NU 578
Unit 3 (SG)
the uidedNP
STUDY GUIDE SERVICE
, Cn. f1 – ÐlURCTlCS
Increases urine output!
Two major applications: treat HTN, mobilize edematous fluid from HF, prevent renal failure (maintain
urine flow)
Overview of Kidney Function: cleanses ECF and maintains ECF volume/composition (affected MOST
by diuretics); maintain acid-base balance; excretes metabolic wastes/foreign substances (drugs, toxins)
Three Basic Renal Processes:
▪ Filtration (non-selective process)
▪ Reabsorption (important, selective process; 99% of electrolytes [active transport], nutrients,
water [passive] are filtered at glomerulus via active transport; diuretics INTERFERE with
reabsorption)
o Proximal Convoluted Tubule: 65% of filtered sodium / chloride is reabsorbed
o Loop of Henle: freely permeable to water → urine is more concentrated
(descending limb; 20% of filtered sodium and chloride is reabsorbed, NOT
permeable to water → urine returns to original filtrate (ascending)
o Distal Convoluted Tubule (Early Segment): 10% of filtered sodium / chloride =
water follows passively
o Distal Nephron (Late Convoluted Tubule / Collecting Duct): exchange of
sodium for potassium (under influence of aldosterone); determines final
concentration of urine (regulated by ADH) – little to do with action of diuretics
▪ Active tubular secretion (eliminates waste from the system)
How Do Diuretics Work: blockade of sodium and chloride reabsorption → increases urine flow [drugs that act early in nephron = block greatest amount of solute reabsorption →
greatest diuresis]
Adverse Impact on ECF: diuretics cause hypovolemia (excess fluid loss), acid-base imbalance, altered electrolyte levels (minimize by using short-acting diuretics, time administration so
kidney can operate in drug-free manner between periods of diuresis)
LOOP DIURETIC THIAZIDE DIURETIC POTASSIUM-SPARING DIURETIC
Furosemide (Lasix) Hydrochlorothiazide (HCTZ) Spironolactone (aldosterone antagonists)
MOA: acts on ascending limb of Henle’s loop (blocks Increase renal excretion of sodium, chloride, Produce modest increase in urine production; produce substantial
reabsorption of Na / Chloride → prevents passive reabsorption potassium, water; elevate plasma levels of decrease in potassium excretion (rarely employed to promote
of water → profound diuresis (20% filtration rate) uric acid and glucose; low levels of diuresis diuresis BUT OFTEN USED TO COUNTERACT POTASSIUM LOSS
and cannot diuresis with renal impairment CAUSED BY THIAZIDE / LOOP DIURETICS)
Administer: PO (onset 60min, 8hr duration); IV (onset 5 min, 2hr
duration) given in critical situations – pulmonary edema; Hepatic MOA: blocks reabsorption of sodium and MOA: blocks actions of aldosterone in distal nephron → retains
metabolism with renal excretion chloride in early segment of distal convoluted potassium and increases excretion of sodium
tubule → water is retained → produces
Uses: situations that require rapid/massive mobilization of fluid increased flow of urine (only 10% filtration Effects: delayed, takes up to 48hr to develop (due to blocking
(pulmonary edema with CHF, edema of hepatic, cardiac, renal rate); ineffective if GFR is low (less than 15- synthesis of new proteins, forcing existing proteins to do the work,
origin less responsive to other meds; HTN uncontrolled with 20mk/min) a process that takes 1-2 days)
other diuretics); USE FOR PATIENT WITH RENAL
IMPAIREMENT – WILL DIURESIS EVEN WHEN RENAL BLOOD PO: onset 2 hr.; 4-6 hr. peak; 12hr duration; Use: HTN, edema; most commonly used in combo with thiazide or
FLOW / GFR IS LOW excreted in urine loop diuretic; severe HF (reduces mortality and hospital admits);
primary hyperaldosteronism, pre-menstrual syndrome, PCOS, acne
Adverse Effects: hypotension, hypokalemia, ototoxicity, Use: essential HTN (1st drug of choice); in young women
hyperglycemia, hyperuricemia, hyponatremia, hypochloremia, edema, DI, protection against
dehydration (dry mouth, unusual thirst, oliguria, excessive loss of postmenopausal osteoporosis Adverse Effects: hyperkalemia (>5 mEq/L – fatal dysrhythmias;
weight) – HOLD LASIX WITH DEHYDRATION! discontinue drug, restrict intake, inject insulin); endocrine effects
(gynecomastia, menstrual irregularities, impotence, hirsutism,
▪ Complications of Dehydration: thrombosis / Adverse Effects: hyponatremia
embolism (headache, pain in chest calves or pelvis) hypochloremia, dehydration, hypokalemia, deepening of voice); benign/malignant tumors
▪ Reduce Dehydration Risk: initiate at low dose, adjust hyperglycemia, hyperuricemia (retain uric
dose carefully, monitor weight loss daily, administer acid → precipitate gout) Drug Interactions: thiazide/loop diuretics (counteracts potassium
at intermittent schedule wasting); agents that raise K+ levels (potassium supplements, salt
Pregnancy: TOXIC! Increases LDL, cholesterol, total cholesterol, substitutes, and ACE inhibitors, angiotensin receptor blockers,
triglycerides direct renin inhibitors)
Decreases HDL, Increases and LDL/triglycerides → reduce risk of Increases excretion of Mag
coronary heart disease by 25% Triamterene (non-aldosterone antagonists):
Drug Interactions: antihypertensive drugs,
see book pg. 466-46
Electrolytes: lithium, NSAIDs, NO OTOTOXICITY!
