IHD - CSAP drug therapy - Nitrates

Question 1

Major mechanisms of action

Answer 1

• Systemic venodilation with concomitant reduction in LV end-diastolic volume and pressure, thereby reducing myocardial wall tension and oxygen requirements
• Dilation of epicardial coronary vessels
• Increased blood flow in collateral vessels

Question 2

How does organic nitrates cause vascular relaxation?

Answer 2

When metabolized, organic nitrates release nitric oxide

↓

NO binds to guanylyl cyclase in vascular smooth muscle cells, leading to an
increase in cyclic guanosine monophosphate

↓

CGMP causes relaxation of vascular smooth muscle

• Super summary:*
• When metabolized, nitrates release NO which increases the CGMP

Question 3

Aside from its vasodilatory effect, what is the other effect of nitrates?

Answer 3

Antithrombotic activity by NO-dependent activation of platelet guanylyl cyclase, impairment of intraplatelet calcium flux, and platelet activation

Question 4

The absorption of these agents is rapid and complete through ____; for this reason, nitroglycerin is most commonly administered ____ in tablets of ____ mg

Answer 4

• Mucous membranes
• Sublingually
• 0.4 or 0.6

Question 5

Patients with angina should be instructed to take the medication when?

Answer 5

• both to relieve angina; and
• ~5 min before activities that are likely to induce an episode
• Note:*
• The value of this prophylactic use of the drug cannot be overemphasized

Question 6

T/F. Nitrates can relieve ischemia even in Prinzmetal angina

Answer 6

True

Question 7

Long term nitrates provide effective plasma levels for up to ____ h, but ____

Answer 7

• 24 hours
• The therapeutic response is highly variable

Question 8

What are the steps to minimize the effects of nitrate tolerance?

Answer 8

• Minimum effective dose should be used
• Minimum of 8 h each day kept free of the drug to restore any useful response(s)

Question 9

What are the agents considered as nitrates and their preparation?

Answer 9

• Nitroglycerin
  
  • Ointment
  • Patch
  • SL tablet
  • Spray
• ISDN
• ISMN

Question 10

Schedule and dosing of NTG

Answer 10

• Nitroglycerin
  
  • Ointment
    
    • 0.5–2 in BID or TID
  • Transdermal patch
    
    • 0.2–0.8 mg/h q24 h; remove at bedtime for 12–14 h
  • Sublingual tablet
    
    • 0.3–0.6 mg prn, up to three doses 5 min apart
  • Spray
    
    • One or two sprays prn, up to three doses 5 min apart

Question 11

In NTG use, a ____ nitrate-free interval is recommended

Answer 11

10- to 12-h

Question 12

Schedule and dosing of ISDN and ISMN

Answer 12

• Isosorbide dinitratea
  
  • Oral
    
    • 10–40 mg BID or TID
  • Oral sustained release
    
    • 80–120 mg OD or BID (eccentric schedules)
• Isosorbide 5-mononitrate
  
  • Oral
    
    • 20 mg BID (given 7–8 h apart)
  • Oral sustained release
    
    • 30–240 mg OD