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NU 600

Exam 6 - Antihypertensives

What is the definition of HTN? Persistent BP of 140/90 or greater
The diagnosis of primary HTN is seen in _____% of all cases. 95
In what states is the renin-angiotensin-aldosterone (RAA) system activated? Low renal perfusion
With activation of the RAA, sodium delivery to the ________ is decreased. distal nephrons
Activation of the RAA results in decreased (sympathetic/parasympathetic) stimulation. sympathetic
Renin is released from what part of the kidneys? Juxtoglomerular network (synthesize, store, and secret renin)
What is the most common disease in the U.S.? HTN
Give 4 examples of diseases secondary hypertension? Renovascular dz/renal artery stenosis, hyper-aldosteronism, pheochromocytoma (correctable w/surgery), coarctation of the aorta (correctable w/surgery)
What is the function of a sympatholytic? Depress/inhibit SNS function (i.e. anxiolytic)
What are 5 subtypes of sympatholytics? 1)Centrally acting 2)adrenergic neuron blocker 3)alpha adrenergic receptor antagonists 4)beta adrenergic receptor antagonists 5)mixed adrenergic receptor antagonists
What sympatholytic subcategory does labetalol fall under? What is its beta:alpha ratio when taken IV vs. PO? Mixed adrenergic receptor antagonist; 7:1 beta:alpha IV // 3:1 beta:alpha PO
Impulse transmission from the spinal cord to the SNS occurs through what two types of neurons? pre- and post-ganglionic neurons
Which neurons originate at the thoracolumbar region of the spinal cord? Pre-ganglionic
Pre-ganglionic nerve fibers are (short/long) fibers that synapse with the ____________. short; paravertebral ganglion
What are two characteristics of the paravertebral ganglion? fast conducting; ACH is the neurotransmitter
What is the neurotransmitter of the post-ganglionic fibers and what do they communicate with? norepi; communicate with the target organ
Post-ganglionic fibers are (short/long). long
There is a release of the neurotransmitter ________ at the pre-ganglionic site. ACh
What does Ach serve to activate in the sympathetic outflow tract? Activates nicotinic ACh receptor on the post-ganglionic neuron
After receiving stimulation from ACh, what is the response of the post-ganglionic neuron? Release of norepi
What is the function of norepi after being released from post-ganglionic stimulation? Norepi activates the adrenergic receptor on the peripheral target tissue.
What is the function of centrally acting antihypertensive agents? Prevent the brain from sending signals to the nervous system.
What are 5 different centrally acting alpha 2 agonists? Dexmedetomidine, methyldopa, clonidine, guanfacine, gauanabenz
In what application is methyldopa still being used today? Gestational hypertension
What are some side effects of methyldopa that have decreased its popularity as a centrally acting sympatholytic? N/V, diarrhea, dizziness, decreased mental acuity, dry mouth
Which medication is considered to be the prototypical centrally acting anti-adrenergic agent? Clonidine
What is the alpha2:alpha1 ratio of effect for clonidine? alpha2:alpha1 = 220:1
Besides hypertension, what are other uses for clonidine? Anxiety, addiction, chronic pain, spasticity, regional blocks
By how much % does clonidine decrease MAC? 35%
What is the effect ratio of alpha2:alpha1 for dexmedetomidine? 1620:1 (alpha2:alpha1)
Which medication has a higher affinity for alpha2 receptors: clonidine or dexmedetomidine? dex
What is the biphasic response that occurs with dex? Spike in BP caused by initial release of norepi from the nerve terminal, followed by decreased BP d/t overall sympatholytic activity (alpha2 agonism)
Phenoxybenzamine is a (selective/nonselective) alpha adrenergic receptor antagonist. nonselective (blocks a1 and a2)
Phenoxybenzamine forms a/an (reversible/irreversible) bond with alpha receptors. irreversible
What is the T1/2 of phenoxybenzamine? 24h
What are three uses of phenoxybenzamine? HTN in pheochromocytoma, relieve ischemia 2/t PVD, BPH
Phenoxybenzamine blunts the response to which vasopressor? Phenylephrine
What is "epi reversal" and what causes it? Condition associated w/phenoxybenzamine where epinephrine worsens hypotension and tachycardia d/t beta stimulation of epi with alpha blockade by phenoxybenzamine
Why is norepi preferred over epi after phenoxybenzamine administration? Norepi produces a primarily alpha response
Pretreatment/Stabilization of pheochromocytoma begins _____ weeks prior to surgery. 1-3
Which medication is used prior to surgery to diminish the response to endogenous catecholamines? Phenoxybenzamine
Phenoxybenzamine (does/does not) cross the BBB. does
