Physiologic Basis of Cardiovascular Therapy

THE PHYSIOLOGICAL BASIS OF CARDIOVASCULAR DRUG THERAPY
Carol Jacobson RN, MN

.
Drugs that keep blood from clotting:

Aspirin
Plavix
Reopro Integrilin, Aggrastat
Coumadin, Heparin
Angiomax
Drugs to treat angina:

Nitrates (nitroglycerin, isordil, etc)
Beta blockers
Calcium channel blockers
Drugs that increase

cardiac contractility:
Dobutamine
Dopamine
Milrinone
Digitalis
Drugs that dilate veins (preload

reducers):
Nitrates (nitroglycerin, etc)
ACE Inhibitors
ARBs
Aldosterone blockers
Nesiritide
Drugs that reduce blood volume:

Diuretics
ACE Inhibitors
ARBs
Aldosterone blockers
Drugs that dilate arteries and help

lower BP (afterload reducers):
Calcium channel blockers
Antihypertensive agents
ACE Inhibitors
ARBs
Milrinone
Nitroprusside (Nipride)
Nesiritide
Drugs that cause vasoconstriction and

support BP:
Neosynephrine
Levophed
High dose dopamine
Epinephrine
Vasopressin
PHYSIOLOGICAL BASIS FOR CARDIOVASCULAR DRUG THERAPY

PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEM AS RELATED TO
CARDIOVASCULAR DRUGS
HEART = the pump
ARTERIES = carry oxygenated blood to all cells in the body
VEINS = return blood to the heart
BLOOD VOLUME - must be adequate for size of the vascular space
All have to be working optimally for hemodynamic stability.
The sympathetic nervous system, the endocrine system, and various substances produced by the body
that constrict or dilate blood vessels or alter inotropic function of the heart affect how the cardiovascular
system does its job.
SYMPATHETIC NERVOUS SYSTEM

Alpha Receptors
(Arteries & Veins)
Beta Receptors
Beta 1
(Heart)
Vasoconstriction
Beta 2
(Arteries & Veins, Lungs)
heart rate
Vasodilation
contractility
Bronchodilation
conduction velocity
automaticity
Renin release
CO = HR X SV
Preload Afterload Contractility
Venous tone Body Position
Intrathoracic
pressure
Blood Volume Distribution of

blood volume
Intrapericardial
pressure
Atrial Kick
LV Function
PRELOAD
Sympathetic NS
Arteriolar Tone
SVR
Aortic Pressure
& Compliance
Aortic Stenosis
HOCM
Conditions that Alter Preload

Hypovolemia
Hemorrhage
Dehydration
Burns
Overdiuresis
Third Spacing
Hypervolemia
Overhydration
CHF
Renal Disease
Altered Size of Vascular Space
Sepsis
Spinal or Epidural Anesthesia
Anaphylaxis
Venous vasodilating drugs
Conditions that Alter Afterload

Vasodilation
Sepsis
Spinal or Epidural Anesthesia
Anaphylaxis
Arterial Vasodilating Drugs
Vasoconstriction
Hypertension
Compensatory vasoconstriction
Drugs
AFTERLOAD
SNS
Adrenals
Ventricular
Catecholamines
Muscle Mass
H+ CO2 O2
Metabolic
State
CONTRACTILITY
Drugs
Conditions that Alter Contractility

Increase
Pheocromocytoma
Hyperthyroidism
Positive Inotropic Drugs
Decrease
Myocardial Infarction
Cardiomyopathy
Ischemia
Hypoxia
Acidosis
Negative Inotropic Drugs
Drug Therapy to Alter Cardiac Output
O2 SUPPLY
O2 DEMAND
Open arteries
CO
paO2
Hb
Heart Rate
Preload
Afterload
Contractility
Demand
preload
Diuretics
NTG
ACEI
ARBs
SARAs
Morphine
Natrecor
Supply
afterload
contractility
Ca++ blockers
ACEI
ARBs
Arterial dilators
O2
Beta blockers
Ca++ blockers
Drugs to
blood flow
NTG
Ca++ blockers
ASA
Platelet inhibitors
Anticoagulants
Angiomax
Open occluded
coronary arteries
Thrombolytics
PTCA
Atherectomy
Stents
Rotablation
CABG
Renin-Angiotensin System
Renal Flood Flow
Renin release
Angiotensinogen
Angiotensin I
(converting enzyme)
Angiotensin II
Vasoconstriction
Aldosterone release
Na+ & H2O retention
BP
Organ perfusion
ACE INHIBITORS
Effects of ACE inhibitors:
Block conversion of angiotensin I to angiotensin II. This results in less vasoconstriction and less
Na+ and H2O reabsorption by the kidney. Block breakdown of bradykinin and increase
prostaglandin production.
The net effects of ACE inhibitors:
1. Preload reduction due to decreased Na+ and H2O reabsorption
2. Afterload reduction due to decreased vasoconstriction
3. levels of bradykinin (a vasodilator) due to inhibition of the enzyme that breaks down
bradykinin
4. Increased prostaglandin production = more vasodilation
5. ventricular remodeling due to filling pressures in ventricle which results in less
thinning and dilation of ventricular myocardium (especially late remodeling)
Indications for ACE Inhibitors:
Acute MI - to reduce ventricular remodeling (? prevention of reinfarction?)
CHF - mild to severe; alone or in combination with diuretics, inotropes, and vasodilators.
Hypertension - mild to moderate; alone or combined with diuretics.
Diabetic nephropathy (Captopril)
Class Side Effects of ACE Inhibitors:
1. Cough - most common SE, probably due to bradykinin and prostaglandin levels
2. Hypotension - especially in patients with low Na+ levels (<130 mEq/L), diuretic
therapy, volume depletion, or with severe CHF - all of which cause high renin levels.
Because of the risk of hypotension, a test dose is recommended before initiating
therapy.
3. Hyperkalemia - lower aldosterone levels cause K+ retention by renal tubules
especially if given with K+ sparing diuretics or in patients with renal failure.
4. Renal failure - can be precipitated by excessive hypotension, severe CHF, renal artery
stenosis (bilateral renal artery stenosis is a contraindication to ACE inhibitors).
5. Angioedema (swelling of face, tongue, larynx) - rare but very dangerous.
6. Rash - most common with captopril.
7. Neutropenia & agranulocytosis - occur with high dose captopril and may occur with
others.
Contraindications for ACE Inhibitors:
Bilateral renal artery stenosis
Renal artery stenosis of a single kidney
Immune based renal disease (especially collagen vascular disease)
Severe renal failure
Pregnancy
Combination therapy and drug interactions:

1. Diuretics - thiazides and lasix are OK and enhance hypotensive effects. Risk of K+
with K+ sparing diuretics. Diuretic dose should be decreased or DCd on initiation of
ACE inhibitor therapy and reinstituted as needed for BP or CHF control.
2. Digoxin - good combination for CHF. Captopril increases dig levels.
3. blockers - additive effects (both classes of drug renin effects).
4. Ca++ blockers - good combination for hypertension, additive effects on BP, may cause
excessive hypotension.
5. Nitrates - additive effects on preload reduction so may cause excessive hypotension
6. NSAIDS - decrease cough side effect but also decrease effects of ACE inhibitors.
7. Increase lithium levels.
Patient Teaching:
Report swelling of face, eyes, lips, tongue; difficulty breathing or swallowing
(angioedema).
Report lightheadedness. Be aware that vomiting, diarrhea, or excessive sweating can
cause hypovolemia and result in hypotension. Report to MD if nausea or vomiting.
Do not take K+ containing salt substitutes.
Report signs of infection: sore throat, fever.
Report jaundice (ACE inhibitors have been linked to hepatic necrosis, although rarely.)
Several ACE inhibitors have active metabolites that are formed by breakdown of the parent drug
(pro-drug) in the liver. Patients with liver disease may not be able to form the active metabolite
and will not respond to therapy. The metabolite is the name of the parent drug with an at on
the end: enalapril / enalaprilat.
ACE INHIBITORS
DRUG
Benazapril
(Lotensin)
[Benazaprilat]
Captopril
(Capoten)
Enalapril
(Vasotec)
[Enalaprilat]
Enalaprilat IV
PEAK
RESPONSE
2-4 hr
DURATION
1-1.5 hrs
6-12 hrs
4-6 hrs
24 hrs
24 hrs
DOSE: TEST\
MAINTENANCE
10 mg/
20-40 mg qd
One or two doses
6.25 mg/
25-50 mg bid or tid
2.5 mg/
5-40 mg qd PO
1.25 mg IV q 6 h
PRECAUTIONS
NURSING IMPLICATIONS
No effects from food.
Monitor labs: Na+, K+, creat, BUN
Initial dose 5 mg/day if renal impairment
Take one hour before meals. Take 2 hours
apart from antacids.
Sulfhydryl group may cause bad taste,
neutropenia, rash, renal disease (immune
based side effects). Neutropenia more
common in patients with collagen vascular
disease and renal failure.
Monitor BP response carefully.
Monitor labs: Na+, K+, BUN, creat, WBC.
Elevates digoxin levels.
Less risk of immune based side effects (no
sulfhydryl group).
Food does not affect absorption.
Monitor BP response
If taking diuretic or has renal failure, initial
dose 2.5 mg, adjust slowly for BP control.
7
Fosinopril
(Monopril)
[Fosinoprilat]
3 hrs
24 hrs
10 mg/
20-40 mg qd
Max 80 mg/day
Lisinopril
(Zestril,
Prinivil)
7 hrs
24 hrs
2.5 mg/
20-40 mg qd
Once a day dosing
Moexipril
(Univasc)
1.5 hr
24 hrs
3.75mg/
7.5-30 mg qd
One or two doses
1 hr
Unknown
4 mg/
4-8 mg qd
Max 16 mg/day
Quinapril
(Accupril)
[Quinaprilat]
2-6 hrs
24 hrs
10 mg/
20-80 qd
Ramipril
(Altace)
[Ramiprilat]
1-3 hrs
24 hrs
2.5 mg/
2.5-20 mg qd
Once a day dosing
Trandolapril
(Mavik)
1-10 hrs
24 hrs
1 mg/
2-4 mg/day
One or two doses
Perindopril
(Aceon)
Take antacids 2 hrs apart from drug.

