LAVIMOL DROPS​ ​OPHTHALMIC SOLUTION

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

• 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

• 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

• 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)

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

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.