Fcm Pharm - Atherosclerosis, Cad, Mi

Front 1

What percent of MIs are fatal?
What is usually the first symptom?

Back 1

1/4th of all MIs are fatal
Sudden death is usually the first symptom

Front 2

What are the MOST VIRULENT risk factors for CAD?

Back 2

- dyslipidemia
- hypertension
- diabetes
- cigarette smoking
- family history

Front 3

What are the recommended LDL and HDL levels?
Total Cholesterol?

Back 3

LDL </= 100 mg/dL

HDL >/= 40 mg/dL

Total Cholesterol </= 200 mg/dL

Front 4

Explain the idea behind plaques and atherosclerosis: stable --> vulnerable --> ruptured

Back 4

Atherogenesis is a proliferative disease - i.e., an inflammatory response

LDL sticks to vessel walls and causes oxidative injury to endothelial cells --> activates NFKB and induces inflammatory pathways

There is lipid accumulation with lipid-laden macrophages and smooth muscle cells (foam cells) --> collagen deposition forms fibrous cap, which stabilizes the plaque and prevents rupture - "stable plaques"

Some stable plaques are transformed into unstable plaques - "vulnerable plaques" - with a thinner collagen cap and a large lipid core

The vulnerable plaque ruptures - "Ruptured Plaque" - blood is exposed to the collagen --> platelet aggregation and thrombogenesis --> acute occlusion

Front 5

What is atheroprotection?

Back 5

Prophylactic therapy for the prevention of atherosclerotic syndromes

Front 6

STATINS
- mechanism of function

Back 6

Competitive inhibitors of HMG-CoA --> decrease synthesis of cholesterol

Increase synthesis of LDL receptors (benefit is on hepatic cells) --> increases clearance of circulating LDL and IDL via liver

Some statins increase HDL levels

**Little effect on plaque size

Other:
- Stimulate NO production in vascular wall (decreases monocyte and platelet adhesion, thereby slowing plaque progression)
- Reduce proinflammatory mediators
- Reduce hs-CRP (marker of inflammation)
- Inhibit SMC proliferation
- Reduce synth of MMPs

Front 7

What is first line atherosclerosis therapy?

Back 7

STATINS

Front 8

What can be taken in conjunction with statins to increase their pharmacologic value?
How does it work?

Back 8

Bile Acid Resins
- Not absorbed by the gut --> bind to bile acids and promote their excretion in the stool --> further reduce hepatocellular cholesterol levels

Front 9

ACE-Inhibitors
- what are they typically indicated for?
- mechanism?
- which drugs, specifically?

Back 9

Indicated for hypertension and heart failure; reduce mortality due to MI as well!

- Inhibit Angiotensin II formation (ang II increases atherogenesis by increasing oxidative stress on arterial wall cells)

Other:
- Stimulate NO production in vascular wall
- Inhibit local tissue formation of ang II
- Reduce oxidative stress on arterial wall cells
- Inhibit SMC proliferation
- Inhibit oxLDL uptake by inhibiting synth of LOX receptor

*Only the TISSUE ACE-inhibitors are indicated = enalopril and ramipril

Front 10

What is the angiotensin pathway?

Back 10

Angiotensinogen --(renin)--> Angiotensin I --(ACE)--> Angiotensin II

Front 11

What are the different types of ACE enzymes?

Back 11

- Circulating ACE

- Tissue ACE - essential in embryonic development, then deactivated; in some people, gets turned back on and causes increased BP
**this is the type we target for MI protection

Front 12

CALCIUM CHANNEL BLOCKERS
- which drugs, specifically?
- mechanism

Back 12

Only 3rd generation dyhydropyridines = AMLODIPINE(only one available in US)

*Amlodipine is the only CCB safe in HF patients

Mechanism:
- Stimulates NO production in vascular wall
- Inhibit SMC proliferation
- Inhibit collagen synth by SMC
- Inhibit lipid peroxidation
- Inhibit expression of atherogeneic genes in SMC

Front 13

What is "nature's atheroprotective molecule"?
How can it be naturally increased?

Back 13

= NO!
... naturally increased by exercise

Front 14

APIRIN
- Mechanism
- What is the downfall?

Back 14

= COX inhibitor
--> decrease TXA2 synthesis
(COX pathways lead to iflammation and platelet aggregation)

**Most widely used drug for protection against chronic and acute atherosclerotic syndromes

*Reduced incidence of first non-fatal MI

- Risk/Benefit ration questionable in pts with peptic ulcer or hypertension bc at doses >500 mg/dL, increased peptic ulcers and gastic bleeding

Front 15

ANTIOXIDANTS
- mechanism

Back 15

NOT PROVEN EFFECTIVE IN HUMANS (in vitro and animal studies only...)

- inhibit many oxidative pathways that cause atherogenic stimuli --> inhibit lesion formation

Front 16

What is one of the main common actions of Statins, ACE-inhibitors and CCBs?

Back 16

Stimulate NO production in arterial wall

Front 17

What is the main concept behind acute MI therapy?

Back 17

**Manage tissue ischemia

- Requirement: O2 supply (coronary blood flow) > O2 consumption (ventricular work)

- If unmet, ischemia results and contractility in myocardium fails... increasing risk of developing life-threatening cardiac arrhythmias (e.g., V-tach, V-fib)

Front 18

What are Caduet and Vytoran?

