Antianginals Flashcards
Goals of antianginals
↑delivery O2 to cardiac by ↑ coronary blood flow &/ or ↓ O2 demand by ↓ cardiac work. Stable Angina: ↓ work via systemic vasodilation
Organic Nitrates
Nitroglycerine
Isosorbide Dinitrate
Isosorbide-5-mononitrate
Amyl Nitrite
Nitroglycerine
-Organic Nitrate
-Mechanism: Release NO @ target tissues → activate guanylate cyclase → ↑cGMP → dephos of myosin light chain → myosin can’t interact w/ actin→relaxation, vascular smooth muscle
-Major: Venodilation: ↓PreLoad → ↓O2 demand
-Minor: redistributes flow from epi to endo providing some ischemic relief
- not coronary dilators
-Use: acute management of stable and variant angina
Admin: sublingual; rapid onsent
-slow-release buccal (chronic/prophylactic use limited by tolerance, avoid w/ eccentric dosing)
-extensive 1st-pass metabolism (low bioavilability!) if delivered orally
AE: hypotension, reflex tachycardia (use w/ β blocker, Ca++ channel blocker)
-Tolerance: repeated admin. → ↓effectiveness
- cross-tolerance between nitrates
- possibly due to diminished release of NO, systemic compensation (Na+/H20 retention)
- recovery ~8 hrs allows eccentric dosing (withdraw drug overnight)
Isosorbide Dinitrate
-Organic Nitrate
-Mechanism: Release NO @ target tissues → activate guanylate cyclase → ↑cGMP → dephos of myosin light chain → myosin can’t interact w/ actin→relaxation, vascular smooth muscle
-Major: Venodilation: ↓PreLoad → ↓O2 demand
-Minor: redistributes flow from epi to endo providing some ischemic relief
- not coronary dilators
-Use: acute management of stable and variant angina
Admin: sublingual; rapid onsent
-slow-release buccal (chronic/prophylactic use limited by tolerance, avoid w/ eccentric dosing)
-extensive 1st-pass metabolism (low bioavilability!) if delivered orally
AE: hypotension, reflex tachycardia (use w/ β blocker, Ca++ channel blocker)
-Tolerance: repeated admin. → ↓effectiveness
- cross-tolerance between nitrates
- possibly due to diminished release of NO, systemic compensation (Na+/H20 retention)
- recovery ~8 hrs allows eccentric dosing (withdraw drug overnight)
Isosorbide-5-mononitrate
-Organic Nitrate
-Mechanism: Release NO @ target tissues → activate guanylate cyclase → ↑cGMP → dephos of myosin light chain → myosin can’t interact w/ actin→relaxation, vascular smooth muscle
-Major: Venodilation: ↓PreLoad → ↓O2 demand
-Minor: redistributes flow from epi to endo providing some ischemic relief
- not coronary dilators
-Use: acute management of stable and variant angina
-Admin: not subject to first pass metabolism so it can be delivered orally and has a longer duration of action
AE: hypotension, reflex tachycardia (use w/ β blocker, Ca++ channel blocker)
-Tolerance: repeated admin. → ↓effectiveness
- cross-tolerance between nitrates
- possibly due to diminished release of NO, systemic compensation (Na+/H20 retention)
- recovery ~8 hrs allows eccentric dosing (withdraw drug overnight)
Amyl Nitrite
-Organic Nitrate
-Mechanism: Release NO @ target tissues → activate guanylate cyclase → ↑cGMP → dephos of myosin light chain → myosin can’t interact w/ actin→relaxation, vascular smooth muscle
-Major: Venodilation: ↓PreLoad → ↓O2 demand
-Minor: redistributes flow from epi to endo providing some ischemic relief
- not coronary dilators
-Use: acute management of stable and variant angina
-Admin: inhalation (bypasses liver)
AE: hypotension, reflex tachycardia (use w/ β blocker, Ca++ channel blocker)
-Tolerance: repeated admin. → ↓effectiveness
