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ANTIANGINAL DRUGS

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

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Types of Angina

Angina occurs in three overlapping patterns: Stable angina Unstable angina Prinzmetal (variant) angina

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Stable Angina

“Stable” indicates the reproducible nature of the angina; the same activity at the same intensity faithfully produces symptoms.

Typically this type of angina is relieved by rest or acute use of nitroglycerin.

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Unstable Angina

Unstable angina occurs when anginal symptoms occur with

less cardiac demand; previously tolerated activities elicit symptoms,

of great concern is angina at rest. These episodes are less or un-

responsive to nitroglycerine or rest. Crescendo angina describes a rapid

progression of myocardial ischemia often heralding infarction.

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Prinzmetal (Variant) Angina1. Uncommon pattern of myocardial ischemia usually occurring

at rest and often in young individuals (particularly women). 2. The anginal attacks in PVA tend to have a circadian rhythm

and generally occur in the early morning hours. 3. These attacks can be triggered by alcohol, rapid eye

movement sleep, atrial pacing, cocaine, nicotine, acetylcholine, and hyperventilation.

4. It is induced by coronary artery vasospasm it generally responds promptly to vasodilators.

5. PVA has been associated with other vasospastic disorders such as migraine headaches and Raynaud’s phenomena.

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CLASSIFICATION

I ORGANIC NITRATES a) Rapid onset slow acting-AMYL NITRATE,

NITROGLYCERINE b) Slow onset, long acting- ISOSORBIDE DINITRATE,

ISOSORBIDE MONONITRATE, ERYTHRITYL TETRANITRATE, PENTAERYTHRITOL TETRANITRATE

II. CALCIUM CHANNEL BLOCKERS VERAPAMIL, DILTIAZEM, NIFEDIPINE,

NICARDIPINE, NITRENDIPINE, ISARDIPINE, AMLODIPINE, BENIDIPINE

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CLASSIFICATION

III BETA BLOCKERSPROPRANOLOL, ATENOLOL, METAPROLOL, NADOLOL,

BISOPROLOL AND CELIPROLOL

MISCELLANEOUS1. Potassium Channel Openers: NICORANDIL2. Cytoprotective Drugs: TRIMETAZIDINE, RANOLAZINE3. Antiplatelet Drugs: ASPIRIN, TICLOPIDINE, CLOPIDOGREL,

DIPYRIDAMOLE, CILASTAZOL4. Bradycardic Drugs: IVABRADINE5. HMG-Co A Reductase Inhibitors: STATINS6. PVD: NAFTIDOFURYL AND PENTOXIPHYLLINE

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NITRATES- MOA

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NITRATES

ORGANIC NITRATES a) Rapid onset slow acting-AMYL NITRATE,

NITROGLYCERINE(GTN)-t1/2-2min b) Slow onset, long acting- ISOSORBIDE DINITRATE-s/l and oral, t1/2-40min, ISOSORBIDE MONONITRATE t1/2-4-6hrs,

ERYTHRITYL TETRANITRATE, PENTAERYTHRITOL TETRANITRATE--chronic prophylaxis

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NITRATES- pharmacokinetics

The difference between nitrate preparations is mainly in time of onset of action.

1. Nitroglycerin suffers marked 1st pass metabolism so administration is sublingual (rapid absorption and onset (<1 minute), t1/2 ~10 minutes. Occasionally as nitroglycerin is metabolized anginal symptoms will return. Transdermal administration either as patch or paste provides a depot of agent for a steady availability.

2. Isosorbide mononitrate & isosorbide dinitrate are long acting nitrates that are relatively resistant to hepatic catabolism t1/2 ~ 1 hour.

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Uses

Angina pectoris Acute coronary symptoms Biliary colic Cyanide poisoning CHF and acute LVF Myocardial infarction(MI) Esophagial spasm

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NITRATE TOLERANCE

decrease in the effect of drug whenadministered in long acting form. develops with all nitrates is dose dependent disappears in 24hrs after stopping the drug Tolerance can be avoided

-Using the least effective dose -Creating discontinuous plasma levelsD/I: Sildenafil

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NITRATES CONTRAINDICATIONS

1. Previous hypersensitivity2. Hypotension ( < 80 mmHg)3. AMI with low ventricular filling

pressure 4. 1st trimester of pregnancy

5. Constrictive pericarditis6. Intracranial hypertension7. Hypertrophic cardiomyopathy

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BETA BLOCKERS

PROPRANOLOL, ATENOLOL, METAPROLOL, NADOLOL, BISOPROLOL AND CELIPROLOL

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Beta blockers-MOA

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ß-ADRENERGIC BLOCKERSCONTRAINDICATIONS

