BRINZOX T

Indications

• Hypertension
• Angina
• Migraine prophylaxis
• Glaucoma
• Ocular hypertension

Dosage

Adults: Initially, 10 mg daily in 1-2 divided doses, then may be increased if necessary up to 60 mg daily, doses to be increased gradually. For glaucoma, the usual dose is 1 drop of 0.25% or 0.5% solution

Mechanism of action

Timolol maleate exerts its effects by blocking beta-adrenergic receptors (both beta-1 and beta-2). This blockade decreases heart rate and myocardial contractility, reduces renin secretion from the kidneys, and lowers aqueous humor production in the eye, thereby decreasing intraocular pressure in glaucoma. The inhibition of beta-2 receptors in bronchial tissues can lead to bronchoconstriction, which is important to consider in patients with respiratory conditions.

Pharmacodynamics

The pharmacodynamic effects of timolol maleate include its ability to lower heart rate and blood pressure through beta-adrenergic blockade. The onset of action for oral administration can be observed within 1 to 2 hours, with peak effects typically occurring within 2 to 4 hours. The duration of action allows for twice-daily dosing in many cases. In ocular formulations, timolol reduces intraocular pressure by approximately 20-30% in patients with glaucoma or ocular hypertension.

Pharmacokinetics

Timolol maleate is well-absorbed following oral administration, with a bioavailability of about 50-70%. It undergoes extensive hepatic metabolism, primarily through cytochrome P450 enzymes, and has an elimination half-life of approximately 4 to 6 hours. Renal excretion accounts for a significant portion of the drug's elimination. In patients with hepatic impairment, caution is advised due to altered metabolism.

Contra-indications

• Bradycardia
• Heart block
• Asthma or a history of bronchospasm
• Severe chronic obstructive pulmonary disease (COPD)
• Cardiogenic shock
• Uncontrolled heart failure
• Hypersensitivity to timolol or any of its components

Adverse effects

• Bradycardia
• Hypotension
• Dizziness
• Fatigue
• Depression
• Cold extremities
• Nausea
• Diarrhea
• Insomnia
• Shortness of breath
• Visual disturbances
• Ocular irritation (when used as eye drops)

Interactions

• Caution with other beta-blockers
• Caution with antihypertensives
• Caution with antiarrhythmics
• May enhance effects of oral hypoglycaemics
• May mask symptoms of hypoglycemia
• Caution with calcium channel blockers

Precautions

• Monitor heart rate and blood pressure regularly
• Use with caution in patients with hepatic impairment
• Use with caution in patients with renal impairment
• Consider potential for systemic absorption when used as eye drops
• Discontinue in case of severe allergic reactions

Pregnancy

Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Manufacturer advises avoidance during breastfeeding due to potential for serious adverse effects in the infant.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Timolol maleate 0.25% eye drops
• Timolol maleate 0.5% eye drops
• Timolol maleate oral tablets 5 mg
• Timolol maleate oral tablets 10 mg
• Timolol maleate oral solution

Indications

• Cerebral edema
• Elevated intracranial pressure
• Acute kidney injury
• Oliguria
• Glaucoma
• Renal function diagnostic aid

Dosage

Adults: For cerebral edema, administer 0

Mechanism of action

Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. This action reduces cerebral edema and intracranial pressure. As a diuretic, it increases the osmolality of glomerular filtrate, leading to increased urinary excretion of water and preventing sodium and chloride reabsorption in the renal tubules. Mannitol also facilitates the urinary excretion of toxic substances and can help in assessing renal function by measuring glomerular filtration rate (GFR).

Pharmacodynamics

Mannitol is classified as an osmotic diuretic. It is chemically similar to other sugar alcohols but has a unique ability to promote diuresis by remaining unabsorbed in the renal tubules. Its use is indicated for conditions associated with increased body fluids, such as cerebral edema and glaucoma. Mannitol may be combined with other diuretics to enhance diuretic efficacy. Inhaled formulations are used in cystic fibrosis, though they may cause bronchospasm and hemoptysis.

Pharmacokinetics

Mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption, which allows for its urinary excretion rate to serve as a measurement of GFR. It does not undergo significant metabolism and is eliminated primarily through the kidneys. The onset of action occurs within 30 to 60 minutes after intravenous administration, with effects lasting for several hours. Administration may require monitoring of renal function and fluid balance.

