Test 2 Cardiology-All Lapinsky Combined (Lapinsky-Diuretics, Lapinsky-RAAS , Lapinsky-CCB+ Beta Blockers)

diuretics are useful in the treatment of hypertension as "___ ___" due to a reduction in blood volume via increased urination

water pills

increased blood volume = ____ blood pressure

increased

Diuretics increase the rate of urine excretion by the kidneys primarily by:

-decreasing tubular reabsorption of ___ and its osmotic equivalent ___

Na+, H2O

diuretics decrease tubular reabsorption of Na+ and H2O from __ back into ___

urine, blood

Key concept: Na+ leads and __ follows

H2O

a kidney contains about 2 million ___ that are responsible for filtering the blood and regulating blood and urine levels of multiple chemical species such as H2O, K+, Na+, Ca2+, and Cl-

nephrons

filtration means from ___ to ___

blood, urine

reabsorption means from ___ to ___

urine, blood

secretion means from ___ to ___

blood, urine

excretion moves from __ to __ __

urine, external environment

___= increased urine output due to more H2O excreted from blood→ urine

diuresis

____= increased Na+ from blood→urine

natriuresis

in general, increased natriuresis means ___ diuresis

increased

Diuresis

-key substance lost is __ (and maybe electrolytes)

H2O

Natriuresis

-key substance lost is ___

Na+

Diuresis

-can result from excess fluid intake, osmotic effects, or ___

diuretics

Natriuresis

-usually caused by __ or __ that block Na+ reabsorption from urine→blood

drugs, hormones

Diuresis

-used to reduce __ __ (like from edema or high bp)

fluid overload

Natriuresis

-important for lowering __ __ and reducing fluid volume since Na+ retention in the blood drives H2O retention into blood

blood pressure

____ fluids and high __ __ can cause diuresis

IV, blood sugar

loop/thiazide ___ and ____ can cause natriuresis

diuretics, ANP

What does ANP stand for?

atrial natriuretic peptide

does all natriuresis cause some diuresis?

yes

does all diuresis involve natriuresis?

no

A significant concern of the most commonly used diuretics is ___ blood levels because even small deviations can be life threatening

potassium

what medications cause Hypokalemia?

loop diuretics, thiazide diuretics

what medications cause Hyperkalemia?

potassium-sparing diuretics, ACE inhibitors, ARBs

Hypokalemia causes everything to be "__ and __"

low, slow

Main dangers of HYPOkalemia:

1) muscle weakness

2) cramps

3) ____

4) life threatening _____ ______

paralysis, cardiac arrhythmias

Main takeaway of HYPOkalemia:

there is risk of __ weakness and __ weakness

muscle, heart

Main dangers of HYPERkalemia:

1) __ __ disturbances

2) risk of sudden ___ ___

cardiac conduction, cardiac arrest

Main takeaway of HYPERkalemia:

there is risk of dangerous __ __

heart rythym

at the ascending limb of the loop of henle, an active transport system functions to reabsorb Na+, K+, and Cl- from urine→blood via what active transport protein?

NKCC2

the ascending limb of the loop of henle functions to reabsorb ____% of filtered Na+ from urine→blood

25

Loop Diuretics bind to and inhibit function of ____

NKCC2

Loop Diuretics bind to and inhibit function of NKCC2, resulting in desired diuresis BUT ALSO potentially dangerous ____

hypokalemia

must know loop diuretics:

-_____ (Lasix)- most widely prescribed

-______ (Bumex)

-_______ (Soaanz)

-_____ _____ (Edecrin)

Furosemide, Bumetanide, Torsemide, Ethacrynic Acid

furosemide is most widely prescribed but its oral ____ can be unreliable

absorption

______ has a more reliable oral absorption than furosemide

torsemide

furosemide, bumetanide, and torsemide all have ___ ___ group

aryl sulfonamide

some patients may have a "sulfa" ___ ____ in response to the aryl sulfonamide in furosemide, bumetanide, and torsemide

drug allergy

__ ___ is the drug of choice in sulfa-allergic patients

ethacrynic acid

ethacrynic acid is the drug of choice in sulfa-allergic patients, but is rarely used due to high cost and highest ___ (ear) risk

ototoxicity

the most common culprits for "sulfa" drug allergies are ___ ___

sulfonamide antibiotics

some sulfonamide-containing drugs (like some diuretics, diabetes, celecoxib) are chemically different and usually don't trigger the same allergy, but there can sometimes be ___-____

cross-reactivity

in general, the body will identify part of the sulfonamide molecule as ___ the first time it encounters it; the immune cells process and remember it

foreign

when the sulfonamide is taken again, the immune system overreacts via __ or __-cell mediated reactions like rash and anaphylaxis

IgE, T

Loop diuretics (via inhibition of NKCC2):

-decrease ___ of Na+ from urine→blood

-increase ___ of Na+ from blood→urine

reabsorption, excretion

loop diuretics ____ Ca2+ excretion from blood→urine

increase

loop diuretics can cause ___calcemia in the blood, and undesirably increase risk of ____

hypo, osteoporosis

thiazide diuretics ____ Ca2+ excretion from blood→urine

decrease

thiazide diuretics can cause ___calcemia in the blood, which can be potentially ___

hyper, beneficial

loop diuretics have a ___ ceiling/efficacy

high

thiazide diuretics have a __-___-___ ceiling/efficacy (means inc dose will eventually lead to plateau)

low-to-moderate

Of the 3 major diuretic drug classes, which produces the strongest natriuresis and diuresis?

