Timolol

BRAND NAMES:
Azarga – Azarga is an eye drop suspension available with the composition of Brinzolamide 10 mg and Timolol 5 mg.
Betimol -  Betimol is available as a Timolol ophthalmic solution of 0.25% and 0.5% used to treat glaucoma.
Timopic – Timopic is supplied as Timolol maleate ophthalmic solution with strengths of 0.25% and 0.5%.
Cosopt – Cosopt contains two active ingredients, Dorzolamide 20 mg and Timolol 5 mg, available in the form of eye drops.

MECHANISM OF ACTION:
For Glaucoma and Ocular Hypertension: Timolol is thought to inhibit beta-receptors on the ciliary epithelium, which functions to enhance the production of aqueous humor. By inhibiting these receptors, timolol reduces aqueous humor production and reduces intraocular pressure. The exact mechanism of action of timolol in ocular hypertension is unknown. It appears to be similar to the mechanism of open-angle glaucoma.
Migraine: The mechanism involves the antagonism of beta-adrenergic receptors, which decreases the synthesis and release of norepinephrine, a main intermediate in migraines. The exact mechanism of timolol in preventing migraine was unknown. Another mechanism of timolol in migraine is explained as migraine prophylactic properties are based on the ability of beta-blockers to regulate the neuronal firing of periaqueductal grey matter using gamma-aminobutyric acid. It also appears to regulate the serotonergic system by inhibiting serotonin, which is another important mediator in the pathology pathway of migraines. The distortion of serotonin effects seems to contribute to the ability of beta-blockers to reduce the sensitivity of the auditory system by decreasing the frequency of migraine attacks. 
PHARMACOKINETICS:
Absorption: Timolol is completely absorbed orally with a bioavailability of 90%.The peak concentrations are reached approximately 1 to 2 hours after oral administration. 
When it is an ophthalmic solution, the bioavailability ranges from 60% to 78%. The peak plasma concentration was reached within 15 minutes of ocular administration.
Distribution: In oral administration, it exhibits low plasma protein bound with less than 10%. When it is administered, timolol is distributed in many ocular tissues, which include aqueous humor, retina, choroid, and vitreous body.
Metabolism: It is metabolized in the liver by the cytochrome P450 enzyme CYP2D6 and other hepatic enzymes.
Excretion:  Timolol and its metabolites are predominantly excreted through urine.
PHARMACODYNAMICS:
When it is administered ophthalmically, it rapidly reduces intraocular pressure and helps in preventing the loss of eye vision. Timolol when administered orally, decreases blood pressure, and heart rate and decreases sympathetic activity. 
DOSAGE AND ADMINISTRATION:
Timolol is available as tablets, eye drops, solutions, and gels. Tomolol opthamalic formulations of solution and gels are available in 0.25% and 0.5%. Oral tablets of timolol are available in 5 mg, 10 mg, and 20 mg. The dose recommended is based on the patient's condition and could vary from patient to patient.

• Adults with open-angle glaucoma and ocular hypertension should apply one drop of 0.25% gel to the affected eye once a day. Twice a day, one drop of the 0.2% solution is applied to the afflicted eye. The concentration in the affected eye is increased to 0.5% twice a day, depending on the reaction.
• For migraine in adults, the oral timolol of 10 mg is taken twice a day. And can be increased to 30 mg.
• The starting dose for atrial fibrillation is 10 mg twice day, and this can be increased to a maximum of 10 mg twice day if necessary. 
• Adults may take up to 10 mg twice a day of oral timolol to prevent myocardial infarction. The recommended starting dose is 5 mg.
• For hypertension, oral timolol 10 to 20 mg is recommended to be taken twice daily. The dose can be increased to a maximum of 60 mg daily.
  To treat infantile haemangioma, apply one drop of 0.5% timolol gel to the affected area 2-3 times daily.

CONTRAINDICATIONS:
It is contraindicated in patients with chronic obstructive pulmonary disease, asthma cardiovascular conditions, and bradycardia.

DRUG INTERACTIONS:
While timolol some drugs may interact and can decrease the efficacy of the drug or can cause some severe adverse effects. Below are the drugs that timolol interacts with

• Heart-related medicines -  Digoxin
• Antimalarial drugs  -  Quinidine
• Allergic reaction drugs – Adrenaline
• Antidepressants – paroxetine, fluoxetine
• High blood pressure lowering medicines- Clonidine, reserpine, verapamil, diltiazem, nifedipine, amlodipine.
  FOOD INTERACTIONS: 
  Avoid marijuana as it can interact with timolol and can increase heart rate.
  ADVERSE EFFECTS:
• Atrioventricular block
• Blurry vision
• Headache
• Bronchoconstriction
• Perioclar atopic dermatitis
• Itching
• Irritation
• Stinging
• Dryness
• Bronchospasm
• Conjunctival hyperemia
• Watery eyes
• Hair loss
• Sexual impotence
• Depression
• Disorientation
• Elevated low-density cholesterol levels
• Fatigue
• Headache
  TOXICITY:
  Taking an overdose of Timolol can have some toxic effects.
• Hypotension
• Bradycardia
• Decreased oxygen consumption
• Fatigue
• Hypoglycemia
• Decreased myocardial contractility