Brimonidine Tartrate (Alphagan):
- It is a recently introduced 2nd generation α-adrenergic receptor agonist, with high degree selective to α2 receptors.
- It has a dual action.
- It decreases aqueous humor production like β-blockers and also increases the uveo scleral out flow like prostagladins.
- It has binding sites in the iris epithelium, ciliary epithelium, ciliary muscle, retina and retinal epithelium and choroid.
- After administration its peak plasma level is achieved in 2-4 hours, and declines with a systemic half life period of approximately 3 hours.
Dosage: It is available in 0.2% solution (5, 10, 15ml Packs). Instill one drop twice daily.
Indications: Open Angle Glaucomas and OHT.
The IOP decreasing ability decreases over a period of time so one must keep this in mind while treating patients.
Contraindications: In hypersensitivity to brimonidine tartrate, in patients receiving MAO inhibitor therapy, it should be used in caution with patients with depression and coronary insufficiency. Caution while using it in pregnant and lactating mothers.
Caution in contact lens users. They have to wait for at least 20 mins before using the lens as it gets absorbed in to the lens.
Adverse reactions: Lid crusting, burning and stinging sensation, ocular hyperemia, headache, oral dryness, blurring, fatigue, Hypertension, depression, anxiety, abnormal taste, palpitation and syncope.
Dapiprazole:
Dapiprazole hydrochloride is α adrenergic blocker. It blocks α adrenergic receptors in the smooth muscles and produces miosis. It brings about safe and fast reversal of mydriasis. It is used for iatrogenically induced mydriasis. It has not much effect on IOP in normal people or in patients with raised IOP.
Sympathomimetics
1. Epinephrine:
It is a non selective α and β adrenergic agonist. Its mechanism of action is not fully understood. It is said to have a three stages:-
- β- adrenergic stimulation of the ciliary muscle may increase uveoscleral outflow (the major effect) and trabecular outflow.
- β- adrenergic stimulation of the adenoreceptors in the ciliary epithelium increases the aqueous outflow.
- α adrenergic stimulation may result in reduction of aqueous flow.The net result is that IOP is lowered.
Preparation and Dosage: Epinephrine hydrochloride drugs are stable and are available in concentrations of 0.25, 0.50, 1.0 and 2%. They contain anti oxidants to prevent oxidation.
Borate solutions are less irritating and less stable than hydrochloride or bitartrate solutions.
Epinephrine polymeric matrix releases the drug osmotically over 12 hours period at a rate of 1 to 4 mgm.
Its effect on IOP is proportional to the concentration of the drug. Its onset of action is at 1 hour, with a peak effect at 4 hours, its effect last up to 12 hours.
Additive Effects: It has an additive effect when used with pilocarpine and CAI. It is more effective with betaxolol, maybe because it has less effect on IOP than other β blockers.
It has an advantage over miotics in patients with cataract or in young patients as it does not induce myopia. It can be used in asthmatics.
Contradictions: Severe hypertensive, cardiac disease, thyrotoxicosis, patients taking MAO inhibitors.
Side Effects:
Ocular:
Lid and conjunctiva |
Cornea |
Hyperemia, Burning, Tearing, Skin |
Epithelial oedema, Endothelial toxicity, |
blanching, Adrenochrome deposits, |
Epithelial erosion, Adrenochrome |
Madrosis, Ocular Pemphigoid |
deposits, Stain soft contact lens |
Lacrimal System |
Iris and uveal tract |
Punctal stenosis, epidermalisation of |
Mydriasis and angle closure, visual |
puncta, lacrimal stones |
Distortion, photophobia and iridocyclitis. |
Systemic side effects:
Headache / Browache, tachycardia, premature ventricular contractions, palpitations, tremor, increased BP, Cerebrovascular accidents, myocardial infarctions.
2. Dipivefrin:
It is a pro drug of epinephrine, used to enhance corneal penetration and minimize toxicity by lowering the concentration of epinephrine. The penetration is 17 times more than epinephrine. Its 0.1% is equal to 1% of epinephrine. Side effects are much less when compared to epinephrine. Indicated as the 1st line of therapy in open angle glaucomas and OHT.
Adrenergic Blocking Agents
- Betaxolol.
- Carteolol.
- Levobunolol.
- Metipranolol.
- Timolol Maleate.
