Opt Hal Mo Pharmacology

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M.Djamaludin,dr.,SpFK.,M.Kes

Achmad Yani School of Medicine


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A.TOPICAL ANESTHETICS The efficacy of TA is usually determined by

ability to suppress corneal sensitivity.

Concentration for each drug is obtained beyond whichno further increas in activity occurs


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Maximum effective concentration The concentration at which this maximum efficacy

occurs.

Increasing the concentration of the anesthethicbeyond the MEC serves no useful purpose butincreases the risk of local and systemic toxicity.


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MEC of Procaine,Tetracaine, and Cocaine are 0.5 %,

1 % and 2.0 %. In clinical practice,however,the OEC(Optimum

Effective Concentration) may be less than MEC.


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For instance,0.5 % tetracaine is less irritating to theeye than the MEC 1% and thus is better suited forclinical use.

Combination of two or more local anesthetics dosenot produce and additive effect,but it dose increase the

risk of side effects and so is contraindicated.


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Toxicity It is uncommon for topically applied anesthetics,

benoxinate and tetracaine,to cause mild localstingging or burning after installation.

In some patients,especially who over 50 years.......a diffuse desquamation of corneal epithelium;Punctate

keratitis


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Typical manifestation of systemic

intoxication CNS :

Excitement,restlesness,headache,delirium,convulsion

CVS :Rapid and irregular pulse Ocular : Dilated pupils

GIT :Nausea,vomitus,abdominal pain

Note:Acute systemic (10 drops of a 4% sol)


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Hypersensitivity. Ocular

Allergic episode occur mainly with use of the ester

group of anesthetics,that is,the commonly used fortopical.

Lidocaine,mepivacaine and bupivacaine,lessfrequently than with the ester other group.

Systemic anaphylactic reactions topicalanesthetics are extremely rare


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Psychomotor Reactions.

Psychomotor reactions such as vasovagal syncope mayusuallyoccur from anxiety related to the office visit\

Respiration and cardiovascular status should bemonitored to eliminate drug-induced anaphylaxis as apossible cause of the collapse


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Prevention of Adverse Systemic

ReactionsAdverse reactions to local anesthetic drugs usually

occur depend dose.

Limitthedosagesofdrugs to those comparable

with effective anesthesia without substantial risk ofsystemic toxicity


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INDICATIONS 1.Operative

2.Remove corpus alineum


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ROUTE OF ADMINITRATION1.Injected2.Topical


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CONTRAINDICATIONS Hypersensitivity

Liver disease

Concommitans medications Dry Eye Testing

Perporatory Ocular Injury

Self Administration of Topical Anesthetics


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Mechanism of pain and analgesia Primaryeye care practitioners often encounter

patients who experiencing substantial pain from anunderlying ocular disease.

For example patients with corneal or conjunctivalforeign bodies,abrasions or traumatic hyperemiausually complain of pain as their primary complain


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Cocaine Cocaine exhibits both anesthetic and adrenergic

activity

The usual concentration for ocular1 topical 1% t0 4%but the 10 % solution is often used,for the diagnosis ofHorners syndrome

One drop of 2 % solution produces exellent corneal

anesthesia within 5 to 10 minutes


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Cocaine is used as a nasal spray or in

dacryocystorhinostomy.

Cocainogic due to its adrenergic effects (blocksreuptake of norephinephrine).


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Cocaine contraindicated to Systemic hypertension

Retinal detachment surgery Routine opthalmoscopy

Gonioscopy

Angle close glaucoma (mydriatic effect)


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Tetracaine Ester PABA

Available 0,5%solution Intensity,DOA comparable with proparacaine and

benoxinate

Sol. 1 % successfully to provide anesthesia during

phacoemulsification cataract surgery andintraocular lens implantation


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Benoxinate (Flurasafe)It most commonly combined with sodium fluoescein0.25 %,but recently it was combined with 0.35 %disodium flurexon

Primary used for implanation tonometry.

Side effects:

Stingging,burning,increase or decrease corneal

thickness and allergic reaction.


