Podcast
Questions and Answers
Which of the following is true about ranolazine?
Which of the following is true about ranolazine?
What is the effect of ranolazine on sodium and calcium accumulation in myocardial cells?
What is the effect of ranolazine on sodium and calcium accumulation in myocardial cells?
What is a potential concern associated with ranolazine therapy?
What is a potential concern associated with ranolazine therapy?
Why should strong or moderate CYP3A4 inhibitors be avoided with ranolazine?
Why should strong or moderate CYP3A4 inhibitors be avoided with ranolazine?
Signup and view all the answers
What sets ranolazine apart from most other antianginal drugs in terms of its effects on heart rate and blood pressure?
What sets ranolazine apart from most other antianginal drugs in terms of its effects on heart rate and blood pressure?
Signup and view all the answers
Which other drugs can ranolazine be combined with as part of angina treatment?
Which other drugs can ranolazine be combined with as part of angina treatment?
Signup and view all the answers
Which of the following is NOT a common effect of ranolazine?
Which of the following is NOT a common effect of ranolazine?
Signup and view all the answers
What is one of the potential risks associated with ranolazine therapy?
What is one of the potential risks associated with ranolazine therapy?
Signup and view all the answers
What is the primary mechanism of action through which ranolazine works?
What is the primary mechanism of action through which ranolazine works?
Signup and view all the answers
Why is ranolazine now approved as a first-line drug for angina despite its limitations?
Why is ranolazine now approved as a first-line drug for angina despite its limitations?
Signup and view all the answers
How does ranolazine differ from most other antianginal drugs in terms of drug interactions?
How does ranolazine differ from most other antianginal drugs in terms of drug interactions?
Signup and view all the answers
What is the potential cardiovascular effect of ranolazine on blood pressure?
What is the potential cardiovascular effect of ranolazine on blood pressure?
Signup and view all the answers
Which type of inhibitors should be avoided when using ranolazine to reduce the risk of torsades de pointes?
Which type of inhibitors should be avoided when using ranolazine to reduce the risk of torsades de pointes?
Signup and view all the answers
What is the new paradigm in the management of stable angina mentioned in the text?
What is the new paradigm in the management of stable angina mentioned in the text?
Signup and view all the answers
Which type of drugs can increase levels of ranolazine and thereby increase the risk for torsades de pointes?
Which type of drugs can increase levels of ranolazine and thereby increase the risk for torsades de pointes?
Signup and view all the answers
What is a unique feature of ranolazine's effect on heart rate and blood pressure compared to other antianginal drugs?
What is a unique feature of ranolazine's effect on heart rate and blood pressure compared to other antianginal drugs?
Signup and view all the answers
What sets ranolazine apart from other antianginal drugs in terms of its mechanism of action?
What sets ranolazine apart from other antianginal drugs in terms of its mechanism of action?
Signup and view all the answers
Which drug can be combined with ranolazine as part of angina treatment, unlike most CCBs?
Which drug can be combined with ranolazine as part of angina treatment, unlike most CCBs?
Signup and view all the answers
Study Notes
Nitroglycerin and Nitrates
- Nitroglycerin and other nitrates can cause tolerance with high-dose therapy and uninterrupted therapy.
- To prevent tolerance, use the lowest effective dosage and intermittent therapy with at least 8 drug-free hours per day.
- Tolerance can be reversed by withholding nitrates for a short time.
- Long-acting preparations should be withdrawn slowly.
Angina Treatment
- Nitroglycerin is used for acute treatment of angina pectoris in sublingual tablets and translingual spray.
- Nitroglycerin is used for sustained prophylaxis against angina in transdermal patches, topical ointment, and sustained-release oral capsules.
- Isosorbide mononitrate and isosorbide dinitrate have pharmacologic actions identical to those of nitroglycerin.
Beta Blockers
- Beta blockers are first-line drugs for exertional angina but not effective against vasospastic angina.
- Beta blockers can provide sustained protection against effort-induced anginal pain and reduce the risk of death.
- Beta blockers reduce anginal pain primarily by decreasing cardiac oxygen demand and increasing oxygen supply.
Calcium Channel Blockers (CCBs)
- CCBs (verapamil, diltiazem, and nifedipine) block calcium channels in arterioles, leading to arteriolar dilation and reduction of peripheral resistance.
- CCBs are used to treat both stable and variant angina.