Contra-indications

• Anuria
• Severe dehydration
• Severe renal impairment
• Intracranial bleeding

Adverse effects

• Asthenia
• Gastrointestinal disturbances
• Dry mouth
• Confusion
• Visual impairment
• Hypotension
• Electrolyte imbalances
• Pulmonary edema
• Hemoptysis (with inhalation use)
• Bronchospasm (with inhalation use)

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• Other diuretics may have additive effects
• Caution with nephrotoxic agents

Precautions

• Caution in patients with diabetes mellitus
• Caution in the elderly
• Caution in patients with gout
• Caution in patients with hepatic impairment
• Monitor renal function and electrolytes regularly
• May cause blue fluorescence of urine

Pregnancy

Manufacturer advises avoid due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises avoid due to lack of information available.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Solution for injection
• Inhalation powder
• Oral solution

Indications

• Glaucoma
• Ocular hypertension
• Primary glaucoma
• Secondary glaucoma

Dosage

Children: For children, apply 1 drop into the affected eye(s) twice daily; may increase frequency if necessary.

Adults: Instill 1 drop into the affected eye(s) three times daily.

Mechanism of action

Brinzolamide inhibits the enzyme carbonic anhydrase, which decreases the production of aqueous humor in the eye, thereby lowering intraocular pressure.

Pharmacodynamics

By reducing the secretion of bicarbonate ions, brinzolamide decreases the osmotic gradient and reduces fluid movement into the aqueous humor, leading to decreased intraocular pressure.

Pharmacokinetics

Brinzolamide is administered topically as an eye drop. Systemic absorption can occur, but it is generally limited. The drug is metabolized in the liver and excreted primarily in urine. Its half-life varies, but significant systemic exposure is rare with topical use.

Contra-indications

• History of sulfonamide hypersensitivity
• Hyperchloraemic acidosis
• Renal tubular immaturity or abnormality

Adverse effects

• Eye discomfort
• Vision disorders
• Bitter taste
• Angioedema
• Bronchospasm
• Dizziness
• Dry mouth
• Dyspnoea
• Epistaxis
• Local reaction
• Pain
• Arrhythmias
• Asthenia
• Severe cutaneous adverse reactions
• Chest discomfort
• Cough
• Depression
• Diarrhoea
• Throat irritation
• Urolithiasis

Precautions

• Monitor blood count and plasma electrolyte concentrations with prolonged use
• Chronic corneal defects
• History of intra-ocular surgery
• History of renal calculi
• Systemic absorption follows topical application

Pregnancy

Manufacturer advises avoid, especially in first trimester (toxicity in animal studies).

Breast-feeding

Amount too small to be harmful; use only if benefit outweighs risk.

Storage

Store in a cool, dry place away from light.

Formulations

• Topical eye drops

Indications

• Topical drug formulations
• Ophthalmic solutions
• Cosmetic products
• Transdermal drug delivery systems

Dosage

Children: Refer to specific product guidelines as carbomer is used as a formulation agent and does not have standard dosing.

Adults: Refer to specific product guidelines as carbomer is used as a formulation agent and does not have standard dosing.

Mechanism of action

Carbomer works by absorbing water and swelling to form a gel, which increases the viscosity of the formulation. This property is utilized in topical preparations to improve the delivery and stability of active ingredients, allowing for a more controlled release of the drug.

Pharmacodynamics

The pharmacodynamics of carbomer are primarily related to its physical properties as a gelling agent. It enhances the stability and viscosity of formulations, which can improve the bioavailability of drugs when used in topical applications. Carbomer itself has no systemic pharmacological effects since it is not absorbed into the bloodstream when applied topically.

Pharmacokinetics

Carbomer is not significantly absorbed through the skin or gastrointestinal tract, which means it does not have a traditional pharmacokinetic profile characterized by absorption, distribution, metabolism, and excretion. It primarily acts locally at the site of application.

Adverse effects

• Local irritation
• Allergic reactions
• Redness
• Swelling

Precautions

• Avoid contact with eyes
• Use caution in individuals with known allergies to carbomers
• If irritation occurs, discontinue use

Pregnancy

Carbomer is generally considered safe for use during pregnancy, but it is always advisable to consult a healthcare provider before use.

Breast-feeding

Carbomer is not known to be absorbed systemically, making it likely safe for use while breastfeeding, but consulting a healthcare provider is recommended.

Storage

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

Formulations

• Gel
• Cream
• Ointment
• Powder

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Indications

• Lead poisoning
• Mercury poisoning
• Calcium overload
• Certain diagnostic procedures involving heavy metals

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, considering factors such as the severity of metal poisoning and renal function.

Mechanism of action

Edetate functions by forming stable complexes with divalent and trivalent metal ions, including lead and calcium, through its multiple carboxylate and amine groups. This chelation renders the metals more soluble and promotes their renal excretion, thereby reducing their toxic effects in the body.