No effects from food.
Monitor WBC, Na++, K+, creat, BUN
Can cause pancreatitis, hepatitis,
bronchospasm.
Less risk of immune based side effects (no
sulfhydryl group).
Not metabolized by liver.
Monitor labs: Na++, K+, creat, BUN
Take 1 hour before meals
If renal impairment, 3.75 mg/day, adjust to
maximum of 15 mg/day
If renal impairment, 2 mg/day, maximum 8
mg/day. If patient taking diuretic, 2-4
mg/day and watch BP closely for several
hours. Monitor labs: Na+, K+, creat, BUN
Take on empty stomach.
If taking diuretic start with 5 mg bid, if renal
impairment, 2.5-5 mg/day.
If renal impairment, 1.25 mg/day, max
5mg/day. Risk of hypoglycemia with insulin
or oral diabetic agents.
If hepatic or renal disease, initial dose is 0.5
mg daily.
Can cause first-degree block, bradycardia,
pancreatitis, neutropenia, leukopenia.
ANGIOTENSIN RECEPTOR BLOCKERS

Block effects of angiotensin II at receptor sites.
Blocks angiotensin II that is formed in non-ACE pathways.
Results in vasodilation and decreased volume retention like ACEI do, but no effect on
bradykinin.
Less cough and angioedema than with ACEI
Same cautions in renal impaired patients as with ACEI.
Same patient teaching: avoid potassium containing salt substitutes, get up slowly to avoid
postural hypotension, report signs of infection, report facial or lip swelling.
Angiotensin Receptor Blockers

Drug
Candesartan
(Atacand)
Peak
Response
3-4 hrs
Eprosartan
(Teveten)
Irbesartan
(Avapro)
Losartan
(Cozaar)
Telmisartan
(Micardis)
1-3 hrs
Valsartan
(Diovan)
Dose Range
8-32 mg/day
Once or twice
daily
1.5 2 hrs
400-800
mg/day
75-300 mg/day
1-4 hrs
25-100 mg/day
0.5 1 hr
20-80 mg/day
2-4 hours
80-320 mg/day
Recommended
Precautions
Initial Dose
Nursing Implications
16 mg/day
Fatigue, peripheral edema, back
pain, headache, dizziness, upper
respiratory symptoms, N&V,
abdominal pain, small in
creat, BUN, K+, liver enzymes,
bilirubin. May take with food.
May take with diuretics or other
antihypertensives.
600 mg/day
May take with food.
Same as candesartan.
150 mg /day
May take with food.
Same as candesartan
25-50 mg/day
May take with food.
Same as candesartan
40 mg / day
May take with food. Dont open
blister pack until ready to take,
discard unused scored tablets.
Same as candesartan
80 mg/day
May take with food.
Same as candesartan
Effects of Aldosterone in Heart Failure:

Aldosterone Blockers
+
Promotes retention of Na (increased preload)
Spironolactone (Aldactone) (non-selective)
Loss of Mg++ and K+
29% reduction in mortality in 3 years
Activation of SNS
compared to placebo
Inhibits parasympathetic NS
Blocks
aldosterone and androgen,
Myocardial and vascular fibrosis (contributes to
stimulates progesterone
ventricular remodeling in heart failure)
Major side effects = gynecomastia,
Dysfunction of endothelium (increases formation
sexual dysfunction,menstrual problems
of endothelin, a potent vasoconstrictor, so
Causes K+ reabsorption
increases afterload)
Selective Aldosterone Receptor Antagonists (SARAs)
Eplerenone (Inspra)
Indicated for treatment of hypertension and heart failure
1000 fold less binding to androgen receptor
100 fold less binding to progesterone receptor
Blocks aldosterone receptor without side effects associated with spironolactone
Dose (oral): for hypertension = 50 mg qd or bid; for heart failure = 25-50 mg qd
9
BETA BLOCKERS
Effects of Beta Blockers
Heart: heart rate (sinus bradycardia)
contractility ( LV function, CHF)
AV conduction (AV block)
Blood Vessels: Prevents vasodilatation in arterioles and veins so allows receptors to work
unopposed, resulting in vasoconstriction . Can worsen angina that is due to coronary vasospasm
and peripheral vascular disease.
Lungs: Prevent bronchodilation so can cause bronchospasm. Contraindicated in patients with
obstructive airway
disease.
Kidney: Decreases renin secretion so may lower BP in renin related hypertension.
Side Effects of Blockers:
Cardiac:
1. Bradycardia - depresses sinus node
2. AV block - due to conduction through AV node
3. CHF - due to contractility
4. Hypotension - due to contractility
Pulmonary:
1. Bronchoconstriction (with non-selective agents) - due to 2 blockade which prevents
bronchodilation.
2. Pulmonary edema - due to LV function
Peripheral Vascular:
1. Worsening of peripheral vascular disease due to 2 blockade which leaves receptors
unopposed and causes vasoconstriction.
Metabolic:
1. Masks signs of hypoglycemia (tachycardia, sweating, etc.) in diabetics.
2. Non selective agents decrease formation of glucose in liver and can augment
hypoglycemic action of insulin.
3. serum triglycerides
Central Nervous System:
1. Fatigue
2. Sleep disturbances: insomnia, nightmares
3. Depression
Combination Therapy and Drug Interactions
blockers can be used with diuretics, vasodilators, ACE inhibitors, digoxin for angina and
hypertension. Additive effects can occur between blockers and other drugs that slow heart rate,
decrease AV conduction, and depress contractility.
10
CLINICAL APPLICATION OF BETA BLOCKERS

USE
Hypertension
Classic Angina
Acute MI and
MI follow-up
Arrhythmias
Obstructive
Cardiomyopathy
(IHSS or HOCM)
Migraine Headaches
MECHANISM OF ACTION
heart rate = CO = BP
contractility = CO = BP
renin release in kidney causes less angiotensin I to angiotensin II
O2 demand by HR, contractility, BP
O2 supply by HR which increases diastolic filling and coronary
perfusion time
automaticity in ventricle so risk of VF early in MI
Preserves ischemic myocardium by O2 demands ( HR,
contractility, BP
automaticity so VT, VF
AV conduction so can slow ventricular response to atrial fib,
flutter, and may terminate PSVT.
contractility so reduces outflow track obstruction
HR allows longer diastolic filling time so more blood in ventricle
outflow tract obstruction
Inhibits mediated vasodilatation in cerebral vessels
Blockers in Use:
Nonselective blockers (block both 1 and 2 receptors:
Propranolol (Inderal)
Nadolol (Corgard)
Sotalol (Sotacor)
Penbutolol (Levatol)
Timolol (Blocadren)
Oxprenolol (Trasicor)
Cardioselective blockers (preferentially block 1 receptors in heart but not 2 , so have less
undesired peripheral and pulmonary effects):
Acebutolol (Sectral)
Atenolol (Tenormin)
Betaxolol (Kerlone)
Metoprolol (Lopressor)
Esmolol (Brevebloc)
Third generation blockers with vasodilating properties (ISA = intrinsic sympathomimetic
activity which causes partial stimulation of receptors and results in less depression of HR and
contractility than with other blockers)
Cartelol (Cartrol)
Pindolol (Visken)
Celiprolol (Selecor)
Combined and blocking capabilities:
Labetalol (Trandate, Normodyne)
Carvedilol (Coreg)
11
Beta Blockers
DRUG
DOSE / Half life
ADDITIONAL
INFORMATION
PRECAUTIONS
SIDE EFFECTS
Non-cardioselective Agents (block beta-1 and beta-2 receptors)
ISA (intrinsic sympathomimetic
Angina: 80 mg bid. (may Cardiac effects: decrease sinus
give 160 mg bid)
rate; decrease conduction velocity activity): partial agonist activity
that provides low-grade beta
Hypertension: 10-40 mg through AV node; decrease
stimulation at rest but acts as
contractility.
bid.
Mean dose 160-320
Anti-ischemic effects: decreased typical beta blocker when
sympathetic activity is high.
mg/day (1 or 2 doses)
HR and contractility decrease
Long acting: 80-320 mg myocardial O2 demand; decreased Drugs with ISA can cause
peripheral vasodilation and has
HR increases LV filling time and
qd
less effect on slowing HR.
coronary perfusion time.
IV: 1-6 mg
Peripheral vascular effects:
Half life 1-6 hours; long
blockade of beta-2 receptors
Cardiac side effects:
acting form 8-11 hours
bradycardia, AV block,
leaves alpha vasoconstrictor
2.5 10 mg qd
exacerbation of HF, hypotension.
receptors
unopposed
and
can
lead
Half life 5-6 hours
Pulmonary side effects:
to peripheral vasoconstriction.
increased airway resistance in
Pulmonary
effects:
blockade
of
40-80 mg qd up to 320
bronchospastic disease.
beta-2 receptors in bronchial
mg
Metabolic side effects:
smooth muscle can lead to
Half life 20-24 hours
decreased glucose metabolism
broncho10-20 mg qd
(may facilitate hypoglycemia in
constriction/bronchospasm.
diabetics), mask symptoms of
Renin-angiotensin system:
hypoglycemia;
decreases renin release
80-320 mg/day
Others: depression, sexual
(beneficial in HTN and HF).
80-240 mg bid for
dysfunction, fatigue, weight gain.
ventricular arrhythmias;
Abrupt withdrawal of beta
160 mg bid for atrial fib, Indications:
blockers can cause accelerated
Cardiovascular: angina, acute
flutter.
coronary syndromes, arrhythmias angina, myocardial infarction, or
sudden death.
(atrial, ventricular, termination
(mean 12 hours)
Contraindications: severe
and prevention of SVT,
10-20 mg bid
bradycardia, high-degree AV
congenital
LQTS),
rate
control
in
Half life 4-5 hours
block, sick sinus syndrome, overt
atrial fib/flutter, hypertension,
heart failure, asthma, severe
HOCM, neurocardiogenic
broncho-spasm, severe PAD with
syncope.
rest ischemia.
Other: migraines, anxiety states
(esp. propranolol),
Cardioselective Agents (block primarily beta-1 receptors)
400-1200 mg/day
Cardioselective agents at normal
Block beta-1 receptors so have
doses dont block beta-2
same cardiac effects as
nonselective agents (listed
receptors; therefore there are
50-100 mg qd
above).
fewer pulmonary and peripheral
IV: 5mg over 5 minutes,
vascular side effects.
repeat in 5 minutes
Same cardiovascular indications
Half life 6-7 hours
as nonselective agents (listed
Contraindications: severe
10-20 mg qd
above) plus some cardioselective bradycardia, high-degree AV
agents are indicated for treatment block, sick sinus syndrome,
2.5-40 mg qd
of HF.
decompensated heart failure.
For heart failure:
First dose: 1.25 mg,
Bisoprolol and Metoprolol SR
Week 3: 3.75 mg,
have been shown to reduce
Week 5-6: 5 mg,
mortality in HF. Beta blockers
Final dose: 10 mg
with ISA should be avoided in
HF.
50-400 mg qd (1or 2
12
Check package insert for
specific dosing information
about each drug.
Propranolol
(Inderal,
Inderal LA)
Carteolol
[ISA]
(Cartrol)
Nadolol
(Corgard)
Penbutalol
[ISA]
(Levatol)
Sotalol
(Betapace
Betapace AF)
(also Class III
antiarrhythmic)
Timolol
(Blocadren)
Acebutolol
[strong ISA]
(Sectral)
Atenolol
(Tenormin)
Betaxolol
(Kerlone)
Bisoprolol
(Zebeta)
Metoprolol
MAJOR EFFECTS/
CLINICAL USES
DRUG
DOSE / Half life

