Cvs pharm

Quinidine causes a fall in blood pressure due to alpha-adrenergic blocking and direct myocardial depressant effects. It also prolongs the QRS complex and QT interval on the ECG.

The important adverse effects of Quinidine include diarrhea, thrombocytopenia, fall in blood pressure, torsades de pointes, and in rare cases, hepatitis and fever. Large doses can lead to 'cinchonism', which manifests as tinnitus, deafness, headache, blurring of vision, diplopia, photophobia, confusion, delirium, disorientation, and psychosis.

Procainamide, like Quinidine, is a class IA antiarrhythmic drug, but it does not have anticholinergic and alpha-adrenergic blocking effects. It is also metabolized in the liver by acetylation, producing a major metabolite, N-acetyl procainamide (NAPA), which has K+ channel-blocking activity.

The main adverse effects of Procainamide include hypotension (due to ganglion blockade), heart block, nausea, vomiting, mental confusion, depression, hallucinations, and psychosis. Long-term use can lead to a lupus-like syndrome with arthralgia and arthritis.

Disopyramide is primarily used for the treatment of ventricular arrhythmias and can also be used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter.

• Adenosine
• Verapamil
• Esmolol

In the SA node, phase 0 is due to slow inflow of Ca2+ ions through activated calcium channels, and these cells undergo spontaneous depolarization. In contrast, Purkinje fibres have a rapid depolarization phase primarily due to the influx of Na+ ions and also exhibit spontaneous depolarization.

Automaticity is the ability of cardiac cells to undergo spontaneous depolarization, with the SA node being the fastest, thus acting as the heart's pacemaker.

The two main types of arrhythmias are tachyarrhythmias (due to increased automaticity, after depolarization, or re-entry of an impulse) and bradyarrhythmias (due to reduced automaticity or abnormal slowing/blockade of impulse conduction).

The four classes of antiarrhythmic drugs are:

1. Class I: Na+ channel blockers

   • IA: Quinidine, procainamide, disopyramide
   • IB: Lignocaine, mexiletine
   • IC: Flecainide, propafenone

2. Class II: β-adrenergic blockers (e.g., propranolol, atenolol)

3. Class III: Drugs that prolong the duration of action potential (e.g., amiodarone, sotalol)

4. Class IV: Calcium channel blockers (e.g., verapamil, diltiazem)

Vasodilators help to relieve symptoms of congestion in congestive heart failure by reducing the workload on the heart and improving blood flow. They are often used in combination with other medications such as diuretics, dobutamine, dopamine, digoxin, milrinone, and inamrinone to manage the condition effectively.

Quinidine blocks Na+ channels in the open state, leading to:

• Decreased automaticity
• Decreased excitability
• Reduced rate of phase 0 depolarization
• Decreased conduction velocity

Quinidine blocks potassium channels, which increases the duration of the action potential. It also prolongs the effective refractory period (ERP) by blocking both Na+ and K+ channels, suppresses ectopic foci, and blocks re-entry of impulses.

The effective refractory period (ERP) is the minimal interval between two successive, propagated action potentials, during which a new action potential cannot be initiated.

• Amiodarone
• Verapamil
• Propafenone
• Digoxin

• Esmolol
• Verapamil
• Amiodarone
• Propafenone

• Amiodarone
• Propranolol

• Amiodarone
• Lignocaine

1. HMG-CoA reductase inhibitors (statins): Atorvastatin, pravastatin, pitavastatin, lovastatin, simvastatin, rosuvastatin.
2. Fibric acid derivatives: Gemfibrozil, fenofibrate, bezafibrate, clofibrate.
3. Bile acid–binding resins: Cholestyramine, colestipol, colesevelam.
4. Inhibitor of triglyceride production and lipolysis: Nicotinic acid.
5. Dietary cholesterol absorption inhibitor: Ezetimibe.

Common adverse effects include:

• Urinary retention (especially in benign prostatic hyperplasia)
• Dryness of mouth
• Blurring of vision
• Constipation
• Precipitation of an attack of glaucoma

Lignocaine blocks sodium channels in the inactivated and active states, primarily affecting depolarized (ischaemic) tissues. It decreases automaticity of ectopic foci by reducing the slope of phase 4 depolarization and depresses conduction in depolarized (diseased) tissue, while usually leaving action potential duration unaffected or possibly shortened.

Lignocaine is not effective orally due to extensive first-pass metabolism, which significantly reduces its bioavailability.

Lignocaine is used for the emergency treatment of:

• Ventricular arrhythmias associated with myocardial infarction (MI)
• Digitalis toxicity
• Cardiac surgery

Common adverse effects of mexiletine include:

• Nausea
• Dizziness
• Tremors

Lignocaine's rapid onset and short duration of action allow for immediate therapeutic effects while minimizing prolonged exposure, reducing the risk of toxicity and allowing for quick recovery after treatment is stopped.

Propranolol reduces lignocaine elimination by decreasing hepatic blood flow, which increases the risk of lignocaine toxicity.

Common adverse effects of propafenone include metallic taste, constipation, bradycardia, and bronchospasm. For flecainide, blurring of vision is a common side effect.

Propafenone and flecainide are primarily used for the treatment of supraventricular arrhythmias and can also be used in ventricular arrhythmias. Both drugs are administered orally.

Class II antiarrhythmic agents block the effects of catecholamines on the heart, leading to:

1. Depressed phase 4 depolarization - decreases automaticity in the SA node and ectopic foci.
2. Prolonged refractory period - useful in treating re-entrant arrhythmias involving the AV node (PSVT) and controlling ventricular rate in atrial flutter and atrial fibrillation.

Amiodarone has a broad spectrum of antiarrhythmic activity, including:

• Blocks potassium channels - increases duration of action potential and prolongs refractory period.
• Blocks sodium channels in the inactivated state - decreases conduction mainly in partially depolarized tissue.
• Weak β-adrenergic blocking and calcium channel-blocking actions - decreases heart rate and AV conduction.

The side effects of esmolol include hypotension, dizziness, and bronchospasm in asthmatics.

Sotalol is used to treat life-threatening ventricular tachyarrhythmias and to maintain sinus rhythm in atrial fibrillation. It has additional K+ channel-blocking properties, which prolong the duration of action potential, but can also cause torsades de pointes as an adverse effect.

The bioavailability of amiodarone following oral administration is about 30%.

Amiodarone is used for:

1. Treatment of atrial and ventricular arrhythmias.
2. Maintaining normal sinus rhythm in atrial fibrillation.
3. Preventing recurrent ventricular tachycardia.

Common adverse effects of amiodarone include:

1. CVS: Hypotension, CHF, exacerbation of arrhythmias.
2. Neurological: Peripheral neuropathy.
3. Respiratory: Pulmonary fibrosis.
4. GIT: Nausea, hepatitis.
5. Skin: Photosensitivity, pigmentation.
6. Eye: Corneal deposits.
7. Thyroid: Hypothyroidism, hyperthyroidism (monitor TSH, T3, T4 levels).

Amiodarone has an additive depressant action on the SA and AV nodes when used with beta-blockers or verapamil, potentially leading to SA block and AV block, respectively.

