SM 133 Hypertension Pathophysiology Flashcards
What are the major side effects of ARBs?
Generally rare, Hyperkalemia only
No cough because ARB’s do not affect ACE, unlike ACE Inhibitors
What are the major side effects of ACE Inhibitors?
Cough, Angioedema, and Hyperkalemia + Kidney Damage
What is the Aortic Arch a readout for?
The Aortic Arch detects blood pressure to measure blood flow to the body
How should blood pressure be measured, procedurally, in clinic?
Patient should be seated, relaxed, with arm cuff used on sleeveless arm held at the same level as the heart
How do blood pressures in children compare to adults?
Blood pressure is lower in children than adults, so blood pressure is an age dependent measurement
How is hypertension related to CVD?
Hypertension is a risk factor for CVD
What is the major effect of a1 blockers?
Decreased PVR leading to decreased Blood Pressure
Increased Cardiac output due to Reflex Tachycardia
Increased Intravascular volume due to increased Capacitance
What are the blood pressure ranges for Stage 2 Hypertension?
Systolic >= 140 OR Diastolic >= 90mmHg
What are the side effects of Phenylalkylamine Calcium Channel Blockers?
Verapamil; Bradycardia
How does Hydralizine work?
Lowers blood pressure by relaxing arteriolar smooth muscle
Why do we treat hypertension?
To reduce the risk of cardiovascular events
How do ARBs differ from ACE inhibitors and why?
ARBs and ACE all decrease SNS stimulation, smooth muscle vasoconstriction, and Na/H2O retention
However, ARBs do not decrease Bradykinin because Angiotensin Converting Enzyme is not inhibited, only its receptor is
What clinical criteria must be met to diagnose Hypertension?
Hypertension is diagnosed if two elevated measurements are observed 1-4 weeks apart
Which class of Calcium Channel Blockers is most effective at lowering Cardiac Output?
Verapamil, similar to Beta Blockers
What are the major side effects of Furosemide and other drugs that target the Na-K-Cl symporter?
Hypokalemia
Hypocalcemia
Hypomagnesia
What are the three main processes that regulate arterial pressure?
Volume regulation, vascular tone, and cardiac output
Where are low pressure receptors found?
Low pressure receptors are found in:
The Cardiac Atria
Right Ventricle
Pulmonary Vessels
What are the blood pressure ranges for normal blood pressure?
Systolic < 120 AND Diastolic < 80mmHg
What are the main side effects of Loop diuretics?
Electrolyte abnormalities and volume depletion
When would Furosemide be used?
Rapid diuresis to treat volume overload, such as in Hypertension not controlled with Thiazides
How do Calcium Channel Blockers work?
Block L-type calcium channel Ca influx to keep MLC dephosphorylated, promoting vasodilation of smooth muscle
Decreases PVR
Where is Aldosterone produced?
The Zona Glomerulosa of the Adrenal Cortex
Why do labs evaluate for Hyperkalemia and Creatinine when ACE-I or ARB are used?
Hyperkalemia is a common side effect from blocking the effects of Aldosterone
Creatinine indicates Kidney damage, a less likely side effect
What drugs fall into the class known as Diuretics?
Hydrochlorothiazide (HCTZ) and Chlorthalidone
What causes secretion of Renin from the Juxtaglomerular Apparatus?
The composition of ions reaching the Macula Densa
Stretch of the Afferent Arteriole
SNS stimulation of the Juxtaglomerular Apparatus
What could cause secondary hypertension?
Renal Artery stenosis, Hyper Aldosteronism, Hyperthyroidism, Pheochromocytoma, and Medications
Why is hypertension relative to a patient’s population?
Reflects the idea that the evidence available is being tailored to each individual patient
What is the effect of Sympathetic Tone and Calcium on smooth muscle?
Sympathetic Tone and Calcium favor contraction of arterial vascular smooth muscle to increase blood pressure
Drugs that end with -pril are?
ACE inhibitors
What are the centrally acting agents?
Methyldopa and Clonidine
Where are a1 receptors found?
On postsynaptic neurons in the effector organ
What factors suggest secondary hypertension?
Elevated Blood Pressure in:
People younger than 40 or older than 60
Sudden onset with very high blood pressures
What are the effects of centrally acting sympatholytics?
Major = decrease PVR via Vasodilate Minor = increase Intravascular Volume via increased capacitance Minor = decrease in Cardiac Output via Less Sympathetic Tone on the Heart
What are the effects of Alpha blockers?
Major = decrease PVR Minor = increase intravascular volume and CO
How does Amiloride effect water retention?
Amiloride inhibits Sodium transport from the lumen into Principal cells, leading to decreased sodium reabsorption and water loss to decrease blood volume
When should a thiazide diuretic be used instead of a loop diuretic?
