Rimonid Eye Drops

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

Store in a cool, dry place away from heat and direct sunlight.

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Indications

• Seborrhoeic dermatitis
• Dandruff
• Scalp psoriasis
• Bacterial infections affecting the scalp

Dosage

Children: For children, apply 3 times a week for 1 week, then apply twice weekly as needed. Refer to BNF for Children for further details.

Adults: Apply to the affected area as directed, typically 1-3 times weekly depending on the condition being treated. Refer to specific product guidelines for detailed dosing.

Mechanism of action

Benzalkonium chloride exerts its antimicrobial effect by disrupting the cell membrane of microorganisms, leading to leakage of cellular contents and ultimately cell death. This is facilitated by its cationic nature, which allows it to bind to negatively charged bacterial surfaces.

Pharmacodynamics

Benzalkonium chloride demonstrates rapid bactericidal activity, with effectiveness observed against gram-positive and gram-negative bacteria, fungi, and some viruses. Its antiseptic properties may be enhanced in the presence of moisture and are typically influenced by the concentration of the solution used.

Pharmacokinetics

Benzalkonium chloride is poorly absorbed through the skin. After topical application, it remains primarily at the site of application, where it exerts localized effects. Systemic absorption is minimal, and it is primarily eliminated through the skin and urine. However, specific pharmacokinetic data may vary based on formulation and application site.

Pregnancy

Benzalkonium chloride should be used with caution during pregnancy. Refer to specific guidelines or consult a healthcare professional.

Breast-feeding

Benzalkonium chloride should be used with caution while breastfeeding. Refer to specific guidelines or consult a healthcare professional.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Shampoo
• Soap or detergent
• Topical solution

Indications

• Open-angle glaucoma
• Ocular hypertension

Dosage

Children: For paediatric dosing, consult the BNF for Children.

Adults: Apply one drop to the affected eye(s) once daily.

Mechanism of action

Brimonidine tartrate stimulates alpha-2 adrenergic receptors in the eye, which reduces the release of norepinephrine, leading to decreased production of aqueous humor and increased outflow. This action lowers intraocular pressure, making it effective for treating glaucoma and ocular hypertension.

Pharmacodynamics

Brimonidine exhibits a selective action on alpha-2 adrenergic receptors, leading to a decrease in presynaptic release of norepinephrine. This results in reduced aqueous humor production and enhanced outflow. The reduction in IOP is significant and can be sustained over time, although tolerance may develop with prolonged use.

Pharmacokinetics

Brimonidine is absorbed through the cornea after topical application. Peak plasma concentrations occur within 2 hours, and the drug undergoes extensive hepatic metabolism, primarily via glucuronidation. The elimination half-life is approximately 2 hours, and it is excreted primarily in the urine as metabolites.

Contra-indications

• Cerebrovascular disease
• Severe depression
• Heart failure
• History of angina
• Hypertension
• Parkinson's syndrome
• Raynaud's phenomenon
• Severe vasovagal attack

Adverse effects

• Eye disorders
• Ocular pruritus
• Conjunctival hemorrhage
• Dry eye
• Eye discomfort
• Eye inflammation
• Increased lacrimation
• Oedema of the eyelids and conjunctiva
• Bradycardia
• Diarrhea
• Gastrointestinal discomfort
• Irritability
• Decreased libido
• Nasal dryness
• Palpitations
• Postural hypotension
• Abnormal sensation
• Sleep disorders
• Syncope
• Vision disturbances
• Fatigue
• Dry mouth

Interactions

• Beta blockers
• Non-selective sympathomimetics

Precautions

• Use with caution in patients with chronic respiratory conditions
• Monitor intraocular pressure and visual fields regularly
• Monitor for excessive reduction in intraocular pressure following peri-operative use

Pregnancy

Manufacturer advises avoiding use due to lack of information on safety.

Breast-feeding

Manufacturer advises avoiding use due to lack of information on safety.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Eye drops containing Brimonidine tartrate 0.2% (2 mg/ml)

Indications

• Disinfection of surfaces
• Antiseptic for skin
• Preservative in pharmaceuticals
• Treatment of minor cuts and abrasions

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric populations.

Adults: Refer to the BNF for specific formulations and concentrations as doses may vary based on the application and preparation.

