nemoci-sympt/METABOLISMUS/wilsonova-choroba/terapie
Avoiding anything hepatotxic
- Alcohol consumption
- Potential hepatotoxic drug therapy [1]
Ammonium tetrathiomolybdate
- Investigational chelating drug
- University of Michigan as an initial treatment if neurologic or psychiatric manifestations
- Chelating agent
- Inhibitor of cosorption from the GI tract [2]
Blokáda ATP7A
- Rising concentrations of copper in trans-Golgi network
- ATP7A releases copper into the portal vein to the liver
- In Menkes disease
Blokáda copper membrane transporter 1 (Ctr1; SLC31A1)
- Carries copper inside the intestine cells
Impairment of intestinal copper absorption
- Various acquired malabsorptive processes
Lifelong, uninterrupted chelation therapy
- Necessary in all patients with Wilson disease
- Frequent follow-up with patients is necessary
- Decompensation due to noncompliance
- One of the major causes of fulminant liver failure [1]
D-penicillamine
- Can cause serious side effects
- Skin and kidney problems
- Bone marrow suppression
- Worsening of neurological symptoms
- Should be used cautiously if you have a penicillin allergy
- Keeps vitamin B-6 (pyridoxine) from working
- Must be administered with pyridoxine 25 mg by mouth daily [2]
Další symptomatická terapie
To treat parkinsonism and dystonia symptoms
- Anticholinergics
- Baclofen
- Gamma-aminobutyric acid (GABA) antagonists
- Levodopa [2]
Antiepileptics
Neuroleptics
- To treat psychiatric symptoms [2]
Hepatic encephalopathy
- protein restriction
- Lactulose [2]
Denture cream containing zinc
- Unusual cause of acquired copper deficiency is excess zinc intake
- For example chronic use of denture cream containing zinc (Nations et al., 2008; Trocello et al., 2011) [5]
Dimercaprol (BAL in Oil)
- For refractory cases of Wilson disease that are not responding to first- or second-line chelation treatment [2]
Dimercaptosuccinic acid
Drinking water
- Should be analyzed for copper content
Avoid foods with a higher copper content
- Liver
- Chocolate
- Nuts
- Mushrooms
- Legumes [1]
- Shellfish (especially lobster)
Gastric and bariatric surgery
- Several cases of copper deficiency
- Probably due to malabsorption
Intravenous hyperalimentation
Skladování potravin - kontaminace mědí
- Vyhnout se
- Acidic food or beverage that has had prolonged contact with a copper container
- Ingesting milk that has been boiled or stored in corroded copper or brass vessels
Molecular Adsorbents Recirculating System (MARS)
- Extracorporeal liver support system
- Hollow-fiber dialysis module
- Patient’s blood is dialyzed across an albumin-impregnated membrane
- Constant flow of albumin-rich (20%) dialysate in the extracapillary compartment
- Case reports and very small series
- Presented a role for this as a bridge to liver transplantation [2]
Vyhnout se copper salt (eg, copper sulfate) - modrá skalice - síran měďnatý
- From absorption of large amounts through the skin
- Compresses saturated with a solution of a copper salt applied to large areas of burned skin [4]
- Obsahuje 25 % mědi
- 4 g skalice obsahují 1 g mědi
- Levný a dobrý způsob jak dostat měď nebo spíše měďnaté ionty do vody v bazénu
- Tlumí růst nežádoucích organizmů
- Dostatečně účinná a zároveň životu bezpečná koncentrace mědi je 1 až 2 mg/l
- Odpovídá 4 až 8 mg/l skalice modré, tedy 4 až 8 g/m3 [5]
- Jak velká je schopnost zdravé kůže absorbovat měď z takové vody ? Má to vliv nebo nemá ? [5]
After initiation of therapy with a chelating agent
- Aware of potential adverse effects of the agents
- Aware of the potential to develop worsening of some symptoms when chelation is started
- Neurologic signs and symptoms can see worsening of these with chelation
- In some instances, therapy needs to be reduced or stopped
Screen siblings on Wilson disease
- Estimated frequency is 1 in 4
- In situations in which the siblings have the same parents [1]
Sodium dimercaptosuccinate
Tetrathiomolybdate
Surgical decompression or transjugular intrahepatic shunting (TIPS)
- Treatment of portal hypertension
- Reserved for individuals with recurrent or uncontrolled variceal bleeding
- Unresponsive to standard conservative measures
Orthotopic liver transplantation
- Curative treatment for Wilson disease
- Consideration for liver transplantation is less likely with advancing age [1]
Trientine (Syprine)
- Works much like penicillamine
- Tends to cause fewer side effects
- Neurological symptoms can worsen when taking trientine
Prevence nedostatku železa
Zdraví jedinci
- copper accumulates in the liver during iron deficiency
- Iron accumulates during copper deficiency
- Copper levels also increase in the intestinal mucosa and blood during iron deprivation [4]
- copper-transporting ATPase 1 (Atp7a)
- Strongly induced during iron deficiency in rats and mice
- Via a hypoxia-inducible transcription factor (Hif2?)
- Also invoked to increase expression of the
- Intestinal iron importer (divalent metal-ion transporter 1 [Dmt1])
- Principle intestinal iron importer, Dmt1, could transport copper during iron deficiency
- Brush-border membrane (BBM) ferrireductase (duodenal cytochrome b [Dcytb])
- Basolateral membrane (BLM) iron exporter (ferroportin 1 [Fpn1]) [4]
- Significant hepatic copper loading occurred in the LFe/HCu group
- Consistent with previous observations that liver copper content increases in iron deficiency [4]
Jak je to u nadbytku mědi?
- Nadbytek mědi může dělat deficit železa
- Ale také může vést k lepšímu vstřebání a uložení železa
- železo navíc může dál zhoršit stávající poškození tkání oxidačním stresem
- Tuším, že nadbytek železa může být hodně špatně, ale deficit taky
Jak je to s vitamínem C při vyšších hladinách mědi ?
- Tuším, že podobně jako u vyší kumulace železa, tak podobně nevhodný by mohl být nadybtek vitamínu C při kumulaci mědi
Zinc salts
- Inductors of methallothioneins
Zinc acetate (Galzin)
- Prevents body from absorbing copper from the food
- Used as maintenance therapy to prevent copper from building up again after treatment with penicillamine or trientine
- Might be used as primary therapy if penicillamine or trientine is not tollerated
- Zinc acetate can cause stomach upset
Zinc
- Excess zinc is known to stimulate the synthesis of metallothionein in intestinal enterocytes