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Proparacaine C:0.25 % - 0.5 % solution,both with or without sodium

fluorocein

The OOA,intensity,and DOA f anesthesia are similarwith tetracain and benoxinate.

It produce little or no discomport or irritation oninstillation and therefore readily accepted by more

patient.Allergicreaction: Characterized conjunctival

hyperemia and edema,edematous eyelids,andlacrimation. Corneal tickness instally can occur


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B.OCULAR HYPOTENSIVE DRUGS OVERVIEW

Glaucoma can often lead to visual impairment andeven blindess.

Management of these disorders is almost alwaysdirected at the existing intraocular pressure (IOP)lowering

This can be accomplished eithher pharmacologicallyor surgically bydecreasingaqueousproduction orbyincreasingaqueous outflow


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Drugs classification

1.Prostaglandin AnaloguesLatanoprost

Travoprost

Bimatoprost

Prostaglandin Combination Compunds

Prostaglandin and B-blocker


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2.Beta-Adrenergik Antagonist Timolol

Levobunolol

Betaxolol Metipranolol

Carteolol


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3.ADRENERGIC AGONISTAdrenalin

Noradrenalin


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Latanoprost (Xalatan)

Prostaglandin were originally discovered in the eye asmediators of the ocular inflamatory response andmost of the preliminary research focused on theirpotensial role in uveitis and otherinflamatory

disease.


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Latanaprost demonstrates sufficient ocularhypotensive activity with minimal side effect.

Latanaprost is an analogue of prodrug prostaglandinPGF2a-isopropyl ester.When instilled topically intohuman eye .Latanaprost is converted by cornealesterase into lanataprost acid, which exerts itsbiological activity at the FP receptor on the cilliarymuscle.(FP is recepor for PGF2a).


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As a selective FP receptor agonist ,latanaprost appearsto exert its ocular hypotensive effects exclusively byincreasing uveoscleral outflow.

In long-term clinical trial ,latanaprost has been shownto be at least as effective as timolol maleat,beta-blocker in reducing IOP

Latanaprost should be dosed only once daily in theevening or bed time.


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The additive ocular hypotensive effects achived withcombination of latanaprost and timolol are greaterthan than when brimonidine, dorsolamide, or

pilocarpine is used with timolol. And the effectachived with miotics and pikocarpine seems to bemost effective when the bed time dosed isadministered 1 hour after lantanaprost

Latanaprost available in concentration 0.005 %peserved with 0.02 benzalkonium chloride (BAC)


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Side Effects Iris color darkning

Increased eyelid pigmentation

Ypertrichosis Conyunctival hyperemia

Allergy


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Cystolid macular edema

Anterior uveitis

Punctate corneal erosions Corneal pseudodendrites


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Contraindications Lanaprost may be relatively contraindicated in

patients with a history of uveitis or prior incisionalocular surgery.

Previous episodes of herpes simplex virus keratitis

Lanaprost should be used cautiously after cataractsurgery in patients who have risk favouring the

development of CME(Crystoid Macular Edema).


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Travoprost (Travatan)

Travoprost is a PGF2a analog used for treatment ofpatients with open-angle glaucoma or ocularhypertension.Its mechanism of action is similar to thatof latanaprost.

The drugs is formulated as an aqueous solution in a

concentration of 0.004 % preserved with 0.015 % BAC


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Bimatoprost (Lumigan).

Bimatoprost is generally considered to be part of theprostaglandin family of ocular hypotensive analogues.

Bimatoprost is formulated as a 0.03 % solution incitrate/phosphate buffer preserved with BAC (0.005%)


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Bimatoprost dosed once daily provider lower meanIOP than doses timolol used twice dail

Side Effect.

Similar to latanaprost and travoprost,bimatoprostreported to cause changes to pigmented tissues

Contraindications:

Similar with lanataprost


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Prostaglandin combination

Compounds Prostaglandin and B-blocker

These products include a combination of latanaprostor travanost with timolol

Studies have demonstrated comparable efficacy and inthe case of travoprost-timolol combination,a favorableIOP reduction product and the separate compounds

administered concomitantly.


