SYMPATHOLYTICS Flashcards
Beta Adrenergic Receptor Antagonists bind where? create what response?
beta receptors
interfere with the ability of catecholamines or other sympathomimetics to provide beta responses
Beta Adrenergic Receptor Antagonists- prevents effects of ____ and _____ on the _____ and ______ of the airways and blood vessels.
Beta adrenergic blockade prevents the effects of catecholamines and sympathomimetics on the heart and smooth muscles of the airways and blood vessels.
Beta Adrenergic Receptor Antagonists- why must these be give periop?
must be maintained periop to maintain effects and avoid sympathetic nervous system hyperactivity with abrupt D/C of these drugs
Beta Adrenergic Receptor Antagonists- what drug is the standard to which all other beta adrenergic antagonist are compared
Propranolol
Beta Adrenergic Receptor Antagonists: mao- are they competitive or noncompetitive binders?
Exhibit selective affinity for beta adrenergic receptors, where thy act by competitive inhibition.
Beta Adrenergic Receptor Antagonists: mao- because its reversible what does that mean for beta agonist
Binding of an antagonists to beta adrenergic receptors is reversible such that the drug can be displaced if enough agonist drugs are available. Sufficiently large doses of an beta agonist may still exert a full pharmacologic effect.
Beta Adrenergic Receptor Antagonists: mao- chronic administration of beta adrenergic antagonist means what for the receptors?
up regulation of beta receptors
beta receptors mao- tell me about the G protein on these receptors. If NE or EPI occupy a beta receptor what happens
Beta adrenergic receptors are G protein-coupled receptors and their occupancy by agonists (norepinephrine, epinephrine) stimulates G proteins that in turn activate cAMP.
what is the net effect of beta adrenergic agonist stimulation in the heart
positive effects of:
Chronotropic - heart rate
Inotropic- contractility
Dromotropic- electrical condition
Beta Adrenergic Receptor Antagonists- net effect of beta adrenergic antagonist blunt what effects
chronotropic
inotropic
dromotropic
what percent of beta receptors are beta 1 in the myocardium what percent are beta 2
~ 75% of beta receptors in the myocardium are Beta 1 while ~ 20 % are Beta 2
Beta Adrenergic Receptor Antagonists- derivatives of what drug?
Beta agonist drug isoproterenol
Beta Adrenergic Receptor Antagonists- what determines the ability of the drug to act as a agonist or antagonist.
Substitutions on the benzene ring determine whether the drugs acts as an agonists or antagonist
Beta Adrenergic Receptor Antagonists- which drugs are non selective beta 1 & beta 2
Propranolol
Nadolol
Timolol
Pindolol
Cardioselective Beta 1: (6)
Metoprolol Atenolol Acebutolol Betaxolol Esmolol Bisoprolol
beta antagonist receptor selectivity is… dependent on what?
what makes it less selective?
Beta receptor selectivity is dose dependent and is lost when large doses of the antagonist are administered.
Beta Adrenergic Receptor Antagonists- what are they classified as?
how do they classify that?
Beta adrenergic antagonists are also classified as partial or pure antagonists based on the presence or absence of intrinsic sympathomimetic activity.
Beta Adrenergic Receptor Antagonists- which patient population is better suited for cardiac selective beta 1 receptor drugs?
Cardiac selective Beta 1 receptor drugs are better suited for administration to patients with asthma and reactive airway disease
what patients are better suited for cardio selective drugs beta 1?
Theoretically, cardioselective drugs are better suited for treatment of patients with essential hypertension since these drugs lack inhibition of peripheral Beta 2 receptors that produce vasodilation
beta 1 receptor blockade effects
Slows sinus rate
Slows conduction of cardiac impulses through AV node
Decreases inotropy
Beta Adrenergic Receptor Antagonists- when are beta 1 effects greater?
These effects are relatively greater during activity than during rest
Beta Adrenergic Receptor Antagonists
beta 1 effects on the 02 demand during exercise
Decreases myocardial O2 demand with subsequent decrease in occurrence of myocardial ischemia during exercise.
