Toxicity of the Lithium Ion - PowerPoint PPT Presentation

1 / 20
About This Presentation
Title:

Toxicity of the Lithium Ion

Description:

Hawley's Condensed Chemical Dictionary (12th Edn). Van Nostrand Rheinhold Company, New York. ... Occupational Medicine (3rd Edn)., St. Louis. ... – PowerPoint PPT presentation

Number of Views:144
Avg rating:5.0/5.0
Slides: 21
Provided by: toshi181
Category:
Tags: ion | lithium | toxicity

less

Transcript and Presenter's Notes

Title: Toxicity of the Lithium Ion


1
Toxicity of the Lithium Ion
  • Robyn Fullerton
  • Environmental Sciences Program
  • Southern Illinois University Edwardsville
  • ENVS531

2
Outline
  • I. Introduction/Background
  • II. Toxicity
  • III. Mechanism of Toxicity
  • IV. Treatments
  • V. Current Status

3
Introduction/Background
  • Compounds addressed
  • lithium aluminum hydride
  • lithium chloride
  • lithium carbonate
  • Sources of lithium
  • minerals
  • spodumene
  • petalite
  • lake brines

4
Introduction/Background
  • Common uses of lithium
  • manufacturing
  • ceramics and glass
  • batteries
  • 80 of lithium consumed
  • pharmaceuticals
  • major source of lithium toxicity
  • 13 of lithium consumed
  • treatment for acute mania and bipolar disorder

5
Toxicity
  • Acute (single-exposure)
  • typically mild
  • occurs when absorptive peak reached in patient
  • effects
  • gastrointestinal disturbances
  • vomiting, nausea, diarrhea, abdominal pain
  • neurological disturbances
  • fine tremors
  • sedation
  • mimics sodium deficiency

6
Toxicity
  • Acute (continuous intake)
  • occurs after build-up of lithium from a
    week/month of continuous intake
  • effects
  • gastrointestinal disturbances
  • profuse diarrhea and vomiting
  • cardiovascular system
  • arrhythmias, hypotension, and pulmonary edema

7
Toxicity
  • Acute (continuous intake)
  • effects, cont.
  • neurological disturbances
  • delirium, hyperreflexia, seizures, coma and death
  • persist for several days after poisoning
  • 10 of cases have irreversible effects
  • respiratory failure
  • nephrogenic diabetes

8
Toxicity
  • Chronic
  • teratogenicity
  • lithium freely crosses placental barrier
  • full equilibrium in maternal and umbilical cord
    blood
  • newborn plasma lithium levels identical to mother
  • diminishes quickly after birth

9
Toxicity
  • Chronic
  • transported via breast milk
  • milk/infant blood concentration 1/3 to 1/2 of
    maternal blood concentration
  • lower dose still harmful
  • lessened ability for detoxification
  • effects
  • cardiovascular defects
  • dextrocardia and aortic coarctation
  • Epsteins anomaly most common

10
Toxicity
  • Chronic
  • theories for teratogenic effects
  • longer half-life in infants
  • 68 hours for infants
  • 20 hours in adults
  • hormonal interaction
  • reduction in circulating thyroid hormone
  • altered growth hormone levels

11
Mechanism of Toxicity
  • Ingestion and absorption
  • rapidly absorbed from G.I. tract
  • appears in tissue fluid and organs within minutes
  • eight hours for complete absorption
  • peak concentration observed after 2-4 hours
  • distributed throughout body
  • initially in extracellular fluid
  • accumulates slowly in various tissues

12
Mechanism of Toxicity
  • Attack of target site
  • target central nervous system
  • carried via circulatory system to brain
  • can cross blood-brain barrier
  • cerebrospinal fluid concentration 40-50 of
    plasma concentration
  • no binding to plasma proteins
  • chemically intact at target site
  • important for transport across membranes

13
Mechanism of Toxicity
  • Transport across membranes
  • several hypotheses
  • similar to transport of sodium and potassium
  • monovalent cations
  • may substitute for sodium and potassium in
    transport processes
  • voltage-gated ion channels
  • allow sodium ions into cell
  • lithium ions replace sodium and cross membrane

