Flashcards in antianginal Deck (24):
1. What is the primary cause of angina?
Imbalance b/t the oxygen demand of the heart and the oxygen supplied to it via the coronary vessels. When the heart becomes hypoxic there is a trigger of pain receptors leading to the classical chest pain characterized by pre-cordial pressure-like discomfort.
2. What are the different classifications of angina?
1. Chronic stable angina → chronic narrowing of the arteries due to atherosclerosis
2. Unstable angina → transient formation and dissolution of a thrombosis within the coronary artery due to ruptured plaque
3. Prinzmetal’s (variant) angina → coronary vasospasm that reduces coronary blood flow, sympathetic activity can precipitate vasospastic angina
3. What are the different classes of chronic stable angina?
Class 0 → asymptomatic
Class 1 → angina with strenuous exercise
Class 2 → angina with moderate exercise
Class 3 → angina with mild exertion (walking a block, climbing 1 flight of stairs)
Class 4 → angina at any level of physical exertion
4. What is the goal of tx of angina?
Increasing blood flow (increase O2 delivery or supply via vasodilators or anti-thrombotic drugs) or decreasing oxygen demand (decrease myocardial O2 consumption via vasodilators or cardiac depressant drugs)
5. What are the different categories of drugs used to treat angina?
1. vasodilators → calcium channel blockers or nitrates that will increase O2 supply and decrease O2 demand
2. Cardioinhibitory drugs → B-blockers or calcium channel blockers that will decrease O2 demand
3. Ranolazine → Na+ channel blocker
4. Anti-thrombotic drugs → anticoagulants, anti-platelet drugs
6. What are examples of calcium channel blockers (vasodilators) used to treat angina?
7. What is the use and mechanism of action of calcium channel blockers (CCBs) used for angina?
CCBs are used to treat HTN, angina (all 3 types) and arrhythmias. CCBs block voltage-sensitive calcium channels (L-type) located in vascular SM, cardiac myocytes and cardiac nodal tissue. By blocking these channels there is a decrease in calcium entry into the cell thereby causing relaxation (vasodilation), decreased HR and decreased contractility. Because of their ability to cause reflex tachycardia post peripheral vasodilation, dihydropyridines are used in combination with B blockers. The anti-anginal effects seen with CCBs are due to their vasodilator and cardiodepressant actions. These drugs are administered orally.
8. How would you know with CCB to use in the treatment of angina?
1. Dihydropyridine (Amlodipine, Nifedipine (short acting), Felodipine) → more selective for vascular SM therefore can relieve variant angina. Short acting (Nifedipine) should be used with B blocker to reverse a strong reflex tachycardia, but long acting has a reduced reflex response.
2. Verapamil → greater negative inotropic action than other CCBs, but has a weak vasodilatory effect. By reducing HR and contractility symptoms can be relieved.
3. Diltiazem → intermediate effect on vascular calcium channels b/t Dihydropyridine and Verapamils. Diltiazem can relieve coronary vasospasms by dilating coronary arteries and relieving symptoms of variant angina.
9. What are the adverse effects of using Dihydropyridines for angina?
1. reflex tachycardia
2. dizziness, flushing, headache, Hypotension, constipation, peripheral edema
10. What are the adverse effects of using Verapamil an Diltiazem for angina?
1. cardiac conduction abnormalities → bradycardia, AV block, HF
2. anorexia, nausea, peripheral edema, hypotension
3. verapamil is associated with constipation
**if pt has bradycardia, conduction defects or HF DO NOT GIVE CCBs
11. What are examples of nitrates used to treat angina?
1. Isosorbide Dinitrate – long term management, oral admin → 100% bioavailability
2. Isorbide Mononitrate – used orally for prophylaxis of angina (long term management), oral admin → 100% bioavailability
3. Nitroglycerin – 1st line therapy for tx of acute angina symptoms, rapid onset
4. Sodium Nitroprusside – used in ICU and emergency settings (ex. hypertensive emergencies), rapid onset, IV prep, short half life
12. What clinical symptoms are nitrates used for and what is their mechanism of action in the tx of angina?
All types of angina are treated by nitrates. In the CVS, NO is produced by vascular endothelial cells leading to the activation of guanylyl cyclase → GTP → cGMP. Increased cGMP inhibits Ca2+ entry into cells causing SM relaxation. NO also activates K+ channels leading to hyperpolarization and relaxation. cGMP also activates myosin light chain phosphatase leading to relaxation.
