Renal Disorders Pharmacotherapy: Fluid and Electrolyte Homeostasis
1. Renal disorders Pharmacotherapy:
Disorders of Fluid and Electrolyte
Homeostasis
By: Aster Wakjira
[B.Pharm ,MSc,clinical Pharmacist]
E-mail: asterwakjira@gmail.com Or
aster.garedow@ju.edu.et
2. Learning Objectives
Upon completion of the session, the students will be
able to:
Estimate the volumes of various body fluid
compartments.
Calculate the daily maintenance fluid requirement for
patients given their weight and gender.
Differentiate among currently available fluids for volume
resuscitation.
Identify the electrolytes primarily found in the
extracellular and intracellular fluid compartments.
Describe the unique relationship between serum sodium
concentration and total body water (TBW).
Review the etiology, clinical presentation, and
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3. BODY FLUID COMPARTMENTS
Distribution of total body water (TBW):
% varies with age, gender, degree of obesity
Adult ♂ = 50 - 60%; adult ♀ = 45 - 55%
TBW = 0.6 × weight (kg) ♂; 0.5 × weight (kg) ♀
The ICF represents the water contained within cells
and
is rich in electrolytes such as K, Mg, phosphates, and
proteins.
The ICF is 2/3 of TBW regardless of gender.
For a 70-kg person, this would mean that the TBW is 42 L
and the ICF is 28 L.
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4. Cont’d…
The extracellular fluid (ECF) is the fluid outside the
cell and is rich in Na, chloride, and bicarbonate.
The ECF is 1/3 of TBW (14 L in a 70-kg person)
and is subdivided into two compartments:
Interstitial fluid = ¾ ECF ∼25% of TBW
Intravascular fluid (plasma) = ¼ ECF ∼8% of TBW
The interstitial fluid represents the fluid occupying the
spaces between cells and
is about 25% of TBW (10.5 L in a 70-kg person).
The intravascular fluid (also known as plasma) represents
the fluid within the blood vessels and
is about 8% of TBW (3.4 L in a 70-kg person).
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5. Cont’d…
The trans cellular fluid includes
the viscous components of the peritoneum, pleural
space, and pericardium, as well as the cerebrospinal
fluid, joint space fluid, and the gastrointestinal (GI)
digestive juices.
the trans cellular fluid accounts for about 1% of
TBW, can increase significantly during various
illnesses favoring fluid collection in one of these
spaces
(eg, pleural effusions or ascites in the peritoneum).
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6. Cont’d…
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To maintain fluid balance, the total amount of fluid gained
throughout the day (input, or “ins”) must equal the total amount
of fluid lost (output, or “outs”).
For a normal adult on an average diet, ingested fluids are easily
measured and average 1400 mL/day.
Other fluid inputs, such as those from ingested foods and the
water by-product of oxidation, are not directly measurable.
Fluid outputs such as urinary and stool losses are also easily
measured and referred to as sensible losses.
Other sources of fluid loss, such as evaporation of f
luid through the skin and/or lungs, are not readily measured and
are called insensible losses.
The measurable I&Os are routinely measured in hospitalized
patients
7. Cont’d…
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TBW depletion (often referred to as “dehydration”) is
typically a gradual, chronic problem.
Because TBW depletion represents a loss of hypotonic
fluid (more water is lost than sodium) from all body
compartments, a primary disturbance of osmolality is
usually seen.
The signs and symptoms of TBW depletion include
central nervous system (CNS) disturbances (mental status
changes,
seizures, and coma), excessive thirst, dry mucous membranes,
decreased skin turgor, elevated serum sodium, increased plasma
osmolality,
concentrated urine, and acute weight loss.
8. Cont’d…
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Calculations for the Estimation of Patient Maintenance Fluid
Requirements
Neonate (1–10 kg) = 100 mL/kg
Child (10–20 kg) = 1000 mL + 50 mL for each Kg > 10
Adult (> 20 kg) = 1500 mL + 20 mL for each Kg > 20
The volume of fluid required to correct TBW depletion = the basal fluid
requirement + ongoing exceptional losses +the fluid deficit.
