Toxicology 1 (Management, Chelators, Lead)

Question 1

SUPPORTIVE CARE of poisoned patient (A-G)

Answer 1

A Airway protection B (breathe) Oxygenation/ventilation C (cardiac issues) Treatment of arrhythmias D HemoDynamic support E (Epilepsy) Treatment of seizures F (farenheit) Correction of temperature abnormalities G (Gap) Correction of metabolic derangements H Prevention of secondary complications

Question 2

GI decontamination methods (7)

Answer 2

1.) Induction of emesis 2.) Gastric lavage -If necessary protection of airway by endotracheal tub 3.) Activated Charcoal 4.) Whole bowel irrigation (with balanced polyethylene glycol-electrolyte solution) 5.) Catharsis (with laxative agents) 6.) Dilution 7.) Endoscopic/surgical removal

Question 3

How to induce emesis

Answer 3

1.) Syrup of ipecac 2.) Apomorphine

Question 4

Which patients do we not induce emesis?

Answer 4

1.) unconscious patient 2.) poisoned with corrosive agents (acid, base) 3.) poisoned with petroleum distillate 4.) poisoned with convulsants

Question 5

Which patients do we do not do a gastric lavage?

Answer 5

1.) Poisoned with corrosive agents (acid, base) 2.) Poisoned with convulsants

Question 6

Decontamination of other sites (3)

Answer 6

1.) Eye decontamination (for at least 20 minutes) 2.) Skin decontamination 3.) Body cavity evacuation

Question 7

Enhancement of poison elimination (7)

Answer 7

1.) Multiple-dose activated charcoal (gut dialysis) 2.) Forced diuresis (infusion, loop diuretics) 3.) Alteration of urinary pH -Excretion of weak acids increased if the urine if more basic (NaHCO3) -Excretion of weak base increased if the urin is more acidic (NH4Cl infusion) 4.) Chelation (see heavy metal section) 5.) Neutralization 6.) Extracorporeal removal 7.) Hyperbaric oxygenation

Question 8

Neutralization therapy (4)

Answer 8

1.) Alkali-therapy (5% NaHCO3, 2% Na lactate) 2.) Specific antitoxins 3.) Osmotherapy (10-20% NaCl, 40% glucose) 4.) Neutralization by antibodies

Question 9

Extracorporeal removal

Answer 9

1.) Peritoneal dialysis 2.) Hemodialysis

Question 10

What are chelators? When to give them?

Answer 10

Flexible molecules with electronegative groups (OH, SH, NH) which bind cavalently the cationic metal atoms (even Ca2+ or Zn2+ or Cu2+) Administer them as quick as possible High affinity, high solubility

Question 11

Dimercaprol (BAL) used for?

Answer 11

Used for acute arsenic and mercury and severe lead poisoning (in this later case together with EDTA)

Question 12

Dimercaprol (BAL) pharmacokinetic characteristic

Answer 12

• not stabile in water, dispensed in peanut oil - given always im. !!! - good permeability, binds intracellulary located cations - excretion by kidney

Question 13

Dimercaprol (BAL) Adverse effects

Answer 13

-nausea, vomiting, hypertension, tachycardia, fever -pain at the site of injection -increased secretions (rhinorrhea, lacrimation, salivation)

Question 14

Succimer (DMPS) is similar to which drug?

Answer 14

Water soluble form of dimercaprol

Question 15

Succimer (DMPS) use

Answer 15

1.) Acute arsenic 2.) Acute mercury (effective only for some hours after intoxication) 3.) Lead poisoning

Question 16

Succimer (DMPS) Pharmacokinetic characteristic

Answer 16

Pharmacokinetic characteristic - oral administration (DMPS also parenterally) - moderate intracellular distribution /less adverse effect - faster excretion

Question 17

Succimer (DMPS) Adverse effects

Answer 17

Adverse effects — better tolerated than dimercaprol 1.)nausea, vomiting, diarrhea 2.) mild / moderate neutropenia

Question 18

Pencillamine similar to which drug?

Answer 18

water soluble derivative of penicillin, orally administered

Question 19

Pencillamine used for?

Answer 19

Used for 1.) Copper intoxication or to prevent copper accumulation (Wilson’s disease) 2.) Rheumatoid arthritis 3.) Cystinuria

Question 20

Pencillamine Adverse effects

Answer 20

-hypersensitive reactions -in case of long-term treatment autoimmune reactions -B6 vitamin depletion leading to peripheral neuropathy

Question 21

Chelator drugs

Answer 21

1.) Dimercaprol 2.) Succimer 3.) Penicillamine 4.) Trientine 5.) Edetate Calcium Disodium 6.) Deferoxamine 7.) Deferasirox

Question 22

Trientine is used for?

