CARDIAC Part I & II- CAD, CHF, Arrythmias Flashcards Preview

Pharmacology > CARDIAC Part I & II- CAD, CHF, Arrythmias > Flashcards

Flashcards in CARDIAC Part I & II- CAD, CHF, Arrythmias Deck (94):

Left coronary artery

Supplies the anterior and lateral portions of
the left ventricle
• 2 branches
– Left anterior descending – supplies AV node, the septum,
anterior LV
– Circumflex – supplies the left atrium and posterior LV


Right coronary artery

Supplies SA node, right atrium, most of the
right ventricle


CAD Risk Factors

Family history: the younger the event in a 1st
degree relative, the higher the risk
• Male > Females
• Smoking
• Metabolic Syndrome: constellation of 3 or more
– Abdominal obesity
– Triglycerides > 150mg/dl
– HDL 110mg/dl
– hypertension
• Physical inactivity
• Stress


Classes I-IV Cardiac Disease: descibe

Class I: ordinary physical activity does not cause angina. Angina = with strenuous/ prolonged physical activity.
Class II: Comfortable at rest; slight limitations to physical activity, resulting in palpitations, fatigue, dypsnea, anginal pain.
Class III: Marked limitation of activity; walking 1-2 blocks or 1 flight stairs then issues... resulting in palpitations, fatigue, dypsnea, anginal pain.
Class IV: Inability to carry on any physical activity without discomfort; angina may be present at rest.


Pathophysiology of CAD

A pathologic continuum resulting in ineffective
pumping action of the heart resulting from:
– Myocardial infarct
– Myocardial ischemia
– all deprive heart muscle of oxygen and
– Coronary arteries supply O2 to the heart
– When there is an increase in demand, ischemia
• Deposition of lipids and macrophages in
vascular wall – plaque formation
– Plaque can be stable and just cause stenosis
or unstable and ready to rupture
• HTN increases risk of plaque formation & rupture
• Stable plaques – fibrous cap, calcification, vascular
• Unstable plaques – rupture, release of plaques
contents into blood vessel, clot formation
• Local inflammation: macrophages release
inflammatory mediators


Angina =

=pain/ discomfort in chest when some part of heart does not receive enough oxygen.
Symptoms can be atypical (location) or
even silent
• Typical angina: provoked with exertion,
relieved with rest


ST Elevation on EKG:

1 mm (perihperal lead) or 2mm (chest lead) elevation above baseline
**look for in 2 + leads facing same area


Causes of Angina Pectoris

• Imbalance in myocardial oxygen
– Increased HR, contractility, ventricular wall
tension (R/T HTN, LVH)
– Decreased blood flow: occlusion of the
coronary arteries
•Atherosclerosis/plaque formation, thrombi,
Prinzmetal’s angina
– Decreased oxygenation: anemia,
asphyxiation, hypoventilation, altitude


Types of Angina Pectoris

Variant angina (Prinzmetal’s)
– Vasospastic-coronary artery spasm
• Stable angina
– Predictable precipitants, location, duration,
alleviating factors
• Unstable angina - “pre-infarction angina”
– Unpredictable pattern; increasing symptoms


Treatment of Angina

Lifestyle modifications
• Surgical interventions: stents, CABG
• Pharmacologic approaches
– Aspirin
– Beta-adrenergic blockers
– Long-acting calcium channel blockers (CCB’s)
– Angiotensin-converting enzyme inhibitors (ACEi)
– 3-hyroxy-3methylglutaryl coenzymeA (HMG CoA)
– Reductase inhibitior (statins)
– Nitrates
– Ranolazine


Drug Treatment of Coronary
Heart Disease (CHD/CAD)

Reduce ischemia by improving myocardial O2
supply &
demand, dilating coronary vessels and/or decreasing
demand by reducing cardiac work
– Nitrates
– Beta-adrenergic Blockers
• may help decrease risk MI
– Calcium channel blockers
– ACEI (recommended in chronic stable angina)


Other Meds in Angina

Plaque stabilization
– Antiplatelets
• Thioenopyridines:clopidogrel (Plavik), prasugrel
• Glycoprotein Iib/IIIa inhibitors: (abciximab
(Reopro), tirofiban (Aggrastat), and eptifibatide



Have maintained an important treatment
factor due to their ability to affect oxygen
supply rapidly
• Affect supply/demand on both sides;
– Low doses dilate veins > arterioloes, causing
a decrease in venous return; decreasing left
ventricular end-diastolic pressure, (preload)
– Higher doses, dilate arterioles; decreasing
systemic vascular resistance, (afterload).


