Pharmacotherapy 2 - CV pathophysiology and Anti-HTN Pharmacology
Terms in this set (227)
What is the RAAS?
Renin Angiotensin Aldosterone System
What does aldosterone do to the heart?
Myocardial fibrosis, ventricular arrhythmias, and left ventricular hypertrophy
What does aldosterone do to the kidneys?
Na retention and Mg and K loss
What does aldosterone do to the vasculature?
HTN, endothelial dysfunction, inhibits NO synthesis, and prothrombotic
What does aldosterone do to the CNS?
Sympathetic activation and parasympathetic inhibition
What converts angiotensin into angiotensin I?
What does angiotensin II AT1 receptor do?
Constricts arterioles, increases CO, increases renal sodium reabsorption, and increases GFR, ADH, thirst, and aldosterone stimulation
What does angiotensin II AT2 receptor do?
Vasodilation, anti-proliferation, tissue repair, and cell differentiation
The pressure stretching the ventricle of the heart after atrial contraction and subsequent passive filling of the ventricle is known as what?
Preload (end diastolic volume)
The tension or pressure used by the chamber of the heart in order to contract and eject blood out of the chamber is known as what?
Afterload (end systolic volume)
Ejection Fraction (EF)
The fraction of blood ejected by the LV during contraction or ejection phase of cardiac cycle
Stroke Volume (SV)
End diastolic volume - end systolic volume
The amount of blood pumped per unit of time is known as?
Cardiac Output (CO)
The CO adjusted for BSA is known as?
Cardiac Index (CI)
What is the Pulmonary Capillary Pressure (PCWP) used for?
Under most circumstances, it provides an accurate estimate of the diastolic filling (preload) of the left heart
What is the LVEDP?
An index of left ventricular end-diastolic volume (preload)
What happens to the stroke volume in severe LV dysfunction?
It quickly decreases (as does vascular resistance)
When does the PCWP reflect the LVEDP?
During diastole; when the mitral valve is open
Where is the sinoatrial node (SA)?
Right atrium near the superior vena cava
The discharge rate of the ____ determines the heart rate
Sinoatrial node (SA)
What will pulmonary crackles, S3 heart sound, and peripheral edema tell you about the patient?
If a patient has an increased pulse pressure and vascular diastolic pressure, what could be wrong?
What links the atrial and ventricular depolarization?
Atrioventricular node (AV)
Where does the impulse from the AV node travel to?
The bundle of His
What are the Purkinje fibers?
Fibers in the AV bundle of the heart that send nerve impulses to the cells in the ventricles of the heart and cause them to contract and pump blood either to the lungs or the rest of the body.
What is systole?
The contraction phase of the cardiac cycle that results in the ejection of blood into an adjacent chamber or vessel
What is diastole?
When the heart muscle relaxes and allows the chambers to fill with blood
What are the key clinical findings suggesting an increase in afterload?
Vascular diastolic pressure, pulse pressure, and pulses
Hardening of the arteries
Formation of atheroma (fatty plaques) in arterial walls (subset of arteriosclerosis)
What is ischemic heart disease (IHD)?
The lack of O2 tension at the cellular level that results in the loss of high energy phosphates due to the disruption of aerobic metabolism. The imbalance between myocardial oxygen supply and demand cause CV dysfunction
What is ASCVD (also known as CAD and CHD)
Atherosclerotic cardiovascular disease (atherosclerosis)
What are the 4 steps in the development of atherosclerosis?
Endothelial dysfunction, fatty streak formation, fibrous plaque formation, and thrombus formation
What is endothelial dysfunction?
Diminished ability of the endothelium to regulate the vascular tone, clotting, and inflammation. Can also result in vasoconstriction
What does endothelium do?
Maintains permeability membrane and the non-thrombogenic blood-tissue interface, regulates immune and inflammatory reactions and the growth of smooth muscle cells, modifies lipoproteins, and to modulate the vascular tone and blood flow
What are the main risk factors for developing Endothelial Disease?
Age, sex (M>F), family hx, obesity, HTN, diabetes, dyslipidemia, and an increase in homocysteine
Which of the 4 steps of atherosclerosis is taking place when the artery wall monocytes differentiate into macrophage which engulf lipoproteins and turn into foam cells and release growth factors?
