Drugs Affecting the Cardiovascular System

Question 1

What are cardiovascular drugs and their classification?

Answer 1

Cardiovascular drugs are diverse group of pharmacological agents used to treat various conditions related to the heart and blood vessels.

These drugs can be classified based on their mechanism of action and therapeutic use which include:
1. Antihypertensive
2. Antiarrhythmic
3. Inotropes
4. Vasodilators
5. Anticoagulants
6. Antiplatelet Agents
7. Cholesterol-Lowering Drugs.

Question 2

What are Antiarrhythmic drugs and their classification?

Answer 2

Antiarrhythmic drugs are used to treat abnormal heart rhythms (arrhythmias). They work by modifying the electrical impulses that regulate the heartbeat, helping to restore a normal rhythm.

These drugs are classified into several classes based on their mechanisms of action which include: Class I: Sodium Channel Blockers, Class Ib, Class Ic.

Class II: Beta-Adrenergic Blockers, Class III: Potassium Channel Blockers, Class IV: Calcium Channel Blockers

Question 3

What are Class I: Sodium Channel Blockers?

Answer 3

These drugs block sodium channels, which are involved in the depolarization phase of the cardiac action potential. They are further divided into three subclasses:

Class Ia: Moderate sodium channel blockade, which prolongs the action potential duration.

Examples: Quinidine: Used for atrial fibrillation and ventricular arrhythmias (side effect is cinchonism)

Procainamide: Used for ventricular arrhythmias and atrial fibrillation.

Disopyramide: Used for ventricular arrhythmias, but has significant anticholinergic effects.

Question 4

Class Ib

Answer 4

Mechanism: Weak sodium channel blockade, primarily affects ischemic or depolarized cardiac tissue, and shortens the action potential duration.

Examples: Lidocaine: Primarily used for ventricular arrhythmias, especially post-myocardial infarction.

Mexiletine: Similar to lidocaine, used for chronic ventricular arrhythmias.

Question 5

Class Ic:

Answer 5

Mechanism: Strong sodium channel blockade, markedly slows conduction velocity without significantly affecting the action potential duration.

Examples: Flecainide; Used for atrial fibrillation and ventricular arrhythmias.

Propafenone; Used for atrial fibrillation and ventricular arrhythmias; also has beta-blocking activity.

Question 5

Class II: Beta-Adrenergic Blockers

Answer 5

These drugs block beta-adrenergic receptors, which reduces sympathetic nervous system activity and slows down the heart rate.

Examples: Metoprolol; used for atrial fibrillation, atrial flutter, and ventricular arrhythmias.

Atenolol: Used for various arrhythmias, including atrial fibrillation.

Propranolol: Used for both atrial and ventricular arrhythmias, and has additional uses in reducing anxiety and preventing migraines.

Question 6

Class III: Potassium Channel Blockers examples and side effects

Answer 6

These drugs block potassium channels, which prolong the repolarization phase of the cardiac action potential, thus prolonging the refractory period.

Examples: Amiodarone; A broad-spectrum antiarrhythmic used for both atrial and ventricular arrhythmias, including atrial fibrillation and ventricular tachycardia. It can cause a variety of side effects, including thyroid and lung issues.

Sotalol: Used for atrial fibrillation and ventricular arrhythmias. It also prolongs the QT interval, which can lead to torsades de pointes.(a form of polymorphic ventricular tachycardia)

Dofetilide: Used for atrial fibrillation and flutter, also prolongs the QT interval.

Question 7

Class IV: Calcium Channel Blockers & other anti arrhythmic agents

Answer 7

These drugs block calcium channels, which affects the conduction through the atrioventricular (AV) node and reduces heart rate.

Examples: Verapamil; Used for atrial fibrillation, atrial flutter, and certain types of supraventricular tachycardias. It slows AV nodal conduction and can reduce heart rate.

Diltiazem: Similar to verapamil, used for atrial fibrillation and supraventricular tachycardias.

Nifedipine

Other Antiarrhythmic Agents: Adenosine; Used for the rapid termination of certain types of supraventricular tachycardias (SVTs) by briefly blocking AV node conduction.

Digoxin: Used primarily for atrial fibrillation and flutter, particularly in patients with heart failure. It increases vagal tone, which can slow AV nodal conduction.

Question 8

What are Antianginal Drugs?
How are nitrates antianginal?

Answer 8

Antianginal drugs are used to relieve or prevent angina pectoris, which is chest pain or discomfort caused by inadequate blood supply to the heart muscle. They work by improving blood flow to the heart or reducing the heart’s oxygen demand. Examples include;

Nitrates: Nitrates are used to relieve angina by dilating blood vessels, which reduces the heart’s workload and improves blood flow to the heart muscle (Short- Acting Nitrates- Nitroglycerin, Isosorbide dinitrate; Long-Acting Nitrates: Isosorbide mononitrate).