▪ Increased excretion of Mag: muscle weakness,
tremor, twitching, dysrhythmia Amiloride (Midamor)
▪ Increased excretion of Calcium: secondary tx of
FASTING ONSET OF K+ SPARING 2hr with 24hr duration; inhibit
hypercalcemia (CALCIUM KIDNEY STONES)
potassium loss by direct blockade of sodium-potassium exchange
in distal nephron (modest diuresis); used primarily to counteract K+
Drug Interactions: dig toxicity (with low K+); concurrent use of
loss from powerful diuretics (loop/thiazide); hyperkalemia, caution
ototoxic drugs (gentamicin + Lasix = hearing loss); lithium
when combining with ACE inhibitor / angiotensin receptor blocker
toxicity; hypertension drugs (increased hypotension); NSAIDS
/ direct renin inhibitor
(partially blunt effects of diuretics)
OSMOTIC DIURETIC
, Mannitol (Osmitrol)
Simple six-carbon sugar embodies the four properties of an ideal osmotic diuretic; freely filtered at glomerulus, undergoes minimal tubular reabsorption, undergoes minimal metabolism
(most filtered drug remains in the nephron → osmotic force that inhibits passive reabsorption of water → urine flow increases), has no direct effects on biochemistry or physiology of cells
(K+ and other electrolytes); the AMOUNT OF DIURESIS IS DETERMINED BY THE CONCENTRATION OF MANNITOL IN THE FILTRATE (more mannitol present – the greater the
diuresis)
▪ MOA: does not diffuse across the GI epithelium; cannot be transported by uptake systems that absorb dietary sugars → to reach circulation MUST BE GIVEN IV (distributes
freely to ECW; onset 30-60mins, duration 6-8hr; urine excretion
▪ Use: prophylaxis of renal failure; reduction of intracranial pressure; reduction of intraocular pressure
▪ Adverse Effects: edema (extreme caution in patients with HF due to precipitation of pulmonary edema; cease drug if symptoms or renal failure develops); headache, nausea,
vomiting; fluid or electrolyte imbalance
▪ Infusion rate: set to elicit urine flow at 30-50ml/hr.; observe preparations for crystals prior to use (warm to dissolve crystals mannitol then cool to body temp for
administration); use filtered needle to withdraw mannitol from vial and in-line filter to prevent crystals from entering bloodstream
Cn f2 – AfiCJtS ACCCCtlJfi VOLUJC 3 lOJ COJtCJt OC BOÐY CLUlÐS
Kidneys: maintain volume and osmolality (disturbances of renal function → disruption of fluid volume, osmolality or both)
DISORDERS of FLUID VOLUME & OSMOLALITY
Volume Contraction Volume Expansion
decrease in total volume water increase in total body water
Isotonic contraction Hypertonic contraction Hypotonic contraction Can be isotonic, hypertonic, or
Volume contraction in which Na & volume contraction in which loss of water Volume contraction in which loss of Na exceeds loss of hypotonic
water are lost in isotonic proportions exceeds loss of Na → reduced ECF with water → both volume & osmolality are reduced →
→ decrease in total volume of ECF increase in osmolality → water drawn out of water moves into cells → ECF diminished further May be caused by overdose of
but no change in osmolality cells → intracellular dehydration & partial therapeutic fluid (NaCl infusion)
compensation for lost extracellular volume or d/t disease (HF, nephrotic
Causes: vomiting, diarrhea, kidney Causes: excessive sweating, osmotic Causes: principle cause is excessive loss of Na through syndrome, cirrhosis)
disease, misuse of diuretics; diuresis, feeding excessively concentrated kidneys (d/t diuretic therapy, chronic renal insufficiency,
characteristic of cholera foods to infants; may also develop s/t or lack of aldosterone) Principle drugs to treat:
extensive burns or disorders of CNS that diuretics & agents used for HF
Treatment: replace with fluids isotonic leave patient unable to experience or report Treatment:
to plasma → 0.9% NaCl in sterile thirst ▪ if hyponatremia mild & renal function If hypervolemic hyponatremia:
water → Na & Cl present at Treatment: replace volume with hypotonic adequate: infuse isotonic (0.9%) NaCl treat with vasopressin
concentration of 145 mEq/L; replenish fluids (0.45% NaCl) or with fluids that ▪ if hyponatremia severe: infuse hypertonic (3%) antagonist (conivaptan,
volume slowly to avoid pulmonary contain no solutes at all (drinking water, 5% NaCl solution, continue until Na is >130 mEq/L tolvaptan)
edema dextrose IV); replenish volume in stages → o Monitor for s/s fluid overload (JVD,
replace 50% of loss in 1st few hours of pulmonary or peripheral edema)
treatment, then remaining over 1-2 days ▪ if d/t aldosterone insufficiency: treat with HRT
+ isotonic NaCl
ACID-BASE DISTURBANCES
Respiratory Alkalosis Respiratory Acidosis
Produced by hyperventilation: deep, rapid breathing increases CO2 loss → lowers Retention of CO2 s/t hypoventilation: reduced CO2 exhalation raises plasma pCO2 →
pCO2 of blood → increase pH lowers pH
