Antianginal And Other Anti-Ischemic Drugs
Question 1. Give The Pharmacological Explanation For Why Nitroglycerine Tablet May Not Be Effective When Swallowed But Works Very Well For Patient Of Angina Pectoris When Kept Under The Tongue?
Or
Explain Why Nitroglycerin Is Used Sublingually In The Treatment Of Acute Attack Of Angina Pectoris.
Answer:
Nitroglycerine has a very high first-pass metabolism. So the drug achieves low plasma concentration when given orally. Thus its bioavailability is less through the oral route. To circumvent this drug is administered by the sublingual route.
Through the sublingual route drug directly reaches the blood vessel and has a faster onset of action to stop an acute attack of angina.
Read And Learn More: Pharmacology Question And Answers
Self-administration of drugs is possible by sublingual route.
Mechanism Of Action
Nitrates cause smooth muscle relaxation of veins and cause peripheral pooling of blood and reduce venous return, decrease preload, end-diastolic size, and pressure is decreased due to which cardiac work is reduced.
Question 2. Explain Why Nifedipine Is Referred Over Verapamil In Vasospastic Angina.
Answer:
Nifedipine is referred over verapamil in vasospastic angina because nifedipine is an arteriolar dilator so it decreases total peripheral resistance, decreasesBP, and reflex sympathetic stimulation of the heart causing increased coronary flow.
It does not depress the AV node or AV conduction and hence no decrease in venous return and cardiac work but in the case of verapamil there is depression of cardiac work and causes cardiogenic shock so that’s why nifedipine is refereed over verapamil in vasospastic angina.
Question 3. Discuss The Basic Use Of Propranolol In Classical Angina Pectoris.
Or
Write The Basic Use Of Propranolol In Classical Angina Pectoris.
Or
Write Basic Use Of Β Blockers In Angina Pectoris.
Answer:
Propranolol is a β-blocker.
- Propranolol causes a reduction of cardiac work and oxygen consumption by reducing total peripheral resistance due to which there is a redistribution of blood in the ischemic area.
- Propranolol reduces coronary flow without affecting the subendocardial area, which is overall effective in decreasing the frequency and severity of attacks as well as increasing exercise tolerance in classical angina.
Question 4. Write A Short Note On Drugs In Classical Angina.
Answer:
Angina is a discomfort resulting from acute myocardial ischemia due to coronary atherosclerosis, thromboembolism, pulmonary hypertension, and congenital abnormalities.
- The primary drug used in classical angina is nitrate or glycerine trinitrate which is sublingually administered and causes vasodilatation of the coronary artery as well as relief in pain.
- Morphine can be IV or orally administered it relieves pain as well as anxiety.
- Fibrinolytic enzymes like streptokinase or urokinase can be employed.
- Heparin can be used as an anticoagulant in classical angina.
- After the patient gets stabilized it can be switched over to oral drugs like β-blockers or calcium channel blockers.
- Aspirin is also given as an antiplatelet drug.
Question 5. Write A Short Note On Glyceryl Trinitrate.
Answer:
Glyceryl trinitrate is an anti-anginal drug.
- It is a volatile liquid that is adsorbed on the inert matrix of the tablet and rendered nonexplosive.
- The sublingual route is used when terminating an attack or aborting an imminent one is the aim.
- The tablet may be crushed under the teeth and spread over the buccal mucosa.
- It acts within 1–2 min because of direct absorption into the systemic circulation.
- Plasma t1/2 is 2 min, the duration of action depends on the period it remains available for absorption from buccal mucosa. The remaining part of the tablet may be spit or swallowed when no longer needed.
- A sublingual spray formulation has been recently introduced which acts more rapidly than the sublingual tablet.
- Hepatic metabolizing capacity can be overwhelmed by administering a large dose (5–15 mg) orally.
- Sustained-release oral capsules containing much larger amounts of glyceryl trinitrate can be used for chronic prophylaxis.
Question 6. Explain The Drug Interaction Between Nitrates And Β Blockers.