Nitrates are converted to nitric oxide (NO), which relaxes smooth muscle cells in blood vessels, leading to vasodilation. This reduces preload (venous return) and, consequently, myocardial oxygen demand.
Considerations: Tolerance can develop with prolonged use, so nitrates should be used with a nitrate-free interval. Side effects include headaches, dizziness, and hypotension.

Question 9

Antihypertensive Drugs and their classification

Answer 9

Antihypertensive drugs are used to manage high blood pressure (hypertension) and reduce the risk of complications such as heart attack, stroke, and kidney damage.

These medications work through various mechanisms to lower blood pressure,

Major classes of antihypertensive drugs include:
* Diuretics, (e.g., hydrochlorothiazide, furosemide)
* ACE inhibitors (e.g., enalapril, lisinopril).
* Angiotensin II receptor blockers (ARBs) (e.g., losartan, valsartan),
* Beta-blockers (e.g., carvedilol, metoprolol)
* Alpha blockers eg. Prazosin, Terazosin, Doxazosin Phentolamine, Phenoxybenzamine
* Direct renin inhibitors e.g Aliskren
* Calcium channel blockers (e.g. amlodipine, nifedipine)
* Vasodilators e.g hydralazine, minoxidil

Question 10

Diuretics, types and examples

Answer 10

Diuretics help reduce blood pressure by eliminating excess sodium and water from the body, thus decreasing blood volume.

Classes include:

• Thiazide Diuretics: Act on the distal convoluted tubule of the nephron to inhibit sodium reabsorption (Hydrochlorothiazide, chlorthalidone).
  Contraindication: not given to pregnant women

Indications: Often used as first-line treatment for hypertension, particularly effective in uncomplicated hypertension.

• Loop Diuretics: Act on the ascending limb of the loop of Henle to inhibit sodium reabsorption (Furosemide (Lasix), bumetanide)

Indications: Used in cases of heart failure or renal impairment where more potent diuresis is needed.

• Potassium-Sparing Diuretics: Act on the distal part of the nephron to inhibit sodium reabsorption while retaining potassium (Spironolactone, eplerenone)

Indications: Often used in combination with thiazide diuretics to prevent potassium loss

Question 11

ACE inhibitors

Answer 11

ACE inhibitors block the enzyme angiotensin-converting enzyme (ACE), which reduces the production of angiotensin II, a potent vasoconstrictor.

Examples: Enalapril; Reduces blood pressure by decreasing angiotensin II levels and reducing aldosterone secretion.

Lisinopril: Similar to enalapril, often used for hypertension and heart failure.

Ramipril: Provides cardiovascular protection and is used in various cardiovascular conditions.

Question 12

Angiotensin II Receptor Blockers (ARBs)

Answer 12

ARBs block the receptors for angiotensin II, preventing its vasoconstrictive effects.

Examples: Losartan; Blocks angiotensin II receptors to reduce blood pressure and improve kidney function.

Valsartan: Similar to losartan, used for hypertension and heart failure.

Candesartan: Effective in reducing blood pressure and providing renal protection.

Question 13

Alpha-blockers
Characteristic use in males

Answer 13

Alpha-blockers reduce blood pressure by blocking alpha-adrenergic receptors, leading to vasodilation.

Examples:
Doxazosin; Used for hypertension and benign prostatic hyperplasia (BPH).

Prazosin: Effective for hypertension and post-traumatic stress disorder (PTSD)-related nightmares.

Question 14

Discuss Anticoagulants
(Particularly vitamin k antagonists and warfarin)

Answer 14

Anticoagulants are medications that help prevent blood clots from forming or growing larger. They are used to treat or prevent conditions such as deep vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation, and to reduce the risk of stroke or heart attack. Examples include;

Vitamin K Antagonists: These drugs inhibit the vitamin K epoxide reductase enzyme, which is necessary for the synthesis of vitamin K-dependent clotting factors (Factors II, VII, IX, and X) in the liver. By reducing these factors, they slow down the blood clotting process.

Examples: Warfarin (Coumadin); One of the most commonly used vitamin K antagonists. It requires regular monitoring of the INR (International Normalized Ratio) to ensure therapeutic levels and prevent bleeding complications.

Considerations: Warfarin’s effect can be influenced by diet (e.g., foods high in vitamin K) and other medications. It has a delayed onset and requires regular blood tests to monitor its effect.

Question 14

Direct renin inhibitors and
vasodilators

Answer 14

Direct renin inhibitors prevent the conversion of angiotensinogen to angiotensin I, which reduces the production of angiotensin II.

Examples: Aliskiren; Reduces blood pressure by directly inhibiting renin.

Vasodilators: Vasodilators directly relax the smooth muscles of blood vessels, leading to reduced systemic vascular resistance and lower blood pressure.