14
Mechanism of Toxicity
  • Transport across membranes
  • direct active transport
  • utilizes ATPase
  • generates action potential and transmits nerve
    impulse
  • lithium displaces sodium in this process
  • can only support single action potential
  • affects nerve excitation, synaptic transmission,
    and neuronal metabolism

15
Mechanism of Toxicity
  • Manifestation of mechanism
  • lithium affects neurotransmitters in brain
  • inhibitory effect
  • norepinephrine
  • dopamine
  • stimulatory effect
  • serotonin
  • superstimulation/superinhibition responsible for
    toxic effects
  • seizures, delirium, coma and death

16
Mechanism of Toxicity
  • Excretion
  • rapid
  • half-life of 20 hours in adult humans
  • primarily via kidneys
  • 80 of lithium reabsorbed in kidneys
  • 97 of dose excreted within 10 days
  • secondary excretion routes
  • feces
  • sweat

17
Treatments
  • Diuretics
  • lowers plasma concentration of lithium
  • counteracted with fluid administration to avoid
    dehydration
  • Acetazolamide
  • facilitates excretion via kidneys
  • used alone and with other drugs
  • Dialysis
  • extremely severe poisonings

18
Current Status
  • Remains commonly used for therapeutic purposes
  • Additional study required to isolate specific
    mechanism of toxicity
  • Chronic effects remain widely debated
  • Patients using lithium carefully monitored for
    any evidence of toxicity

19
References
  • Amdur, M.D., J. Doull, and C.D. Klaassen (Eds.),
    (1991). Casarett and Doulls Toxicology (4th
    Edn). Macmillan Publishing Company, New York.
  • Baselt, R.C. and R.H. Cravey, (1995).
    Disposition of Toxic Drugs and Chemicals in Man
    (4th Edn). Year Book Medical Publishers,
    Chicago.
  • Bureau of Mines (1992). Minerals Yearbook. U.S.
    Government Printing Office, Washington, D.C.
  • Chang, Y.C., H.N. Lin, and H.C. Deng, (1990).
    Subclinical lithium neurotoxicity correlation
    of neural conduction abnormalities and serum
    lithium levels in manic-depressive patients with
    lithium treatment. Acta Neurologica
    Scandinavia, 82, 82-86.
  • Clayton, G.D. and F.E. Clayton (Eds.), (1982).
    Pattys Industrial Hygiene and Toxicology (3rd
    Edn). John Wiley Sons Publishers, New York.
  • Ellenhorn, M.J. and D.G. Barceloux, (1988).
    Medical Technology-Diagnosis and Treatment of
    Human Poisoning. Elsevier Science Publishing
    Company, New York.
  • Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N.
    Gleason, (1976). Clinical Toxicology of
    Commercial Products (4th Edn). Williams and
    Wilkins, Baltimore.

20
References
  • Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W..
    Ruddon, and A.G.. Goodman (Eds.), (1996).
    Goodman and Gilmans The Pharmacological Basis of
    Therapeutics (9th Edn). McGraw-Hill, New York.
  • Lewis, R.J. (Ed.), (1993). Hawleys Condensed
    Chemical Dictionary (12th Edn). Van Nostrand
    Rheinhold Company, New York.
  • Moore, J.A., (1995). As assessment of lithium
    using the IEHR evaluative process for assessing
    human developmental and reproductive toxicity of
    agents. Reproductive Toxicity, 9/2, 175-210.
  • Mroczka, D.L., K.M. Hoff, C.A. Goodrich, and P.C.
    Baker, (1983). Effect of lithium on
    reproduction and postnatal growth of mice.
    Biology of the Neonate, 43, 287-296.
  • Rane, A., G. Tomson, and B.Bjarke, (1978).
    Effects of maternal lithium therapy in a newborn
    infant. The Journal of Pediatrics, 93, 296-297.
  • Zenz, C., O.B. Dickerson, and E.P. Horvath,
    (1994). Occupational Medicine (3rd Edn)., St.
    Louis.
Write a Comment
User Comments (0)
About PowerShow.com