about each drug.
(Lopressor)
Metoprolol
SR
Esmolol
(Brevibloc)
Carvedilol
(Coreg)
Labetalol
(Trandate,
Normodyne)
Pindolol
[ISA]
(Visken)
Nebivolol
(Bystolic)
doses)
For heart failure:
First dose: 12-25 mg,
Week 3: 50 mg,
Week 5-6: 100 mg,
Final dose: 200 mg
Half life 3-7 hours
Only available IV.
For SVT or atrial fib:
Initial bolus of 500
mcg/kg/min over 1
minute followed by 4
minute infusion of 50
mcg/kg/min. If necessary,
rebolus and increase
infusion every 4 minutes
to 100 mcg/kg/min, then
150 mcg/kg/min, up to
300 mcg/kg/min.
For urgent HTN: 80 mg
over 30 seconds, infuse
at 150-300 mcg/kg/min.
Transfer to oral therapy
with beta blocker or
Ca++ blocker: Infusion
should be reduced by
50% 30 minutes
following the first dose
of the alternative agent.
Half life is 9 minutes.
12.5 25 mg bid
For heart failure:
First dose: 3.125 mg,
Week 3: 6.25 mg bid,
Week 5-6: 12.5 mg
bid;
Final dose: 25 mg bid
Half life 6 hours
300-600 mg qd in three
doses; max dose 2400
mg/day.
IV drip: up to 2 mg/min;
up to 300 mg for severe
HTN
Half life 6-8 hours
10-40 mg twice daily
MAJOR EFFECTS/
CLINICAL USES
Ultra short-acting cardioselective

beta blocker indicated for acute
management of SVT, rate control
in atrial fib with rapid ventricular
response, or hypertension.
ADDITIONAL
INFORMATION
PRECAUTIONS
SIDE EFFECTS
Risk of skin necrosis with

infiltration.
Full recovery from beta blockade

occurs within 30 minutes.
Vasodilatory Agents
Carvedilol and labetalol are
noncardioselective and have
alpha blocking effects that cause
vasodilation.
Side effects similar to other beta

blockers.
Carvedilol is indicated for

treatment of HF and has been
shown to reduce mortality in HF.
Labetalol is useful for
management of hypertensive
emergencies.
Nebivolol is cardioselective and
causes a nitric oxide mediated
vasodilation. Indicated for
treatment of HF.
5 mg once a day;
maximum dose 40 mg
daily.
2.5 mg if renal or hepatic
impairment
13
DRUG
DOSE / Half life

about each drug.
MAJOR EFFECTS/
CLINICAL USES
ADDITIONAL
INFORMATION
PRECAUTIONS
SIDE EFFECTS
For heart failure:

First dose: 1.25 mg qd
Week 3: 2.5 mg qd
Week 5-6: 5 mg qd
Final dose: 10 mg qd
Half life 10 hours (24
hours for metabolites)
Abbreviations used in table: AV, atrioventricular; HF, heart failure; HTN, hypertension; HOCM, hypertrophic
obstructive cardiomyopathy; IV, intravenous; LQTS, long QT syndrome; PAD, peripheral arterial disease; SVT,
supraventricular tachycardia
References:
Brunton L., Lazo J., Parker K. Goodman & Gilmans The Pharmacological Basis of Therapeutics, 11th Ed.
McGraw-Hill, 2006
Opie LH, Gersh BJ. Drugs for the Heart, 7th Ed. Philadelphia, Saunders Elsevier, 2009.
Uptodate at www.uptodate.com
CALCIUM CHANNEL BLOCKERS

Effects of Ca++ on the heart and blood vessels:
Ca++ is responsible for depolarization of the sinus node and the AV node.
Ca++ binds to actin and myosin proteins in cardiac and smooth muscle fibers to facilitate
contraction of the heart and of the smooth muscle layer of peripheral vessels.
Effects of Ca++ Channel Blockers:
Heart: heart rate (except for Nifedipine)
conduction velocity through AV node
contractility
Blood Vessels: prevents contraction of muscle layer in blood vessels.
Coronary - vasodilation (prevents coronary vasospasm)
Peripheral - vasodilation (afterload reduction)
Side Effects of Ca++ Channel Blockers:
1. Bradycardia - due to sinus rate
2. AV block - due to AV node conduction, especially with Verapamil
3. Hypotension - due to vasodilation, especially Nifedipine
4. CHF - due to contractility, especially Verapamil
5. Flushing, headaches, peripheral edema, constipation.
Combination Therapy and Drug Interactions:
1. Can be used with blockers, digoxin, for angina and hypertension but may have
additive effects.
2. Additive effects with blockers on HR and AV conduction (Verapamil &
Diltiazem).
3. Additive effects with other vasodilators (ACE inhibitors, nitrates) on BP (Nifedipine,
Diltiazem).
4. Verapamil and Diltiazem can dig levels.
14
USE
Angina:
Coronary Spasm
Classic Angina
(Diltiazem, Nifedipine)
Hypertension
(Nifedipine, Diltiazem)
Arrhythmias: SVT
Verapamil
Diltiazem
Hypertrophic
Cardiomyopathy
(Verapamil & Diltiazem)
CLINICAL USES OF Ca++ CHANNEL BLOCKERS

MECHANISM OF ACTION
Prevents vasoconstriction by decreasing amount of Ca++ available for contraction
Coronary vasodilation collateral blood flow.
MVO2 by heart rate, contractility, and afterload
CO by contractility, SVR by vasodilation
Slows AV conduction so ventricular response to atrial fib & flutter.
Can terminate AV nodal active arrhythmias (AVNRT, accessory pathway
tachycardias)
contractility lessens outflow tract obstruction.
HR allows longer diastolic filling time so more blood in ventricle outflow tract
obstruction.
Nifedipine (and similar agents) contraindicated due to more profound SVR which
increases pressure gradient between LV and aorta.
Calcium Channel Blockers

DRUG
DOSE
Check package insert for specific
dosing information about each drug.
Verapamil
(Calan,
Isoptin,
Covera,
Verelan)
Diltiazem
(Cardizem,
Cartia,
Dilacor,
Diltia,
Diltzac,
Taztia,
Tiazac)
MAJOR EFFECTS/
CLINICAL USES
Heart Rate Lowering (Nondihydropyridines)

