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Questions and Answers
Which of the following drugs is primarily used to reduce oxygen requirements in patients with atherosclerotic angina?
Which of the following drugs is primarily used to reduce oxygen requirements in patients with atherosclerotic angina?
What is the primary mechanism by which drugs like nitrates and nitroprusside relax vascular smooth muscle?
What is the primary mechanism by which drugs like nitrates and nitroprusside relax vascular smooth muscle?
Which treatment is specifically indicated for unstable angina?
Which treatment is specifically indicated for unstable angina?
Which drug is used to increase intracellular potassium levels to maintain the vascular smooth muscle membrane at resting potential?
Which drug is used to increase intracellular potassium levels to maintain the vascular smooth muscle membrane at resting potential?
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What is a common side effect of drugs that increase cAMP in vascular smooth muscle?
What is a common side effect of drugs that increase cAMP in vascular smooth muscle?
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Which of the following compounds is a stable product of Nitric Oxide?
Which of the following compounds is a stable product of Nitric Oxide?
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In what condition are calcium channel blockers most beneficial?
In what condition are calcium channel blockers most beneficial?
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What is the role of beta blockers in the treatment of angina?
What is the role of beta blockers in the treatment of angina?
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What is the duration of action for inhaled nitrates?
What is the duration of action for inhaled nitrates?
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Which is NOT a nitrate drug mentioned?
Which is NOT a nitrate drug mentioned?
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Who discovered nitroglycerin?
Who discovered nitroglycerin?
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What did Alfred Nobel mix to create dynamite?
What did Alfred Nobel mix to create dynamite?
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What is the mechanism of action for nitroglycerin?
What is the mechanism of action for nitroglycerin?
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In which year did Ascanio Sobrero discover nitroglycerin?
In which year did Ascanio Sobrero discover nitroglycerin?
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Which of the following forms of nitrates has the longest duration of action?
Which of the following forms of nitrates has the longest duration of action?
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What is the percentage of diatomaceous earth in dynamite?
What is the percentage of diatomaceous earth in dynamite?
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What effect does Ach have on aorta muscle relaxation in the presence of endothelium?
What effect does Ach have on aorta muscle relaxation in the presence of endothelium?
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Which isoform of Nitric Oxide Synthase (NOS) is found in neurons?
Which isoform of Nitric Oxide Synthase (NOS) is found in neurons?
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What is unstable angina primarily characterized by?
What is unstable angina primarily characterized by?
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What is a potential consequence of administering nitrates in high concentrations?
What is a potential consequence of administering nitrates in high concentrations?
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Which of the following factors does NOT determine myocardial oxygen requirements?
Which of the following factors does NOT determine myocardial oxygen requirements?
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In diabetic peripheral neuropathy, how is NO production affected?
In diabetic peripheral neuropathy, how is NO production affected?
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What is the recommended action regarding nitroglycerin patches to avoid tolerance development?
What is the recommended action regarding nitroglycerin patches to avoid tolerance development?
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What role does ejection time play in cardiac oxygen requirements?
What role does ejection time play in cardiac oxygen requirements?
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Which combination of factors could lead to unstable angina?
Which combination of factors could lead to unstable angina?
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What effect do PDE5 inhibitors, like Sildenafil, have when combined with nitrates?
What effect do PDE5 inhibitors, like Sildenafil, have when combined with nitrates?
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Which observation was noted in the double-blind trial of the nitroglycerin patch on healthy subjects?
Which observation was noted in the double-blind trial of the nitroglycerin patch on healthy subjects?
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Which of the following best describes the 'Double Product' in relation to cardiac work?
Which of the following best describes the 'Double Product' in relation to cardiac work?
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What is the effect of Nitric Oxide on microcirculation adjacent to wound sites?
What is the effect of Nitric Oxide on microcirculation adjacent to wound sites?
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In which of the following scenarios would myocardial oxygen supply be considered inadequate?
In which of the following scenarios would myocardial oxygen supply be considered inadequate?
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What primarily determines preload in the heart?
What primarily determines preload in the heart?
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What is considered a significant therapeutic strategy for managing angina?
What is considered a significant therapeutic strategy for managing angina?
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What characterizes 'Monday Disease' in factory workers who made dynamite?
What characterizes 'Monday Disease' in factory workers who made dynamite?
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What is the primary mechanism by which Nitroglycerin induces relaxation of smooth muscle?
What is the primary mechanism by which Nitroglycerin induces relaxation of smooth muscle?
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How does Sildenafil (Viagra®) contribute to smooth muscle relaxation?
How does Sildenafil (Viagra®) contribute to smooth muscle relaxation?
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What is a significant pharmacokinetic feature of Nitroglycerin when administered orally?
What is a significant pharmacokinetic feature of Nitroglycerin when administered orally?
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What role does L-arginine play in the synthesis of nitric oxide?
What role does L-arginine play in the synthesis of nitric oxide?
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What effect does Isosorbide dinitrate have as a medication?