Pharmacodynamics

The chelation of metals by edetate decreases the free metal concentration in the bloodstream, which mitigates the toxic effects associated with heavy metal accumulation. The efficacy of edetate in removing metals such as lead has been well documented, and its ability to bind calcium can influence calcium homeostasis in certain clinical scenarios.

Pharmacokinetics

Edetate is administered intravenously, with rapid distribution throughout the extracellular fluid. It is primarily excreted unchanged by the kidneys. The onset of action occurs quickly after administration, and the duration depends on the dose and the patient's renal function. The elimination half-life is approximately 1 hour but may vary based on renal clearance.

Contra-indications

• Hypersensitivity to edetate or any component of the formulation
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Rash
• Fever

Interactions

• May enhance the effects of anticoagulants
• Concurrent use with calcium supplements may reduce effectiveness
• May interfere with the absorption of certain medications due to changes in gastrointestinal motility

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels, particularly calcium, during treatment
• Assess the patient's hydration status before administration

Pregnancy

Limited data on the use of edetate in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known whether edetate is excreted in human milk. Weigh the risks and benefits before use.

Storage

Store in a cool, dry place, protected from light. Do not freeze.

Formulations

• Edetate disodium injection
• Edetate calcium disodium injection

Dosage

Children: Dosing for pediatric patients should be determined based on specific clinical guidelines and the formulation used, as general dosing information for homopolymers is not established.

Adults: Dosage is dependent on the specific application and formulation of the homopolymer. Refer to specific product guidelines for dosing recommendations.

Mechanism of action

The mechanism of action of homopolymers varies depending on their chemical composition and structure. Generally, they can interact with biological systems through various pathways, including adhesion to cell surfaces, encapsulation of drugs, and modification of drug release profiles. Their inert nature and ability to form hydrogels can aid in controlled drug delivery.

Pharmacodynamics

Homopolymers exhibit pharmacodynamic properties that are influenced by their molecular weight, degree of crystallinity, and functional groups. These properties can impact drug solubility, release rates, and bioavailability. The interactions with biological tissues are primarily physical rather than chemical, affecting factors such as drug absorption and distribution.

Pharmacokinetics

The pharmacokinetics of homopolymers are not defined in the traditional sense as they do not typically undergo metabolism like small molecule drugs. Instead, their behavior in the body is determined by their degradation rate, which can depend on factors such as the polymer's structure and the presence of enzymes. Excretion usually occurs through the kidneys or via biodegradation into smaller, non-toxic components.

Pregnancy

The safety of homopolymers during pregnancy has not been established. Consultation with a healthcare provider is recommended before use.

Breast-feeding

Data on the excretion of homopolymers in human milk are not available. 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.

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.

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

• Hypertension
• Angina pectoris
• Heart attack (myocardial infarction) prevention
• Glaucoma
• Ocular hypertension

Dosage

Children: Refer to the BNF for Children for specific dosing information for pediatric patients.

Adults: For hypertension, the usual starting dose is 10 mg once daily, which may be increased to 20 mg after 1 to 2 weeks if necessary. In glaucoma, the recommended dose is one drop of the 0.25% solution in the affected eye(s) twice daily.

Mechanism of action

Timolol competes with adrenergic neurotransmitters for binding to beta(1)-adrenergic receptors in the heart and beta(2)-receptors in the vascular and bronchial smooth muscle. This leads to diminished actions of catecholamines, resulting in decreased heart rate, cardiac output, and blood pressure. It also decreases peripheral vascular resistance. The exact mechanism for reducing intraocular pressure is not fully understood but may involve decreased secretion of aqueous humor and reduced blood supply to the ciliary body.

Pharmacodynamics

Timolol, when administered ophthalmically, rapidly reduces intraocular pressure, typically within 20 minutes. When taken orally, it lowers blood pressure, heart rate, and cardiac output, with effects lasting up to 24 hours in specific formulations. It has minimal impact on accommodation and pupil size.

Pharmacokinetics

Timolol is absorbed systemically, with a peak effect observed within 1 to 2 hours after oral administration. The drug is extensively metabolized in the liver, and its elimination half-life is approximately 4 to 5 hours. When used topically in the eye, systemic absorption can occur, leading to potential systemic effects.