Most potent Ca++ blocker for
Angina: Initial: 80-120 mg twice
slowing AV conduction: used for
daily (elderly or small stature: 40
ventricular rate control in atrial
mg twice daily); range: 240-480
fib/flutter.
mg/day in 3-4 divided doses
Can be used to terminate and
Hypertension: 80 mg tid; usual
prevent recurrences of SVT
dose range 80-320 mg/day in 2
(AVNRT, narrow QRS AVRT).
divided doses;
Decreases contractility and causes
Sustained release: 240 mg/day;
usual dose range 120-360 mg/day in arterial vasodilation: used to treat
chronic stable angina, unstable
1-2 divided doses;
angina, vasospastic angina, and
Covera-HS: usual dose range 120hypertension.
360 mg once daily at bedtime;
Verelan PM: usual dose range: 200- Can be used for obstructive
cardiomyopathy without resting
400 mg once daily at bedtime.
outflow tract obstruction.
IV: 2.5-5 mg (over 2 minutes);
second dose of 5-10 mg (~0.15
mg/kg) may be given 15-30 minutes Half-life 3-7 hrs; slow release forms
after the initial dose; maximum total 5-12 hours.
dose 20 mg.
Most potent Ca++ channel blocker
Angina: 120-320 mg once daily.
on slowing sinus rate; also has AV
Hypertension: 180-420 mg/day
nodal blocking effects: used for
ventricular rate control in atrial
IV: 0.25 mg/kg over 2 min. May
fib/flutter.
repeat with 0.35 mg/kg.
Can be used to terminate and
Infusion: 5-15 mg/hr for up to 24
prevent recurrences of SVT
hrs.
(AVNRT, narrow QRS AVRT).
PRECAUTIONS
Negative inotropic effect can cause

hypotension and HF.
Potential for severe AV node block
when given IV with beta blockers.
DO NOT use with wide complex
tachycardias (unless known to be
supraventricular) or in WPW
arrhythmias with wide QRS (i.e.
preexcited atrial fib or antidromic
AVRT).
Contraindications: sick sinus
syndrome, AV node disease (heart
block), WPW syndrome, heart
failure, digitalis toxicity.
Same as for verapamil with possibly

less negative inotropic effect.
15
Conversion from I.V. diltiazem to

oral diltiazem: Oral dose (mg/day)
is approximately equal to [rate
(mg/hour) x 3 + 3] x 10:
3 mg/hour = 120 mg/day
Amlodipine
(Norvasc)
Felodipine
(Plendil)
Decreases contractility and causes

arterial vasodilation: used to treat
stable effort , vasospastic angina
and hypertension.
Half-life 4-7 hrs
Dihydropyridines (DHPs)
2.5-10 mg daily; usual dose 5-10
Major advantage is slower onset
mg daily; maximum dose: 10 mg
and longer duration of action
once daily
(elimination half-life is 30-50
hours) so can be dosed once a day.
Used for treatment of hypertension,
symptomatic chronic stable angina,
vasospastic (Prinzmetal's) angina.
Safest calcium blocker in HF
patients who are fully treated with
standard drugs (i.e. beta blockers,
ACEI).
Very little if any effect on sinus or
AV node; no reflex tachycardia.
2.5-10 mg once a day; maximum 20 More vascular effects and fewer
mg/day.
cardiodepressant effects than
nifedipine.
Used for hypertension and angina.
Half life 22-27 hrs
Isradipine
(DynaCirc)
2.5-10 mg/day in 2 divided doses.

Controlled release tablet: 5 mg once
daily; maximum dose 20 mg/day
Nicardipine
(Cardene,
Cardene SR)
20 mg 3 times/day; usual range: 60120 mg/day.

IV infusion:
5 mg/hr to start.
by 2.5 mg/hr q 15 min to
maximum of 15 mg/hr if necessary.
Reduce to 3 mg/hour after response
is achieved.
Nifedipine
(Adalat,
Afeditab,
Nifediac,
Nifedical,
Procardia)
Immediate release tablets: 10-20 mg

3 times/day; maximum: 180 mg/day
Extended release forms: 30 or 60
mg once daily; maximum: 90-120
mg/day
Vascular selective, less cardiodepression.

Used for treatment of hypertension.
Half-life 8 hrs
More vascular specific and less
cardio-depression than nifedipine.
Short duration (half-life 4 hrs).
Used for hypertension and chronic
stable angina.
Can be used IV for acute BP
control.
Most potent Ca++ channel blocker

for arterial vasodilation; very little
if any effect on sinus or AV node.
Used for management of chronic
stable or vasospastic angina;
treatment of hypertension (sustained
release products only). Unlabeled
use for pulmonary hypertension and
Raynauds.
Half-life 2-5 hrs (up to 7 hrs in
elderly)
Peripheral edema, flushing,

palpitations, headache, dizziness,
erectile dysfunction, nausea,
abdominal pain, muscle cramps or
weakness.
Contraindicated in severe aortic
stenosis, obstructive
cardiomyopathy, unstable angina,
acute MI.
Same side effects as amlodipine.

Cimetidine increases felodipine
level; anticonvulsants decrease
levels; grapefruit juice inhibits
metabolism.
Same contraindications as
amlodipine, do not use in HF.
Same as amlodipine. Do not use in
HF.
Do not use for acute angina attacks

(may cause MI).
Contraindicated in obstructive
cardiomyopathy and aortic stenosis
due to peripheral dilation (causes
pressure gradient across valve).
or exacerbate HF.
Hypotension, tachycardia, and
headache, flushing, dizziness due to
vasodilation.
Do not use for acute angina attacks
(may cause MI).
Contraindicated in obstructive
cardiomyopathy and aortic stenosis
due to peripheral dilation (causes
pressure gradient across valve).
or exacerbate HF.
Hypotension, tachycardia, and
headache, flushing, dizziness due to
vasodilation.
16
Antiplatelet Drugs
Pathogenesis of ACS
Plaque rupture
Spontaneous
Induced by PCI (percutaneous coronary interventions)
When plaque ruptures, several substances are released from plaque that attract
platelets and cause platelet activation.
Platelet adhesion at site of rupture
Platelets adhere to injured area in attempt to begin repair process.
Platelet activation
When platelets come in contact with substances
released from ruptured plaque,
they become activated.
There are multiple pathways by which platelet
activation can occur:
- ADP pathway (blocked by Plavix and Effient)
- Epinephrine pathway
- Collagen pathway
- Thrombin pathway (blocked by heparin)
- Thromboxane A pathway (blocked by aspirin)
Platelet aggregation
Once activated, platelets express the IIb/IIIa receptor site which is able to hook up
with other IIb/IIIa receptors via fibrinogin binding. This allows platelets to connect to
each other. Each platelet has up to 80,000 receptor sites.
The platelet plug formed by aggregated platelets is the beginning of the clot that
eventually occludes the coronary artery.
Drugs that inhibit platelet aggregation can prevent clot formation in its earliest stages.
17
Drugs that Inhibit Platelet Activation

Plavix (clopidogrel)
Irreversibly interferes with platelet activation and aggregation by inhibiting binding of ADP
to receptors; inhibition lasts lifetime of platelet (10 days)
Indications: reduces rate of myocardial infarction, stroke, vascular deaths in patients with
recent MI, ischemic stroke, or established peripheral arterial disease; used in patients with
unstable angina, non-ST-segment elevation MI (NSTEMI), or ST-segment elevation MI
(STEMI) managed medically or with percutaneous coronary intervention (PCI) (with or
without stent) or CABG.
Loading dose: 300-600 mg PO
Maintenance dose: 75 mg daily for up to 12 months following stent placement; at least 1
month and preferably up to 1 year for medically treated NSTEMI
Discontinue at least 5 days prior to CABG whenever possible
Effient (prasugrel)
Irreversibly interferes with platelet activation and aggregation by inhibiting binding of ADP
to receptors; inhibition lasts lifetime of platelet (10 days)
More potent platelet inhibition than Plavix, but higher rate of bleeding.
Indications: reduce rate of thrombotic CV events, including stent thrombosis, in patients with
unstable angina, NSTEMI, or STEMI managed with PCI. (Not used with fibrinolytic therapy
or patients treated medically without PCI.) Not used in patients with history of TIA or stroke.
Loading dose: 60 mg PO once coronary anatomy is known, no later than 1 hour after PCI
Maintenance dose: 10 mg daily for up to 12 months
Discontinue 7 days prior to CABG whenever possible
Drugs that Inhibit Platelet Aggregation

IIb-IIIa Inhibitors
Reopro
Integrelin (eptifibatide)
Aggrastat (tirofiban)
These drugs sit on the IIb/IIIa receptor so that fibrinogen cant get
on and bind with other platelets.
Reopro causes platelet inhibition for the life of the platelet (10
days) and is not reversible.
Integrelin and Aggrastat are reversible by stopping the drug. Platelet function returns to normal
within about 6 hours after stopping drug.
18
ANTIARRHYTHMICS
Cardiac Action Potential
Site of action of antiarrhythmic drugs:

Class IV: Calcium Channel Blockers
Class III: K+ Channel Blockers

Class I:
Na+ Channel Blockers
Effects of antiarrhythmics on the action potential:
Class III:
Marked prolongation of refractory
period (prolong QT interval)
Class I:
Slow conduction (widen QRS)
Some prolongation of refractory
period (prolong QT interval)
19
Antiarrhythmic Drug Classification

Class
IA
IB
IC
Action
Sodium channel blockade
Prolong repolarization time
Slow conduction velocity
Suppress automaticity
Accelerate repolarization
Marked slowing of conduction
No effect on repolarization
ECG Effect
QRS, QT
QT
QRS
Beta blockade
HR, PR
II
III
IV
Potassium channel blockade

