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Regulation of Blood Pressure

Regulation of Blood Pressure


Review of the Kidney

Kidney, 3 functions:
Cleansing of extracellular fluid and
maintenance of ECF volume and
Maintenance of acid-base balance
Excretion of metabolic wastes and foreign

Review of Kidney Funcion:

Three Basic Processes: Filtration, Reabsorption,
& Active Secretion
1. Filtration- occurs at the glomerulus; first step in
urine formation
Nonselective process; cannot regulate composition of urine

2. Reabsorption- More than 99% of water,

electrolytes & nutrients filtered at glomerulus
undergo reabsorption
Solutes reabsorbed by active transport
Water follow passively along the osmotic gradient created
by solute reuptake

PD:**Diuretics work by interfering with


Review of the Kidney

Active Tubular Secretion
Kidney: two major pumps for secretion
Organic acid pump
Organic base pump
Excrete a wide variety of molecules:
metabolic wastes, drugs, & toxins
Pumps for active secretion: located in
proximal convoluted tubule

Review of the Kidney

Reabsorption at Specific Sites in
Proximal Convoluted Tubule (PCT)
High absorptive capacity, 65% of filtered
sodium & chloride is reabsorbed in PCT
Almost all bicarbonate & potassium in
filtrate is reabsorbed PCT
When filtrate leaves PCT, sodium &
chloride are only solutes that remain in
significant amounts

Review of the Kidney

Reabsorption at Specific Sites along the
Loop of Henle:
Descending limb is freely water permeable
Water drawn into the interstitial spaces (from
the loop)
Concentrates urine

Ascending limb reabsorbs 20% of filtered

sodium & chloride
This portion is not water permeable, water
stays in, sodium & chloride move out. (Returns
tubular urine to its original tonicity (osmolality)

Review of the Kidney

Reabsorption at Specific Sites Along the Nephron:
Distal Convoluted Tubule (Early Segment)
Reabsorbs 10% of sodium & chloride, water follows

Distal Nephron (Late Distal Convoluted

Tubule & Collecting Duct)
Exchanges sodium for potassium; regulated by
Aldosterone reabsorbs Na+ and gets rid of K+

Determines final concentration of urine, regulated by

antidiuretic hormone (ADH).
ADH allows collecting duct to be permeable to water (body
reabsorbs more water), without ADH large amounts of water
can leave the body

PD: How Diuretics Work

PD: Most diuretics share same mechanism of
action: blockade of sodium and chloride
Creates osmotic pressure inside nephron that blocks
passive reabsorption of water
If water and solutes are not reabsorbed, they are
excreted from the body

The increase in urine flow is directly related to the

amount of sodium & chloride reabsorption blocked
Diuretics that act early in nephron block the
greatest amount of solute reabsorption (greatest
Diuretics increase urine output (UOP) by 1.8 L for
every 1% of solute reabsorption that is blocked; if
give TOO much, = dehydration

Adverse Effect: Impact on ECF

Diuretics can cause:
Hypovolemia (from excessive fluid loss)
Acid-base imbalance
Altered electrolyte levels.
Short-acting diuretics minimize these

Classification of Diuretics
High ceiling (Loop) diureticsFurosemide (Lasix)
Thiazide diuretics
hydroclorothiazide (HCTZ)
Osmotic diuretics mannitol
Potassium-sparing diuretics:
Aldosterone antagonists
spironolactone (Aldactone)
Nonaldosterone antagonists-

High-Ceiling (Loop) Diuretics

Most effective diuretics available
Produce more loss of fluid &
electrolytes than any other diuretic
Furosemide (Lasix) is most frequently
prescribed loop diuretic

Loop Diuretics: Furosemide

Sulfa based drug* assess hypersensitivity
Acts in ascending limb, Loop of Henle;
blocks reabsorption of sodium & chloride
Can produce profound diuresis
Can be given orally (diuresis starts within
60 minutes, lasts 8 hrs), IV (diuresis in 5
minutes, lasts 2 hrs) and IM.
*IV therapy is used in critical situations
(pulmonary edema)
*Typically used when less powerful
diuretics no longer (*but not always)

