4. Pharmacology of chelators

Question 1

What are chelators?

Answer 1

Organic compounds with 2 or more electronegative groups that form stable bonds with metal atoms, stable complexes lack the toxicity of the free metals and often are excreted readily.

Question 2

How is the pharmacokinetic characteristics of Dimercaprol?

Answer 2

1. Its not stabile in water, dispensed in peanut oil. given always im. good permeability. excretion by kidney (6-8 hours)
2. oral administration (DMPS also parenterally) - moderate intracellular distribution/less adverse effect - faster excretion.

Question 3

Therapeutical indication of Dimercaprol?

Answer 3

1. acute arsenic and inorganic mercury(effective only for some hours after intoxication)
2. gold
3. bismuth
4. antimony
5. severe lead intoxication (together with NaCaEDTA) (but not in encephalopathy)

Question 4

What are the adverse effects of Dimercaprol?

Answer 4

1. nausea
2. vomiting
3. hypertension
4. tachycardia
5. fever
6. pain
7. hematoma on the site if injection (thrombocytopenia, increased prothrombin time)

Question 5

Water-soluble analogs of dimercaprol

Answer 5

1. Unithiol and Succimer.
2. Both have higher therapeutic indices and have replaced dimercaprol in many settings!!!

Question 6

What is Succimer?

Answer 6

Water-soluble analog of dimercaprol

Question 7

What are the indications for EDTA Calcium Disodium (ethylenediaminetetraacetic acid, EDTA)?

Answer 7

Used for lead poisoning (binds other cations as well).

Question 8

What is Pencillamine (d-dimethylcysteine)?

Answer 8

Its a white crystalline, water-soluble derivative of penicillin.

Question 9

What are the indications for Deferoxamine?

Answer 9

Used for iron poisoning (hemosiderosis, thalassemia)

Question 10

How is the Pharmacokinetics of Succimer?

Answer 10

1. Oral administration (DMPS also parenterally).
2. Moderate intracellular distribution/less adverse effect.
3. Faster excretion

Question 11

What are the indications for the use of Succimer Therapy?

Answer 11

1. Acute arsenic and mercury (effective only for some hours after intoxication).
2. Lead poisoning but not in encephalopathy.

Question 12

What are the adverse effects accompanied with Succimer use?

Answer 12

• Adverse effects – better tolerated than dicaprol

Question 13

How is the pharmacokinetics of EDTA Calcium Disodium (ethylenediaminetetraacetic acid, EDTA)?

Answer 13

1. No absorption from the GI administration - slow iv. infusion.
2. Distribution only in the extracellular compartment.
3. Fast excretion by kidney (glomerular filtration).

Question 14

What are the indications for Pencillamine (d-dimethylcysteine)?

Answer 14

Chiefly for treatment of poisoning with copper or to prevent copper accumulation, as in Wilson’s disease.

Question 15

What are the adverse effects of Pencillamine (d-dimethylcysteine)?

Answer 15

Adverse effects happens in one third of patients receiving penicillamine. It causes hypersensitivity reactions which include rash, pruritus, drug fever (penicillin allergy). In these cases use Trientine in Wilson and hypersensitivity.

Question 16

How is the pharmacokinetics of Deferoxamine?

Answer 16

1. No absorption from the GI – administration iv. or im.
2. Excretion by kidney and partly by the bile - iron-chelator complex is excreted in the urine, often turning the urine an orange-red color.

Question 17

What are the adverse effects of Deferoxamine?

Answer 17

1. Idiosyncratic reactions
2. Acute respiratory distress syndrome (ARDS)
3. Neurotoxicity