IntroductionAngina pectoris (or chest pain) is a symptom experien ced due to myocardial ischemia, wherein the blood supply to the heart decreases. As a result, theheart muscles do not get sufficient oxygen and nutrient s, and fails to work properly.The following two types of angina are mainly seen:1) Classic Angina (Angina of Exercise): This angina pain occurs w hen the demand of oxygen exceeds the s upply of oxygen, most commonly due to diminished coronary flow.2) Vasospastic (Prinzmetal’s or Variant) Angina: This angina pain occurs at rest and is characterised by reversible coronary vasospasm , which in tu rn reduces the supply of oxygen. Some individuals however show mixed angina, characterised by both exercise -induced and resting attacks of angina.
harmacology of Drugs Acting on CVS (Chapter 1) 41* *Patients may also suffer from symptoms like: 1) Weakness, 2) Heartburn,3) Cramping, 4) Indigestion,5) Sweating, 6) Nausea, and7) Shortness of breath. Anti-anginal drug therapy aims at restoring the balance between the supply and demand of oxygen in the ischemic area of the myocardium.1.4.2. Classification The anti-anginals are divided into the following groups: 1) Vasodilator Drugsi) Organic Nitrites and Nitrates : Amyl ni trite, Isosorbide dinitrate,Isosorbide mononitrate, and Nitroglycerine.ii) Calcium Channel Blockers : Amlodipine, Nifedipine, Diltiazem, andVerapamil.iii) Potassium Channel Opener: Nicorandil.2) -Adrenoceptor Antagonists (-Blockers): Atenolol, Metoprolol, Nadolol, and Propranolol.3) Metabolic Modifiers: Ranolazine and Trimetazidine.1.4.3. Organic Nitrites and NitratesOrganic nitrites and nitrates are simple nitric and nitrous acid esters of glycerol having dif ferent volatilities (e.g., isosorbide dinitrate and isosorbide mononitrate are so lids at room temperature, nitroglycerine is moderately volatile, and amyl nitrite is highly volatile). These compounds are used in angina pectoris. They rapidly reduce the myocardial oxygen demand, followed by rapid relief of symptoms. They are effective in classic as well as in variant angina pectoris.18.104.22.168. Mechanism of ActionNitrates inhibit coronary vasoconstriction or spasm as a result of which perfusion of the myocardium increases, thus, relieving vasospastic angina. Nitrates also cause venodilation, resulting indecreased preload and myocardial oxygen consumption. Due to this action, nitrates are effectively used in classic angina.It is believed that organic nitrates ( e.g., nitroglycerine) act on vascular smooth muscles and relax them by their intracellular conversion to nitrite ions and then to nitric oxide. It results in activation of guanylate cyclase and elevates the levels of cGMP. This leads to dephosphorylation of the myosin light chain, causing vascular smooth muscle relaxation
Therapeutic UsesDrugs categorised under class organic nitrates are used for treating the ischemic symptoms of angina and for congestive heart failure.22.214.171.124. Adverse EffectsThe most common adverse effects of organic nitrates caused by excessive vasodilatation include headache, hypotension, dizziness, and reflex tachycardia.126.96.36.199. Individual DrugsSome commonly used organic nitrates and nitrites are described below:1) Nitroglycerine: It is t he drug of choice for angina pectoris since it is effective, fast acting, and economic. If taken via sub -lingual route , it actsrapidly and its action lasts for an hour.Mechanism of ActionNitroglycerine acts by dilating the blood vessels , thus affecting the vascular smooth muscles. It decreases the cardiac oxygen demand in case of stable angina, and increases the oxygen supply in variant angina. Nitroglycreine is also available in the form of patches and topical ointment. Its transdermal patches are used once daily due to their slower but longer effect.Therapeutic UsesNitroglycerine is administered sublingually for the treatment of acute anginal pain or for prevention of angina; w hile it’s intravenous administration helps to reduce hypertension.Adverse EffectsNitroglycerine causes headache (due to vascular dilation), syncope (due to postural hypotension and reflex tachycardia), apprehension, blurred vision, weakness, vertigo, and dizziness. Some serious adverse effects are circulatory collapse and anaphylactic reactions.2) Isosorbide Mononitrate and Isosorbide Dinitrate: These drugs providelonger duration of action than nitroglycerine. Isosorbide mononitrate is available as chewable tablets; while isosorbide dinitrate is formulated assublingual tablets.Both isosorbide mononitrate and isosorbide dinitrate are long -acting nitrates. The former does not undergo the first-pass metabolism. It decreases pre-load, left ventricular end volume, diastolic pressure, and thus the m yocardial oxygen consumption. The latter relaxes the vascular smooth muscles to dilate the peripheral blood vessels. Both the drugs effectively treat all types of angina pectoris. Isosorbide dinitrate relieves acute anginal attack and manages long -term a ngina pectoris. Isosorbide mononitrate is not used to treat acute attacks of angina.The most common adverse effects of these drugs are headache, hypotension,facial flushing, dizziness, nausea, vomiting, fatigue, and weakness. The adhesives used in transdermal patches can produce allergic reactions, and the sublingual dosage forms can cause burning or stinging under the tongue.
Calcium Channel BlockersThe following f our chemically distinct classes of calcium channel blockers arecurrently used to treat angina: 1) Phenylalkylamines: Verapamil.2) Benzothiazepines: Diltiazem.3) Dihydropyridines: Nifedipine, Nimodipine, and Nicardipine.4) Diarylaminopropylamine Ethers: Bepridil.188.8.131.52. Mechanism of ActionCCBs act by blocking the voltage -sensitive calcium channels. They act on the inner side of the membrane and bind to the channels in depolarised membrane .As a result of drug binding , the channels open rarely after depolarisation. A marked decrease in transmembrane Ca2+ion current relaxes the smooth muscles.184.108.40.206. Therapeutic UsesCCbs are used for the treatment of stable as well as variant angina. In variant angina, they cause relaxation of coronary artery spasm , thus increasing the cardiac oxygen supply; while in stable angina, they cause relaxation of peripheral arterioles, resulting in decreased afterload and cardiac oxygen demand. Verapamil and diltiazem moderately reduce oxygen demand by suppressing the heart rate and contractility.220.127.116.11. Adverse EffectsCCBs give rise to c ardiovascular adverse effects. Blood pressure reduces due to dilation of peripheral arterioles , resulting in induced reflex tachycardia. This reaction mainly occurs with nifedipine and rarely with verapamil and diltiazem. Due to their suppressant effects o n the heart, verapamil and diltiazem should be used carefully in patients taking β-blockers and suffering from bradycardia, heart failure, or AV block. 18.104.22.168. Individual DrugsSome commonly used CCBs are described below:1) Verapamil: It is a calcium channel blocker of class IV anti -arrhythmic agent. It acts by inhibiting the voltage-dependent calcium channels. Due to its effect on L-type calcium channels in the heart, ionotropy and chronotropy is reduced, which further reduces heart rate and blood pressure.Verapamil is used for the treatment of hypertension and angina.The common adverse eff ects of v erapamil are myocardial depression, heart failure, and oedema. Peripheral vasodilating effects may also occur which reduces the afterload and blood pressure. The peripheral effects of verapamil include headache, reflex tachycardia, and fluid retention.2) Nifedipine: This drug is a long – as well as short -acting 1,4-dihydropyridine calcium channel blocker. It acts by decreasing the contractility of arterial smooth muscles and also vasoconstriction by inhibiting the influx of Ca2+ ions through L-type calcium channels.