Vasodilators

Question 1

What classification of medications control vascular tone in the peripheral and pulmonary circulations and is a complex interplay of local metabolism, endothelial function, and regulation of sympathetic nervous and endocrine systems?

Answer 1

Vasodilators

Question 2

List some antihypertensive and vasodilator agents (Dr. C Slide)

Answer 2

Metoprolol
Labetalol
Esmolol
Nicardipine
Clevidine
Hydralazine
Fenoldopam
Nitroprusside
Nitroglycerin

Question 3

What CCB are in the dihydropyridine class?

Answer 3

Amlodipine, nicardipine, clevidipine, nifedipine,

Question 4

What CCB are in the non-dihydropyridine class?

Answer 4

Verapamil - PHENYLALKYLAMINES
and
Diltiazem - BENZOTHIAZEPINES

Question 5

What type/how do calcium channel blocker drugs inhibit?

Answer 5

Reduced frequency of channel opening which slows/inhibits calcium influx into cell at L-Type calcium channels in vascular smooth muscle - mainly arterial specific (little venous effect)
(dihydropyridines and phenylalkylamines

Question 6

Effects of Nicardipine (Cardene)

Answer 6

Potent arterial vasodilator - main coronary and systemic arteries. Relaxation of arterial walls, lowering peripheral vascular resistance which results in lowering Blood Pressure.

Question 7

Bolus and Infusion dosing of Nicardipine

Answer 7

Bolus: 100-400mcg
Infusion: 5-15mg/HOUR

Question 8

Onset and Duration of Action of Nicardipine

Answer 8

Onset: 2-10min
Duration of Action: 20-60min

Question 9

Which CCB has the greatest vasodilating effects of all
the calcium entry blockers, with vasodilation being particularly prominent in the coronary arteries?

Answer 9

Nicardipine

Question 10

Do dihydropyridine calcium channel
blockers significantly depress the sinoatrial node?

Answer 10

No
(Nicardipine and Clevi)

Question 11

Which CCB can also be used as a tocolytic?

Answer 11

Nicardipine
Myometrial L-type voltage-dependent
calcium ion channels, causing them to remain closed,
and thus inhibits uterine contractility.

Question 12

Why can Nicardipine and Clevidipine cause shunting and decreased oxygenation in susceptible patients in the pulmonary system?

Answer 12

The inhibit L-type calcium channels in the pulmonary vascular system leading to vasodilation. In patients who have sections of their lungs not ventilating well, the corresponding vessels around those alveoli constrict and push blood to better ventilated areas in order to maintain perfusion. However, Cardene and Clevi inhibit this compensatory Hypoxic vasoconstriction. Now the areas that are poorly ventilated as receiving the same amount of blood as other areas but do not get perfused, resulting in a net decrease in perfusion/saturation.

Question 13

What patient populations should you be cautious using Nicardipine

Answer 13

Severe Aortic Stenosis - Preload Dependent
CHF
Cardiogenic Shock
Those susceptible to pulmonary shunting effects

Question 14

Biggest difference between Nicardipine and Clevidipine?

Answer 14

metabolism! effects the onset of action and duration,

Question 15

Onset and Duration of Action of Clevidipine

Answer 15

Onset: 2-4min
DOA: 5-15min

Question 16

Metabolism of Nicardipine and Clevidipine

Answer 16

Nicardipine: Hepatic

Clevi: Nonspecific plasma esterases.

Question 17

Redistribution and Terminal Half-life of Clevidipine

Answer 17

Redistribution (Alpha): ~ 1 min after onset
Terminal (beta): ~5-15min after infusion stopped

Question 18

Infusion dosing of Clevidipine

Answer 18

1-2mg/HR, titrated every 5-10min
Max: 16mg/HOUR

Question 19

What kind of vasodilator is Hydralazine?

Answer 19

Direct acting arterial vasodilator

Question 20

MOA of Hydralazine

Answer 20

Inhibits IP3-induced Calcium release from the sarcoplasmic reticulum in the arterial smooth muscle cells. Less calcium in cytoplasm reduces blood pressure tone leading to decreased BP.

Question 21

IV Bolus Dose of Hydralazine

Answer 21

2.5-20mg

Question 22

Onset and Duration of action of Hydralazine

Answer 22

5-20min! Takes time, be patient, easy to stack doses too quick

DOA: 1-8 hours depending on dose

Question 23

What compensatory responses might you see with treatment using hydralazine or minoxidil ? Who might not benefit as much from these?

Answer 23

These are direct arterial vasodilators:
reflex-induced tachycardia or increases in renin
activity can be seen because sympathetic nervous system and reflexes still intact so not generally recommended for patients with myocardial
ischemia or coronary disease

Question 24

Long-term hydralazine is associated with

Answer 24

a ­ systemic lupus syndrome

Question 25

What class of vasodilator is Fenoldopam?

