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Q: Lithium Toxicity ( Answered,   0 Comments )
Question  
Subject: Lithium Toxicity
Category: Health > Medicine
Asked by: fraidknots-ga
List Price: $30.00
Posted: 22 Mar 2005 06:03 PST
Expires: 21 Apr 2005 07:03 PDT
Question ID: 498497
I am looking for information or studies on lithium toxicity. What are
the symptoms of lithium toxicity, both phisical and pshyc?

Clarification of Question by fraidknots-ga on 22 Mar 2005 06:08 PST
I am looking for information of studies dealing with Lithium toxicity.
 I know Lithium can cause physical effects on the liver and kidneys,
but can Lithium toxicity also have detremental physcological effects
on an individual?  What, if any, are the psychologial affects of
lithium poisening or toxicity?
Answer  
Subject: Re: Lithium Toxicity
Answered By: crabcakes-ga on 22 Mar 2005 17:05 PST
 
Hi fraidknots,

    Lithium is not usually known to cause liver damage, when taken
alone. Liver damage may occur if lithium is taken concurrently with
other drugs, which are outlined further down in the answer. Often,
liver and kidney function tests are drawn for baseline values before
therapy is started. The same tests will be repeated by your doctor,
periodically, and compared with the baseline results. Lithium, as a
salt and electrolyte, similar in structure to sodium and potassium, is
cleared by the kidneys. The organs most affected by lithium are the
kidneys, heart, thyroid, and the central nervous system (CNS).


?Question: I have been taking lithium for bipolar disorder from
1990-1999. I was taken off of the lithium due to elevated liver
enzymes - 105 ALT - on last test 5/99. What does this number mean in
terms of current liver damage and how can this be corrected?

Answer: Pretty minimal unless there is concurrent rise in your other
liver enzymes. Also, there are many things that may cause liver enzyme
elevations, lithium is not one or the usual ones, I would suspect
another unknown suspect. If your enzymes are now normal, I would not
be concerned.?
http://www.druginfonet.com/index.php?pageID=faq/new/DRUG_FAQ/Lithium.htm



?Lithium is an element of the alkali-metal group. Preclinical studies
have shown that lithium alters sodium transport in nerve and muscle
cells and effects a shift toward intraneuronal metabolism of
catecholamines, but the specific biochemical mechanism of lithium
action in mania is unknown.?

?Chronic lithium therapy may be associated with diminution of renal
concentrating ability, occasionally presenting as nephrogenic diabetes
insipidus, with polyuria and polydipsia. Such patients should be
carefully managed to avoid dehydration with resulting lithium
retention and toxicity. This condition is usually reversible when
lithium is discontinued.
Morphologic changes with glomerular and interstitial fibrosis and
nephron atrophy have been reported in patients on chronic lithium
therapy. Morphologic changes have also been seen in manic-depressive
patients never exposed to lithium. The relationship between renal
functional and morphologic changes and their association with lithium
therapy have not been established.?
http://www.healthyplace.com/medications/lithium.htm


?It is unclear how they work. Overall, about 50 percent to 80 percent
of patients have some response to either drug. They are generally safe
when used correctly.
Although it can be difficult to predict who will benefit from lithium,
factors associated with a good response include a family history of
bipolar disorder; a previously favorable response to lithium; having
only a few prior episodes of mania and a history of full relief from
symptoms between episodes. Maximal response to the drug usually takes
two to three weeks? ?Persistent thirst and excessive urination, which
occur in about 25 percent of those taking lithium, are due to
lithium's effect on the kidneys. Also, by decreasing the secretion of
the thyroid hormone, lithium can produce hypothyroidism. These effects
are usually reversed once lithium is discontinued.?
http://www.hopkinshospital.org/health_info/Mental_Health/Reading/lithium.html


Symptoms of lithium toxicity include:
=====================================
Nausea and vomiting
Diarrhea
Weakness and fatigue
Lethargy and confusion
Tremor
Seizure
According to eMedicine, the following drugs can increase even
therapeutic amounts of lithium to toxic levels in the bloodstream:
nonsteroidal anti-inflammatory drugs [NSAIDs] such as
Advil(Ibuprofen), Naproxen(Naprosyn) and Orudis (Ketoprofen),
diuretics, tetracyclines, phenytoin, and cyclosporine)


Physical symptoms include:

