CCBs and other vasodilators

Question 1

list the dihydropyridine CCBs

Answer 1

Nifedipine
Nimodipine
Amlodipine
Felodipine

Amlodipine is most commonly used.

Cause primarily Arteriolar dilation
They dilate coronary and peripheral arteries.

Question 2

List the non-DHP CCBs

Answer 2

Verapamil, Diltiazem

Question 3

List the other vasodilators

Answer 3

1) Nitrates: (shortest to longest acting)
Glyceryl Trinitrate - NG
Amylnitrate
Isosorbide dinitrate
Isosorbide mononitrate

2) Hydralazine
- stimulates endothelial NO release

3) Minoxidil
- Opens K+ channels

4) Milrinone, Amrinone
- PDE inhibitors, arteriolar dilation

5) Nesiritide
- synthetic BNP analog. aretriolar and venous dilation

6) Dopamine agonists
Fenoldopam - D1
Dopexamine - nonspecific
Dopamine - nonspecific

Question 4

Verapamil kinetics

Answer 4

High first pass metabolism, 10-30% bioavailability,
Still given orally for chronic treatment. Can be given I.V.

Half life 3-6 hours.

Question 5

Diltiazem administration and bioavail.

Answer 5

Also given roally, about 40% bioavailability.

Question 6

Nitrate formulations

Answer 6

1) Nitrates: (shortest to longest acting)
Amylnitrate
Glyceryl Trinitrate - NG
Amylnitrate
Isosorbide dinitrate
Isosorbide mononitrate

Question 7

What is the main effect of nitrates

Answer 7

Potent VENOUS dilation.
Moderate arteriolar dilation

Decrease PRELOAD, decreasing work and O2 demand.

Question 8

What are the oral nitrates

Answer 8

Isosorbide dinitrite
Isosorbide mononitrite

the Organic nitrates

Question 9

What type of nitrate is nitroglycerine

How is it administered?

Answer 9

Glyceryl trinitrate

It is an inorganic nitrate

Sublingual spray or transdermal patch.

Question 10

What are the kinetics of the different routes of nitroglycerin administration

Answer 10

Sublingual
Onset 1 minute, duration 10-25 minutes

Transdermal patch
onset 30 minutes
duration 10-12 hours.

Question 11

What are the kinetics for
isosorbide dinitrate
isosorbide mononitrate

Answer 11

Dinitrate:
onset 15 minutes
duration 3-6 hours

Mononitrate
onset 30 minutes
duration 8 hours

Question 12

Nitrate SEs

Answer 12

ortho hypo

Reflex tach - usually coadmin with CCBs or BBs to prevent this

Throbbing headache

Cutaenous flushing

Methemoglobinemia - weaker O2 carrying capacity.

Rapid tolerance - Tachyphylaxis
12 hours on 12 off.

Dangerous potentiation of nitrate effects along with PDE-5 inhibitors, sildenafil

Question 13

Nitrate contraindications

Answer 13

Hypertrophic obstructive cardiomyopathy
- inhibition of preload worsens the obstruction and can cause HF

Never coadminister with Sildenafil or toher PDE5 inhibitors, dangerous potentiation of the hypotension.

Never give nitrates during right sided AMI, depends on preload and filling to supply the right side of heart.

Question 14

What are the two types of nitrate tolerance

Answer 14

Pseudotolerance - rapid response to nitrates, activation of the reflex responses to lowered blood pressure.
ie RAAS activation, ANS activation

Vascular tolerance - after about 1 day,

• Sulfhydryl depletion
• Depletion of thiol groups that generate NO
• Free radical damage causing endothelial stress and damage, and decreased responsiveness.

Question 15

Hydralazine mechanism

Answer 15

Unclear, stimulates NO release from endothelial cells.

Question 16

Hydralazine indications and effects

Answer 16

A very potent arteriolar vasodilator.

Used to treat hypertension during pregnancy and severe symptomatic hypertension.

Also causes significant reflex response to the hypotension, significant reflex tachycardia and RAAS activation.
Because of htis, usually required to be combined with Beta blockers and Diuretics.

Not used very often.

Question 17

Hydralazine adverse effects

Answer 17

Reflex tach

Increased RAAS activation and decreased GFR.

Drug induced lupus.

Coronary steal syndrome, angina, MI.

Question 18

Minoxidil mechanism

Answer 18

A prodrug for minoxidil sulfate, which is a K+ channel activator,

Potent arteriolar dilator.
Also suppresses insulin release.

Like hydralazine it has strong effects and strong reflex effects. Should be coadministered wityh BBs and diuretics.

Question 19

Minoxidil indication

Answer 19

Severe emergent hypertension.

Insulinoma

Topical agent to treat baldness

Question 20

Minoxidil SEs

Answer 20

reflex tach
coronary steal
hirsuitism
inhibition of insulin release and hyperglycemia.

Question 21

Sodium Nitroprusside mechanism

Answer 21

Nitroprusside reacts with oxyhemoglobin and generates methehoglobin, cyanide, and NO.

Question 22

Nesiritide mechanism

Answer 22

Synthetic BNP, causes both Arteriorlar and Venous dilation.

increases cGMP.

Question 23

Milrinone mechanism

Answer 23

Along with Amrinone

PDE inhibitor.
Arteriolar dilation.
Increased contractility l

Question 24

Fenoldopam mechanism

Answer 24

Given i.v. duration only about 10 minutes.
Selective D1 agonist.

Potent arteriolar dilation
Renal arterioalr dilation and increased GFR.

Also directly acts on cardiac tissue
-positive inotropic, chronotropic, and dromotropic
Contractility, Heart Rate, Conduction Velocity.

Question 25

Amlodipine dose

Answer 25

5-10 mg once per day.

half life of 30-50 hours

Question 26

Diazoxide mechanism

Answer 26

Another K+ opener.
Given i.v.
Long duration of action up to 12 hours.

Question 27

Nitroprusside kinetics

Answer 27

Light sensitive
Very short acting, only a few minutes duration.
only given parenterally in hypertensive emergencies.

Question 28

What are the kinetics of Amylnitrate

Answer 28

It is an inhaled volatile gas nitrate

1-2 min onset
5-10 minutes duration.