The volume of replacement fluids required for a given patient (the fluid
deficit) can be estimated by the acute weight change in the patient (1 kg = 1
L
of fluid).
Because the precise weight change is not typically known, it is often
calculated as follows: fluid deficit = normal TBW - present TBW.
Normal TBW is estimated based on the patient’s weight using the above
formulas and
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Once TBW has been restored, the volume of “
MF = basal fluid requirement + ongoing exceptional losses.
Compared with TBW depletion, ECF depletion
tends to occur acutely.
rapid and aggressive fluid replacement is required to maintain
ECF depletion manifests clinically as signs and symptoms
associated with
decreased tissue perfusion: dizziness, orthostasis, tachycardia,
decreased UO, increased hematocrit, decreased central venous
pressure, and/or HS.
Common causes of ECF depletion include
external fluid losses (burns, hemorrhage, diuresis, GI
losses, and adrenal insufficiency) and 12/26/2022
10. Therapeutic Fluids
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Therapeutic intravenous (IV) fluids include
Crystalloid solutions and colloidal solutions.
Crystalloids are composed of water and
electrolytes,
all of which pass freely through semipermeable
membranes and
remain in the intravascular space for shorter
periods of time.
are very useful for correcting electrolyte
imbalances
Crystalloids can be classified further according to
their
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11. Cont’d…
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hypertonic solutions (ie, hypertonic saline or 3% NaCl)
have greater tonicity than the ICF (> 376 mEq/L [mmol/L]),
they draw water from the ICF into the ECF.
hypotonic solutions (ie, 0.45% NaCl) have less tonicity than
the ICF (< 250 mEq/L [mmol/L])
leading to osmotic pressure gradient that favors shifts of
water from the ECF into the ICF.
The most commonly used crystalloids include NS,
dextrose/half-normal saline, hypertonic saline, and lactated
Ringer’s (LR) solution.
Glucose is often added to hypotonic crystalloids in
amounts that result in isotonic fluids (D5W, D5 ½ NS, and
D5 ¼ NS).
These solutions are often used as maintenance fluids to
provide basal amounts of calories and water.
12. Colloid
In contrast to crystalloids,
colloids do not dissolve into a true solution and
therefore do not pass readily across semipermeable membranes.
As such, colloids effectively remain in the intravascular
space and increase the oncotic pressure of the plasma.
colloids include 5% albumin, 25% albumin, the dextrans,
hetastarch, and fresh-frozen plasma (FFP).
Because each of these agents contains a substance
(proteins and
complex sugars) that will ultimately be metabolized,
the oncotic agent will be ultimately lost and
only the remaining hypotonic fluid delivery agent will remain.
As such, use of large volumes of colloidal agents is more
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13. Fluid Management Strategies
indications for IV fluid include
maintenance of BP, restoring the ICF volume,
replacing ongoing renal or insensible losses when oral intake is inadequate, and
the need for glucosen as a fuel for the brain.
When determining the appropriate fluid to be utilized, it is important to first
determine the type of fluid problem (TBW vs ECF depletion), and start therapy
accordingly.
For patients demonstrating signs of impaired tissue perfusion, the immediate
therapeutic goal is
to increase the intravascular volume and restore tissue perfusion.
The standard therapy is NS given at 150 to 500 mL/hr until perfusion is optimized.
Although LR is a therapeutic alternative, lactic acidosis may arise with massive or
prolonged infusions.
LR has less Cl content versus NS (109 mEq/L [mmol/L] vs 154 mEq/L [mmol/L])
and has the advantage of use when large volumes of NS produce acidosis during
fluid resuscitation.
In severe cases, a colloid or blood transfusion may be indicated to increase
oncotic pressure within the vascular space.
Once euvolemia is achieved, patients may be switched to a more hypotonic
maintenance solution (D5 ½ NS or 0.45% NaCl) at a rate that delivers estimated
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14. monitoring parameters
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These may include the
subjective sense of thirst, mental status, skin turgor,
orthostatic vital signs, pulse rate, weight changes,
blood chemistries, fluid input and output, central venous
pressure, pulmonary capillary wedge pressure, and cardiac output.
