Guna-Hip
Guna-Hip Uses, Dosage, Side Effects, Food Interaction and all others data.
Arnica montana is a plant/plant extract used in some OTC (over-the-counter) products. It is not an approved drug.
Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298). Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). Canakinumab is marketed under the brand name Ilaris and indicated for patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA). Clinical trials have established the administration of canakinumab every 2 weeks to be safe and effective, offering a considerable advantage over the existing treatment with the human IL-1 receptor antagonist, anakinra, which must be injected daily and which is often poorly tolerated by patients.
Novartis AG has developed canakinumab as a subcutaneous injection and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases.
Metenkefalin is an endogenous opioid and beta-endorphin. It has been shown to reduce chromosomal abberations in patients with multiple sclerosis. Metenkefalin, along with tridecactide, are under investigation as an immunomodulatory therapy for moderate to severe COVID-19.
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 . 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 .
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 . A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria . Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positive S. aureus and Gram-negative E. coli by inhibiting the growth .
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 . 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 .
Trade Name | Guna-Hip |
Generic | Anti-interleukin-1.alpha. immunoglobulin g rabbit + canakinumab + silver + arnica montana + metenkefalin + calcium fluoride + sus scrofa cartilage + sus scrofa collagen + citrullus colocynthis fruit pulp + toxicodendron pubescens leaf |
Type | Injection, solution |
Therapeutic Class | |
Manufacturer | |
Available Country | United States |
Last Updated: | September 19, 2023 at 7:00 am |
![Guna-Hip Guna-Hip](https://www.medicinesfaq.com/media/png/guna-hip.png)
Uses
Canakinumab is an interleukin-1β blocker used to treat Periodic Fever Syndromes such as Cryopyrin-Associated Periodic Syndromes (CAPS) and Familial Mediterranean Fever (FMF), and also to treat active Systemic Juvenile Idiopathic Arthritis (SJIA).
Used in patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA).
Metenkefalin is an investigational endogenous opioid being studied for the treatment of COVID-19.
Metenkefalin is indicated in Bosnia for the treatment of relapsing-remitting multiple sclerosis.
Indicated for the treatment of acne for topical use or the management of dental caries for dental use.
Guna-Hip is also used to associated treatment for these conditions: Localized muscle pain, PainFamilial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), Neonatal-Onset Multisystem Inflammatory Disease (NOMID), Active systemic Juvenile idiopathic arthritisAcne
How Guna-Hip works
In inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra).
Metenkefalin is an agonist of µ and δ opioid receptors. It also causes immunostimulation at low doses and immunosuppression at higher doses. Metenkefalin can also inhibit the production of aldosterone, deoxycorticosterone, and corticosterone. Unfortuneately, the mechanisms by which these effects occur have not been well described in the literature.
The majority of released silver ions precipitate with chloride or phosphate anions or bind to albumins, macroglobulins, or tissue debris . While bound silver ions do not exert antibacterial actions, they may potentially play a role in silver toxicity in case of chronic exposure . 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 . 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 . 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 . They also modulate cellular signal system via inhibition of phosphorylation of essential bacterial proteins to eventually cause cell death . It is also reported that silver ions also attach to guanine in bacterial DNA, which inhibits DNA replication . 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 . Silver compounds may directly interact with hydroxyapatite, a major tooth component .
Toxicity
The most common adverse reactions involved the central nervous system (headache and vertigo), gastrointestinal system (diarrhea and nausea), neuromuscular and skeletal system (musculoskeletal pain), and respiratory system (rhinitis, nasopharyngitis and bronchitis). Influenza was also reported.
Data regarding overdoses of metenkefalin are not readily available. Animal overdose studies have not determined an LD50.
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 .
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 . 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 . The development of argyria through occupational exposure is reported to be a slow process . While argyria does not cause significant pathological damage in any tissue , 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 . Signs from prolonged intake of low doses of silver compound may include fatty degeneration of the liver and kidneys, and changes in blood cells . Silver may cause metal fume fever, and colloidal silver preparations are known to exert harmful effects in humans .
Volume of Distribution
- 6.01 L [typical CAPS patient weighing 70 kg]
Following exposure to large amounts, excess silver is reported to accumulate in skin, liver, kidneys, spleen, corneas, gingival, mucous membranes and nails . In a study of rats with ligated bile ducts, deposition of silver was 48% in the liver and 2.5% in the gastrointestinal tract . 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 .
Elimination Route
The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.
Metenkefalin reaches a Cmax of 1266.14pg/mL, with a Tmax of 0.16h, and an AUC of 360.64pg*h/mL.
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 . 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 . Absorbed silver ions are deposited into elastic and connective tissues throughout the body . 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 .
Half Life
26 days
The half life of metenkefalin is 4.2-39 minutes.
The biological half-life for silver is a few days for animals and up to 50 days for human liver . In humans, the biological half-life of silver in lungs has been estimated to range from 1 to 52 days .
Clearance
- 0.174 L/day [typical CAPS patient weighing 70 kg]
Elimination Route
The route of elimination for canakinumab has not yet been determined.
Silver mainly undergoes biliary elimination to be excreted as feces . 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 .
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