Mild-to- moderate toxicity
Generalized weakness
Fine resting tremor
Mild confusion
Moderate-to-severe toxicity
Severe tremor
Muscle fasciculations
Choreoathetosis (Abnormal body movements usually of the fingers and toes)
Hyperreflexia
Clonus (When muscles alternately flex and contract)
Opisthotonos (Spasms that cause the feet and hands to be drawn backwards)
Stupor
Seizures
Coma
Signs of cardiovascular collapse

http://www.emedicine.com/emerg/topic301.htm


?Any overdose in a patient who has been taking chronic lithium therapy
should be regarded as potentially serious. A single acute overdose
usually carries low risk and patients tend to show mild symptoms only,
irrespective of their serum lithium concentration. However more severe
symptoms may occur after a delay if lithium elimination is reduced
because of renal impairment, particularly if a slow-release
preparation has been taken. The fatal dose, in a single overdose, is
probably over 5g.
If an acute overdose has been taken by a patient on chronic lithium
therapy, this can lead to serious toxicity occurring even after a
modest overdose as the extravascular tissues are already saturated
with lithium.
Lithium toxicity can also occur in chronic accumulation for the following reasons:
Acute or chronic overdosage. 
Dehydration e.g. due to intercurrent illness.
Deteriorating renal function.
Drug interactions, most commonly involving a thiazide diuretic or a
non-steroidal anti-inflammatory drug (NSAID).
In patients with a raised lithium concentration, the risk of toxicity
is greater in those with the following underlying medical conditions:
hypertension; diabetes; congestive heart failure; chronic renal
failure; schizophrenia; Addison's disease.?
http://medicines.mhra.gov.uk/inforesources/infolicapps/spcoverdose/genericoverdose.htm#lit

?Toxicity:
-unlike antipsychotic or antidepressant drugs lithium produces only
mild sedation & no autonomic blocking effects
-adverse effects are diarrhea, tremor, edema, diabetes insipidus
thyroid enlargement?
http://www.ovc.uoguelph.ca/BioMed/Courses/Public/Pharmacology/pharmsite/98-309/CNS/Antidepressants/Antidepressants.html


 Lithium is absorbed totally, first by the digestive tract, in the
intestines, to be exact, about 8 hours after an oral dose. The drug
peaks in the bloodstream at about 3 hours after an oral dose.

Next, about 95% is excreted by the kidneys, into the urine, leaving 1%
to exit the body in stool, and 4% is excreted in sweat.
?Lithium is excreted in milk, so mothers taking lithium must not
breast-feed their babies.?
http://anil299.tripod.com/vol_001_no_002/pg001.html 


?The central nervous system (CNS) is the major organ system affected,
although the renal, gastrointestinal (GI), endocrine, and
cardiovascular (CV) systems also may be involved. Lithium is available
only for oral administration. It is almost completely absorbed from
the GI tract.

Lithium dosing 
The therapeutic dose is 300-2700 mg/d with desired serum levels of 0.7-1.2 mEq/L. 
Lithium clearance is predominantly through the kidneys. Because it is
minimally protein bound, lithium is freely filtered at a rate that is
dependent upon the glomerular filtration rate (GFR). Consequently,
dosing must be adjusted based on renal function. Individuals with
chronic renal insufficiency must be closely monitored if placed on
lithium therapy.

Most filtered lithium is reabsorbed in the proximal tubule; thus,
drugs known to inhibit proximal tubular reabsorption, such as carbonic
anhydrase inhibitors and aminophylline, may increase excretion.
Diuretics acting distally to the proximal tubule, such as thiazides
and spironolactone, do not directly affect the fractional excretion of
lithium (although they may affect serum lithium levels indirectly
through their effects on volume status). Reabsorption of lithium is
increased and toxicity is more likely in patients who are hyponatremic
or volume depleted, both of which are possible consequences of
diuretic therapy.?
http://www.emedicine.com/emerg/topic301.htm


?The most frequent adverse effects are the initial postabsorptive
symptoms, believed to be associated with a rapid rise in serum lithium
concentrations. They include, gastrointestinal discomfort, nausea,
vertigo, muscle weakness and a dazed feeling and frequently disappear
after stabilization of therapy. The more common and persistent adverse
reactions are: fine tremor of the hands, and, at times, fatigue,
thirst, polyuria and nephrogenic diabetes insipidus. These do not
necessarily require reduction of dosage.?
http://www.mentalhealth.com/drug/p30-l02.html#Head_5

?The following adverse effects have been reported usually related to
serum lithium concentrations:

Gastrointestinal:
Anorexia, nausea, vomiting, diarrhea, thirst, dryness of the mouth,
metallic taste, abdominal pain, weight gain or loss.

Neurologic:
General muscle weakness, ataxia, tremor, muscle hyperirritability,
(fasciculation, twitchings, especially of facial muscles and clonic
movements of the limbs), choreoathetotic movement, hyperactive deep
tendon reflexes.

CNS:
Anesthesia of the skin, slurred speech, blurring of vision, blackout
spells, headache, seizures, cranial nerve involvement, psychomotor
retardation, somnolence, toxic confusional states, restlessness,
stupor, coma, acute dystonia. EEG changes recorded consisted of
diffuse slowing, widening of the frequency spectrum, potentiation and
disorganization of background rhythm. Sensitivity to hyperventilation
and paroxysmal bilateral synchronous delta activity have also been
described.

