Antianginals Flashcards
Drugs used to treat Angina?
Nitrates
Isosorbide dinitrate, Isosorbide mononitrate,
Nitroglycerin, Sodium Nitroprusside
b-blockers
Atenolol, Metoprolol, Propranolol
Ca2+ channel blockers
Amlodipine, Nifedipine, Diltiazem, Verapamil
Na+ channel blockers
Ranolazine
Nitrates MOA?
Nitrates mimic the actions of endogenous NO
Rapid reduction in myocardial O2 demand (systemic
vasodilatation) & relief of symptoms
• In CV system, nitrous oxide (NO) is primarily produced by vascular endothelial cells
• NO functions:
• vasodilation
• anti-thrombotic
• anti-inflammatory
(all involve NO-stimulated formation of cGMP)
NItrates cardiovascular action on coronary, cardiac, and systemic vasculature?
Systemic Vasculature
• Vasodilation (venous dilation > arterial dilation)
• Decreased venous pressure
• Decreased arterial pressure (small effect)
Cardiac
• Reduced preload & afterload (decreased wall
stress)
• Decreased oxygen demand
Coronary • Prevents/reverses vasospasm • Vasodilation • Improves subendocardial perfusion • Increased oxygen delivery
Nitrates Clinical applications?
• Variant angina
• Stable & unstable angina
• IV nitroglycerin = unstable angina & acute heart failure
• Nitroglycerin (sublingual or spray) = first-line therapy
for treatment of acute anginal symptoms
• Isosorbide mononitrate = orally for prophylaxis
(sustained release preps available)
Nitroglycerin PK?
• Undergoes sig. first-pass metabolism à taken
sublingually, transdermally, buccal, IV)
• Fast-acting: 2-5 min to onset of action
• Effect usually lasts ~ 30 min
• Longer-acting (12-24 h) preparations are available (eg,
transdermal patches)
Isosorbide mononitrate PK?
• Longer onset of action & duration of action than
nitroglycerin (more useful for long-term prophylaxis)
• Isosorbide mononitrate = >1 h (time to onset of action)
& nearly 100 % oral bioavailability
• Metabolites have longer t1/2’s and significant activity
Describe Nitrate tolerance?
- Develops rapidly (vessels desensitize to vasodilation)
* Can be overcome by daily ‘nitrate-free interval’ (10–12h) eg, nitroglycerin patches: ‘on’ for 12 h, ‘off’ for 12 h
Nitrates AE?
- Headache (cerebral vasodilation)
- High doses = postural hypotension, facial flushing, reflex tachycardia
Contraindications
• Sildenafil
Sodium Nitroprusside MOA, clinical applications, PK, and AE?
Direct NO donor = very effective, immediate vasodilator
Clinical Applications
• ICU & emergency settings
• Used to treat severe hypertensive emergencies &
severe heart failure
Pharmacokinetics
• IV only (t1/2 < 3min)
• Continuous infusion is required
AE • Severe nausea • Vomiting • Headache etc • High doses = cyanide intoxification (nitroprusside releases cyanide along with NO)
B blockers MOA in antianginal. Which ones are used for anti anginal? Clinical applications
• Block b1 receptors
• Reduce both heart rate & contractility
• O2 demand is reduced during exercise and at rest
• Reduce frequency and severity of angina attacks
Drugs
• Propranolol = non-selective
• Metoprolol & atenolol = b1 selective
Clinical Applications
• Recommended in all patients (unless contraindicated)
with stable angina who have had an ACS or who have
left ventricular dysfunction
AE of Beta blockers?
- Bradycardia
- Conduction disturbances
- Bronchoconstriction
- Worsening of symptoms of peripheral vascular disease
- Fatigue,
- CNS effects
- Impotence etc.
Contraindications for beta blockers?
• Variant angina (treated by Ca2+ channel blockers or
nitrates)
• Use with caution in patients with obstructive airway
disease or peripheral vascular disease and, initially at
very low doses in patients with heart failure
• NEVER discontinue abruptly (can cause rebound
hypertension or angina)
Calcium channel blocker MOA for angina alleviation?
