Cardio/Renal 15 - IHD, Heart Failure Drugs, Lipid Disorder Drugs (Dr. Fiaturi)

Define the following:

– Lack of oxygen due to inadequate coronary perfusion

– Results from an imbalance between myocardial oxygen supply and myocardial oxygen demand

Ischemia

What is the primary cause of ischemia?

Atherosclerosis (plaque formation)

what is the most common symptom of ischemic heart disease?

angina pectoris

The following symptoms are signs of what?

•Most patients feel heavy, pressing substernal discomfort

•Symptoms provoked by exertion and relieved by rest

•May occur in a stable pattern over many years or may become unstable

Ischemia (angina)

4 things that will increase heart's O2 demand:

- Contractility

- Preload

- Afterload

- Heart rate

3 things that affect the supply of O2 to the heart:

- Coronary artery flow

- Time

- O2 carrying capacity

the goal of ischemic heart disease drugs is to _______ O2 supply and ______ O2 demand

increase, decrease

Which side of ischemic heart disease drugs is increase O2 by dilating the coronary vasculature? (supply or demand)

Supply

Which side of ischemic heart disease drugs is reducing cardiac "work"?

Demand

3 classes of anti-ischemic drugs:

1. β-adrenergic receptor antagonists (β-blockers)

2. Calcium channel blockers

3. Nitrates

1st line of defense for anti-ischemic drugs:

β-blockers (i.e. atenolol, metroprolol, propronolol/nadolol)

2nd line of defense for anti-ischemic drugs:

calcium channel blockers (use if BB contraindicated/not tolerated)

advantage of β-blockers as an anti-ischemic drug:

reduce myocardial O2 demand

decrease HR, contractility, BP

examples of β-blockers:

atenolol, metoprolol, propranolol

The following are representative drugs of what class?

-Amlodipine

- Nifedipine

- Felodipine,

- Verapamil

- Diltiazem

Ca2+ Channel Blockers (CCBs)

advantages of calcium channel blockers as an anti-ischemic drug:

decrease O2 demand

decrease afterload (decrease oxygen demand)

decrease preload

increase O2 supply

side effects of this CCB include:

- Gingival hyperplasia

- Edema

- Headache

- Hypotension

Nifedipine

The following are adverse effects of what anti-ischemic drug?

- Bradycardia

- Fatigue

- Bronchospasm

- Mask symptoms of hypoglycemia (palpitaion) except sweating

- Insomnia

beta blockers

side effects of these CCBs include:

Bradycardia

AV block

Verapamil, Diltiazem

t/f: CCBs bind to the a1 subunit and reduce Ca2+ flux through the channel

true

what is the ONLY agent to treat an acute angina attack?

Nitrates

major advantages of Nitrates as an anti-ischemic drug:

- Decrease myocardial O2 demand

- Decreased preload

- Decreased afterload

minor advantages of Nitrates as an anti-ischemic drug:

short-lived increase in coronary blood flow

t/f: nitrates are prodrugs that are sources of nitric oxide (NO)

true

Nitroglycerin, isosorbide dinitrate are examples of

nitrates

what is the main problem with Nitrates?

tolerance

this drug requires an interval of at least 8 hours in each 24 hour period with chronic administration to avoid tolerance:

Nitrates

Which anti-ishcemic drug has these side effects?

- Orthostatic hypotension

- Headache

-Reflex tachycardia

- Flushing

Nitrates

Nitrates are contraindicated with:

PDE5 inhibitors (Sildenafil (Viagra), Vardenafil (Levitra), Tadalafil (Cialis))

this drug is contraindicated with PDE5 inhibitors like Sildenafil (Viagra®):

Nitrates

Combination of nitrates with _________ can produce unpredictable excess vasodilation, leading to profound hypotension. SO you need at least 24 hours should elapse after PDE5 administration, before using nitrates

PDE5 inhibitors (eg. viagra, levitra, cialis)

MOA of this drug decrease the inward Na+ current in heart muscle. Inhibiting that current leads to reduction in intracellular calcium levels. This in turn leads to decrease ventricular tension decrease oxygen demand

