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					                SunSPOT
Sun Small Programmable Object Technology
           Peter Perera & Karlo Diamante
'Sensing' and ‘Interacting‘ with our
environment

o   Tracking and Identification
    o   Inventory
           Courier Parcels
           Any object (cup, shirt)
    o   People
    o   Cars
o   Remote Control
    o   Robotics
    o   Toys
    o   Personal Electronics
o   Wireless Sensor Networks
    o   Building Facilities Management


                                         Sun SPOT powered by solar panel
What is the SunSPOT?
• A wireless sensor network
    (WSN) mote developed
    by Sun Microsystems

• A Java Platform for developing
    Applications for wireless networks
    of small devices.

• Features
    – Over The Air (OTA) Programming           Sun SPOT Development Kit
    –




                                         Sun SPOT Sensors and Base station size
                                              comparison with AA battery
What is the SunSPOT?
SunSPOT JAVA Development Kit




     2x Sun SPOT
     Sensors              Sun SPOT
                          BaseStation
What is the SunSPOT?
SunSPOT JAVA Development Kit

           Sun SPOT Sensor
                   MICROCONTROLLER ARM 920T
                         TRANCEIVER 802.15.4

           PROGRAM + DATA MEMORY 512K RAM

                   EXTERNAL MEMORY 4MB Flash
           PROGRAMMING LANGUAGE Java

                              BATTERY 3.7V 750mAh Lithium-ion

                                  SENSORS / ACTUATORS

           3-axis accelerometer (2G/6G)     6 analogue inputs readable by
                                            an ADC
           Temperature                      2 momentary switches

           Light                            5 general purpose I/O pins

           8 Tri-color LEDs                 4 high current output pins
Applications of the SunSPOT

•   Education
•   Industrial Research
•   Government and Military
•   Hobbyists
• Examples
    o Swarm Intelligence
    o Rapid Prototyping and Experimenting
       with Ideas
    o Rocket Launch Monitor

                                            Sun SPOT controlling an iRobot Create Roomba
Programming the SunSPOT




  Code     Deploy   Debug / Simulate
Programming the SunSPOT

- Programming SunSPOT using Netbeans

- Deployment
   - real SunSpot
   - emulator

- Debugging/testing

- Actual demo
                  References - Links
•   http://research.sun.com/spotlight/SunSPOTSJune30.pdf
•   http://wiki.netbeans.org/SUNSPOTusingNetbeans
 of Thiamine:
 * active form of thiamine = thiamine pyrophosphate
 * fxn as a coenzyme in the decarboxylation of α – keto
   acids such as pyruvate and α – ketoglutarate and in the
   utilization of pentose in the hexose monophosphate shunt
   … involves the thiamine pyrophosphate – dependent
      enzyme transketolase
 * requirement of thiamine is related to metabolic rate and is
   greatest where when CHO is the source of energy
   … patients who are maintained by parenteral alimentation
        ---> receive most of their calories in the form of
        dextrose should be given generous allowance of the
        vitamin
* thiamine also serve as a modulator of neuromuscular
  transmission
  … thiamine binds to isolated nicotinic cholinergic
      receptors ---> this can be impaired by pyrithiamine
                     a thiamine antagonist
Thiamine Deficiency:
 * Severe thiamine deficiency – beriberi
    - common among … polished rice eaters
                       … alcoholics
                       … infants
 * Occur in association w/ adequate diet since the vit. is not
   stored in the body to a great extent
    - observed among => increase metabolic rate e.g.
                        hyperthyroidism
         => chronic GIT disturbances e.g. chronic diarrhea
         => consumption of large amount of raw fish ctg.
             thiaminase
         => intake of large quantities of tea---> contains
             thiamine antagonist
* S X S : related to the nervous system – dry beriberi
          : related to the cardiovascular system – wet beriberi
  … Neurological S X S:
      - peripheral neuritis, with sensory disturbances in the
        extremities including localized areas of hyperesthesia
        or anesthesia
     - gradual lost of muscle strength ---> wrist – drop or
        complete paralysis of a limb
    - personality disturbances, depression, lack of initiative
       and poor memory

