ANTI GLAUCOMA DRUG uses and side effects

antiglaucoma drugs classifications uses and side effects

1. ANTI GLAUCOMA DRUGS Moderator- dr vinod sharma Presented by-Tanya Aggarwal roll no.-1693

2. Introduction Glaucoma refers to a group of disorders characterized by- Optic neuropathy. Specific pattern of visual field defect. Raised IOP.

3. Mechanism of action of anti glaucoma drugs

4. AIM of treatment to lower IOP to a level where visual loss does not occur. Ideally, treatment should also delay glaucomatous changes.

5. Classification of anti glaucoma drugs topical drugs Beta blockers e.g. timolol , carteolol , betaxolol,levobunolol and metipranolol Adrenergic agonists e.g. epinephrine, dipivefrin , brimonidine and apraclonidine Prostaglandin analogue e.g. latanoprost , bimatoprost , unoprostone Cholinergic agents e.g. pilocarpine , carbachol,demecarium bromide and echothiophate iodide Carbonic anhydrase inhibitors e.g. dorzolamide and brinzolamide

6. Systemic drugs Carbonic anhydrase inhibitors e.g. acetazolamide and methazolamide Osmotic agents e.g. glycerine, mannitol and urea

7. Prostaglandin analogues Presently, a prostaglandin analogue is being considered the drug of choice for the treatment of PAOG(provided a patient can afford it). Mechanism of action- they act by increasing uveoscleral outflow,possibly by increasing permeability of tissues in ciliary muscle or by an action on episcleral vessels.

8. Latanoprost Concentration -0.005% drop,once daily. Lowers IOP by 25-30% with peak at 10-14 hrs. Side effects- ocular irritation and pain. Blurring of vision, increased iris pigmentation, thickening and darkening of eyelashes. - M acular edema can develop during treatment,especially in aphakic patients.

9. Travoprost Concentration -0.004% drop once daily in evening. The effect starts within 2 hours, peaks at 12 hours and lasts for 24 hours.

10. Bimatoprost Concentration -0.03% drop once in the evening. A synthetic prostamide Tafluprost -0.015 % ,it is the only preservative free prostaglandin analogue. Unoprostone - 0.15%

11. Topical beta blockers First drug of choice for poor and average income patients. Mechanism of action- they reduce IOP by reducing aqueous production. This probably results from downregulation of adenylylcyclase due to beta2 receptor blockade on ciliary epithelium and a secondary effect due to reduction in ocular blood flow.

12. Classification of beta blockers

13. Timolol maleate Concentration - 0.25,0.5% 1-2 times a day. Most popular as initial therapy. Reduce IOP by 20-35%. Effect on IOP persists for 1-2 weeks following discontinuation. Short term escape - it implies marked initial fall in IOP, followed by a transient rise with continued moderate fall in IOP. Long term drift- implies a slow rise in IOP in patients who were well controlled with many months of therapy.

14. Betaxolol Concentration- 0.25% 2 times per day Being a selective beta-1 blocker it is preffered as initial therapy in patients with asthma and other pulmonary problems . Its action starts within 30 minutes, reaches peak in 2hours and lasts for 12 hours.

15. Levobunolol Concentration - 0.25, 0.5% 1-2 times per day. Its action lasts the longest and so is more reliable for once a day than timolol .

16. Carteolol Concentration- 1% 1-2 times per day. it raises triglycerides and lowers high density lipoproteins the least. Therefore it is the best choice in patients with PAOG having associated hyperlipidemia or atherosclerotic cardiovascular diseases.

17. CONTRAINDICATIONS Bronchial asthma Emphysema Severe COPD Bradycardia Severe heart block Overt cardiac failure Drug allergy.

18. Adverse effects(systemic) Central nervous system- depression, anxiety, confusion, drowsiness, disorientation,hallucinations . Respiratory system- bronchospasm and airway obstruction, especially in asthmatics. Cardiovascular – bradycardia, arrhythmias,heart failure and syncope. Miscellaneous- nausea,diarrhoea , decreased libido, skin rashes, alopecia, exacerbation of myasthenia gravis.

19. Adverse effects(ocular) These are infrequent. Include burning and conjunctival hyperaemia, progression of cataract and corneal anaesthesia.

20. ADRENERGIC AGONISTS

21. Non selective adrenergic agonists Epinephrine hydrochloride( 0.5,1,2% 1-2 times per day) and dipivefrin hydrochloride( 0.1% 1-2 times per day)- These drugs lower the IOP by increasing aqueous outflow by stimulating alpha receptors in the aqueous outflow system. These are characterized by a high allergic reaction rate. Their long term use has also been recognized as a risk factor for failure of filteration glaucoma surgery.