Causes: mild hyperventilation may be d/t hypoxia, pulmonary disease, drugs (esp. aspirin Causes: depression of medullary respiratory center; pathologic changes in the lungs
& other salicylates), etc.; severe hyperventilation may be d/t CNS injury & hysteria (status asthmaticus, airway obstruction); over time, kidneys compensate by excreting less
bicarbonate
Treatment:
▪ mild alkalosis: no specific treatment Treatment: primary treatment directed at correcting respiratory impairment; may need
▪ severe respiratory alkalosis from hysteria: have patient rebreathe their CO2- O2 & ventilatory assistance; sodium bicarbonate infusion if acidosis is severe
laden expired breath (hold paper bag over mouth & nose) or sedative
(diazepam) to suppress hysteria
Metabolic Alkalosis Metabolic Acidosis
Increase in plasma bicarbonate & pH Decrease in plasma bicarbonate & pH
Causes: excessive loss of gastric fluid (vomiting, suctioning); administration of alkalinizing Causes: chronic renal failure, loss of bicarbonate during severe diarrhea, & metabolic
salts (sodium bicarbonate); body compensates through hypoventilation (to retain CO2), disorders that result in overproduction of lactic acid (lactic acidosis) or ketoacids
increased renal excretion of bicarbonate, & accumulation of organic acids (ketoacidosis); may also be d/t poisoning by methanol & certain meds (aspirin & other
salicylates)
Treatment: solution of NaCl + KCl → facilitates renal excretion of bicarbonate →
promotes normalization of plasma pH Treatment: correct underlying cause of acidosis
▪ severe alkalosis: correct pH with infusion of dilute (0.1 N) hydrochloric acid ▪ Administer an alkalinizing salt (sodium bicarbonate, sodium carbonate)
through CVC; or give acid-forming salt (ammonium chloride = cannot be ▪ If acidosis severe (when indicated, sodium bicarbonate is preferred; PO if
given in liver failure d/t causing hepatic encephalopathy) mild, IV if severe); use IV sodium bicarbonate with caution to avoid excessive
elevation of pH (rapid conversion from acidosis to alkalosis = hazardous) &
careful to avoid hypernatremia d/t Na content
POTASSIUM IMBALANCES
HYPOKALEMIA HYPERKALEMIA
Defined: Deficiency of K in the blood = < 3.5 mEq/L Defined: Excessive elevation of serum K = > 5 mEq/L
Causes: most common is thiazide or loop diuretics; also insufficient K intake; alkalosis, & excessive insulin (both drive K into Causes: severe tissue trauma, untreated Addison’s
cells); increased renal excretion of K (aldosterone); & K loss associated with vomiting, diarrhea, laxative abuse, & excessive disease, & acute acidosis (all draw K out of cells);
sweating acute renal failure; misuse of K-sparing diuretics; &
▪ K loss always = Cl loss = hypokalemic alkalosis OD with IV K
, Adverse effects: effects are skeletal (weakens or paralysis of skeletal muscle), smooth muscle (intestinal dilation, ileus), BP Adverse effects: disruption of electrical activity of the
(increases risk of HTN & stroke), & heart (risk of fatal dysrhythmias); principle cause of digoxin toxicity in those taking the heart = alterations in ECG & heart rhythm (earliest
drug signs); mild elevation (5-7 mEq/L) = peaked T waves &
prolonged PR interval; @ 8-9 mEq/L = V. tach, V. fib, &
Prevention & treatment: can be treated with 3 K salts: KCl, K phosphate, & K bicarbonate; may also be used cardiac arrest; noncardiac effects = confusion, anxiety,
prophylactically; KCl is preferred d/t Cl loss accompanying K loss (may be PO or IV) dyspnea, weakness or heaviness of legs, & numbness
or tingling of hands, feet, & lips
Potassium Chloride (PO): for prophylaxis & mild deficiency; available as IR tab, SR tab, effervescent tab, & powders; SR tabs
(Klor-Con, Micro-K) preferred d/t convenience & better tolerated than other forms = best chance of adherence Treatment: withhold foods that contain K & any meds
▪ Adverse effects: irritates the GI tract = abd discomfort, n/v/d; solid forms (except SR tab) can = high local that promote K accumulation (K-sparing diuretics, K
concentrations of K = severe intestinal injury (ulcerative lesions, bleeding, perforation), death has occurred; take supplements); counteract K-induced cardiotoxicity &
with meals or full glass of water to minimize; rarely, may cause hyperkalemia lower extracellular levels of K = infuse a Ca salt (Ca
gluconate) to offset effects of hyperkalemia on the
Potassium Chloride (IV): indicated for prevention & treatment of hypokalemia; used more for severe deficiency & pts who heart; infuse glucose & insulin to promote uptake of K
cannot take PO; IV solutions must be diluted d/t extremely irritating to veins by cells to decrease extracellular K levels; if acidosis
▪ SAFETY ALERT: IV K must be infused slowly (no faster than 10 mEq/L); never administer via IV push = cardiac present (likely), infuse Na bicarbonate to move pH to
arrest = lethal injection alkalinity & increase cellular uptake of K; to remove K