--- Cardiovascular S X S:
     - dyspnea on exertion
     - palpitation, tachycardia
     - other cardiac abnormalities ---> abnormal ECG i.e.
        low R wave voltage, T-wave inversion, and prolonged
        Q – T intervals
         ---> cardiac failure of the high – output type
     - extensive edema due to hypoproteinemia together with
          failing ventricular fxn.
 …GIT S X S:
     - in severe thiamine def.---> Loss of appetite followed
           by constipation
* Diagnosis of thiamine deficiency -
    ** oxidation of α – keto acids is impaired ---> increase of
        pyruvate conc. in the blood
    ** more specific test – measurement of transketolase
        activity in erythrocytes
* Human Requirements of Thiamine:
   ** minimum requirement = 0.3 – 0.5mg./1000 kcal.
   ** older people = 1mg/day recommended for adults of all
                ages no matter how low their caloric intake
   ** pregnant and lactating women = additional intake of
                0.6mg/1000 kcal. is recommended
* Food Sources: pork, organ meats, whole grain and enriched
     cereals and bread, legumes and nuts
Pharmacokinetics of Thiamine
 * Absorption:
    > GIT – occurs by sodium-dependent active transport
          - at higher conc. = passive diffusion
    > max. absorption/day = 8 – 15mg. --> can be exceeded
       by oral adm. in divided doses w/ food
 * Distribution and excretion:
    > adults – 1mg/day of thiamine is completely degraded
              by the tissues.~ daily min. requirement--->
              little or no thiamine is excreted in the urine
   > intake exceeds the min. requirement – tissue stores
            - excess ---> urine as intact thiamine or
                          pyrimidine
Thiamine Preparations: Pure vitamin, mixtures of pure vits.,
     vitamin-rich concentrates
   - Vit B1 Hydrochloride => tablets 5-500mg
                          => injections 100mg/ml.
                          => elixir
Thiamine Tx :
  - tx or for prophylaxis of thiamine deficiency
     * to correct the disorder rapidly – I.V. doses of 100mg/li
           of parenteral fluid are used
     * after correction of the vit def. – no need for parenteral
          injection or adm. of excess of the vit. daily
          requirement except :
           GIT disturbances preclude the ingestion or absorption of
               thiamine
- Thiamine def. syndromes:
  * Alcoholic neuritis – a nutritionsl def. due to lack of
           thiamine intake
       -- poor appetite food consumption drops
       -- caloric intake is largely in the form of alcohol
     > characterized by polyneuritis with motor and
          sensory defects
     > tx  40mg of oral thiamine daily
  * Wernicke’s syndrome – an additional serious
        consequence of alcoholism and thiamine deficiency
      > characterized by ophthalmoplegia, nystagmus and
         ataxia--->respond rapidly to thiamine adm. But
                    not to other vitamins
> may also be accompanied by an acute global confusional
     state ---> responds to thiamine
    ---> left untreated chronic disorder i.e. learning
         and memory are impaired out of proportion to
         other cognitive fxns. in the otherwise alert and
         responsive patients => referred to as Korsakoff’s
         psychosis – chararacterized by confabulation and
         is irreversible once established
 > observed to have an abnormality in the thiamine-
     dependent enzyme transketolase i.e.
      affinity of transketolase for Vit. B1 is reduced
      --- hence marginal conc. of thiamine might be =>
          sufficient to produce neurological damage
      > the syndrome represents an acute emergency –
         treated with 100mg/day I.V.
* Infantile Beriberi – an acute disease in infancy which may
      be rapid and fulminating
   - S X S: loss of appetite, vomiting, greenish stools
      followed by paroxysmal attacks of muscular rigidity
          -- aphonia – due to loss of laryngeal nerve fxn.
                is a diagnostic feature of the disease
          -- cardiac involvement - pulse become weak and
              rapid, cyanotic face, neck veins are engorged
              due to cardiac failure
         -- death w/in 24 hours unless vigorous tx is ensued
> mild forms of infantile beriberi  respond to oral
        therapy => 10mg thiamine/day
  > acute collapse =>25mg. Thiamine, I.V. given cautiously
        ---> prognosis remains poor
* Subacute necrotizing encephalomyelopathy – fatal disease
            of children
   > clinical features: difficulties in feeding and
         swallowing, vomiting, hypotonia, external
         ophthalmoplegia, peripheral neuropathy and seizures
    > caused by a genetically linked determined enzyme
       deficiency inhibition of the of the enzyme that
       synthesizes thiamine triphosphate from thiamine
        pyrophosphate in the nervous system
     likewise in the liver and muscle of the affected infants
  > daily adm. of large doses of thiamine  pts. exhibited
     marked temporary improvement
* Cardiovascular Disease
   > present among alcoholics, pregnant women and pts.
      w/ GIT disorders
   - tx if correctly made – response to thiamine adm. is
       striking
       -- increase blood flow due to arteriolar dilatation 
        pathognomonic feature of cardiovascular syndrome
      -- few hours after thiamine adm. cardiac output is
        reduced
      utilization of oxygen begins to return to normal

      diuresis results if edema is present due to

          myocardial insufficiency

- chronic tiamine deficiency pts.:

  -- 10-30 mg thiamine 3x/day

  -- dosage can be reduced but pt. is maintained on:

       oral medication or dietary management after

         S X S of the def. state have been reversed
    -- for individuals w/ marginal thiamine status it is
       emphasized that adm. of glucose may precipitate
       heart failure ---> pts. in this category should
                          receive a prophylactic dose of
                          100 mg. added to the first

                          few liters of I.V. fluid

* Neuritis of pregnancy – 5-10 mg./day of thiamine is adm.
    parenterally if vomiting is severe
RIBOFLAV IN (B2)
 – growth-promoting factor
 - w/ yellow color
 - Caries out its fxn in the body in the form of its two active
    forms:
    * riboflavin phosphate known as flavin mononucleotide
        (FMN)
    * flavin adenine dinucleotide ( FAD)
 - function of rivoflavin:
    * serve a vital role in metabolism as co-enzyme for a side
       variety of respiratory flavoproteins
- diagnosis of riboflavin def. -- recognition is difficult 
     rarely occurs in isolation

- human requirements of riboflavin:
   * young adult males – 1.6 mg/day
   * young adult females – 1.2 mg./day
   * elderly adults – 1.2 mg./day even w/ < 2000kcal. of
                       caloric intake
- Food sources :
   * milk, cheese, organ meats, eggs, green leafy vegetables,
   * whole-grain, enriched cereals and bread
- pharmacokinetics of riboflavin:
     * readily absorbed from the upper GIT by a specific
       transport mechanism involving phosphorylation of
       riboflavin to FMN
       i.e riboflavin   flavokinase   FMN is sensitive to thyroid
                                               hormone status
                                            inhibited by
                                              chlorpromazine and
                                              tricyclic depressant
     * distributed to all tissues -- but concentrations are
        uniformly low and little is stored
* intake ~ min. requirement/daily -- 9% is excreted in the
           urine
   -- as riboflavin intake is increased above minimal
      requirement a large proportion is excreted unchanged
 * riboflavin is present in the feces – represents vitamins
         synthesized by intestinal microorganisms
    -- on low intake of B2 amount excreted in the feces >
        ingested
    -- no evidence that B2 synthesized by bacteria in the
        colon can be absorbed
- preparation:
   * orange to yellow crystalline powder with a slight odor
   * riboflavin tablets 5-10mg          available
   *         injections 50mg/ml
- therapeutic uses:
       * specific therapy with riboflavin 5-10mg/day is given
           on the context of treating multiple nutritional
           deficiencies
NICOTINIC ACID: niacin
 - pellagra preventing vitamin
 - functions in the body in its active forms:
   * Nicotinamide Adenine Dinucleotide (NAD)
   * Nicotinamide Adenine Dinucleotide Phosphate (NADP)
 - pharmacologic actions :
    * Nicotinic acid and nicotinamide are identical in fxns as
      vitamins but as pharmacological agents they differ
      markedly
    Difference Between Nicotinic Acid and Nicotinamide
                 As Pharmacologic Agents
                          Nicotinic Acid                  Nicotinamide
Pharmacologic Used as a vasodilator    No such
Effect        and as a reducing agent cardiovascular
              of plasma cholesterol    effect
Toxicity      Flushing, pruritus, GIT
              distress, hepatotoxicity
              and activation of peptic
              ulcer
  - physiologic fxns:
    * NAD and NADP – serve as a coenzyme for a wide variety of proteins that
        catalyze oxidation-reduction reactions essential for tissue respiration
Vit. B3
- niacin but not niacinimide ---> decreases VLDL
     and LDL levels and Lp(a) in most patients
      ---> often increases HDL levels significantly
- pharmacokinetics:
  niacin is converted in the body into amide


 incorporated niacinamide adenine dinucleotide
                     (NAD)

