Angina Pectoris 1 & 2 (2024) PDF

WEEK 9 MPharm Programme Chronic or Stable Coronary Artery Disease 1 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA222 Angina WEE...

WEEK 9 MPharm Programme Chronic or Stable Coronary Artery Disease 1 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA222 Angina WEEK 9 Chronic or Stable Coronary Artery Disease Pathogenesis, Clinical features & Management Slide 2 of 58 MPharm PHA222 Angina WEEK 9 OUTLINE OF LECTURES Definitions Aetiology & Pathogenesis Clinical subtypes Clinical features Clinical management & therapeutics Slide 3 of 58 MPharm PHA222 Angina WEEK 9 Learning Outcomes At the end of this series of lectures, you should be able to: Describe the causes and underlying coronary pathology of stable coronary artery disease (SCAD) Describe the main clinical signs & symptoms, and the distinguishing features of the subtypes of stable CAD Give an account of the non-pharmacological & pharmacological management of stable CAD Give an account of how the major classes of anti-anginal drugs act to produce their beneficial effects Describe the current NICE care pathway for stable angina Slide 4 of 58 MPharm PHA222 Angina WEEK 9 Stable Coronary Artery Disease Definitions, Aetiology & Clinical features Slide 5 of 58 MPharm PHA222 Angina  Chronic or Stable Coronary WEEK 9 Artery Disease Definitions a chronic / recurrent and acute ischaemic heart disease (IHD) syndrome characterised by episodes of reversible or transient mismatch between myocardial O2 demand and supply related to myocardial ischaemia or hypoxia without myocardial cell necrosis/death commonly associated with transient chest discomfort or strangling & choking pain in the chest (angina pectoris) Slide 6 of 58 MPharm PHA222 Angina WEEK 9 Stable Coronary Artery Disease Aetiology & Pathogenesis arises from a mismatch or imbalance between myocardial O2 demand & supply may be due to: atherosclerotic plaque-related partial obstruction of epicardial coronary arteries  classic angina transient, focal or diffuse, spasm of normal or mildly- diseased epicardial coronary arteries  variant angina a primary dysfunction of small diameter ( 500 µm) intramural coronary arteries  microvascular angina Slide 7 of 58 MPharm PHA222 Angina  Stable Coronary Artery Disease WEEK 9 Clinical subtypes Two Major Clinical Subtypes Angina with obstructive CAD Angina without obstructive CAD (INOCA / NOCAD) Slide 8 of 58 MPharm PHA222 Angina  Stable Coronary Artery Disease WEEK 9 Clinical subtypes Angina with obstructive CAD Classic or Stable Angina (Angina of effort) chest pain on exertion fixed obstructive CAD (atherosclerotic plaque) ST-segment depression Slide 9 of 58 MPharm PHA222 Angina  Stable Coronary Artery Disease WEEK 9 Clinical subtypes Angina without obstructive CAD (INOCA) Variant or Prinzmetal’s Angina (Angiospastic/Vasospastic) Microvascular Angina (Syndrome X) Variant or Prinzmetal’s Angina (Vasospastic) pain at rest or at night focal or diffuse spontaneous coronary artery spasm ST-segment elevation (or ST-segment depression) arrhythmias Slide 10 of 58 MPharm PHA222 Angina  Stable Coronary Artery Disease WEEK 9 Clinical subtypes Microvascular Angina (Syndrome X) chest pain at rest or on exertion – the pain persists after interruption of exertion & slow/poor response to GTN no angiographic evidence of obstructive CAD coronary microvascular dysfunction – endothelial dysfunction, abnormal dilator responses, coronary microvascular spasm, heightened response to vasoconstrictors, reduced coronary flow reserve, etc positive stress test – ST-segment depression during exercise Slide 11 of 58 MPharm PHA222 Angina WEEK 9 Underlying Coronary Pathology & Pathophysiology of Chronic Angina Syndromes Slide 12 of 58 MPharm PHA222 Angina  Stable Coronary Artery Disease WEEK 9 Clinical features (signs & symptoms) Pain location – retrosternal, near the sternum radiation – throat, lower jaw, upper arms, back, epigastrium, character – pressure, tightness, heaviness, discomfort, strangling, constricting or burning duration – brief, lasting a few minutes to arteries > arterioles Prodrugs – need be converted in vivo to the biologically active principle / metabolite (NO) Slide 28 of 58 MPharm PHA222 Angina WEEK 9 Organic Nitrates & Nitrites Pharmacological Actions cellular mechanism of vasorelaxation in vivo conversion to NO activation of guanylate cyclase   cGMP activation of PKG  vasorelaxation Slide 29 of 58 MPharm PHA222 Angina WEEK 9 Organic Nitrates & Nitrites Mechanisms of anti-anginal effect peripheral venodilatation   preload   MVO2 peripheral arterial & arteriolar dilatation   afterload   MVO2 coronary vasodilatation  reversal of spasm prevention of spasm increased collateral BF Slide 30 of 58 MPharm PHA222 Angina WEEK 9 Organic Nitrates & Nitrites Clinical Use relief of acute angina attacks – GTN, amyl nitrite prophylaxis of chronic angina – GTN, ISDN, ISMN choice & mode of therapy – influenced by pharmacokinetic profile sublingual, buccal, inhalation, transdermal, IV Slide 31 of 58 MPharm PHA222 Angina WEEK 9 Organic Nitrates & Nitrites Adverse effects & Precautions flushing & throbbing headaches postural hypotension & syncope reflex tachycardia and  myocardial contractility tolerance depletion of thiol (-SH) groups physiological adaptation Slide 32 of 58 MPharm PHA222 Angina WEEK 9 MPharm Programme Chronic or Stable Coronary Artery Disease 2 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA222 Angina WEEK 9 Drug Treatment of Stable Coronary Artery Disease (SCAD) -Adrenoceptor Antagonists Slide 34 of 58 MPharm PHA222 Angina  -Adrenoceptor Antagonists WEEK 9 History first introduced into clinical medicine in the mid- 1960s for treatment of angina pectoris earned Sir James Black the Nobel Prize in Medicine (1988) Chemistry structural analogues of isoprenaline prototypes – propranolol, atenolol Slide 35 of 58 MPharm PHA222 Angina  -Adrenoceptor Antagonists WEEK 9 Pharmacological Actions antagonise the effects of sympathetic nervous activation (i.e. noradrenaline & adrenaline) at β-adrenoceptors 3 major subtypes of -adrenoceptors 1-ARs – heart & kidney 2-ARs – heart, smooth muscle (e.g. vascular & bronchial) 3-ARs – adipocytes Two broad classes of -blockers ‘non-selective’ – e.g. propranolol 1-receptor selective (‘cardioselective’) – e.g. atenolol Slide 36 of 58 MPharm PHA222 Angina  -Blockers – Receptor Selectivity WEEK 9 Rate Force Slide 37 of 58 MPharm PHA222 Angina  -Adrenoceptor Antagonists WEEK 9 Mechanisms of anti-anginal effect haemodynamic effects   myocardial O2 demand  myocardial contractility at rest & during exercise  heart rate  system blood pressure ancillary effects  diastolic filling time   myocardial perfusion antiarrhythmic activity   electrical stability antiatherogenic & antithrombotic Slide 38 of 58 MPharm PHA222 Angina  -Adrenoceptor Antagonists WEEK 9 Clinical Use prophylaxis of chronic stable angina (first-line) Adverse effects & Precautions  LV size   myocardial O2 consumption rebound phenomenon  aggravation of angina bronchoconstriction  exacerbation of asthma peripheral vasoconstriction  cold extremities myocardial depression  risk of heart failure masking of signs of impending hypoglycaemia sexual dysfunction  poor patient compliance CNS disturbances – nightmares, depression, confusion Slide 39 of 58 MPharm PHA222 Angina WEEK 9 Drug Treatment of Stable Coronary Artery Disease (SCAD) Calcium Channel Blockers Slide 40 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Blockers History introduced into clinical medicine in the 1970s for the treatment of hypertension subsequently licensed for treatment of other CV diseases Pharmacological Actions inhibit entry of Ca into cells via voltage-gated calcium channels main effects on heart & vascular smooth muscle Slide 41 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Blockers Chemistry chemically diverse phenylalkylamines – verapamil dihydropyridines – nifedipine benzothiazepines – diltiazem Slide 42 