unit 05 (C) Anti Anginal Drugs, Educational Platform.pptx

unit 05 (C) Anti Anginal Drugs, Educational Platform.pptx

1. Anti Anginal Drugs By: Muhammad Aurangzeb Lecturer-INS/KMU

2. Objectives By the completion of this section the learners will be able to: Discuss the main classes of drugs that are used for treating AP. Discuss the nursing responsibility of each class of drugs. Calculate the drug dosage accurately while administering oral and parenteral medications. Abdullah Danish, Educational Platform

3. Angina pectoris (AP) Angina pectoris – chest pain due to imbalance between the oxygen requirement of the heart and oxygen supplied to it via the coronary vessels. Abdullah Danish, Educational Platform

4. Definition of terms Angina Pectoris – is the principal symptoms of patient with ischemic heart disease. Manifested by sudden, severe, pressing substernal pain that often radiates to the left shoulder and along the flexor surface of the left arm. Usually precipitated by exercise, excitement or a heavy meal. Abdullah Danish, Educational Platform

5. Cont… Myocardial ischemia which produces a ngina results from imbalances in myocardial oxygen supply & demand relationship such as decreased oxygen supply and/or increased oxygen demand. Etiology Decrease oxygen supply Increase demand for oxygen Abdullah Danish, Educational Platform

6. Types of angina Atherosclerotic angina (classic angina [common form]) : Attacks are predictably provoked (stable angina) by exercise, emotion, eating and subside when the increased energy demand is withdrawn. Rest, by reducing cardiac work, usually leads to complete relief of the pain within 15 min. Atherosclerotic angina constitutes about 90% of angina cases. S econdary to advanced atherosclerosis of the coronary vessels A ssociated with ST-segment depression on ECG Abdullah Danish, Educational Platform

7. Types of angina V asospa s t i c angi n a ( r e s t angina, variant angina, or Prinzmetal’s angina [uncommon form]) : Attacks occur at rest or during sleep. Vasospastic angina is responsible for less than 10% of angina cases. A ssociated with ST-segment elevation on ECG S econdary to vasospasm of the coronary V essels Coronary artery calibre changes in classical and variant angina Abdullah Danish, Educational Platform

8. Types of Angina Unstable angina (crescendo angina, also known as acute coronary syndrome) : It is characterized by increased frequency and severity of attacks that result from a combination of atherosclerotic plaques, platelet aggregation at fractured plaques, and vasospasm. the duration of manifestation is longer than the first two and has the manifestation of Myocardial infarction R e f ere n ce : Drug s Used in t h e T r e a t m e n t o f Ang i n a P e c t o ri s . In : T r ev o r A J , K a t z un g BG, K ru i d eri n g -Hall M. e d s. K at z un g & T r e vor's Phar m a c o l ogy : E x am i na t i o n & B oar d R e vi e w , 1 1 e N e w Y o rk, N Y : M c G r a w -Hill; 2 1 5 . Abdullah Danish, Educational Platform

9. T r e a tme n t of Angina P ec t oris D r ug s use d in angi n a e xp l o it t w o main s t r at egie s: r educt io n o f o x y g en de m and i nc r ease o f o x y g en de li v e r y t o the m y o c a r d i um Abdullah Danish, Educational Platform

10. Classifi c a tion of a n tianginal drugs Nitrates Short acting: Glyceryl trinitrate (GTN, Nitroglycerine) Long acting: Isosorbide dinitrate (short acting by sublingual route), Isosorbide, mononitrate, β Blockers: Propranolol, Metoprolol , Atenolol and others. Calcium channel blockers Phenyl alkylamine : Verapamil Benzothiazepine : Diltiazem Dihydropyridines: Nifedipine,, Amlodipine, Nitrendipine , Nimodipine , Abdullah Danish, Educational Platform

11. Classifi c a tion of a n tianginal drugs Clinical classification Used to abort or terminate attack: GTN ( angisid ), Isosorbide dinitrate (sublingually). Used for chronic prophylaxis: All other drugs. Abdullah Danish, Educational Platform

12. Antianginal drugs I. Agents which ↓ O 2 demand & ↑ O 2 Supply A. Nitrates B. Calcium channel blockers II . Agents which ↓ O 2 demand Beta blockers Abdullah Danish, Educational Platform