 excreted in the urine as is or as metabolite
Toxicity of Vit B3
  - harmless cutaneous vasodilatation and sensation
     felt by most patients as dose is started or
        increased
   - contraindicates: aspirin and ibuprofen
   - doses above 1.5 –3gms daily  tachyphylaxis or
      flushing which may occur within few days
   - niacin should be avoided in patients with severe
      peptic disease
   - hepatic toxicity including acute necrosis
   - hyperuricemia which may precipitate gout
- blurring of vision should be reported if
   experienced upon intake of Vit B3
- may potentiate antiypertensive agents
- birth defects reported in animals given very high
   dosage of niacin
- Niacin (Nicotinic Acid) deficiency:
   * lack of the vit. clinical condition known as pellagra
         pellagra is characterized by S X S referable
             to the skin, GIT and CNS – a triad known
             as dermatitis, diarrhea and dementia or the 3Ds
         occurs w/ : -- chronic alcoholism
                       -- protein-calorie malnutrition
                       -- deficiencies of multiple vitamins
    * S X S : erythematous eruption resembling sunburn
                --->first appear on the back of the hand
                ---> other areas exposed to light =>forehead,
                              neck, and feet
- Human requirements of Niacin:

  * Nicotinic acid requirement is influenced by the quantity
       and quality of dietary protein
  * Dietary requirement of this vitamin can be satisfied by:
       -- nicotinic acid          -- tryptophan
       -- nicotinamide
  * 60mg of dietary tryptophan ~ 1mg of nicotinic acid
  * minimal requirement of nicotinic acid including that formed from
      tryptophan to prevent pellagra = 4.4mg per 1000kcal.
   * recommended dietary allowance expressed in nicotinic
       acid equivalents = 6.6mg/1000kcal.
   * elderly intake of nicotinic acid/day = should not be less than 13mg
- Food sources: liver, meat, fish, poultry, whole-grain and
     enriched bread and cereals, nuts and legumes
   * tryptophan – provided by animal protein
- Pharmacokinetics of nicotinic acid:
   * absorbed from all portions of the intestinal tract
   * is distributed to all tissues
   * administration of therapeutic doses of niacin or its
       amide  only small amounts is excreted in urine
       -- adm. of extremely high doses  unchanged vit.
         represents the major urine component
  * principal route of metabolism of nicotinic acid and
     nicotinamide is by the formation of N-
     methylnicotinamide  N-methyl-2-pyridone-5-
     carboxamide and N-methyl-4-pyridone-3-carboxamide
      -- nicotinuric acid = glycine peptide of nicotinic acid
            ---> additional metabolite

- Preparations:
  * Niacin (nicotinic acid, 3-pyridinecarboxylic acid) –stable
       to heat, oxidation and light
    -- Niacin tablets and capsules =25 – 500mg
    -- Niacin injection = 50 or 100mg/ml.
  * Niacinamide (nicotinamide, nicotinic acid amide)
    -- tablets = 50 – 500mg        -- injection 100mg/ml.
- Treatment for nicotinic acid def.:
   * niacin, nicotinamide and their derivatives – used for
      prophylaxis and treatment of pellagra
        -- acute exacerbation of pellagra  therapy must be
             intensive
           recommended oral dose = 50mg given up to 10x
             daily
           oral medication is impossible = 25mg I.V.
             injection is given 2 or more times/day
        -- Two metabolic disorders through which pellagra
             may occur:
           Hartnup’s disease => defective intestinal and
                renal transport of tryptophan
 patients with carcinoid tumors => large amounts of
  tryptophan are utilized by the tumor for the
  synthesis of 5-hydroxytryptophan and 5-hydroxy-
  tryptamine (serotonin)
PYRIDOXINE (B6):
 - active forms of B6 --- pyridoxal phosphate
                      --- pyridoxamine phosphate
 - pyridoxal is converted to pyridoxal phosphate by the
     enzyme pyridoxal kinase
 - antimetabolites to pyridoxine :
    * 4-deoxypyridoxine = most active antimetabolite of
      pyridoxine attributed to formation in vivo of 4-
      deoxypyridoxine-5-phosphate which is a competitive
    inhibitor of several pyridoxal phosphate-dependent
    enzymes
* Isonicotinic acid hydrazide (isoniacid) combines with
    pyridoxal or pyridoxal phosphate to form hydrazone 
    potent inhibitor of pyridoxal kinase
     enzymatic reactions to which pyridoxal phosphate
        is a co-enzyme are also inhibited
Vitamin K
 Function: participates in the posttribosomal
            modification of prothrombin and
            factors VII, IX, and X


