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103 Cards in this Set
- Front
- Back
1.The ANS works to do what?
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1. maintain normal internal functions and work with the somatic nervous system.
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2. The enteric nervous system is the ___ division of the ___. What is it and what does it innervate?
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2. third; ANS; meshwork of nerve fibers that innervate the viscera (GI, pancreas, and gall bladder)
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The ANS is working when?
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All the time.
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Name some parasympathetic functions in regards to pupils, saliva, heart, bronchi, GI, bile, and bladder.
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Constricts pupils, stimulates flow of saliva, slows heartbeat, constricts bronchi, stimulates peristalsis and secretion, stimulates release of bile, contracts bladder.
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The PNS arises from what structures?
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Ganglion, medulla oblongata, vagus nerve, S2-S4, craniosacral.
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Name some sympathetic functions in regards to pupils, saliva, heart, bronchi, GI, bile, and bladder.
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Dilates pupils, inhibits flow of saliva, dilates bronchi, inhibits peristalsis and secretion, conversion of glycogen to glucose, secretion of adrenalin to noradrenalin, inhibits bladder contraction.
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The SNS arises from what structures?
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T1-L2
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What does "cholinergic" refer to?
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The effects of ACh.
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Where do "cholinergic" effects take place?
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PNS (PS ganglia and effector cells), parts of SNS (sympathetic ganglia, adrenal medulla, sweat glands), some CNS neurons, somatic nerves innervating skeletal muscle.
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What does "adrenergic" refer to?
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Effects of noradrenaline (norepinephrine).
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Where do "adrenergic" effects take place?
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Postganglionic sympathetic fibers at end-organ tissues.
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What are the two types of cholinergic receptors?
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Muscarinic and Nicotinic
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Where are nicotinic receptors located?
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Ganglia (ANS, SNS, PNS) and skeletal muscle.
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Where are muscarinic receptors?
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1. Glands (lacrimal, sweat, gastric)
2. Smooth muscle (bronchial, GI, bladder, blood vessels) 3. Heart (SA and AV node) |
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Alpha blockers bind ___ to alpha receptors.
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Selectively.
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Alpha blockers Interfere with the ability of ____ or other ____to provoke what?
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Alpha blockers interfere with ability of catecholamines or other sympathomimetics to provoke alpha responses on the heart & peripheral vasculature.
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How do alpha blockers affect the effects of epinephrine on insulin production?
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The inhibitory effect of epinephrine on insulin production is prevented, thus insulin production is NOT reduced.
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Name three major side effects of alpha blockers.
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Orthostatic hypotension, baroreceptor-mediated reflex tachycardia, impotence.
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The absence of beta blockade with alpha blockers allows for what?
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Maximum expression of cardiac stimulation from norepinephrine.
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What is competitive inhibition and which alpha antagonist drugs have this property?
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1. reversible binding with receptors
2. phentolamine, prazosin, yohimbine |
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What is a covalent receptor bond and which alpha antagonists bind this way?
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1. irreversible and insurmountable blockade
2. phenoxybenzamine |
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How can you reverse phenoxybenzamine effects?
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You can't. Once the blockade is in effect, even massive doses of sympathomimetics are ineffective UNTIL METABOLISM OF phenoxybenzamine takes place.
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What receptors do phentolamine and phenoxybenzamine antagonize?
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Postsynaptic alpha 1, presynaptic alpha 2
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Prazosin receptor?
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Alpha 1
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Yohimbine receptor?
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Alpha 2
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Phenoxybenzamine (Dibenzyline).
Type of bond, receptor, onset and elimination? |
Selective A1 and 2 blocker, covalent bond (ethyleneimine), a1>a2, slow onset (>60 minutes to reach peak, IV or PO, d/t the long time needed for structural change to take place that renders drug active), Te1/2 24 hours (cumulative)
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What are the cardiac effects of phenoxybenzamine (dibenzyline)?
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*Orthostatic hypotension if hypotension or hypovolemia
*impairment of compensatory vasocx-> exaggerated drop in BP in response to blood loss or vasod. drugs *CO, renal bloodflow unchanged (unless preexisting renal vasocx |
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Cerebral effects of phenoxybenzamine (dibenzyline)?
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*crosses bbb
*N/V, sedation, depression, lethargy |
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Phenoxybenzamine (dibenzyline) effects on insulin, glycogenolysis, eyes, and other tissues?
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*prevents inhibitory effects of epi on the secretion of insulin (more secreted)
*catecholamine induced glycogenolysis in skeletal muscle/fat not altered *nasal stuffiness-d/t unapposed alpha blockade vasod. in mucus membranes |
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What is the main thing phenoxybenzamine (dibenzyline) is used for?
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Preoperative treatment of HTN in pts with pheochromocytoma b/c with chronic alpha blockade, it relieves intense periph. vasocx, allowing expansion of IV volume as reflected by a drop in HCT.
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What is the dose of phenoxybenzamine (dibenzyline)?
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0.5-1mg/kg PO
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What are other indications for phenoxybenzamine (dibenzyline)?
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*Pt with excessive vasocx with assoc. tissue ischemia (hemorrhagic shock) but only after IV resuscitation.
