Generic Name: Timolol Maleate
Brand Names (oral): Blocadren (discontinued in some markets), Timolol (generic forms available)
Drug Class: Non-selective β-adrenergic blocker (Beta-blocker)
Dosage Forms: Oral tablets – 5 mg, 10 mg, 20 mg
Route of Administration: Oral
ATC Code: C07AA06
Timolol tablets are a systemic beta-blocker used to manage cardiovascular conditions such as hypertension and prevent recurrent myocardial infarction. It is also indicated for migraine prophylaxis. Its mechanism involves antagonism of β1 and β2 receptors, leading to decreased heart rate, blood pressure, and sympathetic stimulation.
2. Indications and Therapeutic Uses
2.1 Hypertension (Primary Indication)
Timolol is approved for managing essential hypertension. It can be used as monotherapy or combined with other antihypertensive agents such as thiazide diuretics.
Clinical effect:
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Reduction in systolic and diastolic blood pressure
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Decreased risk of long-term cardiovascular complications
2.2 Secondary Prevention After Myocardial Infarction
Following an acute myocardial infarction, Timolol helps reduce cardiovascular mortality, reinfarction risk, and sudden cardiac death.
Therapeutic role:
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Decreased myocardial oxygen demand
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Reduced risk of arrhythmias
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Long-term improvement in patient survival
2.3 Migraine Prophylaxis
Timolol is one of the beta-blockers approved for preventing episodic migraines.
Clinical use:
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Not effective in aborting acute attacks
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Requires regular daily use for effect
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Effects seen typically after 4–8 weeks
2.4 Off-label Uses
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Chronic stable angina
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Hyperthyroidism symptoms (e.g., tachycardia)
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Certain arrhythmias (e.g., atrial fibrillation rate control)
Note: These uses depend on physician discretion based on the patient’s profile and treatment goals.
3. Dosage and Administration
3.1 Available Strengths
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5 mg oral tablet
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10 mg oral tablet
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20 mg oral tablet
3.2 General Dosing Guidelines
Dosing must be individualized and titrated based on therapeutic response and patient tolerability.
| Indication | Starting Dose | Maintenance Dose | Maximum Dose |
|---|---|---|---|
| Hypertension | 10 mg once or twice daily | 20–40 mg per day | Up to 60 mg per day |
| Post-MI secondary prevention | 10 mg twice daily | 20 mg per day | Usually not exceeded |
| Migraine prophylaxis | 10 mg once or twice daily | 20–30 mg per day | 30 mg per day |
4. Pharmacokinetics and Pharmacodynamics
4.1 Absorption
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Oral bioavailability: approximately 60%
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Peak plasma concentration: 1–2 hours post-dose
4.2 Distribution
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Highly lipophilic
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Widely distributed in body tissues
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Crosses the blood-brain barrier
4.3 Metabolism
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Extensively metabolized in the liver via CYP2D6
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Undergoes first-pass hepatic metabolism
4.4 Elimination
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Elimination half-life: approximately 2.5–5 hours
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Excreted mainly via renal route (both unchanged and metabolites)
4.5 Mechanism of Action
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Competitive blockade of β1- and β2-adrenergic receptors
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Decreases sympathetic activity
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Reduces heart rate and myocardial contractility
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Inhibits renin secretion
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Decreases peripheral vascular resistance over time
5. Contraindications
Timolol tablets are contraindicated in the following scenarios:
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Bronchial asthma or severe COPD
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Second or third-degree atrioventricular block (without pacemaker)
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Sinus bradycardia (<50 bpm)
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Cardiogenic shock
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Overt cardiac failure
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Hypersensitivity to timolol or other beta-blockers
In such cases, alternative therapies should be considered.
6. Precautions and Warnings
6.1 Respiratory Risks
Because of β2 blockade, Timolol may cause bronchospasm or respiratory distress in individuals with respiratory disease. It is contraindicated in asthmatics.
6.2 Cardiac Risks
Use with caution in patients with:
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Heart failure (start only when stable)
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Bradycardia
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AV conduction disorders
6.3 Endocrine Considerations
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May mask symptoms of hypoglycemia in diabetics (e.g., tremor, tachycardia)
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May interfere with glucose recovery
6.4 Psychiatric and CNS Effects
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Depression, fatigue, and dizziness may occur
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Crosses the blood-brain barrier
6.5 Withdrawal
Abrupt withdrawal can exacerbate angina, precipitate MI, or induce arrhythmias. Always taper slowly over 1–2 weeks.
