Potassium nitrate

Identification

Summary

Potassium nitrate is a medication used to cauterize small wounds, remove granulation tissue, warts, and verrucae, and treat tooth sensitivity.

Brand Names
Meijer, Prevident 5000 Sensitive, Styptstix
Generic Name
Potassium nitrate
DrugBank Accession Number
DB11090
Background

Potassium nitrate is an inorganic salt with a chemical formula of KNO3. It is a natural source of nitrate and has been used as a constituent for several different purposes, including food preservatives, fertilizers, tree stump removal, rocket propellants, and fireworks. Potassium nitrate is a common active ingredient in toothpaste, exerting an anti-sensitivity action. It provides increasing protection against painful sensitivity of the teeth to cold, heat, acids, sweets or contact 13,14.

In addition, potassium nitrate is used as a diuretic in pigs, cattle, and horses. It is administered orally doses up to 30 g per animal per day 7.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 101.1032
Monoisotopic: 100.951524732
Chemical Formula
KNO3
Synonyms
  • Potassium nitrate
External IDs
  • E-252
  • INS NO.252
  • INS-252

Pharmacology

Indication

For the relief of tooth sensitivity, and is also used as a pesticide, insecticide, as a food additive, and a rodenticide 10,13,16.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofTooth sensitivity••• •••
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Pharmacodynamics

The potassium cation is an essential electrolyte that is important for the maintenance of intracellular osmotic pressure and for the maintenance of cell membrane potential, in particular, the potential of electrically excitable tissues 7. It is a regular component of the diet and is particularly abundant in fruit and vegetables. The recommended daily intake varies from 350-1275 mg in children to 1875 and 5625 mg in adults. In the United Kingdom, the recommended intake is 3.5 g/day for healthy adults 7. Potassium ions are believed to disturb the synapse between nerve cells, thus decreasing nerve excitation and the associated pain 10.

Potassium nitrates are ignitable fumigants also utilized as rodenticides and insecticides. They are added to other pesticide active ingredients (sulfur and carbon) and placed into fumigant gas cartridges, designed to be ignited and placed in pest-infested areas. The activated cartridge bombs release toxic gases which are lethal to select rodents, skunks, coyotes, and wasps 11.

Potassium ions have demonstrated in animal studies to act directly on the nerves and to reduce sensory activity 10. Tooth hypersensitivity can be relieved by inactivating the intra-dental nerve and inhibiting neural transmission, using suitable medications 10.

It has been found that potassium-to-sodium intake ratios are strongly related to cardiovascular disease risk than either nutrient alone. The data describing this relationship warrants further research for various target tissue endpoints 2.

Mechanism of action

Potassium (K+) is the principal cation modulating the osmotic balance of the body fluids. In animals, the maintenance of normal cell volume and pressure is dependent on Na+ and K+ pumping 17. Potassium transport through the hydrophobic interior of a cell membrane may be facilitated by several naturally occurring compounds that form lipid-soluble alkali metal cation complexes. Potassium has the critical role of a calcium counter-ion for numerous carboxylates, phosphates, and sulfates, and also acts to stabilize macromolecular structures 17.

Potassium is the primary agent for common, over the counter de-sensitizing toothpaste that prevents the transmission of nerve endings to the teeth. Potassium salts, including potassium nitrate, potassium chloride or potassium citrate work by diffusion across the dentinal tubules, causing depolarization of the nerve cells. In turn, these cells become unresponsive to excitatory stimuli. The effect of the potassium nitrate accumulates over time, and it may take several weeks for patients to notice improvement of pain symptoms 10.

Potassium nitrates control pests using a unique mechanism of action. Rather than directly poisoning rodents, nitrates support the combustion of charcoal in gas cartridges, promoting the production of toxic gases, which, are lethal to the target pest. The environmental protection agency in the USA (EPA) is only minimally concerned about the risk of direct human exposure to sodium or potassium nitrates, rather than pesticide accidents--typically involving skin burns or inhalation of toxic gases 17.

TargetActionsOrganism
UPotassium voltage-gated channel subfamily H member 2
agonist
Humans
Absorption

It is established that nitrate is quickly and almost entirely absorbed from the proximal and small intestine subsequent to ingestion in most animals, with little if any absorption from the stomach and lower intestine 13.

The vast majority of intestinal K+ absorption occurs in the small intestine; the contribution of the normal colon to net K+ absorption and secretion is trivial 5.

