Week 5 Flashcards
1
Q
Describe what a unstable plaque is.
A
- AKA Thin Cap Fibroatheroma
- This type of plaque is more likely to rupture
- More inflammatory cells
2
Q
Describe what a stable plaque is.
A
- AKA Thick Cap Firbroatheroma
- Less Likely to rupture because more stable
- Less inflammatory cells
3
Q
Where does a necrotic core form?
A
The intima layer where the lipid core forms → becomes necrotic
4
Q
Describe post occlusion recanalization
A
Absorption of the thrombus → creates multiple small lumens for blood flow
5
Q
What is this a picture of?
A
Thin cap fibroatheroma AKA unstable plaque
6
Q
What is seen here? What is the white substance in the layers?
A
Thick cap fibroatheromas AKA stable plaque
The white substances in the layers is the necrotic core
7
Q
What can be seen here?
A
Post occlusion recanalization
8
Q
For nitroglycerin:
- What is the class?
- What are the methods of intake and what effects do they have?
- What is the mechanism of action?
A
- Class: Nitrate
- Can take sublingually, po, or IV
- PO/SL both work on veins
- IV works on coronary arteries (hence the Nitro drip post-MI)
- MOA: Nitrates → NO @ vessel walls → stimulates guanylate cyclase → produce cGMP → dephosphorylating of MLC → venodilation → decreases preload
- REQUIRE THIOL FOR ACTIVATION
9
Q
For nitroglycerin:
- What are some side effects?
- What are contraindications to worry about?
A
- Side Effects:
- Hypotension with reflex tachycardia
- Tolerance can develop
- Contraindications
- Keep in glass bottle (reacts with plastic)
- No Viagra
- Inhibits PDE 5, which allows for no way to terminate action of cGMP, causing it to accumulate → fatal hypotension
10
Q
For isosorbide mononitrate:
- What is the method of ingestion?
- What class is this drug?
- What is the MOA?
- What are some side effects?
- What is a contraindication?
A
- Ingested po
- Class: Nitrate
- MOA: NO @ vessel walls → stimulates guanylate cyclase → produce cGMP → dephosphorylating of MLC → venodilation → decreases preload
- Completely bioavailable – no need for metabolism
- Side Effects:
- Hypotension with reflex tachycardia
- Tolerance can develop
- Contraindications:
- No Viagra
- Inhibits PDE 5, which allows for no way to terminate action of cGMP, causing it to accumulate → fatal hypotension
- No Viagra
11
Q
For -olol drugs:
- What class are these drugs?
- What is their MOA?
- What are some side effects?
- Who are they indicated in?
A
- Beta-blockers
- MOA:
- Act on beta adrenergic receptors in SA/AV node and vessels
- Decreases HR, contractility, BP (Increasing O2 delivery by increasing diastolic time)
- Side Effects
- Hypotension
- Beta2 blockage is bad for several reasons:
- Inhibits glycogenolysis (beta 2)
- Vasoconstriction
- Bronchoconstriction
- Indicated in people with cardiac conditions
12
Q
For -DHP drugs:
- What class are these drugs?
- What is their MOA?
- What are some side effects?
- Who are they contraindicated in?
A
- Calcium channel blockers
- MOA: Works at vessels: blocks Ca2+ from entering cell → blocking constriction of smooth muscles in vessels → arteodilation
- *decreases afterload
- Side Effects: hypotension
- Contraindicated in: patients taking beta blockers
13
Q
For non-DHP drugs:
- What class are these drugs?
- What is their MOA?
- What are some side effects?
- Who are they contraindicated in?
A
- Class: calcium channel blockers
- MOA: Works at SA/AV nodes: blocks Ca2+ from entering cells → slows contraction of heart → decreased HR
- Side Effects: hypotension
- Conraindicated in people taking beta blockers
14
Q
For Ranolazine:
- What class are these drugs?
- What is their MOA? There are two.
- Side effects?
- Contraindications?
A
- Class: Metabolic modifier (used for patients with angina)
- MOA:
- Inhibits late sodium currents → decreased Ca channel activation → therefore decrease Ca2+ in the cell → less diastolic stress → improved coronary blood flow
- Partial fatty oxidation inhibitor → tissues switches to glucose metabolism → creates more ATP
- *prolongs QT interval
- Side Effects: Dizziness, headaches, nausea
- Contraindications: Metabolized by P450s
15
Q
For aspirin:
- What is the class?
- What is the MOA?
- What are some side effects?
- What are some contraindications?