Verapamil blocks both activated and inactivated L-type Ca2+ channels, which:

• Depresses calcium-mediated depolarization.
• Decreases conduction velocity and increases refractory period of the AV node.
• Reduces slope of phase 4 depolarization in the SA node and ectopic foci, leading to bradycardia.

The duration of action of adenosine is less than 1 minute because it is rapidly transported into red blood corpuscles (RBCs) and endothelial cells.

1. Primary or essential hypertension: Most common type with no specific underlying cause.
2. Secondary hypertension: Caused by renal, vascular, endocrine disorders, etc.

A systolic blood pressure of <120 mm Hg and diastolic pressure <80 mm Hg is considered normal BP.

Mean arterial pressure = DBP + 1/3 PP, where PP (pulse pressure) = SBP - DBP.

The major groups of antihypertensive drugs that act on the VMC include:

• Centrally acting sympatholytics: Clonidine, a-methyldopa.
• β-Adrenergic blockers: Atenolol, metoprolol, esmolol, betaxolol, propranolol, timolol.
• β-Adrenergic blockers with additional α-blocking activity: Labetalol, carvedilol, nebivolol.
• α-Adrenergic blockers:
  • Selective: Prazosin, terazosin, doxazosin.
  • Nonselective: Phenoxybenzamine, phentolamine.
• Vasodilators: Hydralazine, minoxidil, diazoxide, fenoldopam, nitroglycerin, sodium nitroprusside.

ACE inhibitors work by inhibiting the generation of angiotensin II, which leads to:

1. Dilation of arterioles
2. Decreased peripheral vascular resistance (PVR)
3. Lowering of blood pressure (BP)

Dihydropyridines (DHPs) are more likely to cause:

• Headache
• Flushing
• Ankle oedema
• Palpitation
• Reflex tachycardia The use of sustained-release preparations can reduce these side effects.

Verapamil and diltiazem should be avoided in patients with cardiac dysfunction due to their cardiac depressant effect, which can exacerbate heart failure or other cardiac issues.

Calcium channel blockers (CCBs) are particularly useful in:

• Elderly patients
• Patients with angina
• Patients with asthma
• Patients with peripheral vascular disease
• Patients with migraine
• Patients with hyperlipidaemia
• Patients with diabetes
• Patients with renal dysfunction

During initial therapy with beta-blockers, cardiac output (CO) decreases, but peripheral vascular resistance may increase. Over time, with chronic therapy, peripheral vascular resistance gradually decreases due to sustained reduction in CO, leading to a fall in blood pressure (BP).

Beta-blockers can be classified into:

1. Selective β-blockers (block only β₁), e.g., atenolol, metoprolol, esmolol, betaxolol.
2. Nonselective β-blockers (block both β₁ and β₂), e.g., propranolol, timolol.

Beta-blockers are mainly useful in:

• Young hypertensives with high renin levels
• Patients with associated conditions such as angina, post-MI, migraine, and psychosomatic disorders
• Patients receiving vasodilators to counteract reflex tachycardia

1. Stable angina (classical angina): Episodes of chest pain associated with exertion.
2. Unstable angina: Angina at rest or increased frequency and duration of attacks, often due to plaque rupture and thrombosis.
3. Prinzmetal angina (variant angina): Angina that occurs at rest due to coronary artery spasm.

Angina occurs due to an imbalance between oxygen supply and oxygen demand by the myocardium.

Treatment strategies to increase oxygen supply include:

• Restore coronary blood flow through: a) Percutaneous intervention (PCI) including stenting b) Coronary artery bypass graft (CABG)
• Relieve vasospasm using drugs such as CCBs and nitrates
• Break thrombi using thrombolytic agents like Streptokinase/urokinase
• Prevent thrombus formation with antiplatelet drugs.

1. Nitrates: Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, erythrityl tetranitrate, pentaerythritol tetranitrate.
2. B-Adrenergic blockers: Propranolol, metoprolol, atenolol, timolol, bisoprolol.
3. Calcium Channel Blockers (CCBs): Verapamil, diltiazem, nifedipine, felodipine, amlodipine, cilnidipine, nitrendipine, nimodipine, lacidipine, lercanidipine.
4. Potassium channel opener: Nicorandil.
5. Others: Antiplatelet agents (low-dose aspirin, clopidogrel, prasugrel), Statins, Trimetazidine, Ranolazine, Ivabradine.

Organic nitrates release nitric oxide (NO), which stimulates guanylyl cyclase, leading to increased cGMP. This results in the dephosphorylation of myosin light chain kinase (MLCK) and a decrease in Ca2+ concentration in the cytosol, causing relaxation of vascular smooth muscle fibers.

Nitrates relieve anginal pain primarily through venodilation, which decreases preload, and arteriolar dilation, which reduces afterload. They also increase oxygen delivery to the myocardium by dilating large coronary vessels and collateral vessels, leading to improved blood flow to ischemic areas.

The pharmacological actions of nitrates on vascular smooth muscle include:

1. Venodilation (predominant effect) - leads to peripheral pooling of blood and decreased venous return to the heart.
2. Arteriolar dilation - reduces peripheral vascular resistance (PVR) and afterload.
3. Dilatation of large coronary vessels and collateral vessels - increases blood flow to ischemic areas and enhances oxygen delivery.

Organic nitrates are readily absorbed through the buccal mucous membrane, skin, and gastrointestinal tract. However, all nitrates except isosorbide mononitrate undergo extensive first-pass metabolism, resulting in very low oral bioavailability. The sublingual route provides rapid onset (2-5 minutes) but has a short duration of action, while the transdermal route is used for prolonged effects. Metabolites are mainly excreted in urine as glucuronide derivatives.

The common adverse effects of nitrates due to extensive vasodilatation include:

• Headache
• Postural hypotension
• Tachycardia
• Palpitation
• Weakness
• Flushing
• Rarely, syncope To avoid these symptoms, patients may spit out the tablet as soon as pain is relieved. Overdosage may lead to methaemoglobinaemia.

Tolerance to nitrates can occur with prolonged use, but it is rare with intermittent exposure. It is due to decreased NO generation, depletion of sulphydryl radicals, or generation of free radicals. To prevent tolerance, a nitrate-free interval of 8-12 hours each day is recommended.

Isosorbide mononitrate is preferred over isosorbide dinitrate for chronic prophylaxis of angina because it has:

• Longer duration of action
• High oral bioavailability, as it does not undergo first-pass metabolism.

For an acute attack of angina, nitroglycerin is the drug of choice. It is commonly administered sublingually with an initial dose of 0.5 mg, which usually relieves pain in 2-3 minutes. Patients are advised to spit out the tablet as soon as the pain is relieved to avoid side effects. If pain persists, the tablet can be repeated after 5 minutes, but not more than three tablets should be taken in 15 minutes. Sublingual isosorbide dinitrate can also relieve acute angina attacks.

Nitrates are used for:

1. Acute angina attacks:

   • Nitroglycerin (sublingual) is the drug of choice.
   • Isosorbide dinitrate (sublingual) can also be used.

