Cardiotoxicity Flashcards
final exam
what happens if the SA node malfunction?
backup pacemakers take over control of the heart:
1. AV node: slower
2. His-Purkinje system
3. At worst, ventricles can set up their own contraction (will be very slow, but you will be alive)
what modulates the heart rate in response to stress/exercise?
ANS (sympathetic –speed up– and parasympathetic –slow down–) and hormones (noradrenaline or adrenaline –speed up–)
how has the heart developed to keep up its high energy demand?
- highly developed blood supply
- a lot of mitochondria
average heart rate
60 bpm
ways toxins can interfere with mechanisms of the heart
- ion channel trafficking
- electrophysiology
- contractility
- with the function of mitochondria
- generation of ROS
- causing apoptosis or necrosis
- causing fibrosis
- blood-clot formation
- ion channels (Na+, Ca2+, K+)
- receptors for signaling molecules
structure of cardiac glycosides
- sugar portion
- non-sugar (aglycone) portion which is attached to R group that determines its specific type
types of glycosides
- Cardenolides (plants)
- Bufadienolides (toads and south fauna)
action of cardiac glycosides
- inhibits Na+/K+ ATPase pump on cell membrane (which is high in concentration i heart tissue)
- Na+ accumulates in the cell
- higher activity of Ca2+/Na+ exchanger
- more Ca2+ in the cardiac cells, which induces contractions
problems that can occur due to cardiac glycoside toxicity
- atrial fibrillation
- conduction block
what is atrial fibrillation? would it kill the person?
- disorganized electrical signals in the atria, so contractions become independent of pacemaker activity
- non-lethal as AV node or ventricular pacemaker activity allow for ventricular contraction, so blood gets to lungs/periphery
how does conduction block occur? what is seen on an EKG? would this kill the person?
- occurs when electrical impulse from atria cannot pass through the AV
- would see P-wave but no QRS complex
- non-lethal if blocked for a short time, but can lead to ventricular fibrillation of too ling, which is lethal (blood does not get to periphery/brain)
why do fauna contain cardiac glycosides?
evolutionary protective mechanism
what is digoxin and where is it found?
cardiac glycoside found in foxglove/digitalis plant
toxic effects of digoxin
- early symptoms can ne neurological (can affect electrically active tissue in CNS)
- can cause v. fib, v. tach, progressive bradyarrhythmia
- cardiac arrest from v. failure
pharmacokinetics of digoxin
- Absorption: well absorbed orally (peak serum is 1-3 hrs)
- Distribution: concentrates in tissue (large AVD), crosses BB (explains disorientation)
- Metabolism: not well by CYP450s, so excreted by kidney without metabolism (so takes a couple of days)
- Excretion: first-order, so takes a while
what does the oleander plant contain? what is its effect?
- oleandrin (cardiac glycoside)
- fatal to humans (even 1 leaf)
what does lily of the valley produce?
convallotoxin (cardiac glycoside)
why do Monarch butterfly lay their eggs on milkweeds?
since they contain cardiac glycosides so kill predator insects (they are resistant due to genetic mutation)
who is more vulnerable to houseplant toxicity
children and pets
what do Kalanchoe contain?
cardiac glycosides
what toxin does Yew contain and which parts are and aren’t toxic?
- cardiotoxic alkaloids
- leaves, bark, stem flowers are toxic
- red part of the berry is not toxic
is there a treatment for yew poisoning? if so, what is it?
no, takes 30 mins to die
effect/mechanism of Yew cardiotoxic alkaloid
- inhibits cardiac conduction and causes arrythmia via blockage of Ca2+ channels (no contractions)
- causes impairment of HR generated from SA node, AV node, and electrical system (including the electrical-mechanical coupling of the ventricular muscle)
- see a very wide QRS complex
effect of moldy hay (and mode of exposure)
fungus grows on hay and can secrete cardiac glycosides (horse can eat and humans can inhale)
Effect of snake venom (more specifically cobra venom)
- forms a pore/channel that interferes with the conduction system
- causes necrosis of cardiac muscle (affects contractility)
effect of anthracyclines
- early (during or first year after treatment): non-specific ST-segment and T-wave abnormalities
- late (at least one year after completion of treatment): arrythmia or congestive heart failure
- general: mito. damage, leading to apoptosis
what characterizes congestive heart failure?
low CO and other compensatory mechanisms that took place to get enough oxygen, can lead to peripheral edema, pulmonary edema, and kidney retains fluid
effect of Herceptin
HER2/4 present on heart cells, so leads to loss of heart cells, so congestive heart failure
what is Ephedra?
stimulant sold illegally (for weight loss and for athletes)
effect of Ephedra
- increase release of NA and A (and impair reuptake)
- stimulate postsynaptically
- can cause ischemic heart disease (can be severe and cause infarction by inducing vasospasms which can block blood flow)
how can fine particles affect the heart?
- alter endothelium
- affect endothelial barrier
- activate platelet and induce blood clot formation
- trigger inflammation
- atherosclerosis, which can cause clot that can block key areas
what is a method to study the effect of fine particles on heart?
organoids (see which fractions of cells die)
acute vs chronic exposure of fine particles on cardiovascular function
- chronic: gradual buildup of heart disease, gradual increase in mortality risk
- acute: bad exposure can trigger heart attack or sudden death from arrythmia
effect of ozone (with fine particles0 on cardiovascular function
potentiates effects of fine particles
major source of indoor air pollution
candles and incense
mechanism of action of carbon monoxide
- binds to Hb, forming carboxyhemoglobin
- blocks binding of oxygen to Hb
- trigger ROS production, damages the endothelium/myelin (this can occur at even low-level exposure)
symptoms/effects of CO poisoning
first CNS effects (headaches, nausea, dizziness, confusion) then loss of consciousness and cardiac arrest
