Vitamin D - primary regulator Hormone/vitamin which is derived either endogenously or exogenously

- when pts are not exposed to UV light, may supplement w vt D

Disorder of ca homeostasis Assessment of ca concentrations - normal total serum concentration= 8. 5 -10.5 MG/DL

Calcium must be adjusted for hypoalbuminemia - corrected calcium= measured calcium +0.8 (4.0-albumin). Or - corrected calcium= (Measured calcium- albumin) +4.0 Normal ionized serum calcium concentrations=4.6 to 5.1 MG/DL Critically ill pts; varying affinities

Bone Mineral Flashcards by yujeong lee

Osteoclast
Osterblast
Osteocyte

Osteoblast- responsible for removal of bone matrix

Osteoblast- produce protein matrix and control mineralization

Osteoclast- buried in newly formed bone and connect w one another to form a system which controls the rate of ion transport and regulates the rate of mineralization in new bone matrix

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Bone composition

2 major mineral constituents

Calcium, phosphate

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Ca disposition in body

very small amt of ca exists in the free or active form
- 99% exist in crystalline form in your skeleton and teeth
- 1% exist in 2 main compartments
  - 0.9% intracellularly within the soft tissues
  - 0.1% extracellularly
complexed w phosphates, citrate, or other anions (15%)
bound to serum proteins, primarily albumin (40%)
ionized or biologically active (45%)

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Phosphate disposition in body

85% exists in crystalline forms in your skeleton and teeth

- not as tightly regulated as calcium

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Regulators

Regulators of calcium and phosphate homeostasis

2 primary hormones responsible for tight control of mineral homeostasis

parathyroid hormone
vt D

Secondary hormonal regulators of mineral homeostasis

calcitonin
glucocorticoids
estrogen

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PTH

Primary regulator –single chain peptide hormone secreted by the parathyroid gland

main goals of PTH
Increase calcium
Decrease phosphate
collectively targets 3 main areas
Bone
Kidney
Intesine

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PTH effects on kidney

increase calcium and magnesium
Reabsorption at the distal tubule
decrease phosphate reabsorption at the distal tubule (as well as amino acids, bicarbonate, sodium, and chloride)
stimulation of renal production of calcitriol

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PTH effects on the intestine

-PTH has no direct effect on intestine
-indirectly promotes absorption of calcium
From small intestine through its stimulation of renal activation of vt D

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Vitamin D

primary regulator
Hormone/vitamin which is derived either endogenously or exogenously

when pts are not exposed to UV light, may supplement w vt D

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Vt D

Activation of vitamin D: endogenous production

Liver does initial hydroxylation, kidney does 2nd hydroxylation which is required for activation

Calcitriol is the active form

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Vt D

Main goals of vt D

Increase calcium

Increase phosphate

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Vt D

Collective sites of action

intestine
Inc absorption of calcium
Inc absorption of phosphate
bone ( acts indirectly)
Inc responsiveness of bone to PTH
May inc calcium and phosphate resorption
May inc bone formation
kidney
Dec calcium and phosphate excretion

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Secondary regulators of bone mineral homeostasis

hormonal
Calcitonin
Glucocorticoids
Estrogens

- non hormonal
Bisphosphonates
Plicamycin (mithramycin)
Thiazide diuretics
Loop diuretics

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Disordes of bine mineral homeostasis

Hypercalcemis
Hypocalcemia
Hyperphosphatemia
Hypophosphatemia
Osteoporosis
Paget's disease- chronic disorder of adult skeleton in which localized areas of bone become hyperactive softened and enlarged bone

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Disorder of ca homeostasis

Assessment of ca concentrations

normal total serum concentration=
8. 5 -10.5 MG/DL

Calcium must be adjusted for hypoalbuminemia

corrected calcium=
measured calcium +0.8 (4.0-albumin). Or
corrected calcium=
(Measured calcium- albumin) +4.0

Normal ionized serum calcium concentrations=4.6 to 5.1 MG/DL
Critically ill pts; varying affinities

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Disorders of calcium homeostasis

Other factors affecting calcium concentrations

-alkalosis:
Decreased calcium concentrations
Calcium protein binding increased

-acidosis
Increased calcium concentrations
Calcium protein binding decreased

Hypercalcemia

Signs and symptoms

Neurological effects
– Fatigue
– Weakness
– Lethargy

Gastrointestinal effects
– Anorexia
– Nausea/vomiting
– Constipation

Renal effects
– Polyuria
– Nephrolithiasis
– Increase excretion of electrolytes (due to polyuria)

Cardiovascular effects
– EKG changes (shortened QT)
– Bradyarryhthmias; cardiac arrest

Extraskeleton calcification

Hypercalcemia: Etiology

Primary hyperparathyroidism
Multiple endocrine disorders
– MEN-1 or Werner’s syndrome
-Parathyroid hyperplasia
granulomatous diseases (TB/sarcoidosis)
- extrarenal production of calcitriol
pharmacological agents
- Thiazide diuretics (hydrochlorothiazide); not acute
  – Vitamin D supplementation
- lithium ( inc PTH hormone concentrations and raises calcium set-point)

Pharmacologic management of hypercalcemia

Calcium concentration assessment
– Total calcium

Pharmacologic management of hypercalcemia

Initial considerations

Elimination of potentiating agents (thiazides, calcium supplementation, lithium)
Symptomatic relief of constipation, nausea/vomiting, and pain
(Stool softeners, analgesics: Remember pain meds can cause
constipation)

-Increased mobilization

Pharmacologic management of hypercalcemia

Hydration with normal saline (0.9% sodium chloride)

