Antianginal

Front 1

Beta-Blockers (e.g. propranolol)

Back 1

hemodynamic effects:
• Effects that decrease myocardial oxygen demand: ↓ HR, ↓ contractility, ↓ BP
• Effects tending to increase oxygen demand: ↑ LV EDV (↑ radius)
• Effects on oxygen delivery:
o ↓ HR → ↑ diastolic perfusion time → ↑ coronary perfusion
o main benefit is on effort angina (brought about by ↓ oxygen demand)
• Effective in prevention of attacks in patients with effort angina.
o β-blockers may slow HR → ↑ filling → ↑ radius (this would ↑ O2 demand), but net effect is to ↓ oxygen demand
o In atherosclerotic CAD may ↑ perfusion during.
• By ↓ HR → ↑ time in diastole → ↑ perfusion

Front 2

β-Blocker Adverse Effects:

Back 2

• Sudden discontinuation → adverse effects
o Exacerbation of angina
o MI
o Gradual tapering of dose recommended
• Upregulation of β-blockers over time

Front 3

Diltiazem (dil tye’ a zem)

Back 3

• Non- dihydropyridine calcium channel blockers
• Lower vascular selectivity – so targets heart more →
o ↓ HR
o Decrease AV conduction
o Decrease contractility

Front 4

Nifedipine (nye fed’ i peen)

Back 4

• Dihydropyridine calcium channel blockers
• Higher vascular selectivity → vasodilation → ↑ HR
o Little change in HR or may go up a bit
o Little effect on AV conduction
o Not much change in cardiac contractility
• May produce reflexive ↑ in HR

Front 5

Verapamil (ver ap’ a mil)

Back 5

• Non- dihydropyridine calcium channel blockers
• Lower vascular selectivity – so targets heart more →
o ↓ HR
o Decrease AV conduction
o Decrease contractility

Front 6

Isosorbide dinitrate (eye soe sor’ bide)

Back 6

• Organic Nitrate
• Significant first pass metabolism
• Mechanism: Nitrates produce NO → activte guanylylcyclase → ↑ cGMP → smooth muscle relaxation
• Dilate veins and arteries
o Dilate veins more than arteries at low concentrations
o Relaxation of vascular smooth muscle
• Relaxation of other smooth muscle
• Antiplatelet effect (minor effect)

Front 7

Isosorbide-5-mononitrate

Back 7

• Organic Nitrate
• bioavailability = 100% (no significant 1st pass effect)
• Mechanism: Nitrates produce NO → activte guanylylcyclase → ↑ cGMP → smooth muscle relaxation
• Dilate veins and arteries
o Dilate veins more than arteries at low concentrations
o Relaxation of vascular smooth muscle
• Relaxation of other smooth muscle
• Antiplatelet effect (minor effect)

Front 8

Nitroglycerin

Back 8

• Organic Nitrate
• Significant first pass metabolism
• Mechanism: Nitrates produce NO → activte guanylylcyclase → ↑ cGMP → smooth muscle relaxation
• Dilate veins and arteries
o Dilate veins more than arteries at low concentrations
o Relaxation of vascular smooth muscle
• Relaxation of other smooth muscle
• Antiplatelet effect (minor effect)

Front 9

Ranolazine (ra noe’ la zeen)

Back 9

• Mechanism unknown
• Little effect on HR or BP
• Administration: Oral
• Metabolism: Extensive metabolism, p-glycoprotein (drug interactions)
• Adverse Effects:
o Dizziness
o Headache
o Constipation
o Nausea
o ↑ QT interval (risk of arrhythmia) – risk of arrhythmia

Front 10

Adverse effects of organic nitrates:

Back 10

• Headache
• Tolerance
• Orthostatic hypotension
• Sildenafil (Viagra) increases hypotensive effect (phosphodiesterase-5-inhibitor)

Front 11

Calcium Channel Blocker Uses:

Back 11

Hypertension
Angina
Arrhythmias

Front 12

Calcium Channel Blocker Mechanism:

Back 12

Vasodilation (mainly arterial), reflexive ↑ HR
o All lower BP (↓ PVR and BP) → ↓ O2 demand
o ↓ contractility → ↓ O2 demand
o HR – depends on class of CCB
• Nifedipine & other dihydropyridines (higher vascular selectivity)
o Prominent vasodilation → ↑ HR
o Little if any effect AV node conduction
o Minor ↓ in cardiac contractility (direct effect)
• Verapamil, Diltiazem (lower vascular selectivity), major effects on heart
o Direct action on heart → ↓ HR
o ↓ AV conduction
o ↓ in cardiac contractility

Front 13

Adverse Effects of Calcium Channel Blockers:

Back 13

• Excessive vasodilation (dizziness, ↓ BP, headache, flushing)
• Constipation
• Peripheral edema
• Reported concerns about safety of immediate-release nifedipine
• Drug interactions (hepatic metabolism)

Front 14

What are the determinants of myocardial oxygen demand?
Demand:

Back 14

a. Wall stress (pressure, radius, thickness)
o ↑ radius → ↑ stress
b. Contractility
c. Heart Rate

Front 15

List 3 organic nitrates used in the treatment of angina.

Back 15

a. Nitroglycerin
b. Isosorbide dinitrate
c. Isosorbide-5-mononitrate

Front 16

List 4 routes of administration of organic nitrates.

Back 16

a. Sublingual (lingual spray also available) (short-acting)
b. Oral (long-acting)
c. Topical (ointment and transdermal patch) (long-acting)
d. i.v. (hospital use)

Front 17

Describe the importance of first pass metabolism of orally administered organic nitrates.

Back 17

• Oral (NTG & Isosorbide dinitrate) → Significant first pass metabolism
• Isosorbide-5-mononitrate: bioavailability = 100%

Front 18

List the classes of antianginal drugs.

Back 18

a. Organic Nitrates
i. Short acting vs. long-acting
ii. A given drug can be given by several preparations
b. β-Blockers
c. Calcium Channel Blockers
d. Ranolazine

Front 19

Drugs used in vasospastic angina –

Back 19

a. Nitrates
b. Calcium Channel Blockers

Front 20

Uses of β-Blockers

Back 20

• Hypertension
• Heart Failure
• Arrhythmias
• Angina