Nitrates - Pharmacodynamic

Decreases myocardial O2
demand by
causing formation of nitric oxide, a
free radical, in smooth muscle
– Nitric oxide (NO): released by endothelium as
a local vasodilator
• Peripheral venodilation → decreased preload
• Peripheral arteriolar dilation → decreased afterload
Nitrates - Pharmacodynamic
• Increase myocardial oxygen supply by:
– Decreasing coronary spasm
– Dilation of epicardial and collateral vessels
– Seem to preferentially vasodilate areas of
– Dilate coronary arteries to some degree, but
not very well in atheroscleroisis
• Therefore, nitrates increase O2 supply AND
decrease O2 demand
– Lipid soluble
– Cross membranes easily
• Metabolism
– Rapid inactivation by organic nitrate
reductases (hepatic enzymes)


Nitrates - Indications

Short term relief of anginal episodes
•Sublingual: short shelf life (6 months
after opening)
•Sprays: longer shelf life (3 yrs.)
• Anginal prophylaxis (prevention)
•Long-acting preps (i.e., Imdur)


Nitrates - Pharmacokinetics- Absorption

– Sublingual – Tablets; onset 1-3 minutes
– Transmucosal – Sprays
– Transdermal: onset 30 minutes
– Oral – isosorbide dinitrate, isosorbide


Nitrates- Pharmcokinetics- Metabolism and Elimination

– Extensive first-pass effect on oral preps
• NTG (Preg Cat B) metabolized in liver by hepatic NTG
reductase into dinitrates (which have longer half life, but
only 10% of activity). Dinitrates are metabolized into
mononitrate (inactive), then to glycero & CO2
• Isosorbide dinitrate (Preg cat C) → isosorbide
mononitrate → isosorbide


Nitrates -Short-Acting

Sublingual Nitroglycerin (NTG)—
Nitrostat : q 5 mins I tab SL
– 0.3 mg, *0.4 mg, *0.6 mg
•Onset 1-3 minutes; peak effect 4-8 mins
•Short shelf-life
• Nitrolingual spray - 0.4 mg metered
spray1-2 sprays under tongue
•Onset: 2 mins; peak effect: 4-10 mins


Nitrates - Long-Acting

Isosorbide dinitrate
– Extensive 1st pass; rapidly metabolized to
active metabolytes)
– Isordil, Dilatrate-SR
• 10-40 mg bid-tid or
• SR 40-80 mg qd-bid
• Isosorbide mononitrate
– Minimal 1st pass, no active metabolytes
– ISMO, Monoket, Imdur (SR)
• 10-20 mg bid – 7 hours apart
• SR 30-60 mg qAM; up to 240 mg/day
Nitrates - Long-Acting Preps
• Nitroglycerin ointment 2% (Nitro-Bid,
– Dose: 1” = 20 mg; ½” – 2” q 6-8 hrs
– total 12 hrs/day
• Transdermal (Nitro-Dur) patch
– Dose: 10-25 mg/24 hours (0.1 mg/hour)
– total 12 hrs/day.
• Apply to non-hairy areas, tape
application paper (ointment) over
area. Wash hands. Remove at hs.


Nitrogylcerin- Tolerance

Occurs with continued exposure, smooth muscle
develops tolerance, (tachyphlaxis)
• Should have peaks and troughs in the dose (8
hrs/day).Time doses to insure trough,usually
• Mechanism: May be R/T sulfhydryl depletion
resulting in decreased cGMP, leading to
decreased vasodilation


Nitroglycerin - Side-Effects

• Flushing
• Reflex tachycardia
• Orthostatic hypotension
• Occasional syncope (fainting)
• Caution: History of migraines, preexisting


Nitroglycerin -- Drug-Drug

– Added vasodilation/hypotensive effect
• Sildenafil (Viagra)
– Potentiation of vasodilation (synergistic)
• Heparin
– IV nitro may antagonize effects (probably
metabolic). May need to decrease heparin
dose when NTG Dc’d and monitor PTT
Nitroglycerine Drug Interactions
• Aspirin increases serum nitrate levels and may
potentiate the effects
• Drugs with anticholinergic effects may decrease
absorption of SL or buccal NTG
• Increase hypotensive effect seen when given in
patients who are on;
– Beta blockers
– Calcium channel blockers
– Haldol
– phenothiazines


Sublingual Nitrates - Patient

1. Take sublingual while sitting down.
• 2. Pts with dry mouth should take a sip
of water first.
• 3. Store in cool dark place; discard and
replace unused tablets q 6 months.
• 4. Take up to 3 tablets over a 15 minute
period at 5 minute intervals. (if CP
continues, call 911)
• 5. Use prophylactically before
activities that might precipitate angina.
NTG: Patient Teaching
• Don’t carry in pants or shirt pocket – too warm
• Sprays last 3 years, tabs last 6 months – less if
stored improperly


