Hypokalemia - Pharmacotherapy

1. Hypokalemia

2. Potassium:
• Most abundant cation in the body, with total-body stores of≈ 3,000 to
4,000 mEq.
• 98% of this amount is within the intracellular compartment, and the
remaining 2% is distributed within the extracellular compartment.
• Na+-K+-ATPase pump located in the cell membrane is responsible for the
compartmentalization of potassium.
• The normal serum concentration range for potassium is 3.5 to 5 mEq/L,
whereas the intracellular potassium concentration is approximately 150
mEq/L.
• Approximately 75% of the intracellular potassium is located in skeletal
muscle; the remaining 25% is located in the liver and red blood cells.
• Potassium is dynamic.
• Thus, the serum potassium concentration alone does not accurately reflect
the total-body potassium content.

3. • Potassium functions include protein and
glycogen synthesis and cellular metabolism and
growth. It is also a determinant of the electrical
action potential across the cell membrane.
• Hypo- and hyperkalemia are associated with
fatal cardiac arrhythmias, along with other
neuromuscular disturbances.
• Potassium is integral to maintaining blood
pressure, prevention of stroke & other
cardiovascular diseases.

4. Epidemiology:
• Hypokalemia is defined as a serum K+ conc. of <
3.5 mEq/L.
• It’s categorized as mild (3.1-3.5 mEq/L),
moderate (2.5-3 mEq/L), & severe (<2.5
mEq/L).
• It increases mortality in pts w/ CHF and CKD.
• Diagnostic workup: evaluate pts comorbid
diseases states and concomitant medications b/c
hypokalemia won’t exist in a healthy individual.

5. Etiology and Pathophysiology:
• Hypokalemia results when serum K+ is shifted
into intracellular compartment, or when there is
a total body K+ deficit 2/2 poor dietary intake of
K+ or there are excessive renal and GI losses of
K+.
• Our bodies are unable to store K+, that’s why it’s
important to consume K+ in diet.
• In steady state: K+ excretion = K+ intake.
• 90% of K+ is excreted renally & the other 10%
excreted in feces.

6. • Many drugs cause Hypokalemia by intracellular
K+ shifting or increase renal or stool losses.
• Most common drug-induced Hypokalemia is
loop and thiazide diuretic.
1) Loop and thiazide diuretic -> inhibit renal Na+
resorption -> Na+ delivery to the distal tubule
which reabsorbs Na+ and excretes K+.
2) Diuretics result in vascular volume contraction,
aldosterone is secreted -> promotes renal
excretion of K+
That’s why K+ supplements should be provided to
pts taking diuretics.

7. Transcellular Shift
Enhanced Renal
Excretion
Enhanced Fecal
Elimination
β2-Receptor agonists
Epinephrine
Albuterol
Terbutaline
Fomoterol
Salmeterol
Isoproterenol
Ephedrine
Pseudoephedrine
Tocolytic agents
Ritodrine
Nylidrin
Theophylline
Levothyroxine
Decongestants
Caffeine
Insulin overdose
Verapamil overdose
Barium overdose
Diuretics
Acetazolamide
Thiazides
Indapamide
Metolazone
Furosemide
Torsemide
Bumetanide
Ethacrynic acid
High-dose penicillins
Nafcillin
Ampicillin
Penicillin
Mineralocorticoids
Miscellaneous
Aminoglycosides
Amphotericin B
Cisplatin
Laxatives
Sodium polystyrene
sulfonate
Phenolphthalein
Sorbitol
Patiromer

8. Excessive loss of K+rich GI fluid 2/2 diarrhea
&/or vomiting.
Normal K+ loss in feces is 10 mEq/day. Which
increases proportionally with the volume of stool
output in diarrhea.
Metabolic alkalosis develops in pts with severe
diarrhea and vomiting 2/2 loss if bicarbonate-
rich fluids causes intracellular shift of K+
resulting in lower serum conc. of K+.

9. • Hypomagnesemia reduces the intracellular K+
conc & promotes renal K+ wasting.
• hypoMg impairs the function of Na+K+ATPase
pump.
• Important note! hypokalemia and
hypomagnesemia often coexist as a result of
drugs (diuretic administration) or disease states
(diarrhea). When concomitant hypokalemia and
hypomagnesemia occur, the magnesium
deficiency should be corrected first.

10. Goals of therapy:
• Prevent &/or treat serious life-threatening
complication.
• Normalize serum K+ conc.
• Identify and correct the underlying cause.
• Prevent overcorrection of K+ conc.

11. General approach to therapy:
• If serum K+ conc 3.5-4 mEq/L it’s a sign of early K+
depletion, pt should be encouraged to dietary
intake of K+.
• If serum K+ conc 3-3.5 mEq/L pts concomitant
conditions and medications determine whether
pharmacological therapy should be initiated.
• In mild cases there will be no s/s but if s/s are
present K+ supplementation should be initiated.
• Oral K+ should be initiated in pts w/ underlying
cardiac conditions. IV used in severe symptomatic
cases.
• Pts w/ serum K+ conc <3 mEq/L should be treated
to achieve 4-4.5 mEq/L.

12. Sings & Symptoms of Hypokalemia:
• Its often asymptomatic but moderate
hypokalemia is associated w/ cramping,
weakness, malaise and myalgia.
• Signs: CV: ECG shows 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.
• In laboratory tests hypomagnesemia (<1.7
mg/dl) may be present.

