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NU 600
Exam 6 - Antihypertensives
| Question | Answer |
|---|---|
| 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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