Does NTG dilate venous or arterial? Preload or afterload?
- Both
- Venous dilation is more pronounced because relaxation of arterial smooth muscle requires higher NTG levels
- Reduces preload (venous dilation)
How does reducing preload decrease myocardial O2 demand?
Filling pressures in ventricles are reduced
What is an example of a relative CI to BB in SIHD (stable ischemic heart disease)?
- COPD or asthma with non-selective BB
2. Worsen bronchoconstriction by blocking B2 receptors in the lungs
Are cardioselective beta blockers always selective?
- Dose of when it is lost in any patient cannot be predicted
- Metoprolol 50-100mg could cause wheezing
What is the mechanism of aspirin?
- Inhibit cyclooxygenase
- Blocks formation of prostaglandins from arachidonic acid
- Inhibits thromboxane and prostacyclin
- Thromboxane A2, a potent vasoconstrictor, activates platelets
- Prostacyclin counter balances thromboxane A2
What is BB withdrawal syndrome? How to avoid?
- Rebound phenomenon
- BB leads to heighten B receptor sensitivity (upregulation)
- An overshoot in HR
- Increased myocardial O2 demand
- Gradual taper schedule (1-2 weeks)
How was nitrate tolerance first discovered?
- Workers exposed to NTG during production of explosives
- Developed severe HA and dizziness after initial exposure
- Side effects would diminish after days
- If workers were not exposed for several days symptoms would return
How long is needed for a nitrate-free interval? What time of day is best?
- 10-12 hours day
2. Nitrate-free at night; angina most likely during day
Will the use of long acting nitrates alter SL NTG?
No evidence that this occurs
What are the mechanisms for nitrate tolerance?
- Depletion of sulfhydryl groups which are needed for conversion of nitrate to NO
- Chronic nitrate produces a state of oxidative stress; this leads to dysfunction of aldehyde dehydrogenase (in mitochondria) the enzyme responsible for nitrate to NO
How often is isosorbide dinitrate dosed? Schedule?
- BID-TID
- 7 AM, Noon, 5 PM (BID less definite)
- If dosed with a traditional TID dosing, there would be a danger that the nitrate free period would be too short
Which long acting nitrate does not undergo first-pass metabolism?
- Isosorbide mononitrate
2. Bioavailability ~100%
What is first pass metabolism?
- Concentration of drug is greatly reduced before systemic circulation
- Drug enters hepatic portal system and is metabolized
What is the half life of isosorbide mononitrate?
5 hours
What are the differences in dosing schedules for isosorbide mononitrate IR vs ER?
- IR is BID, second dose ~7 hours after first. Asymetrical
2. ER is daily, helps avoid asymmetric IR dosing.
What did the MARISA (Monotherapy Assessment of Ranolazine in Stable Angina) evaluate?
- Cross-over placebo
2. Ranolazine increased exercise duration, and increased time to onset of angina
What are common ADRs with ranolazine?
- HA, dizziness
2. N/V, constipation
How is ranolazine metabolized?
- 3A4 (major)
- 2D6 (minor)
- Also a substrate for P-glycoprotein
What are patient characteristics for those who have variant (Prinzmetal) angina?
- Generally younger than those with stable angina
2. Not high risk
What is observed on ECG with variant angina?
Hallmark of variant angina is ST elevation which denotes complete occlusion of the coronary artery
Why are beta blockers likely to worsen Prinzmetal (variant) angina? Beta 1 blockers?
- Blockade of B2 receptors that mediate vasodilation may allow unopposed alpha-1 mediated vasoconstriction
- Even B1 block could worsen
Do patients with Prinzmetal’s (variant) angina need indefinite therapy?
- Maybe
- Up to 50% of patients experience spontaneous remission by and unknown mechanism
- If a patient is symptom free >1 year a CCB could be tapered and discontinued
What is the dose limit of simvastatin when combined with ranolazine?
Simvastatin 20mg
How is myocardial ischemia affected in NTG treated patients with hypovolemia?
- Myocardial ischemia is worsened
- Decrease in BP
- Reflex tachycardia may increase O2 demand