Mechanism of action

The bactericidal action of benzalkonium chloride is believed to result from the disruption of intermolecular interactions, which leads to the dissociation of cellular membrane lipid bilayers in bacteria. This disruption compromises cellular permeability, causing leakage of vital cellular contents. Moreover, the agent can deactivate important molecular complexes such as enzymes that regulate various respiratory and metabolic activities within the cells. Cationic surfactants like benzalkonium chloride can thus effectively disrupt critical intermolecular interactions and tertiary structures in biochemical systems, impairing bacterial function.

Pharmacodynamics

Benzalkonium chloride is classified as a biocidal agent with a relatively long duration of action. It exhibits a spectrum of activity against various microorganisms, including bacteria, certain viruses, fungi, and protozoa; however, it is ineffective against bacterial spores. The agent tends to demonstrate greater efficacy against gram-positive bacteria compared to gram-negative ones. The mode of action can be bacteriostatic (preventing growth) or bactericidal (killing bacteria), depending on its concentration. The activity of benzalkonium chloride is generally stable across different pH levels but is enhanced at elevated temperatures and with extended exposure.

Pharmacokinetics

The pharmacokinetic properties of benzalkonium chloride, including absorption, distribution, metabolism, and excretion, are not fully characterized. Its topical application limits systemic exposure, and it primarily exerts localized effects at the site of application. The duration of action and efficacy may be influenced by the formulation and concentration used.

Pregnancy

Benzalkonium chloride is generally considered safe for use during pregnancy when applied topically, but systemic absorption should be minimized. Always consult a healthcare provider for use during pregnancy.

Breast-feeding

Benzalkonium chloride is considered safe for topical application during breastfeeding, but care should be taken to avoid exposure to the infant. Consultation with a healthcare provider is recommended.

Storage

Store at room temperature, away from moisture and heat. Keep in a tightly closed container, protected from light.

Formulations

• Topical solution
• Disinfectant wipes
• Liquid antiseptics

Indications

• Open-angle glaucoma
• Ocular hypertension

Dosage

Children: For paediatric patients aged 2 years and older, the usual dosage is one drop of brimonidine 0.1% in the affected eye(s) twice daily. For those aged 2 to less

Adults: The recommended dosage for adults is one drop of brimonidine 0.2% in the affected eye(s) twice daily.

Mechanism of action

In the eye, the activation of alpha-2 adrenoceptors by brimonidine leads to a reduction in aqueous humor production through inhibition of adenylyl cyclase and a decrease in cyclic AMP levels. This results in decreased norepinephrine release, which lowers IOP. Additionally, chronic dosing is proposed to increase uveoscleral outflow, further contributing to IOP reduction. The drug does not significantly affect episcleral venous pressure.

Pharmacodynamics

Brimonidine is highly selective for alpha-2 adrenergic receptors, being 1000-fold more selective than for alpha-1 receptors. This selectivity reduces the risk of systemic side effects, such as hypotension and sedation, and minimizes unwanted ocular effects typically mediated by alpha-1 receptors. The peak ocular hypotensive effect of brimonidine occurs approximately two hours after administration, with studies showing a consistent reduction in IOP over extended treatment periods.

Pharmacokinetics

Brimonidine is rapidly absorbed into the eye upon ophthalmic administration. Its onset of action occurs within a few hours, with a peak effect observed at around two hours post-dosing. The drug is metabolized in the liver, and its elimination half-life in plasma is approximately 2-4 hours. Due to its selective action, brimonidine exhibits a favorable pharmacokinetic profile with limited systemic exposure.

Contra-indications

• Hypersensitivity to brimonidine or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Ocular hyperemia
• Dry mouth
• Fatigue
• Dizziness
• Allergic conjunctivitis
• Blurred vision

Interactions

• Caution should be exercised when using with other CNS depressants
• Potential interaction with antihypertensive medications leading to additive effects

Precautions

• Use with caution in patients with severe cardiovascular disease
• Use with caution in patients with depression or other mood disorders
• Consider monitoring IOP regularly during therapy

Pregnancy

Brimonidine is classified as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Brimonidine is excreted in human milk. Caution is advised when administered to nursing women.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Brimonidine 0.1% ophthalmic solution
• Brimonidine 0.2% ophthalmic solution

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Adjustment of pH in pharmaceutical formulations
• Facilitation of drug absorption
• Used in sterile preparations

Dosage

Children: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Adults: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Mechanism of action

Hydrochloric acid dissociates in aqueous solution to release hydrogen ions (H+), leading to a decrease in pH. This acidic environment promotes the activation of pepsinogen to pepsin, an enzyme essential for protein digestion. Additionally, the acidity aids in the absorption of certain minerals and drugs that require an acidic environment for optimal bioavailability.