Examples: Hydralazine: Used for severe hypertension and heart failure.

Minoxidil: Often used in combination with a diuretic and a beta-blocker due to its potent effects.

Question 15

Direct Oral Anticoagulants (DOACs)

Answer 15

DOACs are a newer class of anticoagulants that target specific clotting factors and generally require less monitoring compared to vitamin K antagonists. Examples include;

Direct Factor Xa Inhibitors: These drugs inhibit factor Xa, a key enzyme in the coagulation cascade e.g Rivaroxaban (Xarelto); Used for conditions such as atrial fibrillation, DVT, and PE.

Direct Thrombin Inhibitors: These drugs inhibit thrombin (factor IIa), which is crucial for converting fibrinogen to fibrin and for clot formation.

Examples: Dabigatran (Pradaxa): Used for stroke prevention in atrial fibrillation and treatment of DVT and PE. It has a reversal agent (idarucizumab) in case of major bleeding.

Considerations: DOACs typically have fewer interactions with food and other medications compared to warfarin and do not require routine blood monitoring. However, their use requires consideration of renal function and potential drug interactions.

Question 16

Heparins

Answer 16

Heparins are administered either intravenously or subcutaneously and work by enhancing the activity of antithrombin III, which inactivates several clotting factors.

Examples include;
Unfractionated Heparin (UFH): Binds to antithrombin III and inhibits thrombin (factor IIa) and factor Xa.

Administration: Typically given intravenously for rapid anticoagulation in acute settings (e.g., myocardial infarction, DVT).
Monitoring: Requires regular monitoring of the activated partial thromboplastin time (aPTT) to adjust dosage.

Low Molecular Weight Heparins (LMWHs): More selectively inhibit factor Xa with less effect on thrombin compared to UFH.

Examples: Enoxaparin (Lovenox): Often used for DVT prophylaxis and treatment, as well as in acute coronary syndrome.
Dalteparin (Fragmin): Used for DVT prevention and treatment.

Considerations**: LMWHs generally have more predictable effects, require less monitoring than UFH, and can be administered subcutaneously.

Question 17

Antiplatelet drugs

Answer 17

Antiplatelet drugs are used to prevent blood clots by inhibiting platelet aggregation, which is a crucial step in clot formation.

They are commonly prescribed to reduce the risk of cardiovascular events such as heart attacks, strokes, and other conditions related to arterial thrombosis.

Aspirin (Acetylsalicylic Acid: Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), an enzyme involved in the synthesis of thromboxane A2 (TXA2).

Thromboxane A2 is a potent promoter of platelet aggregation and vasoconstriction. By inhibiting COX-1, aspirin reduces TXA2 production, thereby decreasing platelet aggregation.

Indications: Primary and secondary prevention of cardiovascular events (e.g., heart attack, stroke).

Question 18

ADP Receptor Inhibitors (P2Y12 Inhibitors)

Answer 18

These drugs inhibit the ADP (adenosine diphosphate) receptor P2Y12 on platelets, which is important for platelet activation and aggregation. Examples include:

Clopidogrel (Plavix): Inhibits the P2Y12 receptor, reducing platelet activation and aggregation.

Indications: Used for secondary prevention of cardiovascular events, particularly in patients with coronary artery disease (CAD) or after stent placement.

Considerations: Pro-drug that requires conversion to its active form in the liver.

Prasugrel (Effient): Also inhibits the P2Y12 receptor, leading to reduced platelet aggregation.

Indications: Used in combination with aspirin for the treatment of acute coronary syndrome (ACS) and during percutaneous coronary interventions (PCI).

Question 19

Bile Acid Sequestrants

Answer 19

These drugs lower cholesterol levels by binding bile acids in the intestine, which are then excreted.

Examples Cholestyramine (Questran): Binds bile acids in the gut, reducing LDL cholesterol levels.

Colestipol (Colestid): Similar to cholestyramine in its action and use.

Colesevelam (Welchol): A newer bile acid sequestrant that also improves glycemic control in type 2 diabetes.

Mechanism of Action: Bile acid sequestrants bind to bile acids in the gut, preventing their reabsorption. This leads to increased conversion of cholesterol to bile acids, lowering LDL cholesterol levels.

Considerations: These drugs can cause gastrointestinal issues such as constipation, bloating, and discomfort. They may also interfere with the absorption of other medications.

Question 19

Niacin (Vitamin B3)

Answer 19

Niacin lowers Low density lipoprotein (LDL) cholesterol and triglycerides while increasing High density lipoprotein (HDL) cholesterol which is a good cholesterol.

Mechanism of Action: Niacin reduces the production of VLDL (very-low-density lipoprotein) in the liver, which leads to a reduction in LDL cholesterol and triglycerides. It also enhances HDL cholesterol levels.