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2.B-ADRENERGIC ANTAGONIST Timolol

Given topically induced a significant and longlasting ocular hypotension.Mean decreases in IOP areapproximately 25 %.

The ocular hypotensive efect of timolol is greater thanof pilocarpine

Drug tolerance of timolol has been described


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Clinical uses

1.Primary open-angle glaucoma

2.Ocular hypotension

3.Secondary glaucoma

4.Prophylactic in IOP after laser

iridotomy,posterior

capsulotomy,and cataract surgeryTimolol is supplied as 0.25 and 0.5 % sterileophthalmic solution of maleate salt.

Given only once or twice installation


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Side Effects:

CVS:

Bradycardia,conduction arrythmias,hypotension,Reynauds phenomenon,fluid

retention

Pulmonary:Bronchocontriction,Asthma,Dyspnea

CNS:

Amnesia,depression,confusion,headache,impotent,

insomnia,myasthenia gravis.


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GIT: Diarrhea,Nausea Dermatologic:Alopecia,Nailpigmentation Other systemic effects: Hypoglycemic

Ocular effects: Allergy:Blepharitis Dry eye Corneal anesthesia Macular edema (aphakics) Macular hemorrhage/retinal detechmaent Uveitis Cataract progression


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Contraindications:

Bronchial asthma

Bradycardia (pulse rate less than 60 bpm) Severe heart block

Overt cardiac failure

Hypersensitivity


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Levobunolol

Similar with timolol is a noncardioselective b-blocker

Clinical Uses: IOP in ocular hypertension

Open angle glaucoma

Prophylactic after cataract surgery

Anterior segment laser procedure

Contraindications: Broncial asthma,COPD


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Betaxolol

Less potent than timolol

Clinical uses:Chronic ocular hypertension

Open-angle glaucoma

Side Effects:

Ocular discomport with 0.25 %

,


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Contraindications:

Bradycardia Severe heart block

Overt cardiac failure

Hypersensitivity


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SystemicEffects:

On average less effect to pulmunary function.A keyclinical advantages is in the treatment of patients withcoexistent open-angle glaucoma and pulmonarydisease


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Metipranolol

It has been used worldwide both orally in thetreatment of systemic hypertension and topically forthe treatment of elevated IOP

Clinical Uses:

Chronic treatment of IOP and open-angle

glaucoma


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Carteolol

Carteolol is a noncardioselective B-blocker similar totimolol,levobunolol and metipranolol

In general,carteolol 1 % demonstartes an ocularhypotensive effect similar to that of timolol maleat 0.5% solution.


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Clinical Uses

Carteolol is used for the chronic treatment of elevatedIOP in patients with ocular hypertension and open-angle glaucoma.

Its ocular hypotensive effects are additive tolanataprost,but its utility in IOP elevations after laserr

or cataract surgery and its additivity with other ocularhypotensive agents have not been fully evaluated


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Beta Blocker CINICAL ISSUES PREFERRED DRUG

Best IOP control Avoid betaxolol

Cost TimololMetipranolo

Timolol hemihydrinante


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Comfort Carteolol

Hypercholesterolemia Carteolol

COPP Betaxolol

Pregnancy Avoid all


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3.ADRENERGIC AGONISTApraclonidine

Apraclonidine a relatively selective a2-adrenoceptoragonist,was developed as a derivate of theantihypertensive agent clonidine.

Clinical Uses:

Prevention of post surgery

Initial treatment of acute-angle glaucoma


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Prevention of postcycloplegic spikes in IOP

Side Effects

After topically using can occurs blanching,eyelidsretaction,and mydriasis

Contraindications:

Patients sensitive to clonidine and taking

monoaminooxidase inhibitors


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Brimonidine

Brimonidine is a relatively potent and highly selectivealfa2-adrenoceptor agonist.

Brimodine,like apraclonidine is additive to otherglaucoma medications

Side Effects:

Hyperemia,burning,stinging,blurred vision,andforeign body sensation.


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Contraindications:

Patients receiving MAOI

It is not contraindicated in cardiopulmonalry diseasepatients but should be used with caution in patientswith severe cardiovascular disease.

