SM 133a - Hypertension Pathophysiology and Pharmacology Flashcards
What is the threshold for medical hypertension treatment if a patient has >10% risk of developing heart disease?
Blood pressure should be treated if it is >130 systolic or >80 diastolic
What is the threshold for medical hypertension treatment if a patient has <10% risk of developing heart disease?
Blood pressure should be treated if it is >140 systolic or >90 diastolic
Home blood pressure readings over the course of 1 week measure 125/85
Which blood pressure category does this fall into?
Stage I Hypertension
(130-139 systolic or 80-89 diastolic)
List the ranges for each category. Note: if systolic and diastolic fall into different categories, go with the higher classification
Normal:
Elevated:
Stage I Hypertension:
Stage II Hypertension:
Normal: <120/<80
Elevated: 120-129/<80
Stage I Hypertension: 130-139/80-89
Stage II Hypertension: >140/>90
How many measurements are required to make a diagnosis of hypertension?
At least 2
What are the 3 major physiologic determinants of blood pressure?
Volume: Stroke volume and total blood volume
Vascular tone
Cardiac Output
List the mechanisms by which Angiotensin II effects blood pressure
- Sympathetic activation
- Smooth muscle vasoconstriction
- Decreased bradykinin -> Prevention of vasodilation
- Na+ and H2O retention
- By increasing aldosterone in the adrenal cortex
- By increasing ADH in the brain
What are the 4 options for first-line hypertension treatment?
- Thiazide diuretics
- Hydrochlorothiazide
- ACE inhibitors
- -pril drugs
- ARBs
- -sartan drugs
- Calcium Channel Blockers
- Verapamil, Diltiazem, Nifedipine
Describe the mechanism and site of action of thiazide drugs
Thiazides like hydrochlorothiazide and chlorthalidone block the Na+-Cl- symporter in the distal convoluted tubule
This traps Na+ in the urinary space, leading to increased K+ excretion via Na+/K+ exchanger activity
(Can combine with an ACE inhibitor to preserve K+)
Give 2 examples of thiazide drugs
hydrochlorothiazide and chlorthalidone
Describe the mechanism and site of action of furosemide, torsemide, and bumetanide
The -(m/n)ide drugs are loop diuretics
They block the Na+-K+-2Cl- symporter in the thick ascending limb of the loop of Henle
This traps these ions in the urinary space, leading to acute volume loss. They are best used for rapid diuresis, while thiazides are better tolerated in the long term
Which diuretics are effective for acute volume loss, but are not recommended for long-term therapy (except in patients who have chronic kidney disease)?
Loop duretics: Furosemide, torsemide, and bumetanide
Note: combine with saline if the patient is hypercalcemic
What blood pressure measurements constitute a hypertensive emergency?
SBP>180 or DBP >120
List 4 K+ sparing diuretics
- Renal epithelial Na+ channel blockers
- Triamterene
- Amiloride
- Renal epithelial mineralcorticoid receptor blockers
- Spironolactone
- Eplerenone
List 3 loop diruetics
Who are these drugs recommended for?
Furosemide, torsemide, and bumetanide
Effective for acute volume loss, but are not recommended for long-term therapy (except in patients who have chronic kidney disease)
Note: combine with saline if the patient is hypercalcemic
Which drugs act by blocking the renal epithelial Na+ channels in the late distal tubule and collecting duct?
Triamterene
Amiloride
(K+ sparing diuretics)
Describe the mechanism and site of action of Triamterene and Amiloride
Triamterene and Amiloride act by blocking the renal epithelial Na+ channels in the late distal tubule and collecting duct of the kidney. They are K+ sparing diuretics
If less Na+ gets into the epithelial cells, less K+ is expelled from them (via decreased activity of the Na+/K+ exchanger)
Describe the mechanism and site of action of spironolactone and eplerenone
Spironolactone and eplerenone are aldosterone receptor antagonists. They block mineralcorticoid receptors (aka the aldosterone receptor) on epithelial cells in the late distal tubule and collecting duct of the kidney. They are K+ sparing diuretics
If less Na+ gets into the epithelial cells, less K+ is expelled from them (via decreased activity of the Na+/K+ exchanger)
What drugs would you give to a hypertensive patient despite thiazide therapy who is also hypokalemic?
K+ sparing duretic
Tiamterene, amiloride, spironolactone, or eplerenone
Describe the effects of aldosterone on blood pressure
Aldosterone acts on the distal nephron to increase blood pressure by promoting Na+ absorption
By promoting the absorption of Na+, K+ and H+ are excreted
Describe the mechanism of action of clonidine
Clonidine is an adrenergic alpha2 receptor agonist
The alpha2 receptors is located on the presynaptic sympathetic neuron. It usually functions as a feedback mechanism that senses and then downregulates norepinephrine.
