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842 Cards in this Set

  • Front
  • Back

path electrical activity takes through the heart

starts at the SA node near the SVC

travels to AV node

moves down the his bundle

to the left and right bundle branches

atria and ventricles are electrically isolated from each other by the

annulus fibrosus

gap junctions

pores that join cytoplasm or neighboring cells
ionsfreely move which allows for electrical propogation

electromechanical coupling

electrical activity is the trigger for mechanical activity

it precedes the mechanical activity

electrical signal disruption can lead to mechanical functional problems

Cardiac muscle action potential phases

0 - upstroke

1 - early repolarization

2 - plateau

3 - late repolarization

4 - back to rest

AP specifics in the nodes

slow upstroke

lack a plateau phase

lack a stable resting membrane potential

as soon as they depolarize, they begin to repolarize

AP specifics in the atria, his bundle, purkinje system, ventricles
stable resting potential

more rapid upstroke

early repolarization

plateau phase is prominent
more prominent plateau phases in atria, ventricles, etc are for...

ca induced ca release to happen

longer AP in purkinje and his bundle...

protect that tissue from the activity initiated in the ventricle propagating backwards

fastest conduction velocity in cardiac tissue
purkinje system
order of conduction speed, fastest to slowest, in cardiac tissue
purkinje system

atrial pathways and bundle of his

ventricular muscle

SA node and AV node
faster conducting tissues are
better aligned, well coupled
distribution of ions

More Na outside
More K inside
More Cl outside
More Ca outside

ionic basis of resting membrane potential

Ik1 current

inward rectifier K channel (K is leaking out of the cell down its electrostatic and chemical gradients)

this channel closes when current moves into the cell

resting heartcells behave like _____________ membranes
experimentally, the RMP in resting heart cells is


cardiac action potentials

fast response




cardiac action potentials

slow response
SA and AV nodes
Fast response action potential

Phase 0
At rest Ik1 is open and Na channel is closed

a depolarizing current triggers activation gate of Na channels

they activate and as cell beginsto depolarize the Ik1 channel closes almost immediately (Magnesium blocks it up)

I(Na) - Sodium in
Fast response action potential

phase 1
early repolarization

Transient outwork K current
voltage gated K channels

I(to) - k moves out of cell at depolarized potentials

fast response action potential

phase 2
I(to) current begins to inactivate and close

activation of delayed rectifier K current
L type Ca channels activate allowing calcium in for CICR for muscle contraction

balance of K out and Ca in keeps membrane potential around 0mV

I(k) - K out
I(Ca) - Ca in

(eventually L type Ca channels will inactivate themselves)
Fast response action potential

phase 3
final repolarization

L type Ca channels inactivate themselves

the delayed rectifier current begins to dominate

the membrane potential moves back to RMP

In late part of phase 3 the magnesium blocking effect on Ik1 is relieved and Ik1 reopens

Ik will eventually close

I(k1) - K out
I(k) - K out

Fast response action potential

Phase 4

After Ik closes it's just Ik1 and the 3Na(out)/2K(in) ATPase

I(k1) - K out

Na/K ATPase

ligand gated current
ATP sensitive in cardiac myocytes
opens when ATP drops

during ischemia, AP duration would shorten
less contraction, save some energy
Voltage gated K channels
4 separate subunits form a channel

voltage sensor is the S4 segment

Pore region is the S5-S6 linker

N terminal is where voltage-dependent inactivation happens
voltage gated Na and Ca channels
similar structure to K channels
each consists of a single subunit containing four repeats

Na and Ca channels are linked together, as opposed to K which are individual
Ik1 - inward rectifier current

resting membrane potential

outward current during phase 3

not voltage gatged

closes at depolarized membrane potentials

not present in pacemaker cells

Ik - delayed rectifier current

outward current during phase 2 and 3

two components I(Kr) and I(Ks)

expressed in pacemaker cells

ways ion currents are modulated
change in available current (carrier concentration or temp)

number of functional channels (changes in gene expression)

probability of activation
Slow response action potential differences
resting potential is less negative because Ik1 is absent

upstroke is due to inward Ca current from L type Ca channels

slow diastolic depolarization during phase 4, instead of remaining locked at rest
rate of sinus node cell firing depends upon
the balance between inward and outward currents
ionic basis of automaticity

currents that contribute to diastolic depolarization

I(f) - inward depolarizing current, induced by hyperpolarization

I(Ca) - inward calcium current

I(K) - outward, delayed rectifier potassium current (I(Kr) and I(Ks))

factors that influence pacemaker rate

slope of diastolic depolarization

threshold potential

minimum diastolic potential

how it affects pacemaker rate

slope of diastolic depolarization
a smaller slope of depolarization means it takes longer to reach threshold potential

it will take longer to fire
how it affects pacemaker rate

threshold potential
increasing threshold potential will make it take longer to reach

it will take longer to fire
how it affects pacemaker rate

minimum diastolic potential
if you have an even more negative minimum diastolic potential, you'll be further away from threshold potential

itwill take longer to fire
pacemaker rate

parasympathetic stimulation
activation of I(KACh channels) - increases K conductance

lowers min diastolic potential

decreases slope of phase 4
pacemaker rate

sympathetic stimulation
activation of I(f) channels -

increases slope of phase 4

no change in min diastolic potential
refractory period
absolute refractory period - during upstroke and depolarization where you can't get another AP to fire at all

relative refractory period - after repolarization has started, an AP could fire but it won't be as effective
positive charge comes at an electrode
positive signal
positive signal moves away from an electrode
(negative signal moves towards it)
negative signal
positive or negative signal passes by an electrode
how many electrodes and how many leads?
10 electrodes

12 leads
all leads are unipolar except
right arm

left leg

left arm
right arm to left arm
right arm to left leg

left arm to left leg


Right sternal 4th intercostal


left sternal 4th intercostal

V3 and V4

mid clavicular


anterior axillary
mid axillary
path of electricity through heart and waveform
starts at SA node

as it travels through RA, the RA contracts and you get a p wave

gets to the AV node iso-electrically

Down the bundle of his to the bundle branches and around is the QRS (ventricular contraction)

Resetting starts from teh outside (repolarization) at the left lateral base
resets outside in and makes the t wave
qrs through the heart
starts in the intraventricular septum, on the edge of the left ventricle

moves away from aVL through the septum going towards aVF

swings around to the rest of the myocardium inside bundle branches to get to rv and lv apex

still going towards aVF and now it's also going towards aVL

moves up the left bundle branch

moving away from aVF and moving rapidly positive towards aVL
1 small box
0.04 sec

40 msec
time 1 big box
.2 sec

200 msec
voltage 1 small box
0.1 mV
volrtage 1 big box
0.5 mV
normal PR interval
120 to 200 msec
normal QRS interval
60 to 100 msec
normal QT interval
less than 440 msec (men) or 460 msec (women)
heart rate method 1
count number of small boxes between qrs complexes

divide 1500 by the number f boxes

most useful for fast heartbeats over 100 bpm
heart rate method 2
count off method

each big box you go down in the sequence

300 - 150 - 100 - 75 - 60 - 50
heart rate method 3

number of QRS in the 3 sec marker and multiply by 20


number of QRS in the 6 sec marker and multiply by 10

helpful for irregular heart rates

p wave
depolarization of the top chambers
R wave
depolarization of the ventricles
T wave

repolarization of the ventricles

U wave
five steps to ecg read
lead I up

aVF up
left axis deviation
I up

aVF down
right axis deviation
I down

aVF up
extreme axis
I down

aVF down
normal axis is between what degrees
-30 (left) and +90 (right)
left axis deviation is between what degrees
-30 to -90
right axis deviation is between what degrees
+90 to +150
extreme axis is between
+150 and -90
left axis deviation causes
inferior wall myocardial infarction

left anterior fascicular block

left ventricular hypertrophy
right axis deviation causes

right ventricular hypertrophy

acute right heart strain (like a massive pulmonary embolism)

left posterior fascicular block

intervals (again)

HR less than 100 bpm

1:1 P to QRS ratio

PR < 200 ms

QRS < 110 ms

QTc < 460 ms

normal p wave in lead II

normal p wave in lead V1

p wave

RA enlargement in lead II

p wave

RA enlargement in lead V1

p wave

LA enlargement in lead II

p wave

LA enlargement in lead V1

RV hypertrophy in V1

RV hypertrophy in V6

RV hypertrophy characteristics on ecg

R > S in V1

right axis deviation

(lead I down, lead aVF up)

LV hypertrophy in V1

LV hypertrophy in V6

LV hypertrophy characteristics in ecg

Deep S wave in V1

R in V5 or V6 is greater than 35 mm

R in aVL is greater than 11 mm

R in lead I is greater than 15 mm



the normal dynamic

all regions start at the same baseline

ekg baseline is set during electrical diastole when everything is quiet.

no significant gradients exist between regions

ekg changes with ischemia

ekg changes with ischemia

ST elevation

ekg changes with ischemia

ekg changes with ischemia

ST elevation

decreased R wave

Q wave begins

ekg changes with ischemia

ekg changes with ischemia

T wave inversion

Q wave gets deeper

ekg changes with ischemia

ekg changes with ischemia

ST normalizes

T wave inverted

ekg changes with ischemia

ekg changes with ischemia

ST and T normalize

Q wave persists

ischemia and potassium

dysfunction I(k) and I(ATP) lead to potassium leak

the cells dont have ATP/energy

region gets necrotic and swells

ischemia in diastole

ischemic cells leak potassium during phase 4 causing the baseline to be more positive

ischemia in systole

ischemic cells are less positive because

shorter action potential

slower upstroke

lower amplitude

ST segment elevation in MI

injury on the outside region of the muscle, leaking potassium

gradient between the epicardium and endocardium

K going away from the electrode creates a vector away from it and that becomes the new normal baseline

ST segment is actually normal, it looks elevated compared to the new normal baseline

NON ST segment elevation in MI

injured on the inside region of the muscle

leaked potassium creates a vector TOWARD the recording electrode, which forms a new higher baseline

ST region looks depressed during depolarization

MI Q wave

in aVL

goes down because aVL cant see a signal coming towards it until really late

jumps up late when the healthy section at the base is seen

Q waves are normal due to

left to right activation

normal in I, aVF, V5, and V6

Pathologic Q waves

> 40 ms

2 mm deep

more than 25% of the QRS amplitude

seen in V1, V2, V3

anteroseptal leads



anteroapical leads



anterolateral leads





inferior leads




current influx at phase 4 of a cardiac pacemaker cell

I(f) influx

AP in a cardiac pacemaker cell

I(f) current

activated by hyperpolarization

channels open when membrane voltage is more negative than -50mV

Mainly conducts Na ions

inward Na flow driven by conc gradient and the negative charge inside the cell

in the pacemaker cells of the SA node...

slow inward Ca current carried by mostly L type Ca channels

progressive decline of outward K current

additional inward Na current via Na/Ca exchanger act by SR Ca (calcium clock)

what are A B and C

what are A B and C

A is normal nodal (slow) AP

B is reduced I(f) which means it takes longer to get to threshold potential so it fires later

C is more negative maximum diastolic potential that makes it take even longer to get to Threshold Potential

natural pacemaker in the normal heart

SA node

beats at 60-100 bpm

faster than other tissues with automaticity

SA node bpm


AV node/Bundle of His bpm


Purkinje System bpm


when an impulse arrives at a cell that has not yet gotten close to threshold

current from the depolarized cell will bring the adjacent cell's membrane potential to threshold level so that it will fire

this is why the fastest autonomic cell will be the dominant pacemaker

latent (ectopic) pacemakers take over if

SA node slows or fails to fire

if conduction abnormalities block the normal depolarization wave from reaching them

enhanced automaticity of latent pacemakers

ectopic beats

impulse premature, relative to normal rhythm

high catecholamine conc can enhance automaticity of latent pacemakers

if the resulting rate of depolarization exceeds that of the sinus node, an ectopic rhythm can develop

ectopic beat commonly induced by



electrolyte disturbances

certain drug toxicities (dig)

Abnormal automaticity

cardiac tissue injury can lead to pathologic changes in impulse formation

myocardial cells outside the specialized conduction system can acquire automaticity and spontaneously depolarize

since they arent designed to be pacemakers, they dont carry I(f), but their membranes become leaky

can't maintain conc gradients of ions and the resulting potential becomes less negative

if it becomes less negative than -60mV, gradual phase 4 depolarization is observed, even in non pacemaker cells

probably the result of a slowly inactivating Ca current and a decrease in outward K current that normally repolarizes

triggered activity

action potentials can trigger abnormal depolarizations that result in extra heart beats or rapid arrhythmias

this can occur when the first AP leads to oscillation of the membrane voltage - Afterdepolarizations

2 types of after depolarizations


occur during repolarization phase


occur shortly after repolarization has been completed

either way, abnormal APs are triggered if the afterdepolarization reaches threshold voltage

Early after depolarization

Delayed after depolarization

repetitive afterdepolarizations (like in an EAD) may produce...