Side effects:

Sleepness,lethargy,and fatigu,young children


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4.CABONIC ANHYDRASE

INHIBITORS Mechanism of Action

Bicarbonat formation is an essential component ofaqueous production.A relatively high concentration ofbicarbonate can be found in the aqueous humor.Thepresence of carbonic anhydrase in cilary processes canbe also bedemonstrated in both humans and animals


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The earliest reported ocular hypotensuive properties ofazetazolamide,a carbonic anhydrase inhibitor (CAI)demonstrated a decrease in IOP induced from

inhibition of aqueous humor production. Clinical Uses:

All type of glaucoma


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Azetazolamide In the treatment of all types of

glaucoma,azetazolamide is the most widely used orallyadministered CAI.Actazolamide tersedia dalam

preparat tablet 125 dan 250 mg dan kapsul SR 500 mg(Damox).

Acetazolamide is readily absorbed fromgastrointestinal tract after oral

administration.Acetazolamide is not metabolized danprimary excreted via urine


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Clinical Uses Oral acetazolamide is often reserved for short-term

IOP reduction only.Acetazolamide produces anadditional decease in IOP when added to drug

regimens including miotics,B-blockers,andprostaglandins.

In acute angle-glaucoma,acetazolamide is oftenadministered soon after the dignosis is made.


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An additional clinical use of acetazolamide isunrelated to its ocular hypertension i.e for

1.Crystaloid Macular Edema

2.Retinitis pigmentosa

3Chronic intermediate uveitis (pars planitis)


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Systemic Effects Numbness,tingling of the fingers,toes and perioral

region are most common events.

Malaise,fatigue,weight loss,depression,

anorexia and decreased libido.

Gastrointestinal symptoms: abdomnal and diarrhea.


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Ocular Effects Drug-induced transient myopia

Myopia probably results from cilliary body edema thatproduces a forward displacement of the lens-irisdiaphragma.

The myopia subsides on reduction or discontinuationof acetazolamide therapy


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Contraindications 1.Liver disease

2.Severe chronic obstructive pulmonary disease

3.Certain secondary glaucomas

4.Renal disease incuding renal stones

5.Pregnancy

6.Known hypersensitivity to sulphonamides


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Pharmacokinetic Of CAI Drug Dose OOA DOA

Actz tab 65-250 mg qid -1 h 4-6 h

Actz cap 500 mg bid 1-2 h 10-18

Actz iv 500 mg 1 min 4

Mtzl 25-100 mg bid/tid 1 h 10-14

Dichp 25-50 mg bid/tid/qid 50 min 6-12


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Methazolamide

Stucturally similar with azetazolamide and designedto decrease ionization and thereby improve

intraokuler penetration.

After oral administration metrazolamide is wellabsorbed from gastrointestinal tract.Only 55%metrazolamide binds to plasma protein comparedwith 90-95% azetzolamide


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Side Effects Compared with azetazolamide produces less acidosis

and has less effect on urinary citrate level and lesscauses paresthesia but often causes more drowsiness.

Skin eruption can also occur


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ContraindicationsAre the same as those associated with the use of

acetazolamide.

Methazolamide can be used more safty in patients

with history of kidney stones or renalimpairment.Patients with COPD may toleratemethazolamide better than acetazolamide ,becausethe netabolic acidosis is less pronouced


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TOPICAL CAI Dorzolamide(Trusopt)

Dorzolamide was the first commercially availabletopical CAI to show significant ocular hypotensve

activity in humans.

Indication:IOP,OAG

SE: Local irritation (stinging,burning,blurring)

Contraindication:Allergic,renal mpairment (CrCl < 30ml/min).