Translingual Nitrates - Patient

Take spray while sitting down.
• 2. Spray onto/under tongue – 3 sprays
over a 15 minute period at 5 minute
• 3. Use prophylactically before
activities that might precipitate angina.
• 4. Do not shake container or inhale
• 5. Do not rinse mouth for 5-10 min after


Newer Antianginal

Ranolazine (Ranexa)
– Approved in first line chronic angina
– Decreases late sodium current; decreases
intracellular calcium overload
– Has no effect on HR, BP, and helps prolong exercise
– Safe to use with erectile dysfunction drugs
– Dose is 500mg BID
– Caution in patients with QT Prolongation
(antiarhythmics)- however, there is a decrease in V.
arrhymias when used after acute coronary syndrome
– Decreased a fib
– Caution in significant liver and renal disease



Recommended by American College of
Physicians ( Snow et. al. 2004).
– For chronic stable angina
– Prevent MI or death
– Reduce symptoms
– VAMC (2003) in diabetics and LVD


Angiotensin II Receptor Blockers (ARB)

Recommended for use in CAD
– Diabetes with HTN
– LV systolic dysfunction
– When patients are intolerant of ACEI
– Can be added to ACEI Rx in uncontrolled HTN, or
insufficient vasodilation


Angiotensin-Converting Enzyme
Inhibitors and Angiotensin II Receptor

Act by affecting the renin-angiotensinaldosterone
(RAA) system to lower blood
• Improve oxygenation to the heart muscle
• Decrease inappropriate remodeling of heart
muscle after an MI, or heart failure
• ARBS have similar effect in treating HTN and
Heart failure
• Work by inhibiting ACE activity
• Decrease angiotensin II and aldosterone
• AII- stimulates sm. muscle contractions;
– Increased blood pressure
– Increases intravascular volume ( stim. Of aldosterone)
– Alters glomerular function
• AII causes remodeling leading to hypertrophy
and fibrosis of cardiac tissue after ischemic
injury in response to persistent afterload
– primary mechanism in Heart Failure


Angina and Ischemic Heart Disease

ACEIs affect MOS (myocardial O2 supply) and MOD
(myocardial O2 Demand)
• Inhibition of A II decreases PVR (peripheral vascular
resistance), decreasing MOD.
• Decreases thickening of coronary arteries, therefore,
increasing MOS
• Decreases thickening of ventricular walls= MOD
• Because they decrease aldosterone, they decrease
sodium and water retention; decreasing ECF
(extracellular fluid volume), and preload
• ACEI are recommended by American College of
Physicians in chronic stable angina


ACEI examples:

start low and go slow
• Captropril: Heart failure; dose 6.25 - 25mg TID, increase
to 50mg TID
• Enalapril: Heart failure: start at 2.5mg daily and increase
to 40mg daily
• Lininopril: heart failure: 5mg daily, maximal dose 20mg


ACEI and ARBs in Heart Failure

These agents reduce remodeling
• An underlying cause of HF is chronic HTN: both are
effective treatments
• ACEIs are the cornerstone for treatment in Heart Failure,
in all the guidelines (Flather et. al, 2000; Hunt et al,
2005; ICSI, 2004; National Collaborating Center for
Chronic Conditions, 2003).
– Improve symptoms
– Decrease morbidity, increase life expectancy
– Only set of drugs that address all of the physiologic causes of
HF, they helpful in patients with ventricular dysfunction who have
no symptoms
– All patients with LVD should be on an ACEI


Drug Interactions

Additive hypotensive effect with diuretics
• Acute alcohol, nitrates, phenothiazides, other
• Hyperkalemia can occur with concurrent use of
potassium supplements, cyclosporin and
potassium-sparing diuretics
• Antihypertensive response is diminished with



Bilateral renal artery stenosis
• Angioedema: occurs in .2%
– Is life threatening and if occurs, can not switch to
another agent in the same category
– Seen with ACEI not ARBs
• Pregnancy; category C in 1st trimester, and
Category X in 2nd and 3rd
• Hyperkalemia
• Hepatic impairment


Adverse Reactions

Reactions are usually mild and transient
• Cough; can change to another drug from
same class: ARBs do not cause cough
• Hypotension: dizziness, headaches,
fatigue, postural hypotension
• Rash: most common with Captopril, not


