Direct Acting Vasodilators

Front 1

What are the general mechanisms of Direct Acting Vasodilators?

Back 1

1. Direct Arteriolar Dilation
2. Decrease TPR
3. Have Reflex Sympathetic Activation (Tachycardia, Increased CO, Fluid retention, and increased renin)
4. Tachyphylaxis (due to reflex mechanisms)

Front 2

True/False: Patients can use Direct Acting Vasodilators alone.

Back 2

False.

Usually used in combination with diuretic and BB to balance effects.

Front 3

Name four Direct Acting Vasodilators.

Back 3

1. Hydralazine
2. Minoxidil
3. Nitroprusside
4. Diazoxide

Front 4

What is the effect on Veins, Arterioles, Tachycardia, and Sodium Retention of Hydralazine?

Back 4

Veins: -
Arterioles: +
Tachycardia: +
Na Retention: +

Front 5

What is the effect on Veins, Arterioles, Tachycardia, and Sodium Retention of Minoxidil?

Back 5

Veins: -
Arterioles: +++
Tachycardia: +++
Na Retention: +++

Front 6

What is the effect on Veins, Arterioles, Tachycardia, and Sodium Retention of Nitroprusside?

Back 6

Veins: +
Arterioles: ++
Tachycardia: +
Na Retention: -

Front 7

What is the effect on Veins, Arterioles, Tachycardia, and Sodium Retention of Diazoxide?

Back 7

Veins: -/+
Arterioles: +++
Tachycardia: +++
Na Retention: +++

Front 8

Which Direct Acting Vasodilator can be used without combination therapy with a diuretic and a BB?

Back 8

Nitroprusside

Front 9

What are the two clinical uses for Direct Acting Vasodilators?

Back 9

1. Chronic hypertension
2. Hypertensive crisis

Front 10

Which two medications are used in combination with a diuretic and a BB for chronic hypertension?

Back 10

1. Hydralazine
2. Minoxidil

Front 11

Which three medications are used in hypertensive crisis?

Back 11

1. Nitroprusside
2. Diazoxide
3. Fenoldopam

Front 12

How are each of the hypertensive crisis drugs administered?

Back 12

IV

Diazoxide - 8-10 hours
Fenoldopam - less than 48 hours

Front 13

What is the mechanism of action of Hydralazine?

Back 13

The mechanism isn't clear. It does not affect veins. It opens Ca++ activated K+ channels, inhibits IP3 induced Ca++, and stimulates NO to increase cGMP.

Front 14

What does cGMP do?

Back 14

cGMP stimulates phosphotases and stimulates movement of Ca++ out of cells

Front 15

What action in the liver is of concern with Hydralazine?

Back 15

Hydralazine is N-acetylated in the liver and their are fast and slow acetylators.

Front 16

What reflex action does Hydralazine cause?

Back 16

Reflex increase in CO and fluid volume.

Front 17

What are the side effects of Hydralazine?

Back 17

Headache, dizziness, flushing, hypotension, palpitations, nausea, black stool, and "Lupus syndrome" - High dose, long term, women, slow acetylators, Caucasians

Front 18

which three conditions are contraindicated for use of Hydralazine?

Back 18

1. Coronary artery disease
2. Elderly
3. Ischemia - vasodilation and increased work load ischemia may be severe enough to induce MI

Front 19

How does Minoxidil work?

Back 19

Acitvated ATP-modulated K+ channels which increases the K+ efflux causing hyperpolarization and muscle relaxation.

Front 20

How is Minoxidil activated?

Back 20

By liver sulfotransferase. Minoxidil-SO4 activates channels

Front 21

What are six effects of Minoxidil?

Back 21

1. Because of more severe hemodynamic actions, the CO is increased 2-3 times which stimulates renin release
2. Myocardial ischemia due to reflexes and sympathetics
3. Arrhythmias due to action on K+ channel, also inverted T waves
4. Salt and water retention increases PCT reabsorption
5. Rashes - Stevens-Johnson syndrome
6. Hypertrichosis - hair growth

Front 22

What is Rogaine?

Back 22

Topical application of Minoxidil developed when side effect of hair growth was noticed. Can have CV effects.

Front 23

True/False: Using diuretics and BB with Minoxidil is optional.

Back 23

False

Always use diuretics and BB for BP effects

Front 24

Describe structure, function, and uses of Nitroprusside.

Back 24

Nitroprusside has one NO and 5 cyanide bound to Fe. The NO activates cGMP and decreases intracellular Ca++. This drug affects veins and arterioles. Given by IV infusion and used in hypertensive emergencies, to control hypotension during surgery, and to improve cardiac output in CHF

Front 25

What are the side effects of Nitroprusside?

Back 25

1. Cyanide toxicity - trembling, vomiting, convulsions
2. Thiocyanate toxicity - weakness, anoxia, tinnitus, muscle spasms, toxic psychosis (long term infusions or renal failure)

Front 26

Is there any way to limit cyanide toxicity with Nitroprusside?

Back 26

Give sodium thiosulfate

Front 27

What is the mechanism of Diazoxide?

Back 27

The mechanism is not fully understood. It's related to thiazides. 3rd line agent. Prolongs open time of ATP-sensitive K+ channels which hyperpolarizes smooth muscle.

Front 28

How is Diazoxide administered?

Back 28

Given by IV. Long acting.

Front 29

When is diazoxide used?

Back 29

Hypertensive emergencies but not often used because of marked fall in BP and the unpredictability of its long action.

Front 30

What are the adverse events associated with Diazoxide?

Back 30

Reflex increase in CO, HR, Renin release, Na+ retention, edema, coronary blood flow.
Cardiac or cerebral ischemia due to decreased pressure

Front 31

What effect does Diazoxide have on insulin?

Back 31

Inhibits insulin which increases glucose in Type II diabetics (action on K+ channels to prolong opening)

Front 32

True/False: Diazoxide is also used orally to treat hypoglycemic conditions.

Back 32

True

Front 33

What is the mechanism of Fenoldopam?

Back 33

Fenoldopam is a dopamine (D1) agonist that stimulates cAMP. It also have Alpha2 antagonist activity. It is a direct renal natriuretic and diuretic.

Front 34

How do you administer Fenoldopam?

Back 34

IV infusion. Short term. Less than 48 hours.

Front 35

What are the adverse events associated with Fenoldopam?

Back 35

Headache, flushing, excessive vasodilation, and dysrhythmias