Ocular pharmacology

Mohammed A. Almasswary, MBBS, FRCSC.

Cornea & Refractive Surgeon

College of Medicine

King Khalid University

1 )Bioavailability-% of unchanged drug delivered to site of potential actionregardless of route of administration

It is a % of availability medication that end in the target organ or structure or target functionYou must have drug which have very good bioavailability it will has available and target a maximum concentration or function

2 )Compartment-body space in which drug is homogeneously distributed

it is a target structer or target cellIt will target a specific structer but some time target another structer

3 )Tissue binding-makes drug unavailable for elimination and prolongs itsretention in a compartment

Relevant anatomic characteristics of the eye

)1Cornea-functions as a permeability barrier)natural barrier) )does not allow drugs to cross by simple diffusion)Some time it is not very good ,it is facet to penetrate intra ocular sturacter by our medication

You must have medication that easy penetrate without affect integrety of eye Properties of different corneal layers

Epithelium- hydrophobicStroma- hydrophilicEndothelium- hydrophobicyou must have medication over come this barrier

ويتجاوز القرنيه يخترق ان يستطسع دواء نجيب الدواء duble barrierالزم يكون بحيث موجود الليhydrophobic, hydrophilic القرنيه يخترق ان يستطيع بالتالي

For maximal corneal drug penetration a molecule must have optimumratio of hydro- and lipo- philicity

2 )Sclera-)another barrier)due to intraocular pressure there is typically a constant outward flow across the sclera, therefore even sub-Tenon’s injections penetrate the globe slowlyThere is inactive pump or inactive process of diffusion of fluid from eye itself into sub tenon or sub connective space due to IOP the fluid moving

3 )Blood ocular barrier-present due to tight junctions of non pigmented ciliary epithelium, retinal pigment epithelium, and retinal capillary endothelial CellsPresent at level of small capillary at the CB , iris, small capillary in retina

There is absolute barrier at this level

Vehicles of drug administration

1) Eyedrops-major route of ocular drug administration)common way) Drops are advantageous because they avoid systemic toxicity

Advantage: put drop dirct on eye it selfDisadvantage: fast flash out by tearing, exposure very limit, drop not act for long time

problems- short duration of availability in the tear film and need to pass through a barrier with limited permeability

tear volume=7ul expanded to 30-50 ul by most commercial eye drops max. bioavailability is afforded by a drop size of 20 ul

For example:حجمها االنسان تقريبا 5كل 10-7دمعه you replace your tear film this tearدقائق

volume can expand 20-25ul if excess become epiphora why mention this? If you take any eye drop the volume from 20-25 some time 50ul the eye take 40% of total

برى وتخرج القطره احط يقول المرضى بعضVolume excess capacity of eye then go out

tear turnover--nonirritated eye-15%/min-following 1 drop-30%/min

-drops therefore wash out in about 5 min, optimum timebetween drops is 5 min

80% of drop egresses through tear duct not into eyeHow improve function of drops?

Add some thing to facilitate the quick penetrationFactors affecting availability of topical meds

1 .Surfactants-increase solubility of hydrophilic drugs by alteringpermeability of epithelial membranes

2 .Drug concentration-concentrated solutions are used tomaximize the amount of drug entering the eye during thelimited availability provided by a drop

تستخدمها ما قبل القطره رج يقول الطبيب كذا عشان

3 .Viscosity-high viscosity solutions increase drug contact timeon the cornea

للدواء ممكن وقت الطول العين نعرض عشان

2) Ointmentsa) Advantages

Increase drug contact time )very long time of exposure)b) Disadvantages

1 .May act as a barrier to vision and penetration of other drops2 .Slow release of some meds from ointment may result in subtherapeutic levels of drug

الرؤيه على وتاثر طبيعي مو شكلها العمل يروح يبغى الواحد اذاHigh bind feature, not fast release as compers to drops

3 )Gel-made of high viscosity acrylics )ex. Ocuserts)- slowly releases drug at a steady state level at overall lower conc. and less systemic side-effects

Small reservoir smellier to contact lens field by medication insertion in upper fornix put up to 2-3 weeks some time 1 month, put in eye then slow release of drug

4) Drug soaked soft CLs/collagen shields-also provide prolonged drugcontact time )rate of drug release may not be constant)

5) Subconjunctival/ retrobulbar injection )sub tenon)-allows drug to bypass conj/cornealepithelial barriers, can allow meds to reach therapeutic levels behind thelens/iris diaphragm

6 )Intraocular injection : inject inside the eye it self can inject in anterior chumper or in vitrouse

7) Systemic administration: oral , IM , IV

Drug familiesAnesthetics )topical and local)

general mechanism-reversible block of conduction through nerve fibers,Use in surgery some time in examenation

toxicity- dose related

injected agents-typically tremor which proceeds to seizure,cardiovascular instability and arrhythmia, respiratory depressionUse in surgery s.e it go to systemic

topical agents-increased corneal epithelial permeability, altered cornealmetabolism with decreased wound repair )common use in clinic) additives for regional blockadea)epinephrine )1:100,000-1:200,000)-causes vasoconstriction toprolong duration of action and provides hemostasisb)hyaluronidase-increases tissue permeability to injection

topical agentsa)proparacaine-OPHTHETIC-0.5% ester solution, onset 15 sec, lasts 20min, good for culture corneal ulcer because not bacteriostatic

b)benoxinate-in FLURESS-0.4% solution, similar to proparacaine

c)tetracaine-0.5% ester solution, longer duration than above.

d)cocaine-1-4%.

Sympathomimetic agents

symathetic fibers innervate dilator muscle dilate of pupil

Do vasoconectraction in systemic and dilation in pupil

this medication very useful in examenation like fundus

epinephrie, vasoconstriction, pupil DILATION. It does not cause cycloplegia.

It is given with local anesthetic inj. To prolong the action of the local