Volume of distribution

Nitrates are absorbed into the general blood circulation and are transported across the body. Radioactive tracer experiments have demonstrated that nitrates are distributed evenly among body organs, and their rate of distribution depends on blood flow 13.

Protein binding

Not Available

Metabolism

Nitrates are reduced to nitrites by the bacteria in saliva and the gastrointestinal system 13. The in vivo reduction of nitrates to nitrites depends on conditions that are subject to much variations such the volume and species of microflora present in the saliva/gastrointestinal tract, and stomach pH. Gastric pH is higher in infants younger than 6 months of age and during certain gastrointestinal tract infections, thereby favoring the reduction of nitrates 13.

Nitrate is metabolized to a small extent. The biotransformation of potassium nitrate consists of nitrate reduction, nitrite formation, nitrite reoxidation to nitrate, and formation of methemoglobin or NO, in a dynamic equilibrium 11, 12, 13.

Hover over products below to view reaction partners

Route of elimination

Nitrates are excreted in the urine primarily as inorganic nitrates 13.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Acute oral toxicity (LD50): 1901 mg/kg in rabbits MSDS and 3750 mg/kg in rats 7.

The primary acute toxic effect of nitrates is the development of methemoglobinemia, a condition in which greater than 10% of the hemoglobin in the body is transformed into methemoglobin. When this conversion exceeds 70% the condition may result in death 9.

The potassium ion by itself possesses very little toxicity; the toxicity of the salts is associated with the anion. Potassium nitrate is rapidly absorbed from the upper gastrointestinal tract and is excreted mostly as the unchanged drug 7. This excludes a small percentage of the ingested dose that is reduced by the microbial action of the gut to nitrite. Nitrites convert the hemoglobin in red blood cells into methemoglobin 7. In male rats given potassium nitrate, intestinal absorption was affected 1.

Adverse increased potassium intake included changes in blood lipids, triglyceride, decreased high-density lipoprotein [HDL] cholesterol), changes in renal function, and increases in catecholamine levels. The decrease in blood volume caused by increased potassium activates the sympathetic nervous system, resulting in the release of adrenaline and noradrenaline. Decreases in blood volume may also contribute to the observed changes in blood lipid concentrations 14.

Death and severe effects of nitrate ingestion are generally associated with doses of the drugs above 10g NO3-. Doses ranging from 2-9 g NO3- have been reported to cause methemoglobinemia. These values correspond to 33 - 150 mg NO3-/kg 9 Potassium nitrate was shown to cause low to moderate acute toxicity. Repeated dose toxicity was investigated in rats given oral doses in the range 10-100 mg/kg per day for 4 months; bronchopneumonia, local hemorrhages, and other circulatory disorders were observed in treated animals. Cattle were given oral doses of 345-450 mg/kg daily (expressed as nitrate) for several months; blood phosphate and magnesium were decreased and blood calcium, urinary magnesium, urea and milk urea were increased 7.

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.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Potassium nitrate which could result in a higher serum level.
AcebutololPotassium nitrate may increase the hyperkalemic activities of Acebutolol.
AceclofenacPotassium nitrate may increase the hyperkalemic activities of Aceclofenac.
AcemetacinPotassium nitrate may increase the hyperkalemic activities of Acemetacin.
AcetaminophenAcetaminophen may decrease the excretion rate of Potassium nitrate which could result in a higher serum level.
Food Interactions
No interactions found.