Answer 22

Used for copper intoxication (Wilson’s disease) in case of penicillamine allergy

Question 23

Edetate calcium disodium (EDTA) used for?

Answer 23

Used for lead poisoning (binds other cations as well)

Question 24

Pharmacokinetic characteristic of EDTA

Answer 24

• no absorption from the GI, but even may enhance the absorption of lead (administration slow iv. infusion) - distribution in the extracellular compartment - fast excretion by kidney (glomerular filtration) *contraindicated in anuria

Question 25

Adverse effect of EDTA

Answer 25

Nephrotoxic (rare)

Question 26

Deferoxamine is used for?

Answer 26

1.) Iron poisoning 2.) Hemosiderosis 3.) Thalassemia 4.) Aluminum toxicity in kidney failure

Question 27

Deferoxamine and deferasirox pharmacokinetic

Answer 27

Deferoxamine - no absorption from the GI (administration iv. or im.) - excretion by kidney and partly by the bile Deferasirox -oral

Question 28

Deferoxamine adverse effects

Answer 28

1.) idiosyncratic reactions 2.) acute respiratory distress syndrome 3.) neurotoxic (long term)

Question 29

Form of lead entering the body

Answer 29

Inorganic lead oxides and salts organic (tetraethyl lead)

Question 30

Most frequent source of lead intoxication

Answer 30

-occupation, environmental, antiknock agent in gasoline (organic)

Question 31

Major route of absorption of lead

Answer 31

-respiratory and GI tract, skin (organic) -absorption from GI ~ 10% , in children 40% -enhanced in case of reduced Fe or Ca intake

Question 32

Lead distribution

Answer 32

Distribution first it bounds to erythrocytes 99% and then soft tissues. Finally it redistributes in the bones. Lead crosses the placenta.

Question 33

Where is Lead eliminated in the body? Half life? What speeds up the half life?

Answer 33

• Elimination via kidney (minor elimination via sweat and feces)
• Elimination half life from tissues takes 1-2 months and 20-30 years
• Mobilization from bone enhances in cases of
  
  • Hyperthyroidism
  • prolongued immobilization
  • pregnancy, during lactation
  • In postmenopause

Question 34

Pharmacodynamics of Lead

Answer 34

• Inhibits enzymes via sulfhydryl binding
• Interferes with action of cations like Ca, Fe, Zn
• Alters the structure of membranes and receptors

Question 35

Major clinical effects of lead in acute and sub chronic?

Answer 35

• Acute
  
  • Acute intoxication is rare and difficult diagnosis
  • encephalopathy, colic, hemolytic anemia
• Subchronic
  
  • Non-specific symptoms like flu, myalgia, abdominal cramps, arthralgia, and headache

Question 36

Chronic clinical effects of lead in blood

Answer 36

• Blood
  
  • lead interferes with heme synthesis by inhibiting the incorporation of Fe into Protoporphyrin
  • Increases the membrane fragility of erythrocytes (in higher dose) leading to hemolysis in case of high exposure
    
    • Leading to anemia and appearance of basophils can stippling (diagnostic clue)

Question 37

Chronic clinical effects of lead in nervous system (in children and adults)

Answer 37

• Nervous system
  
  • In children
    
    • Minimal brain dysfunction (inhibition of NMDA receptors?)
    • Subclinical deficit in cognitive function
    • Decreased hearing acuity
  • In adults
    
    • Slowed reaction time, insomnia, anorexia, irritability
    • Weakness of extensors (month or years after high dose exposure)

Question 38

Chronic clinical effects of lead in GI system

Answer 38

• GI system
  
  • In smaller dose
    
    • Loss of appetite, constipation
  • In higher dose
    
    • Bouts of abdominal pain ‘Lead colic’
    • Gingival lead lines- deposits of lead sulfides

Question 39

Chronic clinical effects of lead in Kidney

Answer 39

• Kidney
  
  • High doses
    
    • Intersititial fibrosis and nephrosclerosis (even after years)
  • Uric acid exertion decreases (symptoms of gout occurs)

Question 40

Chronic clinical effects of lead in cardiovascular system

Answer 40

Hypertension

Question 41

Therapy of Lead intoxication (acute and chronic)

Answer 41

• Acute treatment
  
  • Supportive care
  • CaNa₂EDTA- infusion (or IM) for 5 days
  • Afterwards oral succumbed or penicillamine
• Oral chelators