▪ Adverse effects: hyperkalemia (can be fatal, more common than PO) = measure serum K levels before & = PO or rectal sodium polystyrene sulfonate
throughout treatment & assess renal function to ensure adequate urine output; D/C if renal failure develops; (kayexalate, kionex) to absorb K & peritoneal or
monitor for ECG changes (sign of K toxicity) extracorporeal dialysis
▪ Contraindications: do not use in conditions that predispose to hyperkalemia (severe renal impairment, use of K-
sparing diuretics, hypoaldosteronism); also avoid when hyperkalemia already exists
MAGNESIUM IMBALANCES
HYPOMAGNESIUM HYPERMAGNESIUM
Causes: diarrhea, hemodialysis, kidney disease, prolonged IV feeding with Mg-free solutions; seen in chronic alcoholics, DM, & pancreatitis; Most common in renal
hypocalcemia & hypokalemia may occur with it insufficiency, especially when
Mg-containing antacids or
Adverse effects: low levels of Mg = enhanced ACh release = increased muscle excitability (heart, skeletal), tetany; also increase excitability of cathartics are used; symptoms
CNS neurons = disorientation, psychosis, seizures; in kidneys = nephrocalcinosis = renal injury when stones large enough to block urine flow of mild toxicity = muscle
weakness (from inhibition of
Prevention & treatment: treat with parenteral Mg sulfate; prophylaxis with PO form (Mg oxide) ACh response), hypotension,
sedation, & ECG changes;
Magnesium oxide: PO tablets for prophylaxis; excessive doses can cause diarrhea respiratory paralysis occurs @
Magnesium sulfate: IV or IM; preferred for severe hypomagnesemia levels of 12-15 mEg/L; higher
concentration (> 25) = cardiac
Adverse effects: hypermagnesemia (can cause neuromuscular blockade = paralysis of respiratory muscles; use with caution with other NMBs arrest; counteract muscle
[succinylcholine, atracurium]; counteract effects with calcium (Ca gluconate); hypermagnesemia can also suppress impulse conduction through AV weakness & paralysis with IV
node in the heart = contraindicated in AV heart block; monitor serum Mg levels to minimize risk of toxicity calcium
Cn f3 – RCVlCW OC nCJOÐYJAJlCS
RAAS supports arterial pressure by causing: constriction of arterioles & veins AND retention of water by kidneys
▪ Vasoconstriction: mediated by hormone angiotensin II
▪ Water retention: mediated in part by aldosterone through retention of Na
o Responses develop in hours (vasoconstriction) to days (water retention)
MOA: Low arterial pressure → activates RAAS → levels of angiotensin II & aldosterone rise → constriction of renal blood vessels & kidneys retain Na → renal blood flow and GFR further
decreased & water is retained
▪ Drugs that lower arterial pressure trigger baroreceptor reflex: reflex tachycardia = temporarily negates effort to lower arterial pressure with drugs
▪ Drugs that dilate veins intensify & prolong postural hypotension; venodilators can trigger baroreceptor reflex: reflex tachycardia
Cn ff – ÐRUfiS ACTlJfi OJ tnC RCJlJ-AJfilOtCJSlJ-ALÐOStCROJC SYStCJ
Physiology of RAAS
Angiotensin II (raises BP)
▪ Vasoconstricts = acts on vascular smooth muscle to cause contraction; prominent in arteriole, less so in veins; also
causes vasoconstriction indirectly by acting on sympathetic neurons (promote NE release), adrenal medulla (promote
epinephrine release), & CNS (increase sympathetic outflow to blood vessels
▪ Stimulates release of aldosterone by acting on adrenal cortex
▪ May cause pathologic structural changes in heart (hypertrophy, remodeling) & blood vessels (increase thickness of walls)
o Increased migration, proliferation, & hypertrophy of VSM cells
o Increased production of extracellular matrix by VSM cells
o Hypertrophy of cardiac myocytes
o Increased production of extracellular matrix by cardiac fibroblasts
Aldosterone
▪ Acts on distal tubules of kidney to retain Na & excrete K & H; Na retention = water retention = increased blood volume
= increases BP
▪ Promote cardiac remodeling & fibrosis; activates SNS = suppresses uptake of NE in heart = predisposes to
dysrhythmias; promotes vascular fibrosis = decreases arterial compliance & disrupts baroreceptor reflex (these effects
usually limited to states such as HF when aldosterone levels are extremely high)
Angiotensin II formed by renin & angiotensin-converting enzyme
▪ Renin catalyzes formation of angiotensin I from angiotensinogen; release of renin is increased d/t decline in BP, blood
volume, plasma Na content, or renal perfusion pressure (occurs in renal artery stenosis, reduced SBP, & reduced plasma
volume); release of renin is suppressed with elevated BP, blood volume, & plasma Na content)
▪ ACE catalyzes conversion of angiotensin I (inactive) to angiotensin II (highly active)
o ACE is aka kinase II when it acts on another substrate = bradykinin (hormone)
▪ Renin + angiotensinogen = angiotensin I + ACE = angiotensin II
Regulation of BP by RAAS
Unit 3 (SG)
the uidedNP
STUDY GUIDE SERVICE
, Cn. f1 – ÐlURCTlCS
Increases urine output!