What effect does Isosorbide dinitrate have as a medication?
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What is the primary therapeutic use of both Nitroglycerin and Isosorbide dinitrate?
What is the primary therapeutic use of both Nitroglycerin and Isosorbide dinitrate?
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Which of the following compounds acts as a second messenger in biological systems?
Which of the following compounds acts as a second messenger in biological systems?
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What is the primary mechanism through which cilostazol increases blood flow?
What is the primary mechanism through which cilostazol increases blood flow?
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Which statement about beta-blockers is correct?
Which statement about beta-blockers is correct?
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What effect do nitrates have on smooth muscle cells?
What effect do nitrates have on smooth muscle cells?
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How does hydralazine primarily affect blood vessels?
How does hydralazine primarily affect blood vessels?
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What characteristic is true of minoxidil as a vasodilator?
What characteristic is true of minoxidil as a vasodilator?
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What is the effect of calcium channel blockers (CCBs) on diastolic pressure?
What is the effect of calcium channel blockers (CCBs) on diastolic pressure?
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Which statement is true regarding the pharmacological effects of beta-blockers?
Which statement is true regarding the pharmacological effects of beta-blockers?
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Which of the following is a consequence of high doses of hydralazine?
Which of the following is a consequence of high doses of hydralazine?
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Study Notes
Case Study Examples
- Patient Profile: A 52-year-old male experiencing chest pain induced by exercise, sometimes radiating to the lower jaw, but subsiding with rest.
- Vital Statistics: Cholesterol 245 mg/dL, LDL 160 mg/dL, Blood Pressure (BP) 145/90 mm Hg, Heart Rate (HR) 80 bpm.
- Family History: Father died of a "heart attack" at age 55.
- Diagnosis: Stable effort angina.
- Treatment Options: Sublingual or sprayed nitroglycerin; beta-blocker (metoprolol) or a medium-to-long-acting calcium channel blocker (verapamil, diltiazem, or amlodipine); low-dose daily aspirin; treatment for high cholesterol.
Angina
- Definition: Angina is a chest pain caused by inadequate coronary oxygen supply (from the Latin word angere, to choke), often described as pectoris (chest).
- Prevalence: 6 million US citizens experience various angina forms.
- Frequency: Angina attacks occur approximately 1,000 times per minute in the US.
- Hospitalizations: 8 million ER visits annually related to chest pain, 3 million discharged, 2.5 million are non-cardiac, 1 million diagnosed with AMI, 1.2 million unstable angina cases, 0.3 million deaths.
Types of Angina
- Atherosclerotic Angina: A form of angina characterized by the presence of lipid plaques partially obstructing one or more coronary arteries, most common (90%). Exercise, cold, or stress-induced emotional stimuli can trigger ischemic changes in the arteries, producing pain.
- Vasospastic Angina (Prinzmetal's): Angina occurring at rest and is also known as variant or Prinzmetal's angina. It's caused by spontaneous spasm in atherosclerotic arteries. This type of angina can happen while sleeping. It sometimes transitions into unstable angina.
- Unstable Angina: A serious form, known as crescendo angina. Characterized by unpredictable and high frequency attacks; a precursor to a myocardial infarction (MI). This type of angina is caused by a combination of underlying pathologies, including atherosclerotic plaques, platelet aggregation at affected plaques, and vasospasm in the affected artery.
Myron Prinzmetal
- Physician and Pharmacist: Held degrees in medicine and pharmacy (from UCSF).
- Angina Researcher: First to describe a variant angina form.
Drugs Used to Treat Angina
- Vasodilators (for atherosclerotic angina): Nitrates, Calcium Channel Blockers
- Cardiac Depressants (for all types): Calcium Channel Blockers, Beta-Blockers
Therapeutic Strategies
- Goal: Treat the underlying cause of angina, focusing on inadequate coronary oxygen supply, either increasing the amount of oxygen delivered or decreasing the amount of oxygen required.
- Approaches: Increase oxygen delivery to the heart, reduce oxygen requirement in the heart.
- Nitrate use: Reduce oxygen requirements in atherosclerotic angina.
- Calcium Channel Blockers & Beta-Blocker use Reduce oxygen requirements for all types.
- Special Cases (Unstable Angina): Revascularization techniques (bypass grafting, angioplasty) along with antiplatelet medications may be required.
How Drugs Relax Vascular Smooth Muscle
- Nitroprusside, Nitrates, Nitroglycerin, NO: Increase intracellular cGMP levels by inhibiting phosphorylation of myosin.
- Calcium Channel Blockers, Beta Blockers: Decrease intracellular Ca2+ preventing myosin light chain kinase activity. Decreases calcium levels that cause smooth muscle contraction.
- Minoxidil: Opens potassium channels, hyperpolarizes cells, leading to relaxation.
- Beta-2 agonists: Increases cAMP for myosin light chain kinase inactivation. Usually not used for angina treatment due to excessive heart stimulation.