Prolong repolarization time
QT
Calcium channel blockade
HR, PR
Examples
Quinidine
Procainamide
Disopyramide
Lidocaine
Tocainide
Mexiletine
Flecainide
Propafenone
Moricizine (has IA &
IB effects too)
olols
Atenolol, esmolol,
metoprolol,
propranolol, others
Amiodarone
Dronedarone
Sotalol
Ibutilide
Dofetilide
Verapamil
Diltiazem
20
DYSLIPIDEMIAS
Adult Treatment Panel Classification (mg/dl)
1. Total Cholesterol (the lower the better)
< 200 = desirable
200 239 = borderline high
> 240 = high
2. LDL Cholesterol (the lower the better)
< 100 = optimal
100 129 = near or above optimal
160 189 = high
> 190 = very high
3. HDL Cholesterol (the higher the better)
< 40 = low
> 60 = high (desirable)
4. Triglycerides (lower is better)
< 150 = normal
200 499 = high
> 500 = very high
Cholesterol Risk
1. Total cholesterol > 200 mg/dl
2. LDL > 100 mg/dl (depending on number of risk factors for CHD)
a. LDL is the trigger for therapy
3. HDL < 40 mg/dl
Goals of LDL Lowering Therapy
1. If patient has CHD or CHD risk equivalent = goal is LDL < 100 mg/dl (< 70 is
reasonable goal)
a. Risk equivalent = risk factors that place patient at same risk as if they already
have CHD
1) Diabetes
2) Symptomatic carotid artery disease
3) Peripheral arterial disease
4) Abdominal aortic aneurysm
5) Chronic renal insufficiency
2. If patient has 2 or more risk factors = goal is LDL < 130 mg/dl
3. If patient has 0-1 risk factors = goal is LDL < 160 mg/dl
21
DRUGS FOR DYSLIPIDEMIAS

Mechanism of Action
Drug
Bile acid
binding resins.
Cholestyramine
(Questran)
Colestepol
(Colestid)
Colesevelam
Nicotinic Acid
Niacin
Niacin XR
HMG CoA
reductase
inhibitors:
Atorvastatin
(Lipitor)
Fluvastatin
(Lescol)
Lovastatin
(Mevacor)
Pravastatin
(Pravachol)
Rosuvastatin
(Crestor)
Simvastatin
(Zocor)
Fibric Acid
Derivatives:
Gemfibrozil
(Lopid)
Fenofibrate
(Tricor, Lipantil)
Effect on Lipids
Dose
Precautions
Comments
Cholestyramine:
8-16 Gm/day,
increase slowly q 2-4
weeks to max. of 24
Gm/day in 2-4
divided doses
(Powder or candy
bar)
Colestipol:
15-30 Gm/day in 2-4
divided doses.
(Powder)
Colesevelam:
3.75 g/day
Initial: 100 mg 2-3
times/day
Increase to 1 g/ tid
Side Effects: Mainly GI:

heartburn, constipation,
flatulence, cramps.
Bind bile acids in

intestine, excreted in
feces. Causes increased
conversion of cholesterol
to bile acids in liver, so
cholesterol levels in
blood.
Lowers LDL by 1530%
Blocks release of free

fatty acids from adipose
tissue, resulting in less
hepatic conversion of
FFA into triglycerides.
Results in production
of LDL.
Lowers LDL by 1025%
Suppress synthesis of
cholesterol in liver which
promotes clearance of
cholesterol from
bloodstream.
Lowers LDL by 2060%
Take in evening or
with dinner
Lowers triglycerides
by 10-33%
Atorvastatin: 10-80
mg/day
Fluvastatin: 20-80
mg
Lovastatin: 20-80 mg
/day
Pravastatin: 10-80
mg/day
Little effect on HDL

No effect on TG
Lowers triglycerides
by 25-30%
Raises HDL by 1535%
Increases HDL by 510%
Increase plasma
lipoprotein lipase activity
which enhances lipolysis
of VLDL and lowers
triglyceride levels.
Niacin XR: 1 g HS
Lower triglycerides
by 40-50% (major
indication)
Lower LDL 5-20%
if triglycerides
normal, but may
LDL if triglycerides
high.
Rosuvastatin: 5-40
mg/day
Simvastatin: 20-80
mg/day
Gemfibrozil: 600 mg
bid
Fenofibrate: 200
mg/day
Other meds should be

taken 1 hr before or 4-6
hrs after these drugs
(bind with digoxin,
thyroxine, coumadin,
thiazides)
Side Effects:
Vasodilation resulting in
flushing, hypotension,
dizziness, tachycardia.
Brown skin
discoloration, itching. GI
symptoms,
hyperglycemia, liver
toxicity.
Side Effects: GI
complaints, headaches.
Liver enzyme elevation.
Myopathies - muscle
aching, weakness
Myositis (esp., when
combined with fibrates)
= myoglobinuria and
renal failure.
Side Effects: Liver

enzyme elevations.
Myositis (increased risk
when combined with a
statin) = myoglobinuria
and renal failure.
Pancreatitis at high doses
Occasional bone marrow
inhibition
HDL 15-30%
22
Drugs Used for Heart Rate and Rhythm Control

DRUG / CLASS
INDICATION
Adenosine (Adenocard)
First line therapy to

terminate AV nodal active
SVTs: AV Nodal Reentry
(AVNRT) or AV Reentry
Tachycardia (AVRT) in
WPW syndrome. Does
not prevent recurrences.
Class IV-like: opens K+

channels, indirectly inhibits
Ca++ channels
Can be diagnostic in AV
nodal passive rhythms by
causing AV block and
revealing underlying atrial
mechanism, and in wide
complex tachycardias of
uncertain origin.
DOSE / ADMINISTRATION
Therapeutic Level/ Half Life
6 mg given very rapidly IV
followed by rapid saline flush.
May follow with 12 mg if needed
and repeat 12 mg if no effect.
Reduce initial dose to 3 mg if
patient taking verapamil,
diltiazem, beta blockers or
dipyridamole.
Half life = 9 seconds
Class III primarily, but has

strong class I (Na+ blocker)
and moderate class II (beta
blocker) & class IV (calcium
blocker) activity
COMMENTS
Acute onset of AV block usually

lasting a few seconds. May result in
brief period of asystole or bradycardia
which is not responsive to atropine.
Very short half life so side effects are

transient.
Warn patients about side effects before
giving drug especially dyspnea. It
may be helpful to have patient take a
deep breath while injecting drug to
sensation of dyspnea.
Should not be used when arrhythmia is
known to be atrial fib or flutter.
Monitor ECG during administration
and be prepared for cardioversion.
May accelerate accessory pathway
conduction and should not be used
when antegrade conduction is occurring
over accessory pathway.
May rarely accelerate ventricular rate in
atrial flutter.
Contraindications: asthma, second or
third degree AV block, sick sinus
syndrome.
Drug interactions:
Theophylline (and related drugs) and
caffeine antagonize effects of adenosine
and make it ineffective.
Dipyridamole and carbamazepine may
potentiate effects of adenosine.
Give with meals to GI intolerance.
Baseline chest X-ray, renal, liver,
pulmonary, thyroid function tests.
Takes several weeks to achieve
therapeutic blood levels and for effects
to decrease after stopping drug.
Is not dialyzable.
Monitor K+ and Mg++ levels.
Monitor QTc interval.
Flushing, hot flash, acute dyspnea,

chest pressure. Side effects are
transient due to short half life of drug.
May have proarrhythmic effects:
Torsades can occur in patients who are
susceptible to bradycardia-dependent
arrhythmias; degeneration of SVT or
atrial flutter in to atrial fibrillation;
atrial and ventricular ectopy.
Can precipitate bronchoconstriction in
asthmatic patients that can last for 30
minutes.
VT arising in the right

ventricular outflow tract
that is due to afterdepolarizations may
terminate with adenosine.
Amiodarone
(Cordarone)
SIDE EFFECTS
Main indication: lifethreatening ventricular

arrhythmias ( recurrent
VF, recurrent hemodynamically unstable VT).
Useful to decrease the
number of ICD shocks.
Use as low a dose as possible to

decrease multiple side effects.
Also used for conversion

of atrial fib to sinus
rhythm and prevention of
recurrences of paroxysmal
atrial fib or flutter.
IV for VT: 1000 mg over first 24

hours given as follows:
First rapid infusion: 150 mg over
first 10 min (15 mg/min) [Add
3ml (150mg) to 100ml D5W]
PO: 800-1600 mg qd in divided

doses for 1-2 weeks, then 400-800
mg qd for 1-3 weeks.
Maintenance: 100-400 mg/day.
Bradycardia, heart block, QT

prolongation (TdP is rare unless other
risk factors are present).
Hypotension with IV form.
Pulmonary: pneumonitis, pulmonary
fibrosis (fatal in 10%).
Thyroid dysfunction (hypo and hyper).
Hepatotoxicity (elevated liver
enzymes, hepatitis, cirrhosis).
Drug interactions:
Additive proarrhythmic effects with
other drugs that prolong QT interval
23
DRUG / CLASS
INDICATION
Slows conduction through

