1. Aluminum hydroxide
김윤영

2. ALUMINUM HYDROXIDE IN PEPTIC ULCER DISEASE
MECHANISM
Aluminum hydroxide : direct cytoprotective effect
The exact mechanism of action is UNCLEAR.
The drug binds to and forms an adherent complex with protein in the ulcer base, thus inhibiting further acid-pepsin digestion.
It also forms complexes with pepsin and stimulates endogenous prostaglandin synthesis in the mucosa
Help to relieve the symptoms of heartburn or dyspepsia
1. MECHANISM: Sucralfate is an aluminum hydroxide complex of sucrose which acts to exert a direct cytoprotective effect. The exact mechanism of action is unclear, but the drug binds to and forms an adherent complex with protein in the ulcer base, thus inhibiting further acid-pepsin digestion. It also forms complexes with pepsin and stimulates endogenous prostaglandin synthesis in the mucosa (Hixson et al, 1992).
2. EFFICACY: When given for duodenal ulcer, sucralfate resulted in healing rates of 75% at 4 weeks and 90-95% at 8 weeks, versus ranitidine rates of 85% and 90-95% at 4 and 8 weeks, respectively. When given as treatment for gastric ulcers, sucralfate has been as effective as H-2 antagonists, with equivalent healing rates of 83% seen at 8 weeks and up to 90% after 12 weeks (Hunt, 1991). However, pain relief is not as good with sucralfate as with omeprazole or H-2 blockers, which is probably related to the fact that these agents demonstrate higher healing rates initially. Sucralfate can prevent stress ulcer in mechanically ventilated patients, resulting in less late-onset pneumonia than occurs after prophylactic use of ranitidine or antacids. The agent can also prevent ulcer recurrence when given 1 gm BID (Katz & Hollander, 1992; Hixson et al, 1992; Abramowicz, 1994).
3. ADVERSE EFFECTS: Since sucralfate is not absorbed systemically, it is relatively safe. It has been reported to elevate serum aluminum levels in patients with renal failure, but no more than the aluminum-based antacids used as phosphate binders in these patients (Sucralfate binds phosphate as effectively as the aluminum antacids). Sucralfate can bind to, and affect the absorption of, several medications, including warfarin, phenytoin, norfloxacin, tetracycline, and antacids (Katz & Hollander, 1992).
4. DOSING: Sucralfate is given 1 gm QID on an empty stomach (or 2 gm BID). Maintenance dosing is 1 gm BID (Katz & Hollander, 1992; Gilbert et al, 1991).
5. PLACE IN THERAPY: Although sucralfate produces ulcer healing rates similar to those of the H-2 blockers, pain relief is not as rapid. Maintenance therapy with sucralfate results in relapse rates also similar to H-2 antagonists. As PUD treatment continues to emphasize the H pylori aspect, sucralfate use may very well diminish.

3. ALUMINUM HYDROXIDE IN PEPTIC ULCER DISEASE
EFFICACY : healing rate for duodenal ulcer
Sucralfate 75% at 4 wks, 90-95% at 8 wks
Ranitidine 85% at 4 wks, 90-95% at 8 wks
The agent can also prevent ulcer recurrence when given 1 gm BID
Single doses usually provide mg of aluminum hydroxide
The amount of aluminum hydroxide in various antacid preparations varies greatly, and doses as high as 12,000 mg/d may be taken in extreme cases.
orally as an antacid
Combination with magnesium hydroxide, magnesium carbonate, calcium carbonate, and/or simethicone.
Commonly cause constipation
1. MECHANISM: Sucralfate is an aluminum hydroxide complex of sucrose which acts to exert a direct cytoprotective effect. The exact mechanism of action is unclear, but the drug binds to and forms an adherent complex with protein in the ulcer base, thus inhibiting further acid-pepsin digestion. It also forms complexes with pepsin and stimulates endogenous prostaglandin synthesis in the mucosa (Hixson et al, 1992).
2. EFFICACY: When given for duodenal ulcer, sucralfate resulted in healing rates of 75% at 4 weeks and 90-95% at 8 weeks, versus ranitidine rates of 85% and 90-95% at 4 and 8 weeks, respectively. When given as treatment for gastric ulcers, sucralfate has been as effective as H-2 antagonists, with equivalent healing rates of 83% seen at 8 weeks and up to 90% after 12 weeks (Hunt, 1991). However, pain relief is not as good with sucralfate as with omeprazole or H-2 blockers, which is probably related to the fact that these agents demonstrate higher healing rates initially. Sucralfate can prevent stress ulcer in mechanically ventilated patients, resulting in less late-onset pneumonia than occurs after prophylactic use of ranitidine or antacids. The agent can also prevent ulcer recurrence when given 1 gm BID (Katz & Hollander, 1992; Hixson et al, 1992; Abramowicz, 1994).
3. ADVERSE EFFECTS: Since sucralfate is not absorbed systemically, it is relatively safe. It has been reported to elevate serum aluminum levels in patients with renal failure, but no more than the aluminum-based antacids used as phosphate binders in these patients (Sucralfate binds phosphate as effectively as the aluminum antacids). Sucralfate can bind to, and affect the absorption of, several medications, including warfarin, phenytoin, norfloxacin, tetracycline, and antacids (Katz & Hollander, 1992).
4. DOSING: Sucralfate is given 1 gm QID on an empty stomach (or 2 gm BID). Maintenance dosing is 1 gm BID (Katz & Hollander, 1992; Gilbert et al, 1991).
5. PLACE IN THERAPY: Although sucralfate produces ulcer healing rates similar to those of the H-2 blockers, pain relief is not as rapid. Maintenance therapy with sucralfate results in relapse rates also similar to H-2 antagonists. As PUD treatment continues to emphasize the H pylori aspect, sucralfate use may very well diminish.

