Identification

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Name
Silver
Accession Number
DB12965
Type
Small Molecule
Groups
Approved, Investigational
Description

Silver (Ag) is a chemical element that belongs in the family of transition metals in the periodic table. It has a high electrical conductivity, thermal conductivity, and reflectivity. Silver exists as a pure elemental form, alloy with other metals, and mineral. Having critical roles in various applications inducing chemical and industrial fields, silver compounds have also been used in the field of medicine for centuries due to their broad-spectrum biological actions. Silver nanoparticles especially have been widely used in industrial, household, and healthcare-related products due to their potent antimicrobial activity. Silver nitrate and Silver sulfadiazine have been used as topical antibacterial agents for the treatment of skin infections, while Silver sulfadiazine has also been valued for topical burn treatment 3. Silver and its compounds have been used in trials studying the management of dental caries since the 1800s, and they may be found in dental pastes as an active ingredients. However, some drawbacks of dental use of silver compounds include tooth discolouration and pulp irritation 3.

Structure
Thumb
Synonyms
  • Argentum metallicum
  • Colloidal silver
  • Nanosilver
  • Silver colloidal
  • Silver nanoparticles
  • Silver, colloidal
External IDs
CI 77820 / E-174 / INS NO.174 / INS-174
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Argentyn 23 Professional Silver First Aid GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Argentyn 23 Professional Silver First Aid GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Argentyn 23 Professionele Eerste Hulp Zilver GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Argentyn 23Bio active silver Bio active silver hydrosolLiquid0.023 mg/1mLTopicalNatural Immunogenics Corp2012-08-01Not applicableUs
Argentyn 23Professionele Eer Professionele Eerste Hulp Zilver GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Noble S PlusPaste, dentifrice0.7 g/100gDentalHankuk Bowonbio Co., Ltd2011-09-19Not applicableUs
Sovereign Silver Eerste Hulp GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Sovereign Silver Eerste Hulp GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Sovereign Silver First Aid GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Sovereign Silver First Aid GelGel23 mg/1000mLTopicalNatural Immunogenics Corp.2015-06-01Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Advance Acne CareSilver (0.1 mg/10mL) + Salicylic acid (20 mg/1mL)KitTopicalSwabplus Inc.2008-08-07Not applicableUs
BabyO2Silver (2 mg/240mL) + Glycerin (2 mg/240mL)SolutionTopicalOxigenesis, Inc.2019-02-26Not applicableUs
Disinfectant Deodorant (Waterfos)Silver (0.01 g/100mL) + Ostrea edulis shell (20 g/100mL)LiquidTopicalWorld Sung Ri Co., Ltd2017-06-01Not applicableUs
Disinfectant Deodorant (Waterfos)Silver (0.01 g/100mL) + Ostrea edulis shell (20 g/100mL)LiquidTopicalWorld Sung Ri Co., Ltd2017-06-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BabyO2Silver (2 mg/240mL) + Glycerin (2 mg/240mL)SolutionTopicalOxigenesis, Inc.2019-02-26Not applicableUs
Disinfectant Deodorant (Waterfos)Silver (0.01 g/100mL) + Ostrea edulis shell (20 g/100mL)LiquidTopicalWorld Sung Ri Co., Ltd2017-06-01Not applicableUs
Disinfectant Deodorant (Waterfos)Silver (0.01 g/100mL) + Ostrea edulis shell (20 g/100mL)LiquidTopicalWorld Sung Ri Co., Ltd2017-06-01Not applicableUs
Noble S PlusSilver (0.7 g/100g)Paste, dentifriceDentalHankuk Bowonbio Co., Ltd2011-09-19Not applicableUs
Categories
UNII
3M4G523W1G
CAS number
7440-22-4
Weight
Average: 107.8682
Monoisotopic: 106.90509302
Chemical Formula
Ag
InChI Key
BQCADISMDOOEFD-UHFFFAOYSA-N
InChI
InChI=1S/Ag
IUPAC Name
silver
SMILES
[Ag]

Pharmacology

Indication

Indicated for the treatment of acne for topical use or the management of dental caries for dental use.

Associated Conditions
Pharmacodynamics

Silver exhibits a broad-spectrum antimicrobial activity. Silver ions were shown to mediate an effective antibacterial action against Streptococcus mutans, one of major bacteria present in the human oral cavity and one of etiological microorganism of dental caries 3. A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria 2. Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positive S. aureus and Gram-negative E. coli by inhibiting the growth 4.

