1-8 for the Programme Book- Dr. Rashed

8/14/2019 1-8 for the Programme Book- Dr. Rashed

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For the programme book


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PHARMACOLOGICAL

MANAGEMENT OFOSTEOPOROSIS


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DRUGS FOR TEATMENT OFOSTEOPOROSIS:

1-calcium.2-vitamin D.

3-Antiresorpitive Drugs:a-calcitonin.

b-Bisphosphonates.c-SERMS.

4-Bone forming agents.5-Dual acting Bone agents.


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CALCITONIN


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Important structural elements of bisphosphonates

When R 1 is an OHgroup, binding tohydroxyapatite is

enhanced

Adapted from Russell G, et al. Osteoporos Int. 1999;(Suppl. 2):S6680

The R 2 side chaindetermines potency.Nitrogen-containingbisphosphonatesare most potent

P-C-P is essentialfor binding tohydroxyapatite

OH R 1 OH

OH OH

R 2

O OP PC


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BisphosphonateCellular and Molecular Mechanisms of Action

BP BP

BP BP BP

ActiveOsteoclast

InactiveOsteoclast

ApoptoticOsteoclast

HMG Co-A

Mevalonate

Farnesyl-PP

Squalene

Cholesterol

Geranylgeranyl-PP

Isoprenylation

N-Bisphosphonates


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20

N

CH2

CP

OH

OOH

OH

P

OH

OONa

2.5 H2O

Third Generation Bisphosphonates

R2R2increased Potencyand reduced GIT s/e

R1R1

Risedronate Sodium


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Molecular Structure of Zoledronic Acid

Zoledronic acid is a potent nitrogencontainingbisphosphonate

Green JR, et al. J Bone Miner Res. 1994;9:745-751 .

Core bisphosphonate moiety (red arrows)R 2 side chain: imidazole ring (blue arrows)

NNNN

PP

OO

OO

PP

OHOH

OHOHOHOH

OHOHHOHO

CC


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II-Bone forming agents:Teriparatide:


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Teriparatide:

Is a recombinant human parathyroidhormone acting as an anabolic agent. Itstimulates now bone formation. It is also

claimed to increase resistance to fragilityfarcture. The recommended done is 20micorgrams injected subcutaneously oncedialy. Patient taking Teriparatide must receivespecial training on the injection technique.The maximum total duration of treatment isrestricted by licence to 18 months in Europeand 24 months is USA.


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Dual acting bone agents:

Strontium Ranelate:


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What is Strontium Ranelate?

This compound contains 2 ions of stable(non-radioactive) strontium per molecule and

an organic moiety (ranelic acid)

An

innovative,synthesized drug


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OPG, RANK, RANKL: an essential linkbetween

Osteoblast and Osteoclast Differentiation

OPG Osteoclast

Osteoclast

Progenitor

Osteoblast /Stromal cell

Differentiation and fusion

RANK

RANK L

BONE

Ada ted from Khosla. Endocrinolo . 2001;142(12):5050.

RANK L


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Consider using inhaled Corticosteroids whenever possible.Consider using inhaled Corticosteroids whenever possible.

It is recommended that supplementation with CalciumIt is recommended that supplementation with CalciumCarbonate sufficient to ensure a daily consumption of 1500 mg (or Carbonate sufficient to ensure a daily consumption of 1500 mg (or equivalent) daily and vitamin D of 800 IU dialy may preserve bone mass inequivalent) daily and vitamin D of 800 IU dialy may preserve bone mass inpatients receiving long-term treatment of Corticosteroids.patients receiving long-term treatment of Corticosteroids.Inhibit CIO with pharmacotherapy:Inhibit CIO with pharmacotherapy:

Bisphonnates in addition to vitamin D and Calcium ate effective in bothBisphonnates in addition to vitamin D and Calcium ate effective in bothprevention and treatment of CIO.prevention and treatment of CIO.

Second line therphy include Hormone Replacement therapy in womenSecond line therphy include Hormone Replacement therapy in womenand testosterone in men, calcitonin and thiazide diuretics. Patients whoand testosterone in men, calcitonin and thiazide diuretics. Patients whohave a urine Calcium excretion > 300 mg/ 24 h may benefit from thehave a urine Calcium excretion > 300 mg/ 24 h may benefit from theaddition of a thiazide diuretic ( e.g: hydrochlorthiazide 25 mg/day)addition of a thiazide diuretic ( e.g: hydrochlorthiazide 25 mg/day)

Management of C.I.O.

Documents

1-8 for the Programme Book- Dr. Rashed