Or
Write In Briefdruginteraction Ofnitrates And Β Blockers.
Answer:
Nitrates improve blood flow by relaxing and dilating (expanding) veins and arteries, including the coronary arteries.
They reduce the amount of blood returning to the heart while Beta-blockers reduce the heart rate, blood pressure, and the force of the heart’s contractions, thereby decreasing the amount of oxygen the heart requires to pump blood.
Along with nitrates, beta blockers are usually the first choice for the treatment of stable angina, and are particularly beneficial in people who have angina during exercise or activity.
Another important benefit of beta blockers is that they improve survival and prevent another heart attack in people who have suffered a recent heart attack.
Question 7. Explain Why Β Blockers Are Not Used In Stable Angina Pectoris.
Answer:
β blockers exacerbate stable angina due to unopposed α mediated coronary constriction that may accentuate coronary spasm. That’s why they are not used in stable angina patients.
Question 8. Describe Brief Mechanism Of Action, Therapeutic Uses, Adverse Reactions, And Preparation Of Nitrates When Used For Angina.
Answer:
Nitrates In Angina Mechanism Of Action
- Nitrates reduce coronary vasospasm and increase the perfusion of the myocardium by relaxing the coronary arteries.
- Organic nitrates are rapidly denigrated enzymatically in a smooth muscle cell to release reactive free radical nitric oxide which activates cytosolic guanylyl cyclase.
- This leads to an increase in cGMP which causes dephosphorylation of myosin light chain kinase through cGMP protein kinase.
- There is reduced availability of active phosphorylated myosin light chain kinase (MLCK).
- So myosin fails to interact with actin to cause contraction and relaxation occurs. cGMP also reduces calcium entry and leads to relaxation.
Nitrates In Angina Therapeutic Uses
- Angina:
- Nitroglycerine is used in the acute attack of angina.
- Nitrates are effective in classical as well as variant angina.
- For aborting or terminating the attack sublingual glycertrinitrate or isosorbide dinitrate should be taken.
- Nitrates increase exercise tolerance and postpone ECG changes of ischemia.
- Longer-acting formulations of glycertrinitrate or other nitrates are used on a regular schedule for chronic prophylaxis
- Nitrates are effective in unstable angina as well.
- Myocardial infarction: Carefully titrated IV infusion of glycerin trinitrate to avoid tachycardia and started soon after the arterial occlusion can relieve pulmonary congestion and limit the area of necrosis by favorably altering oxygen balance in a marginally partial ischemic zone by reducing cardiac work.
- Congestive cardiac failure and acute ventricular failure: Nitrates provide relief by venous pooling of blood which decreases preload. This increases end-diastolic volume. This leads to an improvement in left ventricular function.
- Interventional cardiac procedures: Nitrates are used as adjuvant drugs for dilating coronaries in percutaneous coronary angioplasty.
- Biliary colic: Sublingual nitrates subsides biliary colic which is produced due to disease or morphine.
- Esophageal spasm: Nitrates before a meal helps in feeding in esophageal achalasia and decreases esophageal tone.
- Cyanide poisoning: Nitrates produce methemoglobin which forms cyanomethamoglobin. After this sodium thiosulphate is given to the patient which prevents dissociation and release of cyanide by forming sodium Pharmacology thiocyanate which is poorly dissociated and is excreted in the urine.
Nitrates In Angina Adverse Reactions
- Adverse reactions are due to vasodilatation. The following are the adverse reactions:
- Fullness in the head, throbbing headache, and some degree of tolerance develop on continued use.
- Flushing, weakness, sweating, palpitation, dizziness, and fainting.
- Methemoglobinemia. It can reduce the oxygen-carrying capacity of blood in severe anemia.
- Rashes are rare.
Nitrates In Angina Preparation
Question 9. Enumerate The Drugs Used In The Treatment Of Angina Pectoris. Discuss The Other Uses And Adverse Effects Of Nitrates.