In experimental dinitrochlorobenzene-induced inflammatory models in porcine or murine skin, topical application of silver nitrate and nanocrystalline silver were shown to exert anti-inflammatory effects associated with lymphocyte apoptosis, decreased expression of pro-inflammatory cytokines, and reduced gelatinase activity 1. In a rat model of ulcerative colitis, orally or intracolonically administered nanocrystalline silver were shown to suppress matrix metalloproteinase (MMP-9), tumour necrosis factor (TNF), and interleukin-β (IL-β) and IL-12 1.

Mechanism of action

The majority of released silver ions precipitate with chloride or phosphate anions or bind to albumins, macroglobulins, or tissue debris 1. While bound silver ions do not exert antibacterial actions, they may potentially play a role in silver toxicity in case of chronic exposure 1. Silver ions mediate antibacterial effects via disrupting the bacterial, fungal, and protozoal cell membranes; they bind to disulphide in membrane proteins, readily allowing penetration through the membranes and intracellular absorption via pinocytosis 1. They may also bind to negatively-charged peptidoglycans in the cell wall via electrostatic interactions, leading to disruption of membrane transport function and loss of structural integrity 3. Silver ions also bind to and oxidize sulphydryl groups (SH) in bacterial cytoplasmic enzymes to aberrate their function in metabolic processes. Silver nanoparticles may cause an increase in reactive oxygen species (ROS) inside the microbial cells leading to metal-induced oxidative stress and cell damage 2. They also modulate cellular signal system via inhibition of phosphorylation of essential bacterial proteins to eventually cause cell death 2. It is also reported that silver ions also attach to guanine in bacterial DNA, which inhibits DNA replication 3. While it is not fully understood, the mode of action of silver compounds in preventing and arresting dental caries is thought to involve inhibition of the demineralization process in addition to cytoplasmic and membrane function perturbation mentioned above 3. Silver compounds may directly interact with hydroxyapatite, a major tooth component 3.

TargetActionsOrganism
UMetallothionein
binder
Humans
UCeruloplasmin
binder
Humans
USerum albumin
binder
Humans
UAlpha-2-macroglobulin
binder
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Although metallic silver is inert in the presence of human tissues, silver and its compounds may dissociate upon contact with skin surface, body fluids, and secretions, allowing the silver ions to be absorbed into the blood circulation 1. Soluble silver salts are absorbed from the respiratory and gastrointestinal tracts. However, up to 90-99% of orally ingested silver is not absorbed and percutaneous absorption of silver ions through intact or damaged skin is also reported to be low 1. Absorbed silver ions are deposited into elastic and connective tissues throughout the body 5. Biologically active silver ions mainly binds to intracellular proteins as inert complexes, and readily binds and precipitates with inorganic cations like chloride and phosphate, which explains low absorption 1.

Volume of distribution

Following exposure to large amounts, excess silver is reported to accumulate in skin, liver, kidneys, spleen, corneas, gingival, mucous membranes and nails 3. In a study of rats with ligated bile ducts, deposition of silver was 48% in the liver and 2.5% in the gastrointestinal tract 5. Clinical and experimental studies suggest that silver is bound as inert precipitates in lysosomal vacuoles of the blood brain barrier and blood-CSF barrier without being absorbed into neurological tissue 1.

Protein binding

Silver absorbed in the body as Ag+ bind rapidly to various proteins including albumin and macroglobulin as inert complexes for distribution to bone and soft tissues 1,5.

Metabolism

No pharmacokinetic data on metabolic pathways.

Route of elimination

Silver mainly undergoes biliary elimination to be excreted as feces 5. Findings from a rat study demonstrates that biliary excretion accounted for between 24% and 45% of total silver administered, and animal studies indicate that fecal elimination may account for up to 99% of the ingested silver 5.

Half life

The biological half-life for silver is a few days for animals and up to 50 days for human liver 5. In humans, the biological half-life of silver in lungs has been estimated to range from 1 to 52 days 5.

Clearance
Not Available
Toxicity

Acute oral LD50, acute dermal LD50, and acute inhalation LD50 for 4 hours in rat are >5000 mg/kg, >2000 mg/kg, and >5.16 mg/m^3, respectively MSDS.

