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DRUGS USED FOR ANGINA PECTORIS. LAKSHMAN KARALLIEDDE 2011. ANGINA PECTORIS SYMPTOM COMPLEX: CONSTITUTES A CLINICAL SYNDROME RATHER THAN A DISEASE CAUSE: TRANSIENT MYOCARDIAL ISCHAEMIA OCCURS WHEN EVER THERE IS AN INBALANCE BETWEEN MYOCARDIAL OXYGEN SUPPLY AND DEMAND
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DRUGS USED FOR ANGINA PECTORIS LAKSHMAN KARALLIEDDE 2011
ANGINA PECTORIS SYMPTOM COMPLEX:CONSTITUTES A CLINICAL SYNDROME RATHER THAN A DISEASE CAUSE: TRANSIENT MYOCARDIAL ISCHAEMIA OCCURS WHEN EVER THERE IS AN INBALANCE BETWEEN MYOCARDIAL OXYGEN SUPPLY AND DEMAND COMONEST CAUSE: ATHEROMATOUS DISEASE OF CORONARY ARTERIES MAY ALSO BE A MANIFESTATION OF OTHER FORMS OF HEART DISEASE e.g. Severe aortic valve disease, hypertrophic cardiomyopathy
DRUGS USED TO RELIEVE OR PREVENT THE SYMPTOMS OF ANGINA • NITRATES • BETA BLOCKERS • CALCIUM ANTAGONISTS • POTASSIUM CHANEL ACTIVATORS • AS THE FUNDAMENTAL CAUSE OF ANGINA PECTORIS IS INSUFFICIENT OXYGEN SUPPLY TO HEART MUSCLE, IT IS LOGICAL TO ATTEMPT TO INCREASE THE OXYGEN SUPPLY BY ADMINISTERING OXYGEN- THAT IS BY INCREASING THE INSPIRED OXYGEN CONCENTRATION SIMILARLY, PATIENTS WITH ANGINA MAY SUFFER FROM SEVERE PAIN AND PAIN RELIEF WITH A POTENT OPIATE • e.g. Morphine NEEDS TO BE CONSIDERED TO MAKE THE PATIENT MORE • COMFORTABLE, LESS ANXIOUS.
NITRATES • MODE OF ACTION : • ACTS DIRECTLY ON VASCULAR SMOOTH MUSCLE TO PRODUCE ARTERIAL AND VENOUS DILATATION • EFFECT DURING ANGINA • REDUCES MYOCARDIAL OXYGEN DEMAND (LOWERS PRE-LOAD AND AFTER LOAD) • 2. INCREASES MYOCARDIAL OXYGEN SUPPLY (CORONARY VASODILATATION)
NITRATE PREPARATIONS SUBLINGUAL GLYCERYL TRINITRATE (GTN) BUCCAL GLYCERYL TRINITRATE TRANSDERMAL GLYCERYL TRINITRATE ORAL ISOSORBIDE DINITRATE ORAL ISOSORBIDE MONONITRATE INTRAVENOUS GTN- FOR ACUTE MYOCARDIAL INFARCTION/LEFT VENTRICULAR FAILURE -10 -200 µg /MIN INTRAVENOUS INFUSION, TITRATING TO CLINICAL RESPONSE AND BLOOD PRESSURE.
