CCBs and other vasodilators Flashcards
list the dihydropyridine CCBs
Nifedipine
Nimodipine
Amlodipine
Felodipine
Amlodipine is most commonly used.
Cause primarily Arteriolar dilation
They dilate coronary and peripheral arteries.
List the non-DHP CCBs
Verapamil, Diltiazem
List the other vasodilators
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
Verapamil kinetics
High first pass metabolism, 10-30% bioavailability,
Still given orally for chronic treatment. Can be given I.V.
Half life 3-6 hours.
Diltiazem administration and bioavail.
Also given roally, about 40% bioavailability.
Nitrate formulations
1) Nitrates: (shortest to longest acting) Amylnitrate Glyceryl Trinitrate - NG Amylnitrate Isosorbide dinitrate Isosorbide mononitrate
What is the main effect of nitrates
Potent VENOUS dilation.
Moderate arteriolar dilation
Decrease PRELOAD, decreasing work and O2 demand.
What are the oral nitrates
Isosorbide dinitrite
Isosorbide mononitrite
the Organic nitrates
What type of nitrate is nitroglycerine
How is it administered?
Glyceryl trinitrate
It is an inorganic nitrate
Sublingual spray or transdermal patch.
What are the kinetics of the different routes of nitroglycerin administration
Sublingual
Onset 1 minute, duration 10-25 minutes
Transdermal patch
onset 30 minutes
duration 10-12 hours.
What are the kinetics for
isosorbide dinitrate
isosorbide mononitrate
Dinitrate:
onset 15 minutes
duration 3-6 hours
Mononitrate
onset 30 minutes
duration 8 hours
Nitrate SEs
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
Nitrate contraindications
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.
What are the two types of nitrate tolerance
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.
Hydralazine mechanism
Unclear, stimulates NO release from endothelial cells.
Hydralazine indications and effects
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.
Hydralazine adverse effects
Reflex tach
Increased RAAS activation and decreased GFR.
Drug induced lupus.
Coronary steal syndrome, angina, MI.
Minoxidil mechanism
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.
Minoxidil indication
Severe emergent hypertension.
Insulinoma
Topical agent to treat baldness
Minoxidil SEs
reflex tach
coronary steal
hirsuitism
inhibition of insulin release and hyperglycemia.
Sodium Nitroprusside mechanism
Nitroprusside reacts with oxyhemoglobin and generates methehoglobin, cyanide, and NO.
Nesiritide mechanism
Synthetic BNP, causes both Arteriorlar and Venous dilation.
increases cGMP.
Milrinone mechanism
Along with Amrinone
PDE inhibitor.
Arteriolar dilation.
Increased contractility l
Fenoldopam mechanism
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.
Amlodipine dose
5-10 mg once per day.
half life of 30-50 hours
Diazoxide mechanism
Another K+ opener.
Given i.v.
Long duration of action up to 12 hours.
Nitroprusside kinetics
Light sensitive
Very short acting, only a few minutes duration.
only given parenterally in hypertensive emergencies.
What are the kinetics of Amylnitrate
It is an inhaled volatile gas nitrate
1-2 min onset
5-10 minutes duration.
