ITPX: Cardiology III-IV COMBINED

Anticoagulants examples on slide? (five)

Heparin

Enoxaparin

Dabigatran

Rivaroxaban

Warfarin

Fibrinolytic examples on slide?

Alteplase

Anti-thrombotic drug examples on slide? (six)

Aspirin

Clopidogrel

Tirofiban

Vorapaxar

Cilostazol

Argatroban

Define hemostasis

Process of keeping blood within damaged blood vessels by repairing breaks without compromising the fluidity of the blood

Result of impaired hemostasis?

Spontaneous bleeding

Result of stimulated hemostasis?

Thrombus

Platelets stick to the exposed collagen of the damaged endothelium how quickly?

Within seconds

Why is vasospasm the immediate hemostatic response of a damaged vessel?

Close the area that is damaged/bleeding

Role of white thrombus

Forms in high-pressure arteries, decreases arterial flow; stasis triggers fibrin formation -> Stroke, MI

Role of red thrombus

Forms around white thrombus or in low-pressure veins; platelets form a long tail consisting of a fibrin network in which RBC are enmeshed -> DVT -> PE

Blood coagulates by the transformation of soluble fibrinogen into _______ _________

insoluble fibrin

Role of zymogen?

A clotting factor which undergoes limited proteolysis and becomes an active protease, VII -> VIIa

Protease activates the next clotting factor until a solid fibrin clot is formed

Factor X becomes factor Xa via what other two factors

Factor IXa and factor VIIIa

Which factors are inhibited by heparin?

IIa

Xa

IXa

XIa

Which factors are inhibited by warfarin?

II

VII

IX

X

From where do we derive heparin?

Hog intestinal mucosa

Beef lung

Mechanism of action of heparin?

Greatly increases rate of activity of antithrombin

Heparin (-) binds antithrombin (+) which inhibits serine protease clotting enzymes by forming a stable 1:1 molecular complex by association between an arginine-reactive site on antithrombin & the active site of serine protease

Heparin's place in therapy?

Thrombosis/Embolism prophylaxis (after major surgery)

PE, DVT, DIC active treatment

Side effects associated with heparin?

Hemorrhage anywhere in the body, allergy (chills, fever, urticaria), thrombocytopenia (HIT)

What is fondaparinux?

Just really small heparin

5 monosaccharides long

Drug interactions to watch for with heparin?

Cephalosporins, penicillins (altered platelet aggregation)

NSAIDs (inhibit platelet aggregation)

With what do we treat heparin-induced bleeding?

Protamine (rich in ARG "+") will bind to and inactivate the negatively charged heparin

Enoxaparin and Dalteparin are sourced from? What size heparin are they?

Low molecular weight heparins

2-9 KDa depolymerized pig heparin

Administered SQ

How is heparin activity measured?

PTT; partial thromboplastin time

Values 2.0-3.5 times the control yield therapeutic effects

Low molecular weight heparins are more selective for

A. Xa

B. IIa

A. Xa

Side effects associated with low molecular weight heparins

Like heparins but

Also spinal/epidural hematomas

T/F: Low molecular weight heparins have a longer half life as compared to high molecular weight heparin.

True

Fondaparinux selectively inhibits which clotting factor

Xa

Place in therapy for fondaparinux

DVT prophylaxis

Side effects associated with fondaparinux?

Hemorrhage, thrombocytopenia

Direct Xa inhibitors place in therapy?

Nonvalvular afib -> prevent stroke, systemic embolism

Prophylaxis of DCT -> knee, hip replacement

Rivaroxaban can be used in HIT, PAD, ASA

Direct IIa inhibitor examples

Lepirudin

Bivalirudin

Desirudin

Argatroban

Dabigatran

Mechanism of action of Direct IIa inhibitors?

Inhibits thrombin (IIa) by binding to it (1:1 stoich)

Direct IIa inhibitors are derived from?

Polypeptide analog of hirudin from medicinal leech

Place in therapy for direct IIa inhibitors?

HIT (Argatroban, Lepirudin)

DVT prophylaxis (Desirudin)

Acute ischemic complications of percutaneous coronary intervention (Bivalirudin)

Afib (Dabigatran)

A 61-year-old man is being treated with heparin for a pulmonary embolism. Which of the following clotting factors is inhibited by heparin?

A. Ia

B. IIa

C. IIIa

D. IVa

E. Va

B. IIa

T/F: The S-enantiomer of warfarin is 4x more potent than the R-enantiomer.

