dorzolamide

Action and Spectrum

Actions and spectrum: 

Actions: 

• Inhibition of carbonic anhydrase: dorzolamide inhibits the enzyme carbonic anhydrase of the eye. This leads to a decrease in the aqueous humor production and a subsequent reduction in intraocular pressure. 
• Decreased aqueous humor secretion: dorzolamide decreases the secretion of aqueous humor by the ciliary body. This helps to decrease the amount of fluid entering the eye, thereby lowering intraocular pressure. 

Spectrum: 

dorzolamide is primarily used as an ophthalmic medication, meaning it is administered directly into the eye as eye drops. Its effects are localized to the eye, and it is not intended for systemic use. dorzolamide is typically used in combination with other medications, such as beta-blockers or prostaglandin analogs, to achieve better control of intraocular pressure. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Bitter taste (25%) 

Allergic Ocular reactions (10%) 

stinging, Ocular burning, discomfort (33%) 

Superficial keratitis (10-15%)  

Frequency not defined 

Ocular dryness 

Ocular redness 

Stevens-Johnson syndrome 

Angioedema 

Dyspnea 

Blurred vision 

Photophobia 

Tearing 

Toxic epidermal necrolysis 

Bronchospasm 

Epistaxis 

Black Box Warning

Black Box Warning: 

There were no black box warnings specifically associated with dorzolamide 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: dorzolamide is contraindicated in individuals who have a known hypersensitivity or allergy to dorzolamide or any of its components.  
• Severe renal impairment: dorzolamide is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease.  
• Hyperchloremic acidosis: dorzolamide can cause a metabolic acidosis characterized by an increase in blood chloride levels. 
• Concurrent use with oral carbonic anhydrase inhibitors: dorzolamide should not be used concomitantly with systemic carbonic anhydrase inhibitors due to the potential for additive systemic effects and increased risk of side effects. 
• Pediatric use: dorzolamide is not recommended for use in children below two years due to limited data on safety and effectiveness in this age group.

Caution: 

• Hepatic impairment: dorzolamide should be used with caution in patients with hepatic impairment. The drug’s safety and effectiveness may be altered in individuals with liver dysfunction, and careful monitoring is advisable. 
• Renal impairment: Although severe renal impairment is a contraindication, caution should also be exercised in patients with mild to moderate renal impairment. dorzolamide is eliminated by the kidneys, so dose adjustments may be necessary in individuals with impaired renal function. 
• Respiratory disorders: dorzolamide can cause respiratory acidosis in patients having chronic obstructive pulmonary disease or respiratory disorders. Caution is advised in these patients, and close monitoring of respiratory function is recommended. 
• Sulfonamide allergy: dorzolamide is structurally related to sulfonamide antibiotics, and although it is well tolerated, patients with a known allergic or hypersensitivity to sulfonamide drugs. While the risk of cross-reactivity is low, it is important to monitor for any signs of allergic reactions. 
• Contact lens use: dorzolamide contains benzalkonium chloride, that is absorbed by soft contact lenses and may cause eye irritation.  
• Pregnancy and breastfeeding: The use of dorzolamide during pregnancy or breastfeeding should be considered carefully.

Comorbidities: 

• Respiratory disorders: dorzolamide can potentially worsen respiratory acidosis in patients having chronic obstructive pulmonary disease or other respiratory conditions. Careful monitoring of respiratory function is advised in these individuals. 
• Renal impairment: While severe renal impairment is a contraindication, caution should also be exercised in patients with mild to moderate renal impairment. Dose adjustments may be necessary in these individuals due to the drug’s elimination primarily through the kidneys. 
• Hepatic impairment: Patients having hepatic impairment may require close monitoring while using dorzolamide due to potential alterations in drug metabolism. 
• Sulfonamide allergy: Although rare, individuals with a known allergy or hypersensitivity to sulfonamide drugs should exercise caution when using dorzolamide, as it is structurally related to sulfonamides. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: C 

Lactation: It is not known whether dorzalamide is excreted into human milk  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.   
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.     
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.  
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

dorzolamide works by inhibiting the enzyme carbonic anhydrase, specifically the isoform II (CA-II), which is found in the ciliary processes of the eye. By blocking CA-II, dorzolamide reduces the formation of bicarbonate ions from carbon dioxide and water, which are necessary to produce aqueous humor in the eye. This inhibition may decrease in the production of aqueous humor, thereby lowering intraocular pressure.  

