Ocubrex

Uses

No FDA- or EMA-approved therapeutic indications on its own.

Indicated mainly in allergic conditions including urticaria, sensitivity reactions, angioneurotic oedema, seasonal hay fever, vasomotor rhinitis, cough, common cold, motion sickness.

Naphazoline is a sympathomimetic vasoconstrictor used for the symptomatic relief of redness and itching of the eye, and nasal congestion.

Naphazoline is indicated for use as OTC eyedrops for ocular vasoconstriction or as a nasal preparation for nasal congestion.

Sodium Chloride Nasal Drops is used for dry nasal membranes including dry nose resulting from cold and allergy medications. It moistens dry nasal passages from dry climates or from airplane travel, may help dissolve mucus from study noses and clears the nose after surgery. This sterile saline solution is also used to cleanse various parts of the body (wounds, body cavities) and medical equipment (e.g., bandages, catheters, drainage tubes). It is also used as a mixing solution (diluent) for other medications used to irrigate the body (e.g., bacitracin, polymyxin).

Zinc is an essential element commonly used for the treatment of patients with documented zinc deficiency.

Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .

Ocubrex is also used to associated treatment for these conditions: Acne, Asthenopia, Ocular Irritation, Skin Mycoses, Eye discomfort, Skin disinfection, Irrigation of the ocular surface therapyAllergic Contact Dermatitis, Allergic Reaction, Allergic Rhinitis (AR), Allergic cough, Allergies, Allergies caused by Serum, Allergy to House Dust, Allergy to vaccine, Angioneurotic Edema, Asthma, Bronchial Asthma, Bronchitis, Common Cold, Conjunctival congestion, Conjunctivitis, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Drug Allergy, Eye allergy, Fever, Flu caused by Influenza, Food Allergy, Headache, Headache caused by Allergies, Itching of the nose, Itching of the throat, Migraine, Nasal Congestion, Nasal Congestion caused by Common Cold, Pollen Allergy, Productive cough, Pruritus, Rash, Rhinorrhoea, Seasonal Allergic Conjunctivitis, Sinus Congestion, Sinusitis, Sneezing, Transfusion Reactions, Upper Respiratory Tract Infection, Upper respiratory tract hypersensitivity reaction, site unspecified, Urticaria, Vasomotor Rhinitis, Acute Rhinitis, Allergic purpura, Conjunctival hyperemia, Dry cough, Excess mucus or phlegm, Itchy throat, Mild bacterial upper respiratory tract infections, Ocular hyperemia, Throat inflammation, Upper airway congestion, Upper respiratory symptoms, Watery eyes, Watery itchy eyes, Airway secretion clearance therapyBacterial Conjunctivitis, Blepharoconjunctivitis, Conjunctivitis, Conjunctivitis allergic, Dacryocystitis, Dacryostenosis, Dermatitis, Eczematous of the Eyelid, Eye Pain, Eye redness, Iritis, Lacrimation, Nasal Allergies, Nasal Congestion, Noninfective conjunctivitis, Otitis Media (OM), Photophobia, Foreign body sensation in eye, Ocular bacterial infections, Ocular vasoconstrictionAllergic Rhinitis (AR), Corneal Edema, Dehydration, Dehydration Hypertonic, Fluid Loss, Hemodilution, Hypertension Intracranial, Hypokalemia, Hyponatremia, Hypotonic Dehydration, Hypovolaemia, Increased Intra Ocular Pressure (IOP), Inflammation of the Nasal Mucosa, Isotonic Dehydration, Metabolic Acidosis, Nasal Congestion, Nasal irritation, Oliguria caused by Acute Renal Failure (ARF), Potassium deficiency, Sinusitis, Skin Irritation, Sodium Depletion, Dryness of the nose, Hypochloremic state, Mild Metabolic acidosis, Mild, moderate Metabolic Acidosis, Electrolyte replacement, Fluid replacement therapy, Heart-Lung-Machine, Oral rehydration therapy, Parenteral Nutrition, Parenteral rehydration therapy, Peritoneal dialysis therapy, Plasma Volume Replacement, Regional Citrate Anticoagulation (RCA), Renal Replacement Therapies, Urine alkalinization therapy, Wound irrigation therapy, Ear wax removal, Fluid and electrolyte maintenance therapy, Increased renal excretion of toxic substances, Maintenance source of fluid and electrolytes, Parenteral drug administration, Reducing brain massCandidiasis, Common Cold, Diaper Dermatitis, Diaper Rash, Eye redness, Iron Deficiency (ID), Ocular Irritation, Skin Irritation, Sunburn, Wilson's Disease, Zinc Deficiency, Dietary and Nutritional Therapies, Dietary supplementation

How Ocubrex works

Information regarding the mechanism of action of boric acid in mediating its antibacterial or antifungal actions is limited. Boric acid inhibits biofilm formation and hyphal transformation of Candida albicans, which are critical virulence factors . In addition, arrest of fungal growth was observed with the treatment of boric acid .