4. ALUM IRRIGATION THERAPY OF BLADDER HEMORRHAGE
Common causes of intravesical (bladder) hemorrhage : bladder or prostate cancer, radiation cystitis, cyclophosphamide-induced cystitis, and intravesical Bacillus Calmette-Guerin (BCG) immunotherapy of transitional cell carcinoma
Intravesical alum
Tissue contraction and blanching, which produces tamponade of bleeding vessels.
Hardening of the cement substance of capillary endothelium, which inhibits transcapillary movement of plasma protein and reduces local edema, inflammation and exudation.
Alum is minimally absorbed.
More serious side effects such as encephalopathy may result when an instillation rate of 3 grams or more per hour is employed in renally-impaired patients.
Techniques of preparation vary as follows: 1) Rapid preparation without sterilization is accomplished by diluting enough of the powdered alum to make a 1 percent solution with distilled water. 2) If sterilization is desired, the solution may be filtered through a 0.22 micron millipore filter (eg, Ivex No. 2 Filter set). This procedure is often utilized to sterilize TPN solutions. 3) Autoclave procedure is as follows: preparation of a 1 percent solution (50 grams of alum dissolved in 5 liters of distilled water and placed in 500 ml bottles); bottles are autoclaved at 15 pounds per square inch pressure at 117C for 15 minutes at exhaust, then allowed to cool to room temperature. The authors reported utilizing the solution within 4 days of preparation [7]. 4) An additional protocol is to use the 1 percent solution or a stock solution of 400 grams of potash of alum (McCarthy's) in 4 liters of hot sterile water; use a sterilizing filter to add 300 milliliters of the stock solution to 3 liters of 0.9% saline. The bladder is then irrigated with up to 30 liters of this solution over a 24 hour period [4]. [7] administered a continuous intravesical irrigation of 1% alum to control bladder hemorrhage in nine patients refractory to intravesical saline irrigations. In eight of nine patients, hemorrhage was due to untreated transitional cell carcinoma of the bladder. One patient had hemorrhagic cystitis resulting from radiation therapy for cervical carcinoma. Continuous closed irrigations were performed without regional or general anesthesia using a 22F 3-way Foley catheter for 12 to 72 hours at a rate of 5 mL/min (3 grams/hour). Gross hematuria abated promptly in all nine patients, but the exact time until hemostasis occurred was not stated. In three patients, the effect was only transient. None of the patients experienced urinary urgency, increased micturition or dermatitis secondary to inadvertent spillage of the alum irrigation on the mucosa. Cystography was performed in three patients with transitional cell carcinoma of the bladder, and none exhibited vesicoureteral reflux. Five patients with transitional cell carcinoma were able to undergo transurethral resection of the bladder tumor within 2 to 3 weeks after alum irrigation. In all of these patients, the histological characteristics of the tumor were preserved after alum. Absence of epithelial damage as a result of the alum irrigation was confirmed in one patient upon analysis of normal bladder tissue. A 1% alum irrigation was administered to control bladder hemorrhage secondary to bladder carcinoma in eight patients [8]. In seven patients, bladder hemorrhage failed to respond to diathermy, and in one patient, formalin irrigation, balloon distention and selective arterial embolization were unsuccessful. Hemorrhage ceased in all eight patients in approximately 3 days (range, 1 to 4 days) following irrigation with up to 30 liters (300 grams alum). The alum irrigation was generally well-tolerated in all patients. Two patients complained of suprapubic discomfort, two patients had low grade fever (temperature less than 38 degrees C) and two patients developed ileus. Normal aluminum levels (less than 1 micromole/liter) were measured in seven of eight patients, and one patient with an elevated level (1.8 micromol/liter) had no signs of toxicity. Successful control of bladder hemorrhage in five patients refractory to saline irrigations and repeated fulgurations was reported by Mukamel et al (1986). Alum irrigation administered at a rate of 2 to 