13. Nit r a t es / O r g anic Nit r a t es Preload reduction: Peripheral pooling of blood → decreased venous return (preload reduction). Afterload reduction: Nitrates also produce some arteriolar dilatation → slightly decrease total peripheral resistance or afterload on heart. Redistribution of coronary flow: In the arterial tree, nitrates preferentially relax bigger conducting ( angiographically visible) coronary arteries than arterioles or resistance vessels. Abdullah Danish, Educational Platform

14. Nit r a t es / O r g anic Nit r a t es Mechanism of action: The organic nitrate agents are prodrugs that are sources of NO. NO activates the soluble isoform of guanyl cyclase , thereby increasing intracellular levels of cGMP . In turn, cGMP promotes the dephosphorylation of the myosin light chain and the reduction of cytosolic Ca 2+ and leads to the relaxation of smooth muscle cells in a broad range of tissues. References: Eschenhagen T. Treatment of Ischemic Heart Disease. In: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e New York, NY: McGraw-Hill Abdullah Danish, Educational Platform

15. Nitrates Coronary artery dilatation Decrease coronary bed resistance (Relieved coronary vasospasm) Increase coronary blood flow Increase oxygen supply Abdullah Danish, Educational Platform

16. Nitrates Reduction on peripheral resistance (Secondary to dilatation of aorta) Decrease blood pressure Decrease after load Decrease workload Decrease oxygen consumption Abdullah Danish, Educational Platform

17. Nitrates Reduced venous return (Due to dilatation of the veins) Decrease left ventricular volume Decrease preload Decrease workload Decrease oxygen consumption Abdullah Danish, Educational Platform

18. Effects 1. Coronary artery dilatation 2. Reduction of peripheral arterial resistance – decrease after load 3. Reduce venous return – decrease preload Abdullah Danish, Educational Platform

19. Pharmacokinetics of Nit r a t es / O r g anic Nit r a t es Organic nitrates are lipid soluble, well absorbed from buccal mucosa, intestines and skin. Ingested orally, all except isosorbide mononitrate undergo extensive and variable first pass metabolism in liver. They are rapidly denitrated by a glutathione reductase and a mitochondrial aldehyde dehydrogenase. Abdullah Danish, Educational Platform

20. Uses of Nit r a t es / O r g anic Nit r a t es Angina pectoris: GTN produces relief within 3 min in 75% patients, the rest may require another dose or take longer (up to 9 min). Acute coronary syndromes: Nitrates are useful by decreasing preload as well as by increasing coronary flow. Myocardial infarction (MI): GTN is frequently used during evolving MI with the aim of relieving chest pain and limiting the area of necrosis by favorably altering O 2 balance in the marginal partially ischemic zone. Abdullah Danish, Educational Platform

21. Adverse effects Nit r a t es / O r g anic Nit r a t es Headache is the most common adverse effect of nitrates. High doses of nitrates can also cause postural hypotension, facial flushing, and tachycardia. Phosphodiesterase type 5 inhibitors such as sildenafil potentiate the action of the nitrates. To prevent the dangerous hypotension that may occur, this combination is contraindicated. Abdullah Danish, Educational Platform

22. β Blo c k e r s The β-adrenergic blockers decrease the oxygen demands of the myocardium by blocking β 1 receptors, resulting in decreased heart rate, contractility, cardiac output, and blood pressure. All β blockers are nearly equally effective in decreasing frequency and severity of attacks and in increasing exercise tolerance in classical angina, but cardioselective agents (atenolol, metoprolol ) are preferred over nonselective β 1 + β 2 blockers (e.g. propranolol). Abdullah Danish, Educational Platform

23. Hemodynamics Effects Decrease heart rate Reduced blood pressure and cardiac contractility without appreciable decrease in cardiac output B-Blockers Abdullah Danish, Educational Platform

24. B-Blockers Decrease heart rate & Contractility Increase duration of diastole Decrease workload Increase coronary blood flow Increase oxygen supply Decrease O 2 consumption Abdullah Danish, Educational Platform