Fluid replacement requires particular caution in patient
populations at risk of fluid overload, such as those
with renal failure, cardiac failure, hepatic failure, or the elderly.
Other complications of parenteral fluid therapy include IV
site infiltration, infection, phlebitis, thrombophlebitis, and
extravasation
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16. Hyponatremia [serum Na <135 mEq/L]
Excess of extracellular free water relative to Na+
🞑 marked increase in water intake
🞑 impaired water excretion
Assess measured or calculated serum osmolality
🞑 Sosm = 2[Na+] + [BUN]/2.8 + [Glucose]/18
Assess ECF volume status
Measured urine [Na+] &/or measured urine osmolality
🞑 ↑ urine *Na+] (>20mEq/L) implicates the kidney as etiologic
site
🞑 ↓ urine *Na++ ….. appropriate renal response to extrarenal
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17. Hyponatremia
assessment
Based on serum osmolality:hypertonic and
hypotonic
Hypertonichyponatremia
🞑 increased serum osmolality (nonsodium effective
osmoles in the ECF)
🞑 Common in patients with hyperglycemia
🞑 ↑ glucose conc in ECF ….↑ plasma osmoles …result in
diffusion of water from the cells into ECF, diluting
serum Na+ conc.
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For every 100 mg/dL increase in the serum glucose
conc, the serum Na level decreases by 1.7 mEq/L,
and the serum osmolality increases by 2 mOsm/kg.
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18. Hyponatremia
assessment,…
Hypotonic hyponatremia
Decreased plasma osmolality
The most common form of hyponatremia
Based on ECF volume: Hypervolemic, euvolemic,
hypovolemic.
Hypervolemic hyponatremia;
🞑 increase in ECF volume …… edematous
🞑 occurs when there is impaired renal Na & water excretion
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19. Hyponatremia
assessment,…
Euvolemic hyponatremia:
🞑 water intake > kidney excretion, thus ECF volume & TBW
modestly
↑ but not enough to manifest clinically
total serum [Na++ ….. ∼ normal
🞑 Assess urine Na+ handling to determine cause
🞑 SIADH and primary polydipsia
Urine Na: >20 mEq/L (SIADH ); <20 mEq/L (1o polydipsia )
Urine osmolality: >100 mOsm/kg (SIADH ); <100 mOsm/kg (1o
polydipsia)
SIADH: In tumors, CNS disorders (head trauma, stroke,
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20. Hyponatremia
assessment,…
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Hypovolemic hyponatremia
🞑both ECF water & Na+ ↓
🞑Assess urine sodium handling to determine cause
🞑 Urine Na+ > 20 mEq/L ….. excess renal sodium
losses
thiazides (less with loop diuretics); mineralocorticoid
deficiency;
common in head trauma & neurosurgical pts
🞑Urine Na+ < 20mEq/L) ….. Non-renal losses
GI tract most common,
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23. Pharmacological treatment
Hypovolemichypotonic hyponatremia
🞑 Isotonic saline as these patients have both Na & water
deficits
Euvolemic and hypervolemic hypotonic
hyponatremia
🞑 Water restriction….. fluid intake should be <800 mL/day
🞑 Hypertonic saline (3% NaCl) PLUS loop duiretic
(furosemide)
for severe acute cases (serum Na <110 to 115 meq/L )
🞑 Vasopressin receptor antagonists produce a selective
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24. Hypernatremia
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Results from a deficit of water relative to ECF
sodium content
Observed in patients with impaired thirst
response or in those with lack of access to free
water
Causes:
🞑 Renal water loss
🞑 Extra-renal water loss
🞑 Lack of water intake (primary hypodipsia)
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25. Hypernatremia ….
Renal water loss
Diabetes Insipidus (DI)
🞑 ↓ or absent ADH activity; ↑ output of dilute urine
(>3L/day)
🞑Central DI ……..↓ ADH release
head trauma, neoplasm, neurosurgery, CNS infection
present with sudden onset of polyuria
🞑Nephrogenic DI …….ADH resistance
genetic, kidney disease, electrolyte imbalance
(hypercalcemia,
hypokalemia), drugs (amphotericin B, lithium, didanosine)
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26. Hypernatremia ….