5 liters in the initial hours, and then at a rate of 1 liter every 2 to 5 hours (200 to 500 mL/hour; 2 to 5 grams/hour) controlled bleeding in two patients with radiation cystitis in 12 and 48 hours, respectively. Bleeding was controlled in the remaining three patients within 24 to 36 hours. Bleeding recurred in one patient two months after treatment, but was controlled by readministering the alum irrigation. Intraperitoneal spillage of the alum irrigation due to bladder rupture occurred in one patient; however, laparotomy failed to show any evidence of surface irritation to the bowel or peritoneum. These clinicians recommended alum irrigation for the treatment of bladder hemorrhage prior to other pharmacologic measures such as formalin irrigation, or procedures such as embolization of the iliac arteries, due to its lack of toxicity and ease of administration. [9] administered 4 to 30 liters of a 1% alum irrigation (40 to 300 grams) over 6 to 36 hours to ten patients with bladder hemorrhage secondary to amyloidosis, distention, bladder carcinoma, bladder carcinoma with irradiation or drug-induced cystitis. One case of drug-induced cystitis and one case of irradiation-induced cystitis were accompanied by thrombocytopenia. In 7 patients, alum irrigation controlled the hemorrhage within 24 hours, while in the two patients with thrombocytopenia, alum irrigation failed. In one patient, alum worked initially, but hemorrhage recurred. No complications were noted. [10] reported that administration of 3 liters of a 1% alum irrigation over 2 to 4 hours successfully controlled bladder hemorrhage in 28 of 31 patients with a neoplasm, in one of three patients with cystitis due to irradiation, in two patients with prostate hyperplasia and in seven patients with bleeding after transvesical prostatectomy. The overall success rate was 38 of 43 patients (88.4%). Of five treatment failures, three occurred in patients with a neoplasm and two occurred in patients with radiation cystitis as the cause of bladder hemorrhage. For the treatment of bladder hemorrhage, a 1% alum irrigation was administered to fifteen patients [11]. Bladder hemorrhage was due to bladder tumor in thirteen patients and in one patient each, to cystitis and transurethral resection of the prostate. A complete response was attained in ten (66%) of patients, a partial response was seen in two patients, and three patients failed therapy. Side effects such as suprapubic pain, vesical spasms and tenesmus, were noted in seven (47%) patients and were controlled with antispasmodic medication. In two patients (13%), side effects necessitated discontinuation of the alum irrigation. In sixteen patients with bladder hemorrhage due to bladder carcinoma, cyclophosphamide-induced cystitis, radiation-induced cystitis, leukemia or metastasized melanoma in the bladder wall, a 0.5% alum irrigation successfully halted bladder hemorrhage. All patients had failed previous attempts to stop the hemorrhage with clot evacuation, continuous irrigation with physiological saline for 24 hours, and/or electrocoagulation. Hemorrhage was permanently controlled in 6 patients within 48 hours, in 4 patients within 24 hours, in one patient within 12 hours and in one patient within 6 hours. Bleeding was temporarily controlled in four patients. None of the patients experienced any side effects. The investigators stated that a 0.5% alum solution is preferable to a 1% solution because, unlike a 1% alum solution, the solution is clear and remains clear even after autoclaving, does not form a precipitate which can block the catheter, and may be associated with a decreased risk of aluminum toxicity, especially in renally-impaired patients [12]. Favorable outcomes with the use of a 1% alum irrigation for the treatment of bladder hemorrhage have been reported by others [13][14]. Although most clinicians have reported only mild or no adverse effects in patients receiving alum irrigations for a duration of up to 4 days at a time, encephalopathy associated with an elevated serum aluminum level of 17 nanograms/liter (normal 3 to 10 nanograms/liter) was reported in a 74-year-old male with bladder hemorrhage secondary to prostate adenocarcinoma [15]. The authors advised that the rate of a 1% alum