Chelating Agents Mbbs

Chelation" root word, "chele" Greek for the claw of a lobster or crab. 

Chelating Agents[claw] People exposed to heavy metals in

the environment-occupational Metallic contamination of food and water-Ind.pollutants Metals leached from eating utensils and cookware. Toys Pesticides and therapeutic agents Burning of fossil fuels containing heavy metals*

Heavy metals combine with

reactive groups essential for normal physiological functions. “Heavy-metal antagonists possess the common ability to form complexes with heavy metals and thereby prevent or reverse the binding of metallic cations to body ligands.” Complex soluble & non toxic These drugs are chelating agents.*

An ideal chelating agent High solubility in water: Distribution Resistance to biotransformation. Th.efeciency Reach sites of metal storage Form nontoxic complexes with toxic metals Retain chelating activity at the pH of body fluid Ready excretion of the chelat A low affinity for Ca2+ also is desirable The most important property of a therapeutic

chelating agent is greater affinity for the metal than that of the endogenous ligands*

Dimercaprol[British anti-lewisite (BAL)]  Developed as antidote to “Lewisite”.  Chemistry: Oily fluid with a pungent, disagreeable

odor  MOA: Formation of chelation complexes between its sulfhydryl groups and metals.  1:1 with metal not stable. 2:1 stable  More effective in preventing inhibition of sulfhydryl enzymes than in reactivating them.

Uses of BAL I.m. not oral As, Hg, Pb, Au, Bi, Ni, Poisoning Adjuvant in Pb poisonong Adjuant in Cu poisoning C.I. in Fe, Cadmium  ADE: rise BP, Tachycardia, vomiting, tingling,

inflammation of m.m. 2mg/kgx2d. OD 10 d. C.I.Organic or elemental Succimir: Similar to BAL [Dimercatosuccinic acid] *

Edetate Calcium Disodium (CaNa2EDTA)  EthyleneDiamineTetraAcetic acid (EDTA) →

Na2EDTA →cation used to make a water-soluble salt of EDTA →hypocalcemic tetany → “Edetate calcium disodium (CaNa2EDTA)”

 Chelates Pb, Zn, Cd, Mn, Cu and some

radioactive metals  Exchanges with Ca.  Not orally absorbed  i.m., Does not cross BBB*

[CaNa2EDTA]

Uses:

 Lead poisoning- MOST IMP USE  Not in Hg → Hg is bound in inaccessible regions.  Chelation therapy with CaNa2EDTA for

atherosclerotic plaque → without therapeutic rationale ADE:  NO TETANY  Anaphylactoid reaction  Acute febrile  Tubular necrosis*

Penicillamine:

Isolated in 1953 from

the urine of patients receiving penicillin. Uses. Cu, Hg, Zn, Pb poisoning.

Penicillamine uses contd…

Wilson’s disease[Hepatolenticular

degenaration] → Cerulospasmin is deficient → cu accumulates in liver, basal ganglion → life long therapy → 0.5g orally before food. [Trientine is the alternate drug]. Cystin stones. Scleroderma → increases soluble collagen. Rh.Arthritis.*

Deferoxamine[Desferioxamine]

Isolated as the iron chelate from

Streptomyces pilosus Poorly absorbed orally i.v. for acute poisoning, i.m. for chronic(e.g., thalassemia along with blood) Life saving-children Does not affect Fe in Hb.*

ADE; histamine release,

allergic reactions, fall in B.P., urticaria. Iron-BAL complex toxic Deferiprone: orally effective iron chelator, less effective*

Others

Unithol: water soluble analog of

Dimercaprol Deferasirox: orally effective against Fe Prussian blue: Against radioactive Cesium “DIRTY BOMB”*

Oxytocin is most effective in stimulating the uterus during A.  I trimester

II Month of pregnancy C. II Trimester D. III Trimester B.

 Ans: D

Oxytocin usually administered by following route: Orally C. Intravenously D. Sublingually E. All of the above  Ans: B B.

Oxytocin has a half life of 4-6minutes C. 40-60 minutes D. 1-2hours E. 90 minutes  Ans: A B.

Overdose of oxytocin may result in

B. Water intoxication C. Fetal anoxia D. Rupture of the uterus E. All of the above  Ans: D

Which of the following IS NOT true of Oxytocin It is as potent as Vasopressin in antdiuretic activity C. It can not be given orally D. It stimulates milk ejection reflex in humans E. Has greatest pharmacological value in elective induction of labour  Ans: A B.

D.O.C to Lead poisoning is C. BAL D. Penicillamine E. CaNa2Edetate F. Deferoxamine  Ans: C

Chelating agent that can reactivate sulfahydryl groups is B.

CaNa2Edetate

Dimercaprol D. Penicillamine E. All of the above C.

 Ans: B

Chelating agent that produces tetany unless given in Ca chelate form is

B. Na2Edetate C. Dimercaprol D. Penicillamine E. Deferoxamine  Ans: A.