Beta Adrenergic Receptor Antagonists- beta 1 effects on diastolic function
increases diastolic perfusion time which may enhance myocardial perfusion
Beta Adrenergic Receptor Antagonists- beta 2 receptor blockade- have increased risk of
bronchospasm in patients with restrictive airway disease and can worsen symptoms of PVD
Beta Adrenergic Receptor Antagonists half time for esmolol vs other drugs
Principle difference in pharmacokinetics b/t all the beta adrenergic receptor antagonists is the elimination half-time range from:
Brief: esmolol ~ 10 minutes
Other drugs that can be hours
Beta Adrenergic Receptor Antagonists- how is propranolol plasma protein bound?
Among the beta adrenergic receptor antagonists only Propranolol is highly plasma protein bound 90-95%
Beta Adrenergic Receptor Antagonists- what is the volume distribution
Volume of distribution of beta adrenergic receptor antagonists is high and are rapidly distributed following IV administration
Beta Adrenergic Receptor Antagonists- MI what should they receive
It is recommended that all patients who experience an acute MI receive IV beta adrenergic antagonists unless contraindicated
Beta Adrenergic Receptor Antagonists- MI and reperfusion therapy?
They should receive IV beta blocker therapy whether or not they receive reperfusion therapy
Beta Adrenergic Receptor Antagonists- contraindications
Severe bradycardia
Unstable LV failure
AV heart block
Beta Adrenergic Receptor Antagonists- relative contraindications? (4)
Asthma
Reactive airway disease
Mental depression
PVD
Beta Adrenergic Receptor Antagonists- what are the diabetic considerations
DM is not a contraindication to the use of beta adrenergic receptor antagonists but can mask signs hypoglycemia
Beta Adrenergic Receptor Antagonists- which produce cardio protective effect
Cardio protective effect is present with both cardioselective and nonselective beta antagonists
periop- beta blockade is recommended for patients considered at risk for myocardial ischemia name 4 disease risk factors
high risk surgeries include (4)
CAD
Positive Preop Stress Test
DM using insulin
LV hypertrophy
Vascular
Thoracic
Intraperitoneal surgery
Anticipation of large blood loss
Beta Adrenergic Receptor Antagonists- goal of preop resting HR
Goal of preop therapy is resting HR of 65-80 bpm
benefits of beta adrenergic receptor antagonist?
All beta adrenergic receptor antagonists except those with intrinsic SNS activity, decrease mortality
Beta Adrenergic Receptor Antagonists-name the most important potentially reversible risk factor for mortality and cardiovascular complications after noncardiac surgery
Periop myocardial ischemia
Beta Adrenergic Receptor Antagonists- benefits of atenolol for 7 days before and after non cardiac surgery in patients at risk for CAD does what
decrease mortality and incidence of CV complications for as long as 2 years after surgery
beta blocker- Preop. PO can be initiated with either:
drug 1 dose?
drug 2 dose?
drug 3 dose?
Atenolol 50 mg
Bisoprolol 5-10 mg
Metoprolol 25-50 mg
Beta Adrenergic Receptor Antagonists- morning of surgery what 2 drugs can we titrate? and what are their doses?
atenolol 5-10 mg
or
metoprolol 5-10 mg can be titrated.
Beta Adrenergic Receptor Antagonists- what drug is used during surgery and post op ICU
Esmolol is acceptable drug to achieve beta blockade during surgery and postop in ICU
Beta Adrenergic Receptor Antagonists- which drugs can be given IV until patient can take PO
IV atenolol or metoprolol can be administered until pt can take PO atenolol or bisoprolol
Labetalol- which receptors?
Exhibits selective alpha 1 and nonselective Beta 1 and 2 antagonists
Labetalol- what about alpha 2 receptors
Presynaptic alpha 2 receptors are spared by labetalol such that released norepinephrine can continue to inhibit further release of catecholamines via the negative feedback mechanism resulting from stimulation of alpha 2 receptors.
