Tutorial topic for MBBS

2. Heavy metals
80 metals in periodic table
They have corrosive & astringent properties
Acts as a protoplasmic poison by inhibiting essential enzyme
Ability to form complexes with important biological radical like
hydroxyl,Carboxyl,Keto,Sulfhydryl,disulphide,Amino, phosphate etc.
 Heavy metal poisoning is not uncommon
 Commonly implicated metals include- Pb, Hg, As,Cd

3. Drugs used to prevent heavy metal poisoning
Derived from Greek “Chele = Claws”
Chelation:- The process of an equilibrium reaction between a metal
ion & complexing agent what produce a stable, Non-ionized, Non-
toxic and water soluble complex which can be eliminated easily
Two or more reactive groups (ligands)
which can hold the metal from at least two sides so that a ring is formed

4.  Have two or more electronegative groups that forms stable
covalent bonds with the cationic metals
Chelating agents compete with body
Ligands for the heavy metals
 Clinical useful Chelating agents Affinity:-
↑↑ Affinity- Toxic metal
↓ ↓ Affinity- Calcium, body ligands

5. More affinity for metals than endogenous ligands
High solubility in water
Resistance to Biotransformation
Form non-toxic complex's with toxic metal
Cheap & easy to administered
Low affinity for Calcium
Easy excretion of chelating complex

6. Heavy metals
Cu,Fe,Mn,Pb
,Ca
Stable compound
Non-ionized , Non-metabolized
Non toxic
Water soluble
Chelating agents
Forming ring structure
Eliminated Via Kidney

7. Dimercaprol (BAL) & derivatives
EDTA derivatives -Disodium edetate, Calcium disodium edetate
 Calcium disodium DTPA (Diethylene triamine penta acetic acid)
Penicillamine
Desferrioxamine
Deferiprone

8. It is an oily, pungent smelling, viscous liquid
 Developed by Britisher during World War II as an Antidote for arsenic
containing war gases such as Lewisite
 Also called as British Anti-lewisite or BAL
 (-SH) group of BAL responsible for Chelation
 Analogue- 1.DMSA- (2,3 dimarcaptosuccinic acid )/ Succimer
2.DMPS-(2,3-Dimercapto-1-propanesulfonic acid)/ Unithiol

9. Mechanism:-
Form poorly dissociable complex with metal ions
Protect the SH enzymes
Prevent inhibition of enzyme
Pharmacokinetics:-
Can’t be given orally
Given by deep IM injection
t1/2-Short Peak plasma level in 1/2hrs -1 hr( IM)
Metabolized –liver glucuronide conjugated
 Excretion-As via urine (4-6hr)

10. Uses:-
 Poisoning by As(Acute & chronic), Hg, Bi, Au
Dose:- 5mg/kg stat, followed by 2-3 mg/kg every 4-8hrs × 2 days
and then BD ×10 days
# Alkalinisation of urine
 In lead poisoning:- As an adjuvant to Ca-Disodium edetate
 Wilson’s disease:- As an adjuvant to penicillamine

11.  Tachycardia, Hypertension
 Injection is painful and Chances of sterile abscess
 Allergic reaction
 Nausea, vomiting, headache
 Lacrimation, Conjuctivitis, Blepharospasm
 Sialorrhoea, muscle pain
(Antihistaminic given 30 min before injection )
Contraindication:-
 Iron & Cadmium poisoning

12. Water soluble analogue of dimercaprol
Advantage:-
- Less toxic
- orally effective
 Use- DOC for As,
 Also Hg, Pb poisoning.
 SE- Nausea, loose motion, Anorexia

13. 2,3-Dimercapto-1-propane-sulfonic acid
Water soluble analogue
Used orally and IV
Used in severe acute poisoning with As and Hg(Mercary)
IV-DMPS better efficacy over orally Succimer & IM-dimercaprol
Side effect-
Skin reaction