Hypotension: bp < 100 mmhg

Bradycardia: hr < 50 bpm

Chronic bronchitis, asthma

Severe chronic renal

insufficiency

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CALCIUM CHANNEL BLOCKERS

Dihydropyridines:NIFEDIPINE, NICARDIPINE, NITRENDIPINE, ISARDIPINE, AMLODIPINE, BENIDIPINENon-Dihydropyridines: VERAPAMIL, DILTIAZEM,

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Adverse effects

Immediate release capsules- headache, ankle oedema

Headache Tachycardia and gingival hyperplasia Negetive ionotropic effectC/I- unstable angina, LV failure,

aortic stenosis, obstuctive cardiomyopathy

D/I-enzyme inhibitors

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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

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Additive efficacy of nitrates and calcium channel blockers

Preload----------------- After load-------------- Myocardial wall size--

Coronary blood flow---------Collateral blood flow---------Blood flow to ischemic area-

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Miscellaneous drugs

Potassium channel openers Diazoxide, Pinancidil, Minoxidil,

Cromokalin Fall in cytosolic Ca+ concentration Voltage gated K channels Calcium activated K channels ATP sensitive K channels K channel openers- NICORANDIL

- membrane hyperpolarisation - fall in BP

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NICORANDIL

Newer antianginal drug Activates ATP sensitive K+ channels membrane hyperpolarisationArteriolarK+ channel openingVenodilator nitrate like activity

fall in BP 10-20mg BD Chronic stable angina and vasospastic angina S/E- flushing, palpitation, dizziness

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Cytoprotective drugs

TRIMETAZIDINE Calcium channel blocker Cytoprotective effect on myocardial o2

demand Inhibits superoxide cytotoxicity maintains LV function Stable angina FOIS/E-R,A,T

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Ranolazine

PFOI Inhibits inward sodium current during

ischemia Prolongs exercise tolerance to angina 500mg BD orally Safe in combination with ca channel

blockers, Beta-blockers and nitrates S/E –QT prolongation

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Ivabradine (direct bradycardic agent)

-blocks hyperpolarisation- activated current(If)

Decreases the myocardial oxygen demand

No negetive ionotropic effect Less of SA node depression

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Antiplatelet drugs

Aspirin Ticlopidine and clopidogrel

Inhibits binding of ADP to its receptors Reduce platelet aggregation

Cilastozole Phosphodiesterase III inhibitor Vasodilatation and inhibits platelet

aggregation Metabolised by cyp3A4 100mg bd

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Dipyridamole

Inhibits adenosine deaminase and also phosphodiesterase

Inhibit platelet aggregation For prophylaxis of coronary and

cerebral thrombosis S/E- exacerbation of angina, GIT

distress

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HMG-Co A reductase inhibitors

Statins They cause regression of

atheromatous plaque Improvement of endothelial function

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Drugs for peripheral vascular disease

Pentoxiphylline (oxypentifylline) Is a theobromine analogue and inhibits

phosphodiesterase enzyme Reduces blood viscosity Improves the blood flow in ischemic area No coronary steal phenomenon Used in non-haemorrhagic stroke, chronic

cerebrovascular insufficiency 400mg bd

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Cilastozole

NAFTIDOFURYL(5HT2A) receptor antagonist

LEVOCARNITINE-improves the metabolic status of skeletal muscle

CYCLANDELATE –cerebrovascular and peripheral vascular disorders

400mg TDS

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Drugs used in Acute MI

1. Pain and anxiety1. -GTN, morphine

2. General measures-O2 therapy, dopamine, 3. atropine, diltiazem,

4. Maintainance of blood volume-Saline , dextran5. Correction of acidosis- sod. Bicarbonate infusion6. Prevention of treatment of arrhythmias -beta blocker

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7. Pump failure-furosemide, vasodilators, ionotropic drugs

8. Prevention of thrombus extension, venous thrombosis- aspirin, heparin, anticoagulants

9. Thrombolysis and reperfusion-fibrinolytic agents-streptokinase, urokinase

10. Prevention of remodeling and CHF-ACE inhibitors, ARBs- lisinopril, ramipril

11. Prevention of future attacks-platelet inhibitors-clopidogrel, β blockers, statins

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12. Opiod analgesics and Antianxiety agents13. Pethidine, Diazepam, alprazolam14. Anticoagulants –dalteparin, Enoxaparin15. General measures-O2 therapy, dopamine,

atropine, diltiazem,


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Thank you

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