Adrenergic Antagonists Flashcards
MOA of alpha-adrenergic antagonists
- binds competitively or covalently with alpha receptors
- prevents the effects of catecholamines and other alpha agonists from interacting with the alpha receptor
- located in the heart and peripheral vasculature
effects of alpha-adrenergic antagonists
- vasodilation (orthostatic hypotension)
- reflex tachycardia
- blocks inhibition of insulin secretion (hypoglycemia)
what prevents the use of alpha-adrenergic antagonists as essential antihypertensives?
their side effects
(tachycardia, hypoglycemia, orthostatic hypotension)
what happens if taking an alpha-adrenergic antagonist if there is no beta-blockade?
maximal cardiac stimulation is allowed
MOA of phentolamine (Regitine)
competitive binding
non-selective - alpha1 and alpha2
how does phentolamine (Regitine) affect vasculature, HR & CO?
- vasodilation-alpha1 blockade and direct action on vascular smooth muscle
- cardiac stimulation - increased HR and CO
- reflex and α2 blockade - blocks neg. feedback of NE
side effects of phentolamine (Regitine)
- dysrhythmias
- angina
- hyper- peristalsis
- abdominal pain
- diarrhea (due to parasympathetic tone)
uses of phentolamine (Regitine)
- acute HTN emergencies
- pheochromocytoma
- accidental infiltration of a sympathomimetic
dose of phentolamine (Regitine) to use for infiltration?
5-15 mg in 10 ml
phentolamine (Regitine)
onset and duration
onset: 2 min
duration: 10-15 min
phentolamine (Regitine)
bolus/loading dose and infusion dose
bolus/loading: 30-70 mcg/kg (1-5 mg)
infusion: 1-10 mcg/kg/min (300 mg in 500 mL of LR or NS)
MOA of phenoxybenzamine (Dibenzyline)
irreversible covalent binding to α-receptors
nonselective; alpha1 > alpha2
CV effects of phenoxybenzamine (Dibenzyline)
- vasodilation – orthostatic hypotension exaggerated with hypovolemia, HTN
- impairment of compensatory vasoconstriction (lower BP with hypovolemia and vasodilating drugs like volatile agents)
- increased CO
- very little change in renal blood flow even with decreased BP
with phenoxybenzamine (Dibenzyline) is renal autoregulation maintained?
yep
non-CV effects of phenoxybenzamine (Dibenzyline)
- prevents the inhibition of insulin secretion
- pupil constriction
- chronic use may cause sedation
- nasal congestion
uses of phenoxybenzyamine (Dibenzyline)
- control BP in pheochromocytoma
- in trauma patients, used to reverse vasoconstriction (shock), only after volume replacment
- Raynaud’s syndrome
phenoxybenzamine (Dibenzyline) onset, duration, and elimination t½
why is the onset time longer than some of the other drugs in this class?
onset: up to 60 min IV
duration: can last up to 4 days
elim t½: 24 hours
longer onset bc prodrug
what is one thing to be cautious of when using phenoxybenzamine (Dibenzyline)?
the prolonged half-life can lead to accumulation
MOA of prazosin (Minipress)
competitive, reversible binding with alpha receptor
selective – α1 antagonists
effects of prazosin (Minipress) on vasculature and HR
- vasodilation of both arterioles and veins
- less reflex tachycardia (alpha2 not blocked)
uses of prazosin (Minipress)
- HTN
- severe CHF
prazosin (Minipress) onset and duration
onset: within 2 hrs
duration: 10-24 hrs
MOA of doxazosin (Cardura)
selective alpha1 antagonism
doxazosin (Cardura)
dosing, peak time, elimination t½
daily dosing
peak: 2-3 hrs
elim t½: 22 hrs
indications for doxazosin (Cardura)
- benign prostatic hypertrophy
- hypertension treatment
MOA of beta-adrenergic antagonists
- competitive binding to beta receptors
- block the effect of catecholamines and agonists on the heart and smooth muscles of airways and blood vessels
prolonged or chronic use of beta-blockers can cause what?