• Ca2+ is essential for muscular contraction
• Ca2+ is increased in ischemia due to hypoxia-induced
membrane depolarization
• L-type Ca2+ channel is dominant in cardiac & smooth
muscle
Ca2+ channel blockers improve angina symptoms by:
• Coronary & peripheral vasodilatation
• Reducing contractility
Degree to which above changes occur varies with types of blocker
Clinical applications of calcium channel blockers?
• Used in combination with b-blockers when initial
treatment with b-blocker is not successful or, as a bblocker
substitute when b-blockers are
contraindicated
• Relieve symptoms of variant angina
Nifedipine/amlodipine MOA and AE in regards to Angina usage?
• Minimal effect on cardiac conduction or HR
• Short-acting dihydropyridines should be avoided unless
combined with b-blocker (increased mortality)
Adverse Effects
• Flushing
• Headache
• Hypotension
• Peripheral edema (eg, pedal edema)
• Constipation
Verapamil MOA and AE for angina? Contraindications?
• Slows AV conduction directly à HR, contractility, BP &
O2 demand
• Has greater inotropic effects than dihydropyridines
(weaker vasodilator)
Adverse Effects
• Same as other Ca2+ channel blockers
• Constipation
Contraindications:
• Preexisting depressed cardiac function or AV conduction
abnormalities,
• Use with caution in patients taking digoxin (increases
digoxin levels)
Diltiazem MOA, AE, and contraindications?
• Similar effects to verapamil (slow AV conduction)
• HR (lesser extent than verapamil) & BP
Adverse Effects
• Same as other Ca2+ channel blockers but incidence is low
Contraindications
• Same as verapamil
Ranolazine MOA? Clinical applications?
• Blockade of Na+ current that facilitates Ca2+ entry via
Na+/Ca2+ exchanger
• Decreased intracellular Ca2+ reduces ventricular tension &
myocardial O2 demand
• Thought to also produce myocardial relaxation
• May modify fatty acid oxidation
Clinical applications:
• Option for patients who have failed all other
antianginal therapies
Ranolazine PK and AE?
Pharmacokinetics
• Metabolized by CYP 3A4
Adverse Effects • QT interval prolongation (main concern with this new drug) • Nausea • Constipation • Dizziness
Stable angina treatment?
• Acute attacks: promptly relieved by rest or nitroglycerin
• Maintenance therapy: long-acting nitrates & bblockers
are preferred
• Ca2+ channel blockers: when b-blockers are not
successful or are contraindicated
• Ranolazine: when nitrates, b-blockers & Ca2+-blockers
are unsuccessful
Aspirin & aggressive cardiovascular risk reduction should be carried out in all patients
Unstable Angina treatment?
• The link between stable angina & MI. Chest pains occur more frequently & precipitated more easily.
• Symptoms relieved by rest or nitroglycerin
• In addition, therapy with nitroglycerin & b-blockers
should be considered
Variant (prinzmetal’s) angina treatment?
• Episodic angina due to coronary artery spasm. Unrelated to activity, HR or BP.
• Symptoms respond to nitroglycerin & Ca2+ channel
blockers
• All available Ca2+ channel blockers appear to be equally effective.
• Choice of drug is based on each individual patient
Nitrates effect on HR, Arterial Pressure, EDV, Contractility, and Ejection time?
HR: reflex increase Arterial Pressure: decrease EDV: decrease Contractility: reflex increase ejection time: decrease
Beta blockers of calcium channel blockers effect on HR, Arterial Pressure, EDV, Contractility, and Ejection time?
HR: Decrease Arterial Pressure: decrease EDV: increase Contractility: decrease ejection time: increase
Nitrates +beta blockers of calcium channel blockers effect on HR, Arterial Pressure, EDV, Contractility, and Ejection time?
HR: Decrease Arterial Pressure: decrease EDV: none or decreases Contractility: dnone ejection time: none
Drugs commonly used with concomitant disease None? Recent MI? Asthma,COPD? HTN? Diabetes? Chronic Renal Disease?
None-nitrate, b-blocker, ca channel blocker
Recent MI-nitrate, b-blocker
Asthma,COPD-nitrate,
calcium channel blocker
HTN-b-blocker, calcium channel blocker(rarely nitrates)
Diabetes-Nitrate, calcium channel blockers
Chronic Renal Disease-nitrates, calcium channel blockers, (beta blockers rarely)