Loop Diuretics: Furosemide

Therapeutic Uses:
Pulmonary edema associated with congestive
heart failure
Edema of hepatic, cardiac or renal origin that
is unresponsive to less efficacious diuretics
Hypertension that cannot be controlled with
other diuretics
Especially useful in pts with severe renal
impairment, can promote diuresis even when
renal blood flow and glomerular filtration rate
are low

Loop Diuretics: Furosemide

Adverse Effects:
Hyponatremia, Hypochloremia & Dehydration
b/c can produce excessive loss of sodium,
chloride, & water
Severe dehydration can result (hold lasix if
dehydration occurs)
S/S of dehydration: dry mouth, unusual thirst,
oliguria, muscle cramps, anorexia, lethary,
restlessness, excessive weight loss
Dehydration can promote thrombosis & embolism
(headache, pain in chest/clavicle, or pelvis)
Can be minimized by low dose therapy &
adjusting dose daily

Loop Diuretics: Furosemide

Adverse Effects:
Orthostatic Hypotension Due to loss of
volume and relaxation of venous smooth
muscle (reduces venous return to the
Monitor BP regularly (teach to monitor at home)
Can cause acute hypotensive episodes from
rapid changes in FV, can lead to circulatory
collapse *Elderly

Hypokalemia- Potassium loss due to

increased secretion in distal nephron
Encourage potassium rich foods

Loop Diuretics: Furosemide

Adverse Effects:
Ototoxicity- Rarely causes permanent
deafness/hearing impairment, most hearing
impairment is transient, (Usually in high dose, IV,
renal impaired)
In ethacrynic acid (Edecrin), another loop diuretic
hearing loss can be permanent
Use caution when given with other ototoxic meds

Hyperglycemia- Can result from inhibition of

insulin release. Watch closely in diabetic pts.
Hyperuricemia- Frequent, most pts are
asymptomatic, but for pts predisposed to gout can
cause a gout attack

Loop Diuretics: Furosemide

Adverse Effects:
Pregnancy- Class C, Only used if no other
alternative & with caution (not studied on
humans/lab animals caused maternal
death, abortion, & and other adverse
Lipids, Calcium & MagnesiumFurosemide decreases HDL, raises LDL
cholesterol & triglycerides. Increases risk
of magnesium deficiency, increased
excretion of calcium (*elders with
Osteoporosis are at risk for fractures)

Loop Diuretics: Furosemide

Drug Interactions:
Digoxin- If potassium is low, serious risk
of drug-induced toxicity (ventricular
Ototoxic drugs- (Especially gentamycin)
can cause permanent hearing loss. Avoid
combined use of these drugs.
Potassium-Sparing Diuretics- Can reduce
the risk of hypokalemia
Lithium- Can allow lithium levels to
accumulate to toxic levels

Other Loop Diuretics:

Ethacrynic acid (Edecrin) Not sulfa
based, safe for use in sulfa allergy, not for
use in children, for edema only, not HTN
Torsemide (Demadex) metab. to active
& inactive metabolites
Bumetanide (Bumex) for edema only,
more potent, *black box warning: More
profound diuresis (H2O & electrolytes),
not for children, *careful dosing

Loop Diuretics: Furosemide

Drug Interactions:
Anithypertensive Agents- Furosemide can
cause hypotension, potentiated by
antihypertensive drugs
Nonsteroidal Aspirin, Anti-inflammatory
Drugs (NSAIDS)- Decrease the effects of
diuretics, ACE inhibitors (1st dose
hypotension) others see table
Contras: Sulfa allergy/hypersensitivity,
Precautions: *poor renal function, SLE
(lupus) Assess

Thiazide Diuretics
PD: Increase renal excretion of sodium,
chloride, potassium, & water
Elevates plasma levels of uric acid &
Greatest difference between thiazides &
loop diuretics: maximum diuresis of
thiazides is considerably lower than in
loop diuretics
Thiazides are not effective when urine
flow is scant (anuria, severe renal

Thiazides: Hydrochlorothiazide
Hydrochlorothiazide (HydroDIURIL,
HCTZ) most widely used thiazide diuretic
Promotes urine production by blocking
reabsorption of sodium & chloride in the
early segment of the distal convoluted
Since only 10% of filtered sodium &
chloride is normally absorbed where
thiazides act, maximum urine flow is lower
than with Loop Diuretics
Cannot be used to promote fluid loss in pts
with severe renal impairment