Ranolazine
- Ranolazine is a new class of antianginal agent that reduces the number of angina episodes and increases exercise tolerance.
Atherosclerosis
- Atherosclerosis is a chronic inflammatory process involving oxidation of LDLs, which leads to deposition of lipids and inflammation.
- Cholesterol screening is recommended every five years for adults over 20.
Lipid-Lowering Therapy
- Statins (HMG-CoA reductase inhibitors) are the most effective drugs for lowering LDL cholesterol.
- Statins can reduce LDL cholesterol by 25-63% and are used for primary and secondary prevention of ASCVD.
- Statins can also reduce the risk of stroke, hospitalization, cardiac events, peripheral vascular disease, and death.
- Other lipid-lowering drugs include bile acid sequestrants, nicotinic acid, and fibrates.
Metabolic Syndrome
- Metabolic syndrome is diagnosed when three or more of the following are present: high TG levels, low HDL cholesterol, hyperglycemia, high blood pressure, and high waist circumference.
- Treatment of metabolic syndrome includes weight control, increased physical activity, and specific treatment for high blood pressure and high TG levels.
Statin Therapy
- Statins are generally well-tolerated, but side effects include headache, rash, gastrointestinal disturbances, and muscle injury (myopathy).
- Serious adverse effects of statins include hepatotoxicity and rhabdomyolysis.
- Statins are teratogenic and should not be given in pregnancy.### Cholesterol Medications
- Bempedoic Acid (Nexletol) is a new non-statin cholesterol medication approved for patients with familial hypercholesterolemia who require additional cholesterol reduction.
- Does not cause myalgia and lowers LDL cholesterol by 35%.
- Bempedoic Acid/Ezetimibe (Nexlizet) should be reserved for patients with true statin intolerance.
Fibrates
- Fibrates are the most effective drugs for lowering triglyceride (TG) levels.
- They can also raise HDL cholesterol, but have little or no effect on LDL cholesterol.
- There is no evidence that fibrates reduce mortality from atherosclerotic cardiovascular disease (ASCVD).
- Three fibrates are available in the US: gemfibrozil, fenofibrate, and fenofibric acid (a delayed-release preparation).
- Gemfibrozil:
- Decreases TG levels and raises HDL cholesterol levels.
- Does not significantly reduce LDL cholesterol.
- Principally indicated for hypertriglyceridemia.
- Common adverse effects: rash, gastrointestinal disturbances (nausea, abdominal pain, diarrhea).
- Fenofibrate:
- Decreases TG levels and raises HDL cholesterol levels.
- Also available in a micronized formulation.
PCSK9 Inhibitors
- Alirocumab (Praluent) and Evolocumab (Repatha) are PCSK9 inhibitors that reduce LDL cholesterol levels.
- Indicated as an adjunct to diet modification and maximally tolerated statin therapy for reducing total LDL cholesterol.
- PCSK9 inhibitors work by inhibiting PCSK9, a protein that binds to LDL receptors, allowing for increased LDL uptake and decreased LDL cholesterol.
- Administered subcutaneously.
- Adverse effects: hypersensitivity reactions, including vasculitis, rash, and urticaria.
- No significant drug interactions.
Angina Treatment
- Goals of angina drug therapy: prevent myocardial infarction and death, and prevent myocardial ischemia and anginal pain.
- Six major classes of plasma lipoproteins, with VLDL, LDL, and HDL being especially important in coronary atherosclerosis.
- LDLs initiate and fuel the development of atherosclerosis.
Lipid Lowering Therapy
- LDL-lowering drugs: HMG-CoA reductase inhibitors (statins), bile acid sequestrants, and fibrates (triglycerides only).
- Statins are the most effective drugs for lowering LDL cholesterol and reducing the risk of cardiovascular events.
- Bile acid sequestrants: effective in reducing LDL cholesterol, but may cause gastrointestinal disturbances.
Cholesterol Screening and Risk Assessment
- Cholesterol screening recommended every 5 years for adults over 20.
- American Academy of Pediatrics recommends cholesterol testing for children with a family history of cardiovascular disease.
- Cholesterol levels increase during pregnancy but return to normal 6 weeks post-delivery.
- HDL levels should be above 40 in men and 50 in women.
- LDL levels should be less than 100, and triglycerides less than 150.