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Blockers Cardiac effects (verapamil & diltiazem) block of Ca influx into cardiac muscle cells   cardiac contractility block of Ca influx into nodal & conducting cells   HR (Phenylalkylamines & Benzothiazepines only!) Slide 43 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Blockers Vascular effects block of Ca influx into arterioles  arteriolar dilatation peripheral vasodilatation   SVR   arterial BP coronary dilatation   coronary blood flow reversal of spasm prevention of spasm Slide 44 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Blockers Mechanisms of anti-anginal effect Reduced myocardial O2 demand decreased arterial BP (afterload) decreased myocardial contractility verapamil & diltiazem decreased heart rate Increased myocardial blood flow coronary vasodilatation  increased CBF spasm reversal/prevention Slide 45 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Blockers Clinical use management of chronic stable angina (first-line) management of variant angina Adverse effects & Precautions mainly direct extensions of therapeutic effects Slide 46 of 58 MPharm PHA222 Angina WEEK 9 Calcium Channel Antagonists Adverse Effects Non-Dihydropyridines Dihydropyridines (Verapamil, Diltiazem) (Amlodipine, Nifedipine, etc) Cardiodepression Hypotension Bradycardia Light-headedness AV block Flushing Hypotension Headache Headache Peripheral oedema Peripheral oedema Constipation Slide 47 of 58 MPharm PHA222 Angina WEEK 9 Drug Treatment of SCAD Miscellaneous Agents Potassium channel openers Nicorandil – veno-dilatation   preload   MVO2 arterial dilatation   afterload   MVO2 Sinus node (If current) inhibitors Ivabradine – inhibition of If   HR   MVO2 Late Sodium Current Blockers Ranolazine – inhibition of late INa  anti-ischaemic effects Slide 48 of 58 MPharm PHA222 Angina WEEK 9 Stable Coronary Artery Disease Principles of Clinical Management Revascularization procedures Percutaneous Coronary intervention (PCI) Balloon angioplasty (PTCA) Coronary stenting – bare metal stents (BMS), drug eluting stents (DES) Coronary artery by-pass graft (CABG) Slide 49 of 58 MPharm PHA222 Angina WEEK 9 Balloon Angioplasty (PTCA) Slide 50 of 58 MPharm PHA222 Angina WEEK 9 Coronary Stenting Paclitaxel, Sirolimus, Everolimus, Zotarolimus Slide 51 of 58 MPharm PHA222 Angina  PTCA & Stenting WEEK 9 1: Artery With Plaque 2: Pre-Dilatation PTCA 3: Stent Procedure 4: Result After Stent Procedure Slide 52 of 58 MPharm PHA222 Angina  Coronary Artery Bypass Graft WEEK 9 Slide 53 of 58 MPharm PHA222 Angina WEEK 9 Overview of Clinical Management of Stable Angina Treatment Options Percutaneous Medical Coronary CABG Treatment Intervention Slide 54 of 58 MPharm PHA222 Angina WEEK 9 Stable Angina – Drug Treatment Algorithm (NICE 2011) Slide 55 of 58 MPharm PHA222 Angina WEEK 9 Management of Chronic Stable Angina (NICE 2011) Symptom control Secondary prevention of cardiovascular effects Slide 56 of 58 MPharm PHA222 Angina  RECOMMENDED READING WEEK 9 2011 NICE Guideline for the Management of Stable Angina (CG 126) (updated: 25 August 2016) Full Guideline (https://www.nice.org.uk/guidance/cg126/resources/stable-angina- management-pdf-35109453262021) Management of Stable Angina: summary of NICE guidance. BMJ 2011;343:d4147. Doi:10.1136/bmj.d4147 2018 SIGN Guideline for the Management of Stable Angina (SIGN 151) Quick Reference Guide (https://www.sign.ac.uk/media/1461/qrg151.pdf) Full Guideline (https://www.sign.ac.uk/media/1088/sign151.pdf) Slide 57 of 58 MPharm PHA222 Angina WEEK 9 RECOMMENDED READING 2024 ESC Guidelines for the Management of Chronic Coronary Syndromes Full Guideline (https://academic.oup.com/eurheartj/advance-article- pdf/doi/10.1093/eurheartj/ehae177/58966097/ehae177.pdf) Pharmacological treatment of chronic stable angina pectoris (2013). Clinical Medicine 13: 63-70. Treatment of Angina - Where Are We? Cardiology 2018:140:52–67. DOI:10.1159%2F000487936 Slide 58 of 58 MPharm PHA222 Angina