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45 Cards in this Set
- Front
- Back
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What is the key difference between organic nitrates and sodium nitroprusside in terms of mechanism?
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Sodium Nitroprusside diffuses freely to the endothelial cell and into the VSMC to relax the cell.
Organic Nitrates undergo biotransformation in the blood and are therefore dependent on enzymes to penetrate into endothelial cells. |
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In what system do the effects of nitrates predominate?
What are 3 overall effects of nitrates? |
Venous system
- Increased Capacitance, preload, O2 demand - Mild arterial dilation, decreased O2 demand - Mild coronary arterial dilation, increased O2 supply |
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Sodium Nitroprusside is metabolized into these two things.
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NO and Cyanide.
Cyanide is metabolized by the liver to thiocyanate and excreted in the kidney. |
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Name 3 conditions that Nitrates are indicated for.
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Angina (stable and unstable)
CAD HF |
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How are nitrates useful in stable vs unstable angina?
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Stable (narrowing) - induce vasodilation
Unstable (plaque rupture) - inhibit platelet aggregation |
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What is the key difference between organic nitrates and sodium nitroprusside in terms of mechanism?
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Sodium Nitroprusside diffuses freely to the endothelial cell and into the VSMC to relax the cell.
Organic Nitrates undergo biotransformation in the blood and are therefore dependent on enzymes to penetrate into endothelial cells. |
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In what system do the effects of nitrates predominate?
What are 3 overall effects of nitrates? |
Venous system
- Increased Capacitance, preload, O2 demand - Mild arterial dilation, decreased O2 demand - Mild coronary arterial dilation, increased O2 supply |
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Sodium Nitroprusside is metabolized into these two things.
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NO and Cyanide.
Cyanide is metabolized by the liver to thiocyanate and excreted in the kidney. |
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Name 3 conditions that Nitrates are indicated for.
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Angina (stable and unstable)
CAD Pulmonary Congestion in HF |
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How are nitrates useful in stable vs unstable angina?
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Stable (narrowing) - induce vasodilation
Unstable (plaque rupture) - inhibit platelet aggregation |
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Moderate doses of Nitrates cause these 2 adverse effects.
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Headache and Flushing
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High doses of Nitrates required to coronary artery dilation cause this adverse effect.
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Dilation - Hypotension - Reflex Tachycardia - Increased O2 demand
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Why don't HF patients experience reflex tachycardia?
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Their Beta receptors are down regulated
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Name 3 ways to circumvent the first past metabolism of nitrates.
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Sublingual
IV Transdermal |
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Describe the physiological tolerance created by nitrate use.
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Baroreceptors detect low blood pressure
This causes a compensatory SNS and renal effect (Increased Na/H2O reabsorption) |
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Describe the 3 components of Pharmacologic tolerance that develops with nitrate use.
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1) The -SH containing proteins that help to release NO from nitrates become depleted
2) The NO metabolite peroxynitrate is formed and inhibits guanylyl cyclase 3) Increase activation of PDE5 increases cGMP breakdown |
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How can you avoid this tolerance?
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A dosing strategy that involves involves low daily nitrate levels or simply taking off a transdermal patch at night.
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Why are nitrates and PDE5 inhibitors dangerous when taken in combination?
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Nitrates activates guanylyl cyclase, and increase cGMP which activates the phosphatase that dephosphorylates MLC and induces relaxation.
PDE5 inhibitors inhibit PDE5 which breaks down cGMP. Way too much cGMP |
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Besides ED, what else have PDE5 inhibitors been indicated for?
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They are selective for the pulmonary vasculature over the systemic vasculature and therefore have been id indicated for pulmonary hypertension.
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CCB's works predominantly in this area of the body.
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Arterial side to decrease afterload
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What is the MOA for CCB's?
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They block LTCC's and cause vasorelaxation
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What are CCB's used for therapeutically? (3)
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Hypertension
Arrhythmia's Angina |
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CCB selectivity predicts indication used. What are the 3 types of CCB and an example drug for each?
What are each indicated for? |
- Dihydropyridines (Nifedipine, Amlodipine) - VSMC
- Benzothiazepines (Diltiazem) - Heart - Phenylalkylamines (Verapamil) - Heart |
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Why does one class work better in one tissue over another?
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They bind to different parts of the Ca++ channel
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Describe the differences between Amlodipine and Nefedipine
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Amlodipine has a slower metabolism and onset of action, a longer half-life and significantly less reflex tachycardia
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Nefedipine has a tendency to cause flushing and reflex tachycardia. What drug class could possibly be used to prevent this reflex which can aggravate myocardial ischemia?
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Beta Blockers
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What is a potentially detrimental DDI of cardiac CCB's verapamil and diltiazem?
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They are negative chronotropes and inotropes and therefore must be not taken with Beta Blockers.
This increases the risk of mortality in HF patients. |
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What is the primary MOA for K channel openers?
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They open K channels in the VSMC and induce vasorelaxation thereby decreasing afterload.
K efflux hyper-polarizes the cell making depolarization more difficult. |
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What is the indication for K channel openers?
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Resistant hypertension - when other agents aren't working)
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What are the adverse effects?
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Same as CCB's
Flushing and Headache Reflex Tachycardia |
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What is the effect/MOA of Endothelin receptor antagonists?
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They are vasorelaxation effects by competitively antagonizing the ETa and/or b receptor.
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Name two Endothelin receptor antagonists and their selectivities.
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Sitaxsentan - ETaR
Bosentan - ETa/bR |
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What are their therapeutic uses?
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Resistant hypertension
Pulmonary Hypertension |
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What are the adverse effects?
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Headache, flushing
Teratogenic |
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What is an additional consideration for Bosentan?
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It is associated with hepatotoxicity
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What is hydralazine, its effect and MOA?
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A vasodilatory agent
Works in the vasculature MOA unknown Possibly due to membrane hyperpolarization or inhibition of Ca from the SR |
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What is important about Hydralazine's pharmacokinetics?
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Oral bioavailability is low due to extensive first pass metabolism in the liver via acetylation.
Slow acetylator's have an increased bioavailability |
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Hydralazine isn't used in monotherapy anymore but can be used in combination. What is hydralazine predominantly used with?
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In combination with nitrates for hypertension and HF
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What is advantage of using Hydralazine?
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It prevents Nitrate tolerance
ISDN and Hydralazine decrease mortality in AA patients with HF |
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What is the effect of alpha antagonists in lowering BP? What is the MOA?
Name one. |
They block the alpha 1 receptor on VMSC's and decrease afterload by decreasing Ca mobilization.
Prazosin |
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What are the adverse effects of alpha antagonists?
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Hypotension
Na/H2O rentention |
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What can alpha antagonists be used in combination with?
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B-blockers and diuretics
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Why are Beta Blockers efficacious in lowering blood pressure, knowing that Beta 2 stimulation vasodilates?
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Effects on the heart supersede that of the vasculature.
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Beta Blockers work indirectly to lower O2 demand and BP. Name the 3 mechanisms by which this happens.
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1) Decreased Chronotropy, Inotropy (CO)
2) Decreased Renin release (JG cells) 3) Decreased SNS tone |
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What are the therapeutic uses of Beta Blockers?
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Hypertension
Arrhythmia HF Angina Prevention of Reflex tachycardia created by vasodilators |