Healthy people will compensate for the strong effects of loop diuretics, so Thiazides are better for controlling chronic hypertension
When are peripheral vasodilators used?
Last line in patients with difficult to control blood pressure
What are the side effects of Dihydropyridine Calcium Channel Blockers?
Nifedpine; Peripheral Edema
What are the effects of ACE Inhibitors and ARBs on Arterial pressure?
Major = decreased PVR Minor = decreased Intravascular Volume and reflex increased Cardiac Output
When should ACE Inhibitors and ARB not be used?
Women who are pregnant or may become pregnant
Where do Diuretics act?
The Distal Convoluted Tubule, Thick Ascending Loop of Henley, and the Collecting Duct
What is the Stage II Hypertension cutoff for high risk people?
130/80mmHg
What is the effect of inhibiting Aldosterone?
Aldosterone normally promotes Sodium reabsorption and Potassium excretion
Inhibiting Aldosterone leads to Sodium secretion and Potassium reabsorption
What is the Stage II Hypertension cutoff for low risk people?
140/90mmHg
What are the effects of Angiotensin II?
Sympathetic Activation
Smooth Muscle Vasoconstriction
Decreased Bradykinin = Vasoconstriction
Na/H2O Retention via Aldosterone
What are the side effects of Minoxidil?
Tachycardia and hypertrichosis
Why do ACE-I and ARBs work well with Thiazide diuretics?
Thiazides lower blood levels of K while ACE Inhibitors and ARB block Aldosterone to increase K, canceling out eachother negative effects
What reaction does Renin mediate?
Angiotensinogen to Angiotensin I
What is an example of a K sparing diuretic?
Spironolactone - inhibits Aldosterone receptor binding in the Late Distal Tubule and Collecting Duct
Amiloride inhibits sodium reabsorption in the late Distal Tubule and Collecting Duct
What are the effects of Peripheral Vasodilators
Nitroprusside, Minoxidil, Hydralizine
Major = decrease PVR Minor = reflex tachycardia and increase intravascular volume
What reaction does ACE mediate?
Angiotensin I to Angiotensin II
What is the effect of Aldosterone on smooth muscle?
Aldosterone causes contraction of arterial vascular smooth muscle to increase blood pressure
Where are high pressure receptors found?
The Carotid Sinus, Aortic Arch, Left Ventricle, and the Juxtaglomerular Apparatus
What are side effects of Beta Blockers?
Bradycardia, cold extremities, bronchospasm
Where does Spironolactone act?
Spironolactone inhibits the Aldosterone receptor in the Distal Tubule and Collecting Duct
How can a diagnosis of hypertension be confirmed at home?
Blood pressure cuffs record measurements, and devices can monitor blood pressure over time for true values
What drugs target the Thick Ascending Loop of Henle?
Furosemide and Torsemide
What is the effect of Bradykinin?
Vasodilation
What is the significance of Carvedilol a1 blocking activity?
Decrease SVR
What drug interaction effects are dangerous with loop diuretics?
Electrolyte abnormalities and volume depletion, which worsen side effects
What portion of Sodium reabsorption is attributable to the Thick Ascending Loop of Henle?
30% of Sodium reabsorption occurs in the Thick Ascending Loop of Henle
How does the phosphorylation status of Myosin Light Chain affect vasoconstriction?
Calcium-dependent Myosin Light Chain Phosphorylation by MLCK leads to vasoconstriction
Phosphatase dephosphorylates Myosin Light Chain to cause vasodilation
Where does Aldosterone act?
Aldosterone causes Na absorption and K/H secretion in the principal cells of the Collecting Tubule
What is primary/essential hypertension?
Hypertension caused by genetic or environmental factors that worsen with age
Accounts for 95% of all hypertension
What systems control the release of Renin?
The Renin-Angiotensin-Aldosterone System and the SNS control Renin release
What are cardioselective Beta Blockers?
Affect b1 receptors found on heart, lead to Tachycardia, increased contractility, increased renin release
Increase HR, BV, and SV
What is the target population for Beta Blockers?
Patients with CAD
Not for patients with Hypertension or Heart Failure
Where does HCTZ act?
HCTZ inhibits the Na/Cl symporter in the DCT, leading to more Sodium and water excretion
What age group is most susceptible to primary hypertension?
40 - 60 year olds
What is secondary hypertension?
Hypertension caused by a specific defect
Accounts for 5% of all hypertension
What is the major side effect of peripherally acting sympatholytics?
a1 blockers lead to orthostatic hypotension
What is the Juxtaglomerular Apparatus a readout for?
The Juxtaglomerular Apparatus detects blood pressure to measure blood flow to the Kidney, allowing the Kidney to regulate volume
What are the nonselective Beta Blockers?