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

Naphazoline is a vasoconstrictor that functions by stimulating alpha adrenergic receptors in arterioles leading to decreased congestion at the site of administration.

Naphazoline causes the release of norepinephrine in sympathetic nerves. Norepinephrine binds to alpha adrenergic receptors and causes vasoconstriction. Naphazoline is also a mild beta adrenergic receptor agonist, which can cause rebound vasodilation after the alpha adrenergic stimulation has ended. Naphazoline's release of norepinephrine also triggers a negative feedback loop which decreases production of norepinephrine, which can lead to rhinitis medicamentosa after long term use when naphazoline is stopped.

Sodium and chloride — major electrolytes of the fluid compartment outside of cells (i.e., extracellular) — work together to control extracellular volume and blood pressure. Disturbances in sodium concentrations in the extracellular fluid are associated with disorders of water balance.

Zinc has three primary biological roles: catalytic, structural, and regulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .

Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .

In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .

There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .

Zinc deficiency in humans decreases the activity of serum thymulin (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans [A342417].

The change of Th(1) to Th(2) function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells [A3424].

In humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .

In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers [A3424]. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .

The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .

Dosage

Ocubrex dosage

Adults: 4 mg 3-4 times daily.

Children:

• Up to 1( one) year: 1 mg twice daily
• 1-5 years: 1 mg 3-4 times daily
• 6-12 years: 2 mg 3-4 times daily or as directed by the physician

Infants, children & adults: 2-6 drops into each nostril as needed daily

Use in Children: Safe for pediatrics

Side Effects

Drowsiness, dizziness, headache, psychomotor impairment, urinary retention, dry mouth, blurred vision and gastro intestinal disturbances, paradoxical stimulation may rarely occur, especially in high dosage or in children.

No side Effects are expected to occur. However stinging, sneezing, increased nasal discharge, or salty taste may occur in some cases.

Toxicity

Acute oral LD50 is 2660 mg/kg in rat . Individuals are likely to be exposed to boric acid from industrial manufacturing or processing. Local tissue injury from boric acid exposure is likely due to caustic effects. Systemic effects from boric acid poisoning usually occur from multiple exposures over a period of days and involve gastrointestinal, dermal, CNS, and renal manifestations. Gastrointestinal toxicity include persistent nausea, vomiting, diarrhea, epigastric pain, hematemesis, and blue-green discoloration of the feces and vomit . Following the onset of GI symptoms, a characteristic intense generalized erythroderma follows . Management of mild to moderate toxicity should be supportive. In case of severe toxicity, dialysis may be required in addition to supportive treatment.

Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.

In high doses or when ingested, naphazoline can lead to central nervous system depression (which can progress to coma and death), hypothermia, bradycardia, and death. This effect is especially pronounced in children under 6 years.

Long term use of naphazoline can lead to rhinitis medicamentosa once naphazoline is stopped. This condition is a result of norepinephrine release by naphazoline triggering a negative feedback loop.

Safety and effectiveness in children under 12 has not been established. Studies in elderly patients have yet to be performed. Risk in pregnancy, breast feeding, and on overall fertility have not been established, though pregnant and breast feeding patients should consider the risk and benefit before starting naphazoline treatment.

The rare inadvertent intravascular administration or rapid intravascular absorption of hypertonic sodium chloride can cause a shift of tissue fluids into the vascular bed, resulting in hypervolemia, electrolyte disturbances, circulatory failure, pulmonary embolism, or augmented hypertension.

According to the Toxnet database of the U.S. National Library of Medicine, the oral LD50 for zinc is close to 3 g/kg body weight, more than 10-fold higher than cadmium and 50-fold higher than mercury .

The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been measured in rats and mice .

Precaution

Chlorpheniramine may produce mild sedation and it is advised that patients under continuous treatment should avoid operating machinery. Not recommended during pregnancy & lactation.

Interaction

Alcohol, CNS depressants, anticholinergic drugs, MAOIs.

Volume of Distribution

Volume of distribution ranges from 0.17 to 0.5 L/kg in humans, where large amounts of boric acid are localized in brain, liver, and kidney .

