Vasodilators Flashcards
What is enalapril?
An angiotensin converting enzyme inhibitor (pro drug)
Mixed vasodilator
What is losartan?
An angiotensin receptor blocker (the receptor that AII binds to)
Mixed vasodilator
What are two examples of CCB hydropyridines?
Amlodipine and nifedipine
What are two examples of CCB non-dihydropyridines?
Verapamil and Diltiazem
What is clonidine?
An alpha 2 adrenergic receptor agonist
Mixed vasodilator
What is prazosin?
An alpha 1 adrenergic receptor antagonist
Mixed vasodilator
What are some examples of only arteriolar dilators? Which ones involve NO?
Hydralazine (may involve NO) and minoxidil
Increases cardiac output, decreases afterload
What is sodium nitroprusside?
A venous and arterial dilator that releases NO (increases cGMP) and cyanide
Used in severe congestive heart failure (decreases preload and afterload to decrease O2 demand and increase CO)
Rapid onset and offset, given IV
What is thiosulfate?
A sulfur donor used to treat cyanide toxicity possibly from sodium nitroprusside
What do nitrates do?
Increase NO which increases cGMP levels. Relaxes veins (low dose) and larger arteries (high dose) to decrease preload and heart size and prevent coronary steal Decrease pulmonary artery resistance (good for pulmonary hypertension in COPD) Tolerance develops (12 hour treatment intervals)
Which receptors affect preload? How?
Increasing alpha 1 activity vasoconstricts and increases blood pressure
Decreasing beta 2 activity relaxes the heart to allow for more filling
What receptors affect contractility?
Increasing beta 1 receptors increases the force of the muscles
What happens when you increase or decrease preload?
Stroke volume increases or decreases proportionally. More preload, more stretching of the cardiac muscle, more contraction to push it out
What receptors affect afterload?
Increasing alpha 1 activity causes vasoconstriction to push blood out harder
Decreasing beta 2 activity
Decreasing D1 activity
What happens when you increase or decrease afterload?
Stroke volume increases or decreases inversely
What are the blood pressure compensatory responses?
The sympathetic nervous system, renin-angiotensin-aldosterone system and the amount of sodium and water in the body.
When are the blood pressure compensatory responses physiologically useful?
Dehydration, hemorrhage and early heart failure
When are the blood pressure compensatory responses pathophysiologically harmful?
Renal artery stenosis and decompensated heart failure
What happens in response to a decrease in blood pressure?
Renal perfusion pressure decreases to increase Na retention and thus increase blood volume.
Renin is increased to cause the formation of aldosterone which helps retain Na and the formation of angiotensin II which increases afterload and preload
SNS activity is increased to increase afterload, preload, inotropy and heart rate. This increases cardiac output. Causes a correction in blood pressure.
What can cause a decrease in blood pressure?
Standing up and hypovolemia (minor) and shock (severe)
How does arteriolar dilation affect afterload?
Increases cardiac output and decreases afterload
How does venous dilation affect preload?
Decreases preload and pulmonary congestion
When does the RAAS system come into play?
When a drop of blood pressure, blood volume (renal perfusion pressure) or sodium load to distal nephron is sensed
What is renin?
An enzyme that is released from the JGA. The rate limiting step in angiotensin II formation
What is angiotensin II?
Major product of the RAAS system that increases aldosterone secretion, vasoconstriction, SNS and has trophic effects (thickens heart, vessels)
What is bradykinin?
Causes vasodilation, inactivated by ACE
What is does angiotensin converting enzyme do?
Converts angiotension I to AII and deactivates bradykinin
What do agiotensin converting enzyme inhibitors (ACEI) and angiotenin receptor blockers (ARBs) do?
Lower blood pressure by decreasing total peripheral resistance, decreasing Na reabsorption and increasing bradykinin
How are ACEIs and ARBs metabolically?
Metabolically neutral. Don’t increase lipids (LDLs) or glucose
When are ACEIs and ARBs most effective?
When plasma renin is high during hypovolemia or renal artery stenosis
Why would the use of ACEIs and ARBs be dangerous during renal stenosis?
