GLAUCOMA PHARMACOLOGICAL MANAGEMENT
GLAUCOMA
- A condition characterised by progressive damage of optic nerve associated with raised intraocular pressure (>21mm/Hg).
- Raising intraocular tension due to,
- Excessive production
- Less drainage of aqueous humor.
- Hence, anti-gluacomic drugs act by either,
- Decreasing secretion (beta-blockers, alpha-2-agonists & carbonic anhydrase inhibitors).
- Increaseing aqueous humor outflow (Miotics, Dipivefrine & prostoglandins).
CLASSIFICATION OF ANTI-GLAUCOMA DRUGS:
- Topical Drops
- Beta blockers
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- Eg. timolol, carteolol, betaxolol,levobunolol (may show add on effect so contraindicated with other beta-bocker) and metipranolol.
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- Adrenergic agonists
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- e.g. epinephrine, dipivefrin, brimonidine and apraclonidine
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- Prostaglandin analogue
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- e.g. latanoprost, bimatoprost ,unoprostone
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- Cholinergic agents
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- e.g. pilocarpine, carbachol,demecarium bromide and echothiophate iodide
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- Carbonic anhydrase inhibitors
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- e.g. dorzolamide and brinzolamide
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- Systemic Drops
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- Carbonic anhydrase inhibitors.
- e.g. acetazolamide and methazolamide
- Osmotic agents
- e.g. glycerine, mannitol and urea.
SPECIFIC MOA OF ANTI-GLAUCOMA AGENTS:
- Beta blocker, adrenergic (alpha-2 agonist) & Carbonic anhydrase inhibitor – Decrease aqueous secretion.
- Miotics – Increases trabecular outflow.
- Prostaglandin – Increase trabecular & uveaoscleral outflow.
BETA-BLOCKERS:
- First drug of choice for POAG.
- Lower IOP by reducing aqueous secretion due to β2 receptors effect.
- Topical β-blockers reduce aqueous formation by 24% to 48% in awake humans.
- β-blockers are ineffective during sleep.
Drugs included: Timolol, betaxolol (Cardio-selective), levobetaxolol (Longest acting), levobunolol, carteolol, & metipranolol.
Mechanism of action:
- By antagonizing catecholamines effect & causes reduction in aqueous secretion.
Indications:
- Open angle glaucoma (DOC Timilol)
- Angle closure Glaucoma
- Secondary Glaucoma
- Glaucoma in children
Contraindications:
- Bronchial asthma
- Severe COPD
- Bradycardia
- Severe heart block
- Overt cardiac failure
- Children & infants.
Side effects: Blepharoconjunctivities.
Advantages of topical n-blockers (timolol) over miotics (Pilocarpine)
- No change in pupil size (no miosis) → No fluctuation in I.O.T.
- No induced myopia → Convenient once/twice daily applications
- No ciliary spasm (no spasm of accomodation) → Few systemic side effects.
ADRENERGIC AGONIST:
- Alpha 1 vasoconstriction of ciliary vessles decreased acqueous formation.
- Alpha 2 ciliary epithelium: Decreased secretory activity
- Drug used in refractory glaucoma.
Dipivefrine (adrenaline prodrug):
- Decreasing aqueous formation by constricting ciliary blood vessels.
- Increasing uveoscleral outflow by an increased prostaglandin synthesis.
- Increasing trabecular outflow.
Epinephrine:
- Nonselective α- and β-adrenergic agonist
- Onset of action – 1 hr
- Ocular hypotensive effect may last up to 72hours.
- Black pigmentation on conjunctiva – Dueto oxidation product, adrenochrome.
Apraclonidine & Brimonidine:
- Selective alpha-2 agonists.
- Act by decreasing aqueous secretion.
- Apraclonidine – Can cause lid retraction.
- Brimonidine – CNS depression.
Side effects:
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- Stinging
- Browache
- Conjunctival hyperemia
- Adenochrome deposits
- Allergic lid reactions
- Macular edema
- Blepharoconjuntivitis
- Systemic hypertension
- Arrythmia
- Drowsiness
Contraindications:
- Severe Hypertension
- Cardiac Diseases
- Thyrotoxicosis
CHOLINERGIC DRUGS:
Mechanism of action:
- Iris sphincter contraction → Constricts pupil (miosis)
- Contraction of longitudinal fibers of ciliary muscle, producing scleral spur tension → Opening trabecular meshwork & facilitating aqueous outflow.
- Contraction of circular fibers of ciliary muscle, relaxing zonular tension on lens equator → Accommodation
Classification:
Direct-acting:
- Activate cholinergic receptors directly at neuroeffector junctions of iris sphincter muscle & ciliary body.
