Cardio: HTN/RAAS + Some Diuretics

BP = ______ × ______

Cardiac Output = ______ × ______

CO, SVR
HR, Stroke Volume

Hypertension drugs mainly targets (3):

CO, vascular resistance, and blood volume

The 4 main anatomical sites controlling BP are:

arteries/arterioles, heart, kidneys, and capacitance veins

Capacitance veins contain ______ receptors.

When capacitance veins relax, they can hold ______, which ______ BP.

alpha-1
more blood, lowers

Baroreceptors are responsible for ______ BP regulation.

short-term/rapid

Kidneys are responsible for ______ BP regulation.

long-term

RAAS is activated mainly when ______.

RAAS also activates when the kidney senses ______ delivery to the ______.

BP drops
low NaCl, macula densa

The cells that release renin are called ______ cells.

“Juxta” means ______ the glomerulus.

juxtaglomerular
next to

The 3 major triggers for renin release are:

low preglomerular pressure, low NaCl at macula densa, and beta-1 stimulation

Intrarenal ______ sense low pressure entering the glomerulus.

baroreceptors

Less filtration → ______ reaches the macula densa.

less NaCl

Sympathetic activation stimulates renin release through ______ receptors on juxtaglomerular cells.

Beta-1

Fill in the RAAS cascade:
Low BP → kidneys release ______ → converts angiotensinogen into ______ → ______ converts it into ______

renin, Ang I, ACE, Ang II

Angiotensinogen is produced by the ______.

liver

ACE is mainly located on pulmonary and renal ______.

ACE converts Ang I into ______.

ACE also breaks down ______.

endothelium
Ang II

bradykinin

Angiotensin II causes direct ______ of arterioles.

Angiotensin II increases ______ nervous system activity.

Angiotensin II stimulates release of ______ from the adrenal cortex.

vasoconstriction
sympathetic
Aldosterone

Aldosterone increases reabsorption of ______ and ______.

Aldosterone promotes excretion of ______.

sodium, water
potassium

Angiotensin II also stimulates release of ______ hormone (ADH).

ADH increases ______ reabsorption.

antidiuretic

water

Fill in the full BP restoration cascade:
Low BP → renin → Ang I → Ang II → ______ + ______ release + ______ release → ↑ ______ → ↑ ______

vasoconstriction, aldosterone, ADH, blood volume, BP

Renin is initially released as inactive ______.

pro-renin

Pro-renin can either become active renin OR bind the ______ receptor.

Aliskiren only inhibits the ______ form of renin.

Because pro-renin pathways still work, Aliskiren causes ______ blockade of RAAS.

pro-renin receptor (PRR)
active

incomplete

Chronic high Ang II levels cause cardiac and vascular ______.

Chronic Ang II exposure contributes to ______ progression.

ACEIs and ARBs help heart failure by preventing maladaptive ______.

remodeling
heart failure
remodeling

ACE inhibitors increase levels of ______ because ACE normally breaks it down.

Bradykinin

Bradykinin stimulates release of ______ and ______.

Bradykinin causes ______.

nitric oxide, PGI2
vasodilation

ACE inhibitors are often more ______ than ARBs because they increase ______.

vasodilatory, bradykinin

ACE inhibitor cough is usually ______ and ______.

ACE inhibitor cough occurs because bradykinin accumulates in the ______.

ARBs cause ______ cough because they do NOT affect ______.

dry, non-productive
lungs

less, bradykinin

ACE inhibitors block conversion of ______ → ______.

ACE inhibitors usually end in ______.

Example ACE inhibitor: ______

Ang I, Ang II

-pril

Lisinopril

ARBs block the ______ receptor.

ARBs allow Ang II levels to remain ______ or ______.

ARBs block the ______ rather than its formation.

ARBs usually end in ______.

Example ARB: ______

AT1

normal, high

effects of Ang II

-sartan

Losartan

Direct renin inhibitor: ______

IV ACE inhibitor used in hypertensive emergencies: ______

Aliskiren

Enalaprilat

Angiotensin II preferentially ______ the ______ arteriole.

constricts, efferent

The efferent arteriole contains MORE ______ receptors.

Ang II

__________ dilate the efferent arteriole.

ACEIs/ARBs

Efferent arteriole dilation causes glomerular pressure to ______.

decrease

ACEIs/ARBs temporarily decrease ______.

ACEIs/ARBs may temporarily increase ______.

GFR

SCr

Patients with renal artery stenosis rely heavily on efferent arteriole ______ to maintain filtration.

constriction

ACEIs/ARBs are risky in (3):

renal artery stenosis, severe renal impairment, and solitary kidney

Aldosterone normally reabsorbs ______ and excretes ______.

ACEIs/ARBs lower aldosterone, causing potassium ______.

ACEIs/ARBs can cause ______.

sodium, potassium

retention

hyperkalemia

Hyperkalemia risk is especially high in (3):

CKD, aldosterone antagonists, and potassium-raising drugs

ACEIs/ARBs are contraindicated in ______, especially during the ______ and ______ trimesters.

Fetal kidney development depends on ______ and ______.

pregnancy, 2nd, 3rd
Ang II, aldosterone

Diuretics lower BP by reducing ______ volume.

Diuretics increase ______ production.

Different diuretics target different parts of the ______.

The kidney is the primary ______ target.

______ are considered first-line antihypertensives.

Blood

urine

nephron

antihypertensive

thiazides

Carbonic anhydrase inhibitors work in the ______.