rapid sequence of APs and a tachyarrhythmia

DAD may trigger

a propagated AP

Early after depolarizations

changes of membrane potential int he positive direction that interrupt normal repolarization

can occur during plateau of AP (phase 2)

or during rapid repolarization (phase 3)

more likely to develop in conditions that prolong AP duration (longer QT interval conditions)

appear to be the initiating mechanism of torsades

Delayed after depolarizations

most common occur in states of high intracellular calcium like dig intoxication

can lead to tachyarrhythmias

some idiopathic ventricular tachycardias and atrial and ventricular tachycardias associated with dig toxicity

conduction block

a propagation impulse is blocked when it reaches a region of the heart that is electrically unexcitable

can be transient or permanent

block can be unidirectional or bidirectional

functional block

occurs because a propagating impulse encounters cardiac cells that are still refractory from a previous depolarization

a pulse that arrives later might be conducted

fixed block

caused by a barrier imposed by fibrosis or scarring that replaces myocytes

AV block

conduction block within AV node or His purkinje system

prevents normal propagation of cardiac impulse from the sinuse node to more distal sites

removes the normal suppression that ikeeps latent pacemakers in the his-purkinje system in check

av block usualy results in the emergence of

escape beats/rhythms, as more distal sites assume pacemaker function

Re entry

an electric impulse circulates repeatedly around a re entry path, recurrently depolarizing a region of cardiac tissue

2 critical conditions for re entry

unidirectional block

slowed conduction through the re entry path

re entry


the AP propagates in a way that prevents re entry

refractory periods keep any circular paths from being accessible in the wrong direction

unidirectional block and re entry

blocked region prevents normal propagation

normally, at certain junctions cells would be in a refractory period, but since the block was there, the cells are able to accept the AP in the wrong direction

unidirectional block and re entry tends to occur in regions

where the rafractory periosd of adjacent cells are heterogeneous

can also occur when cells are dysfunctional or fibrosis has altered the myocardial structure

unidirectional block and re entry

at normal retrograde conduction velocity

eventuallly when the signal goes around the re entry loop, it will still hit a point that is still refractory and stop

unidirectional block and re entry

slowed retrograde conduction velocity

by the time it gets to the spot past the initial blockage, refractory period is over

this can continue indefinitely and each pass through the loop excites cells of the distal conduction tissue which propagates to the rest of the myocardium at an abnormally high rate


mechanisms of arrhythmia development


altered impulse formation

decreased automaticity

decreased phase 4 depolarization

e.g. parasympathetic stimulation

sinus bradycardia

mechanisms of arrhythmia development


altered impulse conduction

conduction blocks

ischemic, anatomic, or drug induced impaired conduction

1st, 2nd, 3rd degree AV blocks

mechanisms of arrhythmia development


altered impulse formation

enhanced automaticity

sinus node

increased phase 4 depolarization

e.g. sympathetic stimulation

sinus tachycardia

mechanisms of arrhythmia development

altered impulse formation

enhanced automaticity

AV node

increaed phase 4 depolarization

e.g. sympathetic stimulation

AV junctional tachycardia

mechanisms of arrhythmia development

altered impulse formation

enhanced automaticity

ectopic focus

acquires phase 4 depolarization

ectopic atrial tachycardia and some forms of VT

mechanisms of arrhythmia development

altered impulse formation

triggered activity


prolonged AP duration

torsades de pointes

mechanisms of arrhythmia development

triggered activity


intracellular calcium overload

e.g. dig toxicity

APBs, VPBs, digitialis induced arrhythmias, idiopathic VT

mechanisms of arrhythmia development

altered impulse conduction

re entry


unidirectional block and slowed conduction

atrial flutter

AV nodal re entrant tachycardia

VT related to ventricular scar tissue

mechanisms of arrhythmia development

re entry


unidirectional block and slowed conduction

a fib

polymorphic VT

v fib


pharmacologic therapy

anticholinergic drugs

vagal stimulation: reduces rate of sinus node depolarization (slows HR) and decreases conduction through the AV node

so anticholinergics competitively bind to the Mu receptors that ACh binds to, and reduces vagal effect

results in increased HR and enhanced AV nodal conduction


pharmacologic therapy

beta receptor agonists

mimics the effect of endogenous catecholamines

increase HR

speed up AV node conduction



initiate depolarization at a desired rate

assume control of rhythm


pharmacologic therapy

desired drug effects to eliminate rhythms caused by increased automaticity

reduce the slope of phase 4 spontaneous depolarization of the automatic cells

make the diastolic potential more negative (hyperpolarize)

make threshold potential less negative


pharmacologic therapy

desired antiarrhythmic effects to interrupt re entrant circuits

decrease conduction in the re entry circuit to the point htat conduction fayils, thus stopping re entry impulse

increase the refractory period within the re entrant circuit so that a propagating impulse finds tissue within the loop unexcitable and the impulse stops

suppress premature beats that can initiate re entry


pharmacologic therapy

desired drug effects to eliminate triggered activity

shorten AP duration to prevent EADs

correct conditions of calcium overload to prevent DADs

arrhythmia drugs:

vaughn-williams classification

class I

predominantly Na channel blockers

arrhythmia drugs:

vaughn-williams classification

class II

beta adrenergic receptor blockers

arrhythmia drugs:

vaughn-williams classification

class III

predominantly K channel blockers

arrhythmia drugs:

vaughn-williams classification

class IV

non dihydropyridine Ca channel blockers

arrhythmia drugs:

vaughn-williams classification

class V

misc drugs (adenosine, dig)

Class I drugs effect on working myocytes

order of strength of effect

IC > IA > IB

Class I drugs effect on working myocytes

class IA

slows conduction

decreases I(Na)

smaller slope of

prolongs Action Potential Duration

decreases I(k)

prolongs QTc interval

Class I drugs effect on working myocytes

example-s of class IA drugs




Class I drugs effect on working myocytes

effects of IB drugs

mild conduction slowing

decreases I(Na)

decreases slope of upstroke

shortens action potential duration

decreases I(Na) and I(L)

shortens QTc interval

Class I drugs effect on working myocytes

examples of IB drugs



Class I drugs effect on working myocytes

IC effects

slows conduction a LOT

decreases I(Na)

really decreases slope of upstroke

minimal effect on Action Potential Duration

QT lengthens, but only because QRS lengthens

action potential duration doesn't really change

Use dependency?

Class IC > IA drugs

binding to open/inactivated Na channels


slow association/dissociation kinetics

means that more channels are blocked at faster heart rates

that's why these drugs are effective at terminating arrhythmias

Class IA clinical uses

atrial fib

atrial flutter

supraventricular tachy

ventricular tachy

class IA


anticholinergic (moderate)

side effects:

cinchoism (blurred vision, tinnitus, headache, psychosis)

cramping and nausea

enhances dig toxicity

class IA


anticholinergic (weak)

short half life

side effects:

lupus like syndrome

class IA


anticholinergic (strong)

side effects:

negative inotropic effect

Class IB clinical uses

ventricular tachy

dig induced ventricular arrhythmias

class IB


IV only; V tachys and premature ventricular contractions

side effects

good efficacy in ischemic myocardium

class IB


orally active lidocaine analog

side fx

good efficacy in ischemic myocardium

class IC clinical uses

a fib

a fluttter

supraventricular tachy (SVT)

class IC


supreventricular tachy

side fx

can induce life threatening ventricular tachy

class IC


supraventricular tachy

ventricular tachy

side fx

beta blocking and calcium channel blocking activity can worsen heart failure

class IA: Procainamide


conversion of supraventricular tachy

pre excited a fib

a fib/a flutter

ventricular tachy

class IA: procainamide


blocks I(Na)

depresses phase 0 - slows conduction

moderate K channel blocking activity prolongs Action Potential duration

Class IA: procainamide


liver acetylation into NAPA

other 50-60 percent renally excreted

NAPA metabolite is 100 percent renally cleared

has Class III activity as a K cahnnel blocker (markedly prolongs repolarization)

need to watch NAPA levels which are different from procainamide levels

Class IB: Lidocaine


ischemic ventricular tachy

dig induced arrhythmias (delayed after depolarizations)

class IB: Lidocaine


blocks open/inactivated state of Na channel

rapid on/off kinetics

more active in tachy arrhythmias and in depolarized tissues (ischemic)

no effect on atrial tissue because of their short action potential duration

class IB: Lidocaine



more toxicity with hepatic congestion (congestive heart failure)

monitor serum levels to minimize toxic effects

class IB: lidocaine

side fx

mainly CNS: confusion, paresthesias, dizzy, seizures

class IC: Propafenone





class IC: propafenone


binds open state of Na channels

slow on.off kinetics

use dependency - more activity with faster heart rates

good for svt arrhythmia conversion

bad for scar-related, reentrant vt

can make vt incessant

has beta blocking activity like propanolol

class IC: propafenone


hepatic -> hydroxypropafenone

parent propafenone has more beta blocking effect

7% are poor metabolizers that have more parent propafenone and an increased beta blocker effect

class IC: propafenone


coronary disease or LV dysfunction/.structural heart disease

class IC: propafenone

side fx

cardiac - may precipitate ventricular arrhythmias and congestive heart failure

cns - dizziness, taste disturbance

class IC: propafenone


can organize afib to slower flutter allowing for 1:1 av nodal conduction

class II: beta blockers



AFib/AFlutter rate control


Long QT patients

class II: beta blockers


beta 1 receptor blockade reduces cAMP production

reduces PKA activity

reduces cytosolic Ca in myocardial tissue

decreases the slope of phase 4 in upstroke in nodal tissue

prolongs conduction time and refractoriness of nodal tissue

class II: beta blockers

side fx





erectile dysfunction

weight gain



class III drugsdo what...?

block K currents

I(Kr) I(Ks) I(K1)

pure I(Kr) blocker - dofetilide

beta blocking activity - sotalol: 1:1 d,l-isomers (d has no beta blocking activity)

enhances delayed inward Na current - ibutilide

IB, II, IV activity - amiodarone

like amiodarone but lacks iodine moiety - dronedarone

class III: amiodarone






class III: amiodarone






also has Class II effect

class III: amiodarone



half life ~ 100 days

class III: amiodarone

side fx

thyroid, pulmonary, hpeatic, ocular, neurologic, renal

proarrhythmia Torsades - very rare

numerus drug drug interactions - raises warfarin levels

Class IV: Ca channel blockers




slowed rise of action potential

prolonged repolarization at AV node

increase threshold potential of SA node

decrease heart rate

decrease conduction velocity of AV node and increase effective refractory period of AV node

decrease re entry and

decrease av node conduction

class effect on EKG


PR 0

QRS increase

QT increase

class effect on ekg


PR 0


QT 0 or decrease

class effect on EKG


PR increase

QRS incraese

QT 0 or increase

class effect on EKG


PR 0 or increase


QT 0

class effect on EKG


PR 0 or increase

QRS 0 or increase

QT incrase

class effect on ekg


PR increase


QT 0

class V




rate contrial for a fib

class v



blocks Na/K ATPase which leads to inhibition of Na/Ca exchange, increasing intracellular Ca

vagomimmetic effect

class v



renal excretion

half life of 36 to 48 hrs with normal renal function

3 to 5 days in anuric pts

class v


side effects and toxicity

GI sypmtoms: loss of appetite, nausea, vomit, diarrhea

visual: yellow green halos and problems with colors

neuro: confusion, drowsy, dizzy, sleep disturbed, depression

cardiac: increased delayed after depolarizations. APC, VPC, paroxysmal atrial tachy with av block is pathognomonic for dig toxicity, vt or vf, heart block

class v



svt termination and diagnosis

class v



adenosine 1 receptor of av node

stimulates G(i) g proteins to decrease cAMP

increase K efflux and hyperpolarization

decrease Ca channel open probability

decrease I(f)

class v



adenosine deaminase in RBCs

half life ~ 10 sec

dipyridamole blocks adenosine deaminase

class v


side fx


heart block



class v



shortens action potential duration

potentiates Afib induction

class v



afib and wolf parkinson white syndrome: may incrase accessory pathway conduction

asthma - bronchospasms

cardiac transplants - exaggerated responses

class v adenosine


methylxanthines-caffeine, theophylline

common arrhythmias in SA node


sinus bradycardia

sick sinus syndrom

common arrhythmias in SA node


sinus tachycardia

common arrhythmias in atria



common arrhythmias in atria


atrial premature beats (APBs)

atrial flutter

atrial fibrillation

paroxysomal supraventricular tachyarrhythmia

focal atrial tachycardia

multifocal atrial tachycardia

common arrhythmias in AV node


conduction blocks

junctional escape rhythm

common arrhythmias in av node


paroxysomal reentrant tachycardia (av or av nodal)

common arrhythmias in ventricles


ventricular escape rhythm

common arrhythmias in ventricles


ventricular premature beats

ventricular tachy

torsades de pointes

ventricular fibrillation

sick sinus syndrom general

intrinsic SA node dysfunction that causes periosd of inappropriate bradycardia

sick sinus syndrome symptoms




sick sinus syndrome treatment

IV anticholinergics (atropine)

beta adrenergics

if chronic, a pacemaker is requirede

elderly patients with SSS are also susceptible to

SVTs and Afib

this combination = bradycardia-tachycardia syndrome

Escape rhythms

cells in the av node and his purkinje system are capable of automaticity like the sa node, but usually have slower firing rates so they don't take over

if sa node becomes impaired or if there's some kind of conduction block, escape rhythm can emerge from the more distal latent pacemakers

junctional escape rhythm

arise from the av node or bundle of his

characterized by a normal, narrow QRS complex

occur in sequence

appear at a rate of 40-60 bpm

EKG of junctional escape rhythm

qrs complexes are NOT preceeded by normal p waves because the impulse originates below the atria

retrograde p waves can be observed as an impulse propagates from distal pacemakers up to the atria

these p waves typically follow the QRS and are inverted

inverted retrograde p waves in jucntion escape rhythm

negative deflection in leads II, III, aVF

indicating activation of the atria from the inferior direction

ventricular escape rhythms

even slower

30-40 bpm

widened qrs

why widened qrs in ventricular escape rhythms?