accessory pathways in
atrial fib or AVRT.
May be safer for patients
with structural heart
disease and/or heart
failure than other antiarrhythmics.
Infuse 100ml over 10minutes.
Followed by slow infusion: 360
mg over next 6 hours (1
mg/min) [Add 18ml (900mg) to
500ml D5W] Infuse at 33.6ml/hr
Maintenance infusion: 540 mg
over next 18 hours (0.5
mg/min). [Decrease rate of slow
loading infusion to 0.5 mg/min]
Infuse at 16.8ml/hr
May continue with 0.5 mg/min for
2-3 weeks if needed. Central line
recommended for long term
infusions.
If breakthrough VT occurs, may
give supplemental doses of 150
mg over 10 min. [150 mg added
to 100 ml D5W]
For shock-resistant cardiac
arrest: IV bolus of 5 mg/kg, may
repeat with 2.5 mg/kg if needed.
IV for atrial fib:
5mg/kg over 20 minutes, then
500-1000 mg over 24 hours, then
0.5 mg/min. Start oral during
loading if possible.
IV to PO transition:
Duration of IV
PO dose
< 1 week
800-1600mg qd
1-3 weeks
600-800 mg qd
> 3 weeks
400 mg qd
SIDE EFFECTS
Central nervous system: muscle
weakness, peripheral neuropathy,
headache, ataxia, tremors, impaired
memory, bad dreams.
Miscellaneous: nausea, testicular
dysfunction, corneal microdeposits,
photo-sensitivity, blue skin
discoloration
COMMENTS
(1A antiarrhythmics, phenothiazines,
tricyclic anti-depressants, thiazide
diuretics, sotalol).
protime with warfarin, may cause
bleeding. Warfarin dose should be
decreased by 1/3 and retest INR.
serum levels of digoxin (can cause
dig toxicity), quinidine, procainamide,
cyclosporine. May double flecainide
level. Can cause myopathy and
rhabdomyolysis with high dose
simvastatin (>20 mg/day).
Cimetidine serum amiodarone levels.
Cholestyramine and phenytoin
(Dilantin) serum amiodarone levels.
Additive effects on HR and AV
conduction with beta blockers and Ca++
blockers.
Special precautions with IV form:
Physically incompatible with
aminophylline, heparin, cefamandole,
cefazolin, mezlocillin, sodium bicarb.
Must be delivered using a volumetric
pump (not drop counter) because drop
size is altered by drug.
Therapeutic level = 1 - 2.5

mcg/ml
Very long half-life (26-107 days,
average 53 days), up to 6 months.
24
DRUG / CLASS
INDICATION
Atenolol (Tenormin)
Beta blocker
(cardioselective)
Ventricular rate control in

atrial fib/flutter.
Slow conduction through
AV node in AVNRT and
AVRT; can terminate or
prevent recurrences.
Atropine
Anticholinergic,
parasympatholytic
Digoxin (Lanoxin)
cardiac glycoside
Beta blockers are

effective ventricular antiarrhythmics.
Treatment of symptomatic
bradycardia (sinus,
junctional, AV block) and
asystole.
Major indication is
ventricular rate control in
chronic atrial fibrilation in
patients with HF.
Use in NSR controversial.
Also has inotropic effects
in HF.
Plasma concentration falls by
50% in 3-10 days when DCd, but
tissue stores deplete very slowly.
Initial dose: 12.5 25 mg PO qd
Maintenance dose: 50-100 mg PO
qd (can be higher for treating
angina).
IV: 5 mg over 5 minutes, may
repeat in 5 minutes.
Beta blocking plasma
concentration = 0.2-5 mcg/ml
Half life = 6-7 hours
Symptomatic bradycardia: 0.5 mg
IV. May repeat q 3-5 minutes to
total of 3 mg .
Asystole: 1 mg IV, repeat q 3-5
minutes to total of 3 mg.
May be given down ET tube
during cardiac arrest if no IV
available: use 2 to 2.5 mg.
Trend toward lower doses:
PO loading dose: 0.25 mg/day
(0.5 mg q 8 hours for one day still
sometimes used for severely
decompensated HF)
PO maintenance dose: 0.125mg
qd.
IV loading dose: 0.5-1 mg divided
into 3 or 4 doses given at 4-8 hour
intervals.
Use half dose in patients >70 y
and with renal failure.
Therapeutic level = 0.5-1.5 ng/ml
Half life = 36 hours
SIDE EFFECTS
COMMENTS
Hypotension, bradycardia, AV blocks.
Cardioselective beta blocker used

primarily for hypertension and angina.
Drug interactions:
Additive effects on HR, AV
conduction, BP, and potential for HF
when given with negative inotropic
drugs, Ca++ blockers, digoxin.
Contraindications: severe bradycardia,
heart block, cardiogenic shock, overt
untreated HF, severe asthma or severe
claudication.
Doses < 0.5 mg may cause paradoxical
bradycardia.
Causes pupils to dilate (significant
when checking pupils during cardiac
arrest situation).
Drug interactions:
Incompatible with aminophylline,
metaraminol, norepinephrine,
pentobarbitol, sodium bicarbonate.
Cold extremities, fatigue, dreams,

worsening claudication,
bronchospasm, (less likely than
cardioselective agents to cause these
side effects).
May cause erectile dysfunction,
depression, and increase incidence of
diabetes.
CV: tachycardia, chest pain,
ventricular tachycardia/fibrillation
(rare)
CNS: drowsiness, confusion,
dizziness, insomnia, nervousness
GI: dry mouth, GI motility,
constipation, nausea
Other: urinary retention, hot flushed
skin, rash
CV: bradycardia, AV block
Digoxin Toxicity: sinus exit block, AV
block, atrial tachycardia with block,
bidirectional VT, fascicular
tachycardia, accelerated junctional
rhythm, regularization the ventricular
response to atrial fib. Visual
disturbances (halo vision), anorexia,
nausea, vomiting, malaise, headache,
weakness, disorientation, vertigo,
seizures.
Narrow therapeutic-toxic ratio.

Contraindicated in patients with WPW,
HOCM, heart block, sick sinus
syndrome.
Digoxin toxicity is more common in the
presence of hypokalemia, renal failure,
pulmonary or thyroid disease and in
older people.
Drug interactions:
The following drugs digoxin levels:
cholestyramine, antacids, kaopectate,
neomycin, sulfasalazine, ParaAminosalicylate Sodium, rifampin,
metoclopramide (Reglan).
The following drugs digoxin levels:
25
DRUG / CLASS
Diltiazem (Cardizem)
Ca++ channel blocker
INDICATION

atrial fib/flutter.
AVRT; can terminate and
PO: 120-360 mg/day in divided

doses.
IV: 0.25 mg/kg bolus over 2 min.
If needed, repeat with 0.35 mg/kg
after 15 minutes.
IV infusion: 5-15 mg/hr for up to
24 hours.
SIDE EFFECTS
Bradycardia, heart block, sinus node

dysfunction, HF, hypotension,
dizziness, flushing, edema, headache,
nausea.
Less depression of contractility than
with verapamil but watch for HF.
Therapeutic level = 50-300 ng/ml
Disopyramide
(Norpace)
Class IA antiarrhythmic
Dofetilide (Tikosyn)
Class III antiarrhythmic
Effective in preventing
atrial fib and flutter.
Effective in treating PVCs
and VT but not often used
due to proarrhythmic
effects.
accessory pathways.
Conversion of atrial
fibrillation or flutter to
NSR and maintenance of
NSR after conversion.
Effective against VT but
not licensed for
ventricular arrhythmias.

Total daily dose = 400-800 mg in
divided doses, usually 100-200
mg q6h PO.
SR form = 300mg q12h.
Therapeutic level = 3-6 mcg/ml
Half life = 8 hours
Dose based on creatinine
clearance: if normal renal
function, 500 g bid.
If abnormal renal function, 250 g
bid.
Do not give if creatinine clearance
< 20 ml/min.
Anticholinergic effects: dry mouth,

urinary retention, constipation,
precipitation or exacerbation of
glaucoma, increased conduction
through AV node.
CV: marked negative inotropic effects,
HF, prolongs QT interval,
proarrhythmic (less than quinidine or
procainamide), hypotension.
TdP (about 3% incidence), usually
occurs within 3 days after initiating
therapy.
Has no negative inotropic effects and
does not lower BP.
Half life = 9.5 hours
Dronedarone (Multaq)
Prevention of atrial
400 mg bid with meals (no
Fewer side effects than amiodarone.
COMMENTS
Erythromycin, tetracycline, quinidine,
amiodarone, verapamil, propafenone,
spironolactone, nicardipine,
indomethacin.
Contraindicated in patients with wide
QRS tachycardia (unless known to be
supraventricular in origin), sick sinus
syndrome, heart block, WPW, post MI
with EF < 40%.
Drug interactions:
Additive effects on HR, AV conduction
with amiodarone, beta blockers,
digoxin. Decreased BP, and potential
for HF when given with negative
inotropic drugs, beta blockers.
Monitor QT interval and watch for TdP
Drug Interactions:
May potentiate effect of coumadin.
Additive negative inotropic effects with
beta blockers or Ca++ blockers.
Phenobarbitol, dilantin, rifampin
disopyramide levels.
Quinidine disopyramide level.
Patient must be on telemetry during
initiation of therapy or with increase in
dosage (recommendation is for 3 days
monitoring).
Monitor QT interval every 2-3 hours: if
QTc increases > 15% or if QTc is >
500 ms, reduce dose. If QTc after
second dose is > 500 ms, drug should
be discontinued.
Drug Interactions:
Drugs that increase dofetilide levels
include verapamil, ketoconazole,
cimetidine, macrolide antibiotics,
ritonavir, prochlorperazine, magesterol.
Maintain normal K+ and Mg++ levels.
Contraindications: Severe or recently
26
DRUG / CLASS
Class III antiarrhythmic with
Class I, II and IV effects
similar to amiodarone
Epinephrine (Adrenalin)
Esmolol (Brevebloc)
Ultra- short-acting
cardioselective beta blocker
INDICATION
fibrillation/flutter
recurrences.
Can reduce incidence of
VF (not licensed for
ventricular arrhythmias).
Treatment of any cardiac

