Therapeutic Considerations Flashcards
What are the therapeutic considerations of isosorbide dinitrate?
- venous dilation greater than arteriolar dilation
- continuous therapy leads to tolerance; tolerance can be avoided by providing nitrate-free intervals
What are the benefits of isosorbide 5-mononitrate over isosorbide dinitrate?
- same as isosorbide dinitrate with the addition of:
- isorbide 5-mononitrate is preferred over isosorbide dinitrate because it has a longer half-life, better absorption from the GI tract, non susceptibility to extensive first-pass metabolism in the liver, less rebound angina, greater efficacy at equivalent doses
How does nitroglycerin compare to isosorbide dinitrate?
-equivalent doses of nitroglycerin may be less effective than isosorbide dinitrate due to shorter half-life
Which drug may oppose coronary vasodilation of nitrates?
-ergotamine
What are the therapeutic considerations of sodium nitroprusside?
- venous dilation is equal to arteriolar dilation
- thiocyanate toxicity become life-threatening at serum concentrations of 200 mg/L
Which drug can be administered with sodium nitroprusside to prevent cyanide toxicity?
-sodium thiosulfate
What are the therapeutic considerations of inhaled nitric oxide gas?
- inhaled nitric oxide gas has a shorter half-life and is rapidly reversible
- inhaled NO selectively dilates the pulmonary vasculature because NO in the blood is rapidly inactivated by binding to hemoglobin
At higher doses, PDE5 inhibitors have what therapeutic effect?
-systemic vasodilation
Which PDE5 inhibitor can be sussed to treat pulmonary hypertension?
-sildenafil
What are patients with prior episodes of vision loss at risk for when taking PDE5 inhibitors?
-nonarteritic ischemic optic neuropathy
Which PDE5 inhibitor has the longest half-life?
-tadalafil
Do dihydropyridines cause greater arteriolar or venous dilation?
-arteriolar dilation
How do dihydropyridines compare to diltiazem and verapamil?
-they have higher vascular-to-cardiac specificity, less depression of myocardial contractility and minimal effects on SA-node automaticity and AV-node conduction velocity
What is a major adverse side effect of oral nifedipine?
-its rapid onset of action can cause a precipitous fall in blood pressure which can trigger severe reflex tachycardia
How does amlodipine compare to nifedipine?
-it has higher bioavailability, longer time to peak plasma concentration, and slower hepatic metabolism
Which drug administered with nifedipine causes a decrease in nifedipine plasma concentration?
-nafcillin
Which dihydropyridine is administered as an IV infusion for management of hypetensive urgency and emergency?
-clevidipine
What are the therapeutic considerations of benzothiazepine/diltiazem?
- low ratio of vascular-to-cardiac selectivity
- depresses both SA-node automaticity and AV-node conduction velocity
- raises serum carbamazepine levels, which may result in carbamazepine toxicity
- avoid concomitant use of beta-adrenergic blockers
What are the therapeutic considerations of phenylalkylamine/verapamil?
- same as diltiazem, with addition of:
- verapamil has a greater suppressive effect on cardiac contractility than diltiazem
- alcohol consumption with chronic verapamil therapy may result in higher serum alcohol concentrations
- co-administration with pimozide may result in higher pimozide concentration and cardiac arrhythmias
- co-administration with simvastatin increases simvastatin concentrations
Do potassium channel openers cause greater arteriolar or venous dilation?
-arteriolar dilation
Potassium channel blockers are typically used in combination with which other drugs?
-beta-blocker and a diuretic
Potassium channel blockers should be used in which patients?
-patients with impaired renal function or dissecting aortic aneurysm or after acute MI
What are the therapeutic considerations of endothelia receptor antagonists?
- do not use in pregnant women
- monitor liver function tests monthly
- generally avoid use in patients with moderate to severe hepatic impairment
- use with caution in patients with hypovolemia, hypotension, heart failure or anemia
- potential for interactions with other drugs metabolized by P450 2C9 or P450 34A (eg. hormonal contraceptives, simvastatin, warfarin, ketoconazole)
- ambrisentan may have less hepatoxicity than bosentan
Does hyralazine cause greater arteriolar or venous dilation?
-arteriolar dilation