Fatty streak formation (asymptomatic; step 2)
When does atherosclerosis normally start?
Which of the 4 steps of atherosclerosis is taking place when foam cells accumulate and expand; the smooth muscle cells move from the media to the intima, and a fibrous cap of tissue overlays the fibrous plaque?
Fibrous plaque formation (step 3)
Is stable or unstable plaque the primary cause of hardened and narrowed arteries?
Why is unstable plaque dangerous?
It is more likely to rupture, which can trigger a heart attack or stroke
Which of the 4 steps of atherosclerosis are symptomatic?
Thrombus formation and sometimes fibrous plaque formation
In which step of atherosclerosis formation does fibrinogen convert to fibrin after the platelets aggregate and form a thrombus (clot)?
Thrombus formation (step 4)
What classifies Acute Coronary Syndrome?
Unstable angina (new onset or angina at rest) and an acute MI (chest discomfort for ≥ 30 minutes)
What is a very important step for a patient with vulnerable plaques?
What is cardiac/myocardial remodeling?
The process by which the ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors
What are the main modifiable CV risk factors?
Smoking, HTN, cholesterol, HDL, diabetes, obesity, unhealthy diet (daily fruits and veggies), and lack of exercise
What are the main non-modifiable CV risk factors?
Gender, race, hx of CHD, age (men ≥ 45 and women ≥ 55)
What is the highest risk factor for an MI?
ApoB/ApoA-1 ratio (followed by current smoker)
What are the main clinical consequences of atherosclerosis CV Disease?
Stroke or transient attacks in the brain; stable and unstable angina and MI in the coronary arteries, and PVD in the leg arteries
A BMI from 25 - 29.9 is considered what?
What BMI is considered underweight?
A BMI ≥40 is considered what?
Class III or extreme obesity
What are two main clinical causes of CVD?
Central obesity and insulin resistance (can result in inflammation, HTN, hyperglycemia, thrombosis)
What are the main clinical presentation features of a patient with angina?
Substernal chest pressure sensatio, which can radiate back to the shoulder, arm, and neck (short duration)
What are the main clinical presentation features of a patient with ischemic heart disease?
Sudden cardiac death due to electrical instability and angina
What is an electrocardiogram used for?
To get information on a patient's HR, rhythm, conduction times, ischemia, infarction, and hypertrophy
What non-invasive cardiac test represents the sum total of electrical vectors arising from myocardial cells as they depolarize and repolarize
What non-invasive cardiac test is commonly used to evaluate "baseline" heart rhythm(s)?
Ambulatory EKG (typically ordered to evaluate symptoms of palpitations, dizziness, or syncope; normally worn for 24-48 hours)
What non-invasive cardiac test is commonly used to get a "real time" 2D image of the heart?
What information does an echocardiography provide?
A measurement of left ventricular function, valvular morphology, and valve function (can be combined with exercise or dobutamine to evaluate abnormalities)
Which two locations are used for an echocardiography?
Transesophaeal and tranthoracic
What is an echocardiography with doppler?
It looks at blood flow specifically (if there is any regurgitation back into any chambers)
When is exercise stress testing used?
When a patient has chronic cardiac symptoms, a diagnosis of obstructive CAD, a risk assessment, post MI, or in patients that are asymptomatic, have rhythm disorders, or are female
What is the purpose of exercise stress testing?
To increase a patient's HR (max 220 - age) and BP
Which patients should exercise stress testing not be done on?
Patients that cannot exercise to an adequate level and patients taking beta blockers (can not raise HR high enough)
What test is substituted for the exercise stress test in patients who can not use it?
A chemical/pharmacological stress test
What is an ischemic stress test?
Inotropes are used for the induction of true ischemia resulting in regional wall motion abnormalities (dobutamine or arbutamine)
What is a perfusion stress test?
Vasodilators are used for the induction of "coronary steal" results in decreased flow and are then evaluated as a surrogate for ischemia (dipyridamole and adenoside)
What is a Coronary Artery Calcium Score and what is it used for?
