Drugs affecting calcium balance

THIS CLASS IS IN BRIEF FOR UNDER GRADUATE UNDERSTANDING AND EXAMINATION PURPOSE

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. Ca salts in bone provide structural integrity of the
skeleton.
Ca is the most abundant mineral in the body.
Caions in extracellular and cellular fluids is essential to
normal function of a host of biochemical processes
Neuromuscular excitability and signal transduction
Blood coagulation
Hormonal secretion
Enzymatic regulation
Neuron excitation

3. About 1000 mg of Ca is ingested per day.
About 200 mg of this is absorbed into the body.
Absorption occurs in the small intestine, and
requires vitamin D
Milk and dairyproducts-Egg yolk, Fish,beans
Cow’s milk100mg/100ml
Humanmilk30mg/100ml

4. RECOMMENDED DAILY ALLOWANCE (RDA):
Adults –500 mg /day
Children-1200 mg /day
Pregnancy&--1500 mg /day
Lactation
SITE: first part and second part of duodenum
Calcium absorbed against concentration gradient
andrequires energy and a carrier protein.
30–80 % of ingested calcium is absorbed
Actively transported out of the intestinal cells with
the help ofCa
2+
dependent ATPase

5. A) Factors favoring calcium absorption
•An acidic pH
•Presence of sugar acids, organic acids and citric acid
•High protein diet-Lysine and Arginine causeabsorption
•Presence of vitamin D
•Ca : P ratio-A ratio of dietary Ca: P not more than 2:1 is
adequate for optimal absorption, ratio of less than 1:2
reduces absorption
•State of health and intact mucosa-A healthy adult absorbs
about 40% of dietary calcium.
•PTH (Parathormone) stimulates the activation of vitamin
D, thus indirectly increases absorption of vitamin D
5

6. B) Factors inhibiting absorption of calcium
•Alkaline pH
•High fat diet-Fatty acids form calcium soaps that can not
be absorbed
•Presence of Phytates and oxalates-Insoluble calcium salts
are formed
•Dietary fiber in excess inhibits absorption
•Excess phosphates, magnesium and iron decrease
absorption
•Glucocorticoids reduce intestinal absorption of calcium
•Calcitonin reduces calcium absorption indirectly by
inhibiting the activation of vitamin D
•Advancing age and intestinal inflammatory disorders
inhibit absorption of calcium
6

8. The primary site of storage is our bones (about 1000
grams).
Some calcium is stored within cells (endoplasmic
reticulum and mitochondria).
Bone is produced by osteoblast cells which produce
collagen, which is then mineralized by calcium and
phosphate (hydroxyapatite).
Bone isremineralized(broken down) by osteoclasts,
which secrete acid, causing the release of calcium and
phosphate into the bloodstream.
There is constant exchange of calcium between bone and
blood.

9. The major site of Ca excretion in the body is the kidneys.
The rate of Ca loss and reabsorption at the kidney can be
regulated.
Regulation of absorption, storage, and excretion of Ca
results in maintenance of calcium homeostasis.

10. 4/22/2016
By-Professor Namrata Chhabra
(MD Biochemistry) 10

11. The overall action of PTH is to increase plasma Ca
2+
levels and decrease plasma phosphate levels.
PTH acts directly on the bones to stimulate Ca
2+
resorption and kidney to stimulate Ca
2+
reabsorption
in the distal tubule of the kidney and to inhibit
reabosorptioinof phosphate (thereby stimulating its
excretion).
PTH also acts indirectly on intestine by stimulating
1,25-(OH)
2
-D synthesis.

13. UV B Rays(Sun)
+
7-Dehydro-
cholesterol(Skin)
CalcitriolregulatesCalcium,muscle,bonehealthandbloodpressure.
Calcitriolhavingveryshorthalflifehencecannotbeconsideredasacorrectindicatorof
VitaminDstatus
The Renal metabolic pathway
LIVER
KIDNEY
1,25-(OH)2-D3
(Calcitriol)
VitaminD3
(Cholecalciferol)
Calcium Regulation
BONE/BLOOD
25-(OH)-D3
(Calcidiol)
Hydroxylation 1
Hydroxylation 2
Metabolism of Vitamin D

14. PTH increases 1-hydroxylase activity, increasing
production of active form.
This increases calcium absorption from the intestines,
increases calcium release from bone, and decreases loss
of calcium through the kidney.
As a result, PTH secretion decreases, decreasing 1-
hydroxylase activity (negative feedback).
Low phosphate concentrations also increase 1-
hydroxylase activity (vitamin D increases phosphate
reabsorption from the urine).

