Komiskey: Lithium/Metals Flashcards
Can metals be broken down to reduce toxicity?
No
What is lithium mainly used to treat?
Manic episodes of bipolar disorder
Non-FDA approved uses:
- prophylaxis of cluster HA’s
- hyperthyroidism
- adjuvant therapy in resistant depression (unipolar state)
How is lithium metabolized?
It does not undergo metabolism - elimination is RENAL
How much lithium is reabsorbed and where?
70%; proximal convoluted tubule
What Increases Li levels?
DANC! because you're high on Li: Diuretics (thiazides & loops) ACE-inhibitors and ARBS NSAIDS (cox-2 inhibitors, indomethacin) Clonazepam
What Decreases Li levels? (increase Li urinary excretion)
AX it away with carbs
Acetazolamide; xanthine preparations
Sodium Bicarb
What is Li’s affect on ADH?
Li decreases amount of AQP2 channels –> ADH can’t work efficiently –> drink a lot/pee a lot
What is unique about Li toxicity?
It precipitates its own toxicity: polyuria & resistance to ADH = volume depletion and increased renal REabsorption of Li
How much lead in the blood gets filtered through the kidneys?
65%
Pb (lead) redistributes to the ___________ and acts like ______.
bone; Ca2+
Toxicity of Pb
- neurotoxic, nephrotoxic, immunotoxic
- alters heme synthesis, bone/teeth metabolism
- probable carcinogen
- increases BP/HTN
Pb causes a ____________ in GFR
decrease
Which causes more kidney problems - organic or inorganic Pb?
inorganic
What are the three forms of mercury and where do they mainly have effects?
elemental (liquid at room temp)
inorganic: GI effects (10% GI absorption)
organic: mental effects (90% GI absorption)
Common sources of mercury exposure?
Occupational - miners, dental offices
Seafood (bigger fish - bad)
What is the toxicity MOA of mercury?
Most likely binds sulfhydryl
What are mercury’s target organs?
Kidney and CNS
Symptoms of mercury poisoning?
Erethism (irritability, memory loss), mercurialentis (brown band in eye from Hg deposit), cancer, cerebral palsy in fetus
Source of Organic Methyl Hg?
Fish
Sources of organic Ethyl Hg?
Thimerosal (in vaccinations)
Can mercury exposure/thimerosal cause autism?
No - Studies show a stronger correlation with ADD
Sources of Cadmium?
Cigarette smoke
copper, lead, zinc from car exhaust
natural rock weathering
used in fertilizer - FOOD is most common route of exposure
How is Cd distributed in the body?
binds to albumin in plasma & RBCs
gets sent to liver, pancreas, prostate, kidneys (50-75% is in liver & kidneys)
How is Cd trapped in the kidney and what is its half-life?
Metallothionein (it’s synthesis is induced by Cd)
Cd 1/2 life = 20-30 years
**What is the mechanism of Cd toxicity in the kidney?
(bold on ppt):
- Free Cd binds to kidney glomerulus
- causes proximal tubule dysfunction
**What is the effect of Cd on the body’s organs?
TWO MAIN ORGANS EFFECTED: bones and kidneys. kidney damage is irreversible.
Kidneys:leads to increased proteinuria; also: gout, hyperuricemia, hyperchloremia; kidneys can shrink up to 30%
- reduction in GFR, increase in beta2-microglobulin
Other organs: lung damage, osteomalacia (itai-itai), high BP
What staple food contains arsenic?
Rice. Recommendation: cook it in 5-6x rice volume in water. brown rice has more As than white.
How is As distributed in the body?
Mimics phosphate
detoxified by methylation (decreased rates lead to increased toxicity)
can cross placenta
accumulates in LIVER, KIDNEY, heart and lungs
half-life: 10 hours; excretion via kidneys
How to treat metal poisoning?
Chelaters: bind directly with metal ions to form stable complexes that remove the metal from competition within body’s cells
Chelated metals are water soluble -> excreted by kidney
What are the most stable chelates?
Those with 5 or 6 membered ring
What are characteristics of ideal chelating agents?
water soluble, resistant to biotransformation, capable of forming non-toxic complexes with toxic metals, be excreted from the body, have a LOW affinity for essential metals
Common chelating agents?
- Dimercaprol (aka BAL: British Anti-Lewisite) (must be given parenterally)
- Dimercaptosuccinic acid (DMSA) (USA’s oral version of BAL)
- Dimercaptopropanesulfonate (DMPS) (EU’s oral)
- D-penicillamine (copper)
- Deferoxamine (iron)
- Ethylenediamintetraacetic acid (ETDA)
- Calcium Disodium Edetate (CaNa2) (lead)
What can dimercaprol (BAL) treat?
HAPA: Hg As Pb Au
What is the dimercaprol/BAL dosage?
needs to form a 2:1 complex
Side effects of dimercaprol/BAL?
highlighted: Nephrotoxicity
What is used to treat lead toxicity?
CaNa2EDTA
What is DMSA used to treat?
HAPC: Hg As Pb Cu ---> as opposed to dimercaprol, DMSA can treat copper toxicity
Also: Sb (antimony), Bi (bismuth)
Where is DMSA active?
extracellular space
When will nephrotoxicity appear after treatment with D-penicillamine for copper?
4-18 months