What are SE with phenoxybenzamine? Postural hypotension, arrhythmias, HA, N/V
Which is considered to be the prototypical alpha1 blocker? phenoxybenzamine
What disease is phentolamine useful in treating? pheochromocytoma
Hypotension from phentolamine activates what compensatory systems? Activates plasma renin activity and baroreceptors
Which medication is used to treat catecholamine infiltrations? What is the onset, dose, and T1/2? phentolamine; rapid onset, 5-10mg, 20min (T1/2)
Phentolamine is a (selective/nonselective) alpha antagonist. non-selective
What are 3 uses for phentolamine? Infiltration of vasoconstricting agents, management of HTN from clonidine withdrawal, erectile dysfunction
Which alpha blocker produces selective and reversible inhibition of alpha1? Prazosin
Prazosin produces dilatation of (arteries/veins/arteries and veins). arteries and veins
What influence does prazosin have on sodium and water? Encourages sodium and H20 retention
Prazosin is generally used in conjunction with what two types of medications? Beta blockers and diuretics
What are the side effects of prazosin? Hypotension, syncope, edema
Why is prazosin usually combined with a beta blocker? Prazosin can cause a reflex tachycardia d/t compensatory response
Which antihypertensive decreases the spontaneous rate of depolarization? beta blockers
What effects do beta blockers have in the AV node? Slow conduction in the AV node and increases refractory period of the AV node
Blockade of the (beta1/beta2) receptor may result in life threatening bronchospasm. beta2
What caution should be taken with beta1 specific antagonists? Large doses may also antagonize b2 receptors
What undesirable side effects occur with nonselective beta blockers? Blunt glycogenolyssis and may mask clinical signs of hypoglycemia (nervousness, tremor, tachycardia)
Identify 4 contraindications to beta blockers. Pre-existing severe bradycardia, greater than 1st degree heart block, cardiogenic shock, heart failure (most BB)
(Beta1/Beta2) specific agents are felt to be preferred in diabetics. Beta1
Inderal is a (selective/nonselective) beta blocker. nonselective
Inderal is a class ______ antiarrhythmic. II
Besides phenoxybenzamine and phentolamine, what other medication could be useful in the treatment of pheochromocytoma? Inderal
What class of medication should be given prior to giving Inderal? Why? Alpha blocker b/c high levels of catecholamines can stimulate alpha receptors and cause hypertensive crisis
What is the dosing for Inderal? What is the duration and max dose? 2mg IV q5min; duration <10min w/max dose 12mg/qd
What can happen with abrupt withdrawal of Inderal? Severe HTN followed by MI
Inderal should be used with caution in the presence of what two meds common in anesthesia? neostigmine and VAA
Which BB is used in the treatment of glaucoma? Timolol
Nadolol is a (selective/nonselective) BB. nonselective
What is the dose and duration of effects for metoprolol? 1-5mg q3min for three doses; effects may last up to 4hr
Metoprolol should be used with caution in the presence of what two medications? Neostigmine, amiodarone
Metoprolol has a (small/large) margin of safety. large
Atenolol is a (selective/nonselective) beta blocker. selective
What is the dose, peak, duration, and T1/2 for atenolol? 5mg q5min x2 doses//Peak @ 5min//Duration 24hr//T1/2 7hrs
How is atenolol excreted? Excreted unchanged by the kidneys and gut
What is the intraoperative drug of choice in at-risk cardiac patients due to its longer duration? atenolol
What conditions is esmolol used primarily to treat in the operating room? HTN, SVT, Afib/flutter
Esmolol reduce the release of what hormone? Renin
What is the dose for esmolol? What is the T1/2 for esmolol? 1.0mg/kg bolus followed by infusion 150-300mcg/kg/min; T1/2 9min
How is esmolol metabolized? Plasma esterases
10 ampules of esmolol (250mg/ml) is reconstituted in 250cc of solution for a final [] of _______. 10mg/ml
What types of receptors does labetalol antagonize? Both types of beta receptors and alpha1 receptors
What is the ratio of alpha:beta blockade w/labetalol IV? What is the ratio of alpha:beta blockade w/PO? 1:7 (IV); 1:3 (PO)
Labetalol is useful in treating (pre/peri/post)operative HTN. peri
What is the dose, duration and max dose for labetalol? 5-20mg IV; 2-4h; 300mg
What two medications are nonselective beta and alpha1 specific receptor blockers? Labetalol and carvedilol
How much more potent is carvedilol over labetalol? 3-5x more potent
Calcium channel blocking agents affect what types of channels? "L-type" or "slow channels"
Calcium channel blockers control the entry of calcium into what structures? Smooth muscle, cardiac myocytes, and the cardiac conduction system