Beta Blockers

• With no intrinsic sympathominimetic
activity (ISA) recommended as initial Rx
– With or without previous MI
– Decrease MOD
– Drug of choice for exertional angina
(ACC/AHA, all classes)
– Main goal is to prevent recurrence of MI in
patients with CAD
– In patients who have resting tachycardia
Beta Blockers in CAD
• Decreased sympathetic nervous
system stimulation
– Reduced cardiac workload by
decreasing HR and contractility by
blocking beta1
receptors; decrease
afterload .Used for angina prevention.
– Decreased activation of reninangiotensin-aldosterone
•Used post-myocardial infarction
Beta Blockers in CAD
• Slowed Heart Rate
– ➔ Increased diastolic filling time
• → Increased coronary perfusion
• → Increased O2 supply
– ➔ Decreased myocardial workload
• → Decreased myocardial O2 consumption
• → Decreased O2 demand


Beta Blockers in CAD

Atenolol (Tenormin)
• Metoprolol (Lopressor, Toprol XL)
– Best BB for asthma patients
• Nadolol (Corgard)
• Propanolol (Inderal)


Beta Blockers - Dose Titration

Check resting HR and exercise HR.
HR 50-60 is usually good evidence of
beta blockade exertional HR should


Beta Blockers: caution in-

Use cautiously with asthmatics, sick sinus
syndrome, 2nd & 3rd degree heart block,
– Metoprolol is best for asthmatics


Beta Blockers: Side Effects

Dizziness, lightheadedness
– Fatigue, nightmares,
– Heartburn, constipation, diarrhea
– Sudden weight gain
– Sexual dysfunction


Beta Blockers - Patient Teaching

Report dizziness, light-headedness,
faintness with position changes
– Orthostasis
• Do not discontinue suddenly!
– Beta blocker withdrawal syndrome
•Tachycardia, CHF
•Increased platelet aggregation


Beta Blockers: C/I in pts with:

Contraindicated in patients with severe
reactive airway disease


Beta Blockers: most cost effective

Most cost effective Beta blocker is atenolol
(Tenormin), twice day dosing


Beta Blockers: Kaiser Guidelines recommend in pts with....

Kaiser guidelines (2006) recommend in
patients with LV systolic dysfunction
stages I-IV


Calcium Channel Blockers: MOA

Calcium is crucial in the excitation-contraction of
muscles; in electrical excitation and myocardial
• There are 3 types of voltage channels that Ca
uses to enter cells- L-type, N-type, T-type
• L-type channels are predominant in cardiac and
smooth muscle- these are what CCB mostly
• In cardiac conduction, CCBs close calcium
channels (not all of them!) to decrease heart rate
Calcium Channel Blockers
• Cardiac muscle is highly dependent on calcium
influx during each action potential for normal
– Impulse generation in the SA node, and conduction in
the AV node- slow response or calcium dependent
action potentials
• Are all reduced or blocked by CCB’s
– Excitation-concentration coupling in cardiac cells requires
calcium influx
• CCB’s reduce contractility (dose dependent). Decrease CO.
• Ultimately reduce O2 requirement.


CCB's: Indications

Calcium Channel Blockers
• Multiple Indications:
– Angina
– Selected tachyarrhythmias
• Unlabeled Indication:
– Migraine headache prophylaxis
– Raynaud’s syndrome
– Cardiomyopathy
– Esophageal spasm
Used for stable and unstable angina
• Indications
•Vasospastic (variant, Prinzmetal) angina:
relax coronary artery vasospasm
•First choice in patients who don’t tolerate
nitrates and if beta blockers are
– Relax peripheral arterioles, reduce afterload &
cardiac O2


Calcium Channel Blockers in
CAD: 2 Types

Type 1 Nondihydropyridines
– Verapamil (Calan)
– Diltiazem (Cardizem)
• Type 2 (Dihydropyridines)
– Amlodipine (Norvasc)
– Nifedipine (Procardia)
– Nicardipine (Cardene)
– Felodipine (Plendil)


Calcium Channel Blockers -
Actions in CAD

Decrease myocardial oxygen demand
by: There are 3 receptors
– Choice of CCB is dependent on how the
channel is opened.
– Dilation of peripheral vessels (Types 1 and 2),
primarily arteriolar dilation
•Reduced afterload (reduced PVR)
– Depression of cardiac contractility- (Type 1)
– Depression of heart rate - (Type 1)
•Depression of automaticity and conduction
through the SA and AV nodes
Calcium Channel Blockers -
Actions in CAD
• Increase myocardial oxygen supply
•Causing coronary vasodilation and
preventing vasospasm (Types I and II)
– Improve blood supply to both ischemic
and non-ischemic tissue
•Enhancing diastolic relaxation of the
left ventricle (Type I)
– improved filling of the coronary arteries


CCBs: Nifedipine (Adalat, Procardia)- type II

Dihydropyridine-based work to increase reflex
in sympathetic tone, to overcome negative
inotropic effects
– Reduction in afterload, but little effect on
– Slow recovery channel
– Do not affect rate of recovery through
– Do not affect conduction through AV node.