14. EDTA(Ethylene Diamine Tetra Acetic acid)
Chelates divalent or trivalent metals
invitro chelating agents
 Its is a disodium salt of EDTA
 Potent chelator of Ca
 Cause tetany on Iv injection (but not in slow infusion )-not preferred in Pb
poisoning
 Use:-
 Emergency control of hypercalcaemia
 Invitro anticoagulant
Disodium Edetate(Na2Edetate)

15. It is the calcium chelate of Na2 EDTA
Preferred over Na-edetate-Doesn’t deplete Ca++
Higher affinity for –Pb, Zn, Cd, Mn, Cu and some radio active metals
Mechanism:- Removes the metals by exchanging with Ca++
Higher ionized-not absorbed orally
Excretion-kidney
Iv route ,IM-route painful
No CNS penetration
USES:-
1.Pb-Poisoning:-preferred over Na2Edetate
2.Zn,Cu,Mn poisoning
Side effect:-
 Dose related kidney damage-
Toxic metal dissociate in tubule-
↑urine outflow
Chills, body ache,
Malaise,
Tiredness

16. Degraded product of Penicillin (β dimethyl cysteine)
(Cross reactivity with Penicillin)
Prepared by alkaline hydrolysis of benzyl penicillin
White crystalline, water-soluble having
strong Cu Chelating property
D-isomer –More potent than L-isomer (optic neuritis)
Pharmacokinetics:-
 Absorption- orally
 Metabolism-liver
 Peak plasma conc. In 1-3hr
 Excretion- urine & faeces

17. USES:-
-Wilson’s disease-
 An autosomal recessive disorder
 Deficiency of Ceruloplasmin, major Cu transport protein
 Absence of ceruloplasmin- Positive copper balance
 Cu deposition – liver, Substantia nigra, basal ganglia of brain
Rx-
-Cu-poisoning- DOC
-Hg poisoning- alternative drug to dimercaprol
-Cystinuria & cystine stones: It promotes the excretion of cysteine and prevents
its precipitation
-Scleroderma:- Penicillamine benefits by increasing soluble collagen

18. General toxicities:-
Headache, rash, fever, lymphadenopathy, dysguesia
Hematological toxicities
Aplastic anemia, agranulocytosis, thrombocytopenia
Autoimmune syndrome
Good pasture's Syndrome, Myasthenia Gravis
Others
Drug fever, polyarthritis, exfoliative dermatitis
Trientene:- Less potent but safer then d-penicillamine

19.  Obtained from streptomyces pilocus
 Chelator of iron
 Removes iron from hemosiderin and ferritin but not from haemoglobin and
cytochrome
M.O.A:-
Bind ferric iron to form ferrioxamine ( stable , water soluble)
P/K:-
Poorly absorbed after oral administration ,Used parenterally(IV/IM)
Uses:-
 Acute Iron toxicity:- in children DOC iv-desferioxamine
 Chronic iron poisoning(thalassaemia)- IM
 For chelation of aluminum in dialysis patient

20. A/E
Allergic reactions(pruritus, wheal, rash)
Dysuria, abdominal discomfort, diarrhoea
Cataract, neurotoxicity
Pulmonary syndrome
C.I
Renal disease
Pregnant women

21.  Orally effective but less effective then desferrioxamine
Use
 In patient in whom deferoxamine is C .I , unacceptable
or not tolerated
 Transfusion siderosis in thalasaemia
 Fe overload in liver cirrhosis
A/E
 Anorexia, Vomiting, Joint pain, Blood dyscrasia
 Dose 50-100mg/kg daily in 2-4 divided doses

22. Kkk
Drug Route of
Administrat
ion
Affinity for Uses C/I
BAL IM As As,Bi,Pb,Hg poisoning Fe,Cd
Na2Edetate I.v. Ca -Hypercalcemia
-an invitro anticoagulant
-
CaNa2Edetate Iv infusion Pb Pb,Zn, Mn, poisoning Hg poisoning
d-penicillamine Oral Cu -Wilson disease (Cu-
poisoning)
-Sceleroderma
-Cystinuria
desferioxamine IV,IM Fe Acute & chronic Fe poisoning Pregnancy,
Renal
insufficiency
Deferiprone Oral Fe Transfusion siderosis in
thalasaemia