True

Mechanism of action of warfarin?

Vitamin K analog, Blocks the gamma-carboxylation of several glutamate resides in prothrombin (II) factors VII, IX, X

Place in therapy for warfarin?

Venous thrombosis/thromboembolic events (MI, DVT, PE)

Afib/flutter

Mechanical prosthetic cardiac valves (with low dose ASA)

Side effects associated with warfarin?

Hemorrhage

Necrosis

Hypercoagulation (naive patients)

Birth defects

Abortion

Therapeutic INR range for warfarin?

2.0 to 3.0

What is our treatment plan for warfarin hemorrhaging?

D/C warfarin -> give IV vitamin K1 or Fresh-frozen plasma, or prothrombin complex concentrates, or rFVIIa

Drug interactions of concern for warfarin (increase risk for bleeding)?

Pharmacokinetic:

Amiodarone

Metronidazole

SMZ/TMP

Clopidogrel

(CYP 2C9 inhibitors)

Pharmacodynamic:

ASA

Ceftriaxone

Gingko biloba

(Additive effects)

Drug interactions of concern for warfarin (increase risk for clotting)?

Pharmacokinetic:

Phenobarbital

Rifampin

Carbamazepine

St John's Wort

Cholestyramine (bile)

(CYP2C9 inducers)

Pharmacodynamic:

Vitamin K

Hydrochlorothiazide (induce clotting factors)

Three fibrinolytics?

Alteplase

Reteplase

Tenecteplase

Mechanism of action of fibrinolytics

Converts plasminogen into plasmin which degrades fibrin & fibrinogen

Place in therapy for fibrinolytics?

Acute MI (Alteplase, Reteplase, Tenecteplase)

Pulmonary embolism (Alteplase)

Acute ischemic stroke (Alteplase)

Side effects associated with fibrinolytics?

Hemorrhage

We should give fibrinolytics with caution to patients who are at a ....

High bleeding risk

Mechanism of action of aspirin?

Inhibits the synthesis of thromboxane A2 by irreversible acetylation of COX-1/2, A nuclear platelet can't synthesize more COX during its 10-day lifetime

Function of thromboxane A2?

Platelets shape, release granules, and aggregation

Place in therapy for aspirin?

Primary prevention of MI and TIA

Treatment of STEMI & NSTEMI, ischemic stroke (sometimes with plavix)

Treatment of acute ischemic stroke

Side effects associated with aspirin?

Bleeding, GI ulcers

P2Y12 antagonist examples? (four)

Clopidogrel

Prasugrel

Ticagrelor

Ticlopidine

Mechanism of action of P2Y12 antagonists?

Interferes with platelet membrane function by inhibiting ADP-induced platelet-fibrinogen binding & subsequent platelet-platelet interaction, irreversible

Clopidogrel inhibits what enzyme

CYP2C9

Clopidogrel is bioactivated by what enzyme

CYP2C19

GP IIb/IIa inhibitor examples (two)

Tirofiban

Eptifibatide

Mechanism of action of GPIIb/IIIa inhibitors

Inhibits the glycoprotein IIb/IIIa receptor of platelets; leads to decreased platelet aggregation w/ fibrinogen and vWF

Place in therapy for GP IIB/IIIa inhibitors

Acute coronary syndrome

Used with aspirin and/or heparin

Dipyridamole mechanism of action?

Phosphodiesterase inhibitor; increased cAMP within platelets which inhibits their reactivity & adenosine reuptake inhibitor; leads to increased adenosine binding to A2 receptors and increased cAMP

Mechanism of cilostazol?

PDE3 inhibitor which increases cAMP in both blood vessels and platelets that leads to inhibition of platelet aggregation and vasodilation

Place in therapy for cilostazol?

Intermittent claudication

Vorapaxar mechanism of action?

PAR-1 receptor antagonist; inhibits thrombin mediated activation of platelets

Place in therapy for Vorapaxar

MI, PAD; decrease thrombotic cardiovascular events

Mechanism of action of aminocaproic, tranexamic acid?

Bind to lysine sites on plasminogen and plasmin, which interferes with the ability of plasmin to lyse fibrin clots

Mechanism of action of recombinant FVIIa

Activates clotting factors IX & X on the surface of activated platelets to restore the formation of thrombin

Mechanism of action of Efanesoctocog alfa (Altuviiio)

Activates X -> Xa in conjunction with IXa which ultimately leads to a fibrin clot

A 75-year-old woman is diagnosed with an acute MI in the emergency department. Which of the following is most likely to promptly open up her occluded coronary artery?