In what phase of the cardiac conduction cycle do calcium channel blockers achieve their effects? Phase 2
How are calcium channel blockers grouped and what are the different groups? Grouped according to chemical structure: 1)phenyl-alkylamines 2)dihydro-pyridines 3)benzo-thiazepines 4)diphenyl-piperazines 5)diaryl-aminio-propylamine
All calcium channel blockers reduce calcium influx into slow Ca++ channels, where do they differ? Pharmacologic characteristics, interaction, toxicity
What type of a calcium channel blocker is nifedipine? Dihydro-pyridine
How much does nifedipine affect the cardiac conduction cycle? Minimal to no effect
What does nifedipine decrease? What does it increase? Decreases peripheral vascular resistance; increases cardiac output
What significant benefit does nifedipine have on the heart? Dilates coronary arteries more than any other agent
Besides hypertension, what other conditions is nifedipine useful for treating? esophageal disorders (spasm), vascular headaches, cardiomyopathy, asthma, primary pulmonary HTN
Why is nifedipine no longer used intranasal or SL? Significant cardiac and neurologic effects (dizziness, loss of consicous, heart block, MI, sinus arrest)
What class of CCB is nicardipine? dihidryo-pyridine
Nicardipine inhibits calcium influx into what types of tissues? Cardiac and smooth muscle
What was the first dihydro-pyridine CCB approved for IV administration? nicardipine
Essential and chronic stable HTN is effectively treated with which CCB? Nicardipine
What is the bolus and infusion dose for nicardipine? 0.625-2.5mg bolus followed by 5.0mg/hr infusion
In what two patient populations is nicardipine contraindicated? Hepatorenal impairment and CHF
Prolonged QT is dangerous for what two classes of patients? Hepartorenal impaired and CHF
Identify the uses of nicardipine. (4) Perioperative HTN, pheochromocytoma, cerebral vasospasm, myocardial preservation during bypass
Nicardipine (does/does not) cause coronary steal syndrome. does not
Which calcium channel blocker promotes a favorable balance between myocardial O2 supply and demand? nicardipine
What type of CCB is amlodipine? dihydro-pyridine
Where does amlodipine primarily work? Periphery to decrease SVR and increase CO
What makes clevidipine unique in its use as an intraoperative antihypertensive? Short acting (15min) and metabolized by blood and tissue esterases
What is the dose of clevidipine? 0.3-3.0 mcg/kg/min to a max of 16mcg/kg/min
Patients with what condition will have decreased clearance of clevidipine and prolonged recovery? Pseudocholinesterase deficiency
What class of calcium channel blockers is verapamil? phenyl-alkamine
Verapamil inhibits calcium influx into what types of tissues? Myocardial and arterial smooth muscles
What benefits does verapamil have on the heart? Dilates coronary arteries, inhibits coronary artery spasm, slows conduction through the SA and AV nodes w/o altering intraventricular conduction
What are 5 uses for verapamil? HTN, angina, SVT, arrhythmias, migraines
What is the dose for verapamil? 5-10mg IV, may repeat 15-30min
When taken PO, what metabolic effect decreases the absorption of verapamil? 1st pass hepatic metabolism
What classification of CCB is diltiazem? benzo-thiazepine
What 3 agents have been found to be useful for off-pump CABG? Diltiazem, verapamil, esmolol
What is the dose for diltiazem? 0.25mg/kg followed by 15mg/hr infusion
What is the T1/2 for diltiazem? 2hr
What two conditions stimulate the release renin? Reduced renal perfusion or beta1 stimulation
Renin combines with _______ to form _______. Angiotensinogen; angiotensin I
Where is angiotensin I converted to angiotensin II? Lungs
Where is renin stored and released from? Nephron
What are the effects of angiotensin II in the body? Vasoconstriction and aldosterone release from the zona glomerulosa
What does aldosterone encourage? Na+H20 retention and potassium excretion in hte distal tubule and collecting duct
What must be eliminated by the nephrons for every sodium ion that is reabsorbed? A potassium or hydrogen ion
Where do ACE inhibitors work to inhibit the conversion of angioI to angioII? Lungs
True/False: Reflex tachycardia is associated with the lower PVR produced by ACE inhibitors. False=PVR is lowered w/o reflex tachycardia or changes in CO
ACE inhibitors (increase/decrease) sodium reabsorption. decrease
Which two ACE inhibitors cause N/V? Lisinopril, ramapril
Which ACE inhibitor has a SE profile that includes chest pain, fatigue, and nervousness? Enalapril
Which ACE inhibitor has a SE profile that includes angioedema? Ramapril
Angiotensin receptors (1&2) are located in what types of tissues? Vascular and myocardial tissues, brain, kidney, adrenal cells