15. Cholecalciferolwas significantly, more effective than
Ergocalciferoltoincreaseserum5(OH)DCholecalciferol
should be the preferred drug for severe vitamin D
deficiency.
Longerhalf-life of D3 suggests that less frequent
dosing may be needed.
AlfacalcidolandDihydrotachysterolare synthetic
prodrugwhich are rapidlyhydroxylatedin liver to
calcitriol

16. Cholecalciferol orErgocalciferol?
Cholecalciferolwassignificantly,moreeffectivethanErgocalciferolto
increaseserum25(OH)D(JClinEndocrinolMeta,2011;96:981–988)
CholecalciferolshouldbethepreferreddrugforseverevitaminD
deficiency.(EndocrineAbstracts2012;28:19)
Longerhalf-lifeofD3suggeststhatlessfrequentdosingmaybeneeded.
(MayoClinProc.2010;85(8):752-758)

17. Group Condition Dose
Infants and children
Prevention of vitamin D
deficiency
400 IU/Day*(American academy of
Pediatrics)
>1 yr to 12 YrsVitamin D deficiency
1000IU-5000 IU/Day for 3 months*
(American academy of Pediatrics)
Women Pregnancy & lactation
1500-2000IU/Day from II
trimester*
Adults Maintenance 2000 IU/Day or 60 K IU/ Month*
Adults VDD 60,000 IU/ Week for 8Weeks*
Recommended Dose of Vitamin D3
Absorption:WellabsorbedfromtheGItract.Decreasedinpatientswithdecreasedfat
absorption.
Excretion:Mainlyinthebile&faeceswithonlysmallamountsappearinginurine.
*RecommendedbyDr.MichaelF.Folick(TheVitaminDSolution)

18. Vitamin D Deficiency: Consequences

20. Calcitonin acts to decrease plasma Ca
2+
levels.
While PTH and vitamin D act to increase plasma Ca
2+
--
only calcitonin causes a decrease in plasma Ca
2+
.
Calcitonin is synthesized and secreted by the
parafollicularcells of the thyroid gland.
They are distinct from thyroid follicular cells by their
large size, pale cytoplasm, and small secretory
granules.
Synthetic salmon calcitonin-sc,im

22. CARPOPEDAL SPAM
Obstetric hand
Laryngeal stridor
Convulsions
Visceral features like
intestinal spasm,
bronchospasm and
profuse sweating.

23. CALCIUM LEVEL > 12 mg /dL
▪Nervous system is depressed
▪Reflex activities are sluggish
▪Decreased QT interval
▪Lack of appetite

24. A) Cancer with bone
metastases
Carcinoma
Leukemia
Lymphoma
Multiple myeloma
B) Immobilization
Orthopedic casting or traction
Paget's disease of bone
Osteoporosis in the elderly
Paraplegia or quadriplegia
Young, growing patients
C) Parathyroid hormone excess
Parathyroid carcinoma
Primary hyperparathyroidism
Secondary hyperparathyroidism
D) Vitamin Toxicity
Vitamin A toxicity
Vitamin D toxicity
E) Other disorders/causes
Hyperthyroidism
Milk-alkali syndrome
Addison's disease
Granulomatous disorders
Drug therapy such as thiazides
and lithium
24

25. The mnemonic "stones," "bones," "abdominal
moans," and "psychic groans" describes the
constellation of symptoms and signs of
hypercalcemia
The history ofhypercalcemiais dependent on its
cause and the sensitivity of the individual
Mild increase :
Asymptomatic,
Or may have recurring
problems like kidney
stones
Rapid rise or severe
hypercalcemiahave
dramatic symptoms:
conusion, lethargy, may
lead to death

26. Oral PO
4for serum Ca<11.5 mg/dLwith mild
symptoms and no kidney disease
IV saline anddiuretic (furosemide)for more rapid
correction for serum Ca<18 mg/dL
Bisphosphonates or other Ca-lowering drugs for
serum Ca<18 mg/dLand>11.5 mg/dLor moderate
symptoms
26

27. CALCIUM CARBONATE
Ca CITRATE
GLYCEROPPHOSPHATE
LACTATE
GLUCONATE
HEPTAGLUCONATE

28. To correct calcium deficiency
Post-menopausal osteoporosis
Rickets andosteomalacia
Removal of parathyroid adenoma
Chronic kidney disease as phosphate binders
Hyper-magnesemia
Hyperkalemia
Cardiac arrest
Placebo-calciumgluconate

29. Bisphosphonates–
I GENERATION-ETIDRONATE, CLODRONATE
II GENERATION-ALENDRONATE, PAMIDRONATE,
IBANDRONATE
III GENERATION-RISEDRONATE, ZONLENDRONATE,
Synthetic pyrophosphate derivative
Inhibits osteoclast mediated bone resorption
Phosphorus-oxygen-phosphorus moiety is replaced
with stable phosphorus-carbon-phosphorus moiety
BPNs also accelerate theosteoclasticapoptosis after
they ingest the bone matrix

30. Non steroidal synthetic agents who have action on
estrogen receptor is tissue selective
RALOXIFENE-used in post menopausal osteoporosis
Bones-reduces vertebral fractures by 30-50%
CALCIMIMETICS-CINACALCET-calcium sensing
receptors on parathyroid glandsense the Ca levels
and reduce the PTH secretion
30mg once daily

31. It is aranelicacid salt of strontium
Blocksdifferenciationof osteoclasts and promotes
their apoptosis
SEVELAMER-HYDROCHLORIDE-
Posphatebinding gel+ calciumdecreases serum
phosphate levels
Hyperphosphatemiadue tohypoparathyroidism
ADR-constipation,epigastricdistress

32. They reduce renal calcium excretion
They reducehypercalciuriaand reduce incidence of
calcium oxalate stones
They increase the effectiveness of PTH induced calcium
reabsorption
FLUORIDES-
Prophylaxis for dental caries
Dose dependent toxicity
Increase risk of all types of fracturesfluoroapatite
gets deposited in place of hydroxyapatiteloses
biomechanical strength

33. THANK YOU
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