up-regulation of beta receptors
non-selective beta-adrenergic antagonists
- propranolol
- timolol
- nadolol
cardioselective beta-adrenergic antagonists
receptor blocked and examples
- blocks beta1 at normal doses, large doses can impact beta2 receptors too
- metoprolol
- atenolol
- esmolol
effect of partial beta-adrenergic antagonist
- intrinsic sympathomimetic effect
- less myocardial depression and HR reduction
what is a pure beta-adrenergic antagonist?
b-adrenergic antagonist with no sympathetic effect
effects of beta1 blockade
*long
removes sympathetic stimulation to the heart
- negative inotropic effects - myocardial depression
- negative chronotropic effects - slows HR, sinus rate
- negative dromotropic effects - slows the conduction of impulse through the AV node, slows rate of phase 4 depolarization
- increase in lusitropy - ventricular relaxation
- decrease in bathmotropy - reduced degree of excitability
effects of beta2 blockade
- vasoconstriction
- unopposed alpha vasoconstriction can cause decreased LV ejection
- bronchoconstriction
- prevents glycogenolysis, blocks tachycardia related to hypoglycemia, alters fat metabolism (lipolysis)
- inhibits uptake of K into skeletal muscle cells (increased serum K)
effects of beta2 blockade in patient with pre-existing obstructive airway disease
exaggerated airway resistance effects
what patient population needs to avoid non-selective beta-blockers? why?
(other than airway disease pts)
- diabetics
- symptoms of hypoglycemia are masked and glycogen can’t be broken down
effects seen with cardioselective vs non-selective beta-blockers when given SCh?
- ** not demonstrated in pts
- selective - K+ will increase, but will return to normal later
- non-selective - K+ will increase and stay increased due to inhibit uptake into skeletal muscle cells
potential effects of beta-adrenergic antagonists with anesthetic agents
- potential additive myocardial depressant effects
- safe to continue - benefits of continuing outweigh the risks
- halothane > isoflurane
CNS effects of beta-adrenergic antagonists
- cross blood/brain barrier →
- fatigue
- lethargy
- vivid dreams
- memory loss
- depression
beta-adrenergic effects on fetus
Cross placenta →
- fetal bradycardia
- fetal hypotension
- fetal hypoglycemia
GI effects of beta-adrenergic antagonists
- nausea
- vomitting
- diarrhea
effects of chronic use of beta-adrenergic antagonists
- fever
- rash
- myopathy
- alopecia
- thrombocytopenia
contraindications to beta-blockers and why
*long (7)
- AV heart block – slowed conduction may be enhanced
- hypovolemia – eliminates tachycardia that is compensating for decrease in volume
- COPD – increased airway resistance (nonselective or high doses)
- diabetes – mask signs of hypoglycemia (nonselective or high doses)
- peripheral vascular disease, Raynaud’s syndrome, or alpha-adrenergic agonist - vasoconstriction unopposed (nonselective), cold extremities
effects seen with beta-adrenergic antagonist overdose
- bradycardia
- low cardiac output
- hypotension
- cardiogenic shock
- bronchospasm
- prolonged intraventricular conduction of impulses
- hypoglycemia - rarely
overdose of beta adrenergic antagonist - treatment order
(no doses)
- atropine
- isoproterenol
- dobutamine
- glucagon
- calcium chloride
- pacemaker
- hemodialysis (only for minimally protein-bound renally excreted beta-blockers)
AID Generally Can …? idk. i tried.
dose of atropine to use for beta-blocker overdose?
7 mcg/kg IV
dose of isoproterenol to use for beta-blocker overdose?
2-25 mcg/min
dose of glucagon to use for beta-blocker overdose?
1-10 mg
dose of CaCl to use for beta-blocker overdose?
250 mg - 1 g
what two drugs should be avoided when treating a beta-blocker overdose?
why?
- epi and dopamine
- alpha1 vasoconstriction occurs at the high doses required to overcome the beta blockade
MOA of glucagon for beta-blocker overdose treatment
- not via beta receptors
- stimulates adenylate cyclase - increases cAMP
- especially effective in life-threatening bradycardia
considerations for beta-blocker overdose if patient needs a pacemaker
- myocardial thresholds may be raised to prevent capture
- may have to increase settings
what causes acute withdrawal symptoms of beta-blockade?
symptoms and timing?