complexes are wide because the ventricles are not depolarized by the normal rapid simultaneous conduction of the right and left bundle branches

instead, from a more distal point in the conduction system

EKG of ventricular escape rhythms

qrs morphology depends on the site of the origin of the escape rhythm

originating from the left bundle branch will cause a right bundle branch block pattern

originating form the right bundle branch will cause a left bundle branch block pattern

why do we have junctional and ventricular escape rhythms?

they're protective backup mechanisms that maintain a heart rate and cardiac output when the sinus node or normal av conduction fails

treatment of escape rhythms

IV anticholinergics

beta adrenergics

pacemakers if chronic

av conduction system is made up of

av node

bundle of his

left and right bundle branches

what leads to av block

impaired conduction between the atria and ventricles

1st degree av block

prolongation of the normal delay between atrial and ventricular polarization

the impariment is usually within the av node itself and can be caused by a transient reversible influence or a structural defect

1st degree av block ekg

pr interval is lengthend to >5 small boxes

1:1 P:R ratio is maintained

reversible causes of av block

heightened vagal tone

transient av node ischemia

drugs that depress conduction through the av node like:

beta blockers

some ca channel antagonists


other antiarrhythmics

structural causes of av block


chronic degenerative diseases

1st degree av block treatment

usually benign and asymptomatic

requires no treatment

2nd degree av block

characterized by intermittent failure of av conduction

2nd degree av block ekg

some p waves not followed by qrs complexes

2nd degree av block

mobitz type 1

wenkebach block

degree of av delay gradually increases with each beat until an impulse is completely blocked

almost always results form impaired conduction in the av node

2nd degree av block

mobits type 1

wenkebach block


a qrs does not follow a p for one beat

you see a progressive increase in PR interval until a single qrs is absent

then PR goes back to initial length and the cycle starts over

2nd degree av block

mobitz type 1

wenkebach block


usually benign

treatment is typically not necessary

in symptomatic cases administration of atropine or isoproterenol improves av conduction transiently

permanent pacemaker required for symptomatic block that does not resolve spontaneously

2nd degree av block

mobitz type 2

sudden intermittent loss of av conduction without preceeding gradual lengthening of the PR interval

usually caused by a block beyond the AV node in the bundle of his or purkinje system

2nd degree av block

mobitz type 2


PR interval isn't changing but a qrs just gets dropped

may persist for 2 or more beats

multiple Ps are NOT followed by QRSs

known as high grade av block

qrs is often widened in a pattern like right or left bundle branch block

2nd degree av block

mobitz type 2


more dangerous than type I and treatment with a pacemaker is usualy warranted, even in asymptomatic patients

3rd degree av block

complete heart block

presenet when there is complete failure of conduction between the atria and ventricles

electrically disconnects the atria and ventricles

atria depolarize in response to SA node

more distal escape rhythm drives the ventricles independently

caused by MI or chronic degeneration

3rd degree av block


no relationship between p waves and qrs complexes

p wave rate is not related to qrs intervals

3rd degree av block treatments

permanent pacemaker is almost always necessary


when HR is > 100bpm for 3 beats or more

results from:

enhances automaticity

re entry

triggered activity

supraventricular tachyarrhythmia (SVT)

arises above the ventricles

ventricular tachyarrhythmia

arises from within the ventricles


sinus tachycardia

sa node discharge rate >100bpm

normal p waves and normal qrs complexes

usually results from increased sympathetic or decreased vagal tone


atrial premature beats

originate from automaticity or re entry in an atrial focus outside the SA node

often exacerbated by sympathetic tone


atrial premature beats (APBs)


appears as earlier-than-expected p wave with an abnormal shape

qrs is usuallly normal. if they're wide, it's apb with aberrant conduction


atrial premature beats (APBs)


only req treatment if they're symptomatic

caffeine, alcohole, stress can predispose to APB

beta blockers are the initial preferred treatment


Atrial flutter

rapid, regular atrial activity at a rate of 180-350 bpm

many of these impulses reach AV node during refractory period and dont conduct to the ventricles


atrial flutter

example of 2:1 block

300bpm at atria

150 bpm at ventricles


atrial flutter


p waves have a sawtooth appearance

faster rates (>100bpm) cause palpitations, dyspnea, weakness


atrial flutter


vagal maneuvers like the carotid sinus massage decrease AV conduction and further lower ventricular rate

antiarrhythmics that reduce the rate of atrial flutter can be dangerous because they allow the av node more time to recover between impulses.

AV node may begin to conduct 1:1

atria could be 280bpm w/ 2:1 block, 140 bpm ventricles

if the atrial rate slows to 220bpm, the ventricle rate could accelerate to 220bpm


atrial flutter

treatment, drugs etc

electrical cardioversion to restore sinus rhythm

rapid atrial pacing w pacemaker

beta blocker, ca channel blocker, or digitalis to slow ventricular rate

then restore sinus rhythm with antiarrhythmics that slow conduction or prolong refractory period (class IA, IC, III)

catheter ablation


atrial fibrillation

chaotic rhythm with atrial rate so fast that distinct p waves are not discernible on ECG (350-600 discharges/min)

avg ventricular rate in untreated A Fib is 140-160 bpm

mechanism probably involves multiple wnadering re entrant circuits within the atria


atrial fibrillation


irregularly irregular rhythm

ecg baseline shows low amplitude undulations puncutated by QRS complexes and T waves


atrial fibrillation

symptoms and signs

Afib is often associated with enlarged L or R atrium

heart failure, hypertension, coronary artery disease, pulmonary disease

^^^all promote AFib because they promote atrial enlargement

why is a fib so bad?

rapid ventricular rates may compromise cardiac output leading to hypotension and pulmonary congestion

absence of organized atrial contraction promotes blood stasis in atria, increasing risk of thrombus formation, especially in left atrial appendage



treatment considers 3 things

ventricular rate control

methods to restor esinus rhythm

assessment of the need for anticoagulation to prevent thromboembollism



drug treatment

similar to Atrial Flutter

beta blockers and calcium channel antagonists promote block in av node and reduce ventricular rate

digitalis is less effective

class IA, IC, III antiarrhythmics are used to restore sinus rhtyhm

^^have bad side fx so they're not used in asymptomatic patients

AFib for more than 48 hours needs anticoagulation

MAZE procedure and catheter ablation are alternatives to antiarrhythmics

catheter ablation can be used to induce complete AV block and slow ventricular rate. a permanent pacemaker is needed after this


Paroxysmal supraventricular tachycardias (PSVTs)

sudden onset and termination

atrial rates between 140 and 250 bpm

narrow (normal) qrs complexes

mechanism is most often re entry involving AV node, atrium, or an accessory pathway

enhanced automaticity and triggered activity in the atrium or AV node are less common causes



AV Nodal Re Entrant Tachycardia (AVNRT)

most common form of PSVT in adults

there can be multiple potential pathways through the AV node and they can conduct at different velocities

the slower pathway usually has a shorter refractory period



AVNRT pathway

Atrial premature beat travels to the junction between slow and fast pathways

conducts down slow pathway since it has a shorter refractory period and already repolarized

by the time it gets to the compact portion of the AV node, the distal end of the fast pathway has repolarized and the signal can go distal to the bundle of his AND backwards up the fast pathway toward the atrium

at the top of the fast pathway it comes back down thte slow pathway = loop





ecg shows a regular tachycardia with normal width QRS

retrograde p waves usually get hidden in QRS but they can sometimes be seen at the terminal portion of QRS complex

they'l be inverted in leads II, III, aVF since the atrial activation is going "up"




symptoms and signs

usually tolerable with just palpitations

rapid tachycardias can cause lightheadedness or shortness of breath

elder patients can get syncope, angina, pulmonary edema






terminate re entry by imparing conduction in AV node

valsalva maneuver or carotid sinus massage may block AV conduction and terminate the tachycardia


IV adenosine impairs AV nodal conduction and aborts re entrant rhythm

other options= beta blockers and calcium channel antagonists

catheter ablation or class IA, IC antiarrhythmics might be used for chronic problems with AVNRT


Atrioventricular Re entrant Tachycardias (AVRTs)

similar to AVNRTs except one limb of the loop is made up of an accessory tract instead of 2 separate slow and fast pathways through the AV node

accessory tract

bypass tract

an abnormal band of myocytes that spans the AV groove and connects atrial to ventricular tissues separately from the normal conduction system

Ventricular pre-excitation syndrome

Wolff Parkinson White syndrome

atrial impulses can pass in an anterograde direction to the ventricles through both the av node and the accessory pathway

conduction through the accessory pathway is usually faster than that via the AV node

ventricles are stimulated earlier than by normal conduction over the AV node

Ventricular pre excitation syndrome

WPW syndrome


during sinus rhythm:

PR interval is short because ventricular stimulation starts earlier than normal

QRS has a slurred, rather than sharp, upstroke (delta wave) because the accessory pathway activates the ventricle slower than the purkinje system

QRS is widened because it represents the fusion of 2 events (conduction through both pathways)

ventricular pre excitation syndrome

WPW syndrome


pharmacologic management

have to be more careful than with AVNRT patients

beta blockers, calcium channel antagonists, and digitalis all can block condcution through the av node but they do not slow conduction over the accessory pathways

Common ventricular arrhythmias




Ventricular premature beats (VPBs)

similar to APBs, VPBs are common and often asyptomatic and benign

a VPB arises when an ectopic ventricular focus fires an action potential



appears as a widened QRS complex because the impulse travles from its ectopic site through the ventricles via slow cell to cell connections rather than the faster his-purkinje system



in healthy patients, treatment is reassurance and symptomatic use of beta blockers

if patients have advanced structural heart disease with features that place them at risk for life-threatening arrhythmias, placement of an inflatable cardioverter defibrillator (ICD) is recommended

Ventricular Tachycardia

series of 3 or more VPBs

sustained VT

persists more than 30 sec

produces sever symptoms like syncope


requires termination by cardioversion or administration of a drug

unsustained VT

self terminating episodes


qrs complexes are wide (>0.12sec)

100-200 bpm

monomorphic VT

QRS complexes all look the same and rate is regular

polymorphic VT

qrs complexes change in shape and rate varies

symptoms of VT

vary depending on the rate, duration, underlying condition

sustained VT can cause low cardiac output leading to syncope

pulmonary edema

cardiac arriest

but if it's slow (<130bpm) it might only cause palpitations

distinguishing monomorphic vt from supraventricular tachycardia

width of the qrs complex

monomorphic vt = wide

svt = narrow (normal) unless SVT with aberrant ventricular conduction

SVT with aberrant conduction occurs in:

patients with underlying conduction abnormality like a bundle branch block

repetitive rapid ventricular stimulation durign SVT finds one of the bundle branches refractory

pt develops antidromic tachy through an accessory pathway

managing patients with VT

acute treatment = cardioversion

iv administration of antiarrhtyhmics, procainamide/lidocaine

after sinus rhythm is restored: determine whetehr underlying heart disease exists

correct aggravating factors like:
myocardial ischemia

electrolyte disturbances

drug toxicities

beta blockers, calcium channel blockers, catheter ablation are commonly effective to control symptomatic episodes of idiopathic VT

torsades de pointes

a polymorphic VT that presents as varying amplitude of QRS

can be produced by EADs (triggered activity) particularly in patients with prolonged QT intervals

torsades symptomes

light headed


main danger is from degeneration into VFibt

torsades treatment

when it's drug or electrolyte induced, correcting the underlying cause abolishes recurrences

in other cases, administration of IV magnesium represses episodes

also: shorten QT intervals via beta adrenergic stimulating agents or an artificial pacemaker

if torsades is because of a congenital prolongation of QT, beta blockers are preferred

sympathetic stimulation aggravetes the arrhythmia in many such individuals

ventricular fibrillation

immediately life threatening

results in disordered, rapid stimulation of the ventricle with no coordinated contractions

result = no cardiac output and death if not quickly reversed

VF is often initiated by an episode of VT that degenerates into multiple smaller wavelets of re entry that wander the myuocardium

