Toxicology 1 (Management, Chelators, Lead) Flashcards
SUPPORTIVE CARE of poisoned patient (A-G)
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
GI decontamination methods (7)
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
How to induce emesis
1.) Syrup of ipecac 2.) Apomorphine
Which patients do we not induce emesis?
1.) unconscious patient 2.) poisoned with corrosive agents (acid, base) 3.) poisoned with petroleum distillate 4.) poisoned with convulsants
Which patients do we do not do a gastric lavage?
1.) Poisoned with corrosive agents (acid, base) 2.) Poisoned with convulsants
Decontamination of other sites (3)
1.) Eye decontamination (for at least 20 minutes) 2.) Skin decontamination 3.) Body cavity evacuation
Enhancement of poison elimination (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
Neutralization therapy (4)
1.) Alkali-therapy (5% NaHCO3, 2% Na lactate) 2.) Specific antitoxins 3.) Osmotherapy (10-20% NaCl, 40% glucose) 4.) Neutralization by antibodies
Extracorporeal removal
1.) Peritoneal dialysis 2.) Hemodialysis
What are chelators? When to give them?
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
Dimercaprol (BAL) used for?
Used for acute arsenic and mercury and severe lead poisoning (in this later case together with EDTA)
Dimercaprol (BAL) pharmacokinetic characteristic
- not stabile in water, dispensed in peanut oil - given always im. !!! - good permeability, binds intracellulary located cations - excretion by kidney
Dimercaprol (BAL) Adverse effects
-nausea, vomiting, hypertension, tachycardia, fever -pain at the site of injection -increased secretions (rhinorrhea, lacrimation, salivation)
Succimer (DMPS) is similar to which drug?
Water soluble form of dimercaprol
Succimer (DMPS) use
1.) Acute arsenic 2.) Acute mercury (effective only for some hours after intoxication) 3.) Lead poisoning
Succimer (DMPS) Pharmacokinetic characteristic
Pharmacokinetic characteristic - oral administration (DMPS also parenterally) - moderate intracellular distribution /less adverse effect - faster excretion
Succimer (DMPS) Adverse effects
Adverse effects — better tolerated than dimercaprol 1.)nausea, vomiting, diarrhea 2.) mild / moderate neutropenia
Pencillamine similar to which drug?
water soluble derivative of penicillin, orally administered
Pencillamine used for?
Used for 1.) Copper intoxication or to prevent copper accumulation (Wilson’s disease) 2.) Rheumatoid arthritis 3.) Cystinuria
Pencillamine Adverse effects
-hypersensitive reactions -in case of long-term treatment autoimmune reactions -B6 vitamin depletion leading to peripheral neuropathy
Chelator drugs
1.) Dimercaprol 2.) Succimer 3.) Penicillamine 4.) Trientine 5.) Edetate Calcium Disodium 6.) Deferoxamine 7.) Deferasirox
Trientine is used for?
Used for copper intoxication (Wilson’s disease) in case of penicillamine allergy
Edetate calcium disodium (EDTA) used for?
Used for lead poisoning (binds other cations as well)
Pharmacokinetic characteristic of EDTA
- 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
Adverse effect of EDTA
Nephrotoxic (rare)
Deferoxamine is used for?
1.) Iron poisoning 2.) Hemosiderosis 3.) Thalassemia 4.) Aluminum toxicity in kidney failure
Deferoxamine and deferasirox pharmacokinetic
Deferoxamine - no absorption from the GI (administration iv. or im.) - excretion by kidney and partly by the bile Deferasirox -oral
Deferoxamine adverse effects
1.) idiosyncratic reactions 2.) acute respiratory distress syndrome 3.) neurotoxic (long term)
Form of lead entering the body
Inorganic lead oxides and salts organic (tetraethyl lead)
Most frequent source of lead intoxication
-occupation, environmental, antiknock agent in gasoline (organic)
Major route of absorption of lead
-respiratory and GI tract, skin (organic) -absorption from GI ~ 10% , in children 40% -enhanced in case of reduced Fe or Ca intake
Lead distribution
Distribution first it bounds to erythrocytes 99% and then soft tissues. Finally it redistributes in the bones. Lead crosses the placenta.
Where is Lead eliminated in the body? Half life? What speeds up the half life?
- 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
Pharmacodynamics of Lead
- Inhibits enzymes via sulfhydryl binding
- Interferes with action of cations like Ca, Fe, Zn
- Alters the structure of membranes and receptors
Major clinical effects of lead in acute and sub chronic?
- Acute
- Acute intoxication is rare and difficult diagnosis
- encephalopathy, colic, hemolytic anemia
- Subchronic
- Non-specific symptoms like flu, myalgia, abdominal cramps, arthralgia, and headache
Chronic clinical effects of lead in blood
- 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)
Chronic clinical effects of lead in nervous system (in children and adults)
- 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)
- In children
Chronic clinical effects of lead in GI system
- 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
- In smaller dose
Chronic clinical effects of lead in Kidney
- Kidney
- High doses
- Intersititial fibrosis and nephrosclerosis (even after years)
- Uric acid exertion decreases (symptoms of gout occurs)
- High doses
Chronic clinical effects of lead in cardiovascular system
Hypertension
Therapy of Lead intoxication (acute and chronic)
- Acute treatment
- Supportive care
- CaNa2EDTA- infusion (or IM) for 5 days
- Afterwards oral succumbed or penicillamine
- Oral chelators
