Nitrates + Everything else (Stable Angina CAD)

Question 1

Nitrates MOA

Answer 1

Short and long acting forms

Mixed venous AND arterial dilating drugs
Venous>arterial dilation
↑ venous capacity
↓ventricular preload
improved venous and later arterial filling

Question 2

Nitrates Indications

Answer 2

Adjunctive
To reduce sx (only) aka sx relief!!!! NO CV outcome

Controls SX and delays ED/urgent care visits

Question 3

Nitrates Metabolism

glutathione depletion is:

Answer 3

extensive 1st pass met with ORAL nitrates
SL rout avoids 1st pass = rapid vasodilation but only lasts for 30 min

glutathione depletion = nitrate tolerance Bioactivated- needs redox: small amount gets into circulation and depletes glutathione causing tolerance so don’t use less then 12 hrs apart!

Question 4

Nitrates- monitor

Answer 4

Monitor: anginal relief (frequency of anginal episodes), activity tolerance, ortho hypo

Intolerance/toxicity: activity intolerance or worsening angina, hypotension, orthostasis, dizzy, h/a, blurry vision, perioheral edema, falls, reflux

Question 5

Nitrates SE

Answer 5

• Orthostasis from venous pooling (dangerous if dehydrated, upright, not moving, or etoh)
• Temporal and meningeal arteries vasodilate—intense headache 60%
• Rebound tachycardia & enhanced Na retention in response to venous dilatation
• nitrate tachyphylaxis from long term exposure to short acting nitrates(sulfahydryl/glutathione depletion)
• nitrate toxicity

Question 6

Nitrates Considerations

Answer 6

Reduces hospitalizations

No cv outcome

hold phosphdieesterase inhibitors for 24 hrs after giving nitrate circulatory collapse from too much dilating

Question 7

Nitroglycerine MOA

Answer 7

Vascular smooth muscle relaxes via increased cGMP
↓O2 demand, preload, afterload, SX, hospitalizations
improved collaterals

Question 8

NTG indications

Answer 8

Rapid relief of angina—not for background vasodilation

can be used to prevent exercised induced angina

Paste:1-2 inches applied to chest wall USE GLOVES

Patch: clean dry skin for 12 hrs on, then off 12 hrs

Question 9

NTG metabolism

Answer 9

SL duration: 20-30 min
TD duration: 6-8 hrs remove patches before MI and defibrillation
Half life 1-4 minutes

Nitrate free interval of 10-12 hrs required to avoid tolerance to oral

Give first dose under observation for h/a or reflux

Question 10

NTG DI

Answer 10

NO ALCOHOL!!

Question 11

NTG SE/ Considerations

Answer 11

(if they don’t improve call asap bc prob ACS not stable CAD)—take 2 doses every 5 min while waiting

Question 12

Isosorbide Mononitrate MOA

Answer 12

Systemic vasodilation by increasing cGMP

↓preload, LV end diastolic volume and pressure

Question 13

Isosorbide Mononitrate indications

Answer 13

Tx sx only—24 hour control of angina

Can be added with SL nitroglycerine

Question 14

Isosorbide Mononitrate

Metabolism

Answer 14

XR tablet allows increase of dose every 3 days—make sure the pt isn’t confusing this with SL nitro or chewing this like ASA

schedule adjust for nocturnal angina

Question 15

Isosorbide Mononitrate DI

Answer 15

NO alcohol!!!!

Space PDE5 inhibitors 24 hrs apart

Question 16

Ranolazine MOA

Answer 16

Inhibits late phase Na current in ischemic myocytes
Reduces intracellular Na = reduced Ca influx
–aka it decreases Na/Ca exchange
reduction in Ca = reduced ventricular wall tension and MVO2 = enhanced metabolic efficiency without changing hemodynamics: no change in bp or hr!! ****

Question 17

Ranolazine Indications

Answer 17

Use when BB, CCB, and nitrates are maximized to increase functional tolerance –helps with cardiac rehab too

Question 18

Ranolazine metabolism

Answer 18

Higher doses inhibit delayed rectifier K current = prolongs ventricular contraction and QT interval (can lead to vtach and sudden death!)

Met by CYP3A4

Question 19

Ranolazine cosiderations

Answer 19

Limit dose with verapamil/diltiazem and substrate/inhibitors of P gylcoproteins

*improves tradmill exercise tol by 30 seconds

Question 20

Ivabradine MOA

Answer 20

Selective Na channel blocker reduces HR, and hyperpolarizes the SA node: alternative node blocker

Question 21

Ivabradine Indications

Answer 21

Pts with LVD, HF with EF 35-40%, stable CAD if HR >70,

Considered in HF/LVD when BB, digoxin not tolerated

Question 22

Ivabradine Metabolism

Answer 22

Mod CYP3A4 substrate
PGP inhibitor

Half life 6 hrs
70% protein bound
Hepatic metabolism
Metabolite has 40% of parent activity

Question 23

Ivabradine considerations

Answer 23

Food increases exposure 20-40%

Can cause new AF, bradycardia, av block sick sinus dynrome: decompression (better used in pts with higher HR)

Question 24

Max Medical Management

Answer 24

Aspirin +/- Clopidogrel (if stented)
Ace-I/ARBs, BBlockers, BP management
Statins: LDL tx goals or minimum 40% reduction from baseline
Quit smoking
Treat depression
Nutritionist –cals, food quality, fiber
CV rehab, personal trainer
Bmi 25-27
Cal expenditure targets

Question 25

ABCDE

Answer 25

A – Aspirin, ACE-I, Anti-anginals B –Beta-blockers, blood pressure control (↓rate, co, myocardial demands) Goal:

Question 26

Platelet functions in Atherothrombosis

Answer 26

-Adhesion -Activation -Aggregation (AAA)

Question 27

Platelet Activators

Answer 27

``` ADP –inhibited by: (irreversible) Clopidogrel Prasugrel Ticagrelor Arachodonic Acid inhibited by: Aspirin (irreversible) Thrombin Heparin LMW Heparin Direct Thrombin Inhibitors Epinephrine Collagen GP IIB/IIIA receptors ```