Alphagan P

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)

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as this varies widely.

Adults: Refer to specific drug guidelines for adult dosing, as this varies widely.

Mechanism of action

The mechanism of action will vary depending on the specific drug referred to as 'adjust'. Generally, medications designed to 'adjust' physiological parameters may work by modulating neurotransmitter systems, altering hormonal levels, or affecting enzyme activity to achieve therapeutic effects.

Pharmacodynamics

Pharmacodynamics will depend on the specific drug, but typically involves the interaction of the drug with its receptor sites, leading to a biological response. The efficacy and potency of the drug are influenced by its affinity for the target receptors and the subsequent signaling pathways activated.

Pharmacokinetics

Pharmacokinetics, including absorption, distribution, metabolism, and excretion, will vary by drug. Common factors influencing pharmacokinetics include bioavailability, half-life, and the presence of food or other drugs that may affect the drug's metabolism and elimination from the body.

Indications

• Antiseptic treatment
• Antifungal treatment
• Management of minor burns and cuts
• Treatment of eye infections (as boric acid solution)

Dosage

Children: Refer to the BNF for Children for specific guidance on pediatric dosing.

Adults: Refer to specific product guidelines, as dosing can vary based on formulation and indication.

Mechanism of action

Borate compounds, such as boric acid, exhibit their effects primarily through the disruption of bacterial and fungal cell membrane integrity. They can interfere with the metabolism of microorganisms, leading to their death. Additionally, borates have anti-inflammatory properties, which may contribute to their therapeutic effects.

Pharmacodynamics

The pharmacodynamics of borate compounds involve their ability to inhibit enzyme activity in microbial cells, leading to the disruption of essential metabolic processes. They also have a mild antiseptic effect, which can help in reducing inflammation and promoting healing in affected tissues.

Pharmacokinetics

The pharmacokinetics of borate compounds can vary depending on the specific formulation and route of administration. Generally, borates are poorly absorbed through the gastrointestinal tract when ingested, which limits systemic exposure. However, topical applications can lead to localized effects. Borate compounds are known to be excreted primarily through the kidneys.

Pregnancy

Borate should be used in pregnancy only if clearly needed, as its safety has not been established.

Breast-feeding

Caution is advised when borate is used during breastfeeding due to insufficient data on its excretion in human milk.

Storage

Store in a tightly closed container, protected from moisture.

Indications

• Vulvovaginal candidiasis
• Fungal infections
• Antiseptic for minor cuts and abrasions
• Ocular antiseptic
• Insecticide in pest control

Dosage

Adults: Refer to specific guidelines for formulations. Commonly used as a 2-3% solution

Mechanism of action

Boric acid exerts its antifungal effects by disrupting the cell membrane integrity of fungi. It interferes with the synthesis of essential cellular components, leading to cell lysis and death. The acid also has mild antibacterial properties, which can help in reducing bacterial load in infected areas. The exact molecular pathways involved in these actions are not fully elucidated, but it is known to alter the pH of the environment, making it less conducive for fungal growth.

Pharmacodynamics

Boric acid demonstrates a low toxicity profile in humans when used appropriately. Its antifungal activity is primarily effective against Candida species, and it can be used as a second-line treatment for vulvovaginal candidiasis, particularly in cases of recurrent infections. The effectiveness of boric acid is also attributed to its ability to maintain an acidic environment, which is unfavorable for the growth of many pathogens. Its antiseptic properties help in reducing inflammation and promoting healing in infected tissues.

Pharmacokinetics

Boric acid is poorly absorbed through the gastrointestinal tract but can be absorbed through the skin and mucous membranes. Once absorbed, it is distributed throughout the body, with a tendency to accumulate in various tissues, including the liver and kidneys. The elimination half-life of boric acid is variable, depending on dosage and route of administration. It is primarily excreted unchanged in the urine. Due to its potential for toxicity with high systemic exposure, it is important to adhere to recommended dosages.

Contra-indications

• Hypersensitivity to boron or any component of the formulation
• Severe renal impairment

Adverse effects

• Skin irritation or rash
• Nausea
• Vomiting
• Diarrhea
• Headache
• Fatigue
• Tremors
• Confusion

Interactions

• May interact with other topical medications
• Caution with nephrotoxic agents

Precautions

• Use with caution in patients with renal insufficiency
• Careful monitoring is advised in long-term use
• Not recommended for use in large areas of broken skin

Pregnancy

Boric acid is classified as category C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited data available. It is advisable to avoid use while breastfeeding.

