Pharm management of CAD and angina - Lee

Question 1

drugs that can decrease O2 demand on the heart

Answer 1

• dihydropyridine Ca2+ channel blockers

- beta blockers

Question 2

types of angina

Answer 2

1. exertional/class angina
   - most common
   - partial coronary occlusion –> atherosclerosis
   - during exercise, relieved by rest
2. variant (prinzmetal) angina
   - cause by vasospam
   - during rest and at night
3. unstable angina (ACS)
   - fracture plaque –> platelet aggregation and thrombosis
   - longer duration
   - can lead to MI

Question 3

what do you not use with prinzmetal angina?**

Answer 3

• beta blockers**

- use nitrates and Ca2+ channel blockers

Question 4

drugs for angina and CAD

Answer 4

Nitrates:
Nitroglycerin, Isosorbide Dinitrate

Beta Blockers:
Propranolol, Metoprolol, Atenolol, and others

Calcium Channel Blockers:
Nifedipine, Verapamil, Diltiazem, Amlodipine

Metabolism Modifiers:
Ranolazine

Question 5

treatment algorithm for stable angina

Answer 5

-sublingual nitrates > beta blockers > Ca2+ blockers OR long acting nitrates > renolazine

Question 6

Nitrates

Answer 6

• increase blood flow through coronary arteries –> more O2 supply
• decrease preload on heart to vasodilation in veins –> decreased O2 demand

Question 7

nitrates

Answer 7

MAO

• nitrates enter vascular smooth muscle –> NO (mtALDH2, GST)–> guanylyl cyclase –> cGMP –> dephosphorylates myosin light chain (phosphatase) –> relaxation
• NTG conversion greater in venous smooth muscle
• low dose –> venodilation –> decrease preload
• high dose –> arterial vasodilation –> reduce afterload (can cause reflexive tachycardia***)
• increase collateral flow in coronary vessels to ischemic areas, reverse coronary vasospasm in prinzmetal, decrease platelet aggregation by + guanylyl cyclase

acute use

• immediate relief of angina***
• given sublingual due to high 1st pass metabolism (avoids liver metabolism)**

prophylaxis
-dermal patches (long acting) –> concern with tolerance** (reduced by free nitrate gap 8hr per night)

Question 8

Nitroglycerine (NTG)

Answer 8

-drug of choice for acute angina –> rapid onset of action

indications
-all types of angina

pharmacokinetics

• liver contains nitrate reductase –> inactivates NTG –> low bioavailability
• short half life (1-4 min)
• worry about tolerance*

adverse effects

• headache (meningeal vasodilation)
• reflexive tachycardia at higher doses (baroreceptors)**
• hypotension (dizzy, syncope)
• nausea

contraindications

• don’t give with Sildenafil/Tadalafil(type 5 PDE inhibitors) –> exacerbate hypotension with vasodilation
• hypovolemia
• increased intracranial pressure (head trauma)
• inadequate circulation

Question 9

isosorbide dinitrate

Answer 9

• heavy 1st pass metabolism
• variable bioavailable –> can play with dosage
• half life 1 hr. (longer than NTG)

adverse effects

• headache
• methemoglobinemia

Question 10

Ca2+ channel blockers

Answer 10

• normally - Ca2+ binds to calmodulin –> + myosin light chain –> contraction
• blockers prevent influx of Ca2+

-nondihydropyridines (verapamil, diltiazem) –> more effects on heart than smooth muscle

Question 11

beta blockers

Answer 11

common adverse effects

• bronchospams –> high [] binding to beta2
• bradycardia
• AV block
• unstable LV failure
• unpleasant dreams
• erectile dysfunction

Question 12

ranolazine**

Answer 12

-metabolism modifier

MOA
-blocks late Na+ plateau current –> reduced Na+ influx during ventricular depolarization –> inhibit Na+/Ca2+ exchanger –> low intracellular Ca2+ –> reduce contractility*

indications
-not 1st go to, either last resort or an add on option

adverse effects**
-dose dependent QT prolongation** –> pro-arrhythmic effects

Question 13

dipyridamole

Answer 13

-vasodilatory effects*

MOA

1. antiplatelet
   - PDE inhibition –> increase cAMP
   - inhibit adenosine uptake by RBCs (adenosine inhibits platelet reactivity)
2. vasodilator
   - due to increasing cAMP

indications
-combined with aspirin (inhibit platelets) or with coumadin (anticoagulant)

Question 14

emergency room treatment for chest pain

Answer 14

MONA
M - morphine 
O - O2 
N - nitroglycerin 
A - aspirin 

add beta blockers if HR is high (but not if ischemia is caused by prinzemetal angina)

Question 15

fibrinolytics (ex. tPA) in angina

Answer 15

-help with MI associated with ST elevation

1. unstable angina
   - no benefit
2. STEMI (complete occlusion)
   - if used early, can restore blood flow and reduce mortality
3. NSTEMI (partial occlusions)
   - not recommended bc can cause excessive bleeding