test 7 Flashcards
What is Angina Pectoris?
- Sudden, severe, crushing chest pain
* can radiate to neck, jaw, back, shoulders, and arms
Types of Angina
- Stable, effort-induced, classic, or typical angina
- Unstable angina
- Prinzmetal, variant, vasospastic, or rest angina
- Acute coronary syndrome
Classic Angina
- Most common form
- Caused by a fixed coronary artery obstruction
- Usually due to atherosclerosis
- Pattern of pain remains stable
- Does not always present as pain
* More common in women, DM, and elderly
Classic Angina pain relieved by
- rest or nitroglycerin
Unstable Angina
- Chest pain occurs with increased frequency, duration, and intensity
* Result of less effort - Rest angina lasting longer than 20 min.
- Increasing (crescendo) angina
- Sudden onset of shortness of breath
- Pain not relieved by rest or nitroglyce
Rest Angina
- Pain occurs at rest due to coronary artery spasm
- Pain is unrelated to exertion
- Treated with calcium channel blockers and nitroglycerin
Acute Coronary Syndrome
- Rupture of an atherosclerotic plaque
- Disruption of an atherosclerotic lesion
* Inflammatory cells and platelets are activated
* Thrombus forms and propagates
* Vasoconstriction occurs - Necrosis of cardiac muscle
- Increase in serum levels of biomarkers
* Troponins
* Creatine kinase (CK) - Present as ST elevation, MI, or unstable angina
Angina Drug Strategies (2)
1. Increase O2 delivery
•Increasing coronary flow
2. Decrease O2 demand
• Altering determinates of myocardial oxygen
consumption
• Wall stress
• Heart rate
• Contractilityβ-blockers
- Decrease oxygen demand by blocking β1 receptors
- Decrease in HR, contractility, and BP
- Reduce the frequency of angina attacks
- Increase exercise duration and tolerance
- Recommended at initial antianginal therapy
* Not for vasospastic angina - Reduce the risk of MI and death
* Prior MI - Improve mortality in patients with HTN and HF
β-blockers: Adverse Effects
- Bradycardia
- Hypotension
- Fatigue
- Insomnia
- Sexual dysfunction
- Alter lipid panel
* Decrease HDL
* Increase triglycerides
Calcium Channel Blockers
- Cardiac ischemia leads to membrane depolarization, increasing calcium flow into the cells
- Leads to activation of ATP-consuming enzymes which depletes energy stores worsening ischemia
- Block the inward movement of calcium into the cell
- Causes relaxation of smooth muscle and a decrease in contractility in cardiac muscle
- Decrease afterload which decreases myocardial oxygen demand
- Dilate the coronary arteries which increases myocardial oxygen delivery
Diphenylalkylamines: Verapamil
- Effects cardiac and vascular smooth muscle
* More selective for cardiac muscle - Slows AV conduction
- Decreases HR, contractility, and BP
- Negative inotropic effects
Benzothiazepines: Diltiazem
- Non-selective
- Slows AV conduction
- Coronary artery vasodilator
* Relieves coronary artery spasm - Negative ionotropic effects
Dihydropyridines: Amlodipine, Felodipine, Nifedipine
- Greater affinity for vascular smooth muscle calcium channels
- Minimal effect on cardiac conduction
- Do not use in patients with CAD
* Increase mortality after an MI
Summary of what Dihydropyridines do
- Produce arterial dilation
- Reduces PVR
- Reduces BP
- Reduces myocardial oxygen demand
Nifedipine
• Extended release tablet
• Treats angina
- Probably don’t need to know, but used for pregnancy pts
Amlodipine
• Treats angina caused by coronary spasm
Calcium Channel Blockers: Adverse Effects
- First-degree AV block
* Especially with Verapamil (dose dependent) - Dizziness
- Headache
- Low BP
- Peripheral edema
Organic Nitrate effects
- Causes vascular smooth muscle relaxation
- Converts nitrite ions to nitric oxide which causes an increase in cGMP leading to dephosphorylation of myosin light chain
- Causes dilation of large veins
* Reduces preload - Dilates the coronary vasculature
* Increasing blood supply to heart - Used to prevent angina attacks
Effects of Organic Nitrates on Smooth Muscle
- Increases nitrites => increases nitric oxide => increases cGMP => dephosphorylation of myosin light chain => vascular smooth muscle relaxation
High doses of organic nitrates effect on resistance of vessels
- decreases afterload
- decreases myocardial O2 demand
Low doses of organic nitrates on capacitance of vessels
- decreases preload
- decreases myocardial O2 demand
Organic Nitrates pharmacodynamics
- Onset of action varies
* 1 min. – 30 min. - Nitroglycerin recommended
* Prompt relief - Sublingual/Patch
* Avoid first-pass effect (much quicker onset)
Isosorbide mononitrate
- Higher bioavailability
* Longer duration of action
Organic Nitrates: Adverse Effects and at high doses
•Throbbing headache
-High doses
• Postural hypotension
• Facial flushing
• Reflex tachycardia
•Do not use with phosphodiesterase inhibitors
• Potentiates the action of nitrates
Sodium Channel Blocker
•Inhibits late phase sodium current that facilitates Ca entry via the Na+
/Ca2+ exchanger
•Reduces intracellular sodium and calcium overload
• Reduces contractility and work
•Used to treat chronic angina
•No significant effect on HR or BP
Sodium Channel Blocker: Adverse Effects
- Prolongs QT interval
- Constipation
- Nausea
- Dizziness
- Headaches
Papaverine
- Opium alkaloid antispasmodic drug
- Direct acting smooth muscle relaxant
- Mechanism unclear
* Inhibits phosphodiesterase
* Inhibits Ca2+ channels
* Causes relaxation - Injected into LIMA
* Prevent spasm
Adenosine
- Naturally occurring nucleoside
- Acts on the A2A membrane receptor of vascular smooth muscle
* Increases cAMP which decreases myosin phosphorylation
* Causes coronary artery relaxation - Inhibits Ca2+ entry into the cell
* Reduced intracellular Ca2+ causes relaxation
Adenosine: Cardiac Tissue
- Binds to A1 receptor
* Opens K+ channels causing hyperpolarization
* Promoting less contraction
* Decrease cAMP inhibiting Ca2+ channels => less contraction
* Inhibits pacemaker cells in SA node
* Inhibits AV node conduction - Used with cardioplegia for rapid induction cardiac arrest
Adenosines use in cardiac imaging
- Used in cardiac imaging during stress test
* Measure coronary fractional flow reserve (FFR) - Slows AV conduction
* Anti-arrhythmic
Adenosine pharmacokinetics
- Short acting
* 10 seconds - Intravenous administration
- Produce coronary steal
- Cause headache and flushing
Management of Stable Angina
- Relieve symptoms
* Improve prognosis
Principles of angina Management
- Life style change
- Sublingual nitroglycerin
- Prophylactic anti-anginal drugs
* Frequent anginal attacks
* β-blocker or Ca2+ -channel blocker - Low-dose aspirin therapy
* Prevent MIs - Treatment of high cholesterol
- CABG
Angina Treatment Algorithm
- Pain -> sublingual nitroglycerin for immediate relief -> give beta blocker -> (if that doesn’t work) -> Ca2+ channel blocker or longer acting nitrate -> (if that doesn’t work) -> give Ranolaxine