- increased sympathetic stimulation due to up-regulation of beta receptors
- within 24-48 hours
- profound hypertension, tachycardia, contractility
how to avoid acute withdrawal symptoms of beta-blockade?
- continue preoperative beta-blockade therapy
- infusion of propranolol 3 mg/hr IV
uses of beta-blockers (6)
(not intra-op uses)
- treatment of HTN
- management of angina
- post-MI
- dysrhythmias
- prevent excessive SNS activity
- management of CHF
MOA for beta-blockers treating HTN
- decrease HR, decrease CO
- decrease contractility in larger doses
- with vasodilator, prevention of reflex tachycardia
- decrease renin, decrease aldosterone, prevention of Na, water retention
MOA of beta-blockers in mgt of angina
- decreased myocardial oxygen consumption
- decreased HR, contractility
MOA of beta-blockers for post-MI treatment
*long
- decreases mortality and reinfarctions
- increases chances of survival 20-40%
- within 12 hours of onset of infarct may actually decrease infarct size and dysrhythmias
- not used with acute coronary syndrome with ST-elevation or cardiogenic shock
- both selective and nonselective drugs have a cardioprotective effect
- nonselective effect on K (prevents reduction) may decrease dysrhythmias
MOA of beta-blockers for treatment of dysrhythmias
- decrease activity of SA node and conduction through the AV node
- slows depolarization of ectopic pacemakers
- suppresses both supraventricular and ventricular ectopy
- rapid suppression of excessive sympathetic stimulation (thyrotoxicosis, pheochromocytoma, perioperative stress)
uses of beta-blockers for prevention of excessive SNS activity
- minimizes response to laryngoscopy
- hypertrophic obstructive cardiomyopathies
- pheochromocytoma, hyperthyroidism
- tetralogy of Fallot – minimize cyanosis
- prevent reflex tachycardia with vasodilation use in deliberate hypotension
- public speaking - anxiety
beta-blockers use in management of congestive heart failure?
drugs used?
- improve EF
- increase survival rate in chronic HF
- doses initially small and gradually increase
- metoprolol, carvedilol, bisoprolol
non-cardiac surgery patients that benefit from use of beta-blockers intra-op
what benefit is seen?
- rhinoplasties - decreased post op pain
- decreased pain and morphine use when esmolol given
- less variation in HR, BP for first 3 hours
- lap choles - decreased intra-op and post-op analgesic need with esmolol given during case
- less analgesic/opioid needed
- less PONV
“modulation of the sympathetic component of pain”
benefits of beta-blockers for cardiac patients
- reduced 30 day mortality in coronary surgery
- reduced peri-op ischemia, mortality, CV complications for up to 2 years post-op
- improved M&M in CABG pts
effect of beta-blockers in elderly pts having non-cardiac surgery
- reduced analgesic requirements
- faster recovery from anesthesia
- improved hemodynamic stability
pre-op beta-blockate to uncontrolled hypertensive pts reduced myocardial ischemia how much?
from 28% to 2%
T/F: beta-blockade reduces perception of noxious stimuli and has an anxiolytic effect
true
effects of beta-blockade that cause cardioprotection during surgery (6)
*long
- improves the myocardial oxygen supply-demand balance
- decreases oxygen requirements by slowing HR and decreasing contractility
- blocks catecholamines from the receptors to avoid increased SNS stimulation
- prolongs diastole and increases time for oxygen delivery
- suppression of dysrhythmias – improves long-term mortality
- increase blood flow to ischemic myocardium
no idea how to put this on a card…. so there’s some POISE info on the back of this
POISE = Peri-Operative Ischemic Evaluation
- randomized, controlled clinical trial
- 8,351 patients, 190 hospitals
- 23 countries
- pts accepted from 2002-2007
- non-cardiac surgical procedures
- > 45 years of age
- hospitalized at least 24 hours post-op
what drug did patients receive during the POISE trial?
overall results?
- metoprolol ER 2-4 hrs before surgery continued for 30 days
- increased risk of stroke, bradycardia, hypotension, and all cause mortality
- decreased risk of non-fatal MI
what was thought to be the cause of the increased risk of strokes from beta-blockers in the POISE trial?
hypotension causing ischemic strokes
ACCF/AHA recommendations for peri-op beta-blockers
peri-op beta-blockers recommended in patients who are already receiving beta-blockers
ACCF/AHA “probably recommends” peri-op beta-blockers in what patients?