Pharmacodynamics

The primary pharmacodynamic action of hydrochloric acid is the maintenance of gastric acidity, which is essential for normal digestive processes. The acidic environment helps in denaturing proteins, activating digestive enzymes, and providing a barrier against pathogenic microorganisms. Its effects can influence the absorption and efficacy of various medications, particularly those that are pH-dependent.

Pharmacokinetics

Hydrochloric acid does not undergo significant systemic absorption when used in its normal contexts, as it acts locally within the gastrointestinal tract. The amount of hydrochloric acid produced by the stomach varies with food intake and physiological needs. It is secreted by parietal cells in the gastric mucosa, and its secretion is regulated by neural, hormonal, and local factors. The half-life of hydrochloric acid is not applicable as it is continuously produced and neutralized within the gastrointestinal tract.

Contra-indications

• Hypersensitivity to hydrochloric acid or any of its components
• Severe renal impairment
• Active gastrointestinal bleeding

Adverse effects

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Esophageal irritation
• Gastric mucosal irritation
• Electrolyte imbalances

Interactions

• May interact with alkaline substances, potentially neutralizing hydrochloric acid
• Caution with antacids as they may affect the efficacy of hydrochloric acid

Precautions

• Use with caution in patients with a history of gastritis or gastric ulcers
• Monitor electrolytes in prolonged use
• Use cautiously in patients with respiratory conditions due to potential aspiration risks

Pregnancy

Hydrochloric acid is classified as a category C drug. Use during pregnancy only if clearly needed and the potential benefits justify the risks to the fetus.

Breast-feeding

There is limited data on the excretion of hydrochloric acid in human milk. Use with caution during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight and heat. Ensure the container is tightly closed.

Formulations

• Oral solutions
• Injectable forms
• Tablets

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Cryotherapy for the destruction of abnormal tissue
• Treatment of warts, moles, and other skin lesions
• Nitrogen narcosis in diving

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations in paediatric patients.

Adults: For cryotherapy, the dosage and duration depend on the specific condition being treated and should be determined by the healthcare provider. Refer to specific guidelines for each condition.

Mechanism of action

In cryotherapy, the mechanism of action involves three stages: heat transfer, cell injury, and inflammation. The boiling point of liquid nitrogen is -196°C, which initiates heat transfer, leading to cell injury during the thawing process. The inflammation stage follows, characterized by edema and erythema, resulting from cellular death and contributing to local cell destruction. Additionally, nitrogen can cause direct toxic effects on brain functions, leading to nitrogen narcosis, which impairs cognitive abilities and motor functions due to its impact on nerve conduction.

Pharmacodynamics

Nitrogen's pharmacodynamics relate to its behavior in cryotherapy and asphyxiation. In cryotherapy, it induces tissue destruction through rapid cooling, leading to apoptosis of abnormal cells. In high-pressure environments, nitrogen narcosis affects the central nervous system, producing symptoms similar to alcohol intoxication, ultimately decreasing reasoning, decision-making abilities, and manual dexterity.

Pharmacokinetics

Nitrogen does not undergo metabolism in the traditional sense, as it is an inert gas at physiological conditions. Its pharmacokinetics involve physical principles of gas exchange and partial pressures. In the case of nitrogen narcosis, the effects are influenced by the partial pressure of nitrogen in the bloodstream, which increases with depth during diving. Nitrogen is primarily eliminated from the body through respiration.

Adverse effects

• Narcotic effect at high pressures
• Stupor or euphoria
• Decreased motor function and manual dexterity
• Asphyxiation due to oxygen displacement

Precautions

• Careful monitoring in environments with high nitrogen pressures
• Avoidance of rapid ascents in diving to prevent nitrogen narcosis
• Use in controlled settings to prevent asphyxiation risks

Pregnancy

Nitrogen is generally considered safe in terms of direct effects during pregnancy; however, the safety of exposure in high-pressure environments should be assessed.

Breast-feeding

Nitrogen is not known to affect breastfeeding; however, caution is recommended in environments where nitrogen levels may displace oxygen.

Storage

Store in a cool, dry place away from heat sources; liquid nitrogen should be handled with care due to extreme cold.

Formulations

• Liquid nitrogen
• Nitrogen gas (compressed)

Indications

• Used in medical devices and containers for fluids
• Used in drug delivery systems

Dosage

Children: Polyvinyl is not a drug and therefore does not have a dosage.