A
- Class: Platelet Aggregation
- MOA: Irreversibly inhibits COX-1/2 → reduces TXA → prevents platelet aggregation
- *COX-1 found in platelets
- Side Effects: GI bleeding/GI irritation
- Contraindications: Patients taking NSAIDS
16
Q
For clopidogrel:
- What is the class?
- What is the MOA?
- What are some side effects?
- What are some contraindications?
A
- Class: Platelet aggregation
- MOA: Prodrug that inhibits to the P2Y (ADP receptor) → allows for Prostacyclin to have anti-platelet activity
- Side Effects: rash diarreah, bleeding
- Contraindication: metabolized by CYP540
17
Q
For Tenecteplase:
- What is the class?
- What is the MOA?
- In what time period should it be administered following an MI?
- What are some side effects?
- What are some contraindications?
A
- Class: Thrombolytic:
- MOA: Binds to fibrin at clot site → activating plasminogen → degrades fibrous clot
- Administer within 70 minutes
- Side Effects: Bleeding Thrombocytopenia, allergy/hypotension/fever
- Contraindicated: patients with active bleeding
18
Q
Define what is meant by altered impulse formation and by altered impulse conduction.
A
- Altered impulse formation = decreased automaticity of SA node
- Altered impulse conduction = conduction block
19
Q
Explain the ionic process of automaticity.
A
- Hyperpolarization of SA nodal cell → If (Na+) channels are activated → sloped phase 4 → threshold potential is reached → L-type Ca++ channels open → depolarization → K+ efflux out of the cell →
20
Q
- What are the native pacemaker) and their characteristics (including bpm)?
- What are the latent pacemaker) and their characteristics (including bpm)?
A
- Native: SA Node (60-100bpm) because it has faster rate, and its repeated discharges prevent spontaneous firing of other potential pacemaker sites
- Latent: AV node (50-60bpm), Bundle of His (50-60pm), and Purkinje system (30-40bpm)
21
Q
How the heart rate controlled autonomically? Inhibited and stimulated pathways?
A
- Cholinergic stimulation
- Hyperpolarizes the cell, causing less depolarization
- Adrenergic stimulation
- Increases the rate of phase 4 diastolic depolarization
- Causes less hyperpolarization of pacemaker cells
- Makes the threshold potential for depolarization more negative (lowers the threshold)
22
Q
Define normal sinus rhythm.
A
- Normal Sinus Rhythm = 60-100bpm
- Pw followed by QRS complex
- QRS complex preceded by Pw
- Pw is upright in leads I, II, and III
- The PR interval is between 0.12 seconds and 0.20 seconds
23
Q
Define sinus bradycardia and sinus tachycardia.
A
- Sinus Bradycardia = <60bpm
- Sinus Tachycardia = >100bpm
24
Q
What does conduction block mean?
A
- Normal rate of conduction is slowed or completely blocked which leads to slowed ventricular depolarization or bradyarrhythmias
25
What are the 4 types of conduction block?
* SA nodal exit block
* First Degree AV Block
* Second Degree AV Block
* Third Degree AV Block
26
What occurs in the SA nodal exit block?
* What can it initate?
* What can it be caused by?
* What is the symptomatic version of this called?
* SA nodal exit block – problem with automaticity
* Results in sinus pauses, sinus arrest
* Initiates escape rhythms that require latent pacemakers
* Can be caused by old age, structural heart disease, cardiac surgery, increased vagal tone, and drugs
* If symptomatic, sinus node dysfunction is identified as sick sinus syndrome
27
What occurs in a first degree AV Block?
* What is shown on the EKG?
* Are there symptoms?
* First Degree AV Block – problem with conduction
* PR interval is prolonged (\>.20 seconds) with no dropped QRS complex
* Asymptomatic
28
What occurs with second degree AV blocks?
* What are the two types?
* What occurs on the EKG for both types?
* Second Degree AV Blocks – problem with conduction
* AV nodal block – Mobitz I or Wenckeback Block
* Pw with progressively lengthening PR interval until there is a Pw with no QRS interval
* His bundle block – Mobitz II
* Constant PR interval leading up to a Pw with a dropped QRS complex
29
What occurs with third degree AV block?
* What do you end up seeing on the EKG?
* Third Degree AV Block – problem with conduction
* Ventricle and atria are completely dissociated and are marching to the beat of their own drums
* Not necessarily sequential p-wave then QRS.
30
What are the 4 main causes of heart blocks?
* AV nodal fibrosis or calcification
* Acute MI
* Structural heart disease
* Cardiac surgery
31
How can you tell that a pacemaker is being used based on the EKG?
* Sharp vertical spike before the Pw indicates atrial pacemaker
* Sharp vertical spike before the QRS complex indicates ventricular pacemaker
32
For plaque rupture:
* Do they have minimal lipids or are they lipid rich?