Cardiovascular:
Arrhythmia, hypotension, ECG changes consisting of flattening or
inversion of T waves, peripheral circulatory failure, cardiac
collapse.

Genitourinary:
Albuminuria, oliguria, polyuria, glycosuria. 

Allergic:
Allergic vasculitis. 

Dermatologic:
Dryness and thinning of the hair, leg ulcers, skin rash, pruritis

Hematologic:
Anemia, leucopenia,(low white blood cell count) leucocytosis (High
white blood cell count).
 
Metabolic:
Transient hyperglycemia, slight elevation of plasma magnesium, goiter formation. 
 Hypercalcemia, associated with lithium induced hyper- parathyroidism,
has also been reported.
 
Miscellaneous:
General fatigue, dehydration, peripheral edema.?
http://www.mentalhealth.com/drug/p30-l02.html#Head_5


?Lithium carbonate may provide relief from acute episodes of mania or
depression and can help prevent them from recurring.
Lithium is often helpful in treating manic episodes that are not mixed
with any depressive mood.Long-term use of lithium has been shown to
reduce the risk of suicide related to bipolar disorder.?
?High blood levels of lithium carbonate can be life-threatening.
People who take lithium carbonate need to have their blood checked
regularly about every two weeks to measure the amount of the drug in
their blood.
Your doctor will need to periodically test the function of your
kidneys and thyroid gland if you are taking lithium.
Sometimes other medications cause higher- or lower-than-expected
amounts of lithium carbonate in a person's blood. People who take
lithium carbonate need to tell their health professional if they take
other medications.

Mood stabilizers may interact negatively with other medications. Mood
stabilizers should not be used along with:
Medications used to treat indigestion, such as cimetidine (Tagamet).
Medications used to treat seizures, such as phenytoin (Dilantin).
Antibiotics, such as erythromycin (E-Mycin).
Heart medications, such as diltiazem (Cardizem) (in combination with lithium).
 Nonsteroidal anti-inflammatory drugs (in combination with lithium). 
http://my.webmd.com/hw/bipolar_disorder/ty1913.asp

?Unfortunately, Lithium has also been known to produce numerous side
effects. As with many other medications used for Bipolar Disorder,
Lithium commonly causes weight gain. Similarly, Lithium may cause
kidney and thyroid changes, and blood tests should be taken frequently
to monitor the level of Lithium in the bloodstream. New, sustained
release versions of Lithium have been designed to maintain stable
Lithium plasma levels, and thus may reduce overall side effects. The
desirable serum Lithium levels are 0.6 to 1.2 mEq/l. Dosage will vary
from one individual to another, but usually 900 mg to 1200 mg per day
in divided doses will maintain this level. Serum Lithium levels in
uncomplicated cases receiving maintenance therapy during remission
should be monitored at least every two months.?
http://remedyfind.com/rm-931-Lithonate.asp


=======
Studies
=======

Lithium toxicity: an iatrogenic problem in susceptible individuals
http://www.blackwell-synergy.com/links/doi/10.1046/j.1440-1614.2001.00963.x

Lithium for maintenance treatment of mood disorders
http://www.biopsychiatry.com/lithiumrev.htm

Lithium and the kidney
http://www.ingentaconnect.com/search/expand?pub=infobike://adis/dsf/1999/00000020/00000003/art00004

Studies on the role of brain cholinergic systems in the therapeutic
mechanisms and adverse effects of ECT and lithium
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3917309&dopt=Citation

Clinical relevance of drug interactions with lithium
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8521679&dopt=Citation


=====================
Psychological Effects
=====================
?Lithium works to curb both the elation and despondence that are the
hallmark of manic depression by stabilizing levels of the
neurotransmitter glutamate, according to new research in animals.
Normally, to send a signal to a neighboring neuron, a nerve cell
releases a flood of glutamate into the space between the two cells.
Then to shut off the signal, the releasing neuron reabsorbs glutamate,
pumping it back into the cell for reuse using a structure called a
reuptake transporter.
Malfunctions in any part of this process can lead to inappropriate
glutamate levels, which in turn may cause depression?in the case of
too little glutamate?or mania?in the case of too much glutamate, the
researchers postulate.
Based on studies in mice, the researchers find that lithium can both
slow down the glutamate reuptake system, and speed it up. Indeed, when
they exposed functioning slices of mouse brain to lithium, glutamate
levels rose as reuptake slowed. In contrast, in live mice exposed to
lithium for two weeks, glutamate dropped as reuptake increased.
Overall, lithium appeared to stabilize glutamate levels within a
narrow range, the researchers report in an article published in the
July 7 issue of the Proceedings of the National Academy of Sciences
(Vol. 95, No. 14, p. 8363?8368).?
http://www.apa.org/monitor/sep98/lith.html

?A recent report on noncompliance asks why a large proportion of
patients, 43 percent in this study, stop taking their lithium. Michael
Gitlin and his colleagues report in the April 1989 Journal of Clinical
Psychiatry that patients most frequently stopped because of weight
gain and mental impairment, with symptoms of "poor concentration,"
"mental confusion," "mental slowness," and "memory problems."