22. Seletive alpha 2 agonists Brimonidine ( 0.2% 2 times per day)- It is a selective alpha-2 adrenergic agonist and lowers IOP by decreasing aqueous production and also by increasing uveoscleral outflow. Because of increased allergic reactions and tachyphylaxis rates, it is not considered the drug of choice in PAOG. It is used as second drug of choice. Its peak action is achieved in about 2 hours and therefore is used perioperatively to prevent IOP spikes postoperatively.

23. Side effects Systemic – hypertension, tachycardia, headache, palpitation, tremors, nervousness and anxiety. Local side effects- burning sensation,conjunctival hyperaemia, conjunctival pigmentation, allergic blepharoconjunctivitis , mydriasis .

24. Carbonic anhydrase inhibitors Topical – Dorzolamide ( 2% 2-3 times per day) and brinzolamide ( 1%BD) – lower IOP by decreasing aqueous production by altering ion transport along ciliary process of epithelium. -These have replaced pilocarpine as the second line of drug and even as an adjunct drug.

25. Oral- Acetazolamide and methazolamide - these are not recommended for long term use because of their side effects. - however Tab. Acetazolamide 250mg tds may be added to control IOP for short term . - methazolamide 50mg tablet is available. Its action is longer than acetazolamide.

26. Side effects paresthesia of the fingers, toes , hands,feet and around mouth. Urinary frequency due to diuretic effect. Serum electrolyte imbalances- these may bi in the form of: a)bicarbonate depletion- leading to metabolic acidosis. This is associated with malaise symptom complex which includes malaise,fatigue,depression , weight loss. b)potassium depletion c)serum sodium and chloride depletion.

27. Gastrointestinal symptom complex- vague abdominal discomfort, gastric irritation, nausea, peculiar metallic taste. Sulfonamide related side effects- include renal calculi,blood dyscrasias , Stevenson Johnson syndrome, transient myopia.

28. MIOTICS

29. Mechanism of action contraction of the longitudinal fibers of the ciliary muscle , producing tension on the scleral spur: ( Opening the trabecular meshwork ) and facilitating aqueous outflow. Contraction of the circular fibers of the ciliary muscle, relaxing the zonular tension on the lens equator : Accommodation Contraction of the iris sphincter: Constricts the pupil: ( miosis )

30. Preparations Pilocarpine ( 1,2,4% 3-4 times per day) Indications – POAG,acute angle closure glaucoma, chronic synechial angle closure glaucoma. Contraindications – inflammatory glaucoma,malignant glaucoma,allergy . Also available as ocuserts (as pilo 20 and pilo 40) and pilocarpine gel.

31. Carbachol – It is a dual action miotic . Indications- it is a very good alternative to pilocarpine in resistant cases. Preparations- it is available as 0.75% and 3% eye drops. Dosage- the action ensues in 40 minutes and lasts for about 12 hours.

32. Echothiophate iodide- It is a long acting drug. Indications- it is very effective in POAG. Preparations- available as 0.03,0.06 and .0125% eye drops. Physostigmine - used as 0.5% ointment twice a day.

33. Side effects Ocular Side Effects systemic side effects - Accommodative spasm -anxiety - Miosis -bradycardia -Follicular conjunctivitis -increased sweating -Myopia - scoline apnoea(due to -Retinal detachment cholinesterase inhibitor) -Frontal headache - Iritis - Anterior subcapsular cataract - Iris cyst formation

34. Hyperosmotic agents mechanism of action -

35. IV preparation- Mannitol ( 1gm/kg body weight)- should be preferred in presence of nausea and vomiting. It should be administered very rapidly over 20-30 minutes. Its action peaks in 30 minutes lasts for 6 hours. Can be used in diabetics. Urea

36. Oral preparation- Glycerol - 1gm/kg body weight of 50% solution in lemon juice may be given if well tolerated and not contraindicated. It starts action in 10minutes peaks in 30 minutes and lasts for 5-6 hours. Isosorbide - it is inert and can be used in diabetics.

37. Calcium channel blockers Mechanism of action- it might be due to its effect on secretory ciliary epithelium. Preparation – verapamil has been tried as 0.125% and 0.25% eye drops twice a day. Indications- they are used where miotics ,beta blockers and sympathomimetics are all contraindicated.eg in patients suffering simultaneously from axial cataract, bronchial asthma and raised blood pressure.