Timolol

Timolol is a noncardioselective beta-adrenoblocker with no intrinsic sympathomimetic activity, local anesthetic or cardiodepressant activity. It reduces intraocular pressure and is used in cases of pathologically elevated pressure. Timolol effectively reduces the formation of aqueous humor in ciliary body processes and is a potent beta-adrenergic antagonist. However, the physiologic basis for the action of this drug to reduce intraocular pressure is not completely clear.

Timolol is widely used for the treatment of glaucoma due to its ability to effectively reduce intraocular pressure. It can be used both in monotherapy and in combination with other antiglaucoma drugs. Timolol has also shown efficacy in reducing mortality and recurrence of myocardial infarction in patients who have acute myocardial infarction.

It should be noted that despite the widespread use of Timolol in ophthalmology, side effects can occur, including allergic contact dermatitis. In addition, Timolol may cause systemic side effects due to its beta-blocking activity, such as bradycardia, heart failure, bronchospasm in patients with bronchial asthma, dizziness and fatigue. Therefore, when prescribing Timolol, it is important to consider the patient's comorbidities and possible risks.

Indications Timolol

The main indication for Timolol is to reduce intraocular pressure in patients with open-angle glaucoma and ophthalmic hypertension. Timolol reduces the production of aqueous moisture in the eye, resulting in a decrease in intraocular pressure.

Release form

Timolol is available in the form of 0.25% and 0.5% eye drops. Packaging may include 1 ml, 2 ml in polymer dropper tubes with valve or 5 ml, 10 ml in screw neck polymer dropper tubes capped with screw caps.

Pharmacodynamics

The pharmacodynamics of timolol is attributed to its ability to block beta-adrenergic receptors, resulting in numerous effects both in the visual organs and at the systemic level:

In ophthalmology:

• Reduction of intraocular pressure: Timolol reduces the production of aqueous moisture in the anterior eye, resulting in a decrease in intraocular pressure. This is the main action of timolol used in the treatment of glaucoma and ophthalmic hypertension.

On the cardiovascular system:

• Antihypertensive action: Blockade of beta-adrenergic receptors of the heart leads to a decrease in heart rate (bradycardia), a decrease in cardiac output and, consequently, a decrease in blood pressure.
• Antianginal effect: Reducing myocardial oxygen demand by decreasing heart rate and reducing the workload of the heart helps reduce symptoms of angina pectoris.
• Antiarrhythmic effect: Timolol may be used to control some types of arrhythmias because it slows the conduction of impulses through the atrioventricular node of the heart.

On the respiratory system:

• Possible increase in bronchospasm: As a non-cardioselective beta-blocker, timolol may cause increased bronchospasm in patients with asthma or chronic obstructive pulmonary disease, which is an important side effect.

Other effects:

• Reducing the risk of recurrent myocardial infarction: Timolol has been shown to reduce the risk of recurrent infarction and mortality in patients after myocardial infarction due to its cardioprotective properties.

Timolol acts by competitively blocking beta-adrenergic receptors, resulting in reduced effects of endogenous catecholamines (e.g., adrenaline and noradrenaline) on the heart and smooth muscle, including blood vessels and bronchi. It is important to note that timolol is a non-cardioselective beta-blocker, which means that it acts on both β1- and β2-adrenergic receptors, which explains its wide spectrum of action and potential side effects.

Pharmacokinetics

Timolol is a non-selective beta-adrenoblocker, which when applied topically in the form of eye drops is able to reduce both normal and elevated intraocular pressure. This is achieved by reducing the formation of intraocular fluid. The maximum decrease in intraocular pressure occurs 1-2 hours after application and persists for 24 hours. Timolol does not affect pupil size and accommodation.

Pharmacokinetic features of Timolol are that after topical application the active substance rapidly penetrates through the cornea. Excretion of metabolites is carried out mainly by the kidneys. Approximately 80% of Timolol, used in the form of eye drops, enters the systemic bloodstream through the conjunctival vessels, nasal mucosa and lacrimal tract. In this case, Cmax of Timolol in the aqueous moisture of the eye is reached approximately 1-2 hours after the injection. In neonates and small children Timolol concentration significantly exceeds its Cmax in plasma of adults.

Dosing and administration

To initiate treatment with timolol, 1-2 drops are usually administered in the affected eye. The concentration of drops used may be 0.25% or 0.5%, depending on the patient's individual reaction and doctor's recommendations. The drops are applied 2 times a day. If after regular use the intraocular pressure normalizes, the dose can be reduced to 1 drop once a day, in the morning.

Treatment with timolol is usually long-term. Any changes in dosage or interruptions in treatment should only be made on the instructions of your doctor. It is important to see your doctor regularly to monitor your condition and adapt the course of treatment if necessary.

Use Timolol during pregnancy

The use of timolol during pregnancy requires caution. As with any beta-blocker, timolol may have effects on the fetus, especially when used in the third trimester of pregnancy. Potential risks include:

1. Fetal bradycardia: Decreased fetal heart rate due to beta-adrenergic receptor blockade.
2. Fetal hypoglycemia: Beta-blockers may mask symptoms of hypoglycemia and contribute to fetal hypoglycemia.
3. Fetal growth retardation: There is evidence for a possible effect of beta-blockers on fetal growth.
4. Early closure of the ductus arteriosus: Use at the end of pregnancy may contribute to premature closure of the ductus arteriosus in the fetus, a serious complication.