Indirect-acting (cholinesterase inhibitors):
- Exert their cholinergic effects primarily by inhibiting cholinesterase, thereby making increased amounts of acetylcholine available at cholinergic receptors.
Indications:
- Acute & chronic narrow angle glaucoma
- Open angle glaucoma
- Primary angle-closure glaucoma prophylaxis (until peripheral iridotomy can be performed).
- Combination of pilocarpine & epinephrine may inhibit pigmented pupillary cyst
Contraindications:
- Presence of cataract
- Patients younger than 40 years of age
- Neovascular and uveitic glaucoma
- History of retinal detachment
- Asthma or history of asthma
- High myopia
- Known hypersensitivity to the drug
PROSTAGLANDIN ANALOGUE:
- Present naturally as mediators for ocular inflammatory response.
- Pro-drugs – Converted to active compound by corneal esterases.
- Pain in absolute glaucoma is best relieved by retrobulbar steroid injection.
MOA:
- Increases uveoscleral outflow PG stimulates collagenase and metalloproteinase to degrade extracellular matrix between ciliary muscle bundles, which inturn leads to hydraulic resistance reduction to uveoscleral flow.
Indications:
- Primary open angle glaucoma
- Normal tension glaucoma
- Chronic closed angle glaucoma
- Pigment dispersion syndrome
- Exfoliation glaucoma
Contraindications:
- Allergy
- Pregnant and nursing mother
- Children
- Uveiticglaucoma
- Immediate postoperative period
- Pt. with healed or active herpes simplex keratitis
Advantage:
- Once daily dosing
- Lack of cardiopulmonary side effects
- Additivity to other anti glaucoma medications
CARBONIC ANHYDRASE INHIBITOR:
Mechanism:
- Inhibit enzyme carbonic anhydrase.
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Reducing aqueous humour formation.
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Lower IOP.
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- Carbonic anhydrase is present in corneal endothelium so drugs that affect it impair its pump mechanism.
- Thus contraindicated in pt. with compromised endothelium & who have gone keratoplasty.
- In humans, aqueous flow rate normally decreases approximately 60% during sleep.
- Acetazolamide has poor lipid solubility & corneal penetration, so not applied topically.
- Reduces aqueous flow, an additional 24% below nocturnal flow rate.
-
Timolol – No significant effect on aqueous flow in sleeping humans.
-
Systemic therapy is considered only last resort.
Contraindications:
- Clinically significant liver disease
- Severe chronic obstructive pulmonary disease
- Certain secondary glaucoma
- Renal disease, including kidney stones
- Pregnancy
- Pt. with known hypersensitivity to sulfonamide
HYPEROSMOTIC AGENTS:
- Osmotic agents are approved for short -term acute glaucoma management in adults.
- Also used in reduction of vitreous volume prior to cataract surgery.
- Acute angle closure glaucoma – First line treatment I.V. mannitol.
- Mannitol must be given intravenously because it is not absorbed from GIT.
Mechanism of action:
Increase blood osmolality
↓
Osmotic gradient between blood & vitreous
↓
Water is drawn out of vitreous
Side effects:
- Hematoma
- Angina
- Diuresis
- Anuria
- Ketoacidosis
Exam Important
- Besides its properties of decreasing intraocular pressure, timolol is preferred in the treatment of glaucoma because it Produces no miosis
- Drug of choice for open angle glaucoma Timolol
- Acetazolamide s contraindicated in sulfonamide hypersensitivity
- Brimonidine can cause drowsiness
- A patient with glaucoma is being treated with systemic beta blocker should not be given Levobunolol
- Acute angle closure glaucoma first line treatment Iv mannitol
- Drug used in refractory glaucoma Alpha agonist
- Latanoprost used topically in glaucoma primarily acts by Increasing uveoscleral outflow
- Main MOA brimonidine in glaucoma Decreased aqueous secretion
- Drug kept as a last resort in the management of primary open angle glaucoma is Oral acetazolamide
- Selective alpha 2 agoinst used in glaucoma is Brimonidine
- Atropine should be avoided in angle closure glaucoma
- Pain in absolute glaucoma is best relieved by Retrobulbar injection of steroid
- Drug CONTRAINDICATED in glaucoma patients suffering from bronchial asthma is Timolol
- Combination of pilocarpine and epinephrine use in glaucoma treatment may inhibit Pigmented pupillary cyst
- In primary angle-closure glaucoma pilocarpine lowers the intraocular pressure by its direct action on the Sphincter pupillae muscle
- In primary open-angle glaucoma pilocarpine eye drops lowers the intraocular pressure by its direct action on the Longitudinal fibres of the ciliary muscle
- In a hypertensive patient with glaucoma Dipivefrine is contraindicated
- Treatment of malignant glaucoma includes Topical atropine, IV mannitol & Vitreous aspiration
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