2. Prophylaxis of angina:

   • Longer acting preparations like isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin sustained-release formulations are used.
   • Transdermal nitroglycerin provides prolonged effects (up to 24 hours) but should be removed for at least 8 hours to avoid tolerance.

Variant angina, caused by coronary vasospasm, is treated with nitrates. For prophylaxis, a combination of nitrates and calcium channel blockers (CCBs) such as amlodipine, nifedipine SR, and diltiazem is effective. The addition of a CCB can enhance treatment outcomes.

Glyceryl trinitrate (GTN) can be administered in the following forms and dosages:

• Sublingual: 0.5 mg (500 mcg)
• Lingual spray: 0.4 mg (400 mcg)
• Transdermal patch: 5-10 mg
• Oral sustained release (SR): 5-15 mg

Duration of action: 10-30 minutes for sublingual and lingual spray; up to 24 hours for transdermal patch (should be removed for a few hours each day to avoid tolerance).

In the management of unstable angina, nitrates such as sublingual nitroglycerin are usually effective. If pain persists or recurs, intravenous nitroglycerin is administered. Nitrates help by:

• Reducing myocardial oxygen consumption
• Relieving coronary vasospasm

Note: Blood pressure should be monitored during intravenous infusion of nitroglycerin.

For the management of acute myocardial infarction (MI), the following treatments are recommended:

• Intravenous infusion of nitroglycerin for persistent or recurrent ischemic pain and treatment of left ventricular (LV) failure.
• Avoid nitroglycerin in cases of hypotension or if the patient has taken sildenafil or tadalafil in the past 24 hours.

In congestive cardiac failure (CCF), nitrates are used primarily through intravenous infusion of nitroglycerin for acute heart failure. Key points include:

• Monitoring of blood pressure is necessary to avoid hypotension.
• Headache may limit the dose of nitrates.

Sublingual nitroglycerin can be used for:

• Relief of biliary colic: It helps relieve biliary spasm and associated pain.
• Cyanide poisoning: Although the oxygen carrying capacity of blood is not affected, nitroglycerin may be used as part of the management strategy.

The main objective is to inactivate cyanide in the cells, preventing it from binding to cytochrome oxidase and inhibiting oxidative phosphorylation.

1. Amyl nitrite and sodium nitrite are administered to convert haemoglobin to methaemoglobin.

2. Methaemoglobin combines with cyanide to form cyanomethaemoglobin.

3. Intravenous sodium thiosulphate converts cyanomethaemoglobin to sodium thiocyanate, which is rapidly excreted in urine.

Beta-blockers provide negative chronotropic and negative inotropic effects, which help to improve exercise tolerance and reduce the frequency of anginal episodes.

Beta-blockers without intrinsic sympathomimetic activity should be started early and continued indefinitely, as they decrease mortality in these patients. Cardioselective beta-blockers are preferred, while those with intrinsic sympathomimetic activity should be avoided as they may worsen angina.

Adverse effects include bradycardia, heart block, and bronchospasm in patients with bronchial asthma.

Beta-blockers can increase left ventricular end-diastolic volume, which may influence cardiac output and myocardial oxygen consumption.

Nifedipine predominantly acts on vascular smooth muscle. Reflex tachycardia and palpitation can be minimized by using a sustained-release preparation or by adding a β-blocker.

Amlodipine has less common side effects of palpitation and reflex tachycardia compared to Nifedipine. It is also more potent and has a longer duration of action than Nifedipine.

Common side effects of Amlodipine include headache and ankle oedema. Ankle oedema is caused by reflex postcapillary constriction, which increases hydrostatic pressure.

Nimodipine has high lipid solubility, freely crosses the blood-brain barrier, and selectively dilates cerebral blood vessels. It is used to prevent cerebral vasospasm and subsequent neurological defects in patients with subarachnoid haemorrhage.

CCBs exert beneficial effects in exertional angina by:

1. Decreasing myocardial O2 consumption through:
   • Decreased heart rate (HR)
   • Decreased force of contraction
   • Decreased afterload
2. Dilation of coronary arteries.

Variant angina is due to coronary spasm. The drugs used for prophylactic treatment include Amlodipine, Nifedipine SR, and Diltiazem, which relieve pain by attenuating the coronary vasospasm.

CCBs are used in unstable angina mainly when symptoms are not relieved by nitrates or β-blockers, or if these drugs are contraindicated.

Verapamil is useful for supraventricular arrhythmias due to its depressant action on the SA and AV nodes. It prolongs the refractory period and decreases the conduction velocity of the AV node, thereby reducing the ventricular rate in conditions like atrial flutter or atrial fibrillation.

DHPs, Diltiazem, and Verapamil are used in hypertension due to their vasodilatory effect, which helps control blood pressure. They can be safely used in hypertensive patients with conditions like asthma, hyperlipidaemia, and renal dysfunction.

The preferred calcium channel blocker for hypertrophic cardiomyopathy is Verapamil, as it improves diastolic function.

Flunarizine is more effective than Verapamil in reducing the frequency of migraine attacks for prophylaxis.

For Raynaud's phenomenon, Nifedipine, Amlodipine, Felodipine, or Diltiazem are used to treat this peripheral vasospastic condition.

Nifedipine is used as a uterine relaxant in cases of premature labour.

Nimodipine is used for the prevention and treatment of cerebral vasospasm and subsequent neurological defects in patients with subarachnoid haemorrhage.

Nicorandil causes arteriolar and venodilation and improves coronary blood flow without developing tolerance. Side effects include headache, hypotension, palpitation, flushing, nausea, vomiting, and mouth ulcers.

For patients with suspected or definite myocardial infarction (MI), Aspirin (162 mg or 325 mg) is administered orally. If the patient is allergic to aspirin, Clopidogrel (300 mg) is given instead. Antiplatelet therapy should be continued once daily.

Ranolazine inhibits the late inward Na+ current, which reduces intracellular Ca2+ overload in the myocardium, decreases contractility and oxygen consumption without altering heart rate and blood pressure.

Trimetazidine inhibits fatty acid oxidation in the myocardium, leading to an increased use of glucose for energy, which decreases myocardial oxygen consumption.

Ivabradine acts on the SA node to decrease heart rate, which in turn reduces myocardial oxygen demand and decreases the frequency of anginal episodes.

Dipyridamole dilates coronary blood vessels and increases blood flow to nonischemic areas, leading to the 'coronary steal' phenomenon where blood flow is diverted away from ischemic regions.

The combination increases effectiveness and reduces adverse effects by counteracting the increase in LV end-diastolic volume, preventing coronary spasm, and blocking reflex tachycardia.

Combining β-blockers with verapamil or diltiazem may cause an additive depressant effect on the SA node, AV node, and cardiac contractility, potentially leading to heart block, heart failure, or cardiac arrest.

The combination of CCBs and nitrates results in an additive reduction in myocardial oxygen demand and improved coronary blood flow, making it useful in severe variant angina.

β-blockers can block the reflex tachycardia associated with nifedipine, preventing coronary vasospasm and enhancing the effectiveness of the treatment for classical angina.