Osmotic diuresis
🞑 Patients undergoing an osmotic diuresis (mannitol,
hyperglycemia, loop diuretics) generally have urine
volumes
>3 L/day.
Patients with severe hyperglycemia, conversely,
present with signs of volume depletion, and the
diuresis is inappropriate, further exacerbating the
degree of ECF volume contraction.
Extrarenal water loss
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27. Hypernatremia ….
Lack of water intake …… uncommon
🞑 destruction of thirst mechanism by neoplasm,
trauma, or neurosurgery
Excess Na+ intake ….. infrequent cause
🞑 hypertonic saline or IV NaHCO3,
🞑 ingestion of large amounts of Na (>4 tbsp of NaCl)
[1,400 mEq Na+]
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28. Hypernatremia ….
Signs/symptoms …..
🞑 postural hypotension, tachycardia,dry oral mucosa,
diminished skin turgor, and reduced or increased
output of dilute or concentratedurine, depending on
cause
🞑 lethargy, weakness, confusion, restlessness, and
irritability, and can progress to twitching, seizures,
coma, and death.
🞑 severe symptoms usually occurs with an acute elevation in
the plasma Na > 160 mEq/L
🞑 values >180 mEq/L ….. high mortality rate
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29. Hypernatremia ….
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Lab. tests
🞑 Serum Na levels >145 mEq/L
🞑 urine osmolality
🞑 Clinically detectable ECF volume depletion might not be
evident until the serum Na concentration exceeds 160
mEq/L.
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30. Hypernatremia treatment
Desired goals
🞑Correction of serum Na
🞑Normalize ECF volume
🞑Rapid correction can result in movement of
excessive water into the brain cells, resulting in
cerebral edema, seizures, neurologic damage,
and potentially death.
requires careful titration of fluids and medications
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31. Pharmacologic therapy
For hypovolemic hypernatremia;
🞑 0.9%NaCl with an initial infusion rate of 200 to 300 mL/h
🞑 Once intravascular volume is restored, infuse 0.45% NaCl
or 5% dextrose in water ….to correct the water deficit
For hyperglycemia-induced osmotic diuresis
🞑 Correction of hyperglycemia …. insulin
🞑 Administer 0.9%NaCl till sign of ECF volume depletion
resolves
🞑 Followed by, correction of water deficit
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32. Pharmacologic therapy
….
Treatment of central DI
🞑 ADH replacement therapy with desmopressin acetate
🞑 a goal to decrease urine volume to less than 2 L per day
🞑 maintain a normal or near normal serum Na
concentration [137 to 142 mEq/L]
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33. Pharmacologic therapy ….
Treatmentof nephrogenicDI
🞑 correct hypercalcemia and hypokalemia
🞑 discontinue contributing medications
🞑 sodium restriction [2g NaCl/day] in conjunction with a
thiazide diuretic to decrease the ECF volume by
approximately 1 to 1.5 L.
🞑 NSAIDs such as indomethacin 50mg tid (potentiate the
activity of ADH) ……. as adjunctive therapy
🞑 for Lithium-induced nephrogenic DI …. Amiloride 5-10mg
daily
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34. Pharmacologic therapy ….
Assess serum and urine Na concentration and
osmolality every 2 to 3 months during chronic
therapy
A 24-hour urine collection
🞑 to measure urine volume and sodium excretion
to guide therapy with diuretics
to determine adherence to sodium restriction
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35. Pharmacologic therapy ….
Treatment of sodium overload …. loop diuretics &
D5W
🞑 Furosemide 20-40 mg IV q6hrs …↑ excretion of excess
Na.
🞑 IV D5W…infuseat a rate that will decrease the serum Na
at
~0.5 mEq/L/h, or 1 mEq/L/hr in cases in
which the hypernatremia developed rapidly
over several hours
🞑 serum Na should initially be measured every 2 to 4 hrs,
and the diuretic continued until signs of ECF volume
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36. Edema
Edema refers to swelling caused by a collection of
fluid in the small spaces that surround the body's
tissues and organs.
