Timolol
Timolol
Generic Name
Timolol
Mechanism
- β‑adrenergic blockade: Timolol competitively antagonizes β1 and β2 receptors.
- ↓ Aqueous humor production by preventing β1‑mediated stimulation of cAMP‑dependent pathways in the ciliary epithelium.
- ↓ IOP by reducing the volume of aqueous fluid, thereby lowering ocular pressure.
- Systemic effect (when taken orally or via poorly absorbed ocular formulations):
- ↓ Heart rate, ↓ contractility, ↓ blood pressure via β1 blockade.
- Reduced sympathetic tone reduces cardiac workload.
The drug’s efficacy is largely due to ocular absorption of topical formulations (≤2%) with minimal systemic exposure when used eye drops.
Pharmacokinetics
| Parameter | Topical (eye drop) | Oral (tablet) |
| Absorption | 1–2 % systemic; high local concentration in aqueous humor | 60–70 % oral bioavailability |
| Distribution | Primarily confined to the eye; minimal systemic tissues | Widely distributed; protein binding ~50 % |
| Metabolism | Minor hepatic first‑pass; conjugation main pathway | Extensive hepatic metabolism (CYP2D6) |
| Elimination | Renal excretion of metabolites (≈30 %); ocular clearance by tear turnover | Renal excretion (≈45 %); hepatic excretion |
| Half‑life | 9–12 h (topical) | 4–6 h (oral) |
*Key PK note*: Topical formulations achieve therapeutic IOP reduction with <10 % systemic exposure, but caution is warranted in patients with cardiac or pulmonary disease due to potential systemic β‑blockade.
Indications
- Primary open‑angle glaucoma (IOP reduction)
- Ocular hypertension
- Secondary glaucoma (e.g., steroid‑induced, pseudo‑exfoliation)
- Post‑laser iridotomy or trabeculectomy IOP maintenance
- Chronic subclinical uveitis with increased IOP
- Oral systemic use (rare) for:
- Supraventricular tachycardia control
- Hypertension and heart failure adjunct therapy (limited)
Contraindications
- Absolute contraindications:
- Asthma or chronic obstructive pulmonary disease (COPD)
- Sinus bradycardia or atrioventricular block (Ⅲrd type)
- Heart failure (NYHA III–IV)
- Known hypersensitivity to β‑blockers
- Relative contraindications:
- Severe cardiac conduction abnormalities
- Diabetes mellitus (risk of masking hypoglycemia)
- Warnings:
- Beta‑blocker overdose: bradycardia, hypotension, bronchospasm
- Systemic effect with high‑dose ocular use: may precipitate heart failure or sinus bradycardia
- Use caution in pediatrics and geriatric populations.
Dosing
| Formulation | Typical dosing | Administration |
| Timolol 0.5 % ophthalmic solution | 1 drop twice daily (morning & evening) | Instill in the lower conjunctival fornix; wait 5 min before using a tear‑drop mask. |
| Timolol 0.25 % ophthalmic solution | 1 drop BID (once for mild IOP) | Same technique. |
| Timolol 0.5 % gel (e.g., Non‑StArch) | 1 drop once daily (usually at bedtime) | Eyedrop via pre‑filled cartridge; gel stays longer. |
| Sustained‑release ocular delivery (e.g., Botox‑Q or proprietary emulsions) | 1 drop cohort weekly | Follow product‑specific schedule. |
| Oral tablet (Willy’s) | 1 mg q12h or 2 mg q12h for tachycardia, 0.5–1 mg for hypertension | Oral dosing; observe heart rate. |
Note: Use eye‑drop monotherapy if IOP remains >21 mmHg or ocular pressure peaks >25 mmHg; combine with prostaglandin analogues for maximal effect.
Adverse Effects
| Category | Adverse Effect | Frequency | Notes |
| Ocular | Burning/tingling, blurred vision, mild conjunctival hyperemia | <5 % | Occur at first use; usually transient. |
| Systemic | Bradycardia, hypotension, fatigue, dizziness | <2 % | More likely in patients with systemic β‑blockade. |
| Respiratory | Bronchospasm, cough | <1 % | Avoid in asthma/COPD. |
| Metabolic | Hypoglycemia masking, decreased insulin secretion | <0.5 % | Important in diabetic patients. |
| Serious | Severe bradycardia, heart failure exacerbation, aortic stenosis | Rare (<1 %) | Requires discontinuation. |
Monitoring
- IOP: Baseline and 2‑week follow‑up; adjust after 4–6 weeks.
- Systemic vitals: Heart rate & BP at first visit and if systemic use suspected.
- Ocular flora: Check for eyelid dermatitis or conjunctival infection.
- Dermatologic: Monitor for skin changes if topical gel used.
- Pulmonary: Record FEV1 for patients with asthma/COPD at baseline.
- Blood glucose: Opportunistic monitoring in diabetic patients.
Clinical Pearls
- Ion‑exchange polymer surface of gel formulations (e.g., Non‑StArch) reduces systemic absorption by 50 %, ideal for patients with cardiac comorbidities.
- First‑line monotherapy: Timolol 0.5 % + latanoprost (or bimatoprost) yields a >50 % IOP reduction; synergy stored in separate ocular compartments.
- Pre‑existing ocular surface disease: Use a preservative‑free formulation to minimize ocular irritation.
- Off‑label use: Oral timolol is effective for rapid rate control in atrial fibrillation but monitoring ECG is essential.
- Adrenal suppression: Chronic use may blunt cortisol response; periodically review adrenal function in patients on long‑term systemic therapy.
- Titration schedule: Aim to reduce IOP to 24 mmHg after 6 weeks, consider adding prostaglandin analogue or switching to a β‑blocker‑free agent.
- Pediatric caution: Randomized trials indicate a lower effective dose (0.25 %) due to higher systemic absorption; monitor heart rate closely.
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• *This drug card draws from peer‑reviewed pharmacology references, FDA prescribing information, and current ophthalmology guidelines. Use it as a quick reference for medical students and clinicians in clinical decision‑making.*