Propanolol affects b1 and b2
What is masked hypertension?
Normal blood pressure in clinic and elevated blood pressure at home
How does Minoxidil work?
Activates a K channel in smoot muscle to cause K efflux, hyperpolarizing and vasodilating smooth muscle
What are the side effects of Benzothiazepine Calcium Channel Blockers?
Diltiazem; Edema and Bradycardia
How does Clonidine work?
Clonidine directly stimulates the central a2 receptor
What does the -zosin suffix indicate?
Peripherally acting a1 blocker
How does calcium regulate blood pressure?
Calcium influx into smooth muscle activates MLCK
MLCK phosphorylates Myosin Light Chain
Phosphorylated Myosin Light Chain leads to vasoconstriction of smooth muscle
What are bronchodilative Beta Blockers?
Affect b2 receptors in lung and arterioles, lead to bronchodilation and decreased PVR
Increase O2 and decrease PVR
How is hypertension defined?
Hypertension is defined based on a population
What are the effects of blocking b2 receptors?
Vasoconstriction = increased BP
How do a1 blokers work?
Prevent binding of Norepi to a1 Receptors, lowering Blood Pressure
How is blood pressure measured using a cuff?
The cuff is inflated above systolic blood pressure, cutting off blood flow through the artery. As the cuff is deflated, the measurement at the first sound represents systolic blood flow, and as it continues to deflate, the second sound represents diastolic blood flow
How do ARBs act?
They block AT1 receptors to prevent Angiotensin from exerting its effect
What are the side effects of centrally acting sympatholytics?
Sedation, dry mouth, depression
What are the sympatholytic a1 receptor blockers?
Prazosin, Terazosin, Doxazosin
Why do smokers have a lower target blood pressure than non-smokers?
Smoking is a risk for CVD, so they compensate by targeting lower blood pressures
What are the blood pressure ranges for Stage 1 Hypertension?
Systolic = 130 - 139 OR Diastolic = 80 - 89mmHg
How do the kidneys manipulate intravascular volume?
The Kidneys can retain Sodium to increase intravascular volume and raise blood pressure
Why are centrally acting agents not first line?
Despite minimal drug interactions, CNS side effects prevent first line usage
Where is the Na-K-Cl symporter found?
The Thick Ascending Loop of Henle
What are the effects of ACE Inhibitors?
Decreased Ang II leads to:
Decreased Sympathetic Activation = VasoDILATE
Decrease Smooth Muscle Contraction = VasoDILATE
Increased Bradykinin = Vasodilate
Decreased Na/H2O Retention = Lower Blood Volume
Drugs that end with -artan are?
Angtiotenin II Receptor Blockers
What are the effects of ARBs?
Decreased Sympathetic Activation = VasoDILATE
Decrease Smooth Muscle Contraction = VasoDILATE
Decreased Na/H2O Retention = VasoDILATE
When should a loop diuretic be used instead of a Thiazide?
People with acute or complicated hypertension that have not controlled their hypertension with Thiazides should receive loop diuretics
Are home blood pressures expected to be higher or lower than clinic blood pressures?
Home blood pressures should be lower than clinic
What are the side effects of Nitroprusside?
Hypotension and lactic acidosis from Cyanide toxicity
How do Thiazide Diuretics work?
Inhibit Na-Cl symporter in the Distal Convoluted Tubule to promote Sodium Excretion and water loss
What portion of Sodium reabsorption is attributable to the DCT?
7% of sodium is reabsorbed in the DCT
Why is the PCT not a good target for diuretics?
The PCT is responsible for 60% of sodium reabsorption, making it an attractive target
However, inhibition of the PCT leads to compensation by other areas to increase Na reabsorption, preventing a diuretic effect
What is the Carotid Sinus a readout for?
The Carotid Sinus detects blood pressure to measure blood flow to the brain
Why can Calcium Channel Blockers be effected by other drugs?
Depend on CYP450 metabolism; do not alter other drugs, but may be altered by other drugs
How do risk factors effect target blood pressures for individual patients?
While there are overall guidelines for blood pressure, an individuals risk factors can result in lower target blood pressures to account for added individual risk
What is the Juxtaglomerular Apparatus?
A group of cells found in the wall of the Afferent Arteriole that secrete Renin
What are the b1 selective Beta Blockers?
Atenolol and Metoprolol
What are Korotkoff sounds?
Sounds heard on a blood pressure cuff that correspond to Systolic and Diastolic blood pressure
Which is more dangerous, white coat or masked hypertension?
Masked hypertension is more dangerous because in this scenario the patient’s blood pressure is elevated for longer periods of time when they are at home, and only briefly normal in clinic
What are the side effects of K sparing diuretics?
Amiloride and Spironolactone lead to Hyperkalemia
When is Methyldopa used?
