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.
 Ca ions 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 dairy products-Egg yolk , Fish, beans
 Cow’s milk 100mg/100ml
 Human milk 30mg/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
and requires energy and a carrier protein.
 30 – 80 % of ingested calcium is absorbed
 Actively transported out of the intestinal cells with
the help of Ca 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 cause absorption
• 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 is remineralized (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 NamrataChhabra
(MD Biochemistry) 10

11.  The overall action of PTH is to increase plasma Ca2+
levels and decrease plasma phosphate levels.
 PTH acts directly on the bones to stimulate Ca2+
resorption and kidney to stimulate Ca2+ reabsorption
in the distal tubule of the kidney and to inhibit
reabosorptioin of 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)
Calcitriol regulates Calcium, muscle, bone health and blood pressure.
Calcitriol having very short half life hence can not be considered as a correct indicator of
Vitamin D status
The Renal metabolic pathway
LIVER
KIDNEY
1,25 -(OH)2 - D3
(Calcitriol)
Vitamin D3
(Cholecalciferol)
Calcium Regulation
BONE/BLOOD
25 -(OH)- D3
(Calcidiol)
Hydroxylation 1
Hydroxylation 2
Metabolism ofVitamin 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. Cholecalciferol was significantly, more effective than
Ergocalciferol to increase serum 5(OH)D Cholecalciferol
should be the preferred drug for severe vitamin D
deficiency.
Longer half-life of D3 suggests that less frequent
dosing may be needed.
Alfacalcidol and Dihydrotachysterol are synthetic
prodrug which are rapidly hydroxylated in liver to
calcitriol

16. Cholecalciferol or Ergocalciferol ?
 Cholecalciferol was significantly, more effective than Ergocalciferol to
increase serum 25(OH)D (J Clin Endocrinol Meta, 2011; 96: 981–988)
 Cholecalciferol should be the preferred drug for severe vitamin D
deficiency. (Endocrine Abstracts 2012; 28:19)
 Longer half-life of D3 suggests that less frequent dosing may be needed.
(Mayo Clin Proc. 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 12Yrs Vitamin D deficiency
1000 IU-5000 IU/Day for 3 months*
(American academy of Pediatrics)
Women Pregnancy & lactation
1500-2000 IU/Day from II
trimester*
Adults Maintenance 2000 IU/Day or 60 K IU/ Month*
Adults VDD 60,000 IU/ Week for 8 Weeks*
Recommended Dose of Vitamin D3
Absorption: Well absorbed from the GI tract. Decreased in patients with decreased fat
absorption.
Excretion: Mainly in the bile & faeces with only small amounts appearing in urine.
* Recommended by Dr.Michael F. Folick (TheVitamin D Solution)

18. Vitamin D Deficiency: Consequences

20. Calcitonin acts to decrease plasma Ca2+ levels.
While PTH and vitamin D act to increase plasma Ca2+--
only calcitonin causes a decrease in plasma Ca2+.
Calcitonin is synthesized and secreted by the
parafollicular cells 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 of hypercalcemia is 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
hypercalcemia have
dramatic symptoms:
conusion, lethargy, may
lead to death

26.  Oral PO4 for serum Ca < 11.5 mg/dL with mild
symptoms and no kidney disease
 IV saline and diuretic (furosemide) for more rapid
correction for serum Ca < 18 mg/dL
 Bisphosphonates or other Ca-lowering drugs for
serum Ca < 18 mg/dL and > 11.5 mg/dL or moderate
symptoms
26

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

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

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 the osteoclastic apoptosis 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 a ranelic acid salt of strontium
Blocks differenciation of osteoclasts and promotes
their apoptosis
SEVELAMER-HYDROCHLORIDE-
Posphate binding gel + calcium decreases serum
phosphate levels
Hyperphosphatemia due to hypoparathyroidism
ADR- constipation, epigastric distress

32. They reduce renal calcium excretion
They reduce hypercalciuria and 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. THANKYOU
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