8/16/19 update

Medical Pharmacology & Mechanisms of Disease

Mr. Dickey Hart

A Case Based Learning Exercise on

Cardiac Pathophysiology &
Antiarrhythmic Pharmacology
Craig W. Clarkson, Ph.D.
Elma I. LeDoux, M.D.
Girish C. Moudgil, M.D.
Al Hyman, M.D.

Departments of Pharmacology, Medicine and Anesthesiology

Learning Objectives
By the end of the session, you should be able to:
1. List the primary risk factors for ischemic heart disease.
2. Explain the rational for the use of aspirin and beta-blockers in the treatment of patients with a previous
MI.
3. Identify several basic rhythm disturbances based upon a patient's ECG.
4. Discuss the possible etiologies of different rhythm disturbances in patients with a history of heart
disease.
5. Describe the major therapeutic goals in treating patients with atrial fibrillation.
6. Identify drugs of choice for treatment of hemodynamically significant ventricular arrhythmias in and out
of the ICU.
7. Discuss the common clinical symptoms associated with an acute MI.
8. Describe clinically significant side effects of amiodarone and lidocaine.

DRUG LIST: lidocaine, amiodarone, aspirin, warfarin, metoprolol, hydrochlorothiazide, ACE inhibitors, statins
 2

Mr. Dickey Hart, a 52-year-old professor, experiences a retro-sternal “cramp like”

chest pain after a heavy breakfast. The pain, which began 3 hours ago, radiates
towards his neck and shoulder. He looks pale, sweaty, and anxious. He feels
nauseated, and a friend escorts him in his car to the emergency room. His past
medical history indicates that Mr. Hart has had hypertension for the past ten years.
He was diagnosed with NYHA stage III HFrEF two years ago, and suffered an inferior
myocardial infarction six months ago. He has smoked one pack of cigarettes per day
for the past twenty years. He has no known history of hyperlipidemia. He is currently
taking one aspirin a day, 100 mg extended release metoprolol po qd and a
combination tablet of 10 mg lisinopril /25 mg hydrochlorothiazide po qd.

Q1: Generate hypotheses regarding his condition.

Dx: basically anything involving chest pain (not just heart, but probably heart)
Q2: What are the risk factors for ischemic heart disease in this case ?
Smoking, hyperlipidemia, hypertension, sex
Q3: What is the incidence of myocardial infarction in the USA & what is the estimated “cost” involved
with the treatment of coronary artery disease?
800k cases per year; 500k death per year, 10 million cases in population
Q4: Why is this patient taking aspirin, and an ACE inhibitor, a beta blocker, and a thiazide?

Aspirin - decrease risk of platelet aggregation and thrombus

ACE inhibitor - decrease hypertension
Beta blocker - slow down heart rate, contractility, prevent remodeling
Thiazide - diuretic, vs. hypertension
 3

Upon arrival in the Emergency Department Mr. Hart is given a chewable aspirin tablet,
and a nitroglycerin tablet sublingually. A blood sample for measuring cardiac enzyme
levels is obtained. ECG leads, O2 saturation monitor, and a blood pressure cuff were
applied. His ECG (leads I & V1) is shown below. His initial blood pressure readings vary
between 170/110 and 150/85 mm Hg. His pO2 is 93%. Mr. Hart stated that after his MI
six months ago, he developed a chronic irregular heart rhythm for which he has also
been taking both metoprolol and warfarin po qd. Mr Hart added that he missed
taking his daily dose of these two medications this morning due to all the confusion
related to his chest pain.

V1

__
0.2 sec

Q5: What is this patient's basic rhythm & ventricular rate?

atrial fibrillation, 75 bpm
Q6: What are the possible etiologies of these rhythm disturbances?
left bundle branch block (QRS going down), previous MI, atrial remodeling
Q7: Why is the patient on metoprolol and warfarin?
metoprolol - rate control (Arrythmia), warfarin - reduce incidence of clotting
Q8: What other medications should this patient probably be taking?
spironolactone, usually reduces mortality
 4

Mr. Hart is a well-developed man who weighs 90 kg. He is 5’6” tall. While in the
Emergency Department his B.P. suddenly falls to 104/60 mm Hg. His radial pulse is
fast and irregular in rate, rhythm and amplitude. His ECG indicates a similar rhythm
disturbance, but now his ventricular rate has increased to 160-180 min-1 . His
respirations are 20/min, and his body temperature is 99.6oF. His skin is moist and
cold. His neck veins are distended. The E.R. physician starts an I.V. Blood samples for
PT/PTT, INR and arterial gases are obtained.