Ventricular feibrillation


only effective therapy is prompt electrical defibrillation

after the heart has been converted to a safe rhythm, correct underlying issues:

electrolyte imbalances, hypoxemia, acidosis

IV antiarrhythmics can be administered to prevent immediate recurrences

inherited arrhythmogenic disease

familial arrhythmia

monogenic diseases with mendelian inheritance

conditions include:



ion channels proteins

muscle proteins



long qt syndrome

short qt syndrome

brugada syndrome

catecholaminergic vt

idiopathic vt/vf





arrhythmogenic RV/LV


non compaction

background of IADs

relative rare -> 1:500 to 1:10000

young people [childhood -> midlife]

high risk of sudden cardiac arrest/arrhythmia

3 representative examples of genetic mutations leading to arrhythmias

long qt syndrome

brugada syndrome

hypertrophic cardiomyopathy

where to you measure the QT interval?

lead II or V5

Long QT Syndrome 1


k current


mostly exercise triggered

Long QT Syndrome 2


k current


mostly emotional stress triggered

Long QT Syndrome 3


Na current


mostly triggered during sleep/repose


HERG channel

hERG channel makes the alpha subunit of the k channel that does the I(kr) current

conducts K out of the cell to make repolarization happen

if it's blocked or doesn't correctly undergo conformational changes, it can be deficient in the amount of K it pumps out

pumping out K less effectively can prolong the repolarization phase of a cardiac myocyte's action potential

LQTS risk by QTc

there is stratification among the quaqrtiles

the shortest QTs (closest to normal) are associated with better survival than the longer QTs

LQTS mechanisms

abnormal impulse can lead to triggered event

DAD reaches threshold and fires off in a triggered way

EAD can trigger arrhythmia

LQTS treatment

beta blockers

work best for LQT1

then LQT2

then LQT3

Brugada syndrome

right bundle branch block and ST segment elevation in leads V1, V2, V3

a marker for sudden death in patients without demonstrable structural heart disease

brugada syndrome ekg

ST segment elevation and what looks like RBBB but it's "coved" or elongated/wide

especially in v2

the ekg is really dynamic though. it can change through out the day,

brugada symptoms

cluster by age

most abundant in 31-40 year olds and 41-50 year olds


the Na channel messed up in brugada

has three states: resting, open, inactivated

resting state is closed compoletely

depolarization causes it to open up and Na can come into the cell

eventually it inactivates. It stays open but it's plugged on the cytosolic end. This plug is responsible for the refractory period

once inactivated the channel needs repolarization to reactivate

phenotypic heterogeneity in brugada

different presentations from the same channel

coving of the QRS can be highlly variable from pt to pt

what is this notch

what is this notch

the I(to) current activates at phase 1 and pumps K out, but the balancing action of Na in is defective, so membrane potential gets negative more quickly than usual, without the gradual plateau

brugada causes a gradient between what?

between endocardium and epicardium

the epicardium is the one that has the deeper notch. the endocardium looks relatively less affected.

brugada re entry

endocardium and epicardium fire cardiac action potentials but the epicardium ap collapses

an early afterdepolarization fires off and stimulates another part of the Epi. that part fires backwards to the first part of epi and then back up to the endocardium

brugada treatment


catheter ablation

whatever you do, the most important thing is to prevent the v fib in the first place

mutations in hypertrophic cardiomyopathy

just about anythign int he cardiac sarcomere

troposin I, troponin T, tropomyosin, actin

pathologic elements to HOCM

LVOT obstruction

impaired disatology

Mitral regurg/papillary muscle displacement



treatable at all levels

for sudden death: ICD

for progressive heart failure: drugs, myectomy

for end stage: transplant

for AFib and stroke: drugs like warfarin

relation between LV wall thickness and sudden death

incidence of sudden death rises with LV wall thickness

above 30 milimeters there's a super high risk


scrape out the thick portion of the septum

increases survival

prior cardiac arrest or sustained vt

ICD recommended

family history - SD in first degree relative

or LV wall thickness >30 mm

or recent unexplained syncope

ICD reasonable

nonsustained VT

abnormal BP response

ICD can be useful if there's

LVOT obstruction


LV apical aneurysm


alcohol and caffeine causing arrhythmias

caffeine can release norepi

heavy drinking can make you lose elctrolytes(?)

what does it tell you if an arrhythmia is or isn't exercise induce?

if it's not exercise induced then it's probably not related to a coronoary problem

what do diving into a swimming pool or defecation do to help alleviate arrhythmia?

induce vagal tone

if this works, it implies that the arrhythmia is related to the AV node

you wouldn't expect a ventricular arrhythmia to respond to vagal toneh

hyp[ertension and diabetes with arrhythmia?

they're risk factors for heart diseasec

chest trauma with arrhythmia?

could be scarring

where do atrial premature beats come from

pulmonary veins

if atrial premature beat hits the right atrium

it can find its way into a pathway involving the whole thing:



tricuspid annulus

coronary sinus

leads to atrial flutter

p wave morphologies

p wave morphologies

first one is normal

second one implies the LA is enlarged

third one implies the RA is enlarged

a fib would be most likely if LA was enlarged

PR interval changes

if av node was diseased the PR interval would get longer

a shorter PR interval could occur if the AV node is getting bypassed

narrow complex tachycardia

implies it's going through the normal pathwayw

wide complex tachycardia

would imply that a different pathway is being used and that they tachy is ventricular

if you give a patient adenosine and it breaks the tachycardia

it means the tachycardia involves the AV node

what clinical and ecg features suggest a supraventricular etiology?

vagal maneuvers stop it

narrow qrs, preceded by p wave, looks "normal"

what is differential from a wide qrs tachy

svt with rbbb


wpw syndrome - delta waves

sudden on, sudden off in ekg suggests which mechanism for tachy


why are beta blockers successful in controlling this arrhythmia

beta blockers impair AV nodal conduction and there are exta-atrial beats

arrhythmia conference chart

sinus tachycardia

not dependent on av node

has organized atrial activity

regular rhythm but could warm up and cool down

gradual onset/offset

arrhythmia conference chart

atrial tachycardia

ectopic atrial focus

not dependent on av node

has organized atrial activity


gradual onset/offset

arrhythmia conference chart

atrial fibrillation

not dependent on AV node (originates in pulmonary veins in LA)

no organized atrial activity

not regular

rapid onset/offset

arrhythmia conference chart

atrial flutter

not dependent on av node - caval tricuspid isthmus

has organized atrial activity (250-240ms) sawtooth waves

v1 has what look like p waves

could be regular or irregular

rapid onset/offset

arrhythmia conference chart


dependent on av node

organized atrial activity


rapid onset/offset

arrhythmia conference chart


dependent on av node activity and accessory pathway

organized atrial activity


rapid onset/offset with delta wave

blood flow

actual volume of blood flowing through a vessel, organ, or the entire circulation in a given period

measured in ml/min

equivalent to cardiac output

relatively constant at rest

varies through individual organs according to immediate needs

which tissue has the most blood flow at rest?


radial artery: inactive hand

high pulsatility waveforms are a feature of circulatory systems with high resistance to blood flow (High peripheral resistance)

radial artery: active hand

lower resistance to blood flow?

bernoulli's principle

as the speed of a moving fluid increases, the pressure within the fluid decreases

to keep the total energy the same, if velocity goes up, pressure has to go down

pressure and flow relationship

as stenosis severity increases, blood velocity increases to maintain flow

at 75% stenosis, flow begins to decrease and the pressure generated downstream decreases creating a pressure gradient

vascular physiology principles (3)

diastolic flow is important to maintain adequate tissue perfusion

an increase in blood velocity occurs at a stenosis

at 75% stenosis flow and pressure decrease

aneurysm definition

to widen or dilate

focal dilatation with at least 50% increase over normal arterial diameter

>3cm in abdominal aorta

1.8cm for iliac arteries

abdominal aortic aneurysm present in 6-9% of men over 65 years old in US

ascending aortic aneurysm

characterized by cystic medial degeneration

degeneration and fragmentation of elastic fibers, accumulation of collagenous and mucoid material within the medial layer

occurs most commonly with aging and hypertension

other causes:

marfan syndrome

loeys-dietz syndrome

ehlers danlos syndrome

bicuspid aortic valve



abdominal aorta epidemiology

traditional risk factors

increasing age


male sex


screening for AAA in old men improves morbidity and mortality

CT scan of abdominal aortic aneurysm

at what diameter does rupture risk start for AAA

4-5 cm

aortic wall tension

pascal's principle requires that pressure is the same everywhere inside the balloon at equilibrium

but examination revelas that there are great differences in wall tension on different parts of an aortic aneurysm

variation is described by laplace's law - wall tension is proportional to the product of pressure and radius

pressure stays the same, radius goes up, so tension goes up - leading to rupture

AAA therapy


smoking cessation

hypertension therapy like beta blockers, ace inhibitors, angiotensin receptor blockers

endovascular therapy

lower early risk -problems over time

open therapy

up front risk - better durability over time

Peripheral Artery disease - how many patients have symptoms

1 in 5 people over 65 has PAD

only 1 in 10 of these patients has classical symptoms of intermittent claudication (walking leading to pain. stopping and it gets better)

clinical presentations of peripheral artery disease

50% asymptomatic

33% atypical leg pain

15% classic claudication

1-2% critical limb ischemia (gangrene or pain at rest)

relationship between increased age and peripheral vascular disease

for PAD, once you reach 70 incidence exponentially goes up

ultrasound velocity signal in PAD

monophasic waveform

only see broad upstroke through all of systole, no diastolic backflow

normal vessel characteristics

laminar flow

endothelial cell mediated vasodilation

distal pressure and flow maintained

PAD vessel characteristics

high resistance

collateral vessel

turbulent flow

pressure drop across stenosis

impaired endothelial function

inability to increase flow with exercise

dx of PAD includes...



fibromuscular dysplasia


thrombotic disorders

vascular tumor


cramping, tightness, aching, fatigue

exercise induced

does not occur with standing

standing up relieves it

goes away in less than 5 minutes


cramping, tightness, aching, fatigue, tingling, burning, numbness

variably induced by exercise

does occur with standing

sitting relieves it

takes 30 minutes to go away

PAD comprehensive vascular exam includes

pulse examination:






dorsalis pedis

posterior tibial

physical exam:
bilateral arm blood pressure (is it the same in both arms)

cardiac exam

palpation of abdomen for potential aneurysm

auscultation for bruits

examination of lower extremities

measureing ankle brachial index ABI

pressure in ankle should be higher or the same, but not lower

take highest pressure in L and R ankles and divide by the highest arm pressure (whichever arm is highest)

anything above 0.91 is normal, below that is pathologic

exercise and leg pressure

should NOT have a drop in pressure when you exercise

ABI vs mortality

as ABI decreases, risk of mortality increases

but once you get to >1.4 you have incompressible arteries - different problem

PAD therapy


exercise does better than intervention

PAD medical therapy

smoking cessation

lipid modification - statins

HTN control


diabetes control

foot care

risk factors

symptomatic relief - cliostazol and pentoxifylline

stroke - vision complaints?

opthalmic artery

one of the first early warning signs

hollenhorst plaque

you can see a cholesterol embolus in the retina from the internal carotid artery

carotid artery disease

medical therapy

antiplatelet therapy


risk factor modification - smoking cessation, statins, HTN, diabetes control

arteriovenous malformations

defects in the vascular system

direct connections between arteries and veins

it is believed that they often result from mistakes during embryonic or fetal development

can happen anywhere but are most common in brain or spinal cord

greatest potential danger is hemorrhage

treated via surgery or focused irradiation

leading cause of death in the US


risk factors for coronary artery disease


mutations and strong family history



Clotting and inflammatory factors


increased LDL, decreased HDL, increased Tg





sedentary lifestyle


baseline levels of the inflammation marker hsCRP in apparently healthy men can predict the riskk of first MI or ischemic stroke

aspirin reduced inflammation which is a component of athersclerosis

atheroma formation

stage 1

retention of Apo B lipoprotein

particles enter the tunica intima from the lumen and are retained

atheroma formation

stage 2

retained lipoprotein particles are likely modified (oxidized and aggregated)

intima gets larger, more lipid shows up

atheroma formation

stage 3

monocytes are attracted to the artery, which they enter and turn into macrophages

atheroma formation

stage 4

macrophages ingest retained lipoproteins

"foam cells" die and make fatty streak

atheroma formation

stage 5

other immune cells enter and area ctivated

inflammatory cytokines, chemokines, proteases, free radicals cause further tissue damage

cap between fatty and thrombogenic mess protects it from rupturing

hallmarks of defective inflammation resolution in atherosclerosis

persisten influx

defective egress

retained lipoproteins


thinning of fibrous cap

thinning of fibrous cap

two processes:

synthesis involves Platelet derived growth factor and TGF-beta inducing smooth muscle cells + collagen and elastin to make the cap


t lymphocytes release interferon gamma which inhibits the synthesis

and make cd40L which causes foam cells to release MMPs that degrade the matrix and thin the cap


when the cap gets too thin, the atheroma can rupture

when blood and fat mix a thrombus forms

endothelial dysfunction

chemical irritants and hemodynamic stress can cause dysfunction of the endothelium

lipoprotein entry, inflammatory cytokines

chemokines and leukocyte adhesion molecules

leykocyte recruitment

you can improve endothelial function by lowering blood pressure and dialyzing lipid

unregulated uptake of modified LDL

foam cell formation

2 major adverse consequences of endothelial dysfunction

increased recruitment of inflammatory cells

loss of NO mediated vasodilation

what does arginine do for vasorelaxation?

