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Questions and Answers
Which combination of drugs is typically used for unstable angina or NSTEMI?
What is a significant adverse effect associated with the use of GP IIb/IIIa inhibitors?
Which drug is known to cause neutropenia as a side effect?
What is the main therapeutic purpose of GP IIb/IIIa inhibitors?
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What condition is directly related to absent or defective GP IIb/IIIa?
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What is the primary mechanism by which aspirin exerts its antiplatelet effects?
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Which drug class is considered a prodrug that requires metabolic activation?
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What potential adverse effect is associated with aspirin use?
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Which of the following antiplatelet drugs acts by blocking ADP receptors?
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What is the main function of phosphodiesterase inhibitors in antiplatelet therapy?
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How does low-dose aspirin selectively affect thromboxane A2 and prostacyclin?
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In patients who have mutations affecting 2C19, which antiplatelet drug's efficacy may be reduced?
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What type of patients should NOT be prescribed salicylates?
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What is the primary mechanism by which nitrates alleviate angina pectoris?
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Which type of angina is primarily treated with beta blockers?
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Which of the following is a common adverse effect associated with nitrates?
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What is a primary reason for requiring an '8-hour drug holiday' when using nitrates?
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In patients with erectile dysfunction, which class of angina medication poses a significant drug interaction risk?
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Which type of angina may be managed primarily with calcium channel blockers?
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Which of the following is a risk factor for unstable angina?
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What is the role of ranolazine in angina management?
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What is a primary action of dihydropyridines (DHPs)?
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Which of the following CCBs is most contraindicated in CHF due to its negative inotropic effect?
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Which adverse effect is most commonly associated with verapamil?
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Which drug is a selective beta-1 blocker that can cause AV block as an adverse effect?
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Ranolazine primarily acts by reducing what type of current?
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Which of the following medications is contraindicated in patients with asthma or COPD due to the risk of bronchoconstriction?
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What effect does verapamil have on the heart compared to diltiazem?
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What should be monitored closely due to potential increased plasma levels when using verapamil?
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What effect does nitric oxide (NO) donor have on venous capacitance and preload?
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Which formulation of Nitroglycerin has the shortest duration of action?
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Which of the following is NOT a common adverse effect of nitrates?
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What primary action do Calcium Channel Blockers (CCB) have on the cardiovascular system?
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What is the primary clinical use of Sodium Nitroprusside?
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Which of the following statements is true regarding the interaction between nitrates and erectile dysfunction drugs?
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What is the main purpose of administering sodium thiosulfate or hydroxycobalamin in cases of sodium nitroprusside toxicity?
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How do nitrates primarily affect platelet activation?
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Study Notes
Angina Pectoris Pathophysiology
- Angina occurs due to an imbalance between oxygen supply and demand.
- The heart muscle's oxygen demand increases during physical activity or stress, but supply is restricted by narrowed coronary arteries.
Angina Types and Management
-
Stable Angina:
- Managed with nitrates, beta-blockers (BBs), and calcium channel blockers (CCBs)
-
Vasospastic Angina:
- Managed with nitrates and CCBs
-
Unstable Angina:
- Requires immediate attention
- Managed with nitrates, CCBs, BBs, antiplatelets, angiotensin-converting enzyme inhibitors (ACEIs), statins, and percutaneous coronary intervention (PCI).
Nitrates
- Nitrates are NO donors that increase cyclic guanosine monophosphate (cGMP) levels.
- They are metabolized to release nitric oxide (NO).
- Actions: Causes venous dilation, reducing preload and venous return, leading to decreased cardiac output.
-
Formulations and Duration:
- Sublingual nitroglycerin: 10-30 minutes
- Isosorbide dinitrate (sublingual): 10-60 minutes
- Amyl nitrite (inhaled): 3-5 minutes
- Nitroglycerin (oral): 6-8 hours
- Nitroglycerin (transdermal): 8-10 hours
- Isosorbide dinitrate (oral, chewable): 2-6 hours
- Isosorbide mononitrate (oral; 100% bioavailable): 6-10 hours
-
Adverse Effects:
- Headache
- Hypotension
- Tachycardia
- Salt and water retention
-
Drug Interactions:
- Significant interactions with phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, vardenafil, and tadalafil (Erectile dysfunction drugs).
Sodium Nitroprusside
- Short-acting NO donor used intravenously
- Dilates arterioles and venules.
- Decreases afterload and preload.
-
Adverse Effect:
- Cyanide accumulation (rare).
-
Antidote:
- Sodium thiosulfate or hydroxycobalamin (vitamin B12).