Back 18

First 2 "polypills" available = statin + amlodipine

Front 19

What is the PROTOCOL for management of Acute MI?

Back 19

1. aspirin
2. IV nitroglycerin
3. morphine
4. nasal O2
5. beta-blocker
6. ACE-inhibitor
7. thrombolysis
8. drug-eluting stents
9. discharge meds = "ABC"

Front 20

Nitroglycerin
- mode of administration
- mechanism/purpose

Back 20

IV

Releases NO into arterial wall (vasodilator)
- Coronary arteries
- Peripheral arteries (reduces LV afterload)
- Venous compartments (reduces RV and LV preload)

Front 21

Morphine
- purpose

Back 21

To control pain and discomfort

- pain --> anxiety --> increase in sympathetic tone --> increase O2 consumption --> worsen ischemia --> worsen pain...............

Front 22

Beta-Blocker
- mechanism/purpose
- caution?

Back 22

- Reduce sympathetic effect on heart --> reduce contractility --> reduce O2 consumption (improves supply/demand ratio)

= "unloads the myocardium"

Caution: excessive unloading can reduce contractility too much, and perfusion pressure becomes so low that it worsens ischemia

Front 23

Thrombolysis
- specific drugs?
- functions?
- added efficacy?
- complications?

Back 23

Tissue Plasminogen Activator (tPA) = activates plasminogen into plasmin, which lyses the thrombus from within
Human tPA - Alteplase (recombinant DNA)
Reteplase - great clot selectivity
**tPAs are fibrin-specific - better than streptokinase!

Streptokinase - activates plasminogen

**Best if initiated within 6 hours

- added efficacy of tPA = + aspirin or + heparin (if doing an angioplasty)
- complications: bleeding

Front 24

What are typical discharge meds after MI?

Back 24

Aspirin
Beta-Blocker
Statin
(also prob ACE-inhibitor or ARB)

Front 25

What are the prophylactic therapies indicated for pts with CAD?

Back 25

Aspirin (only effective in men)
ADP Inhibitors
GP IIB/IIIA Inhibitors

Front 26

ADP Inhibitors
- specific drugs
- mechanism

Back 26

- Clopidogrel, Ticlopidine

- inhibit binding of ADP to platelet receptors --> reduce platelet aggregation --> inhibit thrombogenesis

Front 27

GP IIB/IIIA Inhibitors
- mechanism
- specific drugs
- adverse effects

Back 27

= anti-platelet agents:

GP IIB/IIIA Receptor Complex on platelets = receptor for fibrinogen, vitronectin, fibronectin, von Willibrand Factor

- Abciximab
- Eptifibatide
- Tirofiban

- AE: can cause severe thrombocytopenia

Front 28

Drug-Eluting Stents
- specific druge
- mechanism

Back 28

- Sirolimus and Paclitaxel

- Slowly released over the first few weeks of stent placement

- Antiproliferative actions; inhibit cell cycle progression in vascular cells --> reduce restenosis

Front 29

What are the 2 types of angina?

Back 29

1. Variant Angina/Prinzmetal's Angina - coronary artery vasospasm reduces blood flow below O2 demand

2. Effort Angina/Stable Angina - O2 demand greater than coronary blood flow due to stenosis

Front 30

What is the treatment for Variant Angina? Explain...

Back 30

Variant angina due to coronary artery spasms - due increased calcium permeability and impaired NO synthesis

Tx: Organic Nitrates
- Nitroglycerine (NG)
- Isosorbide Dinitrate (ISD)

- release NO into SMCs --> stimulates Guanylyl Cyclase --> increases cGMP --> increases Calcium sequestration in SR --> VASODILATION

CCBs also effective

Front 31

What are the treatments for Stable Angina? Explain...

Back 31

Stable angina due to increased myocardial demand for O2 due to stenosis

Tx:
- Beta Blockers - decrease contractility, so decrease myocardial O2 demand

- Nitrates - reduce peripheral resistance (decrease afterload); dilate venous compartment (decrease preload)

- CCBs

Front 32

What is Unstable Angina?

Back 32

Change in character, frequency, duration, precipitating factors in patients with stable angina at rest...

Due to fissuring of a vulnerable plaque with development of a labile, transiently occlusive platelet aggregate or thrombus

Front 33

What is tx for unstable angina?

Back 33

Anti-platelet drugs: aspirin, ADP inhibitors, GP IIB/IIIA inhibitors

Anticoagulates: heparin, coumadin

Vasoodilators: Nitrates, CCBs

*Catheter-Based Stent Placement or CABG for long-term tx

Front 34

What dosage of Aspirin should be given for acute MI?

Back 34

325 mg

Front 35

What are the names of ACE-inhibitors? (-suffix?)

Back 35

(-opril)

Captopril
Enalopril
Lisinopril
Quinopril
Ramipril

Front 36

What are the Beta Blockers? (-suffix?)

Back 36

(-olol)

Propranolol
Atenolol
Carvedilol

Front 37

What are the Statins? (-suffix?)

Back 37

(-statin)

Atrovastatin
Pravastatin
Simvastatin

Atorvastatin + Amlodipine (Caduet)
Simvastatin + Ezetimibe (Vytorin)