NO synthase makes NO out of arginine

NO can diffuse to smooth muscle cells and induce relaxation by increasing cGMP

atherosclerotic endothelium allowing vasoconstriction

there's a breakdown between the conversion of arginine to NO

instead of NO you make OONO (peroxy nintrates) preventing vasodilatory response

consequence of proximal obstruction

a region becomes inadequately perfused

angina pectoris

discomfort of thoracic cavity that comes on with exercise and goes away after

early atheroma can go two ways

stable plaque

small lipid pool

thick fibrous cap

preserved luman

vulnerable plaque

large lipid pool

thin fibrous cap

many inflammatory cells

vulnerable plaque

ruptures and forms thrombus

it can heal with a narrowed lumen and fibrous intima


you can get an acute MI

angina of two sorts

demand angina

comes on with exercise

resting angina - unstable

a plaque rupturing

therapeutic opportunities for plaque rupture

lower apoB lipoproteins

dampen inflammation and restore homeostasis

enhance efferocytosis and restore fibrous cap

atherosclerosis pathophysiology

stage 1

endothelial dysfunction

HDL prevents cell adhasion, LDL promotes cell adhesion

too much LDL and platelets and monocytes adhere to the vessel wall

atherosclerosis pathophysiology

stage 2

smooth muscle emigration from media to intima

macrophage activation

macrophages come from lumen

sm muscle comes from tunica media

atherosclerosis pathophysiology

stage 3

macrophages and smooth muscle cells engulf lipid

they get engorged and make a fatty streak

atherosclerosis pathophysiology

stage 4

smooth muscle proliferation

collagen and other ecm deposition

extracellular lipid

vessel wall becomes very full because of all the ECM junk

fibrofatty atheroma is visible


4 stages condensed

endothelial injury leads to dysfunction

adhesion of monocytes and platelets and lipid influx

migration of macrophages and smooth muscle cells into the intima

phagocytosis by macrophages and smooth muscle cells of lipids = fatty streaks

proliferation of SMCs and deposition of ECM: fibrofatty atheroma


major role in fibrosis stage 4

an inhibitor of TGF-beta might inhibit atherosclerotic process

what's this?

what's this?

macrophages ldoaded with lipids

dangerous of fibroatheromas

increased demand can't get met because of blockage

in the plaque you can have a hemorrhage

intra plaque hemorhage can make plaque bigger and cause more occlusion

ultimately you can get a thrombus formation in the lumen

atherosclerosis complications



aneurysm and rupture


aneurysm definition

dilatatio of segment of vessel

true aneurysm

bulging because the whole lumen is bulging

false aneurysm

something in the vessel wall is causing the bulge, like an extravasation of blood

difference between fusiform and saccular aneurysms

you can't clip a fusiform aneurysm because the whole thing is bulging

you CAN and probably SHOULD clip a saccular aneurysm

aneurysm etiologies


infectious (syphilis)





aortic dissection

hole in the wall of the vessel

a small local dissection causes pain but a big one is fatal

entry point is an atheromatous lesion

a weak point that lets the blood flow get into the vessel

contributing factors to aortic dissection



hypertension in 60-70 percent

marfan or ehlers danlos syndromes

type a dissection

proximal dissection with variable distal extension

ascending part is dissected

could occlude coronary arteries or carotid arteries and mess with perfusion to heart or brain

these patients need to go to the OR

type b dissection

distal dissection

tend to rupture into the left thorax

only the descending part is dissected

they usually need medical management

aortic dissection complications

external rupture: in 90 percent may be fatal

compression of origins of arteries




mesenteric arteries


classify based on the type of blood vessel they affect

giant cell arteritis - lg vessels

polyarteritis nodosa - med vessels

wegener granulomatosis - small vessels

buerger's disease - mixed

giant cell arteritis

over 50y


palpable tender nodularity of artery

visual problems, blindness

ESR markedly elevated

polymyalgia rheumatica

steroid therapy

polyarteritis nodosa

young adults

acute, subacute, or chronic

rever, weight loss, abdominal pain, melena, muscular aches, peripheral neuritis

untreated, fatal, either during an acute fulminant attack or following a protracted course

corticosteroids - remission or cures in 90% of cases

polyarteritis nodosa

transmural inflammation (neutrophils, eosinophils, mononuclear cells)

fibrinoid necrosis

later, fibrousd thickening

all stages of activity may coexist in different vessels or even within the same vessel

wegener granulomatosis

males > females, 40 yo

syndromes similar to PAN and respiratory involvement

fever, persistent pneumonitis, chronic sinusitis

mucosal ulcerations o fthe nasopharynx

renal disease

skin rashes

muscle pain, joints, neuritis

eye, skin, and heart

untreated, aggressive course; 80% death

buerger's disease

more prevalent in young adult men smokers

immunologic and thrombogenic mechanisms

only smoking cessation stops disease activity

Deep veint thrombosis and pulmonary embolus

thromboembolism is seen in over 275000 americans annually

deep veinsof the calf

therapeutic emergency: heparin

risk factors for dvt


prolonged bed rest


fractures of hip or femur

massive trauma


heart attack


oral contraceptives


pulmonary embolus

often in hospitalized patients

shortness of breath, chest pain, syncope, hemoptysis

chest x ray, CT, pulmonary ventilation/perfusion scan, pulmonary angiogram

pulmonary embolus treatment and prognosis

thrombolytic and anticoagulant therapy

death rate - 30% if undiagnosed, 3% with early diagnosis and treatment

with large emboli mortality >50%

varicose veins

distended veins because valves cant keep the blood up

relationship between cholesterol and coronary heart disease risk

increase cholesterol, increase rate of death from heart disease

naturally occurring lipids and their functions

triglycerides - energy storage

cholesterol - important precursor of steroid synthesis

phospholipids - important components of cell membranes


allow insoluble lipids to travel in blood

apolipoproteins are found on the surface and serve as ligands for cellular receptors


in the liver


catabolism of VLDL


catobolism of IDL

bad cholesterol


liver, intestine, other

good cholesterol

bile salts

solubilize cholesterol coming from the liver

VLDL and LDL cholesterol transport

VLDL loses ApoC-II and becomes IDL

IDL loses ApoE and becomes LDL

LDL has ApoB-100 left and can enter muscle/heart/adipose tissue or participate in atherogenesis

prevention of atherosclerotic cardiovascular disease

primordial prevention

prevent the development of risk factors for CVD

primary prevention

prevent the first CVD event

secondary prevention

prevent subsequent CVD events

benefits of LDL reduction

lowering LDL may slow progression, stabilize, or reverse atherosclerosis

lowering LDL improves endothelial cell function

lowering LDL prevents MI and improves survival

Non HDL calculation

total cholesteral minus HDL cholesterol

this has shown to be a stronger predictor of cardiovascular risk than LDL cholesterol

treatment of dyslipidemia

diet and exercise!!


intestinal acting cholesterol lowering agents like bile acid sequestrants and cholesterol absorption inhibitors

nicotinic acid

fibric acid derivatives

statins-HMGCoA reductase inhibitors

fish oil

new drugs for extremely high ldl

emerging classes - pcsk9

bile acids

breakdown product of cholesterol

40-70% reabsorbed in the small bowel

act as detergent - help - make cholesterol soluble

inhibition of bile acid reabsorption

bile acid sequestrants




^^aka WelChol - also lowers blood sugar (reduces Hba1c)i

nhibition of cholesterol absorption

selective cholesterol absorption inhibitors


if you sequester bile salts

you cant solubilize cholester

cholesterol goes into stool

LDL goes down by 10 or 20 percent

BUT the liver makes more to "compensate" so it kind of buffers the effect in a bad way

remember about Welchol!

it lowers LDL AND blood sugar

bile acid binding resin side effects


may interfere with absorption of fat soluble vitamins

may interfere with absorption of digitalis, thiazides, warfarin, aspirin

can raise Tgs


localizes on the brush border of intestinal epithelial cells

circulates enterohepatically

well tolerated, no effect on vitamin absorption

long biological half life

used mainly as an add on to statins

decrease heart attack and stroke

ezetimibe + statin

wayyy lower LDL levels, even better than with just statin

also lowers event rate percentage

nicotinic acid

decreases vldl production

decreases ldl formation and increases hepatic clearance of LDL precursors

raises HDL levels

lowers Lp(a) levels

^^^particle that has been linked to clots

nicotinic acid


check liver transaminases, glucose levels, lipid levels, and uric acid levels

used infrequently today

was negative for reducing cardiovascular events

niacin side fx

intense flushing and pruritis

hepatic toxicity - increasing transaminases

glucose intolerance (raises blood sugar)

elevate uric acid levels

contraindicated in patients with gout

dont give niacin to patients with gout!!!


lower trigylcerides by 35-50 percent

barely lower ldl ata ll

raises HDL a little

most useful in pts with elevated triglycerides or low HDL

should be avoided in pateitns with hepatic or renal dysfunction

caution with patients on statins - increases risk of rhabdomyolysis

use fenofibrate if you have to add fibrate to statin



slight increase in HDL

decent degrease in TG

no change in LDL



indicated for severe hypertriglyceridemia

pts at risk for pancreatitis

safer than other fibrates when used with a statin

cna elevate creatinine (kidney function)

fibrate evidence

on background statin Rx, fibrate does not reduce CV events

fish oil treatment

used to lower high TGs

efficacy depends on baseline TGs

FDA approved versions for pts with baseline TG above 500

may increase ldl

can increase bleeding time and interact with warfarin!!!

often stopped prior to surgery

what does HMG-CoA reductase do

converts acetate to cholesterol

so an HMG-CoA reductase inhibitor...


lowers cholesterol synthesis

statins and diet

statins reduce cholesterol production


doesn't do anything to the choelsterol you eat, just the cholesterol you make

statin side fx

elevations in transaminases

hepatix toxicity related to ^^ if too much

myositis presenting as muscle pain or weakness with elevated muscle enzyme levels

recent link to increased risk of diabetes (HgA1C goes up)

can affect memory

statin therapy recommended in 4 groups(!!!)

adults with clinical ASCVD (heart diseae)

adults with LDL >190 mg/dL

adults 40 to 75 years old with diabetes

adults >7.5% estimated 10 year risk of ASCVD


stimulates endocytosis of LDL receptors. more pcsk9 means fewer LDL receptors means more LDL floating around

targeting PCSK9

works in, like, everybody

conclusions from lipid therapy lecture

LDL-C strong risk factor for coronary artery disease

LDL-C can be lowered by statins, ezetimibe, pcsk9 antibodies, bile acid resins, niacin

TGs also appear to be a risk factor, though not as strong

can be lowered by fibrates, niacin, fish oil

PR interval normal, but HR < 60 bpm

QRS normal

QTc normal

Sinus bradycardia

brief irregular tachycardia followed by slower beats

bradycardia-tachycardia syndrome

no p waves evident

normal width qrs

HR < 50

junctional escape rhythm

no p waves evident

widenedQRS with a bundle branch block pattern

HR < 40

ventricular escape rhythm

PR interval: 260ms prolonged

QRS normal

QTc normal

prolonged PR and everything else okay = 1st degree AV block

start with short PR interval

PR interval lengthening

until eventually there's a P not followed by a QRS

2nd degree Type I

Mobitz type I

wenkebach block

regular PR interval

missing QRS

back to normal

2nd degree AV block

Mobitz Type II

Multiple QRS missing in a row

high grade 2nd degree type II AV block

P and QRS are unrelated

QRS looks like L or R BBB

3rd degree AV block

P waves and QRS complexes are normal but HR > 100

Sinus tachycardia

P wave occurs earlier than expected and its shape is abnormal

Atrial Premature Beat

rapid sawtooth atrial activity

atrial flutter

chaotic atrial activity without organized p waves

irregular qrs rate

atrial fibrillation

retrograde p waves occur with QRS

Paroxysmal Supreventricular Tachycardia (PSVT) caused by AV nodal re entry

shortened PR interval

delta wave in the QRS

Wolf Parkinson White syndrome


Ventricular Pre Excitation Syndrome

delta wave is fusion of ventricular activation via the av node and an accessory pathway

sinus rhythm

APB triggers orthodromic atrioventricular re entrant tachycardia

no delta wave

signals goes backwards up the accessory path and back down through the av node in this loop

QRS widened because ventricles are stimulated by abnormal conduction through the accessory pathway (it's slower?)

the signal runs backwards and up through the av nodal pathway and comes back down through the accessory pathway

arrows are on ventricular premature beats VPBs

monomorphic VT

widening QRS complexes with a waxing and waning pattern

torsades de pointes

V fibrillation

Myocardial oxygen supply comes from

O2 content

coronary blood flow:

coronary perfusion pressure

coronary vascular resistance

external compression

intrinsic regulation

local metabolites

endothelial factors

neural innervation

other answer:

blood flow

origin carrying capacity

O2 saturation

myocardial oxygen demand comes from

wall stress


heart rate


oxygen supply

myocardial extraction of oxygen is near max at rest (about 75%)

increased supply must result from increased coronary flow - vasodilation and increased cardiac output

hemoglobin saturation with oxygen and hemoglobin level are vital to delivery of oxygen

oxygen supply: optimal flow

external pressure

greatest during systole

subendocardium is most vulnerable as it is adjacent to high intraventricular pressure

oxygen supply: optimal flow

internal factors


during ischemia - cant produce atp

ADP and AMP are converted to adenosine

adenosine is a potent vasodilator and is the prime mediator of vascular tone -> decreased calcium entry into cells -> relaxation/vasodilation

endothelial growth factors like nitric oxide lead to vasodilation via cGMP mechanism

increased shear stress, ACh, thrombin, platelets - NO is released to compensate and lead to vasodilation

the most potent endogenous vasodilator?