Carbonic anhydrase inhibitors are relatively ______ diuretics.

Proximal tubule

weak

Example loop diuretic: ______

Loop diuretics act in the ______ of the loop of Henle.

The loop of Henle normally reabsorbs large amounts of ______.

Loop diuretics cause ______ diuresis.

Loop diuretics are best for _____.

Loop diuretics commonly cause loss of ______.

Furosemide

thick ascending limb

sodium

potent

acute pulmonary edema

potassium

Example thiazide diuretic: ______

Thiazides act in the ______.

Thiazides are preferred for chronic ______.

Thiazides are less intense than ______ diuretics.

Thiazides help retain ______.

hydrochlorothiazide

distal convoluted tubule

HTN

loop

calcium

Potassium-sparing diuretics work in the ______.

Potassium-sparing diuretics are the ______ diuretics in terms of ______.

collecting duct

weakest, fluid removal

Spironolactone blocks the ______ receptor.

Spironolactone causes more ______.

aldosterone

potassium retention

A patient losing too much potassium on loop diuretics may receive a ______.

potassium-sparing diuretic

Centrally Acting Antihypertensives:

• ______ works in the ______ center and reduces sympathetic ______.

• Another centrally acting antihypertensive is ______

Clonidine, CNS vasomotor, outflow

Methyldopa

Alpha blockers cause ______ by blocking alpha-1 receptors.

Alpha blockers decrease ______.

Examples of alpha blockers (3):

vasodilation

SVR

Prazosin, terazosin, and doxazosin

Tamsulosin ______ blocks ______ receptors.

Tamsulosin mainly works on the ______.

Tamsulosin is used to treat ______.

Tamsulosin has minimal effect on ______.

selectively, Alpha-1A

prostate

BPH

BP

Yohimbine blocks ______ receptors (increases ______ release).

Yohimbine acts as a ______.

Yohimbine may cause ______.

alpha-2, NE

stimulant

hypertensive emergencies

Mixed alpha/beta blockers include (2):

labetalol and carvedilol

Beta-1 blockade causes ↓ ______.

Alpha-1 blockade causes ______.

HR

vasodilation

IV ______ is commonly used in hypertensive emergencies.

labetalol

Beta-1 selective blockers include(2):

metoprolol and atenolol

Nonselective beta blocker: ______

Nonselective beta blockers block both ______ and ______ receptors.

Blocking beta-2 receptors in lungs causes ______.

Nonselective beta blockers are contraindicated in ______.

Propranolol

beta-1, beta-2

bronchoconstriction

asthma

Propranolol is highly ______, allowing it to cross the BBB.

Propranolol is useful for ______.

Propranolol may help ______.

lipophilic

migraine prophylaxis

performance anxiety

Chronic uncontrolled hypertension increases risk of (2):

Stroke and kidney failure

Hypertensive crisis is typically BP ≥ ______ / ______.

Hypertensive crisis carries high risk of ______ damage.

180, 120

organ

Arterial blood pressure is mainly determined by ______ and ______ vascular resistance.

cardiac output, peripheral

Cardiac output is the product of ______ volume × ______.

stroke, HR

Arterioles primarily contain ______ receptors involved in BP regulation.

alpha-1

Postcapillary venules primarily contain ______ receptors.

alpha-1

The heart contains primarily ______ receptors involved in sympathetic regulation.

beta-1

The kidney contains ______ receptors that regulate renin release.

beta-1

The kidney helps regulate long-term BP through control of ______.

blood volume

Alpha-1 stimulation of capacitance veins causes ______.

vasoconstriction

The baroreflex pathway responds to changes in ______.

Baroreceptors are located in the ______ and the ______.

blood vessel pressure

carotid sinus, aorta

Renin protects the body against ______ (______ BP).

hypotension, increases

Binding of prorenin to the prorenin receptor causes a ______ change that allows angiotensinogen conversion.

conformational

Removal of the ______ converts prorenin into active renin.

propeptide

ACE inhibitors reduce sympathetic nervous system ______.

activity/output

ARBs are generally administered by the ______ route.

oral

Azilsartan has the ______ AT1 receptor affinity among ARBs listed.

highest

Rank order of AT1 affinity: Azilsartan > Candesartan = Olmesartan > Irbesartan = Eprosartan > Telmisartan = Valsartan > Losartan

KNOW

Hyperkalemia occurs in up to ______% of patients taking ACEIs/ARBs/direct renin inhibitors.

Potassium should initially be monitored within ______ after starting ACEIs/ARBs/direct renin inhibitors.

5

2-4 weeks

Acute renal failure from ACEIs/ARBs alone is ______.

Risk of acute renal failure increases when ACEIs/ARBs are combined with ______ and ______.

uncommon

loop diuretics, NSAIDs

Kidney monitoring for ACEIs/ARBs includes (2):

BUN and Scr

Small SCr increases less than __% from baseline usually do not require therapy changes.

ACEI/ARB-related increases in SCr are generally ______.

30-50

reversible

Patients at risk for orthostatic hypotension should start ACEIs/ARBs (______ BP) at ______ doses.

lowers, low

ACE inhibitor cough is more common in (2):

Women and Asians/Africans

Serious swelling adverse effect associated with ACE inhibitors: ______.

Angioedema from ______ requires immediate ______ of the medication.

ACE inhibitor angioedema has minimal cross-reactivity with ______ or ______.

angioedema

ACE inhibitors, discontinuation

ARBs, direct renin inhibitors