Exam 1 - Drugs Acting on Vasculature (Direct Acting Vasodilators and Nitrodilators) and Reserpine Flashcards
What drugs are considered direct acting vasodilators?
Hydralazine (apresoline)
Minoxidil (loniten)
Are direct acting vasodilators used as primary drugs to treat HTN?
NO - they are used as an alternative
What is the MOA of direct acting vasodilators?
1:
Act directly on vascular smooth muscle
Relaxation of vascular smooth muscle
Decreases SVR
Lowers BP
2:
Produce reflex stimulation of the heart
Increased myocardial contractility, HR, and oxygen consumption
What may be prompted by vasodilators? How can you block this effect?
Angina pectoris, MI, cardiac failure in predisposed pts
Can be blocked w/ a ß blocker
What do vasodilators increase? What does this cause? How can this effect be blocked?
Increase renin concentration
Results in Na+ and water retention (think RAAS)
Can be blocked by concomitant use of a diuretic
What drugs are considered nitrodilators?
Sodium nitroprusside
Nitroglycerin
Isosorbide dinitrate
Isosorbide mononitrate
Erythrityl tetranitrate
Pentaerythritol tetranitrate
What is NO produced by?
vascular endothelial cells
NO causes ___
vasodilation
What does NO inhibit?
Platelet aggregation (anti-thrombotic)
Leukocyte-endothelial interactions (anti-inflammatory)
What are nitrodilators?
Drugs that mimic actions of endogenous NO
This is done by releasing NO or forming NO within the tissues
They act directly on the vascular smooth muscle to cause relaxation
What are the 2 basic types of nitrodilators?
- Those that release NO spontaneously (like sodium nitroprusside)
- Organic nitrates that require an enzymatic process to form NO
What is the MOA of nitrodilators?
1:
NO activation of smooth muscle soluble guanylyl cyclase (GC)
Increased formation of cGMP
Activation of PKG
Activation of K+ channels
Hyperpolarization
Inhibits Ca2+ entry into the cells
2:
Inhibition of IP3 pathway
Inhibition of Ca2+ release from SR
Decreasing intracellular Ca2+ release from SR
Decreasing intracellular Ca2+
3:
Activates myosin light chain phosphatase
Net result: smooth muscle relaxation
What is myosin light chain phosphatase?
enzyme that desphosphorylates myosin light chains
The primary pharmacologic action of nitrodilators (arterial and venous dilation), make them useful in what conditions? What is another beneficial action of them?
Useful in:
- HTN
- Heart failure
- Angina
- MI
Other beneficial action: ability to inhibit platelet aggregation
What are the CV actions of nitrodilators on systemic vasculature?
Vasodilation w/ more venous dilation than arterial dilation
Decreased venous pressure
Decreased arterial pressure (small effect)
CV actions of nitrodilators: cardiac
Reduced preload and afterload (decreased wall stress)
Decreased oxygen demand
CV actions of nitrodilators: coronary
Prevents/reverses vasospasm
Vasodilation - primarily the epicardial vessels
Improves subendocardial perfusion
Increased oxygen delivery
What can occur w/ frequent dosing of nitrodilators? What effect does this have on efficacy?
Frequent dosing can lead to a tolerance to organic nitrates
The tolerance causes a decrease in efficacy
Sodium nitroprusside is a ___ and ___ acting vasodilator
rapidly and consistently
Sodium nitroprusside relaxes both ___ and ___
resistance and capacitance vessels
What effect does sodium nitroprusside have on TPR and CO?
decreases TPR and CO
What effect does sodium nitroprusside have on cardiac work and reflex tachycardia?
Decreases cardiac work
Does not cause reflex tachycardia
What effect does sodium nitroprusside have on ventricular function in heart failure? How does it do this?
Improves ventricular function in heart failure
It does this by reducing the preload
Nitroprusside is converted to ___ by ___
converted to NO by RBCs
Nitroprusside can also cause relaxation by non-enzymatically converting to NO by ___
glutathione
What is reserpine?
A peripheral adrenergic antagonist
What is the MOA of reserpine?
Lowers BP by:
- Depleting NE from sympathetic nerve endings
- Blocking transport of NE into storage granules
Reserpine is used in many landmark ___
clinical trials
What should reserpine be used with? Why?
Should be used w/ a thiazide to diminish fluid retention and reflex tachycardia
How is combination therapy given?
- Combining separate agents (separate meds, separate pills)
- Use of a fixed dose combo pill (one pill with multiple AIs, think Hyzaar)
What differences can be seen between using combination therapy via separate agents vs using a fixed dose combo pill?
Fixed dose combo pill may lower BP a lot faster
May do so with fewer SEs
When should two antihypertensives be used?
When the pt is more than 20/10 mmHg above their goal BP
What is an added benefit of fixed dose combo pills?
better pt adherence
