Coupon Accepted Successfully!




The name angina pectoris denotes chest pain caused by accumulation of metabolites resulting from myocardial ischemia; due of imbalance between myocardial oxygen demand & supply.

The imbalance between oxygen delivery and myocardial oxygen demand can be corrected by decreasing oxygen demand or by increasing delivery (by increasing coronary flow).


Stable/Classical/Atherosclerotic/Effort Angina

Vasospastic/Variant/Prinzmetal Angina

Unstable /Preinfarction Angina

In effort angina, the imbalance occurs when the myocardial oxygen requirement increases, especially during exercise, and coronary blood flow does not increase proportionately. The resulting ischemia usually leads to pain.

Oxygen delivery decreases as a result of reversible coronary vasospasm.


Episodes of angina occur at rest and when there is an increase in the severity, frequency, and duration of chest pain in patients with previously stable angina.

Coronary flow reserve is frequently impaired in such patients because of endothelial dysfunction, which is associated with impaired vasodilation. As a result, ischemia may occur at a lower level of myocardial oxygen demand. In some individuals, the ischemia is not always accompanied by pain, resulting in “silent” or “ambulatory” ischemia.

Transient spasm of localized portions of coronary vessels, which is usually associated with underlying atheromas or vasculitic conditions like Raynauds.


Unstable angina is caused by episodes of increased epicardial coronary artery resistance or small platelet clots occurring in the vicinity of an atherosclerotic plaque. In most cases, formation of labile partially occlusive thrombi at the site of a fissured or ulcerated plaque is the mechanism for reduction in flow.

In effort angina, oxygen demand can be reduced by decreasing cardiac work or, by shifting myocardial metabolism to substrates that require less oxygen per unit of adenosine triphosphate (ATP) produced.

In variant angina, spasm of coronary vessels can be reversed by nitrate or calcium channel-blocking vasodilators.


In unstable angina, vigorous measures are taken to achieve both— increase oxygen delivery and decrease oxygen demand.


Determinants of myocardial oxygen demand:

  1. Wall stress
    1. Intraventricular pressure
    2. Ventricular radius (volume)
  2. Heart rate
  3. Contractility
  1. Wall thickness
  • Drugs that reduce cardiac size, rate, or force reduce cardiac oxygen demand. Thus, vasodilators, βeta-blockers, and calcium blockers have predictable benefits in angina.
  • Drugs (e.g. Ranolazine) that block this late sodium current can indirectly reduce calcium influx and consequently reduce cardiac contractile force.
  • Drugs that shift myocardial metabolism toward greater use of glucose (fatty acid oxidation inhibitors e.g. Trimetazidine) have the potential to reduce the oxygen demand without altering hemodynamics.

Determinants of Coronary Blood Flow & Myocardial Oxygen Supply:

  1. Perfusion pressure
  2. Duration of diastole
  3. Coronary vascular resistance
    * Resistance is determined mainly by intrinsic factors, including metabolic products and autonomic activity (hence, Beta-Blockers).

Determinants of Vascular Tone:

  1. Arteriolar tone: arterial blood pressure thus determines the systolic wall stress
  2. Venous tone: Venous tone thereby determines the diastolic wall stress.

* Vasodilators are mainstay for treatment and they mainly act through:


  1. Increasing cGMP: cGMP facilitates the dephosphorylation of myosin light chains, preventing the interaction of myosin with actin. Nitric oxide is an effective activator of soluble guanylyl cyclase and acts mainly through this mechanism. Important molecular donors of nitric oxide include nitroprusside and the organic nitrates used in angina.
  2. Decreasing intracellular Ca2+: Calcium channel blockers predictably cause vasodilation because they reduce intracellular Ca2+, a major modulator of the activation of myosin light chain kinase. Beta-blockers and calcium channel blockers also reduce Ca2+ influx in cardiac muscle fibers, thereby reducing rate, contractility, and oxygen requirement under most circumstances.
  3. Stabilizing or preventing depolarization of the vascular smooth muscle cell membrane: Potassium channel openers, such as minoxidil sulfate increase the permeability of K+ channels, probably ATP-dependent K+ channels. Certain newer agents under investigation for use in angina (eg, nicorandil) may act, in part, by this mechanism.
  4. Increasing camp in vascular smooth muscle cells: An increase in camp increases the rate of inactivation of myosin light chain kinase, the enzyme responsible for triggering the interaction of actin with myosin in these cells. This appears to be the mechanism of vasodilation caused by β2 agonists, drugs that are NOT used in angina (because they cause too much cardiac stimulation), and by fenoldopam, a D1 agonist used in hypertensive emergencies.