Clonidine “artificially” stimualtes the alpha2 receptors, thus inhibiting norepinephrine release and preventing vasoconstriction
Which blood pressure medication is an alpha2 adrenergeic receptor agonist?
Clonidine
Describe the mechanism of action of methyldopa
Methyldopa replaces norepinephrine in secretory vescicles of adrenergic neurons.
This blocks central adrenergic outflow through negative feedback mechanisms, thus inhibiting vasoconstriction
Which blood pressure medication replaces norepinephrine in secretory vescicles of adrenergic neurons?
Methyldopa
What are the two major centrally acting blood pressure medications?
Methyldopa (replaces norepinephrine in secretory vescicles of adrenergic neurons)
Clonidine (alpha2 adrenergeic receptor agonist)
Which blood pressure medications are alpha1 adrenergic receptor blockers?
-zosin drugs
Prazosin, Terazosin, Doxazosin
Describe the mechanism of action of -zosin drugs (Prazosin, Terazosin, Doxazosin)
-zosin drugs are alpha1 receptor blockers
Inhibiting the alpha1 receptor = inhibition of vasoconstriction in response to adrenergic signaling
The result is decreased peripheral vascular resistance
List 4 cardioselective beta blockers
Which beta receptors are blocked?
Cardioselective = blocks beta1 receptors in the heart
- Atenolol
- Metoprolol
- Carvedilol (also alpha1 blocker)
- Labetalol
Which beta blockers act on beta1 and beta2 receptors?
Propanolol
Timolol
Which drug is both beta1 and alpha1 adrenergic antagonist?
Carvedilol
Are beta-blockers conidered first line agents for hypertension?
When are they used?
No; they are typically used with other agents (ACE inhibitor, thiazide, ARB, Ca2+ channel blocker), especially if the patient has heart failure
List 3 Ca2+ channel blockers that can be used to treat hypertension
- Non-dihydropyridines
- Veramapil (a Phenylalkylamine)
- Diltiazem (a Benzothiazepine)
- Dihydropyridines
- Nifedipine
What precaution should be taken when prescribing non-dihydropyridine drugs?
Do not use in conjunction with another agent that lowers heart rate (beta blocker), or in patients with LV systolic dysfunction
Describe the mechanism of action of verapamil
Verapamil is a non-dihydropyridine Ca2+ channel blocker
It blocks L-type Ca2+ channels in the heart only
Less intracellular Ca2+ = decreased contractility = decreased stroke volume = decreased blood pressure
Describe the mechanism of aciton of diltiazem
Diltiazem is a non-dihydropyridine Ca2+ channel blocker
It blocks L-type Ca2+ channels in the heart AND vascular smooth muscle. This leads to…
- Decreased cardiac contractility, leading to decreased BP
- Decreased constriction in vascular smooth muscle
Describe the mechanism of action of nifedipine
Nifedipine (and other -dipines) are dihydropyridine Ca2+ channel blocker
They L-type Ca2+ channels in vascular smooth muscle. This leads to decreased constriction in vascular smooth muscle, which decreases peripheral vascular resistance
Which Ca2+ channel blocker acts on the heart only?
Veramapil (and other phenylalkylamines)
Which Ca2+ channel blocker acts on the heart and vascular smooth muscle?
Diltiazem (and other Benzothiazepines)
Which Ca2+ channel blocker acts on vascular smooth muscle only?
Nifedipine (and other dihydropyridines)
List 3 hypertension drugs that are peripheral vasodilators
Hydralazine, minoxidil, nitroprusside
Describe the mechanism of action of hydralazine
Peripheral vasodilator
Relaxes arteriolar smooth muscle
Describe the mechanism of action of minoxidil
Peripheral vasodilator
Activates K+ channels on vascular smooth muscle. This promotes K+ efflux, hyperpolarizing the cell. This prevents contraction and promotes relaxation
Describe the mechanism of action of nitroprusside
Peripheral vasodilator
Nitroprusside is metabolzed by endothelial cells to nitric oxide, which activates guanyl cyclase to increase cGMP, leading to vasodilation
Which drugs should not be prescribed with diltiazem? Why?
Beta blockers
Too much decrease in CO due to decreased HR
Which drugs should not be prescribed with ACE inhibitors?
Why?
Spironolactone, eplerenone, triamterene, amiloride (K+ sparing diuretics)
This would lead to hyperkalemia
Which drugs should not be prescribed with nifedipine?
Hydralazine
Leads to edema
Which drugs should not be prescribed with hydralizine?
Nifedipine
Leads to edema
What is the mechanism of action of -sartan drugs?
-sartan drugs are angiotensin II receptor blockers, also known as ARBs. They block the action of angiotensin II at AT1 to promote vasodilation and Na+ excretion
Note: AT1 may also mediate the progression of atherosclerosis and myocardial remodeling; ARBs may inhibit this as well