CCBs: Veraparmil (Calan, Isoptin)

Affects opening of calcium channels
– Decreases rate of recovery, thus causing
depression of the AV nodal conduction- this is
the basis of treating supraventricular
– Has a direct negative inotropic effect.
• Veraparmil has strongest effect and should
avoided in CHF, it can worsen the disorder
– Type I receptor


Calcium Channel Blockers

IN GENERAL: Not drug of choice immediately
after MI. exception is Diltiazem: reduces
mortality in Q-wave MI if EF is > 40 %.
• Otherwise contraindicated due to negative
inotropic and bradycardia
• Patients with SA, AV node disturbances or SBP


Calcium Channel Blockers
Precautions: Dihyropyridines (Amlodipine, Nifedipine)

– Exert strong peripheral vasodilation
– Should be avoided in patients with peripheral edema,
can result in pooling and reflex tachycardia
– Contraindicated in unstable angina, can cause
– If necessary in the above situations, a long acting
preparation is recommended.


Coronary Steal Syndrome

CCBs vasodilate
arterioles, but in areas of
ischemia, arterioles may
already be maximally
dilated. Dilation of
arterioles in non-ischemic
tissues then draws blood
away from ischemic
areas → infarct of
ischemic areas


CCBs: Pharmocokinetics-

Well absorbed
• Significant 1st pass effect
• Highly protein bound
• Excreted urine
• Use cautiously in liver disease


Calcium Channel Blockers:
Treatment Regimens in CAD

Nitrate plus calcium channel blocker
– For patients who are poor candidates for
beta blockers
• Calcium channel blocker (amlodipine) and
beta blocker
– Additive effect in decreasing cardiac
workload, BP
• Calcium channel blocker (amlodipine), beta
blocker, nitrate


CCBs: adverse drug reactions

• Nifedipine: reflex tachycardia*, ?
Increased mortality if MI or angina
• Verapamil: constipation
• All: flushing, HA, dizziness, gingival
hyperplasia, edema
» *reflex tachycardia: BP goes down, baroreceptors
sense decr. BP & HR increases


Aspirin in CAD

Inhibits synthesis of thromboxane A2, in the
production of platelets.
• Recommended after Heart attack
– Stable or unstable angina
– During a heart attack
– Recommended dose is between 81mg to 162.5


Multidrug Therapy in CAD

Combination treatment can be more beneficial than
single agent drugs
• Adequately reduce MOD, using lower doses and
decreasing side effects.
• Lower doses reduce risk of hypotension
• Nifedipine and Amodipine ( dihydropyridine CCB), are
• Combinations of B blockers and Nitrates are safe, cost
• Verapamil and Ditiazem should not be used together as
they can potentiate HF and bradycardia
– Combinations of long acting nitrates and CCB’s not used, as SE
panel is additive


Drug Therapy for Asymptomatic

– Dietary management
– Aspirin
– Statins- aim to decrease LDL to



Prolong clotting time, stabilize thrombi
– Heparin: inhibits anti-thrombin III
– Warfarin (Coumadin): inhibits hepatic
synthesis of coagulation factors



Monitor platelets for heparin induced
thrombocyopemia (HIT)
– HIT=antibody reaction against heparin –
platelet complexes causing thrombosis and
precipitous drop in platelets
• Risk of DVT, PE, MI, stroke
• Nursing implications: monitor CBC/diff, PT/PTT.
Stop heparin if necessary.
• Rx=lepirudan or argatroban
• Antidote heparin OD= protamine sulfate IV



Shorter molecule than unfractionated
– Inactivate factor Xa
– Enoxaparin (Lovenox), dalteparin (Fragmin),
tinzaparin ( Innohep)
– Used for prevention/rx. DVT, PE, MI
– SQ abdomen QD-BID depending


Factor 10A inhibitors

Fondaparinus ( Arixtra)
• Rivaoxaban (Xarelto)



• Antidote: Vitamin K
– Reverses risk bleeding associated with
warfarin (Coumadin)
– May be given IV, IM, SQ,PO