Nitrates
- Forms: Available in various forms with varying durations of action. (inhaled (3-5 min), sublingual (10-30 min), oral (4-6 h), transdermal (8-10 h)).
- Drug Examples: Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate.
Nitroglycerin
- Discovery: Discovered by Ascanio Sobrero, used initially for explosives.
- Mechanism of Action: NG, within smooth muscle, becomes denitrated, releasing nitric oxide (NO) to increase cGMP, thereby dephosphorylating myosin light chains to relax muscle and dilate blood vessels.
- Alternative Drug for Patients with First-Pass Liver Metabolism Issues: Isosorbide dinitrate.
- Adverse effects: Tolerance develops after 8-10 hours (Monday Disease), so patches may be removed after this timeframe. Other possible side effects include tachycardia from baroreceptor reflex, orthostatic hypotension, and severe throbbing headaches caused by meningeal arterial vasodilation.
- Combinations: Sildenafil (Viagra) enhances cGMP effects.
Cardiac Oxygen Requirements
- Physiologic Factors: Myocardial oxygen requirements are governed by muscle fiber tension. This tension is impacted by variables like preload (diastolic filling), afterload (systolic determinant), heart rate, and contractility.
Variables That Determine Fiber Tension
- Preload: Determined by blood volume and venous tone, which reflects the sympathetic outflow.
- Afterload: Systolic determinant controlled by arterial blood pressure.
- Heart Rate: Faster rates lead to lower coronary artery blood flow and less diastolic time.
Terms
- Angina: from L. angere, to choke.
- Pectoral: pertains to the chest
Calcium Channel Blockers (CCBs)
- Activity: Oral absorption is active, with half-lives ranging between 3 and 6 hours.
- Treatment Indications: Widely employed in angina therapy. Many products are FDA approved.
- Mechanism of action: Block the influx of calcium into cardiac smooth muscle. Inhibit the activation of the calcium-calmodulin complex, preventing myosin light chain kinase phosphorylation which prevents actin-myosin cross-bridge formation. This directly relaxes smooth muscle and dilates blood vessels.
- Drugs: Nifedipine, dihydropyridine ,diltiazem, verapamil
CCB Adverse Reactions
- Common: Constipation, nausea, pretibial edema, flushing, and dizziness.
Peripheral Artery Disease (PAD)
- Cause: Atherosclerosis, reducing blood flow.
- Symptoms: Intermittent claudication (pain with exercise relieved with rest)
- Consequences: Chronic ischemic ulcers, infection risk.
Drugs to Treat PAD
- Cilostazol: Phosphodiesterase 3 form inhibitor, leading to increased cAMP, vasodilation, and enhanced blood flow.
- Sildenafil (Viagra): Also has a similar mechanism but inhibits PDE 5 (rather than PDE 3.)
Beta-Blockers
- Treatment Role: Used frequently in angina prophylaxis;
- Use for acute attack: No effectiveness for acute treatment.
- Protection from vasospastic angina: Not effective in preventing attacks.
Summary of All Drugs (effects on various cardiac factors)
- Nitrates: Increase heart rate, decrease arterial pressure, decrease diastolic pressure, increase contractility (r increase), Decrease ejection time (r decrease)
- Beta Blockers or CCBs: Decrease heart rate, decrease arterial pressure, increase diastolic pressure, decrease contractility, increase ejection time
Summary of Drug Mechanisms
- Nitrates: Reduce cGMP which blocks muscle contraction
- CCBs: Block in-flow of calcium.
- Beta Blockers: Increase cAMP to speed up activation of MLCK enzyme.
Vasodilator Mechanisms
- Actions: Dilation of blood vessels are caused by direct action on smooth muscle through methods: Release NO, Hyperpolarization through potassium channels, block calcium channels, and activating dopamine D1 receptors
Other Vasodilators
- Hydralazine: Releases NO; toxic at higher doses (tachycardia, salt retention). Less toxic at less than 200 mg/day
- Minoxidil: Opens potassium channels, leading to hyperpolarization and muscle relaxation.
Nitroprusside
- Action: Releases NO to cause vasodilation; Used intravenously in emergencies to reduce blood pressure.
Fenoldopam
- Action: Dopamine D1 receptor agonist; Causes arterial vasodilation, administered intravenously, used in emergencies to address hypertensive crises.
Other Noteworthy Topics
- Unstable Angina: This is a more serious form requiring revascularization (bypasses or angioplasty); antiplatelet medications are also used.
- Cyanide and Nitrite Toxicity: These substances are metabolized through various processes to cause poisoning..
- Methemoglobinemia (MHb): A condition where hemoglobin iron is in a ferric (rather than ferrous) form and cannot adequately carry oxygen, leading to hypoxia.
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Description
This quiz explores a detailed case study of stable effort angina, including patient profiles, diagnoses, and treatment options. Gain insights into the prevalence and frequency of angina, along with treatment strategies such as medication. Test your understanding of angina and its management.
