol
Metabolism: Rapid hydrolysis by plasma esterase metabolism in RBCs
Elimination: Renally excreted
Caution use of Esmolol in patients with ___
bradycardia, hypotension, CHF, and bronchoconstriction
Direct Vasodilators include which drugs?
Hydralazine
Nitroprusside
Nitroglycerin
Agents that lower blood pressure include: ___
volatile anesthetics, sympathetic antagonists and agonists, calcium channel blockers, β-blockers, and angiotensin-converting enzyme inhibitors
Hypertensive emergency would be?
(blood pressure >180/120 mm Hg) with signs of organ injury (eg, encephalopathy)
Prompt management of hypertension is critical following which types of procedures?
following cardiac and intracranial surgery and other procedures where excessive bleeding is a major concern.
Perioperative hypertension is often secondary to ____.
pain, anxiety, hypoxemia, hypercapnia, distended bladder, and failure to continue baseline antihypertensive medications.
Blood pressure is the product of ____.
cardiac output and systemic vascular resistance. Agents that lower blood pressure reduce myocardial contractility or produce vasodilatation of the arterial and venous capacitance vessels, or both.
Class and Clinical Use of Sodium Nitroprusside
Class: Direct peripheral arterial vasodilator; Non-selective, relaxation of arterial & venous smooth muscle
Clinical Use: Reliable antihypertensive
Dosing of Sodium Nitroprusside
Infusion: 0.3–10 mcg/kg/min
Mechanism of Action of Sodium Nitroprusside
As NTP is metabolized by iron, it releases nitric oxide and cyanide. NO activates guanylyl cyclase which synthesizes (cGMP), decreases intracellular calcium, which causes smooth muscle dilation
Onset and DOA of Sodium Nitroprusside
Onset: 1 minute
DOA: 3 – 5 minutes
Metabolism of Sodium Nitroprusside
An iron (Fe2+) electron of oxyhemoglobin binds to NTP then unstable NTP radical and methemoglobin then unstable NTP radical decomposes into 5 cyanide ions
Cyanide ions can:
- bind to methemoglobin to form cyanmethemoglobin
- undergo a reaction in the liver and kidney catalyzed by the enzyme rhodanese: thiosulfate + cyanide → thiocyanate
- bind to tissue cytochrome oxidase, which interferes with normal oxygen utilization and results in cyanide toxicity
Elimination of Sodium Nitroprusside
Thiocyanate is slowly cleared by the kidney
Caution use of Sodium Nitroprusside in patients with __
aortic stenosis, hypertrophic cardiomyopathy, increased ICP, hypotension, heart failure
Sodium Nitroprusside may cause ___
headache, tachycardia and bronchodilation
Patients who receive sodium nitroprusside may experience a build-up of ___
thiocyantate, which may lead to thyroid dysfunction, muscle weakness, nausea, hypoxia, and an acute toxic psychosis
Special considerations for Sodium Nitroprusside
- Dilation of coronary arterioles may result in an intracoronary steal
- Reductions in pulmonary artery pressure and the hypoxic pulmonary vasoconstriction mechanism may decrease lung perfusion
- Large doses of NTP may lead to methemoglobinemia and is treated with methylene blue to reduce methemoglobinemia to hemoglobin
- NTP must be protected from light because of photodegradation
- Patient’s on NTP infusions benefit from arterial line monitoring
How is cyanide toxicity caused? What are the characteristics?
Cyanide toxicity can occur with cumulative daily dose of NTP greater than 500 mcg/kg or if an infusion rate greater than 2 mcg/kg/min for more than a few hours.
Cyanide toxicity is characterized by metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content
Treatment of Cyanide Toxicity
Mechanical ventilation with 100% oxygen
•administering sodium thiosulfate or 3% sodium nitrite
To oxidize hemoglobin to methemoglobin
Class, Clinical Use and Route of Nitroglycerin
Class: Peripheral vasodilator, with venous dilation predominating over arterial dilation
Clinical Use: Nitroglycerin relieves myocardial ischemia, coronary vasospasm, hypertension, ventricular failure, used for controlled hypotension
Route: IV, SL, transdermal
Dosing of Nitroglycerin
IV Infusion: 5 – 100 mcg/min
SL: 0.4 mg
Why is NTG less effective with arterial vasodilation than NTP?
less release of nitric oxide
Onset and DOA of Nitroglycerin
Onset: 2 – 5 minutes
DOA: 5 – 10 minutes
Metabolism and Excretion of Nitroglycerin
Metabolism: Nitroglycerin undergoes rapid reductive hydrolysis in the liver and blood by glutathione-organic nitrate reductase. One metabolic product is nitrite, which can convert hemoglobin to methemoglobin
Elimination: Renally excreted
What is the ideal agent for MIs and why?