SUBLINGUAL GTN- Administered • as a tablet – 300-500 µg to disolve under the tongue • As metered-dose aerosol (400 µg per spray) • RELIEVES AN ATTACK OF ANGINA IN 2-3 MINUTES • UNWANTED EFFECTS • HEADACHE • SYMPTOMATIC HYPOTENSION –DIZZINESS, POSTURAL GIDDINESS, BLURRING OF VISION • RARELY SYNCOPE – FAINTING • ASK PATIENT TO SPIT TABLET IF ABOVE EFFECTS OCCUR • NOT HABIT FORMING • TEACH PATIENTS TO USE PROPHYLACTICALLY e.g. Before exerting • VIRTUALLY INEFFECTIVE IF SWALLOWED DUE TO EXTENSIVE FIRST PASS METABOLISM IN THE LIVER • CONTINUOUS USE CAUSES PHARMACOLOGICAL TOLERANCE • THERFORE ATTEMPT TO INCLUDE A ‘NITRATE-FREE’ PERIOD OF 6-8 HOURS A DAY
BETA BLOCKERS • MODE OF ACTION: LOWERS MYOCARDIAL OXYGEN DEMAND BY • REDUCING HEART RATE • REDUCING BLOOD PRESSURE • REDUCING MYOCARDIAL CONTRACTILITY • Can exaccerbate symptoms of peripheral vascular disease • May provoke bronchospasm in patients with obstructive airway disease • e.g asthma • Theoretically-Non- selective beta blockers may aggravate coronary vasospasm by blocking the coronary artery beta 2 recetors. • Advice: use a once daily cardio-selective preparation e.g atenolol 50-200mg daily • slow release metoprolol 50-200mg daily • bisoprolol 5-10 mg daily • BETA BLOCKERS SHOULD NOT BE WITHDRAWN ABRUPTLY (SUDDENLY) BECAUSE OF THE POSSIBILITY OF A REBOUND EFFECT AND THE RISK OF PRECIPITATING ARRHYTHMIAS, WORSENING ANGINA OR CAUSING MYOCARDIAL INFARCTION (THE ‘BETA-BLOCKER WITHDRAWAL SYNDROME).
CALCIUM ANTAGONISTS • MODE OF ACTION • DECREASES MYOCARDIAL OXYGEN DEMAND BY REDUCING BLOOD PRESSURE AND MYOCARDIAL CONTRACTILITY • TYPES • DIHYDROPYRIDINE CALCIUM ANTAGONISTS-NIFEDIPINE, NICARDIPINE OFTEN CAUSE REFLEX TACHYCARDIA-BEST USED IN COMBINATION WITH BETA BLOCKER-not used or caution when using • VERAPAMIL AND DILITIAZEM-SUITABLE FOR PATIENTS WHO ARE NOT RECEIVING BETA BLOCKERS AS THEY DECREASE THE HEART RATE ( DANGEROUS ADDITIVE EFFECT) • CALCIUM CHANNEL ANTAGONISTS MAY REDUCE MYOCARDIAL • CONTRACTILITY TO A DEGREE THAT CAN AGGRAVATEOR PRECIPITATE • HEART FAILURE • UNWANTED EFFECTS • PERIPHERAL OEDEMA • FLUSHING • HEADACHE • DIZZINESS
POTASSIUM CHANNEL ACTIVATORS MODE OF ACTION: DILATES ARTERIES AND VEINS DOES NOT EXHIBIT TOLERANCE SEEN WITH NITRATES NICORANDIL- 10-30 mg 12 hourly Caution in: hypovolaemic patients Patients with pulmonary oedema Side effects: Headache Flushing Dizziness Weakness May cause a dose dependent increase in heart rate Myalgia Angioedema
ANTIPLATELET DRUGS • ASPIRIN • CLOPIDOGREL • THROMBOLYTIC AGENTS • STREPTOKINASE • ALTEPLASE • RETEPLASE-