- pts undergoing vascular surgery who suffer from CAD or show ischemia on peri-op testing
- in the presence of CAD or high cardiac risk (> 1 risk factor) who are undergoing intermediate-risk surgery
- where pre-op assessment for vascular surgery identifies high cardiac risk (>1 risk factor)
ACCF/AHA says the use of peri-op beta-blockers is uncertain in what patients?
- pts undergoing vascular surgery with no risk factors who are not currently taking beta-blockers
- pts undergoing either immediate-risk procedures or vascular surgery with a single clinical risk factor in the absence of CAD
time when ACCF/AHA says to not give beta-blockers?
- high-dose beta-blockers without titration are not useful and may be harmful to patients not currently taking beta-blockers who are undergoing surgery
- patients undergoing surgery who have an absolute contraindication to beta-blockade
if beta blockers are indicated peri-operatively, when should they be started?
not that it’s even up to us..
“should be started between 30 days and 1 week before surgery or days to weeks before surgery”
if using beta-blockers intra-operatively, what is necessary to minimize the risk of hypotension?
what are our HR/BP goals?
titrate to minimize risk
HR goal 60-80 bpm
systolic arterial pressure > 100 mmHg
if pt is on beta-blockers pre-op, do we ever d/c them prior to surgery?
nope never
overall outcomes of peri-op beta-blockers in a non-cardiac pt?
no benefit
reduction in arrhythmias and acute MI is offset by an increase in mortality and strokes
if pt having cardiac surgery, what is the benefit of peri-op beta-blockers?
reduced risk of SVT and ventricular arrhythmias
what is propranolol (Inderal)?
effects seen?
- * gold standard - 1st bb
- non-selective, pure antagonist, beta1=beta2
- decreased HR and contractility (& CO)
- increases peripheral vascular resistance (B2), including coronary resistance
effects of coronary O2 supply/demand from propranolol (Inderal)?
decreased O2 requirement is bigger than decreased coronary blood flow due to increased vascular resistance
supply > demand
propranolol (Inderal) dose
0.05 mg/kg IV in increments of 0.5-1.0 mg q 5 minutes
propranolol (Inderal) metabolism and elimination t½
- hepatic - it can decrease its own metabolism (clearance is decreased with decreases in hepatic blood flow)
- elim t½: 2-3 hours
propranolol (Inderal) special effects
- metabolism of amide local anesthetics is decreased by propranolol due to decreased CO and more (?)
- more fentanyl enters the circulation of a pt on propranolol due to decreased pulmonary uptake
nadolol (Corgard)
selectivity, duration, metabolism, elimination t½?
- nonselective beta-adrenergic antagonist
- long duration: once daily
- metabolism: 75% unchanged by kidneys, in the bile
- elim t½: 20-40 hrs
timolol
selectivity, typical use, side effects?
- non-selective beta-adrenergic antagonist
- usually used in eye drops for glaucoma
side effects:
- bradycardia and hypotension can be seen when combined with anesthesia
- can cause apnea in neonates (d/t immature BBB)
metoprolol (Lopressor)
selectivity, effects?
- beta-1 selective beta-blocker
- blocks inotropic and chronotropic response
- beta-2 unblocked - causes bronchodilation, vasodilation, and metabolic stability
- can cause beta 2 blockade at high doses
dose of metoprolol (Lopressor)
if HR > 80: 5 mg IV
if HR 60-80: 2.5 mg IV
hold if HR < 60 or SBP < 100
metabolism and elimination t½ of metoprolol (Lopressor)
metabolism: hepatic
elim t½: 3-4 hours
what is the most selective beta-1 antagonist?
atenolol (Tenormin)
atenolol (Tenormin)
selectivity, elimination and t½
- MOST selective beta1 antagonist
- elimination: renal excretion
- elim ½ life: 6-7 hours
patient population where it would be advantageous to use atenolol (Tenormin) and why
- diabetics
- doesn’t interfere with metabolism
*but if it accumulates it can cause problems
(im guessing bc then it can hit beta2 too? thoughts?)
betataxolol
selectivity, uses, benefits?
