DRUGS USED FOR GLAUCOMADr. Theodorus, MMedScStaf Bagian FarmakologiFK Unsri

GLAUCOMAINTRODUCTION - Glaucoma is a disease of the optic nerve - Nerve damage in glaucoma causes typical pattern of vision loss - Elevated intraocular pressure is a risk factor, but not required for glaucoma to occur - 13,5% of global blindness (5.1 million) - Aging demographics will increase the problem (those over age 80 are up to 10 times as likely to develop glaucoma than those under 40)

1. TIMOLOL (maleate)A beta1 and beta2 (non-selective) blockerIt is white, odorless, and soluble in water and alcoholStable at room temperatureOphtalmic solution is supplied as a sterile, isotonic, bufferedBenzalkonium is added as preservative

TIMOLOL (maleate)MECHANISM OF ACTION - The precise mechanism of the ocular hypotensive action of timolol is not clearly established - Its predominant action maybe related to reduced aqueous formation or the rate of synthesis aqueous humor - Effective in lowering intraocular pressure - Short duration of action

TIMOLOL (maleate)PHARMAKOKINETIC - well absorbed into circulation even not significant - plasma concentration is estimated to be about 5-10 ng/ml - can be found in milk of nursing mother

TIMOLOL (maleate)INDICATION - Patient with open-angle glaucoma - Patient with aphakic glaucoma - Some patient with secondary glaucoma - Other patient with elevated intra- ocular pressure - As additional drug

TIMOLOL (maleate)CONTRAINDICATION - Bronchial asthma - Severe chronic obstructive pulmo- nary disease - Sinus bradycardia - Second and third degree atrio- ventricular block - Cardiac failure - Cardiogenic shock - Hypersensitivity

TIMOLOL (maleate)SIDE EFFECTS - Muscle weakness - Severe respiratory reaction - Cardiac reactions - CNS: headache, depression - GI tract: nausea - Masked symptoms of hypoglycemia in insulin dependent diabetes - Visual disturbance, ocular irritation, diplopia, ptosis - Alopecia

TIMOLOL (maleate)DRUG INTERACTION - The concomitant use with digitalis and calcium antagonis may cause prolonging atrioventricular conduction time - Close observation when this drug is administered to patients receiving reserpine due to hypotension - Can cause mydriasis if this drug given together with epinephrine

a. BETAXOLOL A Selective beta1 A white, crystalinne powder and soluble in water A sterile isotonic solution Benzalkonium is added as preservative

BETAXOLOLExhibit fewer cardiovascular side efects than timololBetter tolerated than timolol in patients with reactive airway disease and asthma

SIDE EFFECTSBrief local discomfort, occasional tearingSystemic: insomnia, depression (rare)

b. LEVOBUNOLOLA beta1 and beta2 ( non selective) blockerSterile solution, colorlessBenzalkonium is added as preservative

SIDE EFFECTSLocal: Transient burning/stingingCardiovascular: may resemble timololCNS: ataxia, dizzines, lethargyDermatologic: urticaria, pruritus (rare)

2. PILOCARPINENatural alkaloidsCholinomimetic or cholinergic agentsMiotics, direct - actingA dominant muscarinic actionSweat glands are sensitive to this drugBenzalkonium is added as preservative

PILOCARPINEMECHANISM OF ACTIONActs on a subtype muscarinic reseptor (M3) causing the muscle to contract and produce miosis. This opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eyes to decrease intraocular pressure

PILOCARPINEPHARMACOKINETIC - Onset of action 10 to 30 minutes and the duration 4 8 hours - Causes pupillary constriction, spasm accommodation, and a transitory rise in intra ocular pressure - Causes marked diaphoresis in man - Gastric glands are stimulated to secrete juice

PILOCARPINEINDICATION - Chronic simple glaucoma or open- angle glaucoma - Chronic angle-closure glaucoma - Acute (angle-closure) glaucoma - Pre and postoperative intraocular tension - Mydriasis caused by mydriatic or cyclopegic agents

PILOCARPINECONTRAINDICATION - Hypersensitivity - Where constriction is undesirable ( acute iritis and uveitis, secondary glaucoma, acute inflammatory disease of the anterior chamber) - Safety and efficacy for children have not been established - Pregnancy: category C

PILOCARPINESIDE EFFECTS - Cloudy vision, transient stinging and burning, tearing, ciliary spasm, detached retina - Hypertension, bronchial spasm and pulmonary edema, sweating, salivation - Headache, nausea, vomiting, diarrhea (rare)

PILOCARPINEDRUG INTERACTIONThere have been reports that both these drug (pilocarpine with non steroid anti-inflammatory drugs), if using together; have been ineffective

a. ACETYLCHOLINE CHLORIDAAqueous solution of acetylcholine is unstableMiotics, direct actingShort duration

INDICATIONMiosis. To produce complete miosis in second after delivery of the lens in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery

Acetylcholine chloridaSIDE EFFECTS - Corneal edema, clouding, decomposition - Bradycardia, hypotension, flushing, breathing difficulties, sweating

3. EPINEPHRINEA direct-acting sympathomimetic Act on and receptorsThe most potent vasopressor drugsTopical application: causes conjunctival decongestion (vasoconstriction), transient mydriasis, and reduction in intraocular pressureAvailable as epinephrine bitartrate and hydrochloride: both therapeutically equalBenzalkonium is added as preservative