- cross-tolerance between nitrates
- possibly due to diminished release of NO, systemic compensation (Na+/H20 retention)
- recovery ~8 hrs allows eccentric dosing (withdraw drug overnight)
Classes of antianginals
Organic nitrates, Calcium blockers, Beta Blockers
Calcium blockers
Dihydropyridines: Nifedipine, Amlodipine (long), Felodipine (long)
Non-dihydropyridines: Verapamil, Diltiazem
Nifedipine
-Dihydropyridine Calcium blocker
-Mechanism: ↓Ca2+ influx through Ca2+ channels to reduce intracellular Ca2+ levels, leading to relaxation
-venodilation (↓PL)
- arterial dilation (↓PL, ↓AL)
- ↑coronary blood flow
Action: ↓ SVR and arterial tone
-Major effect of DHPs is vasodilation
Use: - Stable angina
- Variant (vasospastic, Prinzmetal’s) angina
- Hypertension
-AE: hypotension (no reflex tachycardia), bradycardia, ↓cardiac contractility
Contraindications: HF, hypotension, use with care with B blockers
Amlodipine
-Dihydropyridine Calcium blocker (long)
-Mechanism: ↓Ca2+ influx through Ca2+ channels to reduce intracellular Ca2+ levels, leading to relaxation
-venodilation (↓PL)
- arterial dilation (↓PL, ↓AL)
- ↑coronary blood flow
Action: ↓ SVR and arterial tone
-Major effect of DHPs is vasodilation
Use: - Stable angina
- Variant (vasospastic, Prinzmetal’s) angina
- Hypertension
-AE: hypotension (no reflex tachycardia), bradycardia, ↓cardiac contractility
Contraindications: HF, hypotension, use with care with B blockers
Felodipine
-Dihydropyridine Calcium blocker (long)
-Mechanism: ↓Ca2+ influx through Ca2+ channels to reduce intracellular Ca2+ levels, leading to relaxation
-venodilation (↓PL)
- arterial dilation (↓PL, ↓AL)
- ↑coronary blood flow
Action: ↓ SVR and arterial tone
-Major effect of DHPs is vasodilation
Use: - Stable angina
- Variant (vasospastic, Prinzmetal’s) angina
- Hypertension
-AE: hypotension (no reflex tachycardia), bradycardia, ↓cardiac contractility
Contraindications: HF, hypotension, use with care with B blockers
Verapamil
-Non-dihydropyridine calcium blocker
-Mechanism: Same as DHP plus:
- ↓HR
- ↓ inotropic state (↓ contractile force)
Action: ↓ myocardial contractile force & ↓ SVR
-Major effect is vasodilation AND act as negative chronotrops and inotropes!
-Use: Same as DHP plus: UNSTABLE angina, Supraventricular Tachy (AV nodal arhythmias; blocks calcium conduction at the AV node)
AE: Same as DHP plus: ↑[digoxin] → digitalis toxicity
Contraindications: sick sinus syndrome (→ arrhythmias), AV nodal disease, Beta blockers, heart failure, hypotensioin
Diltiazem
-Non-dihydropyridine calcium blocker
-Mechanism: Same as DHP plus:
- ↓HR
- ↓ inotropic state (↓ contractile force)
Action: ↓ myocardial contractile force & ↓ SVR
-Major effect is vasodilation AND act as negative chronotrops and inotropes!
-Use: Same as DHP plus: UNSTABLE angina, Supraventricular Tachy (AV nodal arhythmias; blocks calcium conduction at the AV node)
AE: Same as DHP
Contraindications: sick sinus syndrome (→ arrhythmias), AV nodal disease, Beta blockers, heart failure, hypotension
Beta Blockers
Atenolol (S)
Metaprolol (S)
Propanolol (NS)
Atenolol (S)
Metaprolol (S)
Propanolol (NS)
-beta blockers
-Mechanism: ↓HR, ↓inotropic state → ↓O2 demand
-not vasodilators
-Use: w/ DHP Ca++ blockers to offset AEs (reflex tachycardia) & somes w/ NG
- All beta-blockers equal antianginal (but not prophylactic in variant angina)
AE: prefer β1-selective agent; contraindicated w/ diabetic & asthma
-Do NOT use with Verapamil or diltiazem!