Edema may be defined as a clinically detectable
increase in interstitial fluid volume of at least 2.5
to 3 L (adults).
It can occur nearly anywhere in the body.
🞑 Some of the most common sites are: the lower legs or
hands (peripheral edema), abdomen (ascites), chest
(pulmonary edema)
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37. Edema ….
Edema can develop as a primary defect in
renal Na handling or as a response to a
decreased effective circulating volume.
The BP resulting from decreased effective
circulating volume …. results in ↓d Na and
water excretion by the kidney.
🞑 the kidneys retain all of the water and sodium
ingested
🞑 lead to an expanded ECF volume and edema
formation
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38. Edema ….
Causes ….
🞑 valves damage in the veins, blood clot in the deep veins
🞑 kidney disease, heart failure, cirrhosis,
🞑 pregnancy, monthly menstrual periods
🞑 drugs such as some oral diabetes medications, high
BP meds, pain relievers (such as ibuprofen), estrogens.
🞑 travel
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39. Clinical Presentation
Symptoms of edema depend upon the cause.
🞑 Swelling of the skin, causing it to appear stretched and
shiny
🞑 Abdominal distension
🞑 Shortness of Breath
🞑 Pitting edema:
severity of the edema can be rated on a semi-
quantitative scale depending on the depth of the pit.
1+ =2mm, 2+ =4mm, 3+ =6mm, 4+ =8mm
🞑 Pulmonary edema …. an increase in lung interstitial &
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40. Edema treatment
Goals of therapy:
🞑 minimize tissue edema and thus improve organ
function
🞑 relieve symptoms of edema
Pulmonary edema requires immediate
pharmacologic treatment because it is life-
threatening.
Other forms of edema may require a
comprehensive approach that includes diuretics,
sodium restriction and treatment of the
underlying conditions.
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41. Pharmacologic therapy
Diuretics (loop or thiazide)
🞑 are the primary pharmacologic therapy for the
management of edema
🞑 but, the presence of edema doesn’t always
require diuretic therapy
🞑 Indicated when treatment of the underlying
disease and daily Na restriction are insufficient to
relieve the edema.
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42. Pharmacologic therapy ….
Patients with renal insufficiency require larger
doses of diuretics
🞑 the natriuretic response is decreased in this patients
because the filtered load of Na falls proportionately
as GFR declines.
🞑 dosing diuretics more frequently
🞑 continuous infusions in critically ill hospitalized
patients
For diuretic resistant patients
🞑 treat with both a loop and a thiazide-type
diuretic (metolazone)
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43. Pharmacologic therapy ….
Diuretic resistance/causes:
🞑 increased uptake of sodium in the distal tubule
🞑 impaired delivery of diuretics to the site of action
🞑 decreased intrinsic diuretic activity
Binding of furosemide to albumin in the tubular
lumen decreases the availability of the drug to
the active site.
🞑 how to overcome diuretic resistance associated with
nephrotic syndrome ….… ?
use combination of different diuretics vs. higher doses of
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44. Pharmacologic therapy ….
Diuretic therapy in patients with nephrotic
syndrome;
🞑If albumin <2g/dL
Furosemide 80mg q8hr PLUS HCTZ 50 mg q12hr, assess
response at 24 hrs
If no response, increase dose or decrease interval
🞑If albumin ≥2g/dL
Furosemide 80mg q8hr, assess response at 24 hrs
If no response, add HCTZ 50–100 mg q12hr
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45. Pharmacologic therapy ….
Diuretic use in patients with CHF;
🞑EF <30%
Furosemide 40mg q8hrs
If no response: increase frequency, add thiazide
🞑EF >30%
GFR>50 mL/min (if <50mL/min, follow the above
regimen)
HCTZ 25–50mg BID and/or Spironolactone 25–
50mg/day
🞑 Patients with CHF & normal GFR may have
impaired oral absorption of furosemide.
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46. Pharmacologic therapy ….