Adults: Polyvinyl is not a drug and therefore does not have a dosage.

Mechanism of action

Polyvinyl does not have a pharmacological mechanism of action as it is a structural material rather than a drug. Its function is primarily physical, providing a safe and effective medium for storage and transport of medical fluids and medications.

Pharmacodynamics

As a polymer, polyvinyl does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its role in medicine is to serve as an inert substance that provides a barrier to contamination and ensures the integrity of the contents it holds.

Pharmacokinetics

Polyvinyl is not absorbed or metabolized in the body in the way that drugs are. It remains in a stable form and is excreted unchanged if it enters the body, with no systemic effects or pharmacokinetic profile.

Pregnancy

Polyvinyl products are generally considered safe for use during pregnancy; however, specific formulations should be assessed for safety.

Breast-feeding

Polyvinyl compounds are unlikely to pose a risk during breastfeeding, but exposure should be minimized when possible.

Storage

Store in a cool, dry place away from direct sunlight and moisture. Keep out of reach of children.

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Mechanism of action

Although not entirely elucidated, the bactericidal action of benzalkonium chloride is believed to be due to the disruption of intermolecular interactions. Such disruption can cause the dissociation of cellular membrane lipid bilayers of bacteria, resulting in compromised cellular permeability control and the leakage of important cellular contents. Additionally, other important molecular complexes like enzymes which control the maintenance of a great range of respiratory and metabolic cellular activities, are also susceptible to such deactivation. Consequently, a variety of critical intermolecular interactions and tertiary structures in very highly specific biochemical systems that allow bacterial agents to function normally can be readily disrupted or deactivated by cationic surfactants like benzalkonium chloride..

Pharmacodynamics

Benzalkonium chloride solutions are generally categorized as biocidal agents with relative long durations of action. Their spectrum of activity has been demonstrated against bacteria, to some viruses, fungi, and protozoa, although bacterial spores are treated as being resistant to the agent. Additionally, the agent generally shows more activity against gram-positive than gram-negative bacteria. Finally, solutions of benzalkonium chloride are bacteriostatic or bactericidal based on their concentration. Bacteriostatic agents act to prevent further growth of bacterial organisms that are present while bactericidal agents function to kill bacteria that are present. In general, the activity of the agent is not largely affected by pH, but such activity does increase substantially at higher temperatures and prolonged exposure times.

Mechanism of action

In the eye, alpha-1 adrenoceptors play a role in vasoconstriction, mydriasis, eyelid retraction, and elevation of intraocular pressure (IOP) whereas alpha-2 adrenoceptors are responsible for IOP reduction via a complex Gi-coupled signaling cascade pathway. Activation of alpha-2 receptors leads to inhibition of adenylyl cyclase and reduction of cyclic AMP levels. As a result, there is a decrease in norpinephrine (NE) release at the synaptic junction, NE-induced stimulation of beta-2 adrenoceptors, and production of aqueous humor by the ciliary epithelium. An elevated IOP is the most significant risk factor for developing glaucomatous optic neuropathy, which is associated with progressive visual field loss and functional disability if left untreated. Regardless of the etiology of the disease, the aim of current therapies for glaucoma is to reduce IOP, as reduction of IOP significantly reduces the risk of progression of vision loss even when IOP is already within the normal range. When administered ophthalmically, brimonidine is rapidly absorbed into the eye, acts as an agonist at ocular alpha-2 adrenoceptors and lowers IOP via a dual mechanism of action. It is proposed that initial dosing of the drug causes a reduction in aqueous humour production and chronic dosing leads to an increase in uveoscleral outflow. Brimonidine does not affect episcleral venous pressure. By reducing IOP, brimonidine aims to reduce the likelihood of glaucomatous visual field loss in ocular hypertension, and slow the progression of visual field defect in established open-angle glaucoma. When applied topically on skin, brimonidine reduces erythema through direct vasocontriction of small arteries and veins. As brimonidine mediates a potent peripheral vasoconstrictive activity by selectively working on the alpha-2 adrenoceptors, the use of brimonidine is thought to be efficacious for the treatment of facial erythema of rosacea, which is thought to arise from vasomotor instability and abnormal vasodilation of the superficial cutaneous vasculature of the face.

