Cardiotoxicology

Question 1

Name 2 drugs and 7 types of drugs that have an impact on the heart

Answer 1

Antibiotics
Bacterial LipoPolySaccharide (sepsis)
Catecholamines (Cardiomyopathy)
CNS drugs (APs ADs, Stimulants, Depressants, Anticonvulsants)
Antineoplastic agents
Steroids

Passive Smoking
Carbon Monoxide

Question 2

Define Cardiovascular disease

Answer 2

Any disease of the heart or vascularization (brain and lower limbs)

Question 3

True/False? If the SA node is damaged the AV node can take up pacemaker activity

Answer 3

True (but less efficient)

Question 4

True/False? If SA and VA nodes are damaged, the his-Purkinje system can take up pacemaker activity

Answer 4

True (but les efficient)

Question 5

What cellular organelle do cardiac myocyes have in abundance and why?

Answer 5

Mitochondria, for energy

Question 6

Name 2 types of Plant toxins

Answer 6

Cardiac Glycosides

Taxine alkaloids

Question 7

Name two cardiac glycosides

Answer 7

Digoxin and Oleandrin

There are MANY

Question 8

How do cardiac glycosides work?

Answer 8

Act on Na/K pump
Acts on ALL excitable tissue (heart is main target)
Sugar section (hydrophillic, gets into blud)
Aglycone section (hydrophobic, biologically active)
Blocks Na/Ca pump - Ca rushes into cell - Stronger contraction
(Can be used therapeutically)

Question 9

What are the 3 mechanisms of Cardiac Glycoside toxicity? Which is/are fatal?

Answer 9

Arrhythmia (not fatal) - SA node no longer controls depolarization
Conduction Block (not fatal) - not QRS/T waves (depolarization cannot pass AV node)
Hyperkalemia (FATAL) - ventricular tachycardia, progressive bradyarrhythmia, heart block, VENTRICULAR FIBRILLATION

Question 10

What is the major route of excretion for cardiac glycosides?

Answer 10

Urination (half life of days)

Not metabolized, excreted mostly unchange

Question 11

Can cardiac glycosides cross BBB/placental wall?

Answer 11

yes

Question 12

What part of the yew is/are nontoxic? Which is/are toxic?

What is the primary toxin?

Answer 12

Every part is toxic except the berry

Cardiotoxic taxine alkaloids

Question 13

What are properties of cardiac taxine alkaloids?

Answer 13

No antidote/effective treatment

Blocks calcium channel (rapid death), interferes with heart contraction

Question 14

Name the toxin found in cobra venom and describe its function

Answer 14

Cobra cardiotoxin

Forms a pore on the heart

Question 15

What is the naming scheme for most anthracyclines?

Answer 15

Doxorubicin

_____-rubicin

Question 16

What are anthracyclines and how do they function?

Answer 16

Anticancer drugs
Might not show toxicity right away
Arrhythmia, congestive heart failure (children more susceptible)

Creates oxidative stress which triggers apoptosis (chemotherapeutic damage to DNA)

Question 17

Define heart failure

Answer 17

Failure of the heart to do its job
Blood enters heart fine but can’t get pumped out
Heart swells

Question 18

What does Herceptin do?

Answer 18

Acts on HER-2 receptors (some tumors express HER-2 preferentially)
HER-2 survival pathway keeps cells alive

Question 19

What does Trastuzumab do?

Answer 19

Inhibits HER-2 survival pathway

Great for tumors, not for cardiac myocytes

Question 20

How can air pollution affect the heart?

Answer 20

Fine particles get into blood

Question 21

How is diesel exhaust cardiotoxic?

Answer 21

Increases risk of plately aggregation, MI, Stroke

Releases inflammatory factors in vessels, buildup of plaque in vessels

Question 22

How are nanoparticles toxic?

Answer 22

Reach all vessels in circulation and cause atherosclerosis

Narrows lumen as well as impairs function of endothelium

Question 23

How is Carbon monoxide cardiotoxic?

Answer 23

Deprives entire body of oxygen, brain and heart preferentially
Anything burnt releases CO
Chronic low doses lowers life expectancy
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