other endogenous vasodilators?




myocardial demand comes from

wall stress


heart rate


why are beta blockers so useful in ischemia

longer time in diastole (increased flow)

lower wall stress (lower demand)

lower heart rate (lower demand)

lower contractility (lower demand)

consequences of an epicardial coronary stenosis

if stenoses < 70%, there is little change in blood flow at rest

with exercise, the artery is able to dilate to increase flow

if stenoses70-90%, there is autodilation of the resistance vessels at rest and the flow is normal

with exercise, cannot dilate further to meet the demand and there is ischemia

if the stenosis is >90%, there is maximal dilation of the resistance vessels at rest to the extent possible

flow at rest may be suboptimal

coronary pressure falls

subendocardial flow vs subepicardial flow

the subendocardial flow decreases prior to subepicardial flow

consequences of ischemia

the cascade

aerobic (fatty acid metabolism) is replaced byu anaerobic (glucose metabolism)

impaired diastolic function (it takes energy to relax!)

impaired systolic function

increased LV end diastolic pressure

increased lactate, serotonin, and adenosine

local metabolites and abnormalities in ion transport lead to ECG changes and arrhythmias

activation of peripheral pain receptors from C7 to T4

different effects of hypoxia

pulmonary vs coronary


hypoxic vasoconstriction (don't want to perfuse a region of lung that isn't carrying oxygen)


hypoxic vasodilation

when the wall motion appears abnormal, the muscle must be...

infarcted, stunned, or hibernating

myocardial infarct

no flow and no metabolically active cells


acute ischemia

time of abnormalities in movement and metabolism are related to time of ischemia

perfusion is normal following ischemia

occurs following coronary bypass surgery

function returns to normal within 1 week


chronic ischemia

can result from frequent or prolonged ischemia

perfusion is usually reduced

down regulation of ATP uptake and oxygen consumption

viable myocardium

ability to improve motion or metabolism if coronary flow is improved

ischemic conditioning

pre conditioning

when the LAD artery of a dog is clamped repetitively for 5 minute intervals prior to prolonged occlusion, the area of infarction is less than if it is clamped without prior occlusion

ischemic conditioning

post conditioning

opening balloon in infarct-related artery to transiently occluded flow after opening the occlusion

upregulation of inducible NO synthase among other proposed mecehanisms

ischemic cascade

metabolic alteration

perfusion abnormalities

diastolic dysfunction

regional wall motion changes

ECG changes


spectrum of coronary artery disease

noninvasive tests normal:


fatty streak


increasing plaque

noninvasive tests abnormal:

obstructive atherosclerotic plaque

plaque fissure results in thrombosis

anginal syndromes


patent lumen

normal endothelial function

platelet aggregation inhibited

anginal syndromes

stable angina

lumen narrowed by plaque

inappropriate vasoconstriction

anginal syndromes

unstable angina

biomarker negative

plaque rupture

platelet aggregation

thrombus formation

unopposed vasoconstriction

anginal syndromes


biomarker positive

plaque rupture

platelet aggregation

thrombus formation

unopposed vasoconstriction

anginal syndromes

variant angina

no overt plaques

intense vasospasm

the spasms can slow flow

tests to assess presence of atherosclerosis

carotid IMT

no radiation

no contrast

thicker intimal lining = worse survival

tests to assess presence of atherosclerosis

coronary calcium scan

minimal radiation

no contrast

more calcium = less survival

tests to assess for atherosclersis

what about the stress test?

stress tests are for obstructive plaques >70%

below 70% you wont see anything on a stress test

if you don't have symptoms, a stress test won't tell you anything

most heart attacks are NOT caused by obstructive plaques, they're caused by non-obstructive plaques that rupture

likelihood of acute coronary syndrome


high likelihood:

chest or left arm discomfort as typical symptoms

worse with exertion or mental stress

alleviated by nitro

known CAD


new chest or left arm discomfort

>70 years old


diabetes mellitus


recent cocaine use

probable angina (in absence of typical symptoms)

likelihood of acute coronary syndrome



mitral regurg



pulmonary edema


extracardiac vascular disease

(bruits or PAD)


chest discomfort reproduced by palpation

likelihood of coronary syndrome



new ST segment changes

T wave inversions with symptoms

intermediate:fixed q waves

abnormal ST/T waves or unclear duration


T wave flattening

normal EKG

likelihood of acute coronary syndrome

cardiac biomarkers


elevated troponin T

atypical angina symptoms



arm discomfort



in women, elderly, diabetics

syndrome X

chest pain and abnormal stress test with normal epicardial coronary arteries

more common in women

more favorable prognosis than with coronary obstruction

may represent endothelial dysfunction or microvascular disease

can perform brachial reactivity test to assess for endothelial dysfunction

may treat with nitrates, ca channel blockers, ace inhibitors, beta blockers, statins

unstable angina features

symptoms at rest

increasing frequency

increasing duration

lower threshold for symptoms

biomarker negative (Troponin)

patients with unstable angina (troponin neg) or NSTEMI/STEMI (troponin pos) SHOULD NOT UNDERGO STRESS TESTING ON PRESENTATION

why do we perform cardiac stress tests>

to provide an exercise prescription

to identify the etiology of a patient's symptoms (Chest discomfort or dyspnea)

to risk stratify patients with known coronary artery disease

to assess for arrhythmias with exercise

when NOT to perform a stress test?

acute MI

high risk unstable angina

decompensated heart failure

uncontrolled cardia arrhythmias

AV block

acute myocarditis or pericarditis

severe aortic stenosis

severe HOCM

uncontrolled HTN

acute systemic illness - PE, Aortic dissection

major categories of stress testing:

one from each group!

group 1:

treadmill or bike/arm ergometry

adenosine or adenosine analogue

dobutamine (beta 1 agonist)

group 2:ECG

nuclear echo

cardiac MRI


ischemic cascade AGAIN

metabolic alteration

perfusion abnormalities

diastolic dysfunction

regional wall motion changes

ECG changes


mechanism of imaging and the step in ischemic cascade it sees

PET - earliest (glucose metabolism -remember the heart switches to this during ischemia)

cardiac MRI - early (perfusion)

echocardiogram - late (systolic dysfunction)

ECG - latest


metabolic equiv

unit of oxygen uptake in a resting state

1 MET is 3.5 ml O2/kg/min

more intense activities = more METs

maximal stress test

85% of maximum predicted heart rate

maximal predicted heart rate = 220-age

ECG evidence of ischemia

ST starts to drop (V4)

J point - compare 80ms after J-point to TP interval (to see baseline?)

non walker

if a patient cannot exercise, one can perform pharmacologic stress test (adenosine, persantine, or dobutamine)

pharmacologic stress testing - adenosine

at rest the distal arteries autodilate in the artery with the epicardial stenosis

during stress (with adenosine), the distal arterioles are already dilated so only the arterioles distal to the normal epicardial artery can dilate

at rest the flow to both septal and lateral myocardial is normal because the lateral coronary arterioles autodilate

with adenosine stress, the relative flow is increased more to the septal wall because the lateral wall arterioles are already maximally vasodilated

sensitivity of a test

likelihood to miss a positive (or correctly call someone as negative)

specificity of a test

likelihood to wrongly label someone as positive

rank of tests, most sensitive/specific to least

adenosine PET

exercise nuclear

exercise echo

exercise ECG

flowing blood to fibrin clot

how does it happen?

a complex "cascade" of events converts flowing fluid blood to a solid fibrin clot

vessel injury...

vasoconstriction (reduce blood flow)

coagulation cascade (thrombin -> fibrin -> stable hemostatic plug)

collagen exposure -> platelet activation -> platelet aggregation -> primary hemostatic plug -> stable hemostatic plug


slows the flow of blood and helps to limit blood loss

mediated by:

local controls (thrombaxane vasoconstricts)

systemic control (epi by adrenal glands stimulates)

the coagulation cascade bullet points

blood has more than a dozen clotting factors

coagulation involves a biological amplification system

sequential activation of a series of proenzymes or inactive precurosr proteins to active enzymes, resulting in significant amplification

culminates in the generation of thrombin

thrombin converts soluble plasma fibrinogen into fibrin

fibrin converts the unstable primary platelet plug to a more stable, firm hemostatic plug

pathwayway from vessel injury

coagulation cascade

VIIa converts tissue factor to TF VIIa

TF VIIa, VIIIA IXa, and V convert X to Xa Va

Xa Va convert prothrombin to thrombin

thrombin turns fibrinogen to a fibrin monomer

fibrin monomers polymerize

fibrin polymers are modified by XIIIa to be stable fibrin

control of the clotting cascade

extrinsic pathway

damage to tissue outside the vessel

tissue thromboplastin

inactive factor x to active factor x

active factor x turns prothrombin to thrombin

thrombin turns fibrinogen to fibrin

XIII turns fibrin to blood clot

control of the clotting cascade

intrinsic pathway

damage to the blood vessel

cascade of clotting factors turns inactive factor X to activated factor X

activated factor X turns prothrombin to thrombin

thrombin turns fibrinogen to fibrin

factor XIII turns fibrin to blood clotq

target sites in the coagulation cascade


Xa Va




the stable fibrin

initiation of the clotting cascade

coagulation is initiated by the interaction of membrane bound TF exposed by vascular injury with plasma factor VIIa

TF-VIIa activates factor IX and factor X

Factor Xa without its cofactor forms small amounts of thrombin and prothrombin

^insufficient to initiate significant fibrin polymerization

activates several coenzymes: factor V, factor VIII, platelets, and factor VI

the initiation pathway is rapidly inactivated by TFPI (tissue factor pathway inhibitor)

after TFPI inactivates initiation pathway

thrombin generation is now dependent on the traditional intrinsic pathway which has been primed by the small amount of thrombin generated during initiation

amplification of the clotting cascade

thrombin generation is now dependent on the traditional intrinsic pathway -> primed by thrombin generated during initiation

in the amplification phase, intrinsice Xase activates sufficient Xa

Xa in combination with Va, PL, and Ca2+ leads to explosive generation of thrombin which acts on fibrinogen to form the fibrin clot

intrinsic Xase

VIIIa-IXa complex

greatly amplifies Xa production from X

prothrombinase complex

Xa, Va, PL, and Ca2+ leads to explosive generation of thrombin from prothrombin

thrombin activates


thrombin also cleaves VIII from its carrier so that it cant help[ turn X into Xa-Va

thrombin activation of XIII

turns XIII into XIIIa and XIIIa turns fibrin polymer into stable fibrin

formation and stabilization of fibrin

thrombin hydrolyzes fibrinogen forming fibrin monomers

calcium acts like a glue to hold the fibrin monomers together to form a loose insoluble fibrin polymer

factor XIII is also activated by thrombin

activated factor XIII stabilizes the fibrin polymers

the stabilized meshwork of fibrin fibers traps erythrocytes, thus forming a clot that stops the flow of blood

coagulation and vitamin k

activity of factors II, VII, IX, and X - as well as protein C and S - is dependent upon vitamin K

vitamin k carboxylates a number of terminal glutamic acid residues on each of these molecules

vitam k comes from green vegetables and bacterial synthesis in the gut

vitamin k deficiency is caused by por diet, sever liver disease, malabsorption, or inhibition by VKA (warfarin)

physiological limitations of blood coagulation

unchecked blood coagulation would lead to dangerous occlusion of blood vessels if protective mechanisms were not in place

coagulation factor inhibitors

blood flow


coagulation factor inhibitors

effect of thrombin has to be limited to the site of injury

TFPI is synthesized in endothelial cells and present in plasma and platelets. it inhibits Xa and VIIa and TF

antithrombin is a circulating plasma portease inhibitor neutralizing many enzymes in the clotting cascade (especially thrombin and factor Xa)

heparin potentiates antithrombins action markedly

heparin is used int he treatment and prevention of clotting disorders

Protein C and Protein S

inhibitors of coagulation cofactors V and VIII (inactivating prothrombinase and intrinsic Xase

Vitamn K dependent proteins

as clot formation progresses, thrombin binds to thrombomodulin causing a confomrational change in thrombin that activates protein C

then protein C destroys factors VA and VIIIa, preventing further thrombin generation

activation of protein C is enhanced by protein S

activated protein C also enhances fibrinolysis


a normal hemostatic response to vascular injury



is converted to plasmin by activators from th e vessel wall or from the tissues

the most important route follows the release of tissue plasminogen activator (tPA) from the endothelial cells