1. NO relaxes vascular SM → vasodilation
2. Inhibits platelet aggregation → anti-thrombotic
3. Inhibits leukocyte-endothelial interactions → anti-inflammatory
Nitrates have more of an effect on veins than arteries thereby decreasing venous pressure → decreasing ventricular preload → decrease O2 demand of heart. There is a risk of reflex tachycardia due to excessive peripheral vasodilation.
13. What is the role of tolerance on nitrates?
Tolerance develops rapidly in nitrates due to vessels becoming desensitized to vasodilatory effects of nitrates. With infrequent, small doses, tolerance can be overcome.
14. What are the adverse effects of Nitrate treatment with angina?
2. Reflex tachycardia
3. Headache – cerebral vasodilation
4. Facial flushing
5. Cyanide toxicity with sodium nitroprusside
6. **DO NOT TAKE WITH SILDENAFIL which inhibits cGMP breakdown thereby causing severe hypotension and impaired coronary perfusion
15. What are the different B-blockers used for angina?
1. Propranolol → non-selective B-blocker, oral admin, extensive 1st pass metabolism
2. Metoprolol → cardioselective B-blocker (more selective for B1 recpetors), extensive 1st pass metabolism
3. Atenolol → cardioselective B-blocker (more selective for B1 recpetors), extensive 1st pass metabolism
16. What is the clinical application of B-blockers used for angina?
B-blockers are used in the tx for HTN, angina (NOT VARIANT), MI, arrhythmias, and HF. By blocking the B-receptors, they are able to…
1. decrease myocardial contractility, HR and CO (blocking cardiac B1 receptors)
2. reduce renin secretion (by blocking B1 receptors on juxtaglomerular cells)
There is no reflex tachycardia evoked by the B-receptors and the anti-anginal effects of B-blockers is attributed to the negative inotropic and antihypertensive actions.
17. What are the adverse effects of B-blockers used for angina?
1. drug withdrawal
2. cardiovascular effects → bradycardia, reduced exercise capacity, HF, hypotension, AV block
3. Disturb lipid metabolism
6. CNS effects
18. When should B-blockers for angina not be used?
1. variant angina → B-blockers can exacerbate variant angina by blocking B2-mediated vasodilation
2. reactive airway disease (asthma, COPD) – avoid use of non-selective B-blockers
3. pts with sinus bradycardia and partial AV block
4. Heart failure – start on low dose due to risk of exacerbation of symptoms
19. What is the function of Ranolazine in the tx of angina?
Ranolazine is a Na+ channel blocker used to treat chronic angina – that has failed all other therapies. Ranolazine blocks late inward Na+ current in cardiomyocytes. Normally the accumulation of intracellular Na+, facilitates an inward current of calcium via the Na+/Ca2+ exchanger. Increased intracellular Ca2+ results in contraction of the myocytes and impaired relaxation. With Ranolazine blocking the influx of Na+, there is a prevention of calcium overload leading to improved coronary blood flow. Once consumed, Ranolazine is metabolized by CYP3A4.
20. What are the adverse side effects of Ranolazine?
1. QT prolongation → b/c this drug causes a QT prolongation, it is not indicated for pts with a long QT interval already
2. Nausea, vomiting, dizziness, constipation
21. How are acute attacks of stable angina managed?
22. What is the maintenance therapy for stable angina?
Preferred therapy → long-acting nitrates plus B blocker, Ca2+ channel blockers can be used if B-blockers are ineffective – if nitrates, B-blockers and calcium channel blockers are all unsuccessful, Ranolazine is used
23. How are acute attacks and long-term tx of unstable angina managed?
Acute attacks → nitroglycerin
Long-term management → nitroglycerine with B-blockers