Drugs For Angina:

  1. Nitrates
    1. Isosorbide mononitrate                
    2. Isosorbide dinitrate                      
    3. Isosorbide trinitrate (NTG)
    4. Amyl nitrite                 
    5. Pentynyl erythritol tetranitrate
  2. Beta-blockers
  3. Calcium Channel blockers
  4. New Drugs
    1. Trimetazidine
    2. Ranolazine
    3. Detanonote
    4. Fasudil
    5. Ivabradine
  5. Other drugs
  • Coronary dilators (potassium channel openers)
  1. Nicorandil          
  2. Chromakalim                
  3. Phenacidil            
  4. Dipyridamol
  1. Nitrates
    1. Prodrugs of NO; polyol esters of Nitric oxide          
    2. Lipid soluble


  1. Act by liberating NO from endothelium
  2. This stimulates cGMP leading to inhibition of actin myosin interaction by blocking phosphorylation of myosin light chain kinase
  3. Repeated use can lead to development of tolerance
  4. Reason for tolerance is saturation of SH group present on receptor
  5. Intermittent use is best use
  6. Rx of tolerance – by free interval regime, SH donors can also reduce tolerance


  1. Well Absorbed orally
  2. High first pass metabolism           Best given Sublingual
  3. ISTN given S/L, acts with in 5 mins
  4. ISMN-least metabolized, highest bioavailability, 100% absorption, longest acting
  5. Metabolism by nitrate reductase
  6. Shortest acting nitrate-amyl nitrite (half life< 1 min). Given via inhalation route


  • DOC
  1. Acute attack of angina but not very effective for prophylaxis
  2. DOC-prophylaxis-beta blockers-C/I-variant angina
  3. Variant angina is treated by CCB like (Verapamil) 

Pharmacological actions of nitrates in coronary arteries:

  1. Venodilators
  2. Arterial dilators
  3. Shift blood from epicardium to subendocardium (Redistribution)
  4. DO NOT cause coronary steal phenomena
  5. Total coronary blood flow decreases a bit
  6. DO NOT increase oxygen requirements

Side effects

  1. MC-pulsatile headache- Monday’s disease                     
  2. Hypotension        
  3. Reflex tachycardia        
  4. Fluid retention-pedal edema         
  5. GERD                  
  6. Constipation                          
  7. Methemoglobinemia   
  1. Beta Blockers
    DOC in Ischemic heart disease


  1. Reduce frequency of angina episodes
  2. Improve exercise tolerance,
  3. Slowing and regularization of heart rate
  4. Prolong survival
  5. Only 3 agents used: Timolol, Propanolol, Metoprolol (PMT)
  6. They are now used as a first line drug for IHD mgmt


  1. Relative contraindications are
  2. Bradycardia, hypotension
  3. Moderate or severe (NYHA III & IV) LVF
  4. Shock
  5. Heart block
  6. Acute airway disease (asthma)

Caution: Beta blockers should not be withdrawn suddenly, because prolonged use might have lead to Upregulation of beta-receptor, can lead to worsening of patient condition. Therefore gradual tapering is recommended specially in case of short acting beta-blockers like propanolol and metoprolol.

  1. Calcium Channel Blockers
  • Verapamil and long acting dihydropyridine like amlodipine are used to for the treatment of angina.
  • CCB are useful by reducing heart rate and by decreases load on the heart.


Test Your Skills Now!
Take a Quiz now
Reviewer Name