Nitroglycerin
- Decrease preload will reduce myocardial oxygen demand and increases endocardial perfusion
- Redistributes coronary blood flow to ischemic areas of the subendocardium
- Relieves coronary vasospasm
Special considerations for Nitroglycerin
- Headache, tachycardia can occur
- Tolerance may develop with prolonged use
- Caution in patients with aortic stenosis, hypertrophic cardiomyopathy, increased ICP, hypotension, heart failure
Class, Use and Route of Hydralazine
Class: Direct acting arterial vasodilator
Clinical Use: Hypertension
Route: IV
Mechanism of Action of Hydralazine
Activate guanylate cyclase to increase cGMP
Dosing for Hydralazine
Intermittent boluses: 2.5 – 20 mg
Onset and DOA of Hydralazine
Onset: 15 minutes
DOA: 2 – 4 hours
Metabolism and Excretion of Hydralazine
Metabolism: Hepatically metabolized
Elimination: Renally excreted
Hydralazine may result in ___
reflexive tachycardia
Caution use of Hydralazine in patients with ___
aortic stenosis, hypertrophic cardiomyopathy, increased ICP, hypotension, heart failure
Class, Clinical Use and Route of Nicardipine
Class: Calcium channel blocker
Clinical Use: treatment of angina, hypertension, arrhythmias, peripheral vascular disease, esophageal spasm, cerebral vasospasm, and controlled hypotension
Route: IV
Mechanism of Action of Nicardipine
By blocking the influx of Ca, it depress electrical impulses in the sinoatrial (SA) and atrioventricular (AV) nodes, resulting in negative chronotropic and inotropic effects and increasing coronary and systemic vasodilation
Dosing of Nicardipine
5 mg/hr, increased by 2.5 mg/h every 15 min up to 15 mg/hr
Onset and DOA of Nicardipine
Onset: 1 – 5 min
DOA: 3 – 6 hr
Metabolism and Excretion of Nicardipine
Metabolism: Hepatically metabolized
Elimination: Renally excreted
Nicardipine may cause ___. Caution in patients with ___.
May cause reflexive tachycardia
Caution in patients with an acute MI, heart failure, bradycardia, hypotension and on dantrolene
The kidneys are responsible for ___ and have a major influence on ___.
Responsible for regulating volume and composition of body fluids & have a major influence on blood pressure
The nephron is a ___. List the structures within it.
The nephron is the functional unit
Structures: glomerulus and the renal tubule.
The components of the renal tubule are Bowman’s capsule (which encapsulates the glomerulus), the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct.
Class, Clinical Use and Route of Furosemide
Class: Loop diuretics
Clinical Use: Treatment for hypertension, heart failure, peripheral and pulmonary edema, ICP, and renal failure
Route: IV, PO
Mechanisms of Action of Furosemide
Inhibits reabsorption of Na, Cl, and 2K in the thick ascending loop of Henle
Dosing of furosemide
Start with 5 mg and titrate up as needed
Onset and DOA of Furosemide
Onset: 5 minutes
DOA: 2 hours
Metabolism and Excretion of Furosemide
Metabolism: Hepatically metabolized
Elimination: Renally excreted
Considerations for Use of Furosemide
Hypotension
Electrolyte abnormalities (decrease K, Mg and Cl levels)
Ototoxic
Potentiates neuromuscular blockers
Class, Clinical Use and Route of Mannitol
Class: Osmotic diuretic
Clinical Use: Increased ICP, renal perfusion
Route: IV
Mechanism of Action of Mannitol
increase the osmolarity of plasma drawing in fluid from ICF & ECF & out of the brain; increased plasma mannitol is filtered, not reabsorbed which draws fluids & electrolytes (Na, Cl, bicarb) into urine & then increases UOP
Occurs in the proximal tube
Dose, Onset and DOA of Mannitol
Dosing (IV)
•0.25-1 g/kg over 30-60 mins
Onset: 15 minutes
DOA: 3 – 6 hours
Metabolism and Elimination of Mannitol
Metabolism: Not metabolized
Elimination: Renally excreted (100% unchanged)
Mannitol puts the patient at risk for ___
Risk for hypovolemia, electrolyte abnormalities, pulmonary edema
Class, Clinical Use and Route of Hydrochlorothiazide
Class: Thiazide diuretic
Clinical Use: Treatment for hypertension, often given with beta antagonists
Route: PO
Mechanism of Action of Hydrochlorothiazide
Inhibits reabsorption of Na & Cl in the ascending loop, proximal & distal tubules
Dosing of Hydrochlorothiazide
25 – 100 mg PO/day
Onset and DOA of Hydrochlorothiazide
Onset: 2 hours
DOA: 6 hours
Metabolism and Excretion of Hydrochlorothiazide
Metabolism: Not metabolized
Elimination: Renally excreted (100% unchanged)
Considerations for Hydrochlorothiazide
Risk for hypovolemia, electrolyte abnormalities, pulmonary edema
Potentiates neuromuscular blockade