Edema (20 hyperaldosteronism)in patients with
cirrhosis;
🞑 treat with spironolactone (50-400mg/day)in the
absence of impaired GFR and hyperkalemia.
🞑 If CLcr: >50 mL/min …. add thiazides (HCTZ 25-50mg
bid)
for diuretic resistantpatients, replace with a loop diuretic
🞑 If CLcr: <40 mL/min (impaired GFR) …. loop diuretic,
and add a thiazide if no adequate diuresis.
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47. Monitoring
Signs and symptoms of edema
Adverse effects of treatment
Physical examination: BP
, pulse
Follow-up monitoring (10–14 days after
initiation of therapy) should include …..
🞑 serum sodium, potassium, chloride, bicarbonate,
magnesium, calcium, BUN, serum creatinine, and uric
acid
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51. Hypokalemia ….
Drugs can cause hypokalemiaby different mechanisms
🞑 intracellular K shifting
🞑 increased renal or stool losses
Loop and thiazide diuretics …. the most common
🞑 inhibit renal Na reabsorption, which results in increased Na
delivery to the distal tubule.
As a result, hypokalemia develops because the distal tubule
selectively reabsorbs Na, and excretes K.
🞑 diuretics result in vascular volume contraction, thus,
aldosterone is secreted that further promotes the renal
excretion of K.
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52. Hypokalemia ….
Signs/symptoms
🞑 Symptoms depend on the degree of hypokalemia
🞑 Mild hypokalemia ….. asymptomatic
🞑 Moderate hypokalemia…. cramping, weakness, myalgias
🞑 Severe hypokalemia ….ECG changes (ST-segment
depression or flattening, T-wave inversion, U-wave
elevation)
🞑 Clinical arrhythmias (include heart block, atrial flutter,
paroxysmal atrial tachycardia,ventricular fibrillation,
and digitalis-induced arrhythmias)
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53. Hypokalemia treatment
Treatment goals ….
🞑 serum K >3.5mEq/L (normalize)
🞑 prevent/treatserious life-threatening complications
🞑 correct underlying cause of hypokalemia
Nonpharmacologictherapy
🞑 dietary K supplementation ….fresh fruits and
vegetables, fruit juices, and meats
Pharmacologicaltreatment
🞑 Potassium supplementation …. Oral vs. IV
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54. Hypokalemia treatment ….
Oral therapy is preferred for asymptomatic patients
Three salts are available for oral K supplementation
K-phosphate >>> used in patient with both
hypokalemic and hypophosphatemic
K-bicarbonate ….most commonly used when K
depletion occurs in the setting of metabolic acidosis
K-chloride …..the most commonly used salt form
🞑 most effective for the most common causes of potassium
depletion (diuretic and diarrhea-induced) as these conditions
are associated with potassium and chloride losses.
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55. Hypokalemia treatment ….
IV potassium use should be limited to….
🞑 symptomaticpatients with severeK depletion
🞑 patients exhibiting ECG changes or muscle spasms
🞑 patients unable to tolerate oral therapy
IV supplementation …..
🞑 it is more likely to result in hyperkalemia, phlebitis,
and pain at the site of infusion
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56. Hypokalemia treatment ….
IV potassium …..
should be prepared in saline-containing
solutions (0.9%-0.45% NaCl)
🞑Avoid dextrose containing solutions
Such solutions stimulate insulin secretion, which
can cause intracellular shifting of K, worsening
the patient’s hypokalemia.
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57. Hypokalemia treatment ….
Spironolactone
🞑 for patients receiving drugs known to deplete potassium
(such as diuretics)
🞑 effectiveas a K-sparing agent in patients with
hyperaldosteronism
🞑 start with a dose of 25 to 50 mg daily and titrate to a
maximum dose of 400 mg/day
In patients with concomitant hypomagnesemia,
the Mg deficit should be corrected before K
supplementation is started.
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58. Hyperkalemia
Serum potassium concentration > 5 mEq/L
Based on its severity;
🞑 mild hyperkalemia ….. 5.1-5.9mEq/L
🞑 moderate …… 6-7 mEq/L
🞑 severe …… >7 mEq/L
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59. Hyperkalemia ….