irrigation should not exceed 300 mL/hour (3 grams/hour) in patients with renal insufficiency. Aluminum is renally excreted, with a potential excretion reserve of up to 30 times normal values. Toxicity may result from renal function impairment or large absorptive surfaces. Aluminum toxicity causes central nervous system neurofibrillary degeneration, which may lead to encephalopathy, malaise, speech disorder, dementia, convulsions, and vomiting. Treatment should be discontinued if the patient develops lethargy, confusion, seizures, metabolic acidosis or elevated aluminum concentration [4]. Alum therapy should be used with caution in patients with renal failure who have also received chemotherapy. Four cases of aluminum intoxication were reported in this patient population. If alum therapy is used in this population, monitor serum aluminum levels and mental status [16]. Studies have not directly compared the efficacy of intravesical alum irrigation with other pharmacologic agents administered in this manner; however, therapeutic outcomes for both intravesical formalin and alum for hemorrhagic cystitis have been reviewed [1]. Compared with 5% and 10% formalin irrigation, alum 1% irrigation results in a statistically significant increase in complete response and a statistically significant decrease in major and minor complications. Mortality and recurrence rates are comparable. For the treatment of bladder hemorrhage, intravesical alum irrigation has a complete response rate of 100%, a recurrence rate of 17.9%, a minor complication rate of 19.4%, a major complication rate of 3.2%, and a mortality rate of 0%. Such comparisons are unavailable for intravesical silver nitrate and alum irrigations. With respect to toxicity, an intravesical alum irrigation appears to have a more favorable adverse effect profile than an intravesical silver nitrate or formalin irrigation. Anuria has been reported with sequential intravesical administration of a 1% silver nitrate irrigation followed by a saline irrigation. The cause of anuria was obstruction of the right collecting system and bladder due to deposition of silver salts formed by an interaction between silver nitrate and sodium chloride [17]. Retropertioneal inflammation secondary to reflux and extravasation of 1% silver nitrate bladder instillation has also been reported [18]. Minor complications associated with an intravesical formalin irrigation in a concentration of 1% to 10% include suprapubic discomfort, tachycardia, reduction in bladder capacity and low grade vesicoureteral reflux [19]; (Likournas et al, 1979)[20]. Although suprapubic discomfort from silver nitrate of formalin irrigation can be minimized or avoided by using regional or local anesthesia during instillation, these measures are time-consuming and may be associated with adverse effects as well. Major adverse effects, such as hydronephrosis, ureterovesical junction obstruction, ureter fibrosis [21], acute tubular necrosis [22][23][24] and bladder rupture [25] have occurred following formalin irrigations in concentrations of 4% or greater. Formalin also produces histological changes in bladder urothelium, an effect which persits for as long as one month after irrigation and necessitates a delay in biopsy of bladder tissue [26].
In the treatment of bladder hemorrhage, intravesical alum irrigation is highly effective, has a low rate of hemorrhage recurrence, and adverse effects are generally limited to suprapubic discomfort and low grade fever. Vesicoureteral reflux as a result of intravesical alum irrigation has not been documented. More serious side effects such as encephalopathy may result when an instillation rate of 3 grams or more per hour is employed in renally-impaired patients. Because alum is minimally irritating to mucous membranes, its administration does not require regional or general anesthesia, as does formalin or silver nitrate. Bladder biopsy may be performed as early as 2 weeks after an alum irrigation, since alum does not alter the histologic characteristics of transitional cell carcinoma. On the other hand, evidence of urothelial damage may persist for as long as one month after an intravesical formalin irrigation, necessitating a delay in biopsy of bladder tissue.
CONCLUSION

