Nagelhout CV Pharmacology - Final Flashcards
Cardiac pharm can be summarized by the treatment of which 4 conditions?
-arrhythmias
-HTN
-Angina
-HF
Clinical predictors of increased periop CV risk:
-major risk factors
-Unstable coronary syndrome (recent MI or unstable or sever angina)
-Decomp HF (Class IV)
-Significant arrhythmias (symptomatic)
-severe valve disease
Clinical predictors of increased periop CV risk:
-intermediate risk factors
-mild angina (class I-II)
-previous MI (Q waves)
-comp HF
-IDDM
-Renal insufficiency (Crt > 2)
Clinical predictors of increased periop CV risk:
-minor risk factors
-old age
-abnormal EKG (LVH, LBBB)
-rhythm other than NSR (Afib)
-low functional capacity (<4 METS)
-hx CVA
-uncontrolled systemic HTN
Surgical case risk factors for periop cardiac events
-High Risk (>5%)
-major vasc surgery
-emergent major operations
-prolonged cases with large fluid shift or blood loss
Surgical case risk factors for periop cardiac events
-Intermediate Risk (1-5%)
-carotid endarterectomy
-endovasc aortic aneurism
-H+N surgery
-intraperitoneal or intrathoracic
-ortho
-prostate surgery
Surgical case risk factors for periop cardiac events
-Minor risk (<1%)
-superficial cases
-cataract surgery
-breast surgery
-ambulatory surgery
Periop cardiac risk reduction
-pharmacologic interventions
-beta blockers (continue thru DOS, don’t start DOS)
-statins (start asap after surgery, ok to take thru DOS)
-alpha-2 blockers
-NTG NOT EFFECTIVE
Periop cardiac risk reduction
-non-pharm interventions
-PCI/CABG mixed results on efficacy for periop risk
-monitoring (PAC, CVC, 12 lead EKG, TEE) not shown to effectively prevent
Typically, drugs that depress the heart are _, whereas drugs that stimulate the heart are _
anti-arrhythmic (propofol, anesthetics)
arrhythmogenic (pressors)
Path of electricity thru heart:
_ -> _ -> _ _
SA -> AV -> Purkinje Fibers
Antiarrhythmics
-Class I
Na channel blockers
-“LA effect on heart”
- depression of depolarization
ex)
IA: Quinidine(IA), Procainamide (IA),
IB: Lidocaine, Phenytoin, Tocainide
IC: Flecainide, Propafenone
Antiarrhythmics
-Class II
Beta Blockers
ex) Esmolol, Propranolol, Metoprolol, Timolol, Carvedilol, Nadolol, Acebutolol
Antiarrhythmics
-Class III
K Channel Blockers
-prolongs AP and delays repolarization
ex) Amiodarone, Bretylium, Ibutilide, Sotalol, Dofetilide (Tikosyn)
Antiarrhythmics
-Class IV
Calcium Channel Blockers
-dominant in AV node
ex) Verapamil, Diltiazem
Antiarrhythmics
-Misc/Class V
ex) Adenosine, ATP, Digoxin, Atropine
Increased _ permeability causes depolarization above the atria.
calcium
-causes SA and AV node depolarization
If pt is having an atrial arrhythmia, treat it with a class _ antiarrhythmic.
Class IV (CCB)
Increased _ permeability causes depolarization below the atria.
sodium
-causes purkinje depolarization
If pt is having a ventricular arrhythmia, treat it with a class _ or class _ antiarrhythmic.
Class I or Class III (Na or K Channel blocker)
How do antiarrhythmics that prolong the refractory time help prevent arrhythmias?
-bc an arrhythmia can’t fire increased APs when the cell is already in the repolarization phase
-concept of absolute vs. relative refractory period
-Nag used an example of jumping up in the air and coming back down. You can’t jump again while you’re coming back down. It is akin to extending the “coming down from the air” phase.
Causes of rhythm disturbances
-General causes
-age
-LA dilation
-adrenergic stim
-drug tox
-hypoxia
-hypovolemia
-hemodynamic instability
-reperfusion after CPB
-HTN
-hypo or hyper glycemia
-pulm disease
-beta blocker withdrawal(upregulation of receptors!)