Answer:
Enumeration Of Drugs Used In Angina Pectoris
- Nitrates:
- Short-acting: Glyceryl trinitrate
- Long-acting: Isosorbide dinitrate, isosorbide mononitrate, erythritol tetranitrate, penta erythritol tetranitrate.
- β Blockers: Propranolol, metoprolol, atenolol, and others
- Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, lacidipine.
- Potassium channel opener: Nicorandil
- Others: Dipyridamole, trimetazidine, ranolazine. Clinical Classification
- Used to abort or terminate attack: Glyceryl trinitrate, isosorbide dinitrate.
- Used for chronic prophylaxis: All other drugs.
Other Uses of Nitrates
- Myocardial Infarction: Carefully titrated IV infusion of glyceryl trinitrate to avoid tachycardia and started soon after the arterial occlusion can relieve pulmonary congestion and limit the area of necrosis by favorably altering oxygen balance in a marginally partial ischemic zone by reducing
cardiac work. - Congestive cardiac failure and acute ventricular failure: Nitrates provide relief by venous pooling of blood which decreases preload. This increases end-diastolic volume. This leads to an improvement in left ventricular function.
- Interventional cardiac procedures: Nitrates are used as adjuvant drugs for dilating coronaries in percutaneous coronary angioplasty.
- Biliary colic: Sublingual nitrates subsides biliary colic which is produced due to disease or morphine.
- Esophageal spasm: Nitrates before a meal helps in feeding in esophageal achalasia and decreases esophageal tone.
- Cyanide poisoning: Nitrates produce methemoglobin which forms cyanomethamoglobin. After this sodium thiosulphate is given to the patient which prevents dissociation and release of cyanide by forming sodium thiocyanate which is poorly dissociated and is excreted in the urine.
Question 10. Write A Short Note On The Basis Of Use Of Nitrates In Angina.
Or
Write Short Note On Organic Nitrates In Angina.
Answer:
Following is the basis of the use of nitrates in angina:
Question 11. Write A Note About Why Nitroglycerine Tablets Are Effective When Given Sublingually In A Patient Of Angina.
Answer:
Nitroglycerine has a very high first-pass metabolism. So the drug achieves low plasma concentration when given orally. Thus its bioavailability is less through the oral route. To circumvent this drug is administered by the sublingual route.
Through the sublingual route drug directly reaches the blood vessel and has a faster onset of action to stop an acute attack of angina.
Self-administration of drugs is possible by sublingual route.
Question 12. Enumerate The Drugs Used In The Treatment Of Angina Pectoris. Describe The Uses Of Β (Beta) Blockers.
Answer:
Enumeration of Drugs Used in Treatment of Angina Pectoris
- Nitrates:
- Short-acting: Glyceryl trinitrate
- Long-acting: Isosorbide dinitrate, Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate.
- β Blockers: Propranolol, metoprolol, atenolol, and others
- Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, lacidipine.
- Potassium channel opener: Nicorandil
- Others: Dipyridamole, Trimetazidine, Ranolazine.
Uses Of β Blockers
- Hypertension: β blockers are used to treat all grades of hypertension. They are also indicated in angina, myocardial infarction, and cardiac arrhythmias.
- In the prophylaxis of angina and myocardial infarction: β blockers decrease the oxygen demand of the myocardium and decrease the heart rate. These drugs reduce the frequency of angina attacks. They are indicated in the acute phase of myocardial infarction so that they limit the size of the infarct.
- In cardiac arrhythmias: They are indicated in atrial arrhythmias i.e. atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia.
- Congestive cardiac failure: Chronic usage of β blockers reduces the rate of mortality during chronic heart failure.
- Pheochromocytoma: These drugs control cardiac manifestations produced by pheochromocytoma.
- Glaucoma: They decrease intra-ocular pressure by decreasing the secretion of aqueous humor. Timolol is the choice of drug.
- In the prophylaxis of migraine: They decrease the frequency of migraine headaches.
- Hyperthyroidism: Signs and symptoms of hyperthyroidism decrease due to the blockade of β receptors.
- Essential tremors: Propranolol provides relief in tremors.
