DRUGS USED FOR DRUGS USED FOR ANGINA PECTORISANGINA PECTORIS

LAKSHMAN KARALLIEDDE2011

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

1. NITRATES2. BETA BLOCKERS3. CALCIUM ANTAGONISTS4. 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

1.REDUCES MYOCARDIAL OXYGEN DEMAND (LOWERS PRE-LOAD AND AFTER LOAD)2. INCREASES MYOCARDIAL OXYGEN SUPPLY (CORONARY VASODILATATION)

NITRATE PREPARATIONS

1.SUBLINGUAL GLYCERYL TRINITRATE (GTN)2.BUCCAL GLYCERYL TRINITRATE 3.TRANSDERMAL GLYCERYL TRINITRATE4.ORAL ISOSORBIDE DINITRATE5.ORAL ISOSORBIDE MONONITRATE6.INTRAVENOUS GTN- FOR ACUTE MYOCARDIAL INFARCTION/LEFT VENTRICULAR FAILURE -10 -200 µg /MIN INTRAVENOUS INFUSION, TITRATING TO CLINICAL RESPONSE AND BLOOD PRESSURE.

DURATION OF ACTION OF SOME NITRTATE PREPARATIONS

PEAK ACTIONDURATION OF

ACTION

Sublingual GTN(Tablet 300-500µg or metered dose aerosol 400µg/spray)

4-8 minutes 10-30 minutes

Buccal GTN (1-5 mg tablet 6 hourly)

4-10 minutes 30-300 minutes

Transdermal. GTN (5-10 daily)

1-3 hours Up to 24 hours

Oral isosorbidedinitrate.(10-20 mg 8 hourly)

45-120 hours 2-6 hours

Oral isosorbide mononitrate( 20-60 mg once or twice a day)

45-120 hours 6-10 hours

SUBLINGUAL GTN- Administered

a.as a tablet – 300-500 µg to disolve under the tongueb.As metered-dose aerosol (400 µg per spray)

RELIEVES AN ATTACK OF ANGINA IN 2-3 MINUTES

UNWANTED EFFECTS

HEADACHESYMPTOMATIC HYPOTENSION –DIZZINESS, POSTURAL GIDDINESS, BLURRING OF VISIONRARELY SYNCOPE – FAINTING

ASK PATIENT TO SPIT TABLET IF ABOVE EFFECTS OCCURNOT HABIT FORMINGTEACH PATIENTS TO USE PROPHYLACTICALLY e.g. Before exertingVIRTUALLY 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

CALCIUM ANTAGONISTSMODE OF ACTION1.DECREASES MYOCARDIAL OXYGEN DEMAND BY REDUCING BLOOD PRESSURE AND MYOCARDIAL CONTRACTILITY

TYPESA.DIHYDROPYRIDINE CALCIUM ANTAGONISTS-NIFEDIPINE, NICARDIPINE OFTEN CAUSE REFLEX TACHYCARDIA-BEST USED IN COMBINATION WITH BETA BLOCKER-not used or caution when usingB.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 EFFECTSPERIPHERAL OEDEMAFLUSHINGHEADACHEDIZZINESS

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 patientsPatients with pulmonary oedema

Side effects:a.Headacheb.Flushingc.Dizzinessd.Weaknesse.May cause a dose dependent increase in heart ratef.Myalgiag.Angioedema

ANTIPLATELET DRUGS

ASPIRINCLOPIDOGREL

THROMBOLYTIC AGENTSSTREPTOKINASEALTEPLASERETEPLASE-

ASPIRIN

ANTIPLATELE T EFFECT BY INHIBITION OF THROMBOXANE A 2NSAID, INHIBITS COX-1 AND COX -2 WHICH LEADS TO DECREASED PROSTAGLANDIN SYNTHESIS

USESTHROMBO-EMBOLIC CVA, ISCHAEMIC HEART DISEASE-PROPHYLAXIS (75MG/DAY) AND ACUTE TREAMENT (300 MG)

CONTRAINDICATIONS1.THOSE UNDER AGE OF 16Y-CAN INCREASE INCIDENCE OF REYE’S SYNDROME, LIVER/BRAIN DAMAGE2.GASTRO-INTESTINAL ULCERS3.BLEEDING DISORDERS4.GOUT5.HYPERSENSITIVITY TO ANY NSAID6.GFR <10ML/MIN

ASPIRINCAUTION1.ASTHMA2.UNCONTROLLED HYPERTENSION3.ANY ALLERGIC DISEASE4.G6PD DEFICIENCY5.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

USEPROPHYLAXIS OF ANTI-THROMBOTIC EVENTS IN NON—ST ELEVATIONMYOCARDIAL INFARCTION AND IN ST ELEVATION MYOCARDIAL INFARCTION-IN COMBINATION WITH ASPIRINMYOCARDIAL INFARCTION (WITHIN A ‘FEW’ TO35 DAYS)ISCHAEMICCEREBROVASCULAR ACCIDENT- WITHIN 7 DAYS TO 6 MONTHSPERIPHERAL ARTERIAL DISEASECONTRAINDICATIONACTIVE 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 AGENTINCREASES PLASMINOGEN CONVERSION TO PLASMIN WHICH INCREASES FIBRIN BREAKDOWN

USES1.ACUTE MYOCARDIAL INFARCTION -1.5 MILLION UNITS INTRAVENOUS INFUSION OVER 60 MIN2.THROMBOEMBOLISM OF ARTERIES3.PULMONARY EMBOLISM4.CENTRAL RETINAL ARTERY THROMBOSIS5.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

USEACUTE MYOCARDIAL INFARCTION (TOTAL DOSE 100MG-REGIMEN DEPENDS ON TIME SINCE ONSET OF PAIN0-6HOURS: 15 MG INTRAVENOUS BOLUS,FOLLOWED BY 50 MG INTRAVENOUS INFUSION OVER 30 MINUTES AND 35 MG INTRAVENOUS INFUSION OVER 60 MINUTES6-12 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

RETEPLASERECOMBINANT PLASMINOGEN ACTIVATOR; THROMBOLYTICUSED ONLY FOR MYOCARDIAL INFARCTIONDOSE-10 UNITS AS SLOW INTRAVENOUS INJECTION OVER 2 MINUTES, REPEAT AFTER 30 MIN