Calcium Channel Blockers
- Calcium is essential for the function of various cells including smooth muscle, cardiac muscle, and skeletal muscle.
- CCBs block L-type calcium channels in arterioles and the heart.
-
Actions:
- Arteriole relaxation, reducing total peripheral resistance (TPR) and afterload.
- Lowering blood pressure
- Decreasing the workload of the heart
-
Classes:
-
Verapamil and Diltiazem (non-DHPs):
- Affect both arterioles and the heart
- Decrease heart automaticity and contractility
-
Dihydropyridines (DHPs):
- "Dipines" - Nifedipine, amlodipine, felodipine
- Primarily affect arterioles
- Reduce TPR and blood pressure
-
Verapamil and Diltiazem (non-DHPs):
-
Adverse Effects:
- Dizziness
- Headache
- Edema
- Tachycardia (DHPs)
- Bradycardia (non-DHPs)
- Constipation (most with verapamil)
- Gingival overgrowth
- Grapefruit drug interactions
Beta-Adrenergic Receptor Antagonists (Beta Blockers)
-
Actions:
- Block beta-1 receptors, decreasing heart rate, cardiac output, and renin release from the juxtaglomerular apparatus (JGA).
-
Uses:
- Hypertension
- Myocardial infarction (MI)
- Congestive heart failure (CHF)
- Angina (except vasospastic)
-
Adverse Effects:
- AV block (beta-1-selective blockers like atenolol, metoprolol)
- Bronchoconstriction, hypoglycemia, and complications with peripheral vascular disease (PVD) (Non-selective beta blockers - nadolol, propranolol, timolol).
- Antidote: Supportive therapy, glucagon
Ranolazine
- Reduces late sodium current, leading to decreased calcium entry via the Na+/Ca2+ exchanger.
- Uses: Angina prophylaxis
-
Adverse Effects:
- Nausea
- Constipation
- Dizziness
- Prolongs QT interval
Other Therapies
- PCI (Percutaneous Coronary Intervention)
- CABG (Coronary Artery Bypass Grafting)
- ACEIs Antihypertensives
- Lifestyle Modifications: Smoking cessation, diet, exercise
- Antiplatelet drugs
- Lipid-lowering agents
- Ivabradine
- Antidiabetics
Antiplatelet Drugs
-
Aspirin:
- Irreversibly blocks cyclooxygenase (COX) 1 and 2.
- Actions: Analgesic, anti-inflammatory, antipyretic.
- Adverse Effects: Gastrointestinal bleeding, hypersensitivity, metabolic acidosis.
-
ADP Receptor Blockers (Clopidogrel, prasugrel, ticagrelor):
- Prodrugs (except ticagrelor)
- Actions: Prevent platelet aggregation and thrombosis
- Uses: Unstable angina, non-ST-elevation acute myocardial infarction (NSTEMI), recent MI, and peripheral artery disease (PAD)
- Adverse Effects: Bleeding
-
Glycoprotein IIb/IIIa Inhibitors (Abciximab, eptifibatide, tirofiban):
- Actions: Block platelet aggregation
- Uses: Acute coronary syndrome and PCI
- Adverse Effects: Bleeding
-
Phosphodiesterase Inhibitors (Cilostazol, dipyridamole):
- Uses: Peripheral artery disease
- Adverse Effects: Headache
Thromboxane Synthesis
- Thromboxane A2 (TXA2) is a potent platelet aggregator and vasoconstrictor.
- Aspirin irreversibly acetylates COX-1, inhibiting TXA2 synthesis.
Low Dose Aspirin
- Low dose aspirin blocks TXA2 synthesis but not Prostacyclin (PGI2) synthesis.
- PGI2 is anti-aggregatory and vasodilator.
Ticlopidine
- Adverse Effect: Neutropenia (low white blood cell count)
Glanzmann Disease
- Absent or defective Glycoprotein IIb/IIIa, resulting in a bleeding disorder.
Summary
- This document provides a comprehensive overview of the pharmacology of angina pectoris.
- It covers the pathophysiology of the disease, various types of angina, and different drug classes used in management.
- It emphasizes the mechanisms of action, clinical uses, adverse effects, and drug interactions of nitrates, calcium channel blockers, beta-blockers, and antiplatelet drugs.
- It also highlights the importance of lifestyle modifications and other therapies in the overall management of angina.
- This information is beneficial for students studying pharmacology and clinicians looking to develop a better understanding of the treatment for angina.
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Description
This quiz covers the pathophysiology of angina pectoris, including its types and management strategies. Review how stable, vasospastic, and unstable angina are treated, as well as the role of nitrates and other medications in managing these conditions.