Answer 25

Dopamine Type 1 Receptor Agonist

Question 26

MOA of Fenoldopam

Answer 26

Net effect, vasodilation due to decreased intracellular calcium in renal, mesenteric, and peripheral vessels. [Fenoldopam binds to the D₁ receptor D₁ receptor is coupled to a Gs protein Gs protein activates adenylyl cyclase Adenylyl cyclase converts ATP → cAMP cAMP activates Protein Kinase A (PKA) PKA phosphorylates multiple targets → leading to: Inhibition of voltage-gated Ca²⁺ channels Reduced intracellular calcium in vascular smooth muscle Result: Smooth muscle relaxation → vasodilation]

Question 27

Onset and Duration of Fenoldopam

Answer 27

rapid onset and 10-minute elimination half-life.

Question 28

Dosing of Fenoldopam

Answer 28

No Bolus IV Infusion: 0.05-1.6mcg/kg/MIN

Question 29

Effects of Fenoldopam and any compensatory reflexes if applicable

Answer 29

Increase renal blood flow increases in urine output splanchnic blood flow Peripheral vasodilation Baroreceptor mediated increase in HR like with other arterial dilators.

Question 30

What condition is contraindicated for Fenoldopam use?

Answer 30

Glaucoma - can increase intraocular pressure

Question 31

What are the nitrovasodilators?

Answer 31

Sodium Nitroprusside Nitroglycerine Isosorbide Nitric Oxide

Question 32

How do nitrovasodilators work?

Answer 32

Donates Nitric Oxide to the endothelium, this activates guanylyl cyclase → ↑ cGMP → vasodilation of both arterioles and veins. cGMP inhibits calcium entry into vascular smooth muscle cells and may increase calcium uptake by the smooth endoplasmic reticulum.

Question 33

Why are nitrates contraindicated in patients with increased ICP?

Answer 33

Vasodilate, cerebral vessels, this increases volume in cranial vault leading to further increased pressures

Question 34

Onset and Duration of action of Nitroprusside

Answer 34

Onset: Rapid. 1-2min Duration: 1-10min

Question 35

Infusion dose of Nitroprusside

Answer 35

0.25-4mcg/kg/MIN

Question 36

What are two possible critical adverse effects of Nitroprusside? How do these occur?

Answer 36

Cyanide Toxicity and Methemoglobinemia(less likely) When infused IV, SNP interacts with oxyhemoglobin, dissociating immediately and forming methemoglobin while releasing cyanide and NO.

Question 37

Signs/symptoms of Cyanide Toxicity related to SNP?

Answer 37

-Mixed venous Po2 is increased in the presence of cyanide toxicity, (indicating paralysis of cytochrome oxidase and inability of tissues to use oxygen.) -Metabolic Acidosis -CNS Disturbance (not using O2) -suspected in any patient requiring an increasing dose especially more than 2 mg/kg/minute or in a previously responsive patient who becomes less or unresponsive to the drug.

Question 38

If it occurs, what is the cause of Cyanide Toxicity related to SNP?

Answer 38

infusion is greater than 2 mg/kg/minute or when sulfur donors and methemoglobin are exhausted, thus allowing cyanide radicals to accumulate

Question 39

Treatment for Cyanide Toxicity related to SNP?

Answer 39

immediate dc of SNP and administration of 100% oxygen despite normal oxygen saturation. Sodium bicarbonate - to correct metabolic acidosis. Sodium thiosulfate, 150 mg/kg IV administered over 15 minutes, is a recommended treatment for cyanide toxicity. (Alternatively, hydroxocobalamin (vitamin B12a), which binds cyanide to form cyanocobalamin (vitamin B12) or methylene blue)

Question 40

Between SNP and Nitroglycerin, which is more likely to cause MetHgb?

Answer 40

Nitrite metabolite of nitroglycerin is capable of oxidizing the ferrous ion in hemoglobin to the ferric state with the production of methemoglobin High doses of nitroglycerin may produce MetHgb especially in patients with hepatic dysfunction.

Question 41

The most common clinical use of nitroglycerin is?

Answer 41

Sublingual or IV administration for the treatment of angina

Question 42

Nitroglycerine is NOT recommended in patients with?

Answer 42

Hypertrophic Obstructive CM Severe Aortic Stenosis these conditions are preload dependent

Question 43

Bolus and Infusion Dose of Nitroglycerin

Answer 43

Bolus: 20-400mcg Infusion: 10-400mcg/MIN

Question 44

Onset and Duration of Nitroglycerin

Answer 44

Onset: 1-2min Duration: 5-10min

Question 45

Vascular and Pulmonary effects of Nitroglycerin

Answer 45

Acts principally on venous capacitance vessels and large coronary arteries to produce peripheral pooling of blood and decreased cardiac ventricular wall tension. However, as the dose of nitroglycerin is increased, there is also relaxation of arterial vascular smooth muscle. can produce pulmonary vasodilation equivalent to the degree of systemic arterial vasodilation.

Question 46

What is the difference in MOA between SNP and Nitroglycerine?

Answer 46

SNP spontaneously produces Nitric Oxide Nitroglycerine has to go through chemical rxns. The nitrate group of nitroglycerin is biotransformed to NO.

Question 47

MOA of Isosorbide Dinitrate

Answer 47

Similar to nitroglycerin but can be taken PO and have a longer duration of action. Can also be given sublingual. PO duration up to 6 hours - good for prolonged angina relief. Active and stronger metabolite. (isosorbide-5-mononitrate)