Contra-indications

• Asthma or a history of bronchospasm
• Severe chronic obstructive pulmonary disease (COPD)
• Bradycardia or heart block
• Cardiogenic shock
• Hypersensitivity to timolol or any of the excipients

Adverse effects

• Bradycardia
• Hypotension
• Dizziness
• Fatigue
• Depression
• Shortness of breath
• Ocular irritation
• Dry eyes
• Systemic absorption leading to bronchospasm

Interactions

• Propafenone: Unknown (increases exposure)
• Other antihypertensives may have additive effects
• Calcium channel blockers may increase the risk of heart failure

Precautions

• Caution in patients with diabetes (may mask hypoglycemia symptoms)
• Use with caution in patients with renal impairment
• Monitor for signs of heart failure
• Caution in patients with a history of severe allergic reactions

Pregnancy

Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Timolol is excreted in human milk, caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Ophthalmic solution (0.25% and 0.5%)
• Oral tablets (various strengths)

Indications

• Bacterial Infections
• Pneumonia
• Urinary Tract Infections
• Skin and Soft Tissue Infections
• Gastrointestinal Infections

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored to pediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the type and severity of infection.

Mechanism of action

Tybe works by targeting specific bacterial enzymes and processes essential for the synthesis of bacterial cell walls. By disrupting these functions, it leads to cell lysis and ultimately the death of the bacteria. This mechanism is crucial in treating infections caused by susceptible strains.

Pharmacodynamics

The pharmacodynamics of Tybe involve its ability to bind to bacterial ribosomes, inhibiting protein synthesis. This action not only halts the growth of bacteria but can also lead to bactericidal effects. The drug exhibits concentration-dependent killing, meaning that higher concentrations can lead to more effective bacterial eradication.

Pharmacokinetics

Tybe is usually well absorbed after oral administration, with peak plasma concentrations occurring within a few hours. It has a bioavailability of approximately 70% when taken orally. The drug is extensively distributed throughout the body, including tissues and fluids. It is metabolized predominantly in the liver and excreted primarily via the kidneys. The elimination half-life is generally around 6 to 8 hours, but this can vary based on individual patient factors.

Pregnancy

Safety in pregnancy has not been established; use only if clearly needed.

Breast-feeding

Use with caution; consult a healthcare provider before use.

Storage

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

Indications

• Chronic bronchitis
• Cystic fibrosis
• Pneumonia
• Other respiratory conditions requiring mucus clearance

Dosage

Children: Refer to clinical guidelines or specific BNF for Children resources for dosing recommendations, as no specific dosing information is provided here.

Adults: Refer to clinical guidelines or specific BNF resources for dosing recommendations, as no specific dosing information is provided here.

Mechanism of action

Tyloxapol reduces the surface tension of mucus, enhancing the clearance of respiratory secretions. By disrupting intermolecular forces in mucus, it promotes easier expulsion through coughing or other means.

Pharmacodynamics

Tyloxapol's pharmacodynamic effects are related to its surfactant properties, which improve mucus rheology and promote ciliary action in the airways. This leads to increased efficiency in mucus clearance and can help alleviate symptoms associated with respiratory conditions.

Pharmacokinetics

The pharmacokinetics of tyloxapol are not fully characterized in the literature. Generally, surfactants like tyloxapol are poorly absorbed from the gastrointestinal tract and are primarily localized to the site of action within the respiratory system. Metabolism and elimination pathways have not been extensively documented.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Vomiting
• Diarrhea
• Dizziness

Precautions

• Use with caution in patients with a history of hypersensitivity to surfactants
• Evaluate liver function prior to use
• Monitor for adverse gastrointestinal effects

Pregnancy

No adequate studies in pregnant women are available. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There are no adequate studies on the excretion of tyloxapol in human milk. Caution should be exercised when administering to nursing women.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Oral solution
• Injectable solution

Mechanism of action

Brinzolamide is a highly specific, reversible, non-competitive inhibitor of carbonic anhydrases (CA), the enzymes catalyzing the reversible reaction of water and carbon dioxide (CO2) to form bicarbonate ions. Although there are 7 isoforms of CA in human tissues, brinzolamide has the highest affinity to CA II. Brinzolamide and its active metabolites were not found to displace any known ligands in vitro from their respective receptors or enzymes commonly involved in producing side effects or ancillary pharmacology, thus explaining brinzolamide's high order of safety.

Pharmacodynamics

Inhibition of carbonic anhydrase II (CA-II) in the ciliary process of the eye slows the formation of bicarbonate and thus fluid flow, lowering intraocular pressure (IOP). The IOP-reducing effect of brinzolamide as adjunctive therapy to the prostaglandin analog travoprost was studied. Following a 4-week run-in with travoprost, patients with an IOP ≥19 mmHg were randomized to receive added treatment with brinzolamide or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the brinzolamide group and 3.2 to 4.2 mmHg for the timolol group were observed. There was an overall higher incidence of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies. A clinical trial was conducted with brinzolamide in 32 pediatric patients less than 6 years of age, diagnosed with glaucoma or ocular hypertension. Some patients were naive to IOP therapy whilst others were on other IOP-lowering medicinal product(s). Those who had been on previous IOP medicinal products were not required to discontinue their IOP medicinal product(s) until the initiation of monotherapy with brinzolamide. Among patients who were naive to IOP therapy (10 patients), the efficacy of brinzolamide was similar to that seen previously in adults, with mean IOP reductions from baseline ranging up to 5 mmHg. Among patients who were on topical IOP-lowering medicinal products (22 patients), mean IOP increased slightly from baseline in the brinzolamide group.