  Source: Fat-soluble substances found
          primarily in leafy green vegetables
        : Synthesized by bacteria that
          colonize the human intestine
     HEMATINICS
Vit B12, Folic Acid, Iron
       And Vit K
Absorption of Vit K
    - both Vit K1 & 2 require bile salts for absorption
      from the intestinal tract
Availability of Vit K
  • K1 = clinically available in 5mgs tablets and
          50mgs ampules
       = effect  delayed for 6 hrs but is complete
          is complete when tx depression of
          prothrombin activity by x’s warfarin
          or Vit K deficiency
Forms of Vitamin K
  • Two Natural Forms
     * Vit K1 – found in food
                 known as phytonadione
     * Vit K2 – found in human tisues
               - synthesized by intestinal bacteria
               - known as menaquinone
  • Water – soluble form
      * Vit K3 - known as menadione
                - never used in therapeutics =
                  ineffective in the tx of warfarin
                  overdose
     I.V. adm. Of Vit K1should be slow => rapid
        infusion can produce dyspnea, chest and
        back pain and even death
     Vit K1= currently adm. to all newborns
                i.e. prevent the hemorrhagic disease
                  of Vit K deficiency – common in
                  premature infants
Occurrence of Vit K deficiency
  • hospitalized patients in intensive care units
    because of poor diet
  • parenteral nutrition
  • recent surgery
  • multiple antibiotic therapy
  • uremia
* Non-response to Vit K  severe hepatic failure
     resulting from loss of protein synthesis and
     hemorrhagic diathesis
* Spontaneous bleeding – occurs in case of
   deficiency factor activity i.e. less than 5-10% of
   normal
     ** Factor VIII def. – classic hemophilia or
          hemophila B
  ** Factor Ix def- Christmas disease or hemophilia
                     B
                  accounts for most of the heritable
                   coagulation defects
Available preparation of Vit K –
   Phytonadione [K1] Mephyton, Aqua Mephyton,
   Konakione
   Oral- 5mgs tablets
   Parenteral: 2,10mgs/ml, aqueous colloidal
               solution or suspension for injection
Vit B12
  - serves as a cofactor for several essential
   biochemical reactions in human
- deficiency leads to:
 * anemia
 * GIT symptoms
 * neurologic abnormalities
-Vit B12 due to inadequate supply in the diet = rare
- common among older adults because of
   inadequate absorption in the diet easily
   treated
- Deoxyadenosyl cobalamine and
    methylcobalamine = active forms of Vit B12 in
    human
- Cyanocobalamine and hydroxocobalamine = avail
    able for therapeutic use
- ultimate source of Vit B12 is from microbial
    synthesis ---> from meat esp. liver, eggs and
    dairy products
- the vitamin is sometimes called extrinsic factor
    i.e. to differentiate it from intrinsic factor
        - protein normally secreted by the stomach
Pharmacokinetics of Vit B12 :
- ave. Vit B12 in the diet = 5-30 ug/day
  --->1-5ug of this ave. B12 in the diet is absorbed
- storage pool = 3000 – 5000 mcg for a normal adult
- normal daily requirement = about 2mcg.
- normal lost of the vit. in urine and stool = trace
    amount
- absorption of Vit B12 :
   … absorb only after it complexes with an intrinsic
      factor ---> a glycoprotein secreted by the
      parietal cells of the gastric mucosa
    i.e. intrinsic factors that is liberated from the
            dietary sources in the stomach and duodenum
            + B12  complex being absorbed
         --- B12-intrinsic factor complex is absorbed in
             the distal ileum by a highly specific receptor
             -mediated transport system
     - Deficiency of B12 in human:
:       * malabsorption of Vit B12 due to :
          ** lack of intrinsic factor
          ** loss or malfunction of the specific absorptive
             mechanism in the distal ileum
* nutritional deficiency is rare but is found among
    strict vegetarian after many years without meat,
    eggs and dairy products
- Distribution
  * absorbed Vit B12---> various cell of the body,
    bound in the plasma glycoprotein,
    transcobalamin II --- > x’s stored in the liver