Two major applications: treat HTN, mobilize edematous fluid from HF, prevent renal failure (maintain
urine flow)
Overview of Kidney Function: cleanses ECF and maintains ECF volume/composition (affected MOST
by diuretics); maintain acid-base balance; excretes metabolic wastes/foreign substances (drugs, toxins)
Three Basic Renal Processes:
▪ Filtration (non-selective process)
▪ Reabsorption (important, selective process; 99% of electrolytes [active transport], nutrients,
water [passive] are filtered at glomerulus via active transport; diuretics INTERFERE with
reabsorption)
o Proximal Convoluted Tubule: 65% of filtered sodium / chloride is reabsorbed
o Loop of Henle: freely permeable to water → urine is more concentrated
(descending limb; 20% of filtered sodium and chloride is reabsorbed, NOT
permeable to water → urine returns to original filtrate (ascending)
o Distal Convoluted Tubule (Early Segment): 10% of filtered sodium / chloride =
water follows passively
o Distal Nephron (Late Convoluted Tubule / Collecting Duct): exchange of
sodium for potassium (under influence of aldosterone); determines final
concentration of urine (regulated by ADH) – little to do with action of diuretics
▪ Active tubular secretion (eliminates waste from the system)
How Do Diuretics Work: blockade of sodium and chloride reabsorption → increases urine flow [drugs that act early in nephron = block greatest amount of solute reabsorption →
greatest diuresis]
Adverse Impact on ECF: diuretics cause hypovolemia (excess fluid loss), acid-base imbalance, altered electrolyte levels (minimize by using short-acting diuretics, time administration so
kidney can operate in drug-free manner between periods of diuresis)
LOOP DIURETIC THIAZIDE DIURETIC POTASSIUM-SPARING DIURETIC
Furosemide (Lasix) Hydrochlorothiazide (HCTZ) Spironolactone (aldosterone antagonists)
MOA: acts on ascending limb of Henle’s loop (blocks Increase renal excretion of sodium, chloride, Produce modest increase in urine production; produce substantial
reabsorption of Na / Chloride → prevents passive reabsorption potassium, water; elevate plasma levels of decrease in potassium excretion (rarely employed to promote
of water → profound diuresis (20% filtration rate) uric acid and glucose; low levels of diuresis diuresis BUT OFTEN USED TO COUNTERACT POTASSIUM LOSS
and cannot diuresis with renal impairment CAUSED BY THIAZIDE / LOOP DIURETICS)
Administer: PO (onset 60min, 8hr duration); IV (onset 5 min, 2hr
duration) given in critical situations – pulmonary edema; Hepatic MOA: blocks reabsorption of sodium and MOA: blocks actions of aldosterone in distal nephron → retains
metabolism with renal excretion chloride in early segment of distal convoluted potassium and increases excretion of sodium
tubule → water is retained → produces
Uses: situations that require rapid/massive mobilization of fluid increased flow of urine (only 10% filtration Effects: delayed, takes up to 48hr to develop (due to blocking
(pulmonary edema with CHF, edema of hepatic, cardiac, renal rate); ineffective if GFR is low (less than 15- synthesis of new proteins, forcing existing proteins to do the work,
origin less responsive to other meds; HTN uncontrolled with 20mk/min) a process that takes 1-2 days)
other diuretics); USE FOR PATIENT WITH RENAL
IMPAIREMENT – WILL DIURESIS EVEN WHEN RENAL BLOOD PO: onset 2 hr.; 4-6 hr. peak; 12hr duration; Use: HTN, edema; most commonly used in combo with thiazide or
FLOW / GFR IS LOW excreted in urine loop diuretic; severe HF (reduces mortality and hospital admits);
primary hyperaldosteronism, pre-menstrual syndrome, PCOS, acne
Adverse Effects: hypotension, hypokalemia, ototoxicity, Use: essential HTN (1st drug of choice); in young women
hyperglycemia, hyperuricemia, hyponatremia, hypochloremia, edema, DI, protection against
dehydration (dry mouth, unusual thirst, oliguria, excessive loss of postmenopausal osteoporosis Adverse Effects: hyperkalemia (>5 mEq/L – fatal dysrhythmias;
weight) – HOLD LASIX WITH DEHYDRATION! discontinue drug, restrict intake, inject insulin); endocrine effects
(gynecomastia, menstrual irregularities, impotence, hirsutism,
▪ Complications of Dehydration: thrombosis / Adverse Effects: hyponatremia
embolism (headache, pain in chest calves or pelvis) hypochloremia, dehydration, hypokalemia, deepening of voice); benign/malignant tumors
▪ Reduce Dehydration Risk: initiate at low dose, adjust hyperglycemia, hyperuricemia (retain uric
dose carefully, monitor weight loss daily, administer acid → precipitate gout) Drug Interactions: thiazide/loop diuretics (counteracts potassium
at intermittent schedule wasting); agents that raise K+ levels (potassium supplements, salt
Pregnancy: TOXIC! Increases LDL, cholesterol, total cholesterol, substitutes, and ACE inhibitors, angiotensin receptor blockers,
triglycerides direct renin inhibitors)
Decreases HDL, Increases and LDL/triglycerides → reduce risk of Increases excretion of Mag
coronary heart disease by 25% Triamterene (non-aldosterone antagonists):
Drug Interactions: antihypertensive drugs,
see book pg. 466-46
Electrolytes: lithium, NSAIDs, NO OTOTOXICITY!