5. ALUMINUM HYDROXIDE Al(OH)3, ATH, Hydrate of alumina
Insoluble forms of aluminum
Properties
Molecular formula
Al(OH)3
Molar mass
78.00 g/mol
Appearance
White amorphous powder
Density
2.42 g/cm³, solid
Melting point
300 °C, 573 K, 572 °F
solubility in water
g/100 mL (20 °C)
Solubility
soluble in acids, alkalis, HCl, H2SO4
Acidity(pKa)
>7

6. CHEMISTRY
Amphoteric
It dissolves in acid, forming Al(H2O)63+ (hexaaquaaluminium(3+)) or its hydrolysis products.
It also dissolves in strong alkali, forming Al(OH)4- (tetrahydroxidoaluminate(1-)).
Gibbsite has a typical metal hydroxide structure with hydrogen bonds. It is built up of double layers of hydroxyl groups with aluminium ions occupying two-thirds of the octahedral holes between the two layers.[1]

7. USE Antacids, antiperspirants, dentifrices
Included as an adjuvant in some vaccines (e.g. anthrax vaccine)
Stimulates the immune system by inducing the release of uric acid, an immunological danger signal.
In a mouse model of allergen sensitization during pregnancy
Aluminum hydroxide is also widely used in the chemical, pharmaceutical, fabric, paper, glass, pottery, and printing industries.
: Fire retardant, polyesters, acrylics,
ethylene vinyl acetate, epoxies, PVC, rubber
Fire retardant 지연제
Aluminium hydroxide also finds use as a fire retardant filler for polymer applications in a similar way to magnesium hydroxide and mixtures of huntite and hydromagnesite.[2][3] It decomposes at about 180 °C, absorbing a considerable amount of heat in the process and giving off water vapour. In addition to behaving as a fire retardant, it is very effective as a smoke suppressant in a wide range of polymers, most especially in polyesters, acrylics, ethylene vinyl acetate, epoxies, PVC, rubber.
[edit] Pharmaceutical
This compound is used as an antacid under names such as Alu-Cap, Aludrox or Pepsamar. The hydroxide reacts with excess acid in the stomach, reducing its acidity.[4] This decrease of acidity of the contents of the stomach may in turn help to relieve the symptoms of ulcers, heartburn or dyspepsia. It can also cause constipation and is therefore often used with magnesium hydroxide or magnesium carbonate, which have counterbalancing laxative effects. This compound is also used to control phosphate (phosphorus) levels in the blood of people suffering from kidney failure.
Aluminium hydroxide is included as an adjuvant in some vaccines (e.g. anthrax vaccine). One of the well-known brands of aluminium hydroxide adjuvant is Alhydrogel, made by Brenntag. Since it absorbs protein well, it also functions to stabilize vaccines by preventing the proteins in the vaccine from precipitating or sticking to the walls of the container during storage. Aluminium hydroxide is often mis-called "alum" even by researchers; however, "alum" properly refers to aluminium sulfate.
Vaccine formulations containing aluminium hydroxide stimulates the immune system by inducing the release of uric acid, an immunological danger signal. This strongly attracts certain types of monocytes which differentiate into dendritic cells. The DCs pick up the antigen, carry it to lymph nodes, and stimulate T cells and B cells.[5] It appears to contribute to induction of a good Th2 response, so is useful for immunizing against pathogens that are blocked by antibodies. However, it has little capacity to stimulate cellular (Th1) immune responses, important for protection against many pathogens.[6]
On the other hand, in a mouse model of allergen sensitization during pregnancy, while the mother mice had a Th2 response to the allergen plus aluminium hydroxide, the offspring showed lower IgG1 and IgE compared to the offspring of mice treated with the allergen alone or plus a Th1 adjuvant.
[edit] Potential adverse effects
So far,[when?] adverse effects in humans resulting from the use of aluminium hydroxide adjuvants have not been proven, although it has been a subject of controversy.[citation needed]
Brain lesions found in Alzheimer's disease sometimes contain more aluminium compared to normal tissue. It is not thought that aluminium causes (etiology) Alzheimer's, but rather that once the disease develops, aluminium may be involved in its progression.[7][8] However, multiple epidemiological studies have found no connection between exposure to aluminium and neurological disorders.[9][10][11]
In 2007, tests in mice of the anthrax vaccine using aluminium hydroxide adjuvant were reported as resulting in adverse neuropathy symptoms.[12]

8. 유통중인 ALUMINUM HYDROXIDE
가스민에프정
Aluminum hydroxide gel 450mg
뉴란타
Aluminum hydroxide gel 250g
Chlorhexidine acetate 0.003g
+Magnesium hydroxide 400mg
다겔정
(건조수산화알루미늄겔)    
Aluminum hydoxide gel 300mg
메빌정
Aluminum hydoxide gel 250mg

9. ADVERSE EFFECTS
Adverse effects in humans resulting from the use of aluminium hydroxide adjuvants have not been proven, although it has been a subject of controversy.
Brain lesions found in Alzheimer's disease sometimes contain more aluminium compared to normal tissue.
It is not thought that aluminium causes Alzheimer's, but rather that once the disease develops, aluminium may be involved in its progression.
Multiple epidemiological studies have found no connection between exposure to aluminium and neurological disorders.
In 2007, tests in mice of the anthrax vaccine using aluminium hydroxide adjuvant were reported as resulting in adverse neuropathy symptoms.