Amount infused depends on degree of
hypercalcemia
In acute management usually 2-6 liters in the first 24 hours
anticipate a 1.6-2.4 mg/dl decrease in calcium concentrations w normal saline alone

Intro to bone mineral homeostasis

Homeostasis
Balance

Homeostasis- immediate
Adjustments required to maintain constant free calcium concentrations on a minute to minute basis

Balance- long term
Adjustments to maintain a constant amt of total calcium concentration within body

Pharmacologic management of hypercalcemia

Loop diuretics
-Mechanism of action

-Decrease calcium concentrations through
increased elimination of calcium in the kidney

-Inhibit calcium reabsorption in the ascending loop of henle

-Agents include:
-Furosemide
-Bumetanide
-Toresemide

Pharmacologic management of hypercalcemia

Bisphosphonates
– Mechanisms of action

Bind to hydroxyapatite in calcified bone matrix and thereby inhibit crystal dissolution
to the mineralized matrix Agents used in acute management of hypercalcemia
-Inhibit attachment of osteoclasts to the mineralized matrix
agents used in acute management of hypercalcemia
– Pamidronate
Zoledronic acid

Pharmacologic management of hypercalcemia Bisphosphonates -Pamidronate (Aredia®)

- Most commonly used bisphosphonate in the treatment of hypercalcemia - Dosage: Depends on the degree of hypercalcemia – Usually given as 60 or 90 mg infusion over 4 to 24 hours Onset and Duration - onset and duration: – Calcium concentrations begin to decline in 3 days – Nadir reached in 7 days – Normalization of calcium occurs in 60 to 90% of patients – Wait at least 7 days following administration to give another dose. Side effects – Transient pyrexia – Rash - renal dysfunction - nausea - fatigue

Pharmacologic management of hypercalcemia | Calcitonin (Intravenous)

– Hormone produced by the C cells of the thyroid gland – Main goals of calcitonin DECREASE calcium DECREASE phosphate – Collective sites of action – bone (primary site of action) – Short term effects: decrease calcium movement from bone fluid - long term effects: decrease bone r sorotion through inhibition of osteoclasts - kidney - decrease phosphate and calcium reabsorption ( as well as other ions)

Pharmacologic management of hypercalcemia | Corticosteroids

– Steroid molecules produced and released by the adrenal cortex – Administered exogenously for a multitude of applications – Collective sites of action of glucocorticoids Intestine - intestine: – Antagonize vitamin D stimulated absorption of calcium and phosphate - Kidney: increase renal excretion of calcium – Bone – Inhibit bone collagen synthesis – Increase bone resorption

Pharmacologic management of hypercalcemia | Corticosteroids

– Dose: Hydrocortisone 200 to 300 mg daily for 3 to 5 days (or equivalent); generally see decrease in calcium within 7 days – Potential usefulness of corticosteroids in treatment of hypercalcemia is limited to granulomatous disease (i.e., tuberculosis, sarcoidosis) and lymphoproliferative disorders – Adverse effects Hyperglycemia Infection Sodium/Water retention Hypokalemia

Hypocalcemia Signs and symptoms | Central Nervous System – Fatigue – Confusion – Hallucinations

Neuromuscular – tetany: due to enhance peripheral neuromuscular irritability; manifests as parathesias around mouth and extremities, muscle spasms, cramps – Muscle spasms/cramps – Parasethesias Cardiovascular – Prolonged QT intervals – AMI – Hypotension Dermatologic – Hair loss – Eczema – Psoriasis

Hypocalcemia: Etiology

Hypoparathyroidism Vitamin D deficient states | – Rickets – Liver/Renal disease Malabsorption

Pharmacologic management of hypocalcemia

- Hypocalcemia associated with hypoalbuminemia does not need treatment Acute symptomatic hypocalcemia - Treatment is usually via the intravenous route - Goal of therapy is to administer 200-300MG of elemental calcium intravenously until symptoms are controlled

Pharmacologic management of hypocalcemia Agents – Calcium chloride: 1g (270mg elemental Ca) - Disadvantages –potential for extravasation and tissue necrosis

– Calcium gluconate: 2 to 3 grams (180 to 270 elemental Ca) Disadvantages –small amounts of elemental calcium per volume and less predictable increases in plasma ionic calcium – Precautions with intravenous calcium administration -Administer no faster than 30 to 60 mg of elemental calcium per minute -Rapid administration associated with hypotension, bradycardia and cardiac asystole - If patient’s symptoms return then may consider slow infusions of calcium (i.e., 15 mg/kg over 4 to 6 hours) or continuous 24 hour infusions)

Pharmacologic management of hypocalcemia – Calcium supplementation with oral calcium salts Calcium salts differ in percentage of elemental calcium (further discussion/explanation in osteoporosis)

– Vitamin D supplementation Vitamin D may need to be added to therapy in patients with malabsorption or concomitant vitamin D deficiency - Agents – Many vitamin D analogues are available – Only dihydrotachysterol 1,25 Pharmacologic management of hypocalcemia Chronic hypocalcemia

Pharmacologic management of hypocalcemia

– Adverse effects associated with chronic vitamin D and calcium administration Hypercalcemia Hypercalciuria Nephrolithiasis – Increase urinary excretion of calcium – The addition of thiazide diuretics (which inhibit calcium excretion) may decrease the risk of nephrolithiasis as well as decrease calcium and vitamin D requirements** - alpha hydroxyvitamin D3 (alfacalcidiol) do not require dihydroxyvitamin D3 (calcitriol) and - hydroxylation in the kidney to produce the physiologically active form of the hormone