- Anxiety: It acts as an anti-anxiety drug.
- Alcohol withdrawal: Propranolol provides benefits for alcohol withdrawal.
- Dissecting aortic aneurysm: β blockers reduce cardiac contractility as well as the development of pressure during systole.
Question 13. Discuss The Types Of Angina And Common Drugs Used In Each Type Of Angina.
Answer:
Types of angina
Classical Angina Or Stable Angina
Attacks (chest pain) are predictably provoked by exercise, anxiety, eating, or coitus and subside when the increased energy demand is withdrawn.
Drugs that are useful, primarily reduce cardiac work. They may also cause a favorable redistribution of blood flow to the ischemic areas.
Angina Drugs Used
- Nitroglycerine is the choice of drug.
- For an acute attack, nitroglycerine is given sublingually with an initial dose of 0.5 mg which relieves pain in 2 to 3 min.
- For prophylaxis, isosorbide mononitrate orally is given.
Variant/Prinzmetal`s/Vasospastic Angina
Attacks occur at rest or during sleep and are unpredictable. They are due to recurrent localized (occasionally diffuse) coronary vasospasm which may be superimposed on arteriosclerotic coronary artery disease. Drugs are aimed at preventing and relieving coronary vasospasm.
Angina Drugs Used
- Episodes of coronary vasospasm should be treated with nitrates
- For prophylaxis nitrates and calcium channel blockers are effective.
- The association of calcium channel blockers with nitrate produces good efficacy in variant angina.
Angina Unstable Angina
The rapid increase in duration and severity of attacks is mostly due to the rupture of an atheromatous plaque attracting platelet deposition and incomplete occlusion of the coronary artery; occasionally with associated coronary vasospasm.
Angina Drugs Used
It needs treatment with multiple drugs:
- Antiplatelet agents: Low-dose aspirin, clopidogrel, etc are used
- Anticoagulants: Low molecular weight heparin or unfractionated heparin is used.
- Nitrates: Nitroglycerin sublingually is effective.
- Beta-blockers: Atenolol or metoprolol are routinely administered in unstable angina.
- Calcium channel blockers: Amlodipine, nifedipine, diltiazem, or verapamil are used if symptoms persist in patients with nitrates
- Statins: They improve outcomes in unstable angina.
Question 14. Write In Brief About Various Antianginals. Write Protocol For Management Of Acute Myocardial Infarction.
Answer:
Various antianginals in brief
Classification Of Antianginal Drugs
Nitrates:
- Short-acting: Glyceryl trinitrate
- Long-acting: Isosorbide dinitrate, isosorbide mononitrate, erythritol tetranitrate, penta erythritol tetranitrate.
- β Blockers: Propranolol, metoprolol, atenolol and others
- Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, lacidipine.
- Potassium channel opener: Nicorandil
- Others: Dipyridamole, trimetazidine, ranolazine.
Antianginal Drugs Clinical Classification
- Used to abort or terminate attack: Glycer trinitrate, isosorbide dinitrate.
- Used for chronic prophylaxis: All other drugs.
Nitrates: Nitroglycerine and isosorbide dinitrate are given sublingually for an acute attack of angina. These are very fast-acting drugs and are useful in both types of angina—classical and variant. Nitrates can also be given for prophylaxis of angina by oral or transdermal route. Major limitations are low oral bioavailability (due to high first-pass metabolism) and the development of tolerance on long-term use. These can also cause hypotension which can be life-threatening in a patient taking sildenafil (for erectile dysfunction).
Beta-blockers: These are first-line drugs for prophylaxis of chronic angina. There are the only drugs that can decrease mortality in ischemic heart disease. However, these are contraindicated in variant angina as it is due to vasospasm and beta-blockers may aggravate coronary vasoconstriction by interfering with β2 mediated vasodilation. Limitations ofβ blockers include
the risk of bradycardia, hypotension, precipitation of asthma, and CHF. These should be avoided in diabetic patients because they can delay their recovery from hypoglycemia.
Calcium channel blockers: Verapamil, diltiazem and long-acting dihydropyridines like amlodipine can be used for prophylaxis of classical as well as variant angina. However, these do not decrease mortality whereas short-acting dihydropyridines like nifedipine can actually increase mortality due to reflex tachycardia.
Ranolazine: It is a new drug that acts by blocking a sodium channel thereby reducing calcium entry intracellularly. It also inhibits fatty acid oxidation. It is useful only for prophylaxis of angina. The advantage of ranolazine as compared to other antianginal drugs is that it has no effect on blood pressure (most other antianginal drugs can cause hypotension) and heart rate and can be safely used with drugs for erectile dysfunction (like sildenafil). The major limitation is a risk for the development of QT pro-location in ECG leading to Torsades’ de pointes (ventricular arrhythmia).
Protocol For Management Of Acute Myocardial Infarction
- Pain, anxiety, and apprehension: When the chest pain is not relieved by 3 doses of sublingual nitroglycerine given 5 min apart, myocardial infarction is suspected and an opioid analgesic (morphine/pethidine) or diazepam should be given parenterally.
- Oxygenation: By oxygen inhalation and assisted respiration, if needed.
- Maintenance of blood volume, tissue perfusion, and microcirculation: Slow IV perfusion of saline/low molecular weight dextran may be instituted if the BP falls, but volume overload is to be avoided.
- Correction of acidosis: It occurs due to lactic acid production; can be corrected by sodium bicarbonate IV infusion.
- Prevention and treatment of arrhythmia: Prophylactic IV infusion of β blocker (unless contraindicated due to fall in BP/bradycardia, etc.) is recommended. Its continuation orally for a few days has been shown to reduce the incidence of arrhythmias and mortality. β blockers used early in evolving myocardial infarction can reduce the infarct size (myocardial salvage) and subsequent
complications. Tachyarrhythmias may be treated with lidocaine, procainamide, or amiodarone. Bradycardia and heart block may be managed with atropine or electrical pacing. - Pump failure: The objective is to increase cardiac output and/or decrease filling pressure without unduly increasing cardiac work or lowering blood pressure. Drugs used for this purpose are:
- Furosemide is indicated if pulmonary wedge pressure is > 20 mm Hg. It decreases cardiac preload.
- Vasodilators: A vasodilator or combined dilator is selected according to the monitored hemodynamic parameters. Drugs like nitroglycerine (IV) or nitroprusside have been mainly used.
- Inotropic agents: Dopamine or dobutamine IV infusion may be needed to augment the pumping action of the heart and tide over the crisis.
- Prevention of thrombus extension, embolism, and venous thrombosis: All patients with myocardial infarction should be immediately given aspirin (150-300 mg) for
chewing and swallowing. This may be supplemented by other antiplatelet drugs (clopidogrel or prasugrel). Anticoagulants (heparin followed by oral anticoagulants) are used primarily to prevent deep vein thrombosis/ pulmonary embolism. Its value in checking coronary artery thrombus extension is uncertain. Any benefit is short-term; anticoagulants are not prescribed on a long-term basis now. - Thrombolysis: Fibrinolytic agents, i.e. plasminogen activators streptokinase/urokinase/alteplase/tenecteplase to achieve reperfusion of the infarcted area. This is beneficial only when started within l to 2 hours of symptom onset. Primary percutaneous coronary intervention with stent placement is the preferred revascularization procedure now.
- Prevention of remodeling and subsequent CHF: ACE inhibitors/ARBs have proven efficacy and afford long-term survival benefits.
- Prevention Of Future Attacks
- Platelet function inhibitors: Aspirin alone or combined with clopidogrel given on a long-term basis is routinely prescribed.
- β blockers: Reduce the risk of reinfarction, CHF, and mortality. All patients not having any contraindications are put on a β1 blocker for at least 2 years.
- Control of hyperlipidemia: Dietary substitution with unsaturated fats along with a statin hypolipidemic drug is recommended irrespective of plasma lipid levels.
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