10. TERATOGENICITY
The frequency of malformations was not increased among the offspring of pregnant rats or mice given mg/kg/d or mg/kg/d of aluminum hydroxide
Respectively Decreased fetal weight and increased frequencies of skeletal variations were seen among the offspring of pregnant rats given 384 mg/kg/d of aluminum hydroxide and also citric acid, which promotes absorption of aluminum, but maternal toxicity was evident under these conditions.
(Gomez et al., 1991)
Similarly, decreased fetal weight was seen along with evidence of maternal toxicity when pregnant mice were treated with 166 mg/kg/d of aluminum hydroxide and also with lactic acid, which increases the solubility of the aluminum.
(Colomina et al., 1992)
768 dose is equivalent to 16 gm of aluminum in a 60 kg woman.

11. TERATOGENICITY
The coadministration of citrate with aluminum hydroxide, to promote the absorption of aluminum, did not increase the incidence of malformations among exposed rats, but it did increase the incidence of developmental variations and fetotoxicity.
As was suggested by the data in this report, other animal studies indicate that parenterally administered aluminum from various aluminum salts can cross the placenta and accumulate in fetal tissues. These exposures have been associated with an increase in fetal death and reabsorptions in rats, as well as abnormal skeletal growth, and impaired learning, memory, and neuromotor development in treated offspring.

12. TERATOGENICITY
In a case report from 1998, the mother of a 9-year-old girl with profound mental retardation, multifocal seizures, spastic tetraplegia, growth retardation, and spasticity (cerebral cortical atrophy and neurological dysfunction) was found to have used an average of 15,000 mg of aluminum hydroxide per day throughout pregnancy, implicating aluminum intoxication as a possible cause of the neurological dysfunction in the child.
(Gilbert-Barness et al., 1998)
In a review of mice, rat, and rabbit studies, Borak and Wise question whether dietary aluminum exposure will lead to significant accumulation in pregnant animals or their fetuses.
It is important to note that in most studies, adverse developmental effects of aluminum have not been associated with orally administered aluminum.

13. Quality and quantity of data on which risk estimated is based
TERATOGENICITY
Magnitude of teratogenic risk to child born after exposure during gestation
: UNDETERMINED
Quality and quantity of data on which risk estimated is based
: LIMITED
A SMALL RISK CANNOT BE EXCLUDED
HIGH RISK OF CONGENITAL ANOMALIES IN THE CHILDREN OF WOMEN WHO TOOK ALUMINUM HYDROXIDE DURING PREGNANCY IS UNLIKELY.
THIS RISK ASSESSMENT IS FOR USE OF ALUMINUM HYDROXIDE AS AN ANTACID. NO INFORMATION IS AVAILABLE REGARDING THE RISK ASSOCIATED WITH OCCUPATIONAL EXPOSURE TO ALUMINUM HYDROXIDE, BUT THE AMOUNT ABSORBED THROUGH OCCUPATIONAL EXPOSURE IS LIKELY TO BE SUBSTANTIALLY LESS THAN THAT INGESTED BY PEOPLE WHO TAKE ALUMINUM HYDROXIDE AS A MEDICATION IN MOST CASES.
No epidemiological studies of congenital anomalies among the children of women who took antacids containing aluminum hydroxide during pregnancy have been reported.

14. ALUMINUM Ubiquitous distribution
The most abundant metal in the earth's crust
(Baselt, 2000; Lewis, 1997)
Sources of exposure are constant through dust particles and ingestion of food and water.
Aluminum has one naturally occurring isotope: Al(27). In addition, ten radioactive isotopes are known
(Budavari, 1996)
Absorption of aluminum through the skin is insignificant. An average adult is estimated to absorb 15 mcg (0.3 to 0.5 %) of the 5 mg/day that is taken in from the environment
(Committee on Nutrition, 1986)

15. ALUMINUM not occur free in its metallic form in nature
it exists naturally combined with fluorine, silicon, oxygen and other substances in the earth's crust
(Bingham et al, 2001; HSDB , 2001; Lewis, 1997)
It often occurs as an oxide and combined with silica (Budavari, 1996)
Soy-based infant formulas may contain a mean aluminum content of 1,478 mcg/L
should probably not be used in infants with renal impairment or in low-birth-weight infants (Committee on Nutrition, 1986).
aluminum content was lowest in breast milk (23.4 +/ mcg/L)
cows milk was 70 mcg/L
reconstituted infant formulas was 226 mcg/L, with wide variation (302 to 1,149 mcg/L) in aluminum content
(Fernandez-Lorenzo et al, 1999 Spain)
ALUMINUM SALT
% ELEMENTAL ALUMINUM
Aluminum hydroxide
34.58
Aluminum oxide
52.91
Aluminum phosphate
22.12
Bismuth aluminate
20.97
Dihydroxy aluminum carbonate
18.74