Mechanism of action

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance. MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER. ...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Pharmacodynamics

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

Mechanism of action

Timolol competes with adrenergic neurotransmitters for binding to beta(1)-adrenergic receptors in the heart and the beta(2)-receptors in the vascular and bronchial smooth muscle. This leads to diminished actions of catecholamines, which normally bind to adrenergic receptors and exert sympathetic effects leading to an increase in blood pressure and heart rate. Beta(1)-receptor blockade by timolol leads to a decrease in both heart rate and cardiac output during rest and exercise, and a decrease in both systolic and diastolic blood pressure. In addition to this, a reduction in reflex orthostatic hypotension may also occur. The blockade of beta(2) receptors by timolol in the blood vessels leads to a decrease in peripheral vascular resistance, reducing blood pressure. The exact mechanism by which timolol reduces ocular pressure is unknown at this time, however, it likely decreases the secretion of aqueous humor in the eye. According to one study, the reduction of aqueous humor secretion may occur through the decreased blood supply to the ciliary body resulting from interference with the active transport system or interference with prostaglandin biosynthesis. beta-Adrenergic blocker Following topical application to the eye, timolol maleate reduces both elevated and normal intraocular pressure in patients with or without open angle (chronic simple, noncongestive) glaucoma or ocular hypertension. Timolol reduces intraocular pressure with little or no effect on accommodation or pupillary size. In patients with elevated intraocular pressure, timolol reduces mean intraocular pressure by about 25-33%. The drug appears to be equally effective in light and dark colored eyes. ... The exact mechanism by which beta-blockers, including timolol, reduce intraocular pressure has not been clearly defined. Fluorophotometric studies suggest that reduced aqueous humor formation is the predominant effect. beta-Adrenergic blocking agents may block endogenous catecholamine stimulated increases in cyclic adenosine monophosphate concentrations within the ciliary processes and subsequent formation of aqueous humor. Timolol appears to cause little or no change in aqueous humor outflow facility. ... In some studies, timolol maleate applied topically to one eye reduced intraocular pressure in both eyes; the mechanism of this effect has not been elucidated. ... A slight decrease in the intraocular hypotensive effect may occur during the first 3 wk of timolol therapy, and tolerance may develop with prolonged use; however, the intraocular pressure lowering effect has been maintained for at least 3 yr with continuous use of the drug in some patients. /Timolol maleate/ Timolol maleate has pharmacologic actions similar to those of other beta-adrenergic blocking agents. The principal physiologic action of timolol is to competitively block beta-adrenergic receptors within the myocardium (beta1-receptors) and within bronchial and vascular smooth muscle (beta2-receptors). Unlike atenolol and metoprolol, timolol is not a beta1-selective adrenergic blocking agent; timolol is a nonselective beta-adrenergic blocking agent, inhibiting both beta1- and beta2-adrenergic receptors. Timolol also does not exhibit the intrinsic sympathomimetic activity seen with pindolol or the membrane stabilizing activity possessed by propranolol or pindolol. ... By inhibiting myocardial beta1-adrenergic receptors, timolol produces negative chronotropic and inotropic activity. The negative chronotropic action of timolol on the sinoatrial node results in a decrease in the rate of sinoatrial node discharge and an increase in recovery time, thereby decreasing resting and exercise stimulated heart rate and reflex orthostatic tachycardia by as much as 30%. High doses of the drug may produce sinus arrest, especially in patients with SA node disease (eg, sick sinus syndrome). Timolol also slows conduction in the atrioventricular node. Timolol usually produces a slight reduction in cardiac output, proba

Pharmacodynamics

Timolol, when administered by the ophthalmic route, rapidly reduces intraocular pressure. When administered in the tablet form, it reduces blood pressure, heart rate, and cardiac output, and decreases sympathetic activity.. This drug has a fast onset of action, usually occurring within 20 minutes of the administration of an ophthalmic dose. Timolol maleate can exert pharmacological actions for as long as 24 hours if given in the 0.5% or 0.25% doses.