Thiazides: Hydrochlorothiazide
Therapeutic Uses:
Essential Hypertension- Primary use is for
HTN, and is often FIRST DRUG OF
Edema- Mild to moderate, heart failure
Diabetes Insipidus- Causes fluid retention
instead (unsure why)
Postmenopausal Osteoporosis
Protection,Promotes tubular reabsorption
of calcium


Adverse Effects:
Hyponatremia, Hypochloremia &
Dehydration- Milder than loop diuretics
Hypokalemia- Eat potassium rich foods,
*careful if taking digoxin.
Pregnancy and Lactation: Direct and
Indirect effects on developing fetus, and
impair fetal blood flow
Should not be used routinely during
pregnancy, caution

Thiazides: Hydrochlorothiazide
Adverse Reaction:
Hyperglycemia- Can elevate glucose
in diabetic pts
Hyperuricemia- Retention of uric acid,
can cause gout.
Lipid and Magnesium- Increase LDL,
total cholesterol and triglycerides. Can
cause magnesium deficiency.


Drug Interactions:
Same as loop diuretics, Slightly different
chemical structure, indications for use, PKs
Other Thiazide-Type diuretics:
True Thiazides:
Chlorothiazide (Diuril)
Methyclothiazide (Enduron)

Related to Thiazides:
Chlorthalidone (Hygroton) not for children, longer
half-life Indapamide (Lozol) specific for edema in
CHF, not for children, highly metab. in liver, caution
liver impaired
Metolazone (Zaroxolyn) not for children

Potassium-Sparing Diuretics
Produce increased urine production, but
limited, so not often used for diuresis
Produce substantial decrease in potassium
excretion, so these drugs are often
used to counteract potassium loss
caused by thiazide & loop diuretics.
Two subcategories:
Aldosterone Antagonists- spironolactone
Non-aldosterone antagonists- triamterene
(Dyrenium) and amiloride (Midamor)

Potassium-Sparing Diuretics:
PD: Blocks the actions of aldosterone in
distal tubule, (blocks all aldosterone
receptors: glucocorticoid, mineral corticoid,
androgen, & progesterone)
Aldosterone promotes sodium uptake in
exchange for potassium secretion
PD: Spironolactone causes retention of
potassium and increased excretion of sodium
Effects of spironolactone are delayed (typically
takes 48 hrs) because it blocks the action of new
proteins but does not stop existing transport

Potassium-Sparing Diuretics:
Spironolactone (Aldactone)
Therapeutic Uses:
HTN & Edema- Most commonly used in
combination with a loop or thiazide diuretic
to counteract the potassium-wasting effects
of the more powerful diuretics
Heart Failure (CHF) Proven to reduce
mortality and hospital admissions
Other Uses- Primary hyper-aldosteronism,
Off label: premenstrual syndrome, polycystic
ovary syndrome, acne * assess what drug is
used for

Potassium-Sparing Diuretics:
Adverse Effects:
Hyperkalemia- Most likely when
spironolactone is used alone, stop use if
hyperkalemia develops
Endocrine effects- Similar to other
steroid hormones (progesterone,
estradiol, testosterone). Can cause
gynecomastia, menstrual irregularities,
impotence, hirsutism & deepening of the

Potassium-Sparing Diuretics:
Drug Interactions
Thiazide & Loop diuretics- given to
counteract the potassium-wasting effects.
Agents that raise potassium levels
should never be given with
potassium supplements, salt
substitutes or another potassiumsparing diuretic
If given with ACE Inhibitors, ARBs, or direct
renin inhibitors can elevate potassium levels

Potassium-Sparing Diuretics: Triamterene

PD: Like spironolactone, triamterene
disrupts sodium-potassium exchange in
the distal nephron
PD:Triamterene is a direct inhibitor of the
exchange mechanism itself
Decreases sodium reabsorption, reduces
potassium secretion
Sodium is excreted, potassium is retained
Acts more quickly than spironolactone
because it inhibits the ion transport
directly. (develops in hours vs. days)

