Antianginals

Types of angina
• Classical/stable/predic • Vasospastic/ • Crescendo/Acute
table coronary
Prinzmetal’s angina syndrome
• Occurs upon exertion, • Unpredictable, • Increased
emotional stress; occurs at frequency and
• relieved by rest rest/sleep severity
(demand decreases • Due to vasospasm • Due to unstable
and becomes equal to of coronary artery plaque that
supply) ruptures leading
• Atherosclerosis is the to platelet
main cause aggregation and
thrombus
• 90% of angina cases formation
 Antianginals
1. Nitrates
• Short acting (GTN) Glyceryl trinitrate or Nitroglycerine
• Long acting: Isosorbide dinitrate (short acting by
sublingual route), isosorbide mononitrate, Erythrityl
tetranitrate, Pentaerythritol tetranitrate
2. β blockers
• Non selective: Propranolol
• Cardioselective: Atenolol, Metoprolol
3. Potassium channel openers:
• Nicorandil
 Classification
4. Calcium channel blockers:
Phenyl alkylamine: Verapamil
Benzothiazepines: Diltiazem
Dihydropyridines: Nifedipine, Felodipine,
Amlodipine, Nitrendipine etc.
5. Others: Dipyridamole, Oxyphedrine,
Trimetazidine, Ranolazine, Ivabradine
 Clinical classification
• Used to abort or terminate attack: GTN,
Isosorbide dinitrate (sublingually)
• Used for chronic prophylaxis: All other drugs
Nitrates
• ADRs: Throbbing headache, palpitation, dizziness and
fainting.
• Tolerance: Cross tolerance occurs among all nitrates.
The most practical way to prevent nitrate tolerance
is to provide nitrate free intervals everyday.
• Dependence: Sudden withdrawal after prolonged
exposure has resulted in spasm of coronary and
peripheral blood vessels. MI and sudden deaths have
been recorded.
 Interactions
• Sildenafil causes dangerous potentiation of
nitrate action: severe hypotension, MI and
deaths are on record.
Haemoglobin
| Sod. nitrite (10 ml of 3% solution i.v.)
Methaemoglobin
| Cyanide
Cyanomethaemoglobin
| Sod. thiosulfate (50 ml of 25% solution i.v.)
Methaemoglobin + Sod. thiocyanate
↓
Excreted in urine
 GTN
• Transdermal patches
• Oral presystemic metabolism: 90%
• Large doses are given orally to counter
hepatic metabolism
• SR tablets for chronic prophylaxis
• IV infusion to manage unstable angina
 Nitrates: Isosorbide dinitrate
• Sublingual (at the time of attack) or oral
(prophylaxis)

• Sustained release formulations-> 6-10 hours

duration
 Nitrates: Isosorbide mononitrate
• Active metabolite of isosorbide dinitrate
• Little first pass metabolism
• High bioavailability
• Longer acting (t1/2- 4 to 6 hours)
• Last dose to be taken in the afternoon
• SR tablets once a day in the morning
 Erythrityl tetranitrate and
pentaerythritol tetranitrate
• Erythrityl tetranitrate and pentaerythritol
tetranitrate
• Longer acting drugs
• Used for chronic prophylaxis
 β blockers
• Β blockers to be taken on a regular schedule
• Dose individualistic
• Cardioselective are preferred over non
selective
• Heart: negative inotropic action
Comparative properties of representative
calcium channel blockers
Verapamil Nifedipine Diltiazem
• Heart rate ↓ ↑ ↓, –
• A-V conduction velocity ↓↓ – ↓↓
• Vascular smooth muscle ++ +++ +
relaxation
• Clinical use in Arrhythmia Angina Arrhythmia
Angina Hypertension Angina
Hypertension Hypertension
 Other antianginal drugs
• Dipyridamole:
• Powerful coronary dilator
• Inhibits platelet aggregation
• Decreases uptake and breakdown of
adenosine leading to increased
concentrations. Adenosine dilates resistance
vessels.
• Prophylaxis for coronary and cerebral
thrombosis
 Trimetazidine
• Adjuvant therapy
• Improves cellular tolerance to ischemia
• Inhibits mitochondrial long chain 3- ketoacyl-
CoA- thiolase (LC3-KAT) and reduces fatty acid
metabolism
• Ischemic myocardium shifts to utilization of
glucose for the same amount of ATP
generated but with less oxygen consumption.
 Ranolazine
• Used for chronic prophylaxis
• Trimetazidine congener
• Shifts ATP production to more efficient carbohydrate
oxidation
• Inhibits late Na+ currents which indirectly facilitate Ca++ entry
--- reduction of Ca++ overload in myocardium

Oxyphedrine: improves myocardial metabolism; vasodilator

 Ivabradine
• Pure heart rate lowering antianginal drug.
• Blockade of cardiac pacemaker (sino-atrial) cell ‘f’ channels.
• Blockade of If current by ivabradine results in heart rate
reduction
• Heart rate reduction decreases cardiac oxygen demand
• Ivabradine is indicated in chronic stable angina in patients
who are intolerant to β blockers or when the latter are
contraindicated
• It can also be used in sinus tachycardia.