For risk assessment in an asymptomatic adult at low to intermediate risk for ASCVD
What is the clinical use of a carotid artery intima-media thickness (CIMT) measurement?
An ultrasound image of the carotid artery walls
What is the indication for a carotid artery intima-media thickness (CIMT) measurement?
Assessment in asymptomatic adults with intermediate risk for ASCVD (not really ever used clinically)
What is the clinical purpose of a coronary CT angiography (CCTA)?
An X-ray machine is used to produce images of your heart and its blood vessels (non-invasive and no recovery time)
When is a coronary CT angiography the most useful?
When a patient is known to have CAD
What are the indications for a coronary angiography?
Suspected CAD or high risk features with exercise stress test
Which patients should not be given a coronary angiography?
Asymptomatic patients (too invasive)
What is Coronary Angioplasty with Stenting (PTCA, PCI) for?
It works to open clogged heart arteries. It can be used to improve sx associated with blocked arteries (chest P) and it can be used during a heart attack to quickly open arteries
Is a Coronary Angioplasty temporary or permanent?
Temporary, but with a stent it is much more permanent
What are the indications for a coronary angiography/PCI?
Acute MI (STEMI/NSTEMI), significant CAD with obstruction, and significant angina symptoms (unstable)
What is a coronary angiography helpful for?
Useful in spotting the specific problem area and can help determine how aggressively the patient should be treated
Which layer is the innermost layer of the arteries?
What is a CABG?
Coronary Artery Bypass; the surgery reroutes blood around clogged arteries to get oxygen and blood to the heart (can relieve chest pain and reduce risk of MI)
What are the indications for a CABG?
Left main coronary stenosis, 2-3 vessel CAD, or medically refractory angina
Which of the arterial layers is smooth muscle?
Which of the arterial layers is made up of simple squamous epithelium and elastic fibers?
What is tunica externa made up of?
Loose connective tissue
Which of the following are considered ASCVD?
History of MI
1 & 3
2 & 3
1 & 3
What test is the usual first test to assess someone with complaints of syncope and dizziness in the outpatient setting?
24 hour holter monitor
If a patient is showing signs of jugular venous distention and pulmonary crackles, what may be the problem?
Are veins or arteries partially collapsed?
Veins (they are not filled to capacity)
Are valves more often present in veins or arteries?
What is the purpose of pulmonary circulation?
Pumps blood through the lungs
Patients that have an ejection fraction of less than what are considered to have heart failure with reduced ejection fraction?
What is the purpose of systemic circulation?
Pumps blood to organs and tissue
Do veins or arteries pump blood away from the heart?
Where is the tricuspid valve located?
Between the R atrium and R ventricle
Which valve is found between the L ventricle and the aorta?
Where is the mitral valve located?
Between the L atrium and L ventricle
Which valve is found between the pulmonary artery and R ventricle?
CO x PVR = ?
What would you want to do to the veins in order to lower BP?
Dilate (PVR decreases)
What would you want to do to the arterioles in order to lower BP?
Dilate (PVR decreases)
What would you want to do to the heart in order to lower BP?
Decrease contractility and decrease HR
What would you want to do to the kidneys in order to lower BP?
Decrease fluid retention (to decrease Na retention)
Do we want to increase or decrease sympathetic activity in order to decrease BP?
In order to lower BP, do we want an increase or decrease in NE?
Will inhibiting or activating a1 and a2 receptors decrease BP?
In order to lower BP, do we want to activate or inhibit the Ca channels?
Inhibit (an influx of Ca will depolarize the Na channel in order to block contraction)
In order to lower BP, do we want to activate or inhibit K channels?
We want to activate it (this hyper-polarizes the membrane)
What do sympatholytic agents do?
Interfere with sympathetic control of BP (They inhibit CV effects of the sympathetic nervous system)
Do vasodilators primarily target arterioles or veins?
Arterioles (HTN is all about resistance)
What do sympatholytic agents do to arterioles and what adrenoceptor is involved?
Decrease PVR, a1
What do sympatholytic agents do to venules and what adrenoceptor is involved?
Decrease VR (dilate), a1
What do sympatholytic agents do to the heart and what adrenoceptor is involved?