The stenosis decreases RPP which causes an increase RAAS to try to correct RPP even though the blood pressure in the rest of the body is okay. High blood pressure. The drugs can cause a dangerous fall in BP
How do ACEIs and ARBs treat post MI?
Decreases the post infarction myocardial remodeling
First line treatment
How do ACEIs and ARBs treat hypertension?
Decrease peripheral resistance with minimal changes in heart rate and cardiac output
First line treatment
How do ACEIs and ARBs treat congestive heart failure?
Decreases the increased renin/AII levels associated with CHF
First line treatment
How do ACEIs and ARBs treat diabetic nephropathy?
Decreases protein excretion and renal deterioration
Effective at doses that don’t decrease blood pressure
First line treatment to prevent/delay
What are some possible problems with the use of ACEIs and ARBs?
Hypotension, hyperkalemia (less aldosterone means less K excretion), may increase protein excretion in normal patients and dry cough (ACEIs)
In what individuals should ACEIs and ARBs be avoided?
Pregnancy or those of child bearing age, cautiously combine with K sparing drugs, renal artery stenosis and diabetes with type 4 tubular acidosis (already no renin or aldosterone)
What do Ca channel blockers do?
Block L type voltage gated Ca channels
What are dihydropyridine calcium channel blockers?
Greater affinity for arterial Ca channels
Decrease cytoplasmic Ca to reduce TPR, CO and BP with out apparent cardiac actions (reflex tachycardia)
Relaxes other tissues (GI tract, uterus, bronchioles)- use in IBS
Want long acting agents
What are non-dihydropyridine calcium channel blockers? When are they used?
Cardiac and some vascular action, decrease sarcoplasmic reticulum release of Ca during depolarization. Decreases contractility Used in hypertension if there is also a concern about rate control in atrial fibrillation or angina
Neutral metabolic profile
What are dihydropyrines used for?
Hypertension, hypertensive crisis, Raynauds, angina
What is diltiazem used for?
Angina and hypertension
What are some cautions or contraindications with verapamil?
Contraindicated in heart failure
Should not be combined with a beta adrenergic receptor blocker (potential for severe or total AV node block)
What are some adverse effects of Ca channel blockers?
Headache, edema, constipation, flushing
What are alpha 1 adrenergic antagonists used for?
Hypertension (lowers LDL and VLDL too)
Benign prostatic hypertrophy (increases urine flow)
Relief of nightmare in PTSD
Caution: First dose may cause postural hypotension
How do alpha 2 adrenergic receptor agonists work? When is it used?
Lower blood pressure by decreasing SNS
Used oral or intrathecally to decrease the amount of general anesthetic needed foe surgery
What are usually given with vasodilators and why?
Given with a diuretic and beta-adrenergic receptor blocker because Na retention and increased SNS and RAAS activity will decrease the vasodilation effects
What is hydralazine?
An arteriolar dilator (may involve NO)
May preceipitate myocardial ischemia (increases O2 consumption)
Extensive first pass metabolism
What is hydralazine used for?
3rd line for hypertension
1st line for hypertension in pregnancy
Combine with a nitrate in heart failure
What are some side effects of hydralazine and minoxidil?
Headache, flushing nausea, hypotension, tachycardia, angina
May cause a lupus like syndrome (hydralazine)
Hirsutism (hair growth) and pericardial effusion (minoxidil)
What is minoxidil?
An arteriolar dilator (reflex activation of SNS could cause problems)
For severe hypertension when others won’t work, effective even if patient has renal failure
What are the forms of nitrates that are available?
Nitroglycerin (rapid onset, short duration) Isorbide dinitrate (longer acting)
How do nitrates prevent coronary steal?
Don’t affect smaller arterioles and precapillary sphincters as much. Thus, prevents blood flow to healthy region and increases blood flow to ischemic regions. Want to dilate larger vessels so we get blood flow to both.
How may hydralazine worsen angina?
By dilating small arterioles
What are some adverse effects of nitrates?
Orthostasis
Blood pressure lowering
Throbbing headache