* What is secreted from the necrotic core that makes plaque more vulnerable to rupture? How does this process start?
* What does plaque rupture cause exposure of and what does it lead to?
Plaque Rupture
* Lipid rich plaques
* Vulnerable plaque: plaques with increased necrotic cores have higher levels of inflammatory cells, which secrete lipoprotein-associated phospholipase A2 (Lp-PLA2), and this enzyme oxidizes LDL and thinning of the fibrous cap, making the plaque more susceptible to rupture
* Plaque rupture causes exposure of subendothelial collagen and tissue factor, activating the intrinsic and extrinsic coagulation cascades respectively
* Many events are asymptomatic or sub-clinical
33
For plaque erosion:
* Do they have minimal lipids or are they lipid rich?
* When/where does this plaque occur?
* What is the overal pathophysiology?
* Who is at more of a risk for this condition and why?
* Lipid poor plaques
* A plaque that causes ridge in the endothelium disrupts the normal laminar flow
* Disrupted laminar flow causes endothelial cells to stop producing NO, decreasing vasodilator effect
* Disrupted laminar flow causes endothelial cells to stop producing prostacyclin, which normally inhibits platelet aggregation
* More likely to be in smokers because it causes an increase in ROS, further damaging the endothelium
34
What labs can be used to figure out if cardiac necrosis has occured (2 main labs)?
* Troponins T and I – elevated after 3-4 hours post-MI and peaks around 24 hours, and levels stay elevated for up to 2 weeks
* CK MB – can be used for 2nd MI because levels of this substance rise and fall rapidly
35
For the following time ranges, provide the general gross appearance of the heart post-MI:
* 0-20 minutes
* \< 4 hours
* 4-24 hours
* 1-3 days
* 3-14 days
* 2 weeks to several months
Gross Cardiac Changes Post-MI
* 0-20 minutes: **No changes**
* \< 4 hours: **No changes**
* 4-24 hours: **Dark discoloration**
* 1-3 days: **Yellow pallor**
* 3-14 days: **Red border emerges as granulation tissue forms**
* 2 weeks to several months: **White scar**
36
For the following time ranges, provide the general microscopic appearance of the heart post-MI:
* 0-20 minutes
* \< 4 hours
* 4-24 hours
* 1-3 days
* 3-14 days
* 2 weeks to several months
Microscopic Appearance Post-MI
* 0-20 minutes: **ATP depletion, mitochondria swelling, glycogen depletion**
* \< 4 hours: **Wavy fibers due to inability to contract; edema**
* 4-24 hours: **Few neutrophils and coagulative necrosis**
* 1-3 days: **Heavy infiltration of neutrophils**
* 3-14 days: **Macrophages with formation of granulation tissue**
* 2 weeks to several months: **Fibrosis, with increased collagen and "ghost-like" acellular myocytes**
37
At what time is this cardiac muscle post-MI?
\<4 hours: “Wavy” fibers due to inability to contract; edema
38
At what time is this cardiac muscle post-MI?
4-24 hours: Few neutrophils and coagulative necrosis
39
At what time is this cardiac muscle post-MI?
4-24 hours: Dark discoloration
40
At what time is this cardiac muscle post-MI?
1-3 days: Heavy infiltration of neutrophils
41
At what time is this cardiac muscle post-MI?
4-14 days: Macrophages with formation of granulation tissue
42
At what time is this cardiac muscle post-MI?
4-14 days: Red border emerges as granulation tissue forms
43
At what time is this cardiac muscle post-MI?
2 weeks to several months: Fibrosis, with increased collagen and “ghost-like” acellular myocytes
44
At what time is this cardiac muscle post-MI?
2 weeks to several months: white scars
45
Name 7 post-MI complications
* **Papillary muscle dysfunction**: leads to mitral valve regurgitation
* **Heart wall rupture**: leads to cardiac tamponade
* **Interventricular septal rupture**
* **Arrhythmia**: can lead to death
* **Mural thrombosis**: can lead to stroke or other embolic event
* **Pericarditis**: inflammation of the myocardium can lead to inflammation of the pericardium
* **Cardiac aneurysm**: thinning of myocardial muscle/wall can cause high blood pressure in ventricle to push out the wall of the heart
46
What are the causes of sudden cardiac death? (3)
* Post-MI complication of fatal arrhythmia
* Aortic dissection with rupture
* Massive pulmonary embolus from akinetic heart wall
47
What are the causes of non-atherosclerotic MIs? (4)
* Congenital (abnormal anatomy of coronary arteries)
* Inflammation (vasculitis, Kawasaki disease)
* TTP/HUS/DIC
* Vasospasms
48
Tachyarrhythmias
Definition?