arrest situation requiring
CPR: VF, pulseless VT,
asystole, PEA
Rapid control of
ventricular rate in atrial
fib/flutter.
Also used for hypertensive emergencies.
grapefruit juice)
Half-life: 13-19 hours
SIDE EFFECTS
Diarrhea, nausea, bradycardia, rash,
and QT-interval prolongation (no
incidence of TdP in study patients).
Increases creatinine level.
1 mg IV bolus every 3-5 minutes

during resuscitation efforts.
May be given via ET tube if IV
access not available: use 2 to 2.5
mg
May be infused at 210 mcg/min
to maintain BP during
symptomatic bradycardia.
CV: tachycardia, hypertension,

arrhythmias, angina
CNS: restlessness, headache, tremor,
stroke
Other: nausea, urine output, transient
tachypnea
Loading infusion: 500

mcg/Kg/min over 1 min.
Maintenance infusion:
50 mcg/kg/min over 4 minutes; if
ineffective, repeat loading dose
and infuse at 100 mcg/kg/min for
4 minutes; if necessary repeat
loading dose and infuse up to 300
mcg/kg/min.
Hypotension, peripheral ischemia,

confusion, thrombophlebitis, skin
necrosis from infiltration. Bradycardia,
Bronchospasm.
claudication.
COMMENTS
decompensated HF; second- or third
degree heart block, or sick sinus
syndrome (except in patients with a
functioning pacemaker); bradycardia
<50 bpm; concomitant use of strong
CYP3A4 inhibitors (eg, ketoconazole,
itraconazole, voriconazole,
cyclosporine, telithromycin,
clarithromycin, nefazodone, or
ritonavir); concomitant use of drugs or
herbal products known to prolong the
QT interval increasing the risk for
torsade de pointes (eg, phenothiazine
antipsychotics, tricyclic antidepressants, certain oral macrolide
antibiotics, or class I and III antiarrhythmics); QTc interval >500 msec
or PR interval >280 msec; severe
hepatic impairment; pregnancy;
breastfeeding.
Monitor K+ and Mg++ levels
Drug Interactions:
Has potential to cause arrhythmias
when given with digoxin, other
sympathomimetic agents.
Physically incompatible with
aminophylline, ampicillin, cephapirin,
sodium bicarbonate and other alkaline
solutions.
Short half life so effects reversed within
10-20 minutes after stopping drug.
Drug interactions:
May increase digoxin level.
Incompatible with sodium bicarbonate,
27
DRUG / CLASS
INDICATION
Use dosing chart that comes with
drug.
SIDE EFFECTS
COMMENTS
lasix, valium, thiopental.
Risk of skin necrosis if infiltrates.
Half life of 9 minutes

Flecainide (Tambocor)
Class IC antiarrhythmic
In absence of structural
heart disease:
Conversion of atrial fib or
flutter to NSR &
maintenance of NSR.
Treatment of SVTs:
AVNRT, AVRT.
100-400 mg PO q 12 h
Therapeutic level = 0.2-1 mcg/ml
(Plasma levels do not correlate
with efficacy but incidence of CV
toxicity greater when levels >
1mcg/ml)
CV: Marked proarrhythmia, marked

negative inotropic effects (HF),
bradycardia, heart block.
CNS: Blurred vision, dizziness,
flushing, ringing ears, drowsiness,
headache.
Other: bad taste, constipation, edema,
abdominal pain

accessory pathways in
WPW
Life-threatening sustained
VT.
Ibutilide (Corvert)
Conversion of atrial fib or

flutter to NSR.
IV infusion of 1 mg over 10
minutes.
May repeat same dose in 10
minutes if needed.
Hypotension, VT, bundle branch

block, AV block, torsades, nausea,
headache.
In patients < 60 Kg: 0.01 mg/kg

Half life = 6 hours (2-12 hours)
Lidocaine
Class IB antiarrhythmic
Treatment of ventricular
arrhythmias: VT, VF
Effective for PVC
suppression but PVC
suppression not usually
For VT: 1 mg/kg IV bolus over 3

minutes followed by infusion at 24 mg/min. Repeat bolus of 0.5
mg/kg in 10 minutes to maintain
therapeutic level. May repeat to
total of 3 mg/kg.
Side effects relatively rare.

CNS: lightheadedness, dizziness,
tremor, agitation, tinnitus, blurred
vision, convulsions, respiratory
depression and arrest.
CV: bradycardia, asystole,
Contraindications: structural heart

disease, bifascicular block (if no
pacemaker), sick sinus syndrome, LV
dysfunction, post MI.
Safest in patients with normal LV
function.
Prolongs QT interval, potential for
proarrhythmia (TdP).
Monitor for HF.
Full therapeutic effect may take up to 5
days.
Drug Interactions:
digoxin levels.
Cimetidine, amiodarone, propranolol
increase flecainide levels.
Additive negative inotropic effects with
beta blockers, Ca++ blockers,
disopyramide.
Prolongs QT interval and may cause
TdP. Proarrhythmia usually occurs
within 40 minutes. Monitor ECG
continuously during administration and
at least 4 hours after.
Conversion to NSR usually occurs
within 20-40 minutes of infusion.
Correct hypokalemia and
hypomagnesemia.
Drug interactions:
Do not give other class I or class III
agents within 4 hours.
dose to half if liver disease or low
liver blood flow (shock, liver disease).
Drug Interactions:
Beta blockers and cimetidine increase
lidocaine levels.
Glucagon and isoproterenol may
28
DRUG / CLASS
INDICATION
recommended.
SIDE EFFECTS
COMMENTS
hypotension, shock
increase liver blood flow and

lidocaine levels.
CV: hypotension, bradycardia, heart

block, cardiac arrest.
CNS: Weakness, drowsiness,
peripheral neuromuscular blockade,
absent deep tendon reflexes.
Other: respiratory rate, respiratory
paralysis.
Drug Interactions:
CNS depression when used with
general anesthetics, barbiturates, opiate
analgesics.
Additive effects with neuromuscular
blocking agents.
Incompatible with calcium, sodium
bicarbonate, ciprofloxacin.
Hypotension, bradycardia, AV block
Drug interactions:
claudication.
Often given in combination with other
antiarrhythmics with increased
effectiveness (quinidine, disopyramide,
propafenone, amiodarone)
Drug interactions:
Phenobarbitol, dilantin, rifampin
mexiletine levels.
Cimetidine mexiletine levels.
For VF or pulseless VT: 1.5

mg/kg IV bolus. May repeat with
same amount and follow with
infusion at 2-4 mg/min.
May be given down ET tube
during cardiac arrest if no IV
available.
Magnesium
Metoprolol (Lopressor)
Cardioselective beta blocker
May be useful for

treatment or prevention of
both supraventricular and
ventricular arrhythmias
following MI or cardiac
surgery.
Treatment of choice for
TdP and VF or pulseless
VT refractory to other
drugs.
atrial fib/flutter.
AVRT.
Half life of bolus = 10 minutes

Half life once therapeutic level
reached = 1.5-2 hours
For TdP:
Pulseless: 1-2 g over 5-20
minutes. With pulse: 1-2 g over 560 minutes.
Infusion of 0.5 1 gm/hr for up
to 24 hours.
PO: 50-200 mg bid.

IV: 2.5-5 mg q 5 minutes up to 15
mg.
concentration = 50-100 ng/ml
Mexiletine (Mexitil)
Class IB antiarrhythmic
Acute and chronic

treatment of symptomatic
VT.
Initial: 100-400 mg every 8 hours.

Usual dose: 200-300 mg every 8
hours.
Therapeutic level = 1 2 mcg/ml
GI: nausea, vomiting, heartburn,

anorexia, diarrhea.
CNS: tremor, dizziness, ataxia, slurred
speech, paresthesias, seizures,
hallucinations, emotional instability,
insomnia, memory impairment.
CV: bradycardia, hypotension, HF,
proarrhythmia (rare)
29
DRUG / CLASS
Procainamide (Pronestyl)
INDICATION
Conversion of atrial fib to

sinus & maintenance of
NSR.
accessory pathways.
Effective in terminating
and preventing VT.
but not recommended due
to proarrhythmic effects.
Oral forms no longer available in

US.
IV loading dose: 17 mg/kg at 25
mg/min. If rapid loading is
needed, give 100mg doses over 5
minutes to total of 1gm in first
hour.
IV drip 2-4 mg/min
Half life = 3.5 hours.
Propafenone (Rhythmol)
Class IC antiarrhythmic,
also has beta blocker effects
Only use in patients

without structural heart
disease.
Active metabolite is NAPA:

therapeutic level = 9-12 mg/L
150-300 mg tid.
IV not available in US.