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Brinzolamide (Azopt)

Heterocyclic sulfonamide

Indication: IOP and OAG

SE:Taste abnormalities

Contraindications:Similar with dorzolamide


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Timolol 0,5% +Dorzolamide 2% COSOPT

Twice dayly

The mean reduction in IOP 22.2% - 27.4%


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Clinical Advantages of Topical CAI CAIs reduced nocturnal aqeous flow rate

by 25 %


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5.CHOLINERGIC AGONIST (MYOTICS)Direct-acting

Acethylcholine

Methacholine

Pilocarpine

Carbachol


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Indirect-acting (Cholinesterase inhibitors)

Reversible

Physostigmine

Neostigmine

Edrophonium

Demecarium

IrreversibleEchothiphate

Diisoprophylflourophosphate


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PilocarpineIts activity at muscarinic receptor sited on the irissphincter ciliary muscle pilocarpine causes pupilarycontriction and varying degrees of accomodative

spasm depending on the patients ageClinical Uses

Primary open-angle glaucoma

Acute-angle closure glaucoma

Many secondary glaucomas


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Side Effects Ocular Effets

Accomodatie spasm,which can last for 2 to 3 hoursafter instillation of the topical solution.

Systemic Effects.sis and weakneiaphore

Nausea,diaphoresis,salivation,lacrimation,vomiting,and diarrhea


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Headache

Browache (Aggresive)

Marked salivation

Profuse perspiration

Nausea

Vomiting

Bronchospasm


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Pulmonary edema

Systemic hypotension

Bradycardia

Generalized muscle weakness

Incread tone and motility of git

(Abdominal pain,diarrhea)

Respiratory paralysis


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Contraindications Cataract (Nuclear sclerotic,an posterior

subcapsular cataract)

To prevent retinal detachment,and with retinaldetachment,and patients with myopia,peripheralretinal disease that predisposes the eye to theretinal detachment ,and with aphakic orpseudophakic eyes


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M i U d f T f


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Myotics Used for Treatment of

Glaucoma

Generic Name. Trade Name.

Pilocarpine HCl sol Pilopine HS gel

Pilocarpine gel Isopto Carbachol

Ethothiophate iodide Phospholine iodide


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RefferenceJimmy D.Barlett,Richard G.Fiscella,Siret D.Jaanus,and

Howard Barnebey

in Ocular Hypotensive Drugs


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/ Cendocaine gtt.opth Fl 1 1-2 dd gtt 2 p.r.n.

-------------------

Pro:Tn Tony Sucipto

Alamat: Mess Persib,Jl.Achmad Yani Bandung


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Lanaprost Timolol Cendocarpine


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Dr.Ocular

Jl.Retina No. 2. Tilt 08134434

Pemandangan Pmd, 1 Mei 2013 Baquinor Fl I 3dd gtt 2 ODS ---------------------------- Clavulanic Acid cap.500 mg No. X 3dd 1 ---------------------------- Cendoxitrol gtt opth. Fl I 3dd gtt 2 OGDS ----------------------------


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THANK YOU


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TREATMENT OF ABNORMALITAS FILM The goal of Ocular Surface Disease (OSD) therapy are:

1.To relieve symptoms of the OSD

2.To prevent serious complications OSD


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Latanaprost 0.005 % Fl I

1dd gtt 2 h.s.

-----------------------


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Chondroitin sulfat (Viscoat) gtt. Fl I

1-2 dd gtt 2 ar.ocular dolens

p.r.n


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The catagories treatment of dry eye 1.Tear suplementation

2.Tear conservation

3.Tear stimulation

In attempt to establish the tear film quantitavely and

qualitatively.

To diagnose and treat coexistent and ancillary condition

that provoke or aggravate dry eye (riskfaktors):Blepharitis,mebomian disease,eyelid

abnormalitis


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Treatment option for dry eye Tear supplement (artificial tears): Lacrisert (Lactic

acid)

Tear conservation ointment: Punctat occlusion

Tear stimulation:Secretogogues,antiinflamatories/immunomodulators


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Tear supplemetationPolymer-based artificial tear are most common tear

supplement product used in dry eye treatment:

Ocular lubricant are used to treat:

1.Corneal abrasions

2.Ultraviolet keratitis

3.Herpes simplex keratitis 4.Herpes zoster keratitis


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5.Phlyctenular disease

6.Giant pappilary conjunctivitis

7.Superior limbic keratoconjunctivitis

8.Vernal disease

9.Adenoviral infection

10.Other ocular surface condition


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The ideal artificial tear 1.Produced the metabolic optic and physicalcharacteristic of nature tear.