Definition: HR \> 100 bpm
49
Supraventricular Tachycardias
* Supraventricular Tachycardias – not dangerous
* Originate in atrium
* Narrow QRS \<120ms
50
Ventricular tachyarrhythmias
* Ventricular tachyarrhythmias – dangerous
* Originate in ventricle
* Wide QRS \>120ms
51
Tachyarrhythmias
Symptoms/Complications
* Symptoms
* Heart racing, palpitations, syncope
* Complications
* Stroke, heart failure
52
Mechanisms of
Tachyarrhythmias
automaticity, triggered, reentry
53
Explain automiticity
* Increased native pacemaker activity – sinus tachycardia
* Enhanced latent pacemaker activity – premature atrial contractions, junctional tachycardia
* Abnormal non pacemaker cells – ventricular, atrial tachycardia
54
Explain triggered abnormal impulse formation
what are the two types?
* Triggered – abnormal activity is stimulated by a preceding depolarization
* Early Afterdepolarizations (EAD)
* Repetitive depolarizations during the repolarization phase of cardiac AP due to membrane potential being more positive
* Caused by channelopathies, drugs, prolonged QT interval
* Delayed Afterdepolarizations (DAD)
* Repetitive depolarizations after repolarization phase of cardiac AP due to HIGH intracellular Ca2+
* DIGOXIN toxicity
55
Explain Reentry
What are the required conditions?
* Reentry – formation of abnormal impulse conduction circuits
* Required conditions
* Initial premature/abnormal impulse/beat
* Unidirectional block
* Functional: interaction with cells still in refractory period (can be caused by certain anti-arrhythmics)
* Fixed: interaction with cells affected by fibrosis or myocardial scar
* 2 pathways with different conduction properties
* 1 with faster conduction or a slower refractory period (normal – non-injured tissue) i.e. alpha
* 1 with slower conduction or faster refractory period (unidirectional blocked – damaged tissue) i.e. beta
56
Sinus Tachycardia
Description & Mechanism
* Description: sinus rhythm with bpm \>100
* Mechanism: increased automaticity
57
Premature Atrial Contractions/Beats
Description & Mechanism & Tx
* Description: early than expected p-wave
* Mechanisms: automaticity, triggered, reentry (occurring outside of SA node)
* Treatment: lifestyle changes or beta-blockers if symptomatic
58
Paroxysmal SVT
Description & Mechanism
* Description:
* Sudden onset and termination of arrhythmia
* Atrial rates of 140-250 bpm
* Narrow QRS complex
* Mechanism: reentry
59
AV nodal reentrant tachycardia (AVNRT)
EKG & Mechanism & Tx
* Mechanism: Reentry via dual AV node pathways with functional unidirectional block creation reentry loop within node --\> repetitive depolarizations --\> tachycardia
* Treatment: block AV node, ablation (stimulates vagal tone), antiarrhythmics
* EKG: no p waves
60
Atrioventricular reentrant tachycardia (AVRT)
Mechanism & Tx
* Mechanism: Reentry pathway where one pathway in from the AV node and the other by congenital accessory pathway (abnormal band that connects atrial to ventricular tissue)
* Treatment: : block AV node, ablation
* most commonly associated with Wolff-Parkinson-White syndrome
61
Ventricular Pre-Excitement/ Wolff Parkinson White Syndrome (WPW)
Two types?
* Accessory pathway known as Bundle of KENT
* Manifested (bidirectional) – slurred upward QRS (delta wave) EKG
* Can induce V-fib
* Concealed (unidirectional) – normal EKG
62
Focal Atrial Tachycardia
Description & Mechanism & Tx
* Description: abnormal p-waves with SVT
* Mechanism: reentry or automaticity of non-pacemaker atrial tissue
* Treatment: underlying cause (can be elevated sympathetic tone)
63
Atrial Flutter
Description & Mechanism & Tx
* Description: Atrial rates of 180-350 bpm resulting in saw-tooth pattern EKG
* Mechanism: Reentry circuit that around the ring of the tricuspid valve (isthmus) not effecting AV node
* Treatment: AV nodal blockers, ablation, cardioversion
64
Atrial Fibrillation
Description, Mech, and Tx
* Description: no discrete p-waves with varying R-R intervals
* Mechanism: automatic (pulmonary veins) and reentry mechanisms
* Treatment: ablation
* Rate control: AV nodal blockers – beta blocker, ca2+ channel blocker, digoxin
* Rhythm control: anti-arrhythmics
65
Ventricular Tachycardia
Description, Mech, and Tx
* Description: series of 3 or more premature ventricular beats – wide QRS complex with tachycardia
* Mechanism: usually re-entrant from fibrosis or prior MI
66
Ventricular Tachycardia
Types
* Sustained: more than 30 seconds with severe symptoms
* Treatment: Cardioversion, anti-arrhythmics
* Benign: rare exception
* Torsade de pointes: associated QT intervals with polymorphic QRS complexes
* Mechanism: Triggered – early afterdepolarizations
67
Ventricular Fibrillation (life threatnening)
Description, mech, & tx
* Description: chaotic rhythm with no discrete p-waves and no contraction/cardiac output
* Mechanism: initiated by an episode of V-tachycardia – reentry circuit becomes overwhelmed
* Treatment: ACLS, defibrillator
68
Premature Atrial Contractions/Beats
69
Ventricular Pre-Excitement/ Wolff Parkinson White Syndrome (WPW)
70
Atrial Flutter
71
Atrial Fibrillation
72
Ventricular Tachycardia
73
Torsade de pointes
74
Ventricular Fibrillation
75
What would ealry afterdepolarization look like?