B-blockers can exacerbate cardiac failure, peripheral vascular disease, and may precipitate bronchospasm in patients with bronchial asthma. They should not be withdrawn abruptly as this may lead to dangerous arrhythmias or myocardial infarction (MI).

B-blockers are contraindicated in variant angina because blockade of β2-receptors leads to unopposed α1-mediated vasoconstriction, which can aggravate variant angina due to coronary vaso-spasm.

1. Phenylalkylamine: Verapamil.
2. Benzothiazepine: Diltiazem.
3. Dihydropyridines (DHPs): Nifedipine, amlodipine, cilnidipine, nicardipine, felodipine, isradipine, nisoldipine, lacidipine.

Calcium Channel Blockers primarily block voltage-sensitive L-type Ca2+ channels by binding to the α1-subunit, preventing the entry of Ca2+ into the cell, which inhibits excitation-contraction coupling in the heart and vascular smooth muscle.

Verapamil decreases the force of contraction (negative inotropic effect) and heart rate (negative chronotropic effect), reducing the oxygen requirement of the myocardium. It also depresses the SA node and slows AV conduction (negative dromotropic effect) by prolonging the effective refractory period (ERP).

Dihydropyridines are potent arteriolar dilators that reduce peripheral vascular resistance. They require higher doses for significant cardiac effects, and their cardiac depressant effect is less than that of Verapamil and Diltiazem.

Diltiazem is used in the treatment of angina, hypertension, and supraventricular arrhythmias. It has negative inotropic, chronotropic, and dromotropic effects, and dilates peripheral and coronary arteries.

Nitrates lead to venodilation, which decreases preload, ultimately resulting in decreased end-diastolic volume and pressure.

Beta-blockers decrease heart rate (HR), force of contraction (FOC), and cardiac output (CO), which leads to increased left ventricular end-diastolic volume and pressure.

Nifedipine causes arteriolar dilation and decreases peripheral vascular resistance (PVR), which lowers blood pressure (BP).

Beta-blockers decrease heart rate (HR), but when used with nifedipine, they can cause reflex tachycardia due to the drop in blood pressure.

Nitrates decrease preload, while calcium channel blockers decrease afterload, improving overall cardiac function.

Nitrates decrease preload, calcium channel blockers decrease afterload, and beta-blockers reduce heart rate and force of contraction, leading to decreased cardiac work.

Sildenafil potentiates the vasodilator action of nitrates, which can lead to myocardial infarction (MI) and sudden death. Therefore, nitrates should be avoided for 24 hours after sildenafil intake.

Aspirin, 162 mg or 325 mg orally (chewed and swallowed), is administered at once. If the patient is allergic to aspirin, clopidogrel 300 mg is given instead. The antiplatelet agent should be continued once daily.

Intravenous morphine 10 mg is recommended for pain relief in acute myocardial infarction.

Intravenous nitroglycerin is used for recurrent or persistent pain and to treat left ventricular (LV) failure in acute myocardial infarction.

Reperfusion therapy, which includes primary percutaneous coronary intervention (PCI) or thrombolytic therapy, is used to restore coronary patency and reperfusion of the infarcted area.

The goals of therapy in CCF are to provide relief from symptoms, slow the progression of the disease, and decrease mortality.

In the initial stages of congestive cardiac failure, compensatory mechanisms include increased sympathetic activity, increased renin-angiotensin-aldosterone activity, and myocardial hypertrophy and remodeling.

The basic hemodynamic disturbances in congestive cardiac failure include increased pulmonary capillary pressure (backward failure) leading to dyspnea and orthopnea, and decreased cardiac output (forward failure) resulting in tissue hypoxia.

Treatment strategies for congestive cardiac failure include preload reduction, afterload reduction, and enhancement of the contractile state of the heart.

The drugs that reduce preload in CCF are:

• Nitrates
• ACE inhibitors
• ARBs

The drugs that reduce afterload in CCF include:

• ACE inhibitors
• ARBs
• Other vasodilators

The drugs that increase cardiac output in CCF are:

• Digitalis
• Dobutamine

Diuretics promote the excretion of sodium and water, helping to manage Na+, H₂O retention and reduce oedema in CCF. They are classified into:

1. Loop diuretics: Furosemide, bumetanide, torsemide.
2. Thiazide diuretics: Chlorothiazide, hydrochlorothiazide, metolazone.
3. Aldosterone antagonists: Spironolactone, eplerenone.

The key β-Adrenergic blockers used in CCF include:

• Metoprolol
• Bisoprolol
• Carvedilol
• Nebivolol

Cardiac glycosides, such as Digoxin, increase the force of myocardial contraction, thereby improving cardiac output in patients with congestive heart failure (CCF).

Phosphodiesterase 3 inhibitors, such as Inamrinone and Milrinone, are used in CCF to increase cardiac output and promote vasodilation, improving overall heart function.

Neprilysin inhibitors, such as Sacubitril, enhance the levels of natriuretic peptides, leading to vasodilation and diuresis, which are beneficial in the management of congestive heart failure (CCF).

Nesiritide, a form of brain natriuretic peptide (BNP), is used in CCF to promote vasodilation and diuresis, helping to alleviate symptoms associated with heart failure.

Diuretics promote salt and water excretion, leading to a decrease in circulating volume and preload, which improves cardiac function and relieves symptoms of congestion such as dyspnoea and peripheral oedema.

The commonly used loop diuretic is furosemide. Other loop diuretics include torsemide and bumetanide, which are better absorbed than furosemide. In severe heart failure, intravenous diuretics are required.

Thiazides can be added to loop diuretics in advanced cases of heart failure for a synergistic effect, enhancing diuretic efficacy.

Aldosterone antagonists can be added to loop diuretics in moderate to severe heart failure to increase diuretic efficacy, counteract potassium loss, and improve survival.

Nitrates primarily act as venodilators, reducing preload, which leads to peripheral pooling of blood, decreased ventricular end-diastolic pressure and volume, and ultimately improves tissue perfusion.

At low doses (<2 mcg/kg/min), dopamine selectively dilates these blood vessels by acting on D₁-receptors, increasing GFR and urine output. At moderate doses (2-5 mcg/kg/min), it stimulates B₁-receptors, increasing myocardial contractility and cardiac output, while also enhancing GFR. However, at high doses (>10 mcg/kg/min), it causes generalized vasoconstriction, increasing afterload and reducing blood flow to vital organs.

Dobutamine is used for short-term treatment of acute heart failure and cardiogenic shock. It has a selective inotropic effect, increasing cardiac output with little effect on blood pressure and heart rate due to the counterbalancing effects of a₁-receptor-mediated vasoconstriction and B2-receptor-mediated vasodilation.

Aldosterone antagonists block the action of aldosterone, reducing salt and water retention, decreasing preload, and preventing hypokalaemia. They also mitigate ventricular remodelling and hypertrophy, slowing disease progression and decreasing mortality in moderate to severe heart failure.