EPINEPHRINEMECHANISM OF ACTION - It is believed IOP (IntraOcular Pressure) reduction is primarily due to reduced aqueous production and increased aqueous outflow - The duration of decrease in IOP is 12 to 24 hours

EPINEPHRINEPHARMACOKINETICS - Onset < 1 hour - Peak plasma : 4 8 hour - Duration : 24 hour - Crosses placenta; passes into breast milk

EPINEPHRINEINDICATION - Open-angle glaucoma - Chronic simple glaucoma

CONTRAINDICATION - Hypersensitivity - Narrow or shallow angle glaucoma - Aphakia patients - Special risk patients: diabetes, hypertension, heart disease, cerebral arteriosclerosis - For elderly: use with caution - Children: Safety and efficacy have not been established

EPINEPHRINESIDE EFFECTS - Local: Transient stinging and burning; eye pain/ache, browache, allergic lid reactions, conjunctival or corneal pigmentation, localized adrenochrome deposits in conjunctiva and cornea (prolonged use) - Systemic: Headche, palpitation, tachycardia, extrasystole, hypertension, cardiac arrhytmia

EPINEPHRINEDRUG INTERACTIONTimolol, apraclonidine and atropine has an additive effect (synergistic) with epinephrineIncreased sympathomimetic with imipramineDecreased vasopressor effects with chlorpromazine and phenotiazinesDo not use while wearing soft contact lenses

4. CARBONIC ANHYDRASE INHIBITORSCarbonic anhydrase is an enzyme found in many tissues of body including the eyeCarbonic anhydrase exists as a number of isoenzymes Acetazolamide (prototype of this agent), dichlorphenamide and metazolamide are given systemically; DORZOLAMID is used topicallyOriginally introduced as diuretics, but their effect on intraocular pressure does not depend upon diuresis

CARBONIC ANHYDRASE INHIBITORSMECHANISM OF ACTION - This drug reduces the rate of aqueous humor formation; intra- oculary pressure in patients with glaucoma is correspondingly reduces - Inhibition of carbonic anhydrase in the cilliary processes of the eye decreases aqueous humor secretion, presumably by slowing formation of bicarbonate ions with subsequent reduction in sodium and fluid transport

CARBONIC ANHYDRASE INHIBITORSPHARMACOKINETICS - Carbonic Anhydrase inhibitors are widely distributed throughout the body - When used topically: this reach the systemic circulation and accumulate in RBCs. Extensive distribution to RBCs yields a long half-life - Plasma protein binding is moderate (33%) - The absorpsion of this drug does not appear to be reduced by food - Primarily excreted unchanged in the urine

CARBONIC ANHYDRASE INHIBITORSINDICATION - Primary open-angle glaucoma - Others chronic glaucoma refractory to other drugCONTRAINDICATION - Renal and liver disease - Obstructive pulmonary disease - Pregnancy - Efficacy and Safety in children have not been established - Do not administered this drug while wearing contact lenses

CARBONIC ANHYDRASE INHIBITORSSIDE EFFECTS - For topical used: have not been fully evaluated - Ocular stinging, burning or discom- port immediately following adminis- tration (33%) - signs and symptoms of ocular aller- gic reactions (10%) - Blurred vision - Headhe, skin rashes, asthenia/fatigue

CARBONIC ANHYDRASE INHIBITORSDRUG INTERACTION - Can cause salicylate intoxication in patients receiving aspirin - Interfere with the action of methe- namine - Drug induced osteomalacia has been reported with the simultane- ous use of phenytoin

5. LATANOPROSTSelective Prostaglandin F2 analogProtect from the light, may be stored at room temperatureIs a lipophilic prodrugIs converted into the active latanoprost by ester hydrolysis of latanoprostBenzalkonium is added as preservative

LATANOPROSTMECHANISM OF ACTION - The primary mechanism by which most of PGs reduce IOP is by increasing outflow, especially through the uveoscleral outflow pathway - Other mechanism maybe the relaxa- tion of the cilliary muscle - PGs do not reduce aqueous humor

LATANOPROSTPHARMACOKINETICS - Latanoprost si absorbed through cornea where the latanoprost ester product is hydrolyzed to biologically active acid. - Peak concentration will be reached 2 hours after application - Reaching systemic circulation is primarily metabolized by the liver - The metabolites are mainly eliminated via the kidney

LATANOPROSTINDICATION - Open- angle glaucoma - Ocular hypertension - Pigment dispersion syndrome

CONTRAINDICATION - Allergic or sensitive to these drugs - Pregnancy and nursing women - Safety and efficacy in children have not been established - DO NOT ADMINISTERED LATANOPROST WHILE WEARING CONTACT LENSES

LATANOPROSTSIDE EFFECTS - Eyelash change (the most frequent) - Eye irritation, conjunctiva hyper- emia - Iris color change (brownish) - Uveitis - Cystoid macular edema - Common cold (4%) - Pain in muscle/joint/back - Rash/allergic skin reaction

LATANOPROSTDRUG INTERACTION - Addictive to the effect of other ocu- lar hypotension agent including timolol, pilocarpine and oral carbo- nic anhydrase inhibitors