Pharmacodynamics

Brimonidine is a highly selective alpha-2 adrenergic receptor agonist that is 1000-fold more selective for the alpha2-adrenergic receptor than the alpha1-adrenergic receptor. This characteristic gives the drug some therapeutic advantages, since it reduces the risk of systemic side effects, such as systemic hypotension, bradycardia, and sedation. In addition, there is a reduction in the risk for developing alpha-1 mediated ocular unwanted effects, such as conjunctival blanching, mydriasis, and eyelid retraction. However, despite high alpha-2 receptor specificity, brimonidine may still produce alpha-1 adrenoceptor-mediated ocular effects, such as conjunctival vasoconstriction. Brimonidine has a peak ocular hypotensive effect occurring at two hours post-dosing. In a randomized, double-blind clinical study, ocular administration of 0.2% brimonidine in healthy volunteers resulted in a 23% reduction of mean intraocular pressure from baseline at 3 hours following administration. In comparative studies consisting of patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive effect of brimonidine was maintained during treatment periods of up to 1 year. Brimonidine mediates vasoconstrictive effects and it was shown to exhibit anti-inflammatory properties in _ex vivo_ human skin model and _in vivo_ inflammation models. In a clinial trials consisting of adults with moderate to severe facial erythema of rosacea, brimonidine was shown to improve the extent of redness at 3 hours after application, compared to placebo. It was shown to be a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200 µm. In _in vivo_ mouse inflammation models, brimonidine displayed anti-inflammatory properties by inhibiting edema. In a randomized, double-blind study, brimonidine reduced erythema for the 12 hours of the study in a dose-dependent manner. When adminsitered systemically, brimonidine was shown to cause cardiovascular effects by decreasing blood pressure, decreasing heart and respiratory rate, and prolonging the PR interval in the electrocardiogram. This is due to the targeting of adrenoceptors by the drug. Although the clinical significance has not been established, there is evidence that brimonidine exhibits neuroprotective activity in experimental models of cerebral ischemia and optic nerve injury. _In vitro_ studies show that brimonidine mediated protective effects on neuronal cells from kainate acid insult and on cultured retinal ganglion cells from glutamate-induced cytotoxicity, which is a possible mediator of secondary neuronal degeneration in human glaucoma. Neuroprotective actions of brimonidine were also demonstrated in rat models of acute retinal ischemia and chronic IOP elevation. It has been proposed that brimonidine may exert neuroprotective effects on the retina and optic nerve by enhancing intrinsic retinal ganglion cell survival mechanisms and/or induction of neuronal survival factors, such as bFGF. However, further investigations are needed to conclude on these possible therapeutic benefits of the drug.

Mechanism of action

In cryotherapy, mechanism of action could be classified into three stages: 1. heat transfer, 2. cell injury and 3. inflammation. Boiling point of liquid nitrogen is -196°C, which is the responsible for creating the initial stage which is heat transfer. The second stage is cell injury which is induced during thawing conditions of the cells. The last step in the cryotherapy is the inflammation stage which is characterized by edema and erythema. Inflammation occurs as a result of cellular death and it helps in local cell destruction. ... Nitrogen also has a direct toxic action of its own, affecting brain functions and inducing a stupor or euphoria. Nitrogen narcosis ("rapture of the deep" or "the martini effect") results from a direct toxic effect of high nitrogen pressure on nerve conduction and produces effects similar to alcohol intoxication. Complex reasoning, decision-making ability, motor function, and manual dexerity decrease. Individuals vary in this response widely, but it typically can be noticed among divers at depths exceeding 100 ft (30 m). For example, certain individuals experience no effect at depths of < or = 130 ft, whereas others feel some effect at around 80 ft. Nonetheless, the narcotic effect increases with increasing depth so that each additional 50 ft incrementally produces the effect of "another martini". A simple asphyxiant, nitrogen's main toxicty arises from its ability to displace O2 and generate an atmosphere that does not support the chemical reactions needed for maintenance of life. The displacement of O2 can be complete or incomplete, leading to varying degrees of hypoxia. Nitrogen is an inert substance and does not exert a direct toxicological effect. Nitrogen acts by the physiological effect of simple asphyxia on the target species within a Controlled Atmosphere Treatment (CAT) bubble. The biocide action of nitrogen is due to its displacement of oxygen from an atmospheric oxygen level of 20.8% to levels < 0.2% v/v in the CAT bubble. The level of oxygen is the critical factor. Victims exposed to atmospheres deficient in oxygen, i.e. < 19%, will begin to display signs and symptoms of oxygen-deficient exposure of air due to an increase in nitrogen.