16. ALUMINUM-DIETARY SOURCES
present in most foods and is used in food packaging
intake may range from 4 to 80 mg/day (Baselt, 2000).
found in a number of commercial teas.
: One study found between 555 and 1,009 mcg Al per gram (dry weight)
the absorption of aluminum from tea may be very low.
The main dietary source of aluminum is food additives.
Food preparation and storage, including soft drink packaging in aluminum cans, contributes little aluminum to the diet. Preparation of acidic foods in aluminum cookware can increase their aluminum content (Muller et al, 1993).

17. ALUMINUM WITH POISONING/EXPOSURE Acute aluminum toxicity is unlikely.
Most cases of aluminum toxicity in humans are in one of two categories:
Patients with chronic renal failure
People exposed to aluminum in the workplace
Soluble forms of aluminum
Aluminum chloride AlCl(3+), aluminum fluoride AlF(3), aluminum sulfate (Al(SO4)3), aluminum citrate (AlC(6)H(8)O(7))
Greater potential for toxicity than , due to their greater absorption
Insoluble forms (such as aluminum hydroxide (AlOH(3)).
Insoluble forms of aluminum are poorly absorbed from the gastrointestinal tract.

18. MEAN ALUMINUM CONTENT (mcg/L)
Aluminum accumulation may occur in individuals with normal renal function and who receive chronic parenteral nutrition with aluminum-contaminated solutions (Klein, 1995).
ADDITIVES & SOLUTIONS
MEAN ALUMINUM CONTENT (mcg/L)
Albumin 5%
486
Albumin 25%
Ca gluconate 10%
Heparin 1000 units/Ml
684
Potassium phosphate
,598
Sodium phosphate

19. ALUMINUM Aluminum is renally excreted
Patients with renal failure are prone to aluminum toxicity, either from aluminum in the dialysate or other exogenous sources, especially aluminum-containing phosphate binders and antacids. Signs and symptoms may include dementia, memory loss, aphasia, ataxia, seizures, altered EEG and osteomalacia.
Chronic exposure to aluminum dust may cause dyspnea, cough, pulmonary fibrosis, pneumothorax, pneumoconiosis, encephalopathy, weakness, incoordination and epileptiform seizures.

20. Respiratory distress and fibrosis with large blebs.
HEENT:
Eye: innocuous
Aluminum salts : may cause eye irritation. mucous membranes, conjunctivitis, dermatoses, and eczema.
CARDIOVASCULAR
Cardiac hypertrophy may occur in chronic hemodialysis patients with aluminum accumulation.
RESPIRATORY
Pulmonary fibrosis, asthma, COPD, chronic interstitial pneumonia, sarcoid-like lung granulomatosis, dyspnea, cough and pneumothorax may occur after chronic inhalation.
SHAVER'S DISEASE –
This illness is caused by industrial exposure to aluminum fumes or dust
Respiratory distress and fibrosis with large blebs.
Symptoms include productive coughing and wheezing, substernal pain, weakness and fatigue; spontaneous pneumothorax is a frequent complication.
Autopsy findings include emphysema and interstitial pulmonary fibrosis. Silicon is often inhaled with the aluminum, and the function of each of these elements is as yet unclear
(Bingham et al, 2001; Hammond & Beliles, 1980; Harbison, 1998).

21. Memory loss, include speech and language impairment
NEUROLOGIC
Dialysis encephalopathy syndrome (DES)
The most widely recognized and probably the most severe manifestation of aluminum toxicity.
DES usually requires serum aluminum levels above 100 mcg/L.
DES was originally secondary to high levels of aluminum in dialysate, mainly in dialysis therapy using softened or untreated water.
Reduction in the aluminum content to 0.4 micromol/L (10 mcg/L) or less resulted in prevention.
Moreover, the switch to aluminum-free phosphate binders (such as calcium carbonate) to treat patients with chronic renal failure has also decreased their per oral aluminum exposure
Clinical features of 'dialysis dementia
Memory loss, include speech and language impairment
epileptic seizures (focal or grand mal), motor disturbance , dementia