Primary causes of hyperkalemia ….
🞑 increased potassium intake
fresh fruits and vegetables contain large amounts of
potassium
🞑 decreased potassium excretion
🞑 tubular unresponsiveness to aldosterone
🞑 redistribution of potassium into the extracellular
space
metabolic/respiratory acidosis (H+ exchanged for K+)
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60. Hyperkalemia ….
Drugs with profound effects on the kidney’s
ability to regulate K …
🞑 ACEIs, ARBs, potassium-sparing diuretics, NSAIDs
Other drugs that can cause hyperkalemia ….
🞑 digoxin, cyclosporine, tacrolimus, cotrimoxazole,
heparin
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63. Hyperkalemia treatment ….
Non-pharmacological
🞑 haemodialysis (renal failure, refractory)
🞑 dietary counselling
Pharmacological treatment (in order of importance)
🞑 ↓ arrhythmia risk → calcium gluconate 1g IV
🞑 Shift K+ intracellular → regular insulin (plus dextrose to ↓
hypoglycemia risk), facilitatesthe uptake of glucose into
the cell, which results in an intracellular shift of potassium.
🞑 NaHCO3 IV (if acidotic)
🞑 furosemide………..promote K+ excretion
5
3
12/26/2022
FE
H
63
64. Disorders of Mg homeostasis
Mg is an important cofactor in many biochemical
reactions in the body, especially those dependent
on ATP.
🞑 Mitochondrial function, protein synthesis, cell membrane
function, parathyroid hormone (PTH) secretion, and glucose
metabolism
Principally distributed in bone (67%) and muscle (20%).
Extracellular measurement of Mg … not accurately
reflect the total-body Mg content.
🞑 because of its predominantly intracellular distribution
Normal serum Mg = 1.4 to 1.8 mEq/L
5
4
12/26/2022
FEH
64
65. Disorders of Mg homeostasis
……
Disorders of Mg homeostasis ……
🞑 manifestedas alterations in cardiovascularand
neuromuscularfunction
🞑 life-threatening conditions such as paralysis and cardiac
arrhythmias can occur
Recommended daily dietary Mg intake for adults ….
🞑 ~420 mg/day …..men
🞑 ~320 mg/day …..women
5
5
12/26/2022
FEH
65
66. Disorders of Mg homeostasis
……
The maintenance of Mg homeostasis depends on the
balance b/n intake and output
🞑 30- 40% of ingested Mg is absorbed in the small bowel
~95% of the filtered Mg is reabsorbed (in the thick
ascending limb of the loop of Henle)
🞑 this is why loop diuretics often cause profound urinary Mg
wasting
🞑 less than 5% is excreted in the urine
5
6
12/26/2022
FEH
66
67. Hypomagnesemia
Commonly caused by excessive GI or renal Mg wasting
🞑 drugs or conditions that interfere with intestinal
absorption or increase renal excretion of Mg
Small bowel disease:↓intestinal absorption…most
common cause
🞑 regional enteritis, ulcerative colitis, diarrhea and vomiting,
chronic laxative abuse
Alcoholism
Reduced intake
5
7
12/26/2022
FEH
67
68. Hypomagnesemia ….
10 renal Mg wasting
🞑 defect in renal tubular Mg reabsorption, or
🞑 Inhibition of Na reabsorption
Renal Mg wasting
🞑 secondary to thiazide and loop diuretics
🞑 AGs, amphotericin B, cyclosporine, digoxin,
cisplatin, …..
5
8
12/26/2022
FEH
68
69. Hypomagnesemia ….
Clinical presentation
Neuromuscular and CV systems are the most
affected systems
Signs/symptoms
🞑 Neuromuscular: tremor, tetany, twitching,
generalized convulsions
🞑 Cardiovascular: heart palpitations, cardiac arrhythmias,
sudden cardiac death, and hypertension, ECG abnormalities
LaboratoryTests
🞑 Serum Mg <1.4 mEq/L; Serum K & Ca also low
5
9
12/26/2022
FEH
69
70. Treatment of
hypomagnesemia
Treatment goals ….