Phosphodiesterase 3 inhibitors increase cAMP levels, providing both positive inotropic and vasodilator effects. They are used for short-term treatment of severe heart failure, increasing cardiac output and decreasing afterload. Adverse effects include nausea, vomiting, arrhythmias, and hepatotoxicity, with milrinone being more potent and not causing thrombocytopenia.

Tolvaptan is a vasopressin-receptor antagonist used for short-term therapy to improve symptoms in congestive heart failure with volume overload and severe hyponatraemia.

Nesiritide, a recombinant form of brain natriuretic peptide (BNP), acts as a vasodilator to reduce dyspnoea in acute decompensated heart failure. It is administered intravenously, but hypotension is a common adverse effect.

Sacubitril inhibits neprilysin, which prevents the metabolism of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), leading to vasodilation and diuresis. It is used in combination with valsartan for severe heart failure.

The beneficial effects of Digitalis in CCF include:

1. Positive inotropic effect leading to increased cardiac output (CO).
2. Improved circulation which enhances renal blood flow.
3. Increased Na+ and H2O excretion, relieving oedema and dyspnoea.
4. Increased tissue perfusion, correcting hypoxia.

In atrial fibrillation, Digitalis has both direct and indirect (vagomimetic) actions on the AV node, which include:

• Depressing AV node conduction by increasing effective refractory period (ERP).
• Decreasing conduction velocity, thus reducing the ventricular rate.

Digitalis is preferred in PSVT when associated with heart failure. It helps to:

• Increase vagal tone, which can terminate the arrhythmia.
• However, it has a slower onset of action and is not suitable for acute therapy; adenosine is the preferred drug for PSVT.

Dopamine and dobutamine are used in acute heart failure for:

• Positive inotropic effect, providing symptomatic relief.
• They are particularly effective in patients with ventricular dysfunction.

Digoxin inhibits the sodium/potassium pump, leading to increased intracellular sodium. This reduces the activity of the sodium/calcium exchanger, resulting in increased intracellular calcium and enhancing the force of heart muscle contraction. Additionally, it decreases the oxygen requirement of the myocardium, allowing the heart to perform more work for the same energy expenditure.

In patients with CCF, Digoxin reduces heart rate through a negative chronotropic effect. At small doses, it decreases heart rate by stimulating the vagus nerve. However, in toxic doses, it can increase sympathetic activity, which may lead to an increased heart rate.

At therapeutic concentrations, Digoxin decreases automaticity and increases resting membrane potential in the atria and AV node due to vagal action. It prolongs the effective refractory period (ERP) and decreases conduction velocity in the AV node, which may lead to bradycardia and AV block.

Common adverse effects of Digoxin include gastrointestinal symptoms such as anorexia, nausea, vomiting, and occasionally diarrhea, which are due to gastrointestinal irritation and stimulation of the chemoreceptor trigger zone (CTZ).

Monitoring of serum digoxin levels, electrolyte levels, and electrocardiogram (ECG) is crucial during Digoxin therapy due to its narrow margin of safety and potential for toxicity, which can manifest as gastrointestinal symptoms and cardiac arrhythmias.

CNS effects include headache, confusion, restlessness, disorientation, weakness, visual disturbances, altered mood, and hallucinations.

Digitalis can cause various arrhythmias, including ventricular premature beats, pulsus bigeminy, ventricular tachycardia, AV block, atrial tachycardia, atrial fibrillation, atrial flutter, and severe bradycardia.

Elderly patients are more susceptible to digitalis toxicity due to declining renal and hepatic function.

The first step is to shift the patient to the intensive care unit (ICU).

Potassium chloride (KCl) is the drug of choice for treating tachyarrhythmias when serum K+ levels are normal or low.

Hypokalaemia increases the binding of digoxin to Na+K+-ATPase, enhancing its toxicity.

Supraventricular arrhythmias are treated with oral or intravenous propranolol.

Digoxin antibodies (Digibind) neutralize circulating digoxin/digitoxin and rapidly reverse toxicity, but they are expensive and used only in serious cases.

Cholestyramine and colestipol bind to cardiac glycosides in the gut, reducing their absorption.

Calcium increases the incidence of digoxin toxicity.

ACE inhibitors lead to:

• Decrease in peripheral vascular resistance, increasing stroke volume and improving tissue perfusion.
• Increase in renal blood flow, promoting diuresis and reducing circulating blood volume.
• Decrease in aldosterone production, leading to reduced sodium and water retention and decreased preload.
• Venodilation, which also decreases preload.
• Reduction in pressure in the atria and pulmonary circuit.
• Retardation or reversal of ventricular hypertrophy and remodeling by lowering angiotensin II and aldosterone levels.

Angiotensin Receptor Blockers (ARBs) like losartan and candesartan competitively block AT₁-receptors, preventing the effects of angiotensin II. They produce effects similar to ACE inhibitors and are primarily used in patients who cannot tolerate ACE inhibitors due to side effects such as cough, angioedema, and neutropenia.

Aliskiren decreases plasma renin, angiotensin I, and II levels, which results in a decrease in blood pressure and left ventricular mass. It may also provide beneficial effects in heart failure.

Advantages of Hydralazine include an increase in cardiac output in heart failure patients. Disadvantages include the potential for reflex tachycardia and fluid retention, although tachycardia is rare with mixed arteriolar and venodilators.

Long-term therapy with beta-blockers improves symptoms, reduces hospitalization, and decreases mortality in patients with mild to moderate heart failure. They block beta-receptor-mediated effects of catecholamines, improving left ventricular structure and function, decreasing wall stress, increasing ejection fraction, and reducing left ventricular size. They also decrease apoptosis and ventricular remodeling, and lower the frequency of arrhythmias.

Cardiac glycosides, which consist of an aglycone with sugar moieties, have a potent action on the heart. Their utility in treating heart failure was demonstrated by William Withering, highlighting their importance in cardiovascular pharmacology.

Cardiac glycosides, such as Digitalis, inhibit the Na+K+-ATPase enzyme, leading to increased intracellular Na+. This results in decreased extrusion of Ca2+ via the Na+/Ca2+-exchanger, which increases intracellular Ca2+. The increased Ca2+ enhances myocardial contractility (positive inotropic effect) and cardiac output.

Digitalis has both cardiac and extracardiac pharmacological actions. The cardiac actions include:

1. Direct action: Inhibition of Na+K+-ATPase.
2. Indirect action: Stimulation of the vagus nerve (vagomimetic effect).
3. Positive inotropic effect: Increases the force of myocardial contraction, especially in a failing heart, leading to improved cardiac output and reduced pulmonary congestion.

Digitalis increases myocardial contractility by enhancing the force of contraction of the myocardium, particularly in the failing heart. This leads to complete emptying of the ventricles during systole, increased cardiac output, and reduced diastolic size of the heart, which decreases pulmonary congestion and systemic venous pressure.

Intravenous adenosine binds to specific G-protein-coupled adenosine (A₁)-receptors, activating ACh-sensitive K+ channels in the atrium, SA, and AV nodes. This leads to hyperpolarization and decreased automaticity of the SA node, resulting in a decreased sinus rate. It also reduces the duration of action potential in the atria, increases the refractory period, and slows conduction in the AV node, ultimately blocking re-entry of impulses and terminating PSVT.