Considerations: Niacin can cause flushing, itching, and gastrointestinal upset. Extended-release formulations are often used to minimize these effects. It may also affect liver function with long-term use.

Question 19

Ezetimibe

Answer 19

Ezetimibe works by reducing cholesterol absorption in the intestines.

Mechanism of Action: Ezetimibe inhibits the Niemann-Pick C1-like 1 (NPC1L1) protein in the small intestine, which reduces the absorption of cholesterol and related phytosterols from the diet.

Indications: Often used in combination with statins to further lower LDL cholesterol levels.

Considerations: Ezetimibe is generally well-tolerated but may cause gastrointestinal side effects.

Question 19

PCSK9 Inhibitors

Answer 19

These are newer agents that significantly lower LDL cholesterol levels by inhibiting PCSK9, a protein that promotes the degradation of LDL receptors.

Examples: Alirocumab (Praluent); Used to lower LDL cholesterol levels in patients who are unable to reach their target levels with statins alone or who have a genetic predisposition to high cholesterol.

Evolocumab (Repatha); Similar to alirocumab, it is used for managing high LDL cholesterol levels, especially in patients with familial hypercholesterolemia.

Mechanism of Action: PCSK9 inhibitors block the interaction between PCSK9 and LDL receptors, allowing more LDL receptors to be available for clearing LDL cholesterol from the bloodstream.

Considerations: These drugs are administered via injection and are typically used in combination with other lipid-lowering therapies. They are generally well-tolerated but can be expensive.

Question 19

Glycoprotein IIb/IIIa Inhibitors

Answer 19

These drugs inhibit the glycoprotein IIb/IIIa receptor on platelets, which is essential for platelet aggregation. Example include:

Abciximab (Reopro): Monoclonal antibody that binds to the glycoprotein IIb/IIIa receptor, preventing platelet aggregation.

Indications: Used during PCI to reduce the risk of thrombotic events.

Considerations: Provides potent antiplatelet effects but is associated with a higher risk of bleeding.

Eptifibatide (Integrilin): Binds to the glycoprotein IIb/IIIa receptor, inhibiting platelet aggregation.
Indications: Used for ACS and during PCI.

Considerations: Administered intravenously with a rapid onset of action.

Question 19

What are Lipid-lowering drugs?
Discuss statins

Answer 19

Lipid-lowering drugs are used to manage dyslipidemia and reduce the risk of cardiovascular events. They work by inhibiting cholesterol synthesis or increasing cholesterol clearance. Examples include:

Statins (HMG-CoA Reductase Inhibitors): Statins are the most commonly prescribed lipid-lowering drugs. They work by inhibiting HMG-CoA reductase, an enzyme crucial for the synthesis of cholesterol in the liver.

Examples are Atorvastatin (Lipitor): Reduces LDL cholesterol and total cholesterol; also has benefits for reducing cardiovascular events.

Pravastatin (Pravachol): A statin with a lower risk of drug interactions, used for lowering LDL cholesterol.

Considerations: Statins can cause side effects such as muscle pain, liver enzyme abnormalities, and, rarely, rhabdomyolysis. Regular monitoring of liver function and muscle symptoms is recommended.

Question 19

Fibric Acid Derivatives (Fibrates)

Answer 19

Fibrates primarily lower triglyceride levels and can have modest effects on increasing HDL cholesterol.

Examples: Fenofibrate (Tricor); Used to lower triglyceride levels and can increase HDL cholesterol.

Gemfibrozil (Lopid): Reduces triglycerides and can modestly increase HDL cholesterol.

Mechanism of Action: Fibrates activate peroxisome proliferator-activated receptor alpha (PPAR-α), which leads to increased oxidation of fatty acids and a reduction in triglyceride levels.

Considerations: Fibrates can cause gastrointestinal symptoms and may increase the risk of gallstones. They should be used cautiously with statins due to the increased risk of myopathy.

Question 20

Combination Therapies

Answer 20

Examples: Vytorin; Combines simvastatin (a statin) and ezetimibe.

Caduet: Combines amlodipine (a calcium channel blocker) with atorvastatin.

Considerations: Combination therapies can provide complementary effects and improve lipid control in patients who do not achieve their goals with monotherapy.

Question 21

Adverse effects of ace inhibitors

Answer 21

Hypotension
hyperkalemia
cough
rashes, urticaria
Angioedema
headache
acute renal failure
granulocytopenia, and proteinuria
Dysgeusia

Question 22

Beta blockers
Major contraindications

Answer 22

Mild antihypertensives (used mostly in stage 1)
Contraindicated in asthma

Question 23

Classes of calcium channel blockers, and examples

Answer 23

1. Phenyl alkylamine: Verapamil
2. Benzothiazepine: Diltiazem
3. Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine, Lacidipine, Lercanidipine, Benidipine