Products

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Active Moieties
NameKindUNIICASInChI Key
Potassium cationionic295O53K15224203-36-9NPYPAHLBTDXSSS-UHFFFAOYSA-N
NitrateionicT93E9Y284414797-55-8NHNBFGGVMKEFGY-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SheerDesenZ Desensitizing TreatmentFilm12 mg/1DentalCao Group, Inc.2010-09-012018-10-11US flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Attitude Adult Fluoride-free - Sensitive - SpearmintGel, dentifrice5 g/100gOralAttitude DBA 9055-7588 Québec Inc.2022-06-01Not applicableUS flag
Dr. Sheffield Sensitive CarePaste, dentifrice50 mg/1gOralSheffield Pharmaceuticals LLC2017-05-15Not applicableUS flag
EcoDent Res-Q-DentPaste50 mg/1gOralLotus Brands, Inc.2013-06-012019-07-29US flag
Jason Oral Comfort Sensitive Teeth Very Berry MintGel5 g/100gOralThe Hain Celestial Group, Inc.2017-10-162019-10-10US flag
Jason Total Protection SensitivePaste, dentifrice5 g/100gTopicalThe Hain Celestial Group, Inc2019-07-01Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
4 PackPotassium nitrate (50 mg/1g) + Potassium nitrate (50 mg/1g) + Sodium fluoride (2.4 mg/1g) + Sodium fluoride (2.4 mg/1g)Kit; PasteDentalSmiletwice, Inc.2018-09-14Not applicableUS flag
4 PackPotassium nitrate (50 mg/1g) + Potassium nitrate (50 mg/1g) + Sodium fluoride (2.4 mg/1g) + Sodium fluoride (2.4 mg/1g)Kit; PasteDentalSmiletwice, Inc.2018-09-14Not applicableUS flag
Advancew White Sensitive Maximum Strength Sensitivity Relief with WhiteningPotassium nitrate (50 mg/1g) + Sodium fluoride (2.4 mg/1g)Paste, dentifriceDentalChurch & Dwight Company, Inc.2001-03-012012-06-01US flag
Aim Sensitive Cavity ProtectionPotassium nitrate (50 mg/1g) + Sodium fluoride (2.4 mg/1g)Gel, dentifriceDentalChurch & Dwight Co., Inc.2015-03-25Not applicableUS flag
Alora SensitivityPotassium nitrate (50 mg/1g) + Sodium fluoride (2.5 mg/1g)Gel, dentifriceDentalAmazon, Inc2019-10-01Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Denta 5000 Plus SensitivePotassium nitrate (57.5 mg/1mL) + Sodium fluoride (5.8 mg/1mL)Gel, dentifriceDentalRising Pharma Holdings, Inc.2024-02-14Not applicableUS flag
DOCTRUST ONE S ToothPotassium nitrate (5.00 g/100g) + Silicon dioxide (17.50 g/100g) + Sodium fluoride (0.02 g/100g)Paste, dentifriceDentalDOCSMEDI OralBiome Co., Ltd.2021-12-01Not applicableUS flag
FluoridexPotassium nitrate (50 mg/1g) + Sodium fluoride (5 mg/1g)Paste, dentifriceDentalDENT-MAT HOLDINGS, LLC.2016-12-21Not applicableUS flag
FluoridexPotassium nitrate (50 mg/1g) + Sodium fluoride (5 mg/1g)Paste, dentifriceDentalDENT-MAT HOLDINGS, LLC.2017-01-06Not applicableUS flag
Fluoridex Daily Defense Sensitivity ReliefPotassium nitrate (0.050 g/1g) + Sodium fluoride (0.011 g/1g)Paste, dentifriceDentalDiscus Dental, Llc2013-09-272016-12-31US flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of inorganic compounds known as alkali metal nitrates. These are inorganic compounds in which the largest oxoanion is nitrate, and in which the heaviest atom not in an oxoanion is an alkali metal.
Kingdom
Inorganic compounds
Super Class
Mixed metal/non-metal compounds
Class
Alkali metal oxoanionic compounds
Sub Class
Alkali metal nitrates
Direct Parent
Alkali metal nitrates
Alternative Parents
Inorganic salts / Inorganic oxides
Substituents
Alkali metal nitrate / Inorganic oxide / Inorganic salt
Molecular Framework
Not Available
External Descriptors
potassium salt, inorganic nitrate salt (CHEBI:63043)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
RU45X2JN0Z
CAS number
7757-79-1
InChI Key
FGIUAXJPYTZDNR-UHFFFAOYSA-N
InChI
InChI=1S/K.NO3/c;2-1(3)4/q+1;-1
IUPAC Name
potassium nitrate
SMILES
[K+].[O-][N+]([O-])=O