APC destroys plasma inhibitors of tPA, thus stimulating fibrinolysis



pjlasmin is capable of digesting fibrinogen, fibrin, factors V and VIII and many other proteins

cleavage of peptide bonds in fibrin and fibrinogen produces a variety of split (degradation) products

fibrinolytics agents

recombinant tPA was synthesized using recombinant DNA technology

the bacterial agent streptokinase is produced by hemolytic streptococci - forms a complex with plasminogen - and converts plasminogen to plasmin

Urokinase is a tPA initially isolated from human urine

endothelial cells

ECs have an active role in the maintenance of vascular integrity

provoides the basement membrane that separates collagen, elastin, fibronectin from the circulating blood

loss or damage to the endothelium results in both hemorrhage and activation of the clotting casade

ECs also have a potent inhibitory influence on the hemostatic response through the synthesis of NO, prostacyclin (PGI2), and the endonucleotidase CD39

In contrast, endothelins can activate fibrinolysis via the release of tPA

things endothelial cells produce

Tissue Factor

initiates coagulation

prostacyclin and nitric oxide

vasodilation/inhibition of platelet aggregation


platelet collagen adhesion, complex with factor VIII

antithrombin/TFPI/Protein S, Binding protein C, Actation of protein C

inhibition of blood coagulation



general causes of thrombosis

increased level of procoagulants

decreased levels of anticoagulants

abnormal fibrinolysis

inherited causes of thrombosis

inreased levels of procoagulants

factor V Leiden

Activaed protein C resistance

Prothrombin mutation

hyper homocysteinemia

factor VIII, IX, XI, VII, VWF

inherited causes of thrombosis

decreased levels of anticoagulants


protein c

protein s



inherited causes of thrombosis

abnormal fibrinolysis

plasminogen deficiency

decreased tPA

increased PAI1

elevated TAFI


produced in bome marry by fragmentation of the cytoplasm in megakaryocytes


a major regulator of platelet production, produced in the l/iver and kidneys

normal platelet life span

7 to 10 days

platelets create interface etween

hemostasis, innate immunity, and inflammation in atherosclerosis


fibrinogen receptor

makes the platelets stick together

platelets at work

damage to the vascular endothelium results in recruitment of platelets which aggregate at the site, forming the primary hemostatic plug

through the processes of adhesion, aggregation, and secretion, platelets successfully coalesce to complete the formation of the primary hemostatic plug

platelets and inflammation

enhanced expression of cell adhesion molecules (p-selectin and e-selectin) in a systemic inflammatory environment

platelets then secrete cytokines, chemokines, growth factors, adhesion molecules, and coagulation factors

platelets bind to circulating leukocytes, dendritic cells, and progenitor cells producing coaggregates that support further leukocyte activation, adhesion, and transmigration

is increased platelet activity important?

platelet hyper-reactivity following ACS predicts 5 year outcomes

hyper reactivity = more patients dying or having cardiac events

anti platelet therapy good and bad news

good news - it decreases cardiovascular events

bad news - it increases the risk of major bleeding

thrombosis versus bleeding in platelet therapy?

platelet activation

heart attacks


blood clots

platelet inhibition

major bleeding



virchow's triad

endothelial injury

abnormal blood flow


all three together can cause thrombosis

etiology of acute MI

coronary atherosclerosis

coronary thrombosis

myocardial necrosis

plaque vulnerability factors

size of atheromatous core

thickness of fibrous cap

inflammation and repair of fibrous cap

(macrophage activation)

acute coronary syndromes

unstable angina



acute MI pathologic phases

ischemic insult




infarct size depends on

distribution of coronary artery

point of total occlusion

chest pain in acute MI

retrosternal, left side of chest, ulnar side of left arm

pressure, squeezing, constricting

>20 minutes, persistent

shortness of breath, diaphoresis

MI triggers

no trigger (51.1%)

emotional upset (18.4%)

moderate physical activity (14.1%)

heavy physical activity (8.7%)

lack of sleep, overeating, other (7.7%)

when do the most MIs happen?

Early in the morning

acute anterior wall MI

wide QRS and elevated ST?

acute anterior wall MI

acute anterior wall MI

see ST elevations start in V1

see reciprocal ST depressions in I, II, III, aVF

acute inferior wall MI

ST elevations in II, III, aVF

ST reciprocal depressions in V1, V2, V3

can't really see ST elevationsin II, III, aVF

but you DO see the reciprocal ST depressions in V2 and V3

acute inferior wall MI

diagnostic criteria of abnormal Q waves

width of q wave > 0.04 sec (40 msec)

depth of Q wave >25% of R wave

width is more importantw

hat causes pathologic q waves?


evolutionary EKG changes of acute MI


ST elevation


ST elevation, decreased R wave, Q wave begins

Days 1-2

T wave inversion

Q wave deepens

Days later

ST normalizes

T wave inverted

Weeks later

ST and T normal

Q wave persists

cardiac markers

yellow is CK-MB

pink is Troponin

green is LDH (not used anymore)

you can see that the troponin level starts earliest and spikes the highest. it also lasts longer.

CK-MB starts a bit after troponin but has a steeper slope and peaks sooner.

myocardial damage

left ventricular dysfunction

decreased ejection fraction

elevated LV volume and pressure

myocardial damage

decreased ejection fraction

leads to decreased stroke volume and cardiac output

systemic hypoperfusion

myocardial damage

elevated LV volume and pressure

elevated left atrial and pulmonary capillary pressures

pulmonary congestion

MI complications

LV dysfunction

pump failure

heart failure - rales

pulmonary edema

cardiogenic shock

MI complications extent of LV dysfunction

depends on degree of necrosis

MI complications

myocardial healing

Ventricular septal defect

ventricular free wall rupture

aneurysm formation

MI complications

involvement of papillary muscle

mitral regurgitation

MI complications

involvement of conduction system

heart block

av node, bundle branch system

MI complications

ventricular arrhythmias

secondary ischemia and scarring

more MI complications


postinfarction ischemia

MI treatment

open the occluded coronary artery

salvage/preserve threatened myocardium

limit the size of the infarction

pathophysiology of STEMI

generally caused by a completely occlusive thrombus in a coronary artery

results from stabilization of platelet aggregates at sites of plaque rupture by fibrin mesh

treated pharmacologically via thrombolysis and platelet antagonists

cather treatments are balloons and stents


plasminogen is activated to plasmin

plasmin attacks fibrin which makes up the thrombus and fibrinogen in the circulation

creates fibrin degradation products


plasminogen activator

streptokinase binds with plasminogen to make the plasminogen streptokinase activator complex wihich converts plasminogen to plasmin

plasmin converts fibrin or fibrinogen to fibrin degredation products

50% successful reperfusion

tissue plasminogen activator

produced by normal endothelia

tPA is a serine protease

it works best whhen already in contact with fibrin

it converts plasminogen to plasmin

plasmin converts fibrin and fibrinogen to fibrin degradation products

less fibrinogen depletion and better targeted at fibrin

75% successful reperfusion

tissue plasminogen activator

fibrin specificity

kringle domains allow tPA to recognize and bind to fibrin

higher affinity for fibrin-bound plasminogen than for free circulating plasminogen

dissolves clots better than streptokinase

has a half life of 5 minutes

given as a bolus plus a 90 min infusion

tPA mutant forms


half life is 5 to 7 x that of tPA

can give in a single bolus

has even better fibrin specificity

retaplase (rPA)

half life is 2-3x tPA

given as a double bolus

complicationsof thrombolysis

intracranial hemorrhage

increased risk over 65 years old, low body weight, severe hypertension

contraindications are prior intracranial hemorrhage, active bleeding, recent trauma

reocclusion is another complication

give thrombin antagonists and platelet inhibitor with the drug

indications for thrombolysis or acute PTCA/Stent

chest pain consistent with acute mI

EKG changes

ST segment elevation > 1mm

new bundle branch block

time from onset of symptoms < 12 hours

principles of reperfusion

determinants of survival

rapidity of reperfusion

magnitude of restoration of flow

persistence of flow

major complications are bleeding and reinfarction

pharmacology for thrombolysis therapy of MI

platelet antagonist



IIb/IIIa inhibitor

thrombin inhibitor

bivalirudin, heparin

beta blocker

ACE inhibitor

ADP P2y12 receptor antagonists


require metabolic actiavtion via CYP2C19 pathway

ADP P2Y12 receptor antagonists


clopidogrel (plavix)

4-8 h for peak onset of action

maximum platelet inhibition of 40-50%

many nonresponders due to genetic polymorphisms

ADP P2Y12 receptor antagonists


prasugrel (effient)

faster onset of action than clopidogrel, works within 15m

more platelet inhibition than clopidogrel, 80% at one hour

greater efficacy and increasing vleeding vs clopidogrel

useful for STEMI

ADP P2Y12 receptor antagonists

cyclopentyl-trazalo pyrimidine

do not require activation

ADP P2Y12 receptor antagonists

cycoplentyl-trazalo pyrmidine

ticagrelor (brilinta)

onset of action similar to prasugrrel

degree of platelet inhibition slightly greater than prasugrel

greater efficacy and increased bleeding vs clopidogrel

useful in STEMI

Pharmacologic therapy post MI

survival benefit as acute therapy and chronic therapy

beta blockers

ACE inhibitors


pharmacologic therapy post MI

NO survival benefit as acute therapy or chronic therapy



calcium blockers

normal medications for MI


beta blocker


calcium channel blocker

general measures:

pain control (morphine)

supplemental O2 if needed




GP IIb/IIIa inhibitor

antithrombotic-anticoagulant (use one)


unfractionated intravenous heparin





ACE inhibitor

single leading killer in the western world

coronary artery disease

angina pectoris

discomfort or pain in the chest

occurs when coronary blood flow is inadequate to supply the oxygen requirements of the heart

stable angina

no change in frequency, severity, duration, or precipitating factors in the previous 60 days

generally occurs with exertion and relieved by rest

good prognosis

pathyphysiology of stable angina

one or more severe narrowings in a large epicardial coronary artery

generally due to ahtersclerosis without superimposed thrombus

stable angina

severely narrowed l umen

thick fibrous cap

distant lipid core

left is stable angina

right is unstable angina or vulnerable

stable angina treatment goals

relieve discomfort with medications that improve oxygen supply and/or reduce oxygen demand of the heart

revascularization by angioplasty or bypass surgery indicated if medical therapy fails

risk stratificataion, prevent progression of disease

useful medications for stable angina

beta adrenergic receptor antagonists

calcium channel blockers




ranolazine for resistant angina on meds

vasospastic angina

can occur at rest or on exertion

may be associated with atherosclerosis

treated with nitrates and calcium channel blockers

statins may treat underlying endothelial dysfunction + aspirin

DONT use beta blockers

unstable angina

angina increasing in frequency, intensity, or duration

angina at rest

transient ecg changes

high risk of myocardial infarction and death in the ensuing months

usually a ruptured plaque -> thrombus in the vessel, not 100% occluded

pathphysiology of unstable angina

ruptured atherosclerotic plaque

partially occluding thrombus in lumen of large epicardial coronary artery

coronary thrombosis

plaque ruptures or fissures at high mechanical stress points

fibrous cap may thin due to monocyte production of proteases, which may chemically digest the plaque cap

coronary thrombosis

fibrous cap rupture

underlying tissue is exposed, clotting mechanisms are activated

thrombus forms

thrombus may be non occlusive and eventually be incorporated into the atherosclerotic plaque.

coronary thrombosis

partially occlusive

leads to the acute coronary syndromes, unstable angina or nonSTEMI

unstable angina = no enzymes

with enzymes its non STEMI

coronary thrombosis

totally occlusive

leads to the most common presentation of acute MI

sever chest pain

ST segment elevations

unstable angina treatment goals

relieve discomfort with medications that improve oxygen supply and/or reduce oxygen demand of the heart

prevent myocardial infarction and death

aggressive revascularization

useful medications in unstable angina

beta adrenergic receptor antagonists

calcium channel blockers



heparin - unfractionated and low molecular weight

newer anti platelet agents - GPIIb/IIIa receptor antagonists and thienopyridines


all antianginal agents work by either...

