Therapeutic Considerations

Question 1

What are the therapeutic considerations of isosorbide dinitrate?

Answer 1

• venous dilation greater than arteriolar dilation

- continuous therapy leads to tolerance; tolerance can be avoided by providing nitrate-free intervals

Question 2

What are the benefits of isosorbide 5-mononitrate over isosorbide dinitrate?

Answer 2

• 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

Question 3

How does nitroglycerin compare to isosorbide dinitrate?

Answer 3

-equivalent doses of nitroglycerin may be less effective than isosorbide dinitrate due to shorter half-life

Question 4

Which drug may oppose coronary vasodilation of nitrates?

Answer 4

-ergotamine

Question 5

What are the therapeutic considerations of sodium nitroprusside?

Answer 5

• venous dilation is equal to arteriolar dilation

- thiocyanate toxicity become life-threatening at serum concentrations of 200 mg/L

Question 6

Which drug can be administered with sodium nitroprusside to prevent cyanide toxicity?

Answer 6

-sodium thiosulfate

Question 7

What are the therapeutic considerations of inhaled nitric oxide gas?

Answer 7

• 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

Question 8

At higher doses, PDE5 inhibitors have what therapeutic effect?

Answer 8

-systemic vasodilation

Question 9

Which PDE5 inhibitor can be sussed to treat pulmonary hypertension?

Answer 9

-sildenafil

Question 10

What are patients with prior episodes of vision loss at risk for when taking PDE5 inhibitors?

Answer 10

-nonarteritic ischemic optic neuropathy

Question 11

Which PDE5 inhibitor has the longest half-life?

Answer 11

-tadalafil

Question 12

Do dihydropyridines cause greater arteriolar or venous dilation?

Answer 12

-arteriolar dilation

Question 13

How do dihydropyridines compare to diltiazem and verapamil?

Answer 13

-they have higher vascular-to-cardiac specificity, less depression of myocardial contractility and minimal effects on SA-node automaticity and AV-node conduction velocity

Question 14

What is a major adverse side effect of oral nifedipine?

Answer 14

-its rapid onset of action can cause a precipitous fall in blood pressure which can trigger severe reflex tachycardia

Question 15

How does amlodipine compare to nifedipine?

Answer 15

-it has higher bioavailability, longer time to peak plasma concentration, and slower hepatic metabolism

Question 16

Which drug administered with nifedipine causes a decrease in nifedipine plasma concentration?

Answer 16

-nafcillin

Question 17

Which dihydropyridine is administered as an IV infusion for management of hypetensive urgency and emergency?

Answer 17

-clevidipine

Question 18

What are the therapeutic considerations of benzothiazepine/diltiazem?

Answer 18

• 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

Question 19

What are the therapeutic considerations of phenylalkylamine/verapamil?

Answer 19

• 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

Question 20

Do potassium channel openers cause greater arteriolar or venous dilation?

Answer 20

-arteriolar dilation

Question 21

Potassium channel blockers are typically used in combination with which other drugs?

Answer 21

-beta-blocker and a diuretic

Question 22

Potassium channel blockers should be used in which patients?

Answer 22

-patients with impaired renal function or dissecting aortic aneurysm or after acute MI

Question 23

What are the therapeutic considerations of endothelia receptor antagonists?

Answer 23

• 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

Question 24

Does hyralazine cause greater arteriolar or venous dilation?

Answer 24

-arteriolar dilation

Question 25

Hydralazine is typically used in combination with which other drugs for the treatment of hypertension?

Answer 25

-beta-blocker and a diuretic in the treatment of hypertension

Question 26

Hyralazine is used with which other drugs in the treatment of heart failure?

Answer 26

-used with isosorbide dinitrate; it may reduce morbidity and mortality in black Americans with heart failure