76
What would delayed afterdepolarization look like?
77
Adenosine
MOA? Effects? Use? Adverse Effects?
**MOA:** Blocks Ca++ channels at SA and AV nodes
**Effects:**
* Prolonged QT interval because prolonged Phase 0 depolarization
**Use**:
* Acute reentrant supraventricular tachycardia
**AE:**
* Bronchospasm
78
Digoxin
MOA? Effects? Use? Adverse Effects?
**MOA:** Blocks Na+/K+ ATPase
**Effects:**
* Increases vagal activity
* Slows AV conduction
**Use**:
* AV reentrant arrhythmias
* Chronic AFIB
**AE:**
79
Non-DHP CCBs (verapamil and diltiazem)
Type? MOA? Effects? Use? Adverse Effects?
**Type:** IV
**MOA:** Blocks calcium channels at SA and AV nodes
**Effects:**
* Prolonged Phase 0 depolarization in nodal tissue
* Prolonged QT interval
**Use**:
* AFIB
**AE:**
* Bradycardia
* Hypotension
80
Dofetilide
Type? MOA? Effects? Use? Adverse Effects?
**Type:** III
**MOA:** Blocks K+ channels
**Effects:**
* Delay repolarization (prolonged QT interval)
**Use**:
* Continuing atrial tachycardia after ablation
**AE:**
* QT prolongation – contraindicated for hypokalemia
81
Sotalol
Type? MOA? Effects? Use? Adverse Effects?
**Type:** III
**MOA:** Blocks K+ channels and beta-blocker
**Effects:**
* Delay repolarization (prolonged QT interval)
**Use**:
* Atrial and ventricular tachycardia
**AE:**
* Bradycardia, bronchospasm
82
Amiodarone
Type? MOA? Effects? Use? Adverse Effects?
**Type:** III
**MOA:** Blocks Na+, Ca++, and K+ channels
**Effects:**
* Delay repolarization (prolonged QT interval)
**Use**:
* Sustained life-threatening arrhythmias
**AE:**
* Thyroid issues
* “Smurfism”
83
Beta Blockers
Type? MOA? Effects? Use? Adverse Effects?
**Type:** II
**MOA:** Blocks beta-adrenergic receptors
**Effects:**
* Slows conduction velocity
* Decreases automaticity, thus increasing PR interval (due to slowed AV conduction)
**Use**:
* Atrial tachycardia because slows conduction at AV node
* Ca++ dependent arrhythmias at AV and SA nodes
**AE:**
84
Flecainide
Type? MOA? Effects? Use? Adverse Effects?
**Type:**Ic
**MOA:** Na+ channel blocker (potent)
**Effects:**
* AV Node: prolonged refractory period
* Atrial, ventricular, Purkinje fibers: prolonged Phase 0 with no change in refractory period
* Raises depolarization threshold
**Use**:
* Ventricular arrhythmias
* AFIB
* Paroxysmal supraventricular arrhythmias
**AE:**
* Metallic taste
* Visual disturbances
85
Quineidine
Type? MOA? Effects? Use? Adverse Effects?
**Type:**Ia
**MOA:**Na+ channel blocker and K+ rectifier channel blocker
**Effects:**
* Prolonged Phase 0 depolarization and prolonged Phase 3 repolarization
* QT and QRS prolongation
* Raises depolarization threshold
**Use**: Historic drug for reentrant arrhythmias
**AE:**
* QT prolongation – Torsades de Pointes
* Anticholinergic properties
* Cinchonism – tinnitus, dizziness, blurred vision, headache,