Pharmacodynamics: 

• Inhibition of Carbonic Anhydrase: Dorzolamide selectively inhibits the enzyme carbonic anhydrase, specifically the isoform II (CA-II), which is found in the ciliary processes of the eye. Carbonic anhydrase plays a crucial role in the production of aqueous humor, the fluid in the eye. By inhibiting CA-II, dorzolamide reduces the conversion of carbon dioxide and water into bicarbonate ions, which are necessary to produce aqueous humor. 
• Reduction in Aqueous Humor Production: By inhibiting carbonic anhydrase, dorzolamide decreases the formation of bicarbonate ions, leading to decrease in the production of aqueous humor in the ciliary processes. This reduction in aqueous humor production helps to lower intraocular pressure, which is beneficial in the treatment of conditions such as open-angle glaucoma or ocular hypertension. 
• Maintaining Fluid Balance: dorzolamide’s pharmacodynamic effect is to maintain the balance between aqueous humor production and outflow, resulting in decreased intraocular pressure. By reducing the inflow of fluid into the eye, dorzolamide helps to alleviate the excessive pressure on the optic nerve, which is characteristic of glaucoma.

Pharmacokinetics: 

Absorption 

When administered as eye drops, dorzolamide is absorbed through the cornea into the anterior chamber of the eye, where it exerts its therapeutic effects. The absorption of dorzolamide from the eye into the systemic circulation is minimal, resulting in low systemic exposure and reduced risk of systemic side effects. 

Distribution 

dorzolamide is primarily distributed within the ocular tissues, including the ciliary processes and the aqueous humor. The drug remains localized in the eye, with limited distribution to other tissues. 

Metabolism 

dorzolamide undergoes minimal metabolism in the body. The drug is not extensively metabolized by the liver, and there are no major active metabolites formed. 

Elimination and excretion 

dorzolamide is primarily eliminated unchanged from the body. The drug is excreted via renal clearance, with a small amount excreted in the feces. The elimination half-life of dorzolamide is approximately four months, which reflects the slow clearance of the drug from the ocular tissues. 

Adminstartion

Administration: 

• Proper Hand Hygiene: Wash hands thoroughly before handling the eye drops. 
• Tilt the Head Back: Tilt your head back slightly or lie down in a comfortable position, whichever is more convenient for you. 
• Gently Pull Down the Lower Eyelid: Use your index finger to gently pull down the lower eyelid, creating a small pocket between the eye and the lower eyelid. 
• Administer the Eye Drops: Hold the dropper close to the eye, being careful not to touch the eye or any surface with the dropper tip. Squeeze the bottle to instill the prescribed number of drops into the lower eyelid pocket. Avoid blinking or squeezing the eyes tightly while administering the drops. 
• Close the Eye: After instilling the drops, close your eyes gently for a moment. This allows the medication to spread evenly over the surface of the eye. 
• Wipe Excess Liquid: If any excess liquid is present around the eye, use a clean tissue or cotton ball to gently wipe it away. Be careful not to rub the eye. 
• Recap the Bottle: Make sure to recap the bottle tightly to prevent contamination and preserve the integrity of the medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dorzolamide 

Pronounced: (dor-ZOL-uh-mide)  

Why do we use dorzolamide? 

• Glaucoma: dorzolamide is used to treat open-angle glaucoma and ocular hypertension. 
• Combination Therapy: dorzolamide is also used in combination with other eye medications such as beta-blockers or prostaglandin analogs for more effective control of intraocular pressure. 
• Cystic Fibrosis: dorzolamide has also been investigated for its potential therapeutic benefits in cystic fibrosis. By inhibiting carbonic anhydrase, dorzolamide can reduce the acidity of airway secretions and improve mucus clearance, potentially improving lung function. 
• Altitude Sickness: dorzolamide has been studied for its potential use in preventing altitude sickness, a condition caused by low oxygen levels at high altitudes that can cause symptoms such as headache, nausea, and fatigue.