Decrease CO, b1
What do sympatholytic agents do to the JGA and what adrenoceptor is involved?
Decrease BP, b1
What do all anti-HTN medications do in the long run?
Decrease PVR, which decreases CO
What do vasopeptidase inhibitors do?
Inhibit angiotensin II formation (or receptor actions) and decrease aldosterone secretion
What do diuretics do?
Inhibit renal absorption of sodium and water (over long term, plasma volume and urinary excretion return to normal)
What are the 5 main side effects that virtually all dilating drugs show?
Flushing, palpitations, dizziness, headache, and peripheral edema
Why would vasodilating agents cause palpitations?
The drop in BP causes an the sympathetic system to kick in, which increases HR
Why would vasodilating agents cause dizziness?
Veins can not constrict so less blood will be returned to the heart
Why would vasodilating agents cause peripheral edema?
Increased P in capillaries from the vasodilation
Why would combination drugs be a good idea when trying to lower BP?
2 or more drugs with different mechanisms may compensate each other and decrease side effects induced by a high dose of a single drug (if we block one pathway of increased BP, the body can figure out how to get around it, which is why combination therapy works)
Decreasing BP with a sympatholytic does what to renal blood flow, renin secretion, and aldosterone?
Decreases renal blood flow and increases renin secretion and aldosterone production
Does decreasing BP with a diuretic decrease or increase blood volume?
What mechanisms tend to counter the actions of sympatholytic agents?
What do centrally-acting sympatholytic drugs do?
Modulate sympathetic nervous system control of BP
a2 adrenoceptor agonist in CNS and periphery
By decreasing sympathetic outflow with clonidine, what happens to BP?
What are the 4 main SEs of clonidine?
Dry mouth, sedation, orthostatic hypotension, and contact dermatitis (patch)
Why does clonidine cause rebound HTN?
By suddenly stopping clonidine, the activity of the sympathetic nervous system increases (causes withdrawal symptoms)
How would you decrease the likelihood of inducing rebound HTN?
Why might clonidine cause severe bradycardia in patients with AV node conduction abnormalities?
Clonidine decreases sympathetic activity and increases parasympathetic activity, which decreases CO
Why is methyldopa not a popular treatment option for lowering BP?
Too many SEs
What does methyldopa do in the vasopressor center?
It acts as an a2 adrenoceptor agonist in the CNS to decrease sympathetic outflow and BP
What are the main SEs of methyldopa?
Sedation, dizziness, HA, hemolytic anemia, and hepatotoxicity (must conduct LFTs in first 3 weeks of therapy)
Why can methyldopa also cause depression, vertigo, and lactation?
Due to a deficiency in the function of dopaminergic nerves; instead of the vessels in the nerves filling with dopamine, they fill with a-methyl-dopamine, which doesn't have the same effects.
Which two centrally acting drugs act as imidazoline I1 agonist in the CNS?
Moxonidine and rilmenidine (decrease sympathetic outflow to decrease BP)
What is the advantage of using moxonidine or rilmenidine over clonidine?
No rebound HTN
What is reserpine?
An adrenergic neuron-blocking drug that inhibits VMAT2
What do adrenergic neuron-blocking drugs
Decreases NE release from sympathetic neurons (partially deplete CCAs)
What are the main SEs of reserpine?
Mental depression, diarrhea, nausea (parasympathetic predominance), and sexual dysfunction
How can reserpine cause SEs similar to Parkinson's?
Reserpine blocks the uptake of dopamine, which causes a deficiency similar to how Parkinson's occurs
Why is reserpine rarely used?
Its effects last long after the medication is stopped
What do adrenoceptor blocking drugs do?
Inhibit CCA or sympathetic nervous system effects of the CV system
What do adrenoceptor blocking drugs do to a1?
What do adrenoceptor activating drugs do to a2?
Decreases release of NE (from sympathetic nerves)
What do adrenoceptor blocking drugs do to b1 in the JGA?
Increases renin release, which increases angiotensin II, which increases PVR and VR
What class of drugs are -azosins (prazosin, terazosin, doxazosin, and trimazosin)?
What do a-1 adrenoceptor antagonists do?