Antiplatelet Agents

Glycoprotein IIb/IIIa receptor blockers
2. Adenosine diphosphate receptor blockers
3. ASA
– Binds irreversibly to cyclooxygenase in
platelets and inhibits platelet aggregation
Glycoprotein IIb/IIIa receptor blockers
– Inhibit enzyme necessary for platelet
– Used if patient having an MI, stroke, PTCA
– IV use only



Used to dissolve blood clots
– t-PA (Activase now most commonly used
– History very important as contraindicated
recent surgery, trauma, childbirth, GI bleed,


CHF: Pathophysiology

Complex clinical syndrome, that includes any
structural or functional cardiac disorder altering
cardiac output, resulting in inadequate supply of
the oxygen demands of the body
• A number of abnormalities
– CAD, underlying cause in about 2/3 of individuals
– Left ventricular dsyfunction, (systolic heart failure)
• progressive


3 Types of Heart Failure

Systolic Dysfunction
– Often acute; following an MI
– Decreased force generated to eject blood
from the ventricles
•Other causes: nonischemic
cardiomyopathy, alcohol and drug that
affect the myocardium, conditions that = vol
Types of HF, cont.
• Diastolic Dysfunction
– Inadequate relaxation and loss of muscle
fiber, with resulting loss of elasticity
– Slower filling rates
– Elevated diastolic pressures, decreased
cardiac output
– May have normal EF
– Causes:
• Uncontrolled HTN, hypothyroidism, hypertrophic
and ischemic cardiomyopathy, elderly
• Highest rate in elderly women, > 70


Classification of Heart Failure

New York Heart Association (NYHA); classified
based on symptoms: See handout
• Four Classes
– Based on Left vs Right ventricular failure
– Lung symptoms (congestion) ,are usually LVF
– Body-focused, edema, are usually RVF


Goals for Tx of CHF

Improvement of symptoms
• Reduction in mortality
• Reduction in morbidity
– Decrease overload, either preload and/or
– Improve contractility
– Decrease heart rate


Treatment According to Stage: A

Stage A: At risk for HF but without
structural heart disease for sx of HF
– Patients using cardiotoxins, FH of
• HTN, smoking cessation, Rx lipid disorder, regular
exercise, discourage ETOH, and illicit drug use
• Treat with ACEI- Captopril 6.25mg, only short
acting ACEI ,can be d/c’d if renal issues, otherwise
go to longer acting ACEI (go to ARB if not


Treatment According to Stage: B

(structural heart disease,
without symptoms or HF)
• Previous MI
• LV systolic dysfunction
• Asymptomatic valvular disease
• Treatment:
– Utilize all Rx measures for Stage A
– ACI I, in appropriate patients- moderate increase in
EF, decrease LV end diastolic pressures, improve
myocardial metabolism, only drug that addresses all
pathophys causes, (Contraindicated in pregnancy and
renal artery stenosis.
– ACEI useful in reducing HF
Stage B, (continued)
• Beta Blockers and ACEI are superior both
as monotherapy and in combination
• Beta Blockers- in appropriate patients; MI
– Unless contraindicated should be given in all
patients with recent MI, and LV dysfunction
– Added to ACEI
– Recommended for all patients who have not
had MI and reduced EF of = 40%
– Careful use in acute MI as these agents can
cause acute decompensation
Stage B, (cont.)
• Beta Blockers:
– Increase life expectancy in HF with LV
– 3 BB with strongest evidence
• Bisoprolol
• Metoprolol 12.5mg qd, up to 200mg qd
• Cavedilol- this one is alpha1, BB starting dose:
3.125mg BID,titrated up to 25mg to 50mg BID max


Treatment According to Stage: C

Stage C (development of symptoms of
Known structural heart disease
• Shortness of breath, and fatigue, reduced
exercise tolerance
– All measures used for Stage A
– Diuretics
– Beta Blockers
– Digitalis
– Sodium reduced diets
Stage C Treatment
• Digoxin: Cardiac Glycoside; indicated in HF and
• Doses -125mg - .375mg/daily
• Inhibits sodium-potassium ATPase, increasing
intracellular Na resulting in increased
intracellular Ca -> + inotropic action: which
reduces sympathetic response and reninangiotensin,
system output, thereby reducing the
heart rate


Treatment According to Stage: D

Stage D-refractory symptoms of HF at
• Patients with marked symptoms at rest, despite
maximal therapies- frequent hospitalizations, not
safely d/c without specialized interventions
– All measures in A,B, C
– Mechanical assist devices, implantable pacers, defib
– Continuous IV inotropic infusions for palpitations
– hospice