Q9: Why is his blood pressure lower than it was previously?

vasodilator did its job
Q10: What is the significance of distended neck veins?
uh oh right-sided heart failure
Q11: In the setting of chronic atrial fibrillation, what are our goals of therapy?
prevent thrombus formation, control rate @ 85 bpm
Q12: Would the absence of ST segment changes exclude the possibility of myocardial ischemia?
no, could have an NSTEMI
Q13: What treatment would you recommend?
want to wait for chest pain, and ST segment changes, to see if you need
to introduce thrombolytics
 5

The patient's blood gases, BUN, creatinine and electrolyte levels are found to be
normal. The INR is within the therapeutic range. The patient’s status is closely
monitored and an initial i.v. bolus of low dose metoprolol (2.5 mg over two minutes)
is administered.

Within 5 minutes, Mr. Hart’s B.P. begins to stabilize at ~130/90 mm Hg, with a
ventricular rate of 90-100 bpm. Approximately 10 minutes later, Mr. Hart comments
on feeling dizzy before suddenly losing consciousness. His blood pressure monitor
indicates an arterial pressure of less than 40/20 mm Hg. His multi-lead ECG is shown
below:

Q14: What is the rhythm and rate in his ECG? Vtach, 300bpm

Q15: What treatment would you recommend? s h o c k

 6

A code blue emergency (cardiac or respiratory arrest) is announced, and an ER nurse

applies DC cardioversion which successfully abolishes the ventricular tachycardia. A
cardiology consult is requested. The cardiology fellow suggests that a defibrillator and
be made available at the bedside in case of the reoccurrence of a ventricular
arrhythmia. In the meantime, she recommends that the ER nurse administer an i.v.
bolus of 150 mg amiodarone, to be given slowly over 10 minutes through a central
line, followed by 360 mg over the next 6 hours, and then an infusion of 0.5 mg/min.
(Alternatively, a 1 mg/kg bolus of lidocaine could have been used to treat a post – MI
ventricular arrhythmia when it occurred).

Q16: What is the indication for the use of amiodarone (or lidocaine) in this setting?
amiodarone cause its a antiarrhythmic
Q17: Should treatment with an i.v. antiarrhythmic have been given prior to DC Cardioversion?
no
Q18: What are the primary antiarrhythmic mechanisms of action of lidocaine and amiodarone?
1b III

Q19: If lidocaine were used, what are the primary warning signs of lidocaine toxicity that you should
watch out for ?
hypotension apparently
Q20: What are some of the clinically significant side effects of long term treatment with amiodarone?

HEART BLOCK!!!!
gray-blue skin
lung fibrosis
neurologic side effects
gray corneal microdeposits
 7

Two days later Mr. Hart has an irregular heart rhythm of 90-110/min and B.P. of
110/80 mm Hg. His neck veins are no longer distended, and he has occasional runs of
ventricular premature beats. The analysis of his serum enzyme profile determined
from blood samples taken at the time of admission, and 6 hours after admission to the
hospital are made available, and are shown below.
Serial Changes in Cardiac Enzymes.
Enzymes Patient Values Patient Values Normal Range
(at admission) (after 6 hrs)
Myoglobin 220 ng/ml 620 ng/ml 0 - 100 ng/ml
Troponin-I 1.1 ng/ml 7.1 ng/ml 0 - 1 ng/ml
Total CPK 220 U/L 320 U/L 20-200 U/L
CPK-MB 5.8 ng/ml 15.8 ng/ml <5 ng/ml
CPK- creatinine phosphokinase; CPK-MB - cardiac specific isoform

increased myoglobin, troponin, CPK, CPK-MB

Q21: What do the enzyme levels indicate?

MI
Q22: Explain the clinical significance of the time course of enzyme elevation .
CPK and CPK-MB peak after days, myoglobin & troponin hours
Q23: What further studies should be performed on this patient?
he had another MI prior to coming to the hospital!! give him an echo
Q24: Should a statin also be given?
yes
Q25: Should an Implantable Cardio-Defibrillator (ICD) be implanted in this patient?

yes

The End