Block vasoconstrictor effects of CCAs on arterioles and veins (block a1 receptors on blood vessels)
What do adrenoceptor blocking drugs do to b1 in the heart?
Increase CO and HR
What do -azosins do to arterioles and veins?
Why would an a1-adrenoceptor antagonist induce orthostatic hypotension?
It prevents veins from constricting, which prevents blood from returning to the heart (dizziness)
Which would increase PVR more, a non-selective b-blocker or a b1-selective blocker? Why?
A non-selective b-blocker because it will block b1 and b2 dilators so when the sympathetic system tells vessels t constrict, they will really constrict (b2 prevents over-constriction)
What would a non-selective b-blocker do to CO?
What class of drugs are -olols?
b-adrenoceptor antagonists (b-blockers)
Would a non-selective b-blocker + ISA affect PVR as much as a non-selective b-blocker?
No because adding ISA is like adding a partial agonist, it will prevent a non-selective b-blocker from over-constricting
If a drug were to be designed as an antihypertensive that acted upon B receptors, what would it do to b1 and b2?
It would block b1 and activate b2 so it could decrease PVR
What 3 drugs are b1-selective blockers?
atenolol, bisoprolol, and metoprolol
What class of drugs are nadolol, propranolol, and timolol?
Why do companies like carvedilol?
It is a non-selective b-blocker, but it is also an a1-antagonist, which prevents vasoconstriction
Why do companies like labetalol?
It is a non-selective b-blocker, but also has ISA and is an a1-antagonist
Which 3 -olols are the best anti-hypertensive agents?
atenolol, bisoprolol, and metoprolol because they are b1 selective
Which b-blocker also inhibits NO?
Why do b-blockers work well as anti-hypertensive agents?
In the long run, they decrease PVR (CO decreases initially, but can return to normal)
Why do b-blockers cause fatigue?
They decrease CO
What are the main SEs of b-blockers?
Fatigue, dizziness, depression, bradydysrhythmias (all occur at higher doses, not likely as anti-HTN)
Why should you use a non-selective b-blocker in patients with asthma?
Using a non-selective b-antagonist may cause the patient to experience bronchoconstriction
Why should you not use a non-selective b-blocker in patients with heart failure?
It can decrease sympathetic activity, which is important in maintaining CO
Why should you use not a non-selective b-blocker in patients with diabetes?
Diabetics have poor circulation; constricting their blood vessels could be problematic
Why should you not use a non-selective b-blocker in patients with PVD?
Poor circulation; constricting their blood vessels would be problematic
Sympatholytic drugs used to treat HTN can decrease sympathetic actions by an action....
Which agent is most likely to cause hepatotoxicity?
Which agent is likely to cause dry mouth?
clonidine and moxonidine
Which are more important in HTN, arterioles or veins?
Arterioles are responsible for increasing PVR, which is our target for anti-hypertensive agents (but therapies that target both arteries and veins function better)
What class of drugs are verapamil, diltiazam, felodipine, nicardipine, amlodipine, etc?
Ca channel antagonists
What is the main type of VOCC?
L-type, which are long lasting and are located in the cardiac and vascular muscle
Which agents cause the most arteriole dilation dihydropyridines or diltiazam and verapamil?
Why is reflex tachycardia observed for nifedipine but not for verapamil or diltiazam?
The latter two greatly decrease cardiac contractility and node conduction by blocking Ca channels in the heart, so when the BP drops and the body tries to raise it by increase HR, these two agents prevent that
What are the key SEs for Ca channel blockers?
Dizziness, peripheral edema, HA, flushing, constipation (Ca is needed for smooth muscle function), and cardiac depression
Why can nifedipine increase mortality in patients with a previous MI?
Dropping BP too quickly can result in reflex tachy. This will cause an increase in oxygen, which causes ischemia and can cause an MI
Does fluid retention occur with Ca channel blockers?
No (vasodilators increase glomerular rate, which increases renal function and fluid excretion)
Why should IV verapamil and propranolol not be co-administered?
Both slow down HR
What are the two pathways the body will try to take to overcome a drop in BP?
Fluid retention or activation of the sympathetic nervous system
What is hydralazine?