14. Non-pharmaocolgical therapy:
• High food content > 250mg:
• kidney beans, lentils, soybeans, lima beans, pinto
beans, halibut, rockfish, cod, tuna, rainbow trout,
evaporated milk, low-fat or reduced fat chocolate
milk, skim milk, low fat milk or butter milk, orange
juice, bananas, peaches, prunes, apricots, plantains,
tomato sauce, pork loin, spinach.
• Very high food content: >500mg:
• Potato, sweet potato, juice (canned), prunes, carrot,
tomato, beet greens, white beans, plain yogurt,
clams.

15. • Dietary K+ intake may add unwanted calories to the
patient’s diet.
• Dietary potassium is almost entirely coupled with
phosphate, rather than chloride, so it is not as
effective in correcting potassium loss associated
with hypochloremic conditions such as vomiting,
nasogastric suctioning, and diuretic therapy.
• Salt substitutes that contain potassium chloride are
another effective, inexpensive source of potassium
and because they provide chloride as well they are
frequently recommended.

16. Pharmacological treatment:
• When deciding how to design the optimal regimen,
one must consider:
1. The patient’s normal, that is, baseline potassium
concentration.
2. Underlying medical conditions that can affect
potassium balance.
3. Concomitant medications that can affect
potassium balance.
4. The patient’s dietary salt intake.
5. The patient’s ability to comply with the therapeutic
regimen.

17. Guideline Comment
Potassium replacement therapy should accompany
dietary consumption of potassium-rich foods.
Potassium-rich foods often cannot completely
replace potassium associated with chloride losses
(vomiting, diuretics, or nasogastric suction) because
it is almost entirely coupled to phosphate.
Furthermore, increasing dietary intake of these foods
can lead to unwanted weight gain.
Potassium replacement is recommended for sodium-
sensitive and hypertensive patients.
A high-sodium diet often results in excessive urinary
potassium excretion.
Potassium replacement is recommended in patients
who are subject to vomiting, diarrhea, or
diuretic/laxative abuse.
These conditions promote excessive renal and GI
potassium loss.
Potassium supplementation is best administered
orally in divided doses over several days to achieve
full repletion.
Laboratory measurement of serum potassium is
convenient, but not always accurate.
Clinicians should be aware of the factors that result in
transcellular potassium shifts. Monitoring 24-hour
urinary potassium excretion can be necessary in
high-risk patients.
Patient adherence to potassium replacement can be
increased with compliance-enhancing regimens.
Microencapsulated products have no bitter smell or
aftertaste and have much better GI tolerance.
Regimens should be made as simple as possible to
follow.
A potassium dosage of 20 mEq/day (mmol/day) is
usually sufficient to prevent hypokalemia from
occurring. Doses of 40-100 mEq (mmol) are usually
sufficient to treat hypokalemia.

18. • For each 1 mEq/L decrease of serum K+ below 3.5
mEq/L there is a corresponding total-body K+
deficit of 100-400 mEq.
• Administration of 10 mEq of IV or oral K+ should
serum K+ conc by 0.1 mEq/L.
• In mild to moderate hypokalemia cause by diuretics
40-100 mEq of oral K+ can treat problem.
• While in severe cases, doses up to 120 mEq are
required to treat it.
• Total daily dose should be divided into 3-4 doses to
prevent GI S.E
• Pts on diuretic may become chronically hypokalemic
so they should be on combination therapy with K+
sparing diuretic.

19. There are 3 salts available for oral
potassium supplementation:
1. Potassium phosphate which is used when pt is
both hypokalemic and hypophosphatemic.
2. Potassium bicarbonate which is used when K+
depletion occurs in the setting of metabolic
acidosis.
3. Potassium chloride which is the most
commonly used amongst all salts. And can
treat hypokalemia in diuretic and diarrhea
induced hypokalemia.

20. Supplement Comment
Controlled-release microencapsulated
tablet
Disintegrates better in GI tract; fewer
GI erosions as compared to wax-
matrix tablets
Encapsulated controlled-release
microencapsulated particles (prefered
less GI effects)
Fewer erosions as compared to wax-
matrix tablets
Potassium chloride elixir Inexpensive, poor taste, poor
compliance, immediate effect
Potassium chloride effervescent
tablets for solution
More expensive than elixir, convenient
Wax-matrix extended-release tablets Easier to swallow; more GI erosions
as compared to other therapies
Differences Among Oral Potassium chloride Supplements

21. • Limit IV administration to
1. severe hypokalemia (<2.5mEq/L)
2. signs and symptoms of hypokalemia
3. inability to tolerate oral therapy.
IV supplementation is more dangerous than oral
therapy due to the potential for hyperkalemia,
phlebitis, and pain at the infusion site.

22. • Potassium should be administered in saline
because dextrose can stimulate insulin secretion
and worsen intracellular shifting of potassium.
Generally, 10 to 20 mEq of potassium is diluted
in 100 mL of 0.9% saline and administered
through a peripheral vein over 1 hour.
• ECG monitoring to detect cardiac changes is
recommended when infusion rates exceed 10
mEq/h (severe cases).

23. Evaluation of therapeutic outcome:
• For ambulatory patients the serum potassium and magnesium
concentrations, as well as renal function should be monitored every 1 to 2
months.
• In hospitalized patients receiving oral therapy for mild hypokalemia, the
potassium concentration should be monitored every 2 to 3 days. If it does
not increase by at least 1 mEq/L within 96 hours, the clinician should
suspect concomitant magnesium depletion.
• Patients receiving IV potassium supplementation require close ECG
monitoring if the infusion rate is greater than 20 mEq/h.
• Additionally, the patient should have potassium concentrations obtained
halfway through, and 30 minutes following completion of the total potassium
dose to guide further potassium administration.
• Finally, the patient should be assessed for adverse effects such as pain at
the infusion site or phlebitis.