Consistent with its toxic effects on the nervous system, lithium
causes a tremor in 30 to 50 percent of patients. Tremors can be a
warning sign of impending serious toxicity of the brain, especially if
it occurs along with other danger signals, such as memory dysfunction,
reduced concentration, slowed thinking, confusion, disorientation,
difficulty walking, slurred speech, blurred vision, ringing in the
ears, nausea, vomiting, and headache. Muscle aches and twitches,
weakness, lethargy, and thirst are other common signs of lithium
toxicity. In the late stages of toxicity, the patient may become
delirious and succumb to seizures and coma. EEG studies indicate an
abnormal slowing of brain waves in a significant portion of patients
routinely treated with lithium; the condition worsens with toxicity.?
http://www.sntp.net/drugs/lithium_breggin.htm


?Cases of suicide due to lithium are on record. This is a very real
possibility and should be kept in mind by a forensic pathologist
conducting post-mortems on suspicious deaths.
Accidental poisoning by lithium tablets is not very common, but can occur.?
http://anil299.tripod.com/vol_001_no_002/pg001.html


Preventing Lithium Toxicity
============================
?How can lithium toxicity be prevented? 
1.Have regular blood tests as advised by your doctor. These tests will
allow your doctor to see how much lithium is in your blood. If you
have a high level of lithium in your blood, your doctor may reduce
your dose of medication for a while to prevent lithium toxicity from
developing.
2.Drink plenty of fluids - at least 6 glasses of water (or milk, fruit
juice, soft drink) each day. If you become dehydrated, the level of
lithium in your blood will increase. Also, hot sweaty weather,
strenuous exercise, and vomiting or diarrhoea all increase water loss.
It will be important to drink extra water if these events occur.
3.Do not start a salt-reduced diet while taking lithium. A low salt
intake can increase the level of lithium in the blood. (Note also that
a high salt intake can lower the level of lithium in the blood.)

What to do if you notice the signs of lithium toxicity? 
1.Contact your doctor immediately or go to a hospital casualty department. 
2.Drink a few glasses of water if possible while waiting to see the doctor. 
3.Do not take any more lithium until you have seen the doctor.?
http://www.nelmh.org/page_view.asp?c=20&did=2307&fc=005185004
 

Additional Lithium Information
==============================

Patients taking lithium should avoid excessive caffeine intake by
consuming only small amounts of coffee, tea, colas and chocolate.
http://www.healthyplace.com/medications/lithium.htm

http://www.healthdigest.org/drugs/lithiumcarbonate.html

http://www.mhsource.com/expert/exp1092903b.html

http://www.bipolarworld.net/Phelps/ph_2004/ph1147.htm

http://psychcentral.com/meds/lithium_carbonate.html


Illustrations:
==============

http://www.ovc.uoguelph.ca/BioMed/Courses/Public/Pharmacology/pharmsite/98-309/CNS/Antidepressants/image%20516.gif

http://www.nature.com/npp/journal/v19/n3/fig_tab/1395201f4.html


Did you know lithium is thought to have been an ingredient of 7-Up? 

?Just in case you where wondering, 7UP did contain Lithium, a
light-weight metal, now used in treating mental illness (and making
long lasting batteries). The lithium was removed from 7UP over 50
years ago, but at the time it appeared in several companies lemon-lime
sodas. When soft drinks were first invented they often had minerals
added that were found in natural springs and springs with lithium were
very popular.?
http://www.sodamuseum.bigstep.com/generic.jhtml?pid=4


?However, the uncola wasn't known as 7Up for the first few years of
its existence. It was originally christened "Bib-Label Lithiated
Lemon-Lime Soda." In his formulation, Grigg had included lithia, a
naturally-occurring substance found in minute quantities in bubbling
waters fed by underground springs. (Lithia is better known as lithium,
a drug used to even out mood swings.) Grigg had the notion that the
chemical's presumed healthful aspects would be a selling point with
the soda-buying public, hence the "Lithiated" in the name.?
http://www.snopes.com/business/names/7up.asp


There you go fraidknots!(Love your screen name!) If any part of my
answer is unclear, please don?t close this question my rating it,
before requesting an Answer Clarification first. This will enable me
to assist you further, if possible.

Regards, Crabcakes

Search Terms
Lithium carbonate metabolism
Lithium toxicity
Lithium carbonate + studies
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