▪ Increased excretion of Mag: muscle weakness,
tremor, twitching, dysrhythmia Amiloride (Midamor)
▪ Increased excretion of Calcium: secondary tx of
FASTING ONSET OF K+ SPARING 2hr with 24hr duration; inhibit
hypercalcemia (CALCIUM KIDNEY STONES)
potassium loss by direct blockade of sodium-potassium exchange
in distal nephron (modest diuresis); used primarily to counteract K+
Drug Interactions: dig toxicity (with low K+); concurrent use of
loss from powerful diuretics (loop/thiazide); hyperkalemia, caution
ototoxic drugs (gentamicin + Lasix = hearing loss); lithium
when combining with ACE inhibitor / angiotensin receptor blocker
toxicity; hypertension drugs (increased hypotension); NSAIDS
/ direct renin inhibitor
(partially blunt effects of diuretics)
OSMOTIC DIURETIC
, Mannitol (Osmitrol)
Simple six-carbon sugar embodies the four properties of an ideal osmotic diuretic; freely filtered at glomerulus, undergoes minimal tubular reabsorption, undergoes minimal metabolism
(most filtered drug remains in the nephron → osmotic force that inhibits passive reabsorption of water → urine flow increases), has no direct effects on biochemistry or physiology of cells
(K+ and other electrolytes); the AMOUNT OF DIURESIS IS DETERMINED BY THE CONCENTRATION OF MANNITOL IN THE FILTRATE (more mannitol present – the greater the
diuresis)
▪ MOA: does not diffuse across the GI epithelium; cannot be transported by uptake systems that absorb dietary sugars → to reach circulation MUST BE GIVEN IV (distributes
freely to ECW; onset 30-60mins, duration 6-8hr; urine excretion
▪ Use: prophylaxis of renal failure; reduction of intracranial pressure; reduction of intraocular pressure
▪ Adverse Effects: edema (extreme caution in patients with HF due to precipitation of pulmonary edema; cease drug if symptoms or renal failure develops); headache, nausea,
vomiting; fluid or electrolyte imbalance
▪ Infusion rate: set to elicit urine flow at 30-50ml/hr.; observe preparations for crystals prior to use (warm to dissolve crystals mannitol then cool to body temp for
administration); use filtered needle to withdraw mannitol from vial and in-line filter to prevent crystals from entering bloodstream
Cn f2 – AfiCJtS ACCCCtlJfi VOLUJC 3 lOJ COJtCJt OC BOÐY CLUlÐS
Kidneys: maintain volume and osmolality (disturbances of renal function → disruption of fluid volume, osmolality or both)
DISORDERS of FLUID VOLUME & OSMOLALITY
Volume Contraction Volume Expansion
decrease in total volume water increase in total body water
Isotonic contraction Hypertonic contraction Hypotonic contraction Can be isotonic, hypertonic, or
Volume contraction in which Na & volume contraction in which loss of water Volume contraction in which loss of Na exceeds loss of hypotonic
water are lost in isotonic proportions exceeds loss of Na → reduced ECF with water → both volume & osmolality are reduced →
→ decrease in total volume of ECF increase in osmolality → water drawn out of water moves into cells → ECF diminished further May be caused by overdose of
but no change in osmolality cells → intracellular dehydration & partial therapeutic fluid (NaCl infusion)
compensation for lost extracellular volume or d/t disease (HF, nephrotic
Causes: vomiting, diarrhea, kidney Causes: excessive sweating, osmotic Causes: principle cause is excessive loss of Na through syndrome, cirrhosis)
disease, misuse of diuretics; diuresis, feeding excessively concentrated kidneys (d/t diuretic therapy, chronic renal insufficiency,
characteristic of cholera foods to infants; may also develop s/t or lack of aldosterone) Principle drugs to treat:
extensive burns or disorders of CNS that diuretics & agents used for HF
Treatment: replace with fluids isotonic leave patient unable to experience or report Treatment:
to plasma → 0.9% NaCl in sterile thirst ▪ if hyponatremia mild & renal function If hypervolemic hyponatremia:
water → Na & Cl present at Treatment: replace volume with hypotonic adequate: infuse isotonic (0.9%) NaCl treat with vasopressin
concentration of 145 mEq/L; replenish fluids (0.45% NaCl) or with fluids that ▪ if hyponatremia severe: infuse hypertonic (3%) antagonist (conivaptan,
volume slowly to avoid pulmonary contain no solutes at all (drinking water, 5% NaCl solution, continue until Na is >130 mEq/L tolvaptan)
edema dextrose IV); replenish volume in stages → o Monitor for s/s fluid overload (JVD,
replace 50% of loss in 1st few hours of pulmonary or peripheral edema)
treatment, then remaining over 1-2 days ▪ if d/t aldosterone insufficiency: treat with HRT
+ isotonic NaCl
ACID-BASE DISTURBANCES
Respiratory Alkalosis Respiratory Acidosis
Produced by hyperventilation: deep, rapid breathing increases CO2 loss → lowers Retention of CO2 s/t hypoventilation: reduced CO2 exhalation raises plasma pCO2 →
pCO2 of blood → increase pH lowers pH
