IHD Pharmacology Flashcards
What are ways we can modify the activity of MLCK-MLC actin pathway? (4)
- Increase cyclic AMP
- Decrease intracelluar calcium
- increasing cyclic GMP
- Stabilizing or prevention depolarization of smooth muscle cell membrane (prevent Na in)
What effect does increasing cyclic AMP have?
Inactivates MLCK –> prevents phosphorylation of myosin light chains
What effect does decreasing intracellular calcium have?
- Reduced influx through calcium channels
OR
reduced endoplasmic reticulum release preventing MLCK activation
What effect does increasing cyclic GMP have?
Facilitates the dephosphorylation of myosin light chains
Which drug can cause reflex tachycardia
Dihyropyridines
What effect do dihydropyridines have?
Vasodilation (vasoselection)
- inc O2 supply
Also Reduces afterload (dec O2 demand)
What effects do NDHP’s have? Diltiazem, verapamil?
Inotropic (contraction) and chronotropic (heart rate) effects
- decrease O2 demand
can also vasodilate and inc O2 supply
What effects do BB have?
Decreasing Heart rate
Decreasing force of contraction
Decrease wall-tension (afterload)
OVERALL dec O2 demand
MOA of organic nitrates
Nitric oxide activates activates guanylyl cyclase
- INC GMP levels
What effects do nitrates have?
Relaxation of VEINS REDUCES preload
- dec O2 demand
Vasodilators the arteries
- inc O2 supply
How does tolerance of nitrates occur?
smooth muscle not producing as much nitric oxide
What are ADRs of nitrates?
Vasodilation effects
- hypotension
- reflex tachy
- syncope
- weakness
- dizziness
- facial flushing
- headache
Explain the MOA of interaction with PDE5 and nitrates
PDEs dec cyclic GMP breakdown while nitrates INC cyclic GMP production
- results in synergistic effects and dec blood pressure
MOA of systemic vasodilators?
When is it used?
Cause reflex increase in SNS activity
- inc BP
- inc RAAS activity (retain salt and water)
used in hypertensive emergencies
MOA of sodium nitroprusside
Dialotes arteries and veins
- reduces peripheral vascular resistance
- inc venous capacitance
MOA of hydralazine
Dialtes arteries much more than veins
- reduces intracellular calcium
MOA of minoxidil
Artery selective
- opens ATP-modulated K channels in smooth muscle
- leads to hyperpolarization (which inhibits calcium influx
MOA of ranolazine
Reduces late phase of inward sodium current
- facilitates calcium entry
reduces intracellular calcium
- reduce contractility (dec O2 demand)
Efficacy is independent of BP and HR effects
ADRs of ranolazine
Inc QT interval
NVD
Headache
Why do traditional vasodilators have limited efficacy in peripheral artery disease PAD?
Distal vessels are typically fully or mostly dilated
Which drug is used for peripheral artery disease? Class?
type of effects?
Cilostazol (PDE3i, in cyclic AMP)
- vasodilating effects
- Antiplatelet effects
- Anti-inflammatory effects
- Positive effects on lipids