-too light anesthesia
Causes of arrhythmias
-Structural heart disease causes
-CAD
-MI
-CHD
-Cardiomyopathy(CM)
-SSS
-Long QT
-WPWS
-SB
-AVB
Causes of arrhythmias
-Transient Disturbances
-stress(metabolic or not), laryngoscopy, hypoxia, hypercarbia, device malfunctions, surgical stim, CVC
The most common arrhythmia is _
A fib
-clotting is a big risk
1st line goal of treating Afib:
rate control THEN rhythm control
-GOAL HR is < 110
For chronic rate control for Afib, consider _ first, then _
CCB
Beta blocker
T/F Avoid CCB in COPD/DMII pts.
false, avoid BETA BLOCKERS
-beta blockers stimulate the B2 receptor, can cause bronchoconstriction, vasoconstriction, and drops BG
Which is the preferred rate control medication class for Afib for a pt with systolic dysfunction or CAD?
Beta blocker-class II
Which type of medication is used as a last resort in treating Afib if other rate control drugs fail or if you want to try to convert quickly to SR?
Antiarrhythmics (Amio)
T/F We should try to convert chronic Afib pts to SR with meds intraop.
false
-don’t do this; leave them unless they’re symptomatic or acutely develop Afib in your care.
T/F A patient has an arrhythmia that originates in the purkinje system, so giving a CCB or beta blocker would work well.
false!
-only give CCB or BB if arrhythmia originates from AV node, won’t work for ventricular arrhythmias
Best way to urgently convert Afib-RVR:
DC cardioversion
Adenosine is an agonist on which receptors?
Purinergic receptors
How are Labetalol and Esmolol the same? How are they different?
Same:
Both are beta blockers
Differences:
Labetalol is an alpha blocker causing vasocontraction. Longer DOA 3-6 hrs.
Esmolol has a short duration of action of 5-10 min as a result of rapid hydrolysis in the plasma by non-specific esterase enzymes (RBC esterase). Can cause bronchoconstriction (potentially bronchospasm, care w/ asthmatics)
How early should a pt be started on a beta blocker before surgery?
7 days at least
T/F heart failure is #1 cause/risk of morbidity in anesthesia
TRUE
Why do people experience chest pain
-blockage of coronary arteries causes ischemia
-ischemia promotes release bradykinin, and other byproducts that stimulate pain receptors in heart
4 cardinal clinical features of angina
- character = pressure/heavy/squeezing pain (burning or vague pain in atypical)
- site and distribution
- provocation
- duration = builds rapidly w/in 30 seconds and lasts 5-15 minutes
T/F if chest pain lasts only 10 minutes, it’s classified as angina and if it is more than 15 mins, it is an MI
TRUE
Most heart tissue is salvageable if reperfusion occurs within ____ mins
100% within 15 mins
60% within 40 mins
first hour is key
Most angina drugs work by ________. Why?
decreasing cardiac demand because increasing supply is much harder
3 categories of angina
- stable = lesion (predictable, progressive, exertional angina, 80%); <15 mins, s/s subside
- unstable = combination of 1 & 3, angina from lesion and spasm (15% people) >15 mins, s/s persist despite rest/NTG -> MI
- variant = spasm (prinzmetal angina, 5% of people, no lesion)
Exercise induced: stable, unstable, variant
stable = yes
unstable = yes
variant = no/rarely
Occurs at rest: stable, unstable, variant
stable = no
unstable = yes
variant = yes
Night pain: stable, unstable, variant
stable = occasionally
unstable = yes
variant = early morning
T/F many sx of angina are masked by anesthesia
TRUE
ST segment: stable, unstable, variant
stable = depressed
unstable = elevated OR depressed
variant = usually elevated
List some conditions that are detrimental to myocardial oxygen balance
-decrease supply
-increase demand
decreased supply = tachycardia, hypotension, coronary artery spasm, hypocapnia, anemia, hypoxic, low 2,3 DPG
increased demand = tachycardia, increased preload, increased afterload (HTN), increased contractility
What is a strong predictor of perioperative ischemia under anesthesia
tachycardia (higher than 100 usually)
Keep patient’s heart rate less than ____ in OR for greatest benefit (and during ischemia!)
70
Why are beta blockers prescribed for ischemia when they constrict vessels?