Dig: Precautions, C/I and SEs

• Contraindicated: hypersensitivity, Vfib
• Precautions: elderly, Av block, weight loss,
– Hypokalemia, hypocalemia, hypomagesemia
– Need a diet high in K, mg
– Hyperthyroidism-may be resistent
– Renal impairment
– Side effects: N,V, Dizziness, mental disorders
(halos, green/yellow), cardiac dysrhythmia,
ischemia, SA block, vasoconstriction,


Dig: pharmacokinetics

Absorption: well absorbed orally- however taking
with high bran/fiber, inhibits absorption and
should be taken ½ hour ac.
• Taking with antibiotics can increase
bioavailability= toxicity
• Metabolized and excreted largely unchanged in
the kidneys, ½ life is 36 to 48 hours and longer
in the elderly
• Pregnancy C


Cardiac Anatomy and Physiology
Properties of Cardiac Tissues

Automaticity - Able to initiate an impulse
spontaneously and continuously

2. Contractility - Ability to respond
mechanically to an impulse

3. Conductivity - Ability to transmit an impulse
along a membrane in an orderly manner

4. Excitability - Ability to be electrically


Cardiac Regulation


- β1 adrenergic receptors (norepi and epi)

- Speed up HR


- Vagus nerve

- Slow HR


Categorization of Antiarrhythmics

(Vaughan-Williams classification)

Class I: Sodium-Channel Blockers

• Class II: Beta-Blockers

• Class III: Potassium-Channel Blockers

• Class IV: Calcium-Channel Blockers

• Miscellaneous: Electrolytes (Mg and K+),
adenosine, digitalis compounds (cardiac

glycosides), atropine (muscarinic receptor


Class I

Reduce the rate and magnitude of depolarization by

blocking sodium channels is a decrease in conduction

velocity in non-nodal tissue (atrial and ventricular muscle,
Purkinje conducting system).

• Blocking sodium channels reduces the velocity of action
potential transmission within the heart (reduced
conduction velocity; negative dromotropy)

• Anticholinergic actions - Inhibit vagal activity -> increase in
sinoatrial rate and atrioventricular conduction -> offset the
direct effects of the drugs on


Class II

Slow pacemaker and decrease conduction
velocity. Also increase action potential

duration and effective refractory period of
non-pacemaker cells


Class III

Blocking potassium channels slows

repolarization and increased the effective
refractory period

• Increase QT interval

• Effective for re-entry mechanism arrhythmias


Class IV

Block calcium entry into cell

• Decrease firing rate of aberrant sites

• Decrease conduction velocity and prolong
repolarization, esp. at the AVN.



Muscarinic receptor antagonists

• Block vagus nerve (parasympathetic system)


Proarrhythmic Risks

• Class I: Greatest risk for proarrhythmia, especially in
patients with structural heart disease (coronary heart
disease and/or left ventricular dysfunction)

• Class II: beta blockers, except sotalol (also has class III
properties). No tachyarrhythmic or proarrhythmic
effects but can cause bradycardia.

• Class III: Prolong repolarization and pose the specific
risk of torsades des pointes ventricular tachycardia.

Proarrhythmic Risks

• Depending upon the medication selected and
other patient-specific factors, initiation of
therapy may need to be done with patient

hospitalized for observation.

• Dofetilide and Sotalol labelings specify
inpatient initiation.

• Flecainide, propafenone, dronedarone, and
amiodarone can generally be initiated on an
out-patient basis in appropriate patients.


Important Questions in assessing and treating arrythmia

Is the arrhythmia causing symptoms or could it?

• Does the arrhythmia pose a risk to the patient?

• Which arrhythmia is present?

• Does the arrhythmia require emergent cardioversion?

• Does the patient require urgent hospitalization?

• Is specialist consultation required, and if so, how

• Should anticoagulation and/or other medical therapy
be started?


Primary Care Scope

Specialist Consultation RECOMMENDED when
considering initiation of antiarrhythmic Rx.

• Must be very familiar with assessing risks.
Strong knowledge required of baseline ECG
characteristics, structural heart conditions,
therapeutic dosing and levels, drug-drug
interactions, and other med side effect



Brand name: Coumadin

• Category: Vitamin K antagonist (II, VII, IX, X)

Risk vs. Benefit

• Reduction in Thromboembolic Events

- >80% risk reduction for non-valvular AFa

- 60-79% risk reduction for prosthetic heart valves as compared to
antiplatelet regimensa

• Increased Risk of Hemorrhagic Events

- 6% per year (RR 3.4; 95% CI 3.0-3.9)b

aHirsh, J., Fuster, V., Ansell, J., & Halperin, J. L. (2003). American heart association/American college of cardiology
foundation guide to warfarin therapy. Circulation, 107(12), 1692-1711.

bOake, N., Fergusson, D. A., Forster, A. J., & van Walraven, C. (2007). Frequency of adverse events in patients with
poor anticoagulation: A meta-analysis. CMAJ: Canadian Medical Association Journal = Journal De
L'Association Medicale Canadienne, 176(11), 1589-1594.