Ranexa

Ranexa is metabolized by ______, should not be used with drugs like ketoconazole, clarithromycin, nelfinavir that strongly inhibit CYP3A

CYP3A

Ranexa blocks ________, might reduce pain relief from codeine

CYP2D6

t/f: Ranexa cannot be used in patients taking oral erectile dysfunction medications

false, Ranexa has no contraindications

Unlike some other angina medications, _________ can be used in patients taking oral erectile dysfunction medications

Ranexa

Define the following:

Inability of the heart to meet the body's metabolic needs

Heart failure

What two additional drugs must all patients with ischemic heart disease take?

- Low dose aspirin

- Cholesterol reduction (statins)

What causes left heart failure?

Pulmonary congestion

What causes right heart failure?

Peripheral edema

Two conditions that can lead to heart failure:

- Hyperthyroidism

- Congestive heart failure

______________ is when the metabolic demands greatly exceed cardiac output

hyperthyroidism

Unlike hyperthyroidism, in ____________, the heart is diseased, typically from heart attacks killing cardiac muscle, etc.

Congestive heart failure

The main goal of heart failure pharmacotherapy is to …?

get rid of the excess fluid that builds up in the body, thereby reducing the volume of fluid that the weakened heart has to pump.

What heart failure therapy is the following:

Reduce left ventricular volume and filling pressure while decreasing total peripheral resistance

ACE inhibitors

What heart failure therapy is the following:

Reduce "preload" by increasing sodium and H2O excretion thusreducing pulmonary congestion and reducing oxygen demand

Diuretics

What heart failure therapy is the following:

Reduce mortality by slowing heart rate , reducing BP, and decreasing risk of arrythmia

beta blockers

What heart failure therapy is the following:

Increase cardiac output by positive inotropic action on the myocardium, which reduces heart size and decreases compensatory tachycardia

Cardiac Glycosides (Digoxin)

Major concern is its narrow therapeutic window

Cardiac Glycosides (Digoxin)

T/F: Nitrates, antiplatelet agents, and anticoagulants can treat heart failure

True

What drug has this combination product for heart failure:

Sacubitril: neprilysin inhibitor

Valsartan: angiotensin receptor antagonist

Entresto

what part of Entresto is a neprilysin inhibitor?

Sacubitril

what part of Entresto is an angiotensin receptor antagonist?

Valsartan

_____________ is the leading cause of death in the US and elevated cholesterol is a major risk factor for the development of _____________ (same word)

Atherosclerosis

Consequences of Atherosclerosis include

• obstruction of blood flow

• impairment of vascular reactivity

• weakening of blood vessels (aneurysm formation).

What is the new guideline recommends moderate- or high-intensity statin therapy for these four groups?

- Patients who have cardiovascular disease;

- Patients with an LDL, or "bad" cholesterol level of 190 mg/dL or higher;

- Patients with Type 2 diabetes who are between 40 and 75 years of age;

- Patients with an estimated 10-year risk of cardiovascular disease

what type of drugs inhibit cholesterol synthesis?

statins

Drugs MOA:

- Competitive inhibition of HMG CoA reductase inhibits cholesterol synthesis

- This increases the number of LDL receptors on cells in the liver and enhances the removal of LDL from the blood

Statins

What is the potency ranking between Atorvastatin (Lipitor), Simvistatin (Zocor) Rosuvastatin (Crestor):

Rosuvastatin (Crestor) > Atorvastatin (Lipitor) > Simvistatin (Zocor)

Adverse effects of what drug?

-Aches and pains, myopathies, rhabdomyelosis

-Liver damage (some reports)

-Mental: memory loss, confusion, ( irritability and extremeagitation reported, still under research)

-Increase in chance of developing type 2 diabetes

Statins

these drugs are associated with:

Cognitive impairment

Type 2 diabetes

muscle damage

statins

_________ interfere with liver metabolism of statins, increasing the risk of myopathy and rhabdomyelosis

Macrolide Antibiotics

DDI with statins

macrolide antibiotics