References

Synthesis Reference

https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/potassium-nitrate

General References
  1. Grudzinski I, Szymanski A: The effect of acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats. Arch Environ Contam Toxicol. 1991 Sep;21(3):453-61. [Article]
  2. Weaver CM: Potassium and health. Adv Nutr. 2013 May 1;4(3):368S-77S. doi: 10.3945/an.112.003533. [Article]
  3. Schultz DS, Deen WM, Karel SF, Wagner DA, Tannenbaum SR: Pharmacokinetics of nitrate in humans: role of gastrointestinal absorption and metabolism. Carcinogenesis. 1985 Jun;6(6):847-52. [Article]
  4. Bychkov R, Gollasch M, Steinke T, Ried C, Luft FC, Haller H: Calcium-activated potassium channels and nitrate-induced vasodilation in human coronary arteries. J Pharmacol Exp Ther. 1998 Apr;285(1):293-8. [Article]
  5. Agarwal R, Afzalpurkar R, Fordtran JS: Pathophysiology of potassium absorption and secretion by the human intestine. Gastroenterology. 1994 Aug;107(2):548-71. [Article]
  6. Potassium Nitrate [Link]
  7. Committee for Veterinary Medicinal Products: Potassium nitrate summary report (EMEA/MRL/232/97-FINAL) [Link]
  8. CHEBI:63043 - potassium nitrate [Link]
  9. POTASSIUM NITRATE [Link]
  10. Mechanism of Action of a Desensitizing Fluoride Toothpaste Delivering Calcium and Phosphate Ingredients in the Treatment of Dental Hypersensitivity [Link]
  11. EPA NITRATES DOCUMENT [Link]
  12. Nitrates [Link]
  13. Potassium Nitrate [Link]
  14. NITRATE [Link]
  15. Guideline-Potassium Intake [Link]
  16. Nitrates in the meat industry [Link]
  17. POTASSIUM CHLORIDE [Link]
  18. Reduction in Dental Hypersensitivity with Nano-Hydroxyapatite, Potassium Nitrate, Sodium Monoflurophosphate and Antioxidants [Link]
  19. Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits [Link]
  20. DailyMed: Dr. Sheffield Sensitive Care (potassium nitrate 5%) [Link]
Human Metabolome Database
HMDB0303531
PubChem Compound
24434
PubChem Substance
347827891
ChemSpider
22843
RxNav
34316
ChEBI
63043
ChEMBL
CHEMBL1644029
Wikipedia
Potassium_nitrate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedOtherCaries1
3CompletedTreatmentDentinal Hypersensitivity1
3CompletedTreatmentHypersensitivity Dentin1
3Not Yet RecruitingTreatmentSensitivity, Tooth / Tooth Bleaching1
3Unknown StatusTreatmentDentin Sensitivity1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Kit; pasteDental
Gel, dentifriceOral5 g/100g
SuspensionOral
SolutionDental; Oral5 g
SolutionBuccal; Oral
GelDental; Oral
Paste, dentifriceOral50 mg/1g
PasteOral50 mg/1g
Paste, dentifriceDental
PasteOral
Paste, dentifriceOral
Gel, dentifriceDental
GelOral5 g/100g
Paste, dentifriceTopical5 g/100g
Gel, dentifriceDental5 g/100g
MouthwashOral
PasteBuccal
Cream; paste, dentifriceTopical
StickTopical
PowderOral100 %
Paste, dentifriceDental6.662 g/133g
Paste, dentifriceDental0.05 g/1g
PasteOral5 g/100mL
GelDental
Paste, dentifriceTopical
SolutionOral
FilmDental12 mg/1
SwabTopical
Gel; kit; liquid; pasteDental; Oral
Paste, dentifriceDental50 mg/1g
PasteDental
Kit; paste, dentifriceDental
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)334MSDS
boiling point (°C)400MSDS
water solubility35g/100mlhttps://www.cdc.gov/niosh/ipcsneng/neng0184.html
Predicted Properties
PropertyValueSource
logP-2.6Chemaxon
pKa (Strongest Basic)-9.9Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area66.2 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity8.35 m3·mol-1Chemaxon
Polarizability3.28 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0udi-0900000000-51dd8cb602ed71d15a99
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-104.642044
predicted
DeepCCS 1.0 (2019)
[M+H]+107.02523
predicted
DeepCCS 1.0 (2019)
[M+Na]+115.628006
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da

Enzymes

Kind
Protein
Organism
Enterobacter cloacae
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity
Specific Function
Not Available
Gene Name
onr
Uniprot ID
P71278
Uniprot Name
Pentaerythritol tetranitrate reductase
Molecular Weight
39488.93 Da
References
  1. Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transcription cofactor activity
Specific Function
The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.The ...
Gene Name
MUC1
Uniprot ID
P15941
Uniprot Name
Mucin-1
Molecular Weight
122100.89 Da
References
  1. Nitrate transport in salivary glands with implications for NO homeostasis [Link]

Drug created at December 03, 2015 16:51 / Updated at March 27, 2024 05:12