Adenosine is preferred for rapid termination of PSVT due to its:

1. High efficacy.
2. Short duration of action, leading to brief adverse effects.
3. Minimal negative inotropic action.

Adverse effects of adenosine include:

• Asystole
• Bronchospasm
• Chest pain
• Dyspnoea
• Flushing
• Hypotension
• Headache
  These side effects are transient due to its short duration of action.

Methylxanthines antagonize the effects of adenosine by blocking its receptors, while dipyridamole inhibits the uptake of adenosine into cells, thereby potentiating its actions.

Intravenous magnesium sulfate is useful in treating torsades de pointes, even with normal serum magnesium levels, and can be used in digitalis-induced arrhythmias if there is hypomagnesaemia.

Atropine is used in the treatment of bradycardia and AV block due to vagal overactivity, such as in acute myocardial infarction and digitalis toxicity, due to its vagolytic action.

Intravenous isoprenaline can be used in cases of second degree or complete heart block following acute myocardial infarction.

ACE inhibitors prevent the effects of angiotensin II by:

1. Decreasing aldosterone production, leading to decreased Na and H₂O retention, which lowers blood pressure (BP).
2. Decreasing sympathetic nervous system activity.
3. Inhibiting the degradation of bradykinin, a potent vasodilator, which contributes to vasodilation.
4. Stimulating the synthesis of vasodilating prostaglandins through bradykinin.
   These actions collectively contribute to their antihypertensive effect and help reverse ventricular and vascular hypertrophy.

The common adverse effects of ACE inhibitors include:

1. Cough (dry cough) due to increased bradykinin levels.
2. Angioedema, which can cause swelling and airway obstruction.
3. Proteinuria, which occurs rarely.
4. Teratogenic effects such as growth retardation and renal failure in pregnancy.
   Mnemonic for adverse effects: 'CAPTOPRIL.'

ACE inhibitors lower blood pressure (BP) by:

• Decreasing aldosterone production, which reduces Na and H₂O retention.
• Decreasing sympathetic nervous system activity.
  Additionally, they reverse ventricular and vascular hypertrophy, contributing to improved cardiac function.

Key pharmacokinetic considerations for ACE inhibitors include:

1. They are usually administered orally.
2. In hypertensive emergencies, enalaprilat can be given intravenously.
3. Food reduces the absorption of captopril; it should be taken 1 hour before meals.
4. ACE inhibitors poorly cross the blood-brain barrier (BBB) and are metabolized in the liver, with excretion occurring in urine.

The prodrugs among the ACE inhibitors listed are Enalapril, Perindopril, Ramipril, Fosinopril, Benazepril, Trandolapril, and Quinapril.

Lisinopril is longer acting than Captopril.

B-Blockers, ACE inhibitors, ARBs

ACE inhibitors, loop diuretics, ARBs

Nonselective B-blockers

Hypertensive emergency involves very high blood pressure with progressive end organ damage, while hypertensive urgency has high blood pressure without end organ damage.

The BP should be reduced by not more than 25% over 1 hour, then to 160/100 mm Hg over the next 2-6 hours, and to normal over the next 48 hours.

Labetalol, nicardipine, nitroglycerin, sodium nitroprusside, furosemide, clevidipine, esmolol, hydralazine, fenoldopam, enalaprilat, phentolamine.

Start i.v. infusion with 5 mg/hour, increase by 2.5 mg/hour every 5 minutes to a maximum of 15 mg/hour.

The maximum dose is 10 mcg/kg/minute.

The selection of antihypertensive drugs depends on:

1. Comorbidity
2. Associated complications
3. Age
4. Sex
5. Cost of the drug
6. Concomitant drugs

The preferred drugs for initial treatment of hypertension include:

• ACE inhibitors
• ARBs
• CCBs
• Thiazides

Therapy for hypertension is usually started with a single agent. If the patient does not respond to a single drug, combination therapy may be used, especially in patients with high blood pressure.

Recommended combinations include:

• ACE inhibitors/ARBs with either thiazides/CCBs/diuretics. If response is not satisfactory, antihypertensives from other classes can be added. Note: ACE inhibitors should not be combined with ARBs, and a combination of non-DHPs (verapamil/diltiazem) with β-blockers should be avoided.

Both Hydrochlorothiazide and Chlorthalidone are indicated for:

• Mild hypertension

Sodium nitroprusside is indicated for:

• Hypertensive emergencies (hypertensive crisis)

a-Methyldopa is indicated for:

• Hypertension during pregnancy

β-blockers may cause:

• Precipitation of congestive cardiac failure (CCF)
• Bronchospasm in susceptible individuals
• Sexual dysfunction in males
• Nightmares
• Caution is advised in diabetes patients receiving hypoglycaemic drugs
• Withdrawal syndrome upon sudden stoppage after prolonged therapy due to sympathetic overactivity

Clonidine acts as a centrally acting antihypertensive drug by stimulating α2A receptors in the vasomotor center of the brain, leading to:

• Decreased sympathetic outflow
• Reduced heart rate (HR) and cardiac output (CO)
• Decreased peripheral vascular resistance (PVR)
• Overall decrease in blood pressure (BP)

Clonidine is useful for:

1. Treating hypertension
2. Managing withdrawal symptoms in opioid and alcohol addicts and aiding smoking cessation
3. Acting as a preanaesthetic agent
4. Serving as an antidiarrhoeal in diabetic neuropathy
5. Reducing postmenopausal hot flushes
6. Prophylaxis of migraine

Withdrawal symptoms after sudden stoppage of clonidine may include:

• Headache
• Nervousness
• Tachycardia
• Sweating
• Tremors
• Palpitations
• Rebound hypertension These symptoms are due to supersensitivity of α-receptors and a precipitous release of stored catecholamines.

Sodium nitroprusside generates nitric oxide (NO), which relaxes vascular smooth muscle leading to vasodilatation. It acts as a venodilator and arteriolar dilator, resulting in pooling of blood in veins, decreased peripheral vascular resistance (PVR), decreased venous return, decreased afterload, decreased preload, and ultimately reduced blood pressure (BP) and cardiac output (CO).

Adverse effects of sodium nitroprusside include vomiting, fatigue, disorientation, and toxic psychosis due to cyanide accumulation, which can lead to severe lactic acidosis and convulsions.

Nitroglycerin is primarily used as a venodilator and is administered intravenously for treating hypertension associated with acute left ventricular failure (LVF) or myocardial infarction (MI). It acts rapidly, but tolerance can develop after prolonged infusion.

Fenoldopam is a D₁ agonist that causes dilatation of peripheral arteries and promotes natriuresis, making it useful in hypertensive emergencies and postoperative hypertension. Adverse effects may include headache, flushing, and reflex tachycardia.

Nonpharmacological approaches to control hypertension include:

1. Weight reduction
2. Sodium restriction
3. Alcohol restriction
4. Exercise
5. Mental relaxation
6. Cessation of smoking
7. Consumption of a potassium-rich diet

ACE inhibitors delay or prevent the progression of renal complications in patients with diabetes. They are also preferred in hypertensives with coexisting congestive heart failure (CHF), left ventricular hypertrophy, and peripheral vascular disease.