What classification antihypertensive is losartan? Angiotensin II receptor blocker (A2RB)
What types of angiotensin II receptors does losartan block and what is the effect? Blocks T1 receptors; lowers aldosterone secretion from the adrenal cortex
What is losartan primarily used to treat? Chronic HTN
T/F - Losartan does not metabolize to active metabolites. False
What is the T1/2 of the active metabolites of losartan? 8h
What are 4 anesthetic considerations for patients rec'ing ACE inhibitors and A2RBs? 1)Hypotension may be profound following GA induction 2)Hypotension first tx'd w/fluids 3)May require vasopressin agonist to treat low BP 4)Ephedrin is not effective for ACE induced hypotension
True/False: Ephedrine is effective for the treatment of ACE inhibitor induced hypotension. False
Refractory hypotension with ACE inhibitors is effectively treated with what two interventions? Vasopressin and IVF
A2RBs can encourage what electrolyte imbalance? Hyperkalemia in the presence of K containing solutions
How do A2RBs affect NMBs? May increase their effect
What anesthetic airway emergency are ACE inhibitors associated with? angioedema
What is the prototypical arterial vasodilator used to treat HTN? Hydralazine
How can hydralazine increase myocardial O2 demand? Stimulates baroreceptor reflex which leads to tachycardia
What is dosing for hydralazine outside of the OR? In the OR? 10-20mg q6h (outside); 2mg q15min (inside)
How is hydralazine supplied and reconstituted? Supplied 20mg/ml --> Diluted to 2mg/cc in a 10ml syringe
In what surgical position should the use of hydralazine be used with caution? Sitting, or any upright position that would encourage pooling of blood in the extremities
Fenoldopam is an antihypertensive that acts on what types of receptors? Dopamine 1 receptors
Fenoldopam is a dopa1 selective receptor (agonist/antagonist). Agonist
Fenoldopam causes what three effects? Decreased peripheral vascular tone, increased renal blood flow, increased diuresis
What is the dosing for fenoldopam? 0.025-2.3mcg/kg/min
What is the T1/2 and duration for fenoldopam? T1/2 5min; duration 15min
True/False: Fenoldopam should never be bolused. True
Which antihypertensive may cause allergic reactions due to the presence of bisulfite? Fenoldopam
Besides fenoldopam, what other agent contains bisulfite? propofol
Bisulfate can cause ________ reactions. anaphylactic
Name two other arterial vasodilators besides hydralazine. What reflexive responses can they elicit? Minoxidil and diazoxide; may initiate reflex tachycardia and increased CO
Nitroglycerin is a potent vasodilator that affects what types of vessels? Venous (first affected) and arterial
Nitroglycerin is a __________ compound. nitric oxide
What is the bolus dose of nitro and the infusion dose? Bolus=20-40mcg; Infusion=5-200mcg/min
What is the duration of nitroglycerin? 5min
SNP is a potent dilator of what types of muscles? Arterial and venous smooth muscle
How does SNP affect preload and afterload? Reduces both
Where is SNP utilized? Hypertensive emergencies, CHF, controlled hypotension for surgery
What is the dose of SNP? 0.5-10mcg/kg/min
SNP solutions must be protected from ______. Sunlight
What type of monitoring is generally used with nipride infusions? Arterial line
Discontinuation of SNP may lead to what two effects? Reflex tachycardia and rebound hypertension
How does SNP influence renal blood flow and what does it inhibit in the lungs? Reduces renal blood flow; inhibits hypoxic pulmonary vasoconstriction
SNP converts to ________ in RBCs. cyanogens
What are cyanogens metabolized to and where does this take place in the body? Metabolized to thiocyanate in the liver
SNP infusion rates of > __________ for over ________h may lead to toxic cyanide. 4mcg/kg/min; 3
What increases the release of free cyanide? Hemolysis
SNP stimulates the release of ______. Nitric oxide
What does the release of nitric oxide generate? Hydroxyl radicals
What are S/S of SNP toxicity? AMS, seizures, coma, cardiovascular instability, HTN 2/t tachyphylaxis, arrhythmias, ST changes, metabolic acidosis
How does sodium nitrate help combat SNP toxicity? Converts Hgb to metHgb, which then competes with cytochrome oxidase for cyanide radicals
How does sodium thiosulfate help combat SNP toxicity? Provides sulfur donors and prevents accumulation of cyanide radicals
How does B12 help combat SNP toxicity? B12 binds cyanide, transporting it to the kidneys for urinary excretion
What are the doses for the three medications used to treat SNP toxicity? 3% sodium nitrate 4-6mg slowly IV // sodium thiosulfate 200mg/kg over 15min // B12 @ 25mg/hr
Created by: philip.truong
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