They decrease the cardiac demand so much that the constriction is a non issue
Why does nitroglycerin make your chest pain go away
dilates veins in legs, blood pools in legs, decrease preload, demand decreases, pain goes away
First line therapy for ACUTE angina attack
Nitrates! = nitroglycerin
Cornerstone for chronic prophylaxis in angina:
beta blockers
Most effective drug class for variant angina (prinzmetal):
calcium channel blockers
Useful drugs for patients with CAD/angina AND diabetes or vascular disease
ACE inhibitors
Canadian classification of angina
I = does not occur w/normal activity but long or strenuous activity
II = slight limitation of ordinary activity, may occur w/walking or climbing stairs, in the cold, etc
III = marked limitation of ordinal physical activity, walking one block or one flight of stairs at normal pace
IV = inability to carry on ANY physical activity without discomfort, **present at rest*
Contraindications for nitrates
significant or symptomatic hypotension
Side effects of nitrates
-reduction of blood pressure
-headache
-dizziness
-palpitations
Renin release from the kidneys happens with ____ stimulation
beta 1
How do calcium channel blockers help with ischemia
-decrease oxygen demand + vasodilate coronaries =
increase supply!
T/F beta blockers are beneficial for variant angina
FALSE
CCB are drugs of choice because beta blockers will vasoconstrict and make spasm worse
Herbals that can cause bleeding
garlic, ginger, ginkgo
Elective noncardiac surgery with high risk of bleeding: how long should you wait for bare metal and drug eluting stent
bare metal = 4-6 weeks
drug eluting = 12 months
T/F patients should discontinue aspirin 7 days prior to surgery always
FALSE
not always !!! Usually only in closed space procedures, like closed eye, cranial or prostate…. otherwise continue
Stage A-D of heart failure
A = high risk of developing HF (HTN, CAD, DM, family hx of cardiomyopathy)
B = asymptomatic HF/Pre HF (previous MI, LV systolic dysfunction, asymptomatic valve disease)
C = symptomatic HF (SOBand fatigue, reduced exercise tolerance)
D = end stage HF (marked symptoms at rest despite maximal medical therapy)
Systolic vs diastolic HF
Systolic = LVEF </= 40%
Diastolic = LVEF >/= 50%
T/F little evidence to suggest drug treatment improves clinical outcomes in diastolic HF
TRUE
Why are ACE inhibitors effective in HF
they vasodilate
All patients with reduced EF should be given _____
ACE inhibitor
2nd thing patient with stable HF and reduced EF should be put on
beta blocker
Benefit of carvedilol
it vasodilates
Addition of aldosterone antagonist or diuretic for which HF patients and why
HF class II-IV with LVEF </= 35%
manage edema
Digoxin for HF
-decreases symptoms (keeps them out of hospital)
-does NOT prolong survival
5 ways we can stimulate heart (inotropic stimulation)
- beta 1 agonism (dopamine, dobutamine)
- Na/K ATPase inhibition (digitalis)
- increase calcium
- PDE III inhibition (milrinone)
- glucagon
2 things we need to control when HF patients present for surgery
- myocardial depression
- peripheral vasodilation
T/F dig levels of 0.7 can be toxic in one patient and therapeutic in another
TRUE
2 reasons patients will be on dig
- a fib
- heart failure
Explain how dig works
-blocks Na/K ATPase enzyme
-Na+ ions increase inside cell
-increased Na+ decreases the exchange of Ca++
-more Ca++ helps heart beat harder
Dig toxicity is related to ______
-potassium
-NEED to look at dig level AND potassium if you’re worried about toxicity
S/sx of dig toxicity
GI = anorexia N/V/D
Neuro = HA, fatigue, confusion, restless, convulsions, coma
Visual = (key) colored vision, green, purple, yellow, halo vision, flickering lights
Cardiac = ANY known arrhythmia !!!!
Normal dig level
anything up to 2
Half life of dig
about 36 hours
Dig and anesthesia
-you’ll almost NEVER give it. Ever.
-just figure out why they’re on it
-check their dig level (if they had one)
-check their potassium (if they have it)
-see if it’s working
If serum K is 2.4 and their dig is 1.9, are they therapeutic or toxic?
Probably toxic because potassium is low !!!!