Causes: mild hyperventilation may be d/t hypoxia, pulmonary disease, drugs (esp. aspirin Causes: depression of medullary respiratory center; pathologic changes in the lungs
& other salicylates), etc.; severe hyperventilation may be d/t CNS injury & hysteria (status asthmaticus, airway obstruction); over time, kidneys compensate by excreting less
bicarbonate
Treatment:
▪ mild alkalosis: no specific treatment Treatment: primary treatment directed at correcting respiratory impairment; may need
▪ severe respiratory alkalosis from hysteria: have patient rebreathe their CO2- O2 & ventilatory assistance; sodium bicarbonate infusion if acidosis is severe
laden expired breath (hold paper bag over mouth & nose) or sedative
(diazepam) to suppress hysteria
Metabolic Alkalosis Metabolic Acidosis
Increase in plasma bicarbonate & pH Decrease in plasma bicarbonate & pH
Causes: excessive loss of gastric fluid (vomiting, suctioning); administration of alkalinizing Causes: chronic renal failure, loss of bicarbonate during severe diarrhea, & metabolic
salts (sodium bicarbonate); body compensates through hypoventilation (to retain CO2), disorders that result in overproduction of lactic acid (lactic acidosis) or ketoacids
increased renal excretion of bicarbonate, & accumulation of organic acids (ketoacidosis); may also be d/t poisoning by methanol & certain meds (aspirin & other
salicylates)
Treatment: solution of NaCl + KCl → facilitates renal excretion of bicarbonate →
promotes normalization of plasma pH Treatment: correct underlying cause of acidosis
▪ severe alkalosis: correct pH with infusion of dilute (0.1 N) hydrochloric acid ▪ Administer an alkalinizing salt (sodium bicarbonate, sodium carbonate)
through CVC; or give acid-forming salt (ammonium chloride = cannot be ▪ If acidosis severe (when indicated, sodium bicarbonate is preferred; PO if
given in liver failure d/t causing hepatic encephalopathy) mild, IV if severe); use IV sodium bicarbonate with caution to avoid excessive
elevation of pH (rapid conversion from acidosis to alkalosis = hazardous) &
careful to avoid hypernatremia d/t Na content
POTASSIUM IMBALANCES
HYPOKALEMIA HYPERKALEMIA
Defined: Deficiency of K in the blood = < 3.5 mEq/L Defined: Excessive elevation of serum K = > 5 mEq/L
Causes: most common is thiazide or loop diuretics; also insufficient K intake; alkalosis, & excessive insulin (both drive K into Causes: severe tissue trauma, untreated Addison’s
cells); increased renal excretion of K (aldosterone); & K loss associated with vomiting, diarrhea, laxative abuse, & excessive disease, & acute acidosis (all draw K out of cells);
sweating acute renal failure; misuse of K-sparing diuretics; &
▪ K loss always = Cl loss = hypokalemic alkalosis OD with IV K
, Adverse effects: effects are skeletal (weakens or paralysis of skeletal muscle), smooth muscle (intestinal dilation, ileus), BP Adverse effects: disruption of electrical activity of the
(increases risk of HTN & stroke), & heart (risk of fatal dysrhythmias); principle cause of digoxin toxicity in those taking the heart = alterations in ECG & heart rhythm (earliest
drug signs); mild elevation (5-7 mEq/L) = peaked T waves &
prolonged PR interval; @ 8-9 mEq/L = V. tach, V. fib, &
Prevention & treatment: can be treated with 3 K salts: KCl, K phosphate, & K bicarbonate; may also be used cardiac arrest; noncardiac effects = confusion, anxiety,
prophylactically; KCl is preferred d/t Cl loss accompanying K loss (may be PO or IV) dyspnea, weakness or heaviness of legs, & numbness
or tingling of hands, feet, & lips
Potassium Chloride (PO): for prophylaxis & mild deficiency; available as IR tab, SR tab, effervescent tab, & powders; SR tabs
(Klor-Con, Micro-K) preferred d/t convenience & better tolerated than other forms = best chance of adherence Treatment: withhold foods that contain K & any meds
▪ Adverse effects: irritates the GI tract = abd discomfort, n/v/d; solid forms (except SR tab) can = high local that promote K accumulation (K-sparing diuretics, K
concentrations of K = severe intestinal injury (ulcerative lesions, bleeding, perforation), death has occurred; take supplements); counteract K-induced cardiotoxicity &
with meals or full glass of water to minimize; rarely, may cause hyperkalemia lower extracellular levels of K = infuse a Ca salt (Ca
gluconate) to offset effects of hyperkalemia on the
Potassium Chloride (IV): indicated for prevention & treatment of hypokalemia; used more for severe deficiency & pts who heart; infuse glucose & insulin to promote uptake of K
cannot take PO; IV solutions must be diluted d/t extremely irritating to veins by cells to decrease extracellular K levels; if acidosis
▪ SAFETY ALERT: IV K must be infused slowly (no faster than 10 mEq/L); never administer via IV push = cardiac present (likely), infuse Na bicarbonate to move pH to
arrest = lethal injection alkalinity & increase cellular uptake of K; to remove K