A. Warfarin

B. Heparin

C. Alteplase

D. Aspirin

E. Enoxaparin

C. Alteplase

CCD includes which 4 types of patients?

1. Discharged after ACS event and after coronary revascularization

2. LV systolic dysfunction and known or suspected CAD or those with established ischemic cardiomyopathy

3. Angina symptoms medically managed without positive results of an imaging test

4. Diagnosed with CCD solely based on screening study (stress test) and concluded to have coronary disease

Define coronary artery disease (CAD)

Build up of plaque in coronary arteries that may lead to ischemia

Define ischemic heart disease (IHD)

Primarily caused by atherosclerosis, which leads to coronary heart disease

Define angina pectoris

Chest pain due to decreased oxygen supply to myocardial tissue

Traditional risk factors for CAD? (six)

1. High LDL

2. Low HDL

3. High BP

4. Family history

5. Diabetes

6. Smoking

Which three ischemic events can be classified as "acute coronary syndrome?"

1. Unstable angina

2. NSTEMI

3. STEMI

Pathophysiology of ischemia put simply?

Decrease in myocardial O2 supply (arterial o2 content, myocardial o2 content, perfusion pressure, resistance)

Increase in myocardial O2 demand (heart rate increase, contractility increase, increase wall tension)

T/F: Clinical presentations of CCD can be silent.

True

T/F: Only about 5.1% of chest pain ED admissions are attributable to ACS.

True

Chest pain which is chronic and associated with consistent precipitants (i.e. exertion or emotional stress) is classified as which of the following?

A. Stable

B. Acute

A. Stable

Chest pain which is new in onset or involves a change in pattern, intensity, or duration compared with previous episodes in a patient with recurrent symptoms is classified as which of the following?

A. Stable

B. Acute

B. Acute

Describe the PQRST assessment of chest pain

Precipitating factors (Exercise, exertion)

Palliative measures (Relieved by rest with/without a sublingual nitroglycerin)

Quality of the pain (Squeezing, heaviness, tightness)

Region (Substernal)

Radiation (Left or right arm, back, neck)

Severity (pain usually 5+)

Temporal pattern (timing (less than 20 min usually)

T/F: 90% blockage of the artery is classified as critical.

True

T/F: 90% blockage of the artery is when we begin to see clinical signs.

False; 70%

T/F: Women are less likely to have timely and appropriate care.

True

T/F: Women frequently present with other symptoms in addition to chest pain, i.e. nausea, fatigue, SOB.

True

Three characteristics for the clinical classification of chest pain?

1. Substernal chest discomfort with a characteristic quality and duration

2. Provoked by exertion or emotional stress

3. Relieved by rest or nitroglycerin

"Cardiac chest pain" must meet how many of the three characteristics for clinical classification of chest pain?

All 3 characteristics

"Possible cardiac chest pain" must meet how many of the three characteristics for clinical classification of chest pain?

Must meet 2 characteristics

"Noncardiac chest pain" must meet how many of the three characteristics for clinical classification of chest pain?

Less than or equal to one characteristic

Describe ECHO testing

Use of emission of ultrasound waves to construct image

Symptomatic relief of angina is achieved through which four pharmacological agents/classes?

1. Nitrates

2. Beta-blockers

3. CCBs

4. Ranolazine

Moderate-intensity statins goal in reduction of LDL-C levels?

30-49%

High-intensity statin therapy goal in reduction of LDL-C levels?

50% or greater

T/F: SGLT2 inhibitors primarily reduce atherosclerosis and reduce incident/worsening HF.

False; do not work as well for atherosclerosis as they do for HF.

T/F: GLP-1 receptor agonists appear to primarily reduce risk of atherosclerotic events (MI, stroke).

True

Agents that decrease myocardial O2 demand? (two classes)

Beta blockers

Non-DHP CCBs

Which of the following is preferred for decreasing myocardial O2 demand?

A. BBs

B. Non-DHP CCBs

BBs (but not based on strong evidence)

Which of the following should be avoided in patients with significant LV dysfunction?

A. BBs

B. Non-DHP CCBs

B. Non-DHP CCBs

Can depress LV dysfunction

Agents that increase myocardial o2 supply? (two)

Nitrates

DHP CCBs

MOA of nitrates?

Relaxation of vascular smooth muscle leading to vasodilation