Anti-Anginal Drugs

Question 1

How can the heart return to balance in angina? (two ways)

Answer 1

1. decrease O2 demand

2. Increase O2 supply

Question 2

What types of drugs decrease O2 demand?

Answer 2

• beta blockers decrease heart rate and contractility
• some calcium channel blockers can also reduce HR and contractility
• nitrates and calcium channel blockers can dilate veins to reduce venous return, reduce preload and after load

Question 3

What types of drugs increase O2 supply?

Answer 3

• dilate coronary blood vessels using vasodilators (calcium channel blockers), statins, and antithrombotics
• myocardial vascularization (bypass or angioplasty)

Question 4

What does ischemia affect?

Answer 4

• affects ATP production and contractile function, which decrease CO
• heart can’t tolerate O2 debt like skeletal muscle
• ST segment depressed, T wave inverted

Question 5

Preload?

Answer 5

• EDV
• determines end diastolic fiber length and tension
• venodilators decrease preload

Question 6

Afterload?

Answer 6

• resistance heart must over come
• determines systolic fiber length and tension
• depends on arterial BP and stiffness
• ateriodilators decrease after load
• determined by PR, HR, contractility, ejection time (stronger contraction equals shorter ejection time)

Question 7

What determines coronary blood flow?

Answer 7

• coronary perfusion pressure (aortic diastolic pressure) and duration of diastole
• inversely proportional to coronary vascular bed resistance

Question 8

Factors that influence coronary vascular bed resistance?

Answer 8

• local metabolic products (decrease O2, increased H+, lactate, adenosine causes more dilation)
• endothelial factors (nitric oxide causes more dilation)
• autonomic activity
• pharmocologic agents (calcium channel blockers, nitrates)

Question 9

What is the most potent vasodilator?

Answer 9

• ischemia- local metabolites accumulate causing a traffic jam, cannot increase blood supply to resolve imbalance
• vasospastic coronary vessels can be relaxed and dilated, can open collaterals

Question 10

What is the problem with atherosclerotic vessels?

Answer 10

• do not dilate like normal vessels
• short acting vasodilators (dipyridamole, adenosine) may cause coronary steal effect (less dilation in ischemic areas, blood flows to normal areas)
• can induce angina
• dont use dipyridamole or adenosine for patients with CHD, can be used to diagnose CHD (stress test)

Question 11

Types of Angina? Treatments?

Answer 11

1. Fixed, stable
   - precipitated by exercise (O2 demand increase)
   - caused by obstruction of coronary arteries, atherosclerosis
   - relieved by rest
   - treat with nitrates, calcium blocker, beta blocker
2. Variant, prinzmetals
   - occurs at rest or during sleep, unpredictable
   - caused by vasospasm or injured coronary artery
   - treat with nitrates, calcium channel blocker
3. Unstable
   - increase in frequency or severity of anginal attacks
   - caused by combo of atherosclerosis, thrombosis, vasospasm
   - treat with angioplasty, nitrates, beta blocker, anti platelet
4. silent ischemia
   - ischemia of myocardium without pain or symptoms

Question 12

Mechanism of action of nitrates?

Answer 12

1. get into blood vessel and release nitric oxide
2. NO is activated by Guanylyl cyclase
3. increase in cGMP
4. cGMP dephosphorylates myosin light chain
5. actin and myosin dissociates
6. smooth muscle relaxes, vessel dilates

Question 13

Why can’t sildenafil (viagra) be used with nitrates?

Answer 13

• phosphodiesterease degrades cGMP to GMP
• viagra blocks phosphodiesterase which leads to an accumulation of too much cGMP
• this causes more relaxed blood vessels and more vasodilation
• could lead to severe hypotension

Question 14

Nitrate effects?

Answer 14

• vasodilation: veins > arteries > arterioles
• preload reduced due to dilation of veins
• afterload reduced due to dilation of arterioles at high doses
• relieves vasospasm in variant angina
• increases collateral flow to ischemic areas
• decreases platelet aggregation

Question 15

Nitroglycerin?