Metabolic Syndrome
- A group of metabolic abnormalities associated with an increased risk for ASCVD and type 2 diabetes.
- Diagnosed when three or more of the following are present: high TG levels, low HDL cholesterol, hyperglycemia, high blood pressure, and waist circumference 40 inches or more for men and 35 inches or more for women.
- Treatment goals: reduce the risk for atherosclerotic disease and reduce the risk for type 2 diabetes.
- Lifestyle modifications: weight control, increased physical activity, and low-dose aspirin to reduce the risk for thrombosis.### Statins
- 7 statins are available for use alone: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin
- Dosages are provided in the book
- If a 30-40% reduction in LDL is desired, any statin will do
- If LDL must be lowered by >40%, atorvastatin or simvastatin may be preferred
- Drugs that inhibit CYP3A4 can raise levels of atorvastatin, lovastatin, and simvastatin, increasing the risk for toxicity, especially myopathy and liver injury
- In patients taking a CYP3A4 inhibitor, other statins may be preferred
- For patients with normal renal function, any statin is acceptable
- For patients with significant renal impairment, atorvastatin and fluvastatin are preferred (because no dosage adjustment is needed)
- The higher the bioavailability of a statin, the lower the first-pass effect and more drug enters systemic circulation, resulting in higher cholesterol reduction
- Rosuvastatin, atorvastatin, and pravastatin have high bioavailability percentages
Nicotinic Acid (Niacin)
- Increases HDL and reduces LDL and triglycerides
- Can cause severe flushing, which can be reduced by taking an ASA prior to niacin
- Clinical outcomes were not changed despite favorable effects on lipids
Bile Acid Sequestrants
- Reduce LDL cholesterol levels
- Primarily used as adjuncts to statins
- Three agents are available: colesevelam, cholestyramine, and colestipol
- Colesevelam is newer and better tolerated
- Can lower LDL cholesterol by 15-30% (on average, 20%) when used alone
- Combined therapy with a statin can reduce LDL cholesterol by up to 50%
- Adverse effects are limited to the GI tract (constipation, etc.)
- Can form insoluble complexes with other drugs, so administer other oral medications 1 hour before or 4 hours after the sequestrant
Ezetimibe
- Acts on cells in the small intestine to inhibit dietary cholesterol absorption
- Also inhibits reabsorption of cholesterol secreted in the bile
- Reduces plasma levels of total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B
- Increases HDL cholesterol
- Generally well tolerated, but can cause myopathy, rhabdomyolysis, hepatitis, pancreatitis, and thrombocytopenia
- May increase risk of liver damage when used with statins
Bempedoic Acid
- New non-statin cholesterol medication
- Approved for patients with familial hypercholesterolemia who need additional cholesterol reduction
- No data on cardiovascular outcomes
- Adverse effects include joint swelling or pain and tendon rupture
Fibrates
- Most effective for lowering triglyceride levels
- Can also raise HDL cholesterol
- No proof that fibrates reduce mortality from ASCVD
- Three preparations available: gemfibrozil, fenofibrate, and fenofibric acid (delayed-release)
- Gemfibrozil reduces triglyceride levels and raises HDL cholesterol
- May increase LDL levels in patients with high triglyceride levels
- Common adverse effects include rash, GI disturbances, and myopathy
PCSK9 Inhibitors
- Alirocumab (Praluent) and Evolocumab (Repatha) are used for patients with high LDL levels, specifically those with heterozygous familial hypercholesterolemia or atherosclerotic heart problems
- Inhibit PCSK9, increasing LDLR and reducing LDL cholesterol
- Administered subcutaneously
- Adverse effects include hypersensitivity reactions, rash, and urticarial
Antianginal Agents
- There are three families of antianginal agents: organic nitrates, beta blockers, and calcium channel blockers
- Nitroglycerin, the most familiar organic nitrate, relieves angina by causing vasodilation
- Beta blockers reduce anginal pain by decreasing cardiac oxygen demand
- Calcium channel blockers (verapamil, diltiazem, and nifedipine) relieve coronary artery spasm, increasing cardiac oxygen supply
- Ranolazine represents a new class of antianginal agents, which reduce the number of angina episodes and increase exercise tolerance
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Test your knowledge on the development of tolerance to nitroglycerin and other nitrates, and how to prevent it. Learn about the impact of dosage, therapy interruption, and formulation on tolerance development.
