11) Anti-Anginal Drugs Flashcards
Evolution of a plaque
- Normal artery
- Fatty streak
- Mature plaque
- Ruptured plaque with thrombus formation
Effects of myocardial injury
- ST wave elevation
- Occurs with or without loss of R wave
Effects of myocardial ischemia
- ST wave depression
- Occurs with or without loss of T wave inversion
- Due to altered repoarization
Effects of myocardial infarction
- Deep Q wave
- Due to absence of depolarization
3 zones of myocardial damage (least to most damaging)
- Zone of ischemia
- Zone of injury
- Zone of infarction/necrosis
Normal response of myocardium to increased needs / demands / requirements of oxygen
- Coronary artery (CA) dilation
In diseased CA (atherosclerosis &/ plaque), the flow/ supply to myocardium
- Is less so the myocardium “starves” for oxygen (ischemia)
Cardinal sign of coronary artery disease (CAD)
- Chest pain/angina
Anti-anginal agents (classes)
- Nitrates
- Calcium channel blockers
- Beta blockers
- Metabolism modifiers
Anti-anginal nitrates (brands/generics)
- Nitrostat (nitroglycerin)
- Ismo (isosorbide mononitrate)
- Bidil (isosorbide dinitrate and hydralazine)
- Isordil (isosorbide dinitrate)
Anti-anginal calcium channel blockers (brands/generics)
- Nymalize (nimodipine)
Anti-anginal beta blockers (brands/generics)
- Metoprolol
- …OLOL
- Anything ending in -olol
Anti-anginal metabolism modifiers (brands/generics)
- Ranexa (ranolazine)
Nitrates (all anti-anginal mentioned) mechanism of action
- Nitroglycerin forms the free radical nitric oxide (NO)
- NO activates cGMP in smooth muscle
- Results in vasodilatation and reduction in preload and afterload
Nitroglycerin duration of action
- 10 to 20 min (sublingual for relief of acute attacks)
- 8 to 10 h (transdermal for prophylaxis)
Nitroglycerin (glyceryl trinitrate) is rapidly de-nitrated in the liver and in smooth muscle to…
- First to the 2 dinitrates (glyceryl dinitrate)…retain a significant vasodilating effect
- More slowly to the mononitrates…much less active
Because of the high enzyme activity in the liver, the first-pass effect for nitroglycerin is
- About 90%
Short-acting nitrates
- Nitroglycerin sublingual (SL): Rapid onset (1 min), short duration (15 min)
- Isosorbide dinitrate SL: Rapid onset (1 min), duration (20–30 min)
Intermediate-acting nitrates
- NTG oral, isosorbide dinitrate and mononitrate, oral
- Slow onset
- Duration: 2-4 h
Long-acting nitrates
- Transdermal nitroglycerin
- Slow onset
- Duration: 10 h
Ultra short-acting nitrate
- Amyl nitrite Volatile liquid
- Vapors are inhaled
- Onset seconds
- Duration: 1-5 min
Nitrates adverse reactions (ADRs)
- Only the smallest dose required for effective relief of the acute anginal attack should be used
- Excessive use may lead to the development of tolerance
- Severe hypotension, including tachycardia (from the baroreceptor reflex), orthostatic hypotension, headache, and blurring of vision
Nitrates drug interactions
- Administration of nitroglycerin is contraindicated in patients who are using PDE-5 inhibitors (e.g. sildenafil (Viagra®), tadalafil, vardenafil and avanafil)
- These compounds have been shown to potentiate the hypotensive effects of organic nitrates
Calcium channel blockers anti-anginal mechanism of action
- Block voltage-gated L-type calcium channels (cardiac and smooth muscle)
- Reduce intracellular calcium concentration and muscle contractility
Dihydropyridine calcium channel blockers
- Amoldipine
- Felodipine
- Isradipine
- Nicardipine
- Nifedipine
- Nimodipine
- Nisoldipine
Amoldipine
- Brand = Norvasc
- Onset = 30min
- DOA = 24h
Felodipine
- Brand = Plendil
- Onset = 2-5h
- DOA = 24h
Isradipine
- Brand = Dynacirc
- Onset = 2h
- DOA = > 12h
Nicardipine
- Brand = Cardene
- Onset = 30min
- DOA = < 8h
Nifedipine
- Brand = Procardia
- Onset = 20min
- DOA = ?
Nimodipine
- Brand = Nimtop
- Onset = ?
- DOA = 6h
Nisoldipine
- Brand = Sular
- Onset = ?
- DOA = 12h
Phenylaklyamine calcium channel blockers
- Verapimil
Verapimil
- Brand = Calan, Verelan
- Onset = 30min
- DOA = 8h
Benzothiazepine calcium channel blockers
- Diltiazem
Diltiazem
- Brand = Cardizem
- Onset = 30-60min
- DOA = 4h
All calcium channel blockers are
- CYP450 substrates
CCB metabolism and excretion
- Hepatic metabolism
- Excreted in urine
CCBs with extensive first pass metabolism
- Felodipine
- Isradipine
- Nimodipine
- Nisoldipine
- Verapamil
- Diltiazem
Beneficial beta-blocking drug actions
- Decreased heart rate, cardiac force, blood pressure
- Reduce cardiac work, and oxygen demand
Detrimental beta-blocking drug actions
- Increased heart size
- Longer ejection period
Beta blockers are used only for prophylactic therapy of
- Angina
- No value in an acute attack
Ranolazine (Ranexa) action
- Relatively new drug
- Reduces a late, prolonged sodium current
(late INa) in myocardial cells - Decrease in intracellular Na causes increased Ca expulsion (via Na/Ca transporter)
- Reduces cardia force and work
- May also alter cardiac metabolism
Ranolazine (Ranexa) ADRs
- QT- prolongation potentially (it affects Na+ currents)
- Renal failure
- Most commonly mild ADR
profile: N/V/D and
constipation - Hypotension
- Contraindicated with concurrent strong CYP3A4 inhibitors and inducers because it is a substrate of CYP3A