Pharmacodynamics:
- Vit. B12 plays an impt. role in two essential
   enzymatic rxns. in human
  > Methyl transfer- methylcobalamine serve as
 intermediate in the transfer of a methyl group
   i.e. N5 –methylhydrofolate to homocysteine
      forming methionine
1. W/o B12 conversion of the major dietary and
   storage folate, N5 – methylhydrofolate to
   tetrahydrofolate => the precursor of folate
    cofactor, cannot occur
    def. of folate cofactors necessary for
     several biochemical reactions involving the
     transfer of one-carbon group develops
     ---> particularly the depletion of tetrahydrofolate
          prevents synthesis of adequate supplies of the
          deoxythymidilate (dTMP) and purines
   ---> necessitated for DNA synthesis in rapid
           dividing cells
2. The accumulation of folate as N5 –
   methyltetrahydrofolate and the associated
   depletion of tetrahydrofolate cofactors in B12
   def referred to as METHYLFOLATE TRAP
   ---> this biochemical step linked B12 and folic
       acid metabolism
   ---> explains why megaloblastic anemia of B12
        def. can be corrected by relatively large
        amount of folic acid intake
* Folic acid    reduce         dihydrofolate
                             dihydrofolate
                              reductase
> the other enzymatic reaction:
 - Isomerization of L-Methyl malonyl – CoA to succinyl –
      CoA by methylmalonyl - CoA mutase
                                   deoxyadenosylcobalamin
    i.e. L -methylmalonyl -CoA isomerization succinyl-CoA
                               methylmalonyl- CoA
                                                  mutase
        * B12 deficiency - the reaction cannot take place
        * methylmalonate -CoA accumulates
* Manifestation of B12 deficiency
   ** megaloblastic anemia – caused either by B12 or folic
         acid deficiency
      -- assessed by measuring serum levels of the vitamins
      -- Shilling test – measures absorption and excretion
             of radioactively labeled B12 ---> further define
             mechanism of B12 malabsorption
 * common causes of B12 deficiency :
        > pernicious anemia – defective secretion of
          intrinsic factor
        > partial or total gastrectomy affecting the distal
            ileum such as malabsorption syndrome,
            inflammatory bowel disease or small bowel rxn.
> Rare causes of B12 deficiency:
    … bacterial overgrowth of the small bowel
    … chronic pancreatitis
    … thyroid disease
    … secondary to congenital deficiency of intrinsic
        factor
    …congenital selective B12 malabsorption due to
       defective receptor sites in the distal ileum
* Tx of B12 deficiency
  > parenteral injections of B12 are required for therapy –
      since deficiency is mainly caused by malabsorption
     … reversible diseases – underlying disease should be
    for 6 mos. before switching to monthly injections
… pernicious anemia – oral doses of 1000mcg/day
    sufficient for those who cannot tolerate injections
Vitamin D:
   - secosteroid produced in the skin from 7-
     dehydrocholesterol under the influence of
     ultraviolet irradiation
   - also found in certain foods
Forms of Vit D
  •Vit D2 –ergocalciferol = plant-derived form
                           = present in diets
                           = differ from the other
                             form as it contains a
                             double bond C22-23
                             and a methyl gp in
                            the side chain
      Vit D3 – cholecalciferol = natural form
Fxn of Vit D
 ° prohormone – serves as a precursor to number
      of biologically active metabolite
Fate of Vit D
    Vit D hydroxylated
                        in the liver
                  25(OH)D                          calcifediol
  kidney
                                       1,25(OH)2D calcitriol
                                       & 24,25(OH)2D


                                            Best studied
25(OH)D calcifediol             available
1,25(OH)2D calcitriol           for clinical use
• Calcipotriene (calcipotriol) – used to treat
      psoriasis
• Doxercalciferol and paricalcitol – tx secondary
      hyperthyroidism in patients with renal failure

Vit D metabolites ---> circulate in plasma

              bound with Vit D binding protein,
               -globulin
             i.e. 25(OH)D--->bound w/ high affinity
                & 24,25 )H)2D

               Vit D & 1,25(OH)2D--->bound with lower
                                   affinity
     Vit D and its Clinical Metabolites and Analogs

        Generic names               Abbreviation
Vit D3 : cholecalciferol     D3
Vit D2 : ergocalciferol      D2
25-Hydroxyvitamin D3:        25(OH)D3
  calcifediol
1,25-Dihydroxyvitamin D3     1,25(OH)2D3
   calcitriol

24,25-Dihydroxyvitamin D3:   24,25(OH)D3
  secalcifediol
Dihydrotachysterol           DHT
Calcipotriene (calcipotriol)   none