*Reynauds, any dz with large component of vasocx. |
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What is the action of phentolamine?
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*transient non-selective alpha blockade (10-15min)
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What are the alpha1 and 2 effects of phentolamine?
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*A1: peripheral vasod and decreased BP within 2 min; elicits baroreceptor-mediated cardiac stim. reflex
*A2: enhances neural release of N.E.; CO/HR, angina, dysrhythmias |
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What are some other effects of phentolamine?
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Parasympathetic override: hyperperistalsis, abdominal pain, diarrhea.
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What are the indications for phentolamine? Doses?
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*Acute HTN emergencies, intraop mgmt of pheochr., ANS hyperreflexia (30-70mcg/kg IV (prompt/transient decrease in BP, may use drip)
*Accidental EV injection of sympathomimetic drug (2.5-5mg in 10ml for local infiltration) |
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What is the action of yohimbine?
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Blocks presynaptic alpha 2 receptors -> enhanced release of N.E. from nerve endings
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What does yohimbine treat?
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*Idiopathic orthostatic hypotension
*Impotence |
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5 other signs of cyanide tox?
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Methhemoglobinemia, increased MVO2 content, tachycardia, increased ICP, met acidosis.
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What is the action of Prazosin?
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*selective postsyn. A1 blocker
*leaves intact the inhibitory action of A2 receptor activity on N.E. release from nerve endings -> less likely than nonselective to cause reflex tachycardia *dilates both arterioles and veins |
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Clinical use of prazosin? Dose?
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*Preop tx of HTN in pt with pheochromocytoma (0.5-1mg/kg PO)
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How do beta blockers work at the receptor level?
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*Bind to beta adrenergic receptors and block effects of cate. and symptathom. on the heart and smooth muscles of the airways and blood vessels
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Why should BB be continued during the perioperative period?
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To avoid reflex SNS hyperactivity.
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What type of inhibition do BB exert?
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Competitive inhibition.
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Can BB be reversed?
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Yes. With beta agonist by displacement if large amt given.
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What happens with chronic BB administration?
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Up-regulation.
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Beta blockes are derived from what?
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Isoproterenol, a beta agonist
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What determines if a a drug is a beta agonist or antagonist?
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Substitutions on benzene ring.
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Which forms are more potent: levorotatory or dextrorotatory?
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Levorotatory; lefties rock! For example, propranolol has <1% the potency of the levorotatory form.
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Which drugs are nonselective BB?
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Propranolol, nadolol, timolol, pindolol.
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Which drugs are cardioselective for B1?
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Esmolol, atenolol, metoprolol, acebutolol, betaxolol.
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Beta-receptor selectivity is ___-___.
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Dose-dependent.
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When is beta receptor selectivity lost?
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When large doses of the antagonist is given.
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Which drugs are pure beta antagonists and what does this mean?
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metoprolol, atenolol, propranolol, nadolol
These have absent intrinsic sympathomimetic activity. |
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Which drugs are partial beta antagonists and what does this mean?
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timolol, pindolol, acebutolol, betaxolol
These have intrinsic sympathomimetic activity. |
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How are partial and pure beta antagonists different?
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*Partial ant. cause less direct myocardial depression and less heart rate slowing than pure BB.
*Partial BB may be better tolerated in pts with poor left ventricular function. |
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What is unique about propranolol?
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*First clinical BB.
*Standard to which all others are compared. |
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What receptors are blocked by propranolol?
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B1 and B2 (equal antagonism) nonselectively
Pure antagonist |
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With propranolol, what heart rate indicates optimal plasma concentration?
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55-60bpm
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What are the cardiac effects of propranolol?
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*Decreased HR, MC, CO d/t B1
*Increased PVR, CVR d/t B2 *although prolongation of sys dilation and dilation of cardiac ventricles increase MO2 requirements, O2 sparing effects of decreased HR and MC predominated (compensate) |
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GI effects of propranolol?
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*rapid GI absorption
*95% 1st pass absorption, limiting bioavailability *Up to 20 fold variation in 1st pass availability in similarly doses pts. |
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Dose of propranolol?
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PO 40-800mg/d
IV 0.05mg/kg in increments of 0.5-1mg q5min (note the large disparity in PO vs IV dosing) |
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Describe clearance, t1/2 of propranolol.
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*hepatic clearance
*t1/2: 2-3 hours *elimination decreased when hepatic BF decreased. May decrease its own clearance rate by decreasing CO and hepatic BF. *Renal failure does not alter but increased metabolites do accumulate. |
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Describe L.A. drug interactions with propranolol.
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*Propranolol decreases clearance of amide L.A. by decreasing hepatic BF and inhibition of liver metab.
*Bupivicaine clearance decreased 35%. *Higher chance of tox |
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Describe opioid drug interactions with propranolol.
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*pulm 1st pass uptake of fentanyl highly decreased.
*2-4x injected fentanyl enters sys. circ (inc. OD risk) *response reflects ability of one basic lipophilic amine to inhibit pulmonary uptake of another. |
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What type of antagonist is metoprolol?