ASPIRIN ANTIPLATELE T EFFECT BY INHIBITION OF THROMBOXANE A 2 NSAID, INHIBITS COX-1 AND COX -2 WHICH LEADS TO DECREASED PROSTAGLANDIN SYNTHESIS USES THROMBO-EMBOLIC CVA, ISCHAEMIC HEART DISEASE-PROPHYLAXIS (75MG/DAY) AND ACUTE TREAMENT (300 MG) CONTRAINDICATIONS THOSE UNDER AGE OF 16Y-CAN INCREASE INCIDENCE OF REYE’S SYNDROME, LIVER/BRAIN DAMAGE GASTRO-INTESTINAL ULCERS BLEEDING DISORDERS GOUT HYPERSENSITIVITY TO ANY NSAID GFR <10ML/MIN
ASPIRIN • CAUTION • ASTHMA • UNCONTROLLED HYPERTENSION • ANY ALLERGIC DISEASE • G6PD DEFICIENCY • DEHYDRATION • OTOTOXIC IN OVERDOSE • MAY INCREASE EFFECTS OF SULPHONYL UREAS AND OF METHOTREXATE • FOR ANALGESIA- 300-900 MG 4-6 HPOURLY –MAXIMUM DOSE4G/DAY • STOP 7 DAYS BEFORE SURGERY IF SIGNIFICANT BLEEDING IS EXPECTED • IF CARDIAC SURGERY OR PATIENT HAS ACUTE CORONARY SYNDROME- • CONSIDER CONTINUING
CLOPIDOGREL ANTIPLATELET AGENT- ADP RECEPTOR ANTAGONIST USE PROPHYLAXIS OF ANTI-THROMBOTIC EVENTS IN NON—ST ELEVATIONMYOCARDIAL INFARCTION AND IN ST ELEVATION MYOCARDIAL INFARCTION-IN COMBINATION WITH ASPIRIN MYOCARDIAL INFARCTION (WITHIN A ‘FEW’ TO35 DAYS) ISCHAEMICCEREBROVASCULAR ACCIDENT- WITHIN 7 DAYS TO 6 MONTHS PERIPHERAL ARTERIAL DISEASE CONTRAINDICATION ACTIVE BLEEDING NOT RECOMMENDED WITH WARFARIN
CLOPIDOGREL • SIDE EFFECTS • HAEMORRHAGE (ESPECIALLY GASTRO-INTESTINAL OR • INTRA-CRANIAL • GASTRO-INTESTINAL UPSET • PEPTIC ULCER • PANCREATITIS • HEADACHE • FATIGUE • DIZZINESS • PARAESTHESIA • RASH/PRURITUS • MONITOR FULL BLOOD AND FOR SIGNS OF OCCULT BLEEDING
STREPTOKINASE THROMBOLYTIC AGENT INCREASES PLASMINOGEN CONVERSION TO PLASMIN WHICH INCREASES FIBRIN BREAKDOWN USES ACUTE MYOCARDIAL INFARCTION -1.5 MILLION UNITS INTRAVENOUS INFUSION OVER 60 MIN THROMBOEMBOLISM OF ARTERIES PULMONARY EMBOLISM CENTRAL RETINAL ARTERY THROMBOSIS DEEP VEIN THROMBOSIS OTHER DOSES-250,000 UNITS INTRAVENOUS INFUSION OVER 30 MIN, THEN 100,000 UNITS EVERYHOUR FOR UPTO12-72 HOURS
ALTEPLASE (RECOMBINANT) TISSUE-TYPE PLASMINOGEN ACTIVATOR. RECOMBINANT FIBRINOLYTIC USE ACUTE MYOCARDIAL INFARCTION (TOTAL DOSE 100MG- REGIMEN DEPENDS ON TIME SINCE ONSET OF PAIN 0-6HOURS: 15 MG INTRAVENOUS BOLUS,FOLLOWED BY 50 MG INTRAVENOUS INFUSION OVER 30 MINUTES AND 35 MG INTRAVENOUS INFUSION OVER 60 MINUTES 6-12 HOURS-10 MG INTRAVENOUS BOLUS FOLLOWED BY 50 MG INTRAVENOUS INFUSION OVER 60 MIN, AND FOUR FURTHER 10 MG INTRAVENOUS INFUSIONS, EACH OVER 30 MIN) DECREASE DOSE IF PATIENT WEIGHS LESS THAN 65 KG RETEPLASE RECOMBINANT PLASMINOGEN ACTIVATOR; THROMBOLYTIC USED ONLY FOR MYOCARDIAL INFARCTION DOSE-10 UNITS AS SLOW INTRAVENOUS INJECTION OVER 2 MINUTES, REPEAT AFTER 30 MIN