Storage

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

Formulations

• Topical ointment
• Powder
• Solution

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

• Dry eye syndrome
• Ocular lubrication
• Thickening agent in pharmaceutical formulations
• Food industry as a stabilizer and emulsifier

Dosage

Children: For paediatric use, refer to specific product guidelines and consult a healthcare professional for appropriate advice.

Adults: For dry eye treatment, apply as needed, typically 1 drop in each affected eye. Refer to specific product guidelines for exact formulation and frequency.

Mechanism of action

Carboxymethylcellulose works by forming a gel-like structure when it interacts with water, which helps retain moisture and provide lubrication. In ophthalmic applications, it acts as a protective agent for the ocular surface, reducing friction and providing comfort to patients with dry eye conditions.

Pharmacodynamics

The pharmacodynamic properties of carboxymethylcellulose are primarily related to its ability to increase viscosity and improve the stability of formulations. It does not undergo significant systemic absorption and exerts its effects locally, particularly in the gastrointestinal tract and on the ocular surface as a lubricant.

Pharmacokinetics

Carboxymethylcellulose is not absorbed significantly through the gastrointestinal tract when ingested, and its systemic bioavailability is negligible. When used in ophthalmic formulations, it acts locally on the eye without significant systemic effects. The elimination pathway is primarily through natural degradation and excretion of unabsorbed material.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal discomfort

Precautions

• Use with caution in patients with known hypersensitivity to cellulose derivatives
• Monitor for allergic reactions

Pregnancy

Carboxymethylcellulose is generally considered safe during pregnancy as it is not absorbed systemically.

Breast-feeding

Carboxymethylcellulose is considered safe during breastfeeding as it is not absorbed systemically.

Storage

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

Formulations

• Eye drops
• Oral suspensions
• Topical gels

Dosage

Children: Refer to specific drug guidelines or BNF for Children for accurate dosing information.

Adults: Refer to specific drug guidelines or BNF for accurate dosing information.

Mechanism of action

The mechanism of action of complex drugs can vary widely depending on their composition. Generally, these agents may act by modulating receptor activity, inhibiting enzyme pathways, or altering cellular signaling pathways. For instance, they may function as agonists or antagonists at specific receptors, influencing physiological responses such as neurotransmission or inflammation.

Pharmacodynamics

The pharmacodynamics of complex drugs involves understanding how they affect the body over time, including their potency, efficacy, and duration of action. These drugs may exhibit dose-dependent effects, where higher doses lead to increased therapeutic actions or side effects. Additionally, the interactions between the components of a complex formulation can result in synergistic or antagonistic effects, impacting the overall therapeutic outcome.

Pharmacokinetics

Pharmacokinetics of complex drugs encompasses the absorption, distribution, metabolism, and excretion (ADME) of the drug components. Absorption can be influenced by the formulation, while distribution may vary based on the lipophilicity and protein binding of each component. Metabolism often occurs in the liver, with various enzymes involved, and excretion typically takes place via renal or biliary pathways. The half-life of complex drugs can vary significantly based on their individual components.

Pregnancy

Consult healthcare provider. Risk-benefit assessment is essential before use.

Breast-feeding

Consult healthcare provider. Monitor for potential effects on the infant.

Storage

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

Dosage

Children: Paediatric dosing information is not specified; refer to specific product guidelines or the BNF for Children for appropriate dosing.

Adults: Dosage for adult patients depends on the specific application and formulation context. Refer to product-specific guidelines for appropriate dosing.

Mechanism of action

The mechanism of action of decahydrate compounds typically involves their role as solubilizing agents or stabilizers in formulations, enhancing the bioavailability of poorly soluble drugs. The presence of water molecules can facilitate the dissolution of the active ingredients, improving their absorption and therapeutic efficacy.

Pharmacodynamics

Pharmacodynamics of decahydrate compounds is largely dependent on their application in drug formulations. They can affect the osmotic pressure of solutions, influence the release rates of drugs from solid forms, and enhance the overall stability of pharmaceutical preparations. However, specific pharmacodynamic effects would vary based on the active ingredients they are combined with.