Labetalol- metabolism by what?
how much unchanged in the urine
Metabolism is by conjugation of glucuronic acid
5% unchanged in the urine
Labetalol- elimination half time?
elimination prolonged in ?
elimination is unchanged by what?
Elimination half time is 5-8 hours
Elimination is prolonged in liver disease
Elimination is unchanged by renal dysfunction.
Labetalol- oral dose? how often?
iv dose?
Oral (100-600 mg BID) and IV doses available
Labetalol- how does it lower BP
Labetalol lower systemic BP by decreasing SVR (alpha 1 blockade) and reflex tachycardia triggered by vasodilation is attenuated by simultaneous beta blockade.
Labetalol- CO
CO unchanged
Labetalol- how does it vasodilate?
Vasodilation is by alpha 1 blockade and maybe by vasodilation mediated by beta 2 agonist activity as well
Labetalol- IV dose? how fast does it work?
Max systemic BP lower effect of an IV dose of 0.1 – 0.5 mg/kg is present in 5-10 minutes
Labetalol- can it be used in hypertensive emergencies
Safe to use in hypertensive emergencies
Labetalol- how is this used with EPI overdose
Has been used to control severe hptn associated with epinephrine overdose
Labetalol- large dose may do what? what is a large dose? what is an appropriate dose
Large doses 2 mg/kg IV may over treat and have excessive decreases in BP. Smaller doses 20 – 80 mg IV are less likely to produce undesirable decreases in BP
Labetalol the appropriate dose can be repeated how often
Repeated doses of 20 – 80 mg every 10 minutes until desired therapeutic response if achieved.
Labetalol- how is it used with pheochromocytoma? how is it used in clonodine withdrawal?
Rebound hptn after withdrawal of clonidine therapy and hypertensive responses in patients with pheochromocytoma can be effectively treated with labetalol.
Labetalol- how is it used for angina
Effective in angina pectoris
Labetalol- what dose is best used for surgical stimulation increased HR and BP
Can be used (0.1 to 0.5 mg/kg IV) when increase in surgical stimulation cause increases in HR and BP
Labetalol- side effects
prolonged used will cause ?
Orthostatic hypotension: most common
Bronchospasm is possible
Prolonged chronic therapy causes fluid retention and a diuretic is given with for prevention.
CCB- what is this also called?
Also called calcium entry blockers and calcium antagonists
ccb- where does it interfere with calcium movement across what two places
Selectively interferes with inward calcium ion movement across myocardial and vascular smooth muscle cells.
ccb-Classified based on chemical structure:
Phenylalkylamines:
Dihydropyridines:
Benzothiazepines:
Phenylalkylamines: selective for atrioventricular node
Dihydropyridines: selective for arteriolar beds
Benzothiazepines: selective for atrioventricular node
ccb- common side effects (4)
Hypotension
Peripheral edema
Flushing
Headache
CCBs produce:
Decreased myocardial contractility
Decreased HR
Decreased activity of the SA node
Decreased rate of conduction of cardiac impulses through AV node
Vascular smooth muscle relaxation with associated vasodilation
Decreases in systemic BP
What were the results of the POISE trial
what were the criticisms of the trial
increased mortality by increase in cerebrovascular events
aggressive BB dosing, without considering patient baseline hemodynamics- leads to cerebrovascular hypo perfusion.
patients had BP reduction >30% below preoperative levels
practitioners now start low dose BB preop- or wait until post op
CCB- which are effective for treatment for coronary artery spasms
All CCBs are effective for treatment of coronary artery spasms
CCB
Decreases vascular smooth muscle contractility
peripheral vasodilation with reduction in systemic vascular resistance
systemic blood pressure
CCB- possess what type of ischemic effects
Possess anti-ischemic effects
CCB- coronary arteries effect?
what drug complements ccb
Dilates coronary arteries via a different mechanism than nitrates thus these two classes complement each other in tx of coronary spasms.
patient has chronic stable angina with fixed obstructive coronary artery lesions. what medication is effective for this
ccb
ccb- which two drugs exert negative inotropic effects
All CCBs exert negative inotropic effects which are most significant with:
verapamil
diltiazem
Phenylalkylamines
verapamil synthetic derivative of ?
supplied how?