22. linked to the histopathology of Alzheimer disease.
NEUROLOGIC
linked to the histopathology of Alzheimer disease.
Alzheimer disease : illness with deterioration of mental functions related to memory, judgment and abstract thinking, plus personality/behavior changes.
The distinctive pathohistological features : neurofibrillary tangles, senile plaques and amyloid deposits. According to some sources, aluminum is linked to these senile plaques and amyloid deposits.
Increased concentrations of aluminum have been found in the brain tissue of patients with Alzheimer disease.
It is still unclear whether aluminum is involved etiologically in this disease or exists merely as a marker of some other pathophysiologic process.
Occupational exposure to aluminum has been associated with cognitive deficits and delayed reaction times
Rather than aluminum having an etiologic function, one theory is that some primary pathogenic event or events responsible for Alzheimer disease may affect the genetically-determined barriers to aluminum, resulting in increased amounts of aluminum being accessible to vulnerable target sites in the brain (Crapper McLachlan, 1986b).

23. GASTROINTESTINAL HEPATIC GENITOURINARY HEMATOLOGIC
Chronic aluminum hydroxide use may cause constipation.
HEPATIC
Linked to liver disorder.
Aluminum-induced osteomalacia was reported in patients with liver failure who were taking aluminum containing antacids.
GENITOURINARY
The dialysis encephalopathy syndrome in patients with renal failure.
Renal failure patients may also develop renal osteodystrophy and a type of microcytic anemia as effects of aluminum toxicity.
HEMATOLOGIC
Microcytic anemia may present as an effect of aluminum toxicity.

24. DERMATOLOGIC MUSCULOSKELETAL ENDOCRINE
Dermatitis, irritation, delayed hypersensitivity, telangiectases and granulomas may occur from dermal contact with aluminum.
MUSCULOSKELETAL
Aluminum-related bone disease is a progressive form of osteomalacia that can lead to severe bone pain, fractures and crippling deformities. Aluminum may contribute to dialysis-associated arthropathy.
ENDOCRINE
May decrease parathyroid hormone secretion.

25. RANGE OF TOXICITY TLV (Al metal/Al oxides) - 10 mg/m.
Reported oral animal LD50 values
0.1 g/kg for aluminum fluoride
1 to 4 g/kg for aluminum chloride
6 g/kg for aluminum sulfate.
LABORATORY/MONITORING
The most common method used for measuring aluminum in serum, water and dialysate is graphite furnace atomic absorption.

26. ALUMINUM HYDROXIDE
Quick take: Based on experimental animal studies, aluminum hydroxide is not expected to increase the risk of congenital malformations. Other toxicity of aluminum may occur if a sufficient amount is absorbed.

27. Study design
Case : 임신중(1st trimester) aluminum hydroxide 에 노출된 산모 271대상
Estimate the gestational age at expose
Estimate the time and dose of exposure to aluminum hydroxide
demographic information, medical, obstetric history, details of any concomitant exposure
Co-exposure to other medication
Other relevant co-exposure

28. Control Age, gravity Co-exposure to other madicine
Other relevant co-exposures
Alcohol, cigarette smoking, X-ray

29. Outcome Spontaneous abortion Live births
Major malformation
:abnormality of structure, function, metabolism present at birth that may result in physical, mental, social disabilities or death
Outcome
Spontaneous abortion
Live births
Gestational age at delivery(weeks)
Birth weight(g)
Low birth weight (>2500g)
Preterm births(<37weeks)
Major malformations
Minor malformations
Chromosomal abnormalities
Minor malformation
: defects with limited medical, mental, or social malformation

30. Data analysis
Continuous variables were compared between groups by Student t test.
Categorical variables including rate of minor and major malformation, were compared between groups by means of a Fisher;s exact test
Value of p <0.05 : statistically significant

31. Age(years) (mean±SD)
30.0±3.6
Gravity (n) (mean±SD)
2.0±1.3
Exposure to Aluminum hydroxide(median range)
gestational age at expose(weeks)
Dose(mg/day)
Duration of exposure(day)
Co-exposure to other medication (n)

32. 감사합니다.

34. TREATMENT OVERVIEW
CHELATION - Aluminum intoxication may be treated with the chelating agent deferoxamine with symptomatic relief of dialysis encephalopathy and osteomalacia and aluminum-induced anemia.
ENHANCED ELIMINATION - Hemodialysis, hemofiltration, and peritoneal dialysis will reduce SERUM aluminum. This may not effect the total body burden of aluminum unless aluminum has been mobilized from the tissues.