Pharmacokinetics

Pharmacokinetics of decahydrate salts is not typically characterized individually, as they generally function as excipients. However, their role in influencing the dissolution and absorption of active ingredients can indirectly affect the pharmacokinetics of the drug formulations they are part of. Factors such as solubility, permeability, and the physiological conditions of the gastrointestinal tract play significant roles in determining the overall pharmacokinetic profile.

Pregnancy

Consult a healthcare provider before use, as safety during pregnancy has not been well established.

Breast-feeding

Consult a healthcare provider before use, as safety during breastfeeding has not been well established.

Storage

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

Indications

• Dietary supplementation
• Metabolic disorders
• Energy provision in specific clinical settings

Dosage

Children: Refer to the BNF for Children for specific dosing instructions.

Adults: Refer to the BNF for specific dosing instructions.

Mechanism of action

Hexa functions primarily as a source of energy through beta-oxidation, where it is broken down into acetyl-CoA units that enter the citric acid cycle. This process ultimately leads to the production of ATP, which is essential for cellular energy.

Pharmacodynamics

Hexa contributes to the regulation of metabolic pathways involving fatty acids. It influences energy homeostasis and can impact lipid profiles in the body. The presence of medium-chain fatty acids like hexa can promote ketogenesis, especially in carbohydrate-restricted diets, providing an alternative energy source.

Pharmacokinetics

Hexa is absorbed through the gastrointestinal tract and is rapidly metabolized in the liver. It has a relatively short half-life, and its metabolites are efficiently utilized or excreted by the body. The pharmacokinetic profile may be affected by dietary factors and individual metabolic rates.

Pregnancy

Hexa should only be used in pregnancy if the benefits outweigh the risks. Consult with a healthcare professional.

Breast-feeding

It is unknown if hexa is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

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

• Topical antiseptic for skin disinfection
• Treatment of minor cuts and abrasions
• Disinfection of medical instruments
• Sanitization in healthcare settings

Dosage

Children: For children, dosage should be determined by a healthcare provider based on age and weight. Refer to specific guidelines for pediatric use.

Adults: For topical use, apply a thin layer to the affected area 1 to 3 times daily, depending on the severity of the condition.

Mechanism of action

Oxychloro exerts its antimicrobial effects primarily through the production of reactive oxygen species (ROS), which can damage cellular components of bacteria, leading to cell death. It disrupts bacterial cell membranes and inhibits enzymatic functions critical for bacterial survival.

Pharmacodynamics

The pharmacodynamic profile of oxychloro indicates that it has a broad spectrum of antibacterial activity. It is effective against both Gram-positive and Gram-negative bacteria. The compound's efficacy is influenced by factors such as concentration, exposure time, and the specific bacterial strain.

Pharmacokinetics

Oxychloro's pharmacokinetics can vary based on formulation and route of administration. Generally, after application, it demonstrates rapid local action at the site of infection or contamination, with minimal systemic absorption when used topically. Its elimination half-life and metabolic pathways are not well defined due to limited clinical data.

Pregnancy

Oxychloro should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare professional before use.

Breast-feeding

It is not known whether oxychloro is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Acidity regulator
• Stabilizing agent in pharmaceutical formulations
• Potential use in metabolic processes

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations, as pediatric dosing should be based on individual clinical scenarios.

Adults: Refer to specific guidelines for formulations containing tartarate, as dosing may vary based on the therapeutic context.

Mechanism of action

Tartarate acts as a salt that can influence the solubility and stability of various pharmaceutical compounds. It is known to interact with calcium ions and may affect the crystallization processes of certain compounds. In metabolic pathways, tartarate may participate in the citric acid cycle, contributing to energy production and various enzymatic reactions.

Pharmacodynamics

The pharmacodynamics of tartarate are largely related to its role as a buffering agent and stabilizer in formulations. It does not have direct pharmacological effects in the way that active drugs do but can influence the solubility and bioavailability of co-administered medications. Its effects on metabolic pathways can indirectly influence physiological responses.

Pharmacokinetics

The pharmacokinetics of tartarate, particularly potassium tartrate, involve absorption in the gastrointestinal tract, where it dissociates into potassium and tartrate ions. These ions can be absorbed and utilized in various biochemical processes. Excretion primarily occurs via the kidneys. The pharmacokinetic profile may vary based on the formulation and route of administration.

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.