أ. م . د. وحدة اليوزبكيDepartment of Pharmacology- College of Medicine- University of Mosul-2014 Antianginal Drugs
1
Objectives
- At the end of this lecture, students should be able to :
1- Define Angina Pectoris.
2- State Physiology of Angina
3- List Classes of Antianginal Drugs.
4- Identify action, clinical uses and side effects of Organic Nitrates (Nitrites)
5- Identify action of B Blocker in Angina
6- Identify action of Calcium Channel Blocking drugs in AP
- At a level accepted to the quality assurance standards for the College of Medicine/ University of Mosul.
Angina Pectoris: Defeniton
- A transient episodes (fifteen seconds to fifteen minutes) of sudden, severe, pressing substernal pain radiating to the to the neck, jaw, back, and arms.
- It is caused by insufficient coronary blood flow to meet the oxygen demands of the myocardium
1- during exertion (physical activity or emotional stress).
2- From a spasm of the vascular smooth muscle.
3- From incomplete obstruction of blood vessels caused by atherosclerotic lesions.
Types of Angina
Angina pectoris has three overlapping patterns:
1. Stable or typical angina (most common).
2. Unstable angina (lies between stable angina on the one hand a myocardial infarction on the other).
3. Prinzmetal or variant angina (due to coronary artery spasm).
Classification of Antianginal Drugs
Three main classes of drugs (alone or in combination):
1- Organic Nitrates.
2- B-Blockers.
3- Calcium Channel Blockers.
4- Other vasodilators (Nicorandil).
Organic Nitrates (Nitrites)
These agents are simply nitrous & nitric acid esters of alcohols.
3 Types:
1- Extremely volatile liquid: Amyl nitrite.
2- Solid: Isosorbide Dinitrate (long action).
3- Moderately volatile liquid: Nitroglycerine (Glycerine Trinitrate, (GTN)) (Angesid). Rapid action. Prototype Drug
Nitroglycerine (Glycerine Trinitrate (GTN)) Mechanism of Action
Nitroglycerine (Glycerine Trinitrate (GTN)) Mechanism of Action
- At therapeutic doses GTN has 2 effects:
1- Dilatation of large veins which decrease venous return to the heart so decrease preload & the work of heart.
2- Dilatation of the coronary vasculature which increase blood supply to heart muscle.
Pharmacokinetic of GTN
1- Nitrates rapidly absorbed through GIT.
2- Organic nitrates undergo extensive 1st pass metabolism, so given sublingually, as sub dermal patches or by inhalation.
3- The time to onset of action varies from one minute for nitroglycerin to more than one hour for isosorbide mononitrate.
4- Bioavailability is low (10% - 20%).
5- Excretion primarily in the form of glucuronide derivative of denitrated metabolites largely by way of kidneys.
Clinical Uses of GTN
- 1- Angina Pectoris (both classical & variant angina).
These compounds cause a rapid reduction in myocardial oxygen demand, followed by rapid relief of symptoms. They are effective in stable and unstable angina as well as in variant angina pectoris.
2- Left ventricular failure.
3- Cyanide Poisoning.
Met Hb Nitrite + Hb
Cyano Met Hb Met Hb + Cyanide
Na Thiosulphate + Cyano Met Hb Thiocyante + urea + Hb
Side Effects of GTN
1- Throbbing headache (the most common) occur in 30-60 %.
2- High doses: Postural hypotension, facial Flushing & tachycardia.
3- Tolerance: develops rapidly.
4- Over doses of Nitrate (poisoning): Nitrate change Hb to met Hb hypoxia.
Death can occur from circulatory collaps & respiratory failure.
B Blocker in Angina
Action in AP:
Beta adrenergic blocking agents decrease the oxygen demands of the myocardium by lowering both the rate and the force of contraction of the heart, which lead to decrease O2 demand of myocardium during rest & exercise.
Uses of B Blocker in Angina
1- B Blocker reduce the frequency & severity of Anginal attacks.
2- Useful in the treatment of patients with myocardial infarction.
Notes:
- Propranolol is the prototype for this class of compounds, but it is not cardio selective. Thus, other B-blockers, such as metoprolol, acebutolol, or atenolol, are preferred.
- It important not to discontinue B-blocker therapy suddenly.
- Propranolol is contraindicated in case of variant Angina ???.
Undesirable B Blocker effects in Angina
Fatigue
impaired exercise tolerance
Insomnia
unpleasant dreams,
worsening of claudication
erectile dysfunction.
Calcium Channel Blocking drugs in AP
Action:
These drugs inhibit entrance of calcium into cardiac & sm.m cells of coronary & systemic arterial bed, so all Ca. Ch. Blockers are vasodilators.
- Nifedipine: Exerts a greater effect on sm.m in the peripheral vessels.
- Verapamil: Causes greater negative inotropic effects than nifedipine, but it is a weaker vasodilator.
- Diltiazem: Intermediate in its action.
Note: B Blockers should not be used with Ca. channel blocker for treatment of angina??? .
Nicorandil: New drug
Effective vasodilator through 2 actions:
1- Acts as nitrate by activating cyclic GMP.
2- Open the ATP-dependent K channel which allow K efflux & hyperpolarization of the membrane which reduce Ca entery & induces muscular relaxation.
Note & Question
Variant (Prinzmetal) angina caused by spontaneous coronary spasm (either at work or at rest, rather than-increased myocardial oxygen requirements is controlled by organic nitrates or calcium channel blockers,
B-blockers are contraindicated. ???