T/F patients should hold dig 2 days prior to surgery
FALSE
keep taking it up to morning of surgery, no need to stop
Antidote to digoxin (life threatening), who gets it and how long do you give it over
digibind
someone that took greater than 10mg in adults or 4mg in children
give over 30 min period
First line therapy for management of supraventricular tachycardias
-ventricular rate control
-NO adenosine… too dangerous under anesthesia
-verapamil, esmolol, other beta blocker
T/F if you witness a patient develop a new afib, it’s okay to try to convert them
TRUE E
NOT if they come in with chronic afib, could have a clot
First line for torsades de pointes
IV magnesium sulfate
3 categories of patients to caution beta blockers in
- asthmatics = block beta 2 receptors in lungs will cause bronchoconstriction
- diabetics = block beta 2 will cause hypoglycemia
- patients with claudication
If a drug slows AV conduction velocity, it is contraindicated in patients with _____ and which classes of meds are included in this
heart block (Ca channel blockers and beta blockers)
Adenosine: class
class = IV-like or other
Esmolol: class, primary use
class = II
primary use = tachycardia
Verapamil and diltiazem: class, primary use
class = IV
primary use = atrial fib or a flutter
Stimulation of purinergic receptors cause:
-slowing of SA and AV node conduction
-bronchoconstriction
-dilation of cerebral and coronary vessels
-modulation of neuotransmitter release
Stage 1 and 2 hypertension and hypertensive crisis categories
stage 1 = SBP 130-139 or DBP 80-89
stage 2 = SBP >/= 140 or DBP >/= 90
crisis = SBP > 180 and/or DBP > 120
T/F patients with stage 1 hypertension are always prescribed medications
FALSE
only if patient has already had cardiovascular event
Difference between hypertensive urgency, emergency, and crisis
urgency = SBP >180 or DBP >120 but no associated end organ damage
emergency = SBP >180 or DBP >120 but there is acute end organ damage and immediate action is needed
crisis = encompasses both urgency and emergency and is more reflective of the high degree of BP elevation
When do the guidelines recommend starting antihypertensive meds
younger than 60 = >140/90
older than 60 = >150/90
CKD or DM @ any age = >140/90
5 groups of drugs to treat HTN
- duretics
- Ca channel blockers
- Beta blockers
- ACE inhibitors
- ARBs
Lifestyle modifications for HTN
-weight reduction
-DASH diet
-low Na+ diet
-exercise
-moderation of ETOH
_____ is first line for HTN treatment (which class)
diuretics
T/F beta blockers are no longer indicated as first line drug for HTN
TRUE
_____ is first line treatment for HF (which class)
ACE inhibitors
ACE inhibitors end in ____ and ARBs end in _____
“pril” and “sartan”
T/F diuretics result in reducing in BP because they make you pee
FALSE
we don’t really know…. (probably vasodilation from affecting potassium channels in blood vessels)
Which 2 antihypertensive drug classes are contraindicated in pregnancy
ACEs and ARBs
Describe how RAAS works
-catecholamine release stimulates beta 1 receptor in kidneys
-renin turns angiotensinogen into angiotensin I
-angiotensin I –> angiotensin II by angiotensin converting enzyme derived from lungs
-angiotensin II stimulates angiotensin receptors and causes increased thirst, vasoconstriction etc.
T/F always start with a lower dose of antiarrhythmics under anesthesia than you would outside the OR
TRUE
usually 1/2 dose to start
How come ARBs do not cause cough
they don’t mess with breakdown of bradykinin, they just bind to angiotensin receptor directly (they are more expensive though)
Current recommendations for beta blocker prior to surgery
- if they are on it prior to, then continue through perioperative period
- preop workup shows major cardiac disease, consult cardiology, maybe start beta blocker
- pts with cardiac index risk >3, it may be indicated
- DO NOT start it the day of surgery
When you inhibit angiotensin converting enzyme, you block the breakdown of ______ which will cause the patient to do what? (hint: inadvertent side effect)
bradykinin, cough!! (very unpleasant for patient)
How do beta blockers make your BP go down
- cardiac depression
- vasomotor depression
- blocking renin release in kidneys
Alpha blockers as antihypertensives: how do they work and why are they bad
-cause vasodilation (opposite of alpha agonists)
-can cause severe orthostatic hypotension
-not good for long term use: lots of side effects
What is a direct vasodilator? List the big 3.