Distribution data for naphazoline are scarce but imidazoline compounds are distributed throughout the body, and can cross the blood-brain barrier.

The volume of distribution is 0.64 L/kg.

A pharmacokinetic study was done in rats to determine the distribution and other metabolic indexes of zinc in two particle sizes. It was found that zinc particles were mainly distributed to organs including the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender .

Elimination Route

Boric acid is well absorbed from the gastrointestinal tract, open wounds, and serous cavities but displays limited absorption in intact skin . Following intraperitoneal injection in mice, the peak concentration was reached in about 1.0-1.5 hr in the brain whereas the value was 0.5 hr in other tissues .

Well absorbed in the gastrointestinal tract.

Absorption data for naphazoline are scarce but imidazoline compounds in general are weakly basic and lipophilic, with high bioavailability from the gastrointestinal tract.

Absorption of sodium in the small intestine plays an important role in the absorption of chloride, amino acids, glucose, and water. Chloride, in the form of hydrochloric acid (HCl), is also an important component of gastric juice, which aids the digestion and absorption of many nutrients.

Zinc is absorbed in the small intestine by a carrier-mediated mechanism . Under regular physiologic conditions, transport processes of uptake do not saturate. The exact amount of zinc absorbed is difficult to determine because zinc is secreted into the gut. Zinc administered in aqueous solutions to fasting subjects is absorbed quite efficiently (at a rate of 60-70%), however, absorption from solid diets is less efficient and varies greatly, dependent on zinc content and diet composition .

Generally, 33% is considered to be the average zinc absorption in humans . More recent studies have determined different absorption rates for various populations based on their type of diet and phytate to zinc molar ratio. Zinc absorption is concentration dependent and increases linearly with dietary zinc up to a maximum rate [L20902].

Additionally zinc status may influence zinc absorption. Zinc-deprived humans absorb this element with increased efficiency, whereas humans on a high-zinc diet show a reduced efficiency of absorption .

Half Life

According to human cases of poisoning, the elimination half-life of boric acid ranges from 13 to 24 hours .

21-27 hours

Half life has not been determined but effects last for 4 to 8 hours. Other imidazoline compounds have half lives varying from 2 to 12 hours.

17 minutes

The half-life of zinc in humans is approximately 280 days .

Clearance

A case report of acute boric acid poisoning following oral ingestion of 21 g of boric acid presents the total body clearance of 0.99 L/h before hemodialysis .

Clearance data for naphazoline is unavailable.

In one study of healthy patients, the clearance of zinc was found to be 0.63 ± 0.39 μg/min .

Elimination Route

Regardless the route of administration, boric acid predominantly undergoes rapid renal excretion of >90% of total administered dose as unchanged form. Small amounts are also excreted into sweat, saliva, and feces. Following administration as ointment, urinary excretion of boric acid accounted for only 1% of the administered dose .

Imidazoline compounds undergo some hepatic metabolism but a large fraction of the dose may be excreted unchanged in the urine. Urinary excretion is higher with more acidic urine.

Substantially excreted by the kidneys.

The excretion of zinc through gastrointestinal tract accounts for approximately one-half of all zinc eliminated from the body .

Considerable amounts of zinc are secreted through both biliary and intestinal secretions, however most is reabsorbed. This is an important process in the regulation of zinc balance. Other routes of zinc excretion include both urine and surface losses (sloughed skin, hair, sweat) .

Zinc has been shown to induce intestinal metallothionein, which combines zinc and copper in the intestine and prevents their serosal surface transfer. Intestinal cells are sloughed with approximately a 6-day turnover, and the metallothionein-bound copper and zinc are lost in the stool and are thus not absorbed .

Measurements in humans of endogenous intestinal zinc have primarily been made as fecal excretion; this suggests that the amounts excreted are responsive to zinc intake, absorbed zinc and physiologic need .

In one study, elimination kinetics in rats showed that a small amount of ZnO nanoparticles was excreted via the urine, however, most of the nanoparticles were excreted via the feces .

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

It is unknown if this medication passes into breast milk. Consult with your doctor before breast-feeding.

Contraindication

There is no definite contraindication to therapy. It should be used with caution in epilepsy, prostatic hypertrophy, glaucoma and hepatic disease. The ability to drive or operate machinery may be impaired.

Tell your doctor about your medical history, especially of heart problems (e.g., congestive heart failure), lung problems (pulmonary edema), kidney problems, low levels of potassium (hypokalemia), high levels of sodium (hypernatremia), and any allergies.

Innovators Monograph

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