ACE inhibitors should be started within 24 hours in patients with MI, as they have shown both short-term and long-term improvement in survival and decrease in reinfarction.

ACE inhibitors should be prescribed to all patients with impaired left ventricular (LV) function to improve outcomes.

Both ACE inhibitors and ARBs decrease systemic blood pressure, dilate the renal efferent arteriole, reduce intraglomerular pressure, inhibit angiotensin II-mediated mesangial cell growth, and decrease microalbuminuria in diabetic nephropathy patients.

Main ARBs include losartan, irbesartan, candesartan, olmesartan, valsartan, and telmisartan. They competitively inhibit the binding of angiotensin II to the AT₁ receptor subtype, blocking its effects, and do not affect bradykinin degradation.

Common adverse effects of ARBs include headache, hypotension, weakness, rashes, nausea, vomiting, and teratogenic effects. They may also cause hyperkalaemia in patients with renal failure or those on potassium-sparing diuretics, but are less likely to produce cough or angioedema compared to ACE inhibitors.

ARBs are used in hypertension, congestive cardiac failure (CCF), myocardial infarction (MI), and diabetic nephropathy. They are particularly indicated for patients who develop cough with ACE inhibitors and are used in CCF and MI for those intolerant to ACE inhibitors.

Aliskiren inhibits renin, preventing the conversion of angiotensinogen to angiotensin I, thereby affecting the renin-angiotensin system.

Minoxidil is a powerful arteriolar dilator used in hypertension treatment. It is effective orally and is often combined with a β-blocker and a diuretic to counteract side effects such as reflex tachycardia and sodium and water retention. Additionally, topical minoxidil is used to promote hair growth in male pattern baldness.

Diazoxide is used in the treatment of hypertensive emergencies and is administered intravenously. It has a long duration of action (6-24 hours) and relaxes uterine smooth muscle. Adverse effects include reflex tachycardia, hyperglycemia, and sodium and water retention.

Hydralazine, a directly acting arteriolar dilator, can cause side effects such as reflex tachycardia, palpitation, sodium and water retention, headache, hypotension, flushing, angina, myocardial infarction, and lupus syndrome. These side effects can be managed by combining hydralazine with a diuretic and a β-blocker.

Sodium nitroprusside is a powerful arteriolar and venodilator that is administered via intravenous infusion. It rapidly decomposes on exposure to light, so the solution must be prepared fresh, and the infusion bottle should be covered with black paper. It has a short duration of action and is titrated according to response, with no tolerance developing to its effects.

α-Methyldopa is converted into α-Methylnoradrenaline, which acts as a false transmitter. It stimulates α2-receptors in the vasomotor center, leading to a decrease in blood pressure (↓↓↓BP) and a reduction in peripheral vascular resistance (↓PVR).

Common adverse effects of α-Methyldopa include nasal stuffiness, headache, sedation, mental depression, dryness of mouth, bradycardia, impotence, gynaecomastia, hepatitis, and rarely hemolytic anemia.

α-Methyldopa is one of the preferred antihypertensive drugs during pregnancy due to its safety profile.

Selective α₁-blockers, such as Prazosin, block only α₁-vascular receptors, leading to vasodilation and a fall in blood pressure without increasing noradrenaline levels, thus minimizing tachycardia. In contrast, nonselective α-blockers block both α₁- and α₂-receptors, causing vasodilation and a fall in blood pressure, but also increasing noradrenaline release, which can lead to prominent tachycardia.

The first-dose phenomenon refers to postural hypotension that occurs after the first dose of Prazosin. To mitigate this effect, the initial dose should be small (1 mg).

Hypotension may occur following the first dose of ACE inhibitors in these patients.

Neutropenia is a rare side effect associated with ACE inhibitors.

Rashes may occur, but discontinuation of the drug is not required for itching.

Loss of taste sensation, also known as dysgeusia, may occur as a side effect.

ACE inhibitors are contraindicated in patients with bilateral renal artery stenosis and in patients with a single kidney with renal artery stenosis.

Simultaneous administration of ACE inhibitors and potassium-sparing diuretics can cause dangerous hyperkalaemia.

NSAIDs inhibit prostaglandin synthesis, promoting sodium and water retention, which decreases the antihypertensive effect of ACE inhibitors.

ACE inhibitors are used to treat all grades of hypertension and decrease cardiovascular and cerebrovascular morbidity and mortality.

Resins bind bile acids in the gut, interrupting their enterohepatic circulation, which promotes the conversion of cholesterol to bile acids in the liver. They also stimulate the formation of hepatic LDL-receptors, leading to increased uptake of LDL-cholesterol from circulation, resulting in reduced LDL levels with little effect on HDL levels.

Common adverse effects of resins include unpalatability, bloating, nausea, flatulence, and constipation. They can also bind to other drugs in the gut, reducing their absorption.

Fibrates are primarily used in the treatment of type III hyperlipoproteinaemia and severe hypertriglyceridaemia.

Fibrates activate peroxisome proliferator-activated receptor alpha (PPAR-alpha), which leads to increased HDL levels, enhanced lipoprotein lipase synthesis and activity, increased clearance of VLDL, and decreased plasma triglyceride levels. They also inhibit triglyceride synthesis in the liver.

Common side effects of fibrates include dyspepsia, nausea, vomiting, diarrhea, muscle pain, and headache. There is also an increased incidence of gallstones with clofibrate.

Niacin reduces plasma triglycerides, VLDL, and LDL levels, while increasing HDL levels. It also decreases lipoprotein(a).

Niacin inhibits lipolysis in adipose tissue, which reduces hepatic triglyceride (TG) and VLDL synthesis, leading to decreased VLDL and triglyceride levels.

The main adverse effects of niacin include flushing, dyspepsia, itching, headache, hyperpigmentation, peptic ulcer, hyperuricaemia, hepatotoxicity, hyperglycaemia, and rarely atrial arrhythmias.

Ezetimibe inhibits the absorption of dietary and biliary cholesterol in the intestine, leading to a reduction in LDL cholesterol levels.

The combination of ezetimibe and statins prevents the increase in cholesterol absorption caused by statins and the increased cholesterol synthesis caused by ezetimibe, resulting in an additive reduction in LDL cholesterol levels.

Monoclonal antibodies such as alirocumab and evolocumab inhibit PCSK9, which increases hepatic clearance of LDL and lowers plasma LDL levels, and are used as adjuncts to statin therapy.

Statins competitively inhibit HMG-CoA reductase, which is the rate-limiting step in cholesterol biosynthesis. This inhibition leads to a decrease in blood LDL and VLDL levels, increases LDL receptors in the liver, and enhances LDL uptake and degradation, effectively reducing plasma LDL levels.

The common adverse effects of statins include:

1. Hepatotoxicity - dose-related increase in serum transaminase levels.
2. Headache and sleep disturbances.
3. Myopathy - muscle pain and weakness, with raised plasma creatinine kinase activity; rhabdomyolysis may occur.
4. Gastrointestinal issues - anorexia, nausea, vomiting, and diarrhea.