Basic Considerations: These drugs compete with sympathomimetic substances for access to receptors, reducing sympathetic activity. They have little effect on pupil size, accommodation. They lower IOP by decreasing aqueous production β-2 receptors (sympathetic activity cause - production of aqueous).
Inhibition of chloride ion pump.
1. Betaxolol: It is a relatively cardio, selective β-1 adrenergic agonist. It is thought to decrease IOP by reducing aqueous formation through blockade of the β-1 receptors. However, the ciliary epithelium is made up of only β-2 receptors. Therefore it may be that it might not be totally a β-1 blocker but also, it may have β-2 blocking properties or it may reduce because of high concentration it may block β-2 receptors.
Comes in a dosage of 0.25 and 0.50%, dosage, 1 – 2 times a day.
Its wash out time is also 2 weeks this may be due to depots in the iris. The IOP lowering response may require a few weeks to stabilize so IOP should be checked after 1 month. IOP lowering effect is 21%.
2. Cartelol: It is a non selective β blocker; its mechanism of action is by decreasing the production of aqueous production. It also has intrinsic sympathomimetic activity possible resulting in few side effects. It also lacks Timolol tendency to raise serum cholesterol and lower high density lipoprotein, a factor to consider in cardiovascular patients.
It is available as topical solution of 1 % used once or twice a day.
Used in all the glaucomas.
IOP lowering effect is 32%.
3. Levobunolol: It is a non selective β blocker. Systemic administration of this agent is used in cardiovascular disorders. Its mechanism of action is to decrease the production of aqueous. It increases the ocular pulse while achieving better IOP control. The long term drift is a little less than timolol.
It is available in 0.5% solution and used once or twice daily. Onset of action is about 1 hour after application. IOP lowering effect is 25-30%.
4. Metipranolol: It is a non selective β-1 and 2 antagonist, given twice daily in a concentration of 0.3 and 0.6%.
It is similar to Timolol, except for the rare production of granulomatous uveitis, especially with 0.6%. IOP lowering effect is 21%
5. Timolol Maleate: It is one of the most common and oldest β blockers available. It is a non selective β blocker. It acts directly on the ciliary epithelium to reduce aqueous production. It lowers IOP both in normal and ocular hypertensive patients.
The drug can lower IOP in the untreated contralateral eye because of systemic absorption which is known as cross over effect.
Timolol penetrates the eye rapidly and its effect is seen in 30 to 60 minutes and lasts upto 24- 48 hours.
Short term escape:The initial dose of timolol produces the maximum effect about 40% or more, followed by a partial decline over the following days or weeks. This may be due to alterations in the β adrenergic receptors in the ocular tissues may be an increase in the no of receptors. The best time to evaluate the effect it is after 1 month.
Long term drift:The IOP slowly increases over a period of time in patients who have well controlled IOP. This may be due to partial adaptation of the ciliary body to long term administration of timolol may be due to decrease in cellular sensitivity.
Preparation & Dosage:It is available in 0.25% and 0.5%. Administered once or twice daily. Maximum action takes place by 2 hours. The washout period for timolol is 14 hours.
It is also available as a gel format applied once daily. It comes in 0.5% concentration. It is more effective with light colors than dark color iris, may be due to its binding effect with melanin. It reduces IOP by 25 to 30%.
Additive effect with other drugs:Pilocarpine and CAIs have an additive effect, where as there is a very small additive effect with epinephrine.
Uses and Side effects:The β adrenergic blockers are useful in all types of glaucomas. They are better tolerated by patients and they don't affect the pupil or the accommodation.
Ocular:
- Burning sensation (B).
- Hyperemia.
- Superficial Punctate Keratitis.
- Corneal Anesthesia.
- Allergic Blepharoconjunctivitis (L)
- Dry eye
- Corneal erosion
- Ptosis
- Visual disturbance
- Hypotony
- Dilated Pupil in case of epinephrine
Systemic:
- Nervous system: Depression, Anxiety, Confusion, Hallucination, Fatigue, Tinnitus, Abnormal taste sensation, Diplopia, Lightheadedness, Cerebrovascular accidents, Psycosis.
- Cardiovascular: Bradycardia, Heart failure, Arrhythmia, Raynaud's phenomenon, Hypotension, Hypertension, Syncope, MI, Death.
- Pu1monary: Dyspnea, Airway obstruction, pulmonary failure, Apnea especially in children (sleep).
- Gastrointestinal: Nausea, Vomiting, Diarrhea, Abdominal cramps