25. Calciu m channe l bloc k e r s Phenyl alkylamine: Verapamil Benzothiazepine: Diltiazem Dihydropyridines: Nifedipine, Felodipine , Amlodipine, Nitrendipine , Nimodipine , Lacidipine , Lercanidipine , Benidipine Abdullah Danish, Educational Platform

26. Calciu m channe l bloc k e r s Pharmacol ogi c al actio n s : S moot h m u scl e : T h e CC B s c a us e r el a x a ti o n b y d ec r eas i ng i n t r a c ell u l a r a v ailabili t y o f Ca 2 + . T h e d i h y d r o p yri d i n e s (DHPs) e.g. amlodipine have the most marked smooth muscle relaxant and vasodilator action; verapamil is somewhat weaker followed by diltiazem . Abdullah Danish, Educational Platform

27. Calciu m channe l bloc k e r s Pharmacological actions: Heart: calcium channel blockers protect the tissue by inhibiting the entrance of calcium into cardiac and smooth muscle cells of the coronary and systemic arterial beds and decreases smooth muscle tone and vascular resistance, afterload . Abdullah Danish, Educational Platform

28. Ca - Channel Blockers Effects 2. Coronary artery dilatation 3. Reduction on peripheral arterial resistance – decrease after load Abdullah Danish, Educational Platform

29. Ca Channel Blockers Coronary artery dilatation Decrease coronary bed resistance (Relieved coronary vasospasm) Increase coronary blood flow Increase oxygen supply Abdullah Danish, Educational Platform

30. Ca channel Blockers Reduction on peripheral resistance ( Secondary to dilatation of aorta ) Decrease blood pressure Decrease after load Decrease workload Decrease oxygen consumption Abdullah Danish, Educational Platform

31. Calciu m channe l bloc k e r s Phenyl alkylamine: Verapamil: It dilates arterioles and decreases total peripheral resistance. It slows atrioventricular (AV) conduction directly and decreases heart rate, contractility, blood pressure, and oxygen demand. It also has some α adrenergic blocking activity. Verapamil has greater negative inotropic effects than amlodipine, but it is a weaker vasodilator. Verapamil should not be given with β blockers, digoxin, cardiac depressants like quinidine and disopyramide . Abdullah Danish, Educational Platform

32. Calciu m channe l bloc k e r s Benzothiazepine: Diltiazem: Diltiazem also slows AV conduction, decreases the rate of firing of the sinus node pacemaker, and is also a coronary artery vasodilator. Diltiazem can relieve coronary artery spasm and is particularly useful in patients with variant angina. It is somewhat less potent vasodilator than nifedipine and verapamil, and has modest direct negative inotropic action, but direct depression of SA node and A-V conduction are equivalent to verapamil. Abdullah Danish, Educational Platform

33. Calciu m channe l bloc k e r s Dihydropyridine (DHP) calcium channel blockers: Nifedipine: Nifedipine is the prototype DHP with a rapid onset and short duration of action. It causes arteriolar dilatation and decreases total peripheral resistance. Nifedipine is usually administered as an extended-release oral formulation. It causes direct depressant action on heart in higher dose. Abdullah Danish, Educational Platform

34. Adverse effects of CCBs Frequent side effects are palpitation, flushing, ankle edema, hypotension, headache, drowsiness and nausea. Nifedipine has paradoxically increased the frequency of angina in some patients. Abdullah Danish, Educational Platform

35. Uses Calciu m channe l bloc k e r s Calcium channel blockers can be safely given to patients with peripheral vascular disease in whom β blockers are contraindicated. CCB are used for the treatment of angina pectoris hypertension cardiac arrhythmias Abdullah Danish, Educational Platform

36. References Karch , A. M., & Karch . (2011).  Focus on nursing pharmacology . Wolters Kluwer Health/Lippincott Williams & Wilkins. [ Link ] Katzung , B. G. (2017).  Basic and clinical pharmacology . McGraw-Hill Education. Lehne , R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B. (2004). Pharmacology for nursing care. Smeltzer , S. C., & Bare, B. G. (1992).  Brunner & Suddarth’s textbook of medical-surgical nursing . Philadelphia: JB Lippincott Abdullah Danish, Educational Platform