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Beta 1, selective. Prevents inotropic and chronotropic responses to beta stimulation.
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Is it ok to use Metoprolol in pts with PVD/COPD? Why or why not?
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Yes, because there are no beta2 blocking properties at normal dose of 2-15mg IV.
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What happens if larger doses of metoprolol are given?
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It becomes nonselective.
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Describe PK of metoprolol.
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*high hepatic first pass metabolism (only 40% reaches systemic circulation)
*poorly protein bound (10%) *T1/2e - 3 hours |
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What is the MOST selective beta blocker?
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Atenolol
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Why is periop tx with atenolol beneficial?
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Prevents post-MI in CAD pts.
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What are the CNS effects?
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Enters CNS in small amounts but still produces fatique/depression.
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Can it be used in IDDM patients? Why/why not?
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*It can in IDDM patients when HTN is not controlled by other antiHTNs.
*It does not potentiate insulin-induced hypoglycemia seen with other nonselective BB. |
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Describe atenolol PK.
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*50% of PO dose absorbed by GI. *Little to no hepatic metab. *Renal excretion. *t1/2e: 6-8 hours
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What are the dosage ranges for atenolol?
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PO: 50-100mg/day
IV: 5mg over 5min followed by another 5mg 10min later (for acute MI). |
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How does renal failure affect elimination of atenolol?
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Prolongs greater than 24 hours.
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What is esmolol?
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Short acting B1 blocker given only IV.
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What is the dose of esmolol?
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0.5mg/kg
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What are the indications for esmolol?
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*Intraop HTN/tachycardia from noxious stim and intubation.
*Prior to ECT. *Pheochromocytoma, thyrotoxicosis, PIH, epinephrine or cocaine induced CV toxicity |
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Why is esmolol used for intraop HTN/tachycardia?
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Lidocaine and fentanyl used perioperatively to blunt stress response only blunts BP, not heart rate.
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Why is esmolol used for ECT?
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Attenuation of HR increase and decrease length of seizure.
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What is the pH of esmolol?
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Ph 4.5-5.5
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Describe the t1/2e and metabolism of esmolol.
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9 min. Metabolized by plasma esterases (different from plasma cholinesterase) completely independent of hepatic and renal function.
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After dosing with esmolol, how long does it take to peak and how long until heart rate returns to pre-drug level?
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Takes 5min to peak, 10-30min to return to pre-drug HR.
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CNS effects of atenolol?
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Poor lipid solubility prevents large amounts from crossing BBB but IT STILL CROSSES.
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What does the magnitude of BB s/e depend on?
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Selectivity and presence/absence of intrinsic sympathomimetic activity.
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BB's have ___ side effects.
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Similar.
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BB's may alter airway ___, ___/___ metabolism and distribution of ___ ___.
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Resistance, carbohydrate/lipid, extracellular ions.
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CNS commonalities of BB's? Placenta?
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All cross the BBB and placenta to some extent.
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GI effects of BB's?
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N/V/D.
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Problems with chronic use?
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Fever, rash, myopathy, alopecia, thrombocytopenia.
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When should you absolutely NOT use BB's?
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In pts with AV block or hx of heart failure caused by tachycardia.
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What types of BB should not be used in COPD, PVD or Diabetes and why?
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Nonselective BB's or high doses of selective BB's. In COPD may cause bronchocx. In PVD, causes peripheral vasocx. In diabetes, hypoglycemia may be masked d/t no increase in HR.
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What type of BB is labetalol?
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Selective A1, nonselective BB. Thought to also have selective B2 agonism.
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With labetalol, ___ ___ receptors are spared, and released ___ continues to ___ further release of ___.
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Presynaptic A1, NE, catacholamines.
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Compare the potency of labetalol to phenatolamine and propranolol.
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1/5-1/10 as potent as phenatolamine
1/3-1/4 as potent as propranolol |
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What is the beta to alpha potency ratio of labetalol?
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7:1 (IV)
3:1 (PO) |
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Describe the metabolism, elimination and t1/2e of labetalol.
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*Metabolized via conjugation of glucuronic acid.
*5% recovered unchanged in urine. *t1/2e: 5-8 hours, prolonged in liver dz, unchanged in renal dz. |
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How does labetalol decrease BP and HR?
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*BP:by decreasing SVR. Causes vasod. via alpha one blockade and partial beta2 agonist activity.
*HR: by attenuating reflex tachy via beta blockade |
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How is cardiac output affected by labetalol?
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Unchanged.
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What is the dose of labetalol and how soon should BP be lowered?
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*0.1-0.5mg/kg and BP is lowered within 5-10 minutes.
*20-80mg IV q10min for HTN emergencies *10mg PRN for controlled hypotension |
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Clinical uses of labetalol?
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*HTN emergencies (ex: epi overdose from local) *Pheo pts with rebound HTN after withdrawal of clonidine *Tx of angina pectoris *Purposeful controlled hypotension
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Labetalol s/e?
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*Most common-ortho hypo *bronchospasm in susceptible pts *CHF, bradycardia, heart block *incomplete alpha blockade in the presence of more complete beta blockade = exc alpha stimulation
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