Potassium-Sparing Diuretics:
Triamterene (Dyrenium)
Therapeutic Uses:
Used alone or in combination with other
diuretics to treat HTN & edema
If Used alone produces mild diuresis
Used in combination, it augments
diuresis &helps counteract the
potassium wasting effects of the more
powerful diuretic

Potassium-Sparing Diuretics:
Triamterene (Dyrenium)
Adverse Effects:
Hyperkalemia- excessive accumulation is
the most significant adverse effect, likely
when triamterene is used alone. Should
never be used with another potassium
sparing diuretic or potassium
supplements or salt substitutes. Use
caution if giving with ACE Inhibitors, ARBs, or
direct renin inhibitor (increase the effect of
Other adverse effects- nausea, vomiting,
leg cramps, and dizziness.

Potassium-Sparing Diuretics:
Amiloride (Midamor)
Think Triamterene
Used primarily to counteract
potassium-wasting from other diuretics
Adverse Effect is hyperkalemia (watch
out with ACE Inhibitors, ARBs, direct
renin inhibitors)

All Potassium Sparing


Evaluation- Pts BP and serum

potassium will remain WNL; edema will
Drugs- amiloride (Midamor);
spironolactone (Aldactone); triamterene
L- Low Sodium
E- Elevated T waves from HYPERkalemia
A- Agranulocytosis with triamterene
K- K+ level must be monitored.

Osmotic Diuretic: Mannitol

Mannitol is the only osmotic diuretic on
the market
Simple, six-carbon sugar
PD: Mechanism of Diuretic Action:
Freely filtered at the glomerulus
Undergoes minimal tubular reabsorption
Undergoes minimal metabolism
Is pharmacologically inert (no direct effects
on biochemistry or physiology of cells)
Pulls off fluid by increased osmotic

Osmotic Diuretic: Mannitol

Administered IV, most of the drug
makes it past the glomerulus, creates
increased osmotic force that inhibits
passive reabsorption of water (Urine
flow increases).
Degree of diuresis is dependent upon
the amount of Mannitol in the filtrate
(more mannitol more diuresis)
Does not affect the excretion of
potassium or other electrolytes

Osmotic Diuretic: Mannitol

Therapeutic Uses:
Prophylaxis of Renal Failure(dehydration, severe hypotension,
hypovolemic shock) causes low blood
flow to the kidney, causing reduction in
filtrate volume. Ceases urine
production, =kidney failure
Mannitol pulls water into the nephron
(even when blood flow is low),
preserves urine output & may prevent
kidney failure

Osmotic Diuretic: Mannitol

Therapeutic Uses:
Reduction of Increased Intracranial
Pressure caused by cerebral edema. Works
because its presence in the blood vessels of
the brain creates an osmotic force that draws
fluid from the brain into the blood (Cannot
exit the capillary beds of the brain).
Reduction of Increased Intra-occular
Pressure- Renders the plasma hyperosmotic
in respect to intra-occular fluids, mannitol
creates the osmotic force that draws occular
fluid into the blood.

Osmotic Diuretic: Mannitol

Adverse Effects:
Sudden increase of ECF / Edemacan leave the vascular space at all
capillary beds except the brain. It will
draw water with it which causes
edema. Watch for *CHF & *pulmonary
congestion (most succeptible: pts with
history of these).
Other Adverse Effects- headache,
nausea, vomiting, major fluid and
electrolyte imbalance.

Osmotic Diuretic: Mannitol

Nursing Interventions
Administer only on a pump, low test dose on
all patients with renal impairment, patient on
heart monitor, monitor ECG tracings
Monitor UOP constantly & carefully
Assess vitals,*BP, pulse
Assess lung sounds
High risk for major F/E changes, *safety,
orthostatic hypotension
Contras/Prec: children, CHF pts, Preg class
C, elderly with caution, renal failure,
electrolyte imbalance, others

D- Diet, increase K (except potassiumsparing)
I- Intake, Output, and Daily Wt.
U- Undesirable effects; fluid and
electrolyte imbalance.
R- Review HR, BP, and electrolytes
E- Elderly-caution
T- Take with or after meals and in AM
I- Increased risk of orthostatic
C- Cancel alcohol