loop diuretics

Boxed warning for loop diuretics:

-profound diuresis can cause __ and ___ depletion!

fluid, electrolyte

Key ADRs of Loop Diuretics

1) ___kalemia

hypo

hypokalemia can potentially be avoided with regular intake of potassium-rich foods, potassium supplements, or concurrent use of a ___-___ ___

potassium-sparing diuretic

Key ADRs of Loop Diuretics

2) ____ (rare but serious)

ototoxiciy

What loop diuretic has highest risk of ototoxicity?

ethacrynic acid

ototoxicity may present itself as:

-hearing loss

-_____ (ear ringing)

-virtigo

tinnitus

the loop diuretic in ascending loop of henle drug target is NKCC2, there is a similar drug target in the ear that drives normal hearing, called ____

NKCC1

Risk factors for ototoxicity from loop diuretics:

1)____ doses and/or rapid ___ administration

high, IV

Risk factors for ototoxicity from loop diuretics:

2) additive risk via concurrent use of other ototoxic drugs, like ____ antibiotics and ___

aminoglycoside, cisplotin

ototoxicity from loop diuretics is usually reversible, but can be ___ at very high doses or with concurrent use of other ototoxic drugs

irreversible

In general, loop diuretics have a __ onset of action

(IV ~ 5 min, Oral ~ 30-60 min)

rapid

In general, loop diuretics have a __ duration of action

(4-6 hours)

short

loop diuretics can be prescribed for treatment of hypertension, but the short duration of action __ their use to some extent

limits

Alternative to treatment of HTN, loop diuretics are typically used for acute ___ or __ ___

pulmonary, peripheral edema

Alternative to treatment of HTN, loop diuretics are typically used for acute pulmonary or peripheral edema because they cause potent ___ diuresis

rescue

loop diuretics are also primarily used in __ ___ (heart muscles cannot pump blood effectively)

heart failure

loop diuretics are used in heart failure bc they:

-decrease preload

-reduce congestive HF symptoms

-make it easier for heart to pump blood

-restore ___ (state of having normal amount of body fluids)

euvolemia

chronic use of a loop diuretic may lead to drug ___ (where increasing dose is not helpful)

resistance

how do loop diuretics cause drug resistance?

loop blockade forces Na+ into urine, wherein the DCT and collecting duct of the nephron adapt by ____ and upregulation of __ and ___ as Na+ transporters

hypertrophy, NCC, ENAC

at the first portion of the distal tubule, ___-___% of Na+ (and H2O) are reabsorbed from urine→blood

5-8

what are the diuretic drug classes that work at the first portion of the distal tubule?

true thiazide diuretics, thiazide-like diuretics

Main Points about Thiazide Diuretics

-effective, cheap, mild side effects

-_____ duration of action vs loop

longer

thiazide-diuretics are effective for __-term bp lowering

long

thiazide diuretics bind to and inhibit ____ in the distal convoluted tubule cell

NCC

thiazide diuretics cause desired diuresis but also ____kalemia

hypo

thiazide diuretics cause desired diuresis by:

-_____ reabsorption of Na+ (and H2O ) from urine→blood

-____ excretion of Na+ (and H2O) from blood→urine

decreased, increased

loop diuretics directly block K+ reabsorption and therefore cause hypokalemia

thiazide diuretics _____ block K+ reabsorption and therefore cause hypokalemia

indirectly

how do thiazide diuretics indirectly cause hypokalemia?

1) because thiazide diuretics inhibit NCC in the DCT, there is increased Na+ (and H2O) delivered downstream to the __ ___

collecting duct

how do thiazide diuretics indirectly cause hypokalemia?

2) in the collecting duct, there is a compensatory reabsorption of Na+ from urine→blood via ____

ENAC

how do thiazide diuretics indirectly cause hypokalemia?

3) as more Na+ arrives in the collecting duct due to this compensatory reabsorption, the more K+ is pumped from blood→urine via ___ channels

ROMK

how do thiazide diuretics indirectly cause hypokalemia?

4) the hypokalemia effect is amplified by ____

aldosterone

the thiazide diuretic-induced volume loss causes activation of RAAS, which causes aldosterone release, which further boosts __+ reabsorption from urine→blood and ___+ secretion from blood→urine

Na+, K+

Aldosterone further boosts Na+ reabsorption from urine→blood and K+ secretion from blood→urine via increased activation of ___ and ___/__/___

ENAC, Na+/K+/ATPase

is the duration of action longer for "true" thiazides or for "thiazide-like" diuretics?

"thiazide-like" diuretics

is the drug potency higher for "true" thiazides or for "thiazide-like" diuretics?

"thiazide-like" diuretics

"true" thiazides are better for what?

routine HTN, mild edema

"thiazide-like" diuretics are better for what?

resistant HTN, resistant edema

hydrochlorothiazide and chlorothiazide are "true" thiazides or for "thiazide-like" diuretics?

"true" thiazides

Chlorthalidone, Indapamide, and Metolazone are "true" thiazides or for "thiazide-like" diuretics?

"thiazide-like" diuretics

hydrochlorothiazide is the most commonly prescribed prescribed thiazide diuretics and widely used in fixed dose HTN combinations with ___ and ___

ARBs, ACE-I

what is the only thiazide available IV?

chlorothiazide

what thiazide has a higher risk of hypokalemia and hyponatremia because it is long acting with a half life of 40-60 hours?

chlorthalidone

metolazone is very ___

potent

there is contraindication for thiazide diuretics with "____" drug allergy

sulfa

Key adverse effect of thiazides is ____

hypokalemia