A vasodilator that relaxes arteriolar smooth muscle by release of NO and hyper-polarization of smooth muscle
What would hyper-polarization of smooth muscle cells do to the operation of VOCC?
Membrane depolarization opens Ca channels so it will be very hard to open Ca channels
What can hydralazine cause?
Palpitations and first pass metabolism by N-acetylation (may need to adjust dose), systemic lupus (only occurs at high doses for long term), and secondary tachyphylaxis
Why should hydralazine not be used for a long period of time?
Eventually it stops working and it can cause lupus syndrome in the long term
What does minoxidil do?
It hyperpolarizes smooth muscle and inhibits VOCCs
What SEs are unique to minoxidil?
Fluid retention (can be problematic in patients with heart failure) and hypertrichosis (hair growth)
What can minoxidil used for besides vasodilation?
Hair growth (not systemically because of its CV side effects)
What class of drugs end in -pril (lisinopril, catopril)?
How do ACE inhibitors lower BP?
By inhibiting ACE, angiotensin I can't be converted to angiotensin II, which increases BP by increasing sympathetic activity, aldosterone synthesis, cardiac contractility, and vasoconstriction
What two things do ACE inhibitors inhibit?
Angiotensin II formation and bradykinin degradation
How does aldosterone increase BP?
It causes Na retention, which increases VR
Which is a more potent agent to increase BP: NE or angiotensin II?
Angiotensin II (40x)
What is ACE-2?
It generates angiotensin 1-7 from angiotensin II
What is Mas?
Ang 1-7's receptor, which causes dependent vasodilation
What are pro-renin receptors?
Receptors located on tissue that bind circulating renin and cause angiotensin formation for tissue remodeling
Why do ACE inhibitors tend to cause a much smaller reflex increase in CO and HR than other vasodilators?
They do not attempt to completely block sympathetic activity
Why do ACE inhibitors cause dry cough?
ACE inhibitors interfere with the metabolism of bradykinin, which accumulates and causes dry cough
What class of drugs ends in -artan (losartan, olmesartan)
Angiotensin II receptor antagonists (increase angiotensin II activity)
What is omapatrilat?
Vasopeptidase inhibitor that inhibits ACE and neutral endopeptidase (vasodilates)
What is aliskiren?
Renin inhibitor (blocks formation of angiotensin I and II)
What class of drugs ends in -sentan (ambrisentan, bosentan)?
Endothelin receptor agonists
What does ambrisentan do?
Blocks ETa, which is how endothelin-1 vasoconstricts
What is hydrochlorothiazide?
A diuretic (prevents fluid buildup)
What does angiotensin II do?
Increases aldosterone synthesis and secretion, causes Na retention/K loss, directly constricts arterioles, and increases sympathetic activity (increases CO and PVR)
Volume of plasma filtered across the glomerulus per unit time (normalized)
What is the controversy with the CCG equation?
It's not standardized so it is likely 10-20% higher than it should be
What is CrCl?
Creatinine is a byproduct of muscle breakdown and is eliminated via GF, so it is an estimate of GFR
What is the normal GFR range?
Which measurement is the best overall index of kidney function?
What 2 things does eGFR take into consideration that normal GFR does not?
Sex and race
When is ClCr not accurate?
When patients do not have stable kidney function
What is KDIGO?
What is the most common cause of end-stage renal disease?
Diabetes followed by HTN, GN, and PKD
What is AKI?
Increased SCr by 0.3 mg/mL in 48 hours or an increase by 1.5 times in the last 7 days. Can also be a urine volume of 0.5 mL/kg/hr for 6 hours
What is CKD?
Abnormalities in kidney structure or function for 3 months or longer, with implications for health
What is a healthy albuminuria range?
How is CKD classified?
By GFR and Albuminuria
What class is G1?
≥90, slight kidney damage (G5 being the worst)
What range is A2?
When should albuminuria not be measured?
Exercise w/in 24 hours, infection, fever, heart failure, pregnancy, UTI, HTN, etc.
If a patient is A2, what must be done?
Repeat tests (2 over the next 2 months)
How long must A2 or A3 be present for to be classified as CKD?
Why is staging important in regards to kidney disease?
It calculates their 2 and 5 year % probability of the development of kidney failure