- cardioselective - beta1 antagonist
- uses: reduced elevated or normal IOP, whether or not if there’s glaucoma
- benefits: less systemic effects vs atenolol, minimal pulmonary and cardiac effects at clinical doses
bisoprolol
selectivity, main effect, uses?
- cardioselective - beta1 antagonist
- prominent effect: decreased HR
- uses: treatment of essential HTN, mild-moderate CHF
esmolol (Breviblock)
selectivity?
dose?
- selective beta1 antagonist
- dose: 0.5mg/kg IV over 60 seconds
esmolol (Breviblock)
onset and duration
onset: within 5 min (sooner per TC)
duration: 10-30 min (shorter per TC)
esmolol (Breviblock)
metabolism and elimination t½
metabolism: rapid hydrolysis by plasma esterases *independent of renal and hepatic function
elim t½: 9 min
uses of esmolol (Breviblock)
*long
- protection against tachycardia and hypertension related to laryngoscopy
- pheochromocytoma, thyrotoxicosis, cocaine-induced cardiovascular toxicity
- tetralogy of Fallot and hypertrophic obstructive cardiomyopathy
- cardiac surgery – off bypass
- reduce requirements of propofol, opioids
- electroconvulsive therapy
dose and timing of esmolol (Breviblock) if giving for laryngoscopy
150 mg given 2 minutes prior
esmolol vs lidocaine or fentanyl for laryngoscopy
better protection than lidocaine or fentanyl against HR
dose of esmolol for electroconvulsive therapy
500 mcg/kg/min
caution when treating excessive SNS activity from cocaine or systemic absorption of topical epi due to what potential outcome?
fulminant pulmonary edema and irreversible cardiac collapse
cant increase HR or contractility to handle the increase in afterload
what is receptors are affected by labetolol (Normodyne, Trandate)?
potency compared to propranolol?
- selective alpha1 antagonist
- nonselective beta1 and beta2 antagonist
- also apparently some intrinsic beta 2 agonism :|
- alpha to beta block ratio is 1:7
- ¼-⅓ as potent as propranolol for beta-blocking effects
CV effects of labetalol (Normodyne, Trandate)
- decreases SVR (vasodilation from alpha1antagonist and beta2 agonist effects)
- prevents reflex tachycardia
- unchanged CO
labetalol (Normodyne, Trandate)
dose and onset
dose: 0.1-0.5 mg/kg IV
onset: peak effect in 5-10 min
labetalol (Normodyne, Trandate)
metabolism and elimination t½
metabolism: conjugation of glucuronic acid (hepatic)
elimination t½: 5-8 hrs
uses of labetalol (Normodyne, Trandate)
- hypertensive emergencies
- increased sympathetic activity
- pheochromocytoma
- angina pectoris
- controlled, deliberate hypotension
side effects of labetalol (Normodyne, Trandate) (6)
- orthostatic hypotension – most common
- bronchospasm – nonspecific beta (offset by alpha block?)
- congestive heart failure - beta *
- bradycardia - beta *
- heart block – beta *
- fluid retention (chronic use necessitates addition diuretics)
*likely incidence and severity decreased
esmolol vs labetalol
receptors effected
esmolol: selective beta1
labetalol: nonselective beta, alpha1
esmolol vs labetalol
duration
esmolol: short (9 min)
labetalol: prolonged (5-8 hrs)
esmolol vs labetalol
metabolism
esmolol: plasma esterases, organ independent
labetalol: hepatic
esmolol vs labetalol
onset
esmolol: rapid (within 5 min)
labetalol: slower (5-10 min)
which is better for deliberate hypotension - esmolol or labetalol?
esmolol
which has an increased risk of “bleeders” that didnt show up with lower BP - esmolol or labetalol?
~need to reword this later pls excuse
labetalol
carvedilol (Coreg)
receptors affected?
- alpha1 blocking activity
- nonselective beta-blocking (no intrinsic beta-agonist effects)
- metabolites produce weak vasodilating effects
uses for carvedilol (Coreg)
- CHF
- essential HTN
- shown to decrease mortality with CHF
