Heavy Metal Pharmacology And Treatment

Front 1

Lead
Chemical forms and sources

Back 1

Forms:
- inorganic (lead salts)
- organic (tetraethyl lead in gas)

Sources:
- Environment
- Workplace
- Homes (pipes and paint)

Front 2

Arsenic
Chemical forms and sources

Back 2

Forms:
- inorganic (As3+ and As5+)
- organic
- arsine gas

Sources:
- Smelting
- manufacture of pesticides and herbicides
- WATER

Front 3

Cadmium
Chemical forms and sources

Back 3

Forms
- inorganic
- elemental

Sources
- Melting
- Industry (batteried, solders, photo chemicals)

Front 4

Mercury
Chemical forms and sources

Back 4

Forms:
- Elemental
- Inorganic
- Organic

Sources
- thermometers and dentalamalgams -- elemental
- industry - inorganic
- fish - organic

Front 5

Lead
Pharmacokinetics

Back 5

- inorganic lead absorbed through GI and inhalation
- organic lead absorbed through skin
- GI absorption much greater in kids
- most lead stored in bones, 4% in soft tissue and 1% in blood
- crosses BBB and placenta
- fecal and renal elimination

Front 6

Lead
Mechanisms of toxicology

Back 6

- divalent cation - substitutes for polyvalent cations in the body
- inhibits heme synthesis (blocks delta-ALAD, buildup of ALA) - reduced heme --> anemia and cell respiration
- increased ALA --> neurotoxin
- inhibits ferrochelatase --> prevents maturations of RBCs
- binds calmodulin and activates signaling cascades
inhibits activity at NMDA receptors

Front 7

Lead
Symptoms

Back 7

Adults:
- basophilic stippling
- microcytic anemia
- bilateral wrist drop

Kids
- hyperactivity
- attention deficits
- lowered IQ
- Convulsions

Front 8

Lead
diagnosis
treatment

Back 8

Diagnosis
- symptoms
- blood lead levels
- levels of EP for adulta

Treatment
- prevention
- remove source
- chelation if acute

Front 9

Arsenic
Pharmacokinetics

Back 9

- inorganic absorbed through GI
- organic absorbed through lungs
- circulates bound to RBC's
- stored in soft tissue and fingernails
- half life is 3-5 days in the body
- excreted in urine, skin, and sweat

Front 10

Arsenic
mechanism of toxicity

Back 10

- As3+ binds sulfydryl and disulfide groups on enzymes --> impairs gluconeogenesis
- As5+ replaces phosphorus in ATP --> "uncouples" ox phos
- hypo and hypermethylates DNA --> alters DNA transcription
- oncogenic -- makes cells secrete growth factors and inhibits DNA repair

Front 11

Arsenic
symptoms

Back 11

Acute
- fatal
- throat constriction, abd pain, V?D, thirst, cardiac arrhythmia, coma, death

Chronic
- skin canter
- skin hyperpigmentation
- paresthesia in hands and feet
- Mee's lines

Arsine exposure
- abdominal pain
- bloody urine
- jaundice
- extensive hemolysis due to binding to hemoglobin

Front 12

Arsenic
diagnosis & treatment

Back 12

Diagnosis:
- proteinuria and ca2+in urine
- As levels in blood, urine and hair

treatment:

- remove source
- chelation for acute poisoning
- acute inhalation: fluid replacement and mechanical ventilation
- acute ingestion: emesis and gastric lavage
- intensive supportive care - blood transfusions and dialysis (arsine poisoning)

Front 13

Cadmium
Pharmacodynamics

Back 13

- main source in general population: cigarette smoke
- 15=50% of inhaled is absorbed
- binds albumin
- deposits in tissues bound to metallothionein
- stored in KIDNEY, liver, pancreas, prostate
- half life in body is 20-30 years
- renal excretion

Front 14

Cadmium
mechanism of toxicity

Back 14

- binds -SH groups
- competes with Zn2+ and Ca2+
- binds kidney glomerulus - proximal tube dysfunction

Front 15

Cadmium
symptoms

Back 15

Acute toxicity
- "metal fume fever"
- respiratory dysfunction

Chronic toxicity
- nephrotoxicity
- bone disorders - osteoporosis, "ouch-ouch" disease
- respiratory dysfunctions
- carcinogenesis

Front 16

Cadmium
Diagnosis and Treatment

Back 16

Diagnosis
- proteinuria, Ca2+ in urine
- Cd levels in urine and blood

Treatment
- remove source/prevention
- chelation, gastric lavage, emesis for acute toxicity
- supportive therapy

Front 17

Mercury
pharmacokinetics

Back 17

- elemental mercury well absorbed by inhalation; fecal excretion
- inorganic mercury not well absorbed, complexes with glutathione and excreted in bile
- methylmercury almost completely absorbed through GI and crosses BBB; fecal excretion
- half life of methymercury is 65 days
- in brain: methylmercury and elemental mercury convert to inorganic mercury
-

Front 18

Mercury
mechanism of toxicity

Back 18

- in brain: methylmercury and c
- binds -SH groups
- disrupts membrane potentials
- alters protein synthesis
- blocks glutamate and aspartate uptake by astrocytes --> oxidative stress --> damage

Front 19

Elemental mercury toxicity

Back 19

Acute:
- similar to Cd "metal fume fever" - flue like + metal taste
- Stomatits, lethargy, pulm complications
- "pink disease - acrodynia: pink rash on exremities, pruritis, paresthesia and pain

Chronic: triad
1. tremors
2. gingivitis
3. erethism

Front 20

Inorganic mercury toxicity

Back 20

primarily affect the renal cortex

Acute
- mouth issues (grey membranes, gingivitis, bad breath, etc)
- renal failure --> proteinuria

Chronic toxicity
- renal failure
- GI symptoms

Front 21

Methylmercury toxicity

Back 21

affects the CNS

No acute toxicity

Chronic:
- neuro symptoms
- developing brain is very sensitive to methylmercury --> congenital minamata disease

Front 22

Mercury
Diagnosis and Treatment

Back 22

Diagnosis
- symptoms
- Hg in hair, nails, urine, blood

Treatment
- remove source
- supportive care
- chelation for acute

Front 23

Chelation therapy

Back 23

- specific
- not dissociate at low pH
- effective orally
- penetrates tissues and storage sites
- effective removal route (renal)
- high therapeutic index

Front 24

BAL

Back 24

Chelation for
- Pb
- inorg Hg
- As

- given IM

Front 25

EDTA (combined with BAL)

Back 25

Chelation for Pb

given IV or IM

Front 26

D-Penicillamine

Back 26

Chelation for Pb

given orally

Front 27

Succimer (DMSA)

Back 27

Chelation for
- Pb
- Hg
- As

given orally

Front 28

dithiocarbamate

Back 28

cheletion for Cd

given IM