increasing O2 supply or decreasing O2 demand

determinants of myocardial O2 supply

oxygen carrying capacity (hemoglobin)

coronary arteriolar resistance

duration of diastole (heart feeds in diastole)

intra-coronary pressure gradients



myocardial O2 demand

wall stress = (PxR)/(2h)

p = intraventricular pressure (vascular resistance)

r = ventricular radius (volume)

h = wall thickness

heart rate


surrogate for O2 demand is systolic PxHR

antianginal medications

first line:


calcium channel blockers

beta blockers

second line:


nitrates: mechanism of action

venodilation and arteriodilation, but more venous

reduction in preload, decrease in blood return to the heart, heart size decreases

reduction in blood pressure and therefore in afterload

attentuation of coronary vasospasm

improved collateral blood flow

nitrate effects in angina

decreased myocardial oxygen requirement by decreasing wall stress both P and R

possible improved oxygen delivery

decrease P, decrease R, then you decrease O2 requirement

nitrates: cellular mechanisms

enzymatic degradation to nitric oxide

activation of intracellular guanylyl cycloase in smooth muscle by NO

increase cGMP

dephosphorylation of myosin light chain phosphate, inactivating myosin-actin interaction leading to vasodilation

effects only on smooth muscle, no effects on cardiac or skeletal muscle

nitrate mechanism

nitrates become ONO2

reduced to NO2

reduced to NO

NO turns on guanylyl cyclase

GTP+ guanalyl cyclase makes cGMP

cGMP causes vasodilation

nitrate mechanism contd

nitric oxide activates guanylyl cyclase

gtp converted to cGMP by guanylyl cyclase

myosin light chain has a phosphate on it that allows it to bind to actin causing vasoconstriction

when the phosphate is removed by cGMP, the myosin light chain can't bind actin and the vessel relaxes



phosphodiesterase breaks cGMP down to GMP

viagra (and any other phosphodiesterase inhibitor) will keep that from happening, meaning you have too much cGMP and too much relaxation

adverse effects of nitrates


orthostatic hypotension

reflex tachycardia due to vasodilation

tolerance to nitrates can develop and they'll stop working

rebound due to nitrate withdrawal

possible mechanisms for tolerance to nitrates

sulfhydryl group depletion

salt and water retention

increased free radicals that degrade NO

nitrates have to get to circulation without

going to the liver first. thats why theyre put sublingual usually

calcium channel blockers

mechanism of action

arterial vasodilation more than venodilation

lowers blood pressure

potent coronary artery dilation

drugs of choice for coronary vasospasm

negative inotropy

negative chronotropy

calcium channel blockers

cellular mechanisms

blockade of voltage dependent L type calcium channels

the L type calcium channel is the dominant calcium channel

it has several receptors and the different classes of drugs bind to different receptors

reduction in transmembrane calcium flux

skeletal muscle isn't depressed by the calcium channel blockers because it uses intracellular pools of calcium to support excitation-contraction coupling and does not require much transmembrane calcium influx

blocking the calcium channel in diferent places...

on vascular smooth muscle it results in vasodilation

on the myocardium results in reduced inotropy

on the SA node and AV node it results in slowed conduction

on the GI tract it results in decreased peristalsis

calcium channel blocker effects in angina

increases O2 supply

relieves vasospasm

some prolong diastole

decreases O2 demand

decreased inotropy

vasodilation decreases arterial pressure (lowers wall stress)

some classes slow the heart rate

classes of calcium antagonists

first gen dihydropyridines

second gen dihydropyridines


modified benzothiazepines

calcium channel blocker

first gen dihydropyridine


potent vasodilator

greater effect on vascular smooth muscle than cardiac muscle

may cause reflex tachycardia so it should be used with a beta blocker

negative inotrope (usually not a problem because of increased CO due to vasodilation)

short acting preparation removed from market due to risk of MI and stroke secondary to hypotension

long acting preparations

nifedipine adverse effects



lower extremity edema (diuretics dont work for this kind of edema)



ca channel blocker

potent negative chronotrope

negative inotrope

systemic and coronary vasodilator

useful as an antiarrhythmic agent for supraventricular tachycardias

verapamil adverse effects



lower extremity edeme

constipation (greater effect on peristalsis)

excessive sinus bradycardia and AV block

CHF exacerbation (because of decreased inotropy)

increases digoxin blood levels


ca channel blocker

less potent vasodilator than nifedipine

less potent negative chronotrope than verapamil

negative inotrope

iv form useful for controlling ventricular rate in a fib (slows the av node)

diltiazem adverse effects



lower extremity edema

excessive sinus bradycardia and AV block

CHF exacerbation


safest ca channel blocker in patients with CHF

well tolerated

once a day

beta receptor subtypes

beta 1

predominate in the heart

stimulation results in increased heart rate, av conduction, and contractility

beta receptor subtypes

beta 2

predominate in the lungs and liver

stimulation results in bronchodilation, vasodilation, and glycogenolysis

beta blocker mechanism of action

negative chronotrope, negative inotrope

lower blood pressure

increase duration of diastole

attenuate exercise mediated increases in contractility and heart rate

anti arrhythmic effect suppresses lethal ventricular arrhythmias

survival benefit in patients post MI and with compensated CHF

beta 1 selective beta blockers



adverse beta blocker effects


exacerbation of chf



excessive sinus bradycardia and av block

masking of hypoglycemia in diabetics

ranolazine (ranexa)

first new class of antianginals in more than 20 years

indicated for patients who continue to have angina on standard antianginals or for those who cannot tolerate standard antianginals

works by blocking the late I(Na) channel

may be used in pts with low heart rate or low bp, CHF, DM, or asthma

origin of late I(Na)

during the plateau phase of the AP, a small proportion of Na channels either do not close, or close and then reopen

these late channel openings permit a sustained Na current to enter myocytes during systole

myocardial ischemia and late I(Na)

it causes enhnaced late I(Na)

enhanced late I(Na) appears to be a major contributor to increased intracellular Na during ischemia

role of altered ion currents in adverse consequences of myocardial ischemia

increase in late I(Na) causes too much sodium entry into the cell which causes too much Ca in the cell

too much calcium causes electrical instability and mechanical dysfunction



arrhythmias (VT)

abnormal contraction and relaxation

increased diastolic tension

sustained contractoin of ischemic tissue during diastole

increases myocardial oxygen consumption

compresses intramural small vessels

reduces myocardial blood flow

overall it exacerbates ischemia

ranolazine mechanism of actionin

creased intracellular calcium does not allow normal LV relaxation

leads to increased O2 consumption and potential compression of hte vascular supply

ranolazine blocks the late I(Na) channels and therefore prevents intracellular calcium overload

pts experience less chest pain and improved exercise duration

strategies in the medical treatment of stable angina

beta blockers are the first line

pts should be given a bottle of sublingual nitro and instructed on use

calcium channel blockers used if beta blockers are contraindicated or not tolerated

may be added if angina persists or to treat HTN

rannolazine for persistent angina

risk stratificatoin (high risk -> cath)

plus aspirin and a statin

strategies in the medical treatment of unstable angina


treatment of angina, usually with nitrates sublingual or IV

often give beta blockers oral or IV

treatment of underlying ruptured plaque with thrombus -




antithrombin like heparin

other antiplatelet agents

risk stratification with cardiac cath

definition of thrombosis

formation of intra-vascular blood clot

thrombosis clinical significance

acute coronary syndrome

embolic stroke

pulmonary embolism

underlying cause of thrombosis

abnormality of normal hemostatic mechanism

thrombosis vs hemostasis


intravascular blood clot

compromises blood vessel lumen and impedes blood flow

thrombosis vs hemostasis


extra vascular blood clot located on external surface of blood vessels

prevents bleeding after vascular injury

thrombosis pathophysiology

endothelial injury

platelet activation

coagulation cascade


endothelial injury...

exposes underlying collagen

releases tissue factor

impairs endothelial cell production and release of anti-thrombotic factors: NO, prostacyclin, tissue plasminogen activator, tissue factor pathway inhibitor

platelet activation

initiated by collagen

shape change and degranulation

platelet delivers drugs

recruit of circulating platelets by ADP

glycoprotein IIb/IIIa receptor stimulation is the final common pathway of platelet aggregation

things platelets deliver on their own

adenosine diphosphate

factor V

platelet factor 4

platelet derived growth factor

tgf beta

thromboxane A2


Glycoprotein IIb/IIIa receptor stimulation on platelet

its normally inside the platelet

it sticks out when activated

they can attach to fibrinogen and attach to each other through the fibrinogen

coagulation cascade simplified schema

endothelial injury leads to TF release

TF activates factor VII

factor VIIa complex activates factor X

Factor Xa+Va (prothrombinase complex) makes thrombin IIa

modulation of thrombin activity


Xa+Va leads to thrombin formation

thrombin converts V to Va to Thrombin generation (positive feedback loop)

modulation of thrombin activity


circulating proteins C and S inactivate Va, leads to reduced thrombin formation

circulating anti-thrombin III directly inactivates thrombin

drug classes used to prevent thrombosis

anti-platelet agents


antiplatelet agents


ADP receptor antagonists

cAMP agonists

Thrombin receptor antagonists

glycoprotein IIB/IIIa antagonists

salicylates (aspirin)

weak platelet antagonists

irreversible acetylation and inactivation of cyclo-oxygenase blocks TxA2 production

indicated for MI and secondary prevention of MI and stroke prevention in low risk a fib

main side effect is GI bleeding

doses of ASA as low as 75mg every other day impair platelet function

ADP receptor antagonists





what adp receptor antagonists do

more potent than ASA

block the P2Y12 receptor to prevent recruitment of circu lating platelets

clinical effects are irreversible for days

thienopyridines are prodrugs metabolized by cytochrome p450 to the active compound

potential for drug drug interactions

CYP2C19 reduced function allele associated with reduced response to clopidogrel

clinical use of ADP antagonists

indicated for stroke prevention in patients with prior stroke or TIA

indicated for a year after acute coronary syndrome

2-4 week course post bare metal stent

prolonged course (possibly for life) after implantation of drug eluting stents

cAMP antagonists


inhibits uptake of adenosine by platelts, endothelial cells, and erythrocytes increasing local adenosine levels leading to platelet adenylate cyclase activation

indicated for stroke prevention in patients with normal sinus rhythm

vasodilator may cause coronary steal

cAMP antagonists


inhibits phosphodiesterase type 3

indicated as a vasodilator in vascular disease

contraindicated in heart failure

thrombin receptor antagonists


approved by fda in may 2014 for secondary prevention post MI

increased risk of intracranial hemorrhage in patients iwth prior stroke

glycoprotein IIB/IIIa receptor antagonists

most potent platelet antagonists available

only available in IV form

used for treatment of acute coronary syndromes

abciximab - chimeric human/mouse FAB fragment derived from a monoclonal antibody

tirofiban and eptifibatide - small molecule short acting specific blockers

main side effect = excessive bleeding

antiplatelet medications



indicated for ACS treatment and prevention, low risk stroke prevention in Afib

antiplatelet medications

ADP receptor antagonist


acs, post stent

anti platelet medications

cAMP antagonist


stroke prevention in NSR, vascular dis

anti platelet medicataions

PAR-1 antagonist


secondary prevention Post-MI

anti platelet medications

GPIIBIII antagonist


treatment of ACS



unfractionated heparin

low molecular weight heparins

Xa inhibitors

direct thrombin inhibitors


oral anticoagulant indicated for chronic use

inhibits synthesis of vitamin K dependent clotting factors II, VII, IX, and X

inhibits synthesis of proteins C and S

indicationsfor warfarin therapy

mechanical heart valve prosthesis

afib (stroke)

pulmonary embolus (secondary prevention)

DVT (secondary prevention)

recent anterior wall myocardial infarction

disadvantages of warfarin

slow onset (2 days of treatment to get effect)

requires monitoring of blood work

interacts with drugs and foods


hemorrhagic skin necrosis

teratogenic (birth defects)

warfarin reversal

oral vitamin K (may lead to prolonged resistance to warfarin)

IV vitamin K

low dose for temprary reversal

high dose for anaphylaxis

iv clotting factors

Noval Oral Anticoagulants


approved by FDA for stroke prevention in setting of non valvular a fib and for prophylaxis and treatment of dvt

rapid onset of action

no monitoring needed

no interaction with food

safer than warfarin


more expensive

list of NOACs


direct thrombin inhibitor


xa inhibitor


Xa inhibitor


Xa inhibitor

unfractionated heparin

mixture of sulfated mucopolysaccharides derived for porcine intestinal mucosa and bovine lung

binds to and activates antithrombin III

heparin-antithrombin III complex inhibits thrombin, inhibits Xa, and enhnaces activity of TFPI

can be reversed by protamine

indications for heparin therapy

anticoagulation during initiation of warfarin therapy

acute coronary syndromes

cardiac cath, cardiac surg, and vascular surge

SQ heparin indicated for prophylaxes of venous thrombo-embolic disease

disadvantages of heparin therapy

non specific binding of heparin to plasma proteinsresults in variable dose response



rebound hypercoagulable period

heparin induced thrombocytopenia

effect of saccharide chain length on anti Xa: anti IIa ratio`

12 sugars on ATIII lets thrombin bind

only the 5 sugars ATIII is bound to lets Xa bind to it

low molecular weight heparin

same mechanism as heparin

less protein binding, more reliable anticoagulant effect

subq administration

fewer side effects

Xa inhibitors




Xa inhibitors


synthetic penteasaccharide results in antithrombinIII mediated inhibition of XA

subq administration

indicated for prevention of dvt

may be used for therapy of acute coronary syndrome

Xa inhibitors


oral therapy approved nov 2011 for stroke prevention in patients with a fib

Xa inhibitors


oral therapy approved jan 2015 for stroke prevntion in patients with a fib

Direct thrombin inhibitors






direct thrombin inhibitors


active component of the leech salivary gland

no longer in clinical use

direct thrombin inhibitors


specific and reversible thrombin inhibitor

used for anticoagulation during coronary intervention

direct thrombin inhibitors


IV therapy for heparin induced thrombocytopenia

direct thrombin inhibitors


IV therapy for heparin induced thrombocytopenia

direct thrombin inhibitors


oral therapy for smoke prevention in pts with a fib

hirudin vs bivalirudin



recombinant DNA