During pregnancy
What is hypertension?
Hypertension is the measured force against the walls of the arteries as the heart pumps blood through them
What are side effects of diuretic drugs?
HCTZ and other diuretics can cause:
Hypokalemia
Hyponatremia
Hypercalcemia
What are the peripheral vasodilators?
NMH
Nitroprusside
Minoxidil
Hydralazine
What is a risk of Clonidine?
Withdrawal symptoms that lead to rebound high BP
What is the risk of Hyperkalemia?
Arrythmias
Why might clinic blood pressures be flawed?
White coat hypertension is falsely high while masked hypertension is falsely low in clinic
Why can HCTZ cause Hypercalcemia?
HCTZ blocks the Na/Cl symporter, leading to low Na in the DCT cells
An Na/Ca antiporter results in Na being drawn into the DCT cells and an efflux of Ca into the bloodstream, resulting in Hypercalcemia
How does Nitroprusside work?
Converted into Nitric Oxide, activating Guanyl Cyclase to increase cGMP and vasodilate
What are the effects of blocking b1 receptors?
Decreased HR, Contractility, and SV
Decreased Renin Release = decreased SVR
What three conditions lead to increased Renin release?
Decreased NaCl delivery to the Macula Densa
Hypotension/hypovolemia leading to decreased stretch of the Afferent Arteriole of the Kidney
Sympathetic stimulation
How does volume regulation affect arterial pressure?
Kidneys maintain intravascular volume and can retain Sodium to increase intravascular volume, raising blood pressure
Renin, Angiotensin, and Aldosterone alter Kidney Sodium regulation
What are the side effects of Hydralazine?
Headache, drug induced Lupus
How does Cardiac Output affect arterial pressure?
Increased cardiac output results in increased blood pressure
Sympathetic tone increases HR which increases CO and blood pressure
Are diuretics a first line treatment for hypertension?
Yes, they are a first line with the risk of causing hypokalemia in high doses
When is Methyldopa used?
Prior to surgery
How does Sodium movement regulate water reabsorption in the DCT?
Sodium movement from the lumen across the DCT and into circulation reabsorbs water
Na/Cl symporter first transports Sodium using Chloride to power the gradient, bringing water inside the DCT
Na/K ATPase then pumps the Sodium out into circulation
Which class of Calcium Channel Blockers are most effective at lowering PVR?
Dihydropyridines; cause reflex Tachycardia
Where are a2 receptors found?
On presynaptic neurons in the brain
What are the major and minor effects of diuretics?
Major = decreased PVR due to decreased Na
Minor = decreased intravascular volume due to Na/Water loss
How does Methyldopa work?
Methyldopa replaces Norepi in the secretory vesicles of Adrenergic neurons, causing vasoconstriction but inhibiting further activity from the brain, leading to overall vasodilation
What are the target population for ACE Inhibitors and ARBs?
Hypertensive patients with:
Heart Failure
Diabetes
CAD/post MI
How does altering sympathetic tone effect blood pressure?
Increased sympathetic tone leads to:
Increased Venous Return = Increased CO
Increased Cardiac Contractility + HR = Increased CO
Increased Arterial Contraction = Increased PVR
Combined, increased BP
What is the effect of drugs that inhibit the Na-K-Cl symporter?
Decreased Sodium influx and ultimately water loss to decrease blood volume
What are the major effects of Beta Blockers?
Decreased Cardiac output (b1) and decreased PVR (despite opposing effects of b1 decreased renin and b2 blockade)
What are the blood pressure ranges for elevated blood pressure?
Systolic = 120 - 129 AND Diastolic < 80mmHg
How does vascular tone affect arterial pressure?
Contraction of arterial vascular smooth muscle raises blood pressure while dilation of arterial vascular smooth muscle lower blood pressure
Which class of Calcium Channel Blockers has roughly equal effects on Cardiac Output and PVR?
Diltiazem
Why is hypertension considered a “silent killer”?
Effects 1/4 adults but presents no symptoms
What is the danger of Hypercalcemia?
Kidney stones
How does Sympathetic Activity alter blood pressure?
Sympathetic Activity:
Increases vascular resistance
Increases Sodium reabsorption
Promote Renin release by the JGA
What is white coat hypertension?
Elevated blood pressure in clinic and normal blood pressure at home
Where do Furosemide and Torsemide act?
They inhibit the Na-K-2 Cl symporter in the Thick Ascending Loop of Henle
Prevent Sodium reabsorption and lead to water loss
How does blood pressure change in older adults?
Blood pressure rises as people get older, especially after 60 years old, and the cutoff is 140/90mmHg
What population are Calcium Blockers contraindicated in and why?
Not safe in patients with Heart Failure due to risk of Bradycardia