Answer 15

• nitrate
• rapidly acting, takes effect in 2 minutes, terminates acute attack
• administer sublingual or spray
• short duration, lasts 25 mins
• avoids first pass effect
• give to patient suspected of angina

Question 16

Isosorbide dinitrate?

Answer 16

• nitrate
• administer sublingual
• takes effect in 5 mins, lasts 1 hour
• use to terminate acute angina attack

Question 17

Amyl Nitrite?

Answer 17

• rapidly acting
• give to patient for acute angina attack
• inhalation

Question 18

Prolonged nitrates used for angina?

Answer 18

-take orally and topically

1. nitroglycerin ointment
2. oral, sustained release nitroglycerin
3. nitroglycerin transdermal patch
4. Isosorbide dinitrate take orally once per day
5. Isosorbide mononitrate

Question 19

When to use nitrates?

Answer 19

• stable angina
• variant angina
• unstable angina
• acute angina attack

Question 20

Monday disease?

Answer 20

• must have a nitrate free interval that lasts at least 8 hours
• adverse effects felt from nitrates, are gone quickly after person builds a tolerance
• tolerance and rebound

Question 21

Adverse effects of nitrates?

Answer 21

• excessive dilation, decrease BP, reflex tachycardia
• headache (meningeal artery dilation)
• potential severe hypotension with erectile dysfunction treatment (sildenafil)

Question 22

Mechanism of calcium channel blocker? effects?

Answer 22

1. block L type calcium channel blocker to prevent influx of calcium in smooth muscle, cardiac nodal and muscle cells
2. decrease in arteriolar tone, decreased after load
3. relieve coronary artery spasm
4. decrease HR and contractility

Question 23

Verapamil and Diltiazem?

Answer 23

• non dihydropyridines
• heart and blood vessels

Effects:

• calcium channel blocker in heart and blood vessels
• vasodilates vessels, decreases after load
• decreases HR and AV node (verapamil)
• decreases contractility of heart (verapamil), high doses or toxicity may cause CHF
• Diltiazem reduces double product, prolongs exercise time

Clinical use:

• relieves variant and stable angina, don’t use for unstable
• use for fast atrial/nodal arrhythmias to slow HR/AV

ADR:

• heart failure
• AV blockade
• sinus node depression

Question 24

Nifedipine?

Answer 24

• dihydropyridines
• calcium channel blocker in blood vessels, not heart

Effects:

• mainly dilates arterioles
• less cardiac depression

Clinical use:
-use for stable and variant anginas

ADR:
-reflex tachycardia due to excessive vasodilation

other drugs:

• amlodipine
• nicardipine

Question 25

Beta blockers mechanism for angina?

Answer 25

1. want to inhibit beta 1 receptors
   - use drugs that won’t vasodilate
   - reduced HR prolongs diastole and coronary perfusion time
   - blocks tachycardia reflex by nitrates and calcium blockers
   - reduce contractility
2. effective for stable, silent, and unstable anginas
   - not effective for variant angina
   - avoid drugs with intrinsic sympathetomimetic activity (pinodolol)
   - caution when combined with calcium channel blocker due to additive cardiac depressant, use dihydropyridines (Nifedipine)

Question 26

What beta blockers should you not use to treat angina? what should you use?

Answer 26

USE

1. Metoprolol
2. Atenolol
   - selective beta 1 blockers, long acting

DO NOT USE

1. Pindolol
   - has intrinsic sympathetomimetic activity
2. Carvedilol, Labetalol, Nebivolol
   - these are vasodilators
3. Verapamil, Diltiazem
   - non dihydropyridines that depress the heart

Question 27

Effects of Nitrates or Dihydropyridine alone? Effects of beta blocker or calcium channel blockers alone? Combination?

Answer 27

Nitrates, Dihydropyridines alone

1. reflex increase in HR
2. reflex increase in contractility
3. decrease in arterial pressure, EDV, ejection time

Beta and calcium channel blockers alone

1. increase in EDV
2. increase in ejection time
3. decreases in HR, arterial pressure, contractility

Combination
-decreases HR, BP, EDV, contractility, ejection time