Because of these potential risks, the use of timolol during pregnancy should be limited to cases where the expected benefit to the mother exceeds the potential risk to the fetus. It is particularly important to weigh the risks and benefits when using timolol in the third trimester of pregnancy.

Contraindications

Contraindications to the use of timolol include:

• Bronchial asthma or other serious chronic obstructive airway disease.
• Sinus bradycardia, atrioventricular block of II or III degree, severe heart failure.
• Decompensated heart failure.
• Dystrophic processes in the cornea.
• Children and adolescents under 18 years of age, as there are no data on the efficacy and safety of the drug in this age group.
• Hypersensitivity to the components of the drug.

The drug should also be administered with caution in pulmonary insufficiency, severe cerebrovascular insufficiency, heart failure, diabetes mellitus, hypoglycemia, thyrotoxicosis, myasthenia gravis, as well as in concomitant administration of other beta-adrenoblockers.

Side effects Timolol

Timolol, like other beta-adrenoblockers, can cause a number of side effects affecting both systemic levels and topical levels when used in the form of eye drops. Here are some of them:

Systemic side effects:

1. Cardiovascular effects: Bradycardia (slowing of heart rate), hypotension (low blood pressure), manifestations of heart failure (dyspnea, edema).
2. Respiratory effects: Bronchospasm or worsening of asthma symptoms, especially in patients with a history of obstructive airway disease.
3. Nervous system: Headaches, dizziness, fatigue, depression, sleep disorders.
4. Hypoglycemia: Timolol may mask the symptoms of hypoglycemia, which is especially important in patients with diabetes mellitus.

Local side effects (when using eye drops):

1. Ocular irritations: Redness, burning, itching, foreign body sensation in the eye.
2. Dry eyes: Reduced tear production can cause discomfort and irritation.
3. Visual disturbances: Temporary decrease in visual acuity, glare or diffuse images.
4. Keratitis: In rare cases, inflammation of the cornea may develop.

Rare but serious side effects:

• Anaphylactic reactions: Extremely rare but potentially life-threatening.
• Allergic reactions on the skin: Rash, urticaria.
• Mental disorders: Confusion, hallucinations, memory disorders.

If any side effects occur, you should immediately consult your doctor for treatment correction or selection of an alternative drug. It is important to remember that side effects may depend on the dosage and individual sensitivity to the drug.

Overdose

An overdose of timolol can occur either by systemic administration (e.g., hypertension tablets) or by topical application as eye drops, especially if the drug is accidentally swallowed. Overdose can lead to a number of serious systemic effects due to extensive blockade of beta-adrenergic receptors.

Symptoms of a timolol overdose may include:

1. Bradycardia (slow heartbeat): One of the most likely and dangerous manifestations of overdose, requiring immediate medical attention.
2. Hypotension (low blood pressure): May lead to fainting and life-threatening conditions, especially in patients with cardiovascular disease.
3. Worsening heart failure: Increased risk in patients with prior heart disease.
4. Bronchospasm: Particularly dangerous in patients with asthma or chronic obstructive pulmonary disease.
5. Hypoglycemia: Uncommon but can be dangerous for diabetic patients.

First aid measures and treatment in case of overdose:

• Discontinuation: Immediately discontinue use of timolol.
• Seekmedical attention: Seek immediate medical attention or call an ambulance.
• Symptomatic and supportive treatment: Measures may be taken in a health care facility to maintain cardiac function, respiration and blood pressure. This may include administration of drugs that stimulate beta-adrenergic activity or temporary use of an artificial external pacemaker in case of severe bradycardia.

When using eye drops, it is important to take precautions to avoid accidental swallowing, especially in children. Always keep medicines out of the reach of children.

Interactions with other drugs

Timolol may interact with other drugs, which requires caution when used in combination with certain medications:

• With other beta-adrenoblockers: concomitant use with other beta-adrenoblockers, including oral forms, may result in increased cardiovascular effects.
• With antiarrhythmic drugs: such as amiodarone, there may be an increased risk of heart block, bradycardia and other heart rhythm disturbances.
• With drugs for the treatment of hypertension and other cardiovascular drugs: an increase in hypotensive effect may occur, which will require dosage adjustment.
• With CYP2D6 inhibitors: such as some antidepressants and antipsychotics, may alter metabolism and increase the concentration of timolol in the blood, which increases the risk of side effects.
• With insulin and oral hypoglycemic agents: timolol may mask symptoms of hypoglycemia, which is important in patients with diabetes mellitus.

Storage conditions

Storage conditions of timolol depend on the form of release of the drug, but in general, you should adhere to the general recommendations for the storage of medical products:

1. Storage temperature: Most forms of timolol, including eye drops and tablets, should be stored at room temperature, usually between 15°C and 25°C. Avoid storing the drug in places with high temperature or direct sunlight.
2. Protection from light and moisture: Store the drug in its original packaging to protect it from light and avoid moisture, which may affect the stability and efficacy of the drug.
3. Child accessibility: Make sure the medicine is out of the reach of children to prevent accidental swallowing or use.
4. After opening: Timolol eye drops should usually be used for a period of time after first opening the vial (e.g. Within 4 weeks) to avoid the risk of contamination. The exact recommendations may vary depending on the manufacturer, so it is important to read the drug instructions carefully.

Following these storage recommendations will help maintain the efficacy and safety of timolol throughout its shelf life.

Shelf life

Do not use timolol after the expiration date indicated on the package. Dispose of expired drug according to local codes and regulations.