🞑resolution of the signs and symptoms
🞑restoration of normal Mg concentrations
🞑correction of concomitant electrolyte
abnormalities
🞑correction of the underlying cause of Mg
depletion
No nonpharmacologic options for the
management of hypomagnesaemia
6
0
12/26/2022
FEH
70
71. Pharmacologic therapy
For mild, chronic Mg loss (serum Mg >1 mEq/L
🞑 treat with oral supplements
🞑 Mg-containing antacids or laxatives, comprised of a
variety of Mg salts in tablet or capsule formulations.
🞑 diarrhea is the most common dose-limiting side effect
of oral therapy
🞑 sustained release Mg products are preferred
b/c they improve patient compliance and reduce GI side
effects
6
1
12/26/2022
FEH
71
72. Pharmacologic therapy ….
Severe Mg depletion
🞑 Serum <1 mEq/L; or if signs and symptoms are
present regardless of the serum concentration
🞑 IV MgSO4: 4 to 6g over 12 to 24 hrs & repeat as
necessary
🞑 For patients with renal insufficiency,reduce dose by 25%
to 50%
Monitor ….
🞑 serum Mg
🞑 GI tolerance and diarrhea in patients taking oral Mg
6
2
12/26/2022
FEH
72
73. Hypermagnesemia
Serum Mg >2 mEq/L; >1 mmol/L
Rare, but generally seen in patients with advanced
CKD and taking concomitant Mg-containing antacids
Mg concentrations steadily increase as the GFR
decreases below 30mL/min/1.73 m2.
Critically ill patients with multiorgan system failure
receiving enteral or parenteralnutrition
Parenteral treatment of eclampsia with MgSO4
6
3
12/26/2022
FEH
73
74. Hypermagnesemia ….
Severe cases of hypermagnesium can result in
neurologic symptoms or cardiac dysrhythmias.
Symptoms: lethargy, confusion, dysrhythmias,
muscle weakness
Goals of therapy
🞑 reverse neuromuscular and CV manifestations
🞑 decrease Mg concentration toward normal values
🞑 treat underlying causes
No nonpharmacologic options
6
4
12/26/2022
FEH
74
75. Pharmacologic therapy ….
Three primary means of treatment ….
🞑 reduce Mg intake
🞑 enhance elimination of Mg
🞑 antagonize the physiologic effectsof Mg
IV calcium can counteract neurologic and cardiac
effects.
Adm’r IV elemental Ca doses of 100 to 200 mg hrly
(e.g., 2g of Ca-gluconate) until the signs or symptoms
resolves and the Mg concentration is normalized.
6
5
12/26/2022
FEH
75
76. Pharmacologic therapy ….
Patients with normal renal function or with stage
1-3 CKD (mild to moderate renal dysfunction),
🞑 Forced diuresis with 0.45% NaCl and loop
diuretics can promote Mg elimination.
Initial IV bolus of furosemide 40mg
Subsequent dosing based on clinical response
Hemodialysis should be reserved for ESRD patients.
6
6
12/26/2022
FEH
76
77. Monitoring
Serum Mg
Sign and symptoms
ECG changes
Dietary education on foods containing large
quantities of Mg
🞑 Rice bran, peanut butter, whole wheat bread, Avocado,
non-fat yogurt, bananas, …………..
6
7
12/26/2022
FEH
77
78. Reading assignment
Management calcium and phosphorus
disorders
🞑 Hypocalcemia and hypercalcemia
🞑 Hypophosphatemia and hyperphosphatemia
6
8
12/26/2022
FEH
78
![Renal disorders Pharmacotherapy:
Disorders of Fluid and Electrolyte
Homeostasis
By: Aster Wakjira
[B.Pharm ,MSc,clinical Pharmacist]
E-mail: asterwakjira@gmail.com Or
aster.garedow@ju.edu.et](https://image.slidesharecdn.com/3-fluidelect-a1-221226083414-668a737f/85/3-Fluid-elect-A-1-pptx-1-320.jpg)