▪ Adverse effects: hyperkalemia (can be fatal, more common than PO) = measure serum K levels before & = PO or rectal sodium polystyrene sulfonate
throughout treatment & assess renal function to ensure adequate urine output; D/C if renal failure develops; (kayexalate, kionex) to absorb K & peritoneal or
monitor for ECG changes (sign of K toxicity) extracorporeal dialysis
▪ Contraindications: do not use in conditions that predispose to hyperkalemia (severe renal impairment, use of K-
sparing diuretics, hypoaldosteronism); also avoid when hyperkalemia already exists
MAGNESIUM IMBALANCES
HYPOMAGNESIUM HYPERMAGNESIUM
Causes: diarrhea, hemodialysis, kidney disease, prolonged IV feeding with Mg-free solutions; seen in chronic alcoholics, DM, & pancreatitis; Most common in renal
hypocalcemia & hypokalemia may occur with it insufficiency, especially when
Mg-containing antacids or
Adverse effects: low levels of Mg = enhanced ACh release = increased muscle excitability (heart, skeletal), tetany; also increase excitability of cathartics are used; symptoms
CNS neurons = disorientation, psychosis, seizures; in kidneys = nephrocalcinosis = renal injury when stones large enough to block urine flow of mild toxicity = muscle
weakness (from inhibition of
Prevention & treatment: treat with parenteral Mg sulfate; prophylaxis with PO form (Mg oxide) ACh response), hypotension,
sedation, & ECG changes;
Magnesium oxide: PO tablets for prophylaxis; excessive doses can cause diarrhea respiratory paralysis occurs @
Magnesium sulfate: IV or IM; preferred for severe hypomagnesemia levels of 12-15 mEg/L; higher
concentration (> 25) = cardiac
Adverse effects: hypermagnesemia (can cause neuromuscular blockade = paralysis of respiratory muscles; use with caution with other NMBs arrest; counteract muscle
[succinylcholine, atracurium]; counteract effects with calcium (Ca gluconate); hypermagnesemia can also suppress impulse conduction through AV weakness & paralysis with IV
node in the heart = contraindicated in AV heart block; monitor serum Mg levels to minimize risk of toxicity calcium
Cn f3 – RCVlCW OC nCJOÐYJAJlCS
RAAS supports arterial pressure by causing: constriction of arterioles & veins AND retention of water by kidneys
▪ Vasoconstriction: mediated by hormone angiotensin II
▪ Water retention: mediated in part by aldosterone through retention of Na
o Responses develop in hours (vasoconstriction) to days (water retention)
MOA: Low arterial pressure → activates RAAS → levels of angiotensin II & aldosterone rise → constriction of renal blood vessels & kidneys retain Na → renal blood flow and GFR further
decreased & water is retained
▪ Drugs that lower arterial pressure trigger baroreceptor reflex: reflex tachycardia = temporarily negates effort to lower arterial pressure with drugs
▪ Drugs that dilate veins intensify & prolong postural hypotension; venodilators can trigger baroreceptor reflex: reflex tachycardia
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Physiology of RAAS
Angiotensin II (raises BP)
▪ Vasoconstricts = acts on vascular smooth muscle to cause contraction; prominent in arteriole, less so in veins; also
causes vasoconstriction indirectly by acting on sympathetic neurons (promote NE release), adrenal medulla (promote
epinephrine release), & CNS (increase sympathetic outflow to blood vessels
▪ Stimulates release of aldosterone by acting on adrenal cortex
▪ May cause pathologic structural changes in heart (hypertrophy, remodeling) & blood vessels (increase thickness of walls)
o Increased migration, proliferation, & hypertrophy of VSM cells
o Increased production of extracellular matrix by VSM cells
o Hypertrophy of cardiac myocytes
o Increased production of extracellular matrix by cardiac fibroblasts
Aldosterone
▪ Acts on distal tubules of kidney to retain Na & excrete K & H; Na retention = water retention = increased blood volume
= increases BP
▪ Promote cardiac remodeling & fibrosis; activates SNS = suppresses uptake of NE in heart = predisposes to
dysrhythmias; promotes vascular fibrosis = decreases arterial compliance & disrupts baroreceptor reflex (these effects
usually limited to states such as HF when aldosterone levels are extremely high)
Angiotensin II formed by renin & angiotensin-converting enzyme
▪ Renin catalyzes formation of angiotensin I from angiotensinogen; release of renin is increased d/t decline in BP, blood
volume, plasma Na content, or renal perfusion pressure (occurs in renal artery stenosis, reduced SBP, & reduced plasma
volume); release of renin is suppressed with elevated BP, blood volume, & plasma Na content)
▪ ACE catalyzes conversion of angiotensin I (inactive) to angiotensin II (highly active)
o ACE is aka kinase II when it acts on another substrate = bradykinin (hormone)
▪ Renin + angiotensinogen = angiotensin I + ACE = angiotensin II
Regulation of BP by RAAS