1-hydroxyvitamin D2:          1(OH)D2
 doxercalciferol
19-nor-1,25-                   19-nor-1,25-(OH)D2
Dihydroxyvitamin D2:
paricalcitol
Elimination of Vit D
  - Clearance of Vit D from the blood = rapid
  - Metabolic clearance of calcitriol in human =
         rapid turnover with a terminal half-life
         measured in hours
  -1,25(OH)2D analogs since bound poorly by Vit D
        binding proteinclearance is very rapid with
        terminal half-life measured in minutes hence:
          * calcitriol will have little hypercalciuric and
              hypercalcemic effect
          * iimpt. in the management of conditions such as
              psoriasis
  - liver = principal organ for clearance
  - x’s Vit D is stored in adipose tissue
Mech. Of Action of Vit D
 • Calcitriol – most potent agent with respect to
                stimulation of intestinal clcium and
                phosphate transport and bone
                resorption
     * acts on the intestine both by:
        ** induction of new proteins e.g.ca2+
           binding protein
        ** modulation of ca2+ flux across the brush
           border and basolateral membranes by a
           means that does not require new protein
           synthesis
       ** induces osteoclast differentiation factor in
 osteoblast and proteins such as osteoclcin 
 regulates the minerlization process
• Metabolites 25(OH)D and 24,25(OH)2D = far less
    potent stimulators of intestinal ca2+ and
    phosphate transport or bone resorption
• 25(OH)D > 1,25(OH)2D in potency regarding
    stimulation of renal reabsorption of ca2+ and
    PO43--->major metabolite regulating ca2+ flux
    and contractility of muscle
• 24,25(OH)2D – stimulates bone formation
• Specific receptors for 1,25(OH)2D exist in target
   tissues such as: bone, gut and kidney
  1,25(OH)2D regulates the ff:
   * secretion of PTH from the parathyroid gland
   * insulin secretion from the pancreas
   * cytokine production by macrophages and T cells
   * proliferation and differentiation of large number
      of cells including cancer cells
Regulation of Vit D involves:calcium
                             phosphate,
                             variety of hormones-
                               PTH = most important

Vit D deficiency- condition known as rickets
        - recognized among pediatric and geriatric
          population on:- vegetarian diet
                         - reduced sunlight exposure
Treatment of Vit D Deficiency:
   - To avoid development of rickets = daily intake of
      400 units of Vit D
   - With a developed ricket = take 4000 units of
       Vit D/day
       = diet should contain adequate calcium and
         phosphate

Two types of Vit D dependent rickets : distinctly
  different autosomal recessive diseases present as
  childhood rickets and does not respond to
  conventional doses of Vit D
 Type I Vit D dependent ricket
       – due to isolated deficiency of 1,25(OH)2D
           production caused by mutations in the 25
           (OH)D 1-hydroxylase
        - serum levels of 1,25(OH)2D is not very
           high
        - tx: 4000units Vit D/day
             or calcitriol 0.25-0.5 ug daily
Type II Vit D dependent ricket
      - cause by a target tissue defect in response
          to 1,25(OH)2D
      - number of point mutation were observed in the
          gene for the 1,25(OH)2D receptor, which
       disrupt the fxn of the receptor--->resulting to this typeII
       syndrome
- serum level of 1,25(OH)2D are very high
- tx: large doses of calcitriol  effective to restore
      normocalcemia
Available Preparations of Vit D, Metabolites and Analogs
 * Calcifediol – Calderol
    oral : 29,25 ug capsules
 * Calcitriol –
    oral - Rocaltrol : 0.25, 0.5 ug capsules
    parenteral – Calcijex : 1, 2 ug/mg for injection
 *Cholecalciferol [D3] – Vitamin D3 , Delta D
    oral : 400, 1000 IU tablets
 * Dihydrotchyterol [DHT] – DHT, Hytakerol
    oral : 0.125 mg tablets, capsules
           0.2- 0.4 mg tablets
           0.2 mg/ml intensol sol’n
          0.25 mg/ml sol’n in oil
* Doxercalciferol – Hectoral
     oral : 2.5 mg capsules
 * Ergocalciferol [D2] – Vit D2 , Calciferol, Drisdol
    oral : 50,000 IU tablets, capsules
             8,000 IU/ml drops
    parenteral : 500,000 units/ml for injection
 * Paricalcitol – Zemplar
    parenteral : 5ug for injection

Ref. Katzung: Basic and Clinical Pharmacology
     10th ed., p-750

				
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