They work directly on the vessel wall
nitroglycerin, nitroprusside, hydralazine
How do nitroglycerin and nitroprusside work
-nitric oxide is a vasodilator
-nitro group in nitroglycerin and nitroprusside act in same way that nitric oxide does: directly on vessel wall to vasodilate
How does hydralazine work
affects potassium channels in blood vessels (opens them)
For vasodilating drugs: which ones affect arteries, which veins, and which both
arterial = hydralazine (reduces afterload)
venous = nitroglycerin (reduces preload)
both = ALL other vasodilating agents
T/F nitroglycerin primarily works by dilating coronary arteries causing reduction of angina
FALSE
it dilates VEINS in the the legs, blood pools there, preload is reduced, workload on heart is less = no pain
What are nonselective beta blockers
-block beta 1 and beta 2
-can get some negative effects from beta 2 blockade, we don’t like
-most common…. standard drugs
What is a beta blocker with ISA
-beta blocker with intrinsic sympathomimetic activity (some intrinsic beta agonism)
-it doesn’t block as strongly (partial efficacy)
-still get bad effects of beta 2 blockade but not as bad as stronger beta blockers
-better for: asthmatics, peripheral vascular disease, etc
What is a beta blocker with MSA
-beta blocker with membrane stabilizing activity
-more antiarrhythmic than typical BB
-propanolol
What are beta blockers with alpha blocking activity: list 2
-just like it sounds
-alpha blocking activity to counteract vasoconstriction caused by beta 2 blockade
labetalol and carvedilol
3 effects of blocking beta 2 receptors
- bronchoconstriction
- vasoconstriction
- reduced energy/fatigue
Labetalol vs esmolol for HTN treatment in OR
labetalol = easy to titrate, 5mg at a time, vasoDILATION properties, longer duration of action, better at treating HTN (superior choice)
esmolol = nice because it wears off so quick, not nice because it wears off so quick… it is a vasoCONSTRICTOR, better at treating tachycardia
Why is esmolol so short acting
rapid hydrolysis by RBC esterases in plasma
T/F esmolol is cardioselective
TRUE AND FALSE
it is labeled as cardioselective but in practice…. no
Metabolism of nitroprussude
-by hemoglobin!!!
-turns oxyhemoglobin -> methemoglobin (steals electron)
-makes nitroprusside unstable and it breaks open releasing 5 cyanide ions and 1 nitric oxide
-free cyanide taken to liver and interacts with thiosulfate (vit B12) and rhodanese enzyme forms thiocyanate
-thiocyante is peed out from kidneys
Problem with metabolism of nitroprusside
-too much = too much free cyanide
-goes into cells and interacts with cytochrome oxidase (CO) - allows cells to use oxygen
-results in hypoxia (because oxygen can’t be used by cells!!!!!)
PINK SKIN because HIGH O2 in VENOUS SYSTEM (can’t be used by cells)
How to treat cyanide toxicity
-stop infusion of nitroprusside
-100% O2
-mechanical ventilation
-correct metabolic acidosis w/bicarb
-3% sodium nitrite 4-6mg/kg slow IV
-sodium thiosulfate 150-200mg/kg over 15 mins
-consider vit B12
What is the cause of rebound hypertension following cessation of nitroprusside
RENIN release
Best drug to treat hypertension with bradycardia and some considerations
Hydralazine
can take up to 10 mins to work…..
give 10mg or 20mg
Best drug to treat hypertension with tachycardia
Labetalol
Clonidine: how does it work and 2 considerations
presynaptic alpha 2 agonist = sympathoLYTIC
last resort drug for refractory HTN !!
most POTENT drug to show withdrawal symptoms (rebound HTN)
T/F ACEs and ARBs should be d/c before surgery (do not take the morning of)
TRUE AND FALSE
conflicting info…. may have refractory hypotension, treat with vasopressin
Dose of labetalol (weight based)
0.25-0.5mg/kg
2-4mg/min
Esmolol weight based dose
0.5-1.0mg/kg bolus then 50-300mcg/kg/min
Initial infusion rate of nitroprusside
0.3-0.5mcg/kg/min
increase by 0.5mcg/kg/min
max of 10mcg/kg/min
Weight based dosing of nitroglycerin
5-200mcg/min titrate by 5mcg/min every 5 mins
Weight based dose for nicardipine
5-15mg/hr (start at 5)
titrate by 2.5mg/hr q15-30mins
Which antihypertensive is contraindicated in liver failure
nicardipine and nitroprusside (also kidney failure)
Phentolamine weight based dose
1-5mg
repeat 5-15 mins
0.5-1mg/hr continuous infusion
what are the 2 ways to treat angina?
- increase supply of blood to the heart (more difficult to do)
- Decrease cardiac demand
Angina is caused by
imbalance between oxygen supply to the heart and oxygen demand. O2 demand is easier to manipulate than O2 supply
Strongest indicator of periop angina:
tachycardia
-causes GREATEST amount of demand, decreases supply too!
-GOAL HR <70
Number 1 tx of angina (or any degree of CAD) =
beta blockers
-vasoconstricts a bit BUT….. DRASTICALLY decreases demand (contractility and HR)
Nitrates
-MOA
decrease O2 demand via a reduction in PRELOAD and some beneficial redistribution of blood flow