Statins should not be taken during pregnancy.

Statins are primarily used for:

• Treatment of primary hyperlipidaemias with increased LDL and cholesterol levels.
• Management of secondary hyperlipidaemias due to conditions such as diabetes or nephrotic syndrome.

Statins can interact with:

• Cyclosporine, erythromycin, and azoles, which inhibit the metabolism of statins (except pravastatin). This can lead to increased blood levels of statins and a higher incidence of myopathy.

In addition to lowering cholesterol, statins have several other actions:

• Atherosclerotic plaque stability
• Antioxidant and anti-inflammatory effects
• Decrease in platelet aggregation
• Increase in production of NO by endothelium

These actions contribute to the cardioprotective effects of statins.

• Decrease heart rate (HR), force of contraction (FOC), and cardiac output (CO), leading to lower blood pressure (BP).
• Decrease renin release and sympathetic outflow from the CNS, further reducing BP.
• Depress SA node and AV nodal activity, decreasing conduction in the atria and AV node.
• Increase refractory period of the AV node and decrease automaticity of ectopic foci.
• Reduce cardiac work and oxygen requirement of the myocardium.

• Hypertension
• Prophylaxis of stable angina
• Management of cardiac arrhythmias (e.g., atrial fibrillation, paroxysmal supraventricular tachycardia)
• Treatment of myocardial infarction
• Congestive cardiac failure (e.g., metoprolol, nebivolol, carvedilol)
• Pheochromocytoma
• Hypertrophic obstructive cardiomyopathy
• Dissecting aortic aneurysm
• Other uses include glaucoma, hyperthyroidism, migraine prophylaxis, essential tremors, acute anxiety states, and alcohol withdrawal.

• Bradycardia
• AV block
• Bronchospasm
• Sedation
• Fatigue
• Muscular weakness
• Mental depression
• Masking of symptoms and signs of hypoglycemia, especially in diabetic patients.

• Potent arteriolar dilators, decreasing peripheral vascular resistance (PVR) and afterload, leading to lower blood pressure (BP).
• Induce coronary vasodilatation with minimal direct effect on the heart.
• Reflex tachycardia and palpitation may occur, especially with nifedipine, but can be minimized with sustained release preparations or by adding a β-blocker.

• Stable angina
• Variant angina
• Unstable angina
• Hypertension
• Raynaud's phenomenon
• Subarachnoid hemorrhage (e.g., nimodipine)
• Other uses include management of premature labor.

• Postural hypotension
• Palpitation
• Reflex tachycardia
• Ankle edema
• Flushing
• Fatigue
• Sedation.

• Prophylaxis of stable angina
• Variant angina
• Unstable angina
• Hypertension
• Supraventricular arrhythmias (AF, AFI, PSVT)
• Hypertrophic cardiomyopathy Other uses: Prophylaxis of migraine

• Headache
• Hypotension
• Bradycardia
• Oedema
• AV block

• Mainly venodilators → Preload
• Arteriolar dilators → Afterload
• Dilate large coronary vessels and collateral vessels
• Have no direct action on heart

• Acute attack of angina
• Prophylaxis of angina (isosorbide mononitrate orally, isosorbide dinitrate orally, nitroglycerin-oral SR preparation/ointment/disc/patch)
• Variant angina (nitrates)
• Unstable angina (NTG: s.l./i.v.)
• Acute MI (NTG: i.v. infusion)
• Acute heart failure (i.v. NTG)
• Hypertensive emergency (i.v. NTG infusion) Other uses: Biliary colic, Cyanide poisoning

Phenoxybenzamine is a nonselective, irreversible α-receptor blocker that also inhibits the reuptake of norepinephrine into adrenergic nerve endings. It is mainly used as a venodilator and for treating pheochromocytoma, particularly in preoperative and inoperable cases.

The adverse effects of Phentolamine include tachycardia, palpitation, arrhythmias, angina, and myocardial infarction (MI).

Prazosin is primarily used for the treatment of hypertension as a selective α₁-receptor blocker.

The adverse effects associated with Terazosin include first dose postural hypotension, nasal congestion, tachycardia, impaired ejaculation, and impotence.

Tamsulosin is a uroselective α₁ (α₁A) receptor blocker primarily used for benign prostatic hyperplasia (BPH).

PDE-5 inhibitors increase levels of cGMP by inhibiting the enzyme PDE, leading to:

1. Relaxation of smooth muscle of corpus cavernosum
2. Increased inflow of blood
3. Penile erection

Additionally, Sildenafil is used for pulmonary hypertension and treats erectile dysfunction.

The common side effects of intravenous adenosine include:

• Asystole
• Bronchospasm
• Chest pain
• Dyspnoea
• Flushing
• Hypotension
• Headache
• Expensive

Amiodarone has a broad spectrum of antiarrhythmic activity and is used for both ventricular and supraventricular arrhythmias. Its side effects include:

• Hypotension
• Peripheral neuropathy
• Pulmonary fibrosis
• Nausea
• Hepatitis
• Photosensitivity
• Corneal deposits
• Hypothyroidism and hyperthyroidism

Lignocaine is a Class IB antiarrhythmic drug that:

• Blocks Na+ channels in the inactivated and active states
• Decreases automaticity of ectopic foci
• Depresses conduction in depolarized tissue
• Usually does not affect or may shorten action potential duration

It is used for ventricular arrhythmias associated with MI, digitalis toxicity, and cardiac surgery. Side effects include:

• Headache
• Drowsiness
• Nystagmus
• Blurred vision
• Confusion
• Convulsion

• Direct action by inhibiting Na+ K+-ATPase
• Indirect action by stimulating vagus (vagomimetic effect)
• Positive inotropic effect
• Decreases heart rate by direct and indirect actions
• At therapeutic concentration, decreases automaticity, prolongs ERP, and decreases conduction velocity in AV node
• At higher concentration, increases automaticity in cardiac tissue by direct action and by increasing sympathetic activity

• Congestive cardiac failure (low output failure)
• Atrial fibrillation
• Atrial flutter
• Paroxysmal supraventricular tachycardia (PSVT)

• Digitalis can cause any type of arrhythmias
• Ventricular premature beats
• Pulsus bigeminy
• Ventricular tachycardia
• AV block
• Atrial tachycardia
• Atrial fibrillation
• Atrial flutter
• Severe bradycardia
• Anorexia
• Nausea
• Vomiting
• Headache
• Confusion
• Restlessness
• Disorientation
• Weakness
• Visual disturbance

They cause vasodilation mainly in pulmonary, coronary, and renal blood vessels.

They are used for the treatment of pulmonary arterial hypertension.

• Increase in hepatic amino-transferases
• Headache
• Flushing due to vasodilation

It decreases the viscosity of blood and improves microcirculation.

It is used for peripheral vascular disease.

• Nausea
• Vomiting

It inhibits PDE 3, causing vasodilation and inhibiting platelet aggregation.

It is used for peripheral vascular disease.

• Nausea
• Vomiting
• Headache