1. New Paradigm of Anti Anginal Therapy dr.Yerizal Karani SpPD,SpJP(K)

2. Angina Pectoris
Angina pectoris  sudden severe pressing chest pain or heaviness radiating to the neck, jaw, back and arms  associated with diaphoresis, tachypnea and nausea.
Angina  insufficient coronary flow to meet oxygen demands of the myocardium  precipitated by any activity/process that creates an imbalance in O2 supply and demand

5. Types of Angina Angina occurs in three overlapping patterns:
Stable angina
Unstable angina
Prinzmetal (variant) angina

13. Nitrat
Nitrogliserin (gliseril trinitrat)  very fast onset sublingually  acute condition
Isosorbide dinitrate  fast onset sublingually (substitute of gliseril trinitrat)
Isosorbide mononitrate  slow onset  used in preventing angina

14. Nitrates Tolerance " Decrease in the effect of a drug
when administered in a long-acting form"
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Tolerance can be avoided
Using the least effective dose
Creating discontinuous plasma levels
Treatment of Heart Failure.
Nitrates: Tolerance
Repetitive administration of nitrates over days is accompanied by a reduction in intensity and duration of its effects (tolerance), that obligates sequential increases in dose to obtain the desired effect. Nitrate tolerance appears with all nitrates, crosses over from one nitrate preparation to another (explaining the poor effect that IV NTG can have in patients on oral nitrate therapy), and is not dose dependent. Additionally, tolerance appears within 8-24 hours of administration of preparations that allow for maintenance of stable plasma nitrate levels (i.v., patch), but disappears rapidly (<48hrs) after stopping treatment. Increasing dosage does not overcome the tolerance effect. Tolerance can be avoided, however, by using the lowest effective dose, and by avoiding continuous plasma levels (drug-free periods).

15. Nitrates Contraindications
Previous hypersensitivity
Hypotension ( < 80 mmHg)
AMI with low ventricular filling pressure
1st trimester of pregnancy
Treatment of Heart Failure.
Nitrates: Contraindications
Nitrates are contraindicated in patients with histories of nitrate hypersensitivity, marked hypertension or shock, acute infarction with low filling pressures, and first-trimester pregnancy. They should also not be given to patients with anemia, increased intracranial pressure, severe aortic or mitral stenosis, cardiac tamponade, constrictive pericarditis or coronary thrombosis. Nitrates can aggravate angina in the setting of hypertrophic cardiomyopathy.
WITH CAUTION:
Constrictive pericarditis
Intracranial hypertension
Hypertrophic cardiomyopathy

17. Contraindication B-Blocker
Hypotension: BP < 100 mmHg
Bradycardia: HR < 50 bpm
Chronic bronchitis, ASTHMA
Severe chronic renal insufficiency
Treatment of Heart Failure. Beta-Blockers: Contraindications
Contraindications to beta-blocker therapy in heart failure patients are the same as those for the general population.

18. Reasons for Using Nitrates and Beta Blockers in Combination in Angina
Beta Blockers prevent reflex tachycardia and contractility produced by nitrate-induced hypotension.
Nitrates prevent any coronary vasospasm produced by Beta Blockers.
Nitrates prevent increases in left ventricular filling pressure or preload resulting from the negative inotropic effects produced by Beta Blockers.
Nitrates and Beta Blockers both reduce myocardial oxygen consumption by different mechanisms.
Nitrates and Beta Blockers both increase subendocardial blood flow by different mechanisms

20. Anti Anginal Effect Endocardial blood flow Collateral Wall tension
Nitrate
B-Blocker
CCB
Endocardial blood flow ↑↑ ↑
Collateral →
Wall tension ↓ →↑
Heart rate
↑ (reflex) ↓↓ ↑↓
Contractility
↓→↑
Cardiac work

21. Take Home Messages
Angina pectoris  imbalance of O2 in supply & demand of the myocardium
Nitrogliserin: very fast onset of nitrate in angina pectoris

22. THANK YOU...