While individuals experiencing mild to moderate silver toxicity remain asymptomatic, chronic inhalation has been associated with mild chronic bronchitis and rare cases of exposure to large amounts of silver have been associated with symptoms of peripheral neuropathy, decreased mental status, and seizures 5. Argyria is a detoxification mechanism for excess silver where the body sequesters and deposits excess silver in the blood vessels and connective tissue to render it in the form of silver protein complexes or silver sulphide 3,5. The development of argyria through occupational exposure is reported to be a slow process 5. While argyria does not cause significant pathological damage in any tissue 1, heavy deposition of insoluble silver precipitates can cause discoloration or blue-grey darkening of the eyes, nasal septum, throat, skin, and other internal organs following repeated exposure 5. Signs from prolonged intake of low doses of silver compound may include fatty degeneration of the liver and kidneys, and changes in blood cells 3. Silver may cause metal fume fever, and colloidal silver preparations are known to exert harmful effects in humans 5.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Lansdown AB: A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686. doi: 10.1155/2010/910686. Epub 2010 Aug 24. [PubMed:21188244]
  2. Dakal TC, Kumar A, Majumdar RS, Yadav V: Mechanistic Basis of Antimicrobial Actions of Silver Nanoparticles. Front Microbiol. 2016 Nov 16;7:1831. doi: 10.3389/fmicb.2016.01831. eCollection 2016. [PubMed:27899918]
  3. Peng JJ, Botelho MG, Matinlinna JP: Silver compounds used in dentistry for caries management: a review. J Dent. 2012 Jul;40(7):531-41. doi: 10.1016/j.jdent.2012.03.009. Epub 2012 Apr 3. [PubMed:22484380]
  4. Jung WK, Koo HC, Kim KW, Shin S, Kim SH, Park YH: Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl Environ Microbiol. 2008 Apr;74(7):2171-8. doi: 10.1128/AEM.02001-07. Epub 2008 Feb 1. [PubMed:18245232]
  5. SILVER, ELEMENTAL - National Library of Medicine HSDB Database - Toxnet [Link]
External Links
KEGG Compound
C06710
PubChem Compound
23954
PubChem Substance
347829105
ChemSpider
22394
ChEBI
9141
Wikipedia
Silver
ATC Codes
D08AL30 — Silver
MSDS
Download (363 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentDental Decay1
1Not Yet RecruitingPreventionHernia / Hernia, Abdominal / Ventral Hernias1
1RecruitingTreatmentBacterial Infections / Foot Infection Fungal1
1WithdrawnNot AvailableMyalgic Encephalomyelitis (ME)1
1WithdrawnTreatmentChronic Rhinosinusitis (Diagnosis)1
1, 2CompletedNot AvailableHealthy Volunteers2
1, 2RecruitingTreatmentAcute maxillary sinusitis caused by M. catarrhalis1
2CompletedTreatmentAtopic Dermatitis (AD) / Dermatitis, Eczematous1
2CompletedTreatmentWound Healing / Wound Infections1
2CompletedTreatmentMinor burns1
2Unknown StatusPreventionDown Syndrome (DS)1
2, 3CompletedTreatmentDeep Partial Thickness Burn1
3CompletedPreventionHygiene2
3CompletedTreatmentHygiene6
3Unknown StatusScreeningNormal Subjects1
4CompletedTreatmentSecond-degree Burn1
4Not Yet RecruitingTreatmentPostoperative pain1
4Unknown StatusSupportive CarePain / Thoracotomy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitTopical
LiquidTopical0.023 mg/1mL
SolutionTopical
LiquidTopical
Paste, dentifriceDental0.7 g/100g
GelTopical23 mg/1000mL
LiquidTopical0.01 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)961MSDS
boiling point (°C)2212MSDS
water solubilityInsolubleMSDS
Predicted Properties
PropertyValueSource
logP-0.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m3·mol-1ChemAxon
Polarizability1.78 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
Kingdom
Inorganic compounds
Super Class
Homogeneous metal compounds
Class
Homogeneous transition metal compounds
Sub Class
Not Available
Direct Parent
Homogeneous transition metal compounds
Alternative Parents
Not Available
Substituents
Homogeneous transition metal
Molecular Framework
Not Available
External Descriptors
elemental silver (CHEBI:9141)

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Activates the metallothionein I promoter. Binds to the metal responsive element (MRE).
Specific Function
Core promoter binding

Components:
References
  1. Scheuhammer AM, Cherian MG: Quantification of metallothioneins by a silver-saturation method. Toxicol Appl Pharmacol. 1986 Mar 15;82(3):417-25. [PubMed:3952727]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Ferroxidase activity
Specific Function
Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iro...
Gene Name
CP
Uniprot ID
P00450
Uniprot Name
Ceruloplasmin
Molecular Weight
122204.45 Da
References
  1. SILVER, ELEMENTAL - National Library of Medicine HSDB Database - Toxnet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Lansdown AB: A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686. doi: 10.1155/2010/910686. Epub 2010 Aug 24. [PubMed:21188244]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Tumor necrosis factor binding
Specific Function
Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for differen...
Gene Name
A2M
Uniprot ID
P01023
Uniprot Name
Alpha-2-macroglobulin
Molecular Weight
163289.945 Da
References
  1. Lansdown AB: A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686. doi: 10.1155/2010/910686. Epub 2010 Aug 24. [PubMed:21188244]

Drug created on October 20, 2016 19:38 / Updated on November 02, 2019 03:05