2.Have a long residence time

3.Contain therapeutical additive to treat primary andsecondary damage to eye

Supplement of natural tear with a substanced that

prolongs residence time,improve tear film break up(TBUP) and superior to tear replacement fluids of flow

retention


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Most artificial tear formulation areWater based,

Polymer to enhance:

ViscosityLubricant

Retention time to promote tear film

stability

Other viscosity increasing agents


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Other viscosity increasing agents

include:Gelatin

Glycerin

PolyethtleneglycolPoloxamer 407

Polysorbate 80


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NaCl

KCl

Other ionsBoric acid

Help to maintain tonicity and pH similar to

normal tear


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Polysacharides and vinyl derivates1.

Not produce constantly

1.The substitutes shoul have properties to enhanceretention in the tear film

2.Additio of polymer to arificial tear improve :-Retention

-Increase corneal surface wetability

-Decrease blink friction

-Minimize surface tension


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Substitutes cellulose ethers Hydroxy ethylene celellulose

Hydroxyprophyl cellulose

Methyl celluloseCarboxymethyl cellose

These colloids have been:

1. Used in artificial formulation

2.Dissolve in water to produce colories solution of

varying viscocity3.Having proper optical clarity reflective similar to

cornea


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VICOELASTIC AGENTS Na hyaluronat

Na chondroitin sulfate}Mucopolysach in

extrcell.matrix

Such as:Vitreous,cornea,and aquous humor

Used for:- Intraoocular surgery

-Severe dry aye disorder

Concentration: 0.1 0.5%Subjective and objective improvement (itching)


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Sodium hyaluronate Hydrophylic

High molecular weight

Polysacharide polymer

Reduce subjective and objective symptoms in dry eyepatients


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Chondroitin sulfate Hyaluronic acid 0.1%

Chondroitin sulfate 1%

Mixture:ChS (0.38%) + HA (0.3%)

Effective in allevating symptoms of:

Itching

Burning

Foreign body sensation

Available in as Viscoat


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Polyvinil AlcoholEnhance contact time of opthalmic

medication

As wetting agent for contactlensConcentration 1.4%

Has good retention time due to adsorptive

propertiesCan be easily sterilized


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VISCOSITY-ENHANCE AGENT

Other vinyl derivates 1.PVP -Non-ionic surfactant

-To increase viscosity -Concentration:3%-5%

2.HP-guar (Hydroxyprophyl guar)

-High molecular weight

-A gallable lubricant,to mimic the mucin layer of

tears


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OTHER INGREDIENTS Electrolyt >>NaCl

BUFFERS Normal ph 7.5 depend on:

Bicarbonate,protein,phaosphateanion and other subtances


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PRESERVATIVESAdded to opthalmic sol. To kill or inhibit growth of

moicrorganism

NUTRIENTS Necessary for corneal and conjunctival meabolim

>>>> mucin synthesis

Vit A deficiency affect a variety of epithelial-linedorgan,including eye


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MUCOLYTIC AGENTS Soften mucus and make it more fluid

Acetylcystein

Available as mucomyst in a 10% or 20% solution of the

sodium salt of acetylcystein


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ARTIFICIAL TEAR INSERT LACRISERT:

-Water soluble

-Contain hydroxypropylcellulose

Indication:

-Blurred vision


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AUTOLOGUS SERUMA source of tear replacement in severe dry efe

Improved ocular surface staining


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OINTMENT Indicated for moderate to severe dry eye

Retain longer than other opthalmic vehicles

Patient acceptance of ointment preparation highly

variable


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LACRIMAL OCCLUSIVE DEVICE Used to preserve existing tears

Absobable insert made with hydroxypropylcellulose,collagen and silicone

Topical anesthetic may be used to minimize eyelidreaction


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ADMINISTRATION OF DRUG TOPICAL EAR


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ADMINISTRATION OF DRUG TOPICAL EAR


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DANKE SEHR

Opt Hal Mo Pharmacology

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