NSR.
accessory pathways.
Life-threatening sustained
VT.
Propranolol (Inderal)
Non-cardioselective beta
blocker.

atrial fib/flutter.
Treatment of SVTs (slow
AV node conduction):
AVNRT, AVRT
Effective in some types of
VT: exercise induced,
Half life = 2-10 hours in normal

metabolizers, up to 32 hours in
slow metabolizers.
PO: 40-240 mg qd in divided

doses.
IV: 1-6 mg (0.15 mg/kg) at rate of
1 mg/min
concentration = 50-100 ng/ml
SIDE EFFECTS
COMMENTS
Other: thrombocytopenia, fever, rash,

positive ANA.
GI: nausea, vomiting, anorexia
CV: bradycardia, heart block,
proarrhythmia (less than with
quinidine). Prolongs QT interval, can
cause TdP. Hypotension with IV use.
CNS: headache, insomnia, dizziness,
psychosis, hallucinations, depression.
Lupus-like syndrome with long-term
use (so oral forms no longer available
in US).
Other: rash, fever, swollen joints,
agranulocytosis, pancytopenia.
Mexiletine theophylline levels.
GI: nausea, anorexia, constipation,

metallic taste
CNS: dizziness, headache, blurred
vision
CV: HF, bradycardia, AV block,
bundle branch block, proarrhythmia.
Watch for proarrhythmia.

Drug interactions:
digoxin levels. Potentiates coumadin.
Has mild beta blocker and Ca++ blocker
effects.
cyclosporin levels.
Quinidine and cimetidine increase
propafenone levels.
Contraindications: sinoatrial, AV, and
intraventricular disorders of impulse
generation and/or conduction (except in
patients with a functioning artificial
pacemaker); sinus bradycardia;
cardiogenic shock; uncompensated
cardiac failure; hypotension;
bronchospastic disorders; uncorrected
electrolyte abnormalities.
Drug interactions:
CV: bradycardia, heart block,

hypotension, HF
GI: Nausea, vomiting, stomach
discomfort, constipation, diarrhea
CNS: dreams, hallucinations,
insomnia, depression
Other: bronchospasm, exacerbation of
Monitor QT interval, QRS width, PR.

Monitor NAPA level (active
metabolite).
Watch for hypotension with IV use.
Drug Interactions:
Amiodarone, cimetadine, ranitidine
increase procainamide levels.
Alcohol procainamide levels.
Additive effects on conduction system
disease when given with other class IA,
class IC, tricyclic antidepressants, or
Ca++ blockers.
30
DRUG / CLASS
Quinidine
Sotalol (Betapace,
(Betapace AF)
Has beta blocker effects
INDICATION
digitalis induced.
Effective in reducing
incidence of VF and
sudden death post MI.
Rarely used anymore.
NSR.
May be used for other
SVTs: atrial tachycardia,
AVNRT, accessory
pathways.
and VT but not
recommended due to
proarrhythmic effects.
NSR & maintenance of
NSR.
accessory pathways.
Life-threatening VT, VF.
Sulfate: 200-400 mg q 6-8 h

Gluconate: 324 mg SR tabs, 1-2 q
8-12 h
Initial: 80 mg twice daily; dose

may be increased gradually to
240-320 mg/day; allow 3 days
between dosing increments
Usual range: 160-320 mg daily in
two divided doses. Some patients
may need 480-640 mg/day.
Betapace AF (for atrial
fib/flutter):
Initial: 80 mg twice daily.
If the initial dose does not reduce
the frequency of relapses of atrial
fibrillation/flutter and is tolerated
without excessive QT
prolongation (not >520 msec)
after 3 days, the dose may be
increased to 120 mg twice daily.
This may be further increased to
160 mg twice daily if response is
inadequate and QT prolongation
is not excessive.
SIDE EFFECTS
COMMENTS
peripheral vascular disease, fatigue,

hypoglycemia, impotence

claudication.
GI: nausea, diarrhea, abdominal pain.

CV: hypotension, bradycardia,
tachycardias, TdP, HF
Prolongs QTc interval, proarrhythmia.
CNS: cinchonism (tinnitus, hearing
loss, confusion, delirium, visual
disturbances, psychosis)
Other: fever, headache, rashes,
leukopenia, thrombocytopenia
Give with food.

Monitor QT interval, QRS width, PR.
Watch for proarrhythmia (torsades).
IV use rare (hypotension).
Drug Interactions:
Digoxin levels.
Increased bleeding when used with
coumadin.
Dilantin, phenobarb, rifampin,
nifedipine, sodium bicarb, thiazide
diuretics all Quinidine levels.
Cimetidine, amiodarone, verapamil all
increase Quinidine levels.
Prolongs QT interval, potential for
proarrhythmia with IA agents or
diuretics.
Watch for bradycardia, AV block and
new or worsening HF.
Contraindications: bronchial asthma;
sinus bradycardia; second- and thirddegree AV block (unless a functioning
pacemaker is present); congenital or
acquired long QT syndromes;
cardiogenic shock; uncontrolled
congestive heart failure.
CV: Bradycardia, heart block, HF,

proarrhythmia.
Other: Bronchospasm, fatigue,
weakness, GI symptoms, dizziness,
dyspnea, hypotension.
31
DRUG / CLASS
INDICATION
Verapamil (Calan)
Ca++ channel blocker

atrial fib/flutter.
AVRT, can terminate and
(not clinically useful)
Half life = 12 hours
PO: 180-360 mg qd in 2-3 doses
IV: 2.5 5 mg over 2 min.
May repeat with 5 10 mg if
needed
Therapeutic level = 80-400 ng/ml
SIDE EFFECTS
Bradycardia, heart block, HF,

hypotension, fatigue, headache,
edema, constipation.
Contraindicated in patients with wide
QRS tachycardias(unless known to be
supraventricular), bradycardia, AV
block, sick sinus syndrome.
COMMENTS
Drug interactions: increases digoxin

levels. Additive effects on HR, AV
conduction with beta blockers, digoxin.
Hypotension, and potential for HF
when given with other negative
inotropic drugs.
Abbreviations used in this table: AV, atrioventricular; AVNRT, atrioventricular nodal reentry tachycardia, AVRT, atrioventricular reentry tachycardia; BP, blood pressure; CNS,
central nervous system; CV, cardiovascular; EF, ejection fraction; GI, gastrointestinal; HF, heart failure; HOCM, hypertrophic obstructive cardiomyopathy; HR, heart rate; ICD,
implantable cardioverter defibrillator; INR, international normalized ratio; IV, intravenous; NSR, normal sinus rhythm; PEA, pulseless electrical activity; PO, per os (oral); SVT,
supraventricular tachycardia; TdP, Torsades de Pointes; VF, ventricular fibrillation; VT, ventricular tachycardia; WPW, Wolff-Parkinson-White;
References:
1. Brunton L., Lazo J., Parker K. Goodman & Gilmans The Pharmacological Basis of Therapeutics, 11th Ed. McGraw-Hill, 2006
2. Field, J. M. (2005). Advanced cardiovascular life support provider manual. Dallas, TX: American Heart Association.
3. Opie LH, Gersh BJ. Drugs for the Heart, 7th Ed. Philadelphia, Saunders Elsevier, 2009.
4. Uptodate at www.uptodate.com
32

Physiologic Basis of Cardiovascular Therapy

Diunggah oleh

Informasi Dokumen

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Physiologic Basis of Cardiovascular Therapy

Diunggah oleh

Hak Cipta:

Format Tersedia

THE PHYSIOLOGICAL BASIS OF CARDIOVASCULAR DRUG THERAPY

Carol Jacobson RN, MN

Drugs that keep blood from clotting:

Drugs to treat angina:

Drugs that increase

Drugs that dilate veins (preload

Drugs that reduce blood volume:

Drugs that dilate arteries and help

Drugs that cause vasoconstriction and

PHYSIOLOGICAL BASIS FOR CARDIOVASCULAR DRUG THERAPY

SYMPATHETIC NERVOUS SYSTEM

Preload Afterload Contractility

Venous tone Body Position

Blood Volume Distribution of

Conditions that Alter Preload

Conditions that Alter Afterload

Conditions that Alter Contractility

Drug Therapy to Alter Cardiac Output

Combination therapy and drug interactions:

Take antacids 2 hrs apart from drug.

ANGIOTENSIN RECEPTOR BLOCKERS

Angiotensin Receptor Blockers

Effects of Aldosterone in Heart Failure:

CLINICAL APPLICATION OF BETA BLOCKERS

DOSE / Half life

DOSE / Half life

Ultra short-acting cardioselective

Risk of skin necrosis with

Full recovery from beta blockade

Side effects similar to other beta

Carvedilol is indicated for

DOSE / Half life

For heart failure:

CALCIUM CHANNEL BLOCKERS

CLINICAL USES OF Ca++ CHANNEL BLOCKERS

Calcium Channel Blockers

Heart Rate Lowering (Nondihydropyridines)

Negative inotropic effect can cause

Same as for verapamil with possibly

Conversion from I.V. diltiazem to

Decreases contractility and causes

2.5-10 mg/day in 2 divided doses.

20 mg 3 times/day; usual range: 60120 mg/day.

Immediate release tablets: 10-20 mg

Vascular selective, less cardiodepression.

Most potent Ca++ channel blocker

Peripheral edema, flushing,

Same side effects as amlodipine.

Do not use for acute angina attacks

Drugs that Inhibit Platelet Activation

Drugs that Inhibit Platelet Aggregation

Site of action of antiarrhythmic drugs:

Class III: K+ Channel Blockers

Effects of antiarrhythmics on the action potential:

Antiarrhythmic Drug Classification

Potassium channel blockade

Calcium channel blockade

DRUGS FOR DYSLIPIDEMIAS

Side Effects: Mainly GI:

Bind bile acids in

Lowers LDL by 1530%

Blocks release of free

Lowers LDL by 1025%

Lowers LDL by 2060%