7. Adverse Effects
7.1 Common Adverse Reactions
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Fatigue
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Dizziness
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Cold extremities
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Bradycardia
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Gastrointestinal upset
7.2 Less Common but Serious Effects
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Hypotension
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Bronchospasm
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Depression
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Sexual dysfunction
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Conduction abnormalities (AV block)
7.3 Rare Events
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Visual disturbances
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Skin rashes
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Alopecia
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Thrombocytopenia
Adverse reactions are dose-dependent and may be more prominent in the elderly or patients with comorbidities.
8. Drug Interactions
Timolol may interact with a variety of other medications, requiring close monitoring or avoidance.
8.1 Cardiovascular Agents
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Calcium Channel Blockers (e.g., verapamil, diltiazem): Risk of bradycardia, AV block, hypotension
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Other beta-blockers: Additive effect leading to significant bradycardia or heart block
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Antiarrhythmics (e.g., amiodarone): Additive depressant effects on heart rate
8.2 Antihypertensives
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Clonidine: May lead to hypertensive rebound upon withdrawal if used with Timolol
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Diuretics and ACE inhibitors: Enhanced hypotensive effects
8.3 CNS Depressants
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Sedatives or alcohol: Enhanced CNS depressant effect, increased risk of dizziness and fatigue
8.4 Antidiabetics
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Insulin and oral hypoglycemics: May mask hypoglycemia symptoms and prolong hypoglycemia
8.5 CYP2D6 Substrates/Inhibitors
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SSRIs (fluoxetine, paroxetine): Can inhibit metabolism of Timolol, increasing plasma concentration and risk of adverse effects
9. Use in Specific Populations
9.1 Pregnancy
Category C – No well-controlled studies in humans. Use only if the potential benefit justifies the potential risk to the fetus.
9.2 Lactation
Timolol is excreted in breast milk. Breastfeeding is generally not recommended while taking systemic beta-blockers due to potential bradycardia in infants.
9.3 Geriatric Use
Elderly patients are more susceptible to hypotension, bradycardia, and fatigue. Start at the lower end of dosing range and monitor closely.
9.4 Hepatic or Renal Impairment
Reduced clearance may occur. Dose adjustment is typically not required, but close monitoring is advised.
10. Monitoring Parameters
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Blood pressure and heart rate (baseline and during therapy)
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ECG (especially in those with cardiac conduction disorders)
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Signs of heart failure (e.g., weight gain, edema)
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Blood glucose levels in diabetic patients
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Respiratory symptoms in patients with suspected bronchospasm
11. Overdose Management
Symptoms of Timolol overdose may include:
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Severe bradycardia
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Hypotension
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Bronchospasm
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Cardiac arrest
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Hypoglycemia
Treatment includes:
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Supportive care and monitoring
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Intravenous fluids
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Atropine for bradycardia
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Glucagon or isoproterenol for severe cardiac depression
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Beta-agonists (e.g., salbutamol) for bronchospasm
Hemodialysis is not effective in clearing Timolol due to high protein binding and distribution.
12. Storage and Handling
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Store tablets at controlled room temperature (20–25°C)
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Protect from excessive moisture and heat
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Keep in original packaging until use
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Keep out of reach of children
13. Summary of Key Features
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Non-selective beta-blocker with systemic action
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Used orally for hypertension, post-MI prevention, and migraine prophylaxis
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Risk of bronchospasm and cardiac conduction defects
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Interacts with calcium channel blockers, antidiabetics, CNS depressants
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Contraindicated in asthma, bradycardia, AV block, and cardiogenic shock
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Monitor BP, HR, ECG, respiratory symptoms, and blood glucose
14. Additional Notes
Timolol tablets are distinct from Timolol ophthalmic preparations (eye drops), which are used for glaucoma but may cause systemic effects as well. Caution is required in switching between different beta-blockers. For optimal blood pressure control or migraine prevention, patient adherence and gradual titration are critical. It is not used to manage acute hypertensive crises or active ischemia
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