Verapamil:
Synthetic derivative of papverine supplied in a racemic mixture
Phenylalkylamines
verapamil side effects- AV node effect
Verapamil Side Effects:
Major depressant of the AV node
Phenylalkylamines
Verapamil Clinical Uses:
Effective in tx of SVT
vasospastic angina pectoris
hptn
As effective as beta blockers in relieving angina pectoris
symptomatic hypertrophic cardiomyopathy with or without LV outflow obstruction
Should not be routinely given for acute MI as a post infarction mortality is not decreased
Verapamil Clinical Uses: fetal and maternal
Useful in tx of maternal and fetal tachy dysrhythmias and premature labor
It prolongs atrioventricular conduction of the fetus despite limited placental transport of the drug.
Fetal hepatic extraction of verapamil is substantial
May decrease uterine blood flow
Use with caution in the parturient with impaired uteroplacental perfusion
Verapamil: protein bound?
elimination half time
90% protein bound
Elimination half time 6-12 hours
Nicardipine (Cardene): mechanism of action
Lacks effects on SA and AV nodes with minimal myocardial depressant effect
Nicardipine
elimination half time
how many hours should elapse before increasing the oral dose
metabolized in the ___
% protein bound?
3-5hr
~72 hours should elapse before increasing oral dosage
Metabolized in the liver
Highly protein bound 95%
Nicardipine Uses: for labor
Tocolytic drug with similar effects as salbutamol but with fewer side effects
It binds to the inside of myometrial L-type voltage-dependent calcium ion channels causing them to remain closed and thus inhibits uterine contractility.
Nicardipine Uses: as a tocolytic with salbutamol?
Pulmonary edema associated with salbutamol used as a tocolytic has also been reported in a parturient treated with nicardipine
Diltiazem does it interact with beta blockers?
Unlikely to interact with beta blockers to decrease myocardial contractility.
Diltiazem Uses:
IV bolus dose
iv drip dose
Similar to those of verapamil
PO and IV
Manages angina pectoris: IV 0.25 - 0.35 mg/kg over 2 minutes repeated in 15 minutes if needed
After initial IV dose can be given continuous IV ~ 10 mg/hr up to 24 hours
Pharmacokinetics: diltiazem
po onset & peak
% protein bound
% excreted bile
% excreted urine
PO: excellent absorption: onset of 15 minutes peak of 30 minutes
70-80% protein bound
Excreted in bile ~ 60% Urine ~35%
Diltiazem Pharmacokinetics:
elimination half time
elimination half time metabolites
liver disease effects?
Elimination half time 4-6 hours for parent drug and 20 hours for metabolites
Liver disease may necessitate decreasing dosage.
Drug Interactions verapamil and diltiazem- cardiac effects?
Verapamil and diltiazem have depressant effects on the generation of cardiac action potentials at the SA node and slows movement of the cardiac impulses through the AV node
what can result in a patient with cardiac conduction abnormalities and concurrent administration of beta blockers or digoxin?
greater degrees of AV heart block
Drug Interactions- ccb and volatile anesthetics
Myocardial depression and peripheral vasodilation produced by volatile anesthetics could be exaggerated by similar actions of CCBs (ppt)
Per page 496- no evidence that patients being treated chronically with CCB are at increased risk for anesthesia.
Yet, it also says patients with decreased ventricular function under anesthesia show further decrease with administration of CCB.
what is the effect of calcium channel blockers in the hypovolemic patient
Exaggerated systemic hypotension if given in hypovolemic patients
can calcium channel blockers be continued until the time of surgery?
Treatment with CCBs can be continued until the time of surgery without risk of significant drug interactions, especially with respect to conduction of cardiac impulses
How do we treat overdoses of CCB
IV administration of calcium or dopamine.
Anesthetic Drugs CCB caution for what patients
CCB must be administered with caution to patients with impaired LV function or hypovolemia
Anesthetic Drugs- patients treated with beta blockers and nifedipine tolerate what?
Patients treated with beta blockers and nifedipine tolerate high dose fentanyl anesthesia and do not show evidence of additive depression of cardiac function when verapamil is infused.
Anesthetic Drugs verapamil and anesthetized patients with preexisting lv dysfunction is associated with
Conversely in anesthetized pts with preexisting LV dysfunction administration of verapamil is associated with myocardia depression and decreased CO.
Anesthetic Drugs verapamil or diltiazem during open chest surgery in patients with depressed ventricular function may be associated with …
IV administration of verapamil or diltiazem during open chest surgery in patients with depressed ventricular function and anesthetized with a volatile anesthetic may be associated with further decreases in ventricular function
treating cardiac dysrhythmias with CCB’s in anesthetized patients results in what type of blood pressure?
what does it do to the PR interval?
Treatment of cardiac dysrhythmias with CCBs in anesthetized patients produces only transient decreases in systemic blood pressure and infrequent prolongation of PR interval
Anesthetic Drugs- verapamil and digitalis or beta blockers caution. why?
Verapamil should be used cautiously in patients being treated with digitalis or beta blockers b/c of the tendency to produce AV heart block.
with chronic use of CCB and Beta blockers do you see cardiac conduction abnormalities in the periop period
no
beta agonist do what to the calcium channels in the myocardial cell membrane
Beta agonists increase the number of functioning slow calcium channels in myocardial cell membrane through a cAMP mechanism and readily counter the effects of CCBs
what is a patient risk for anesthesia if they are chronically treated with ccb
NOT at increase risk for anesthesia
What is the concern with CCB and neuromuscular blocking drugs.
CCBs potentiate the effects of depolarizing and non depolarizing NMBD.
Local anesthetic effects of verapamil and diltiazem reflecting inhibition of sodium ion flux via fast sodium channels may also contribute to the potentiation of NMBD.
explain why ccb affect ACH release..how does this affect NMBD
Antagonism of NMBD may be impaired b/c of diminished presynaptic release of acetylcholine in the presence of a CCB- because you have less calcium.
local anesthetics risk with CCB
verapamil & diltiazem have potent LA activity.
This may increase the risk of LAST when regional anesthesia is administered to patients being treated with these CCB
What is the concern with CCB & potassium infusion?
CCB’s slow inward movement of K+. hyperkalemia in pts treated with verapamil may occur after small amounts of exogenous potassium infusion.
SYMPATHOLYTICS - side effects of alpha adrenergic blockade (3)
orthostatic hypotension
baroreceptor mediated reflex tachycardia
impotence
if you dont have beta adrenergic blockade what happens to cardiac stimulation from norepinephrine
maximim expression of cardiac stimulation from norepinephrine: leads to tachycardia (typically)
what does the dextroisomer of verapamil show its activity?
The dextroisomer of verapamil has no activity at slow calcium channels and instead act on fast sodium channels accounting for local anesthetic effects of verapamil
the fast acting dextroisomer of verapamil on sodium channels means this drug is good for what
local anesthetic
how much more potent is verapamil than procaine
1.6 times as potent as procaine
what is the levoisomer of verapamil responsible for
The levoisomer of verapamil is specific for slow calcium channels and accounts for the classification as a calcium blocking drug
verapamil side effects
sa node
Negative chronotropic effect on SA node
verapamil side effects
effect on cardiac muscle
Negative inotropic effect on cardiac muscle: exaggerated in pts with preexisting LV dysfunction
verapamil side effects - coronary and systemic arteries
Moderate vasodilating effect on coronary and systemic arteries
verapamil should not be administered to 1 2 3 4
heart failure
severe bradycardia
sinus node dysfunction
atrioventricular nodal block
verapamil what effects may be enhanced in the presence of concomitant treatment with beta adrenergic antagonist.
Negative inotropic and chronotropic effects may be enhanced in the presence of concomitant tx with beta adrenergic antagonists.
verpamile & patients with WPW concerns
My precipitate dysrhythmias in pts with WPW
what drug may be useful to increase HR in presence of drug induced heart block.
Isoproterenol may be useful to increase HR in presence of drug induced heart block
metoprolol- what receptor?
beta 1 antagonist
metroprolol prevents what responses
inotropic & chronotropic
what is the concern with large doses of metoprolol
large doses become nonselective betas exerting antagonist effects at b2 receptors as well as beta 1 receptors.
what medication is used to reverse metoprolol’s beta 2 affects of increase in airway resistance
TERBUTALINE! (beta 2 agonist)
protein binding of metoprolol
10% of the drug- low
what does the beta 2 antagonist effects of propranolol do
increase peripheral vascular resistance
how does propranolol affect clearance of local anesthetics
it decreases clearance of amide LA by decreasing hepatic blood flow and inhibiting metabolism in the liver.
how does propranolol affect fentanyl
patients on chronic propranolol have decreased first pass uptake of fentanyl - 2-4x’s as much injected fentanyl enters the systemic circulation in the time period after injection
why is nadolol unique
due to its long duration of action it is only administered 1/daily
how is timolol effective in the treatment of glaucoma?
decreases intraocular pressure by decreasing production of aqueous humor
describe the protein binding of timolol
not extensive
timolol elimination half time
half time elimination is 4 hours
what are the systemic issues of timolol
systemic absorption causes resting bradycardia and hypotension refractory to atropine
how does betaxolol compare with timolol in bronchoconstriction?
betaxolol is cardioselective- less risk of airway hyperreactivity. safer to treat open angle glaucoma if patient at risk for bronchoconstriction.
What is the prominent pharmacologic effect of bisoprolol
negative chronotropic effect- treats hypertension and improves survival in patients with mild to moderate HF
What is the prominent pharmacologic effect of nebivolol
very potent and 3.5 more selective beta 1 than bisoprolol
esmolol why is this useful for intubation
beta 1 when administered prior to intubation proves reliable protection against increases in HR and BP
atenolol- which receptors
most selective beta 1 adrenergic antagonists
why do we give atenolol
patients at risk for CAD who must have non cardiac surgery decreases their mortality if administered preop
carvedilol indication for treatment
mild to moderate CHF & HTN
carvedilol which receptors
nonselective b-adrenergic receptor antagonist and alpha 1 blocking
calcium channel blocker MOA
binds to L type channel diminishing entry of calcium ions into cells.
classification of CCB phenyalkylamine
verapamil
classification of CCB benzothiazepine
diltiazem
classification of CCB dihydropyridines
nifedipine nicardipine nimodipine isradipine felodipine amlodipine
nicardipine dose for ECT. why do we use it for ECT therapy?
40 mcg/kg IV immediately before electroconvulsive therapy is effective in blunting acute hemodynamic responses to the treatment.
name three drugs that can increase VERAPAMIL unbound pharmacological effect
Lidocaine, diazepam, propranolol can increase pharmacologically active, unbound portion of the drug
what drug is first line to treat SVT
adenosine
in addition to SVT what else does diltiazem treat
essential HTN
mechanism of action of diltiazem
Blocks predominantly calcium channels of the AV node
Intermediate effects on the SA and AV nodes and vasodilating properties.
which drug has the greatest vasodilation effect of all CCB
nicardipine
where is vasodilation prominent with nicardipine
Vasodilation is prominent in the coronary arteries
nicardipine..
Of all antianginal drugs, dihyropyridine calcium channel blockers produce the greatest dilation of the peripheral arterioles
Nicardipine and nifedipine may be particularly useful in pts who have residual hyptn despite beta adrenergic blockade
IV and PO preparations