The anticoagulant effect of warfarin is

mediated through inhibition of vitamin K-

dependent coagulation factors, including

clotting factors II, VII, IX, and X.

(Proteins C and S)

Valentine, K. A. & Hull, R. D. (2009). Therapeutic use of warfarin. UpToDate Online. Last
literature review version 18.1

Warfarin (cont.)

• Warfarin is rapidly absorbed in the GI tract,

circulates bound to plasma proteins, and has a
half-life of 36 to 42 hoursa

• Warfarin is a racemic mixture of S and R

enantiomers, and the more potent S form of the
drug is metabolized primarily by the hepatic
CYP2C9 systemb

a(Hirsh, Fuster, Ansell, & Halperin, 2003)
b(Valentine & Hull, 2009)

Warfarin (cont.)

• Variable amounts of dietary intake of vitamin K
will have an effect on warfarin dosing, as will
alterations in vitamin-K producing intestinal flora

• Because warfarin is strongly protein-bound and
only the non-protein-bound fraction is
biologically active, any substance that binds to

albumin may displace warfarin from its albumin

binding sites and increase its biological activity


Diagnostics for Anticoagulant Therapy

The prothrombin time (PT) responds to reduction
of 3 of the 4 vitamin K-dependent procoagulant
clotting factors that are reduced by warfarin and
is therefore a surrogate marker of the

anticoagulation effect exhibited by the therapy.

• The International Normalized Ratio (INR) is the
ratio of an individual’s prothrombin time to a

control sample, raised to the power of the

International Sensitivity Index. Thus, the INR is a
standardized value for a patient’s clotting time͘

Limitations of Testing

• Variable half-lives of clotting factors

- Factor II (prothrombin): half-life approx. 60 to 72

• Long half-life of medication

- Anticoagulation effect half-life 40 to 70 hours

• Non-steady state conditions


Why Anticoagulate?



Mechanical Valve




Warfarin Dosing

Goal Ranges

- 2.5 (2-3) or 3.0 (2.5-3.5)



Brand name: Pradaxa

• Category:

Thrombin Inhibitor

• Major Trial: RE-LY



• Non-valvular AF: 150 mg PO bid

- Renal: CrCl 15-30: 75 mg bid

Pharmacodynamics/kinetics: No CYP450. Primarly
excreted urine. Half-life 12-17 hrs

aPTT provides an approximation of anticoagulant effect

Ecarin clotting time (ECT) more specific measure of effect



Brand name: Xarelto

• Category:

Factor Xa Inhibitor

• Major trial: ROCKET AF



• Non-valvular AF: 20 mg PO qd - give with evening

- Renal: CrCl 15-50: 15 mg qd

• DVT prophylaxis: 10 mg PO qd x 35 days (hip
replacement) or x12 days (knee replacement)

Pharmacodynamics/kinetics: CYP450: 2J2, 3A4/5,
excreted urine 66% - 36% unchanged. Half-life 5-

9 hrs (longer in elderly)



Brand name: Eliquis

• Category:

Factor Xa Inhibitor

• Major trial: ARISTOTLE



• Non-valvular AF: Oral: 5 mg twice daily unless patient has any 2 of the
following: ge ≥80 years, body weight ≤60 kg, or serum creatinine ≥1͘5
mg/dL, then reduce dose to 2.5 mg twice daily.


• Onset: 3-4 hours

• Protein binding: ~87%

• Metabolism: Hepatic predominantly via CYP3A4/5 and to a lesser extent
via CYP1A2, 2C8, 2C9, 2C19, and 2J2 to inactive metabolites;

• Bioavailability: ~50%

• Half-life elimination: 2.5 mg dose (repeated oral administration): ~8 hours;

5 mg single dose: ~15 hours (Frost, 2012)

• Time to peak: 3-4 hours

• Excretion: Urine (~27% as parent drug); feces (~25% of dose recovered as


Antiplatelets vs. Anticoagulants

ASA alone

• ASA + Clopidogrel

• ACTIVE A and W trial data

• It should be kept in mind that as dual antiplatelet

therapy and oral anticoagulation have similar bleeding

risks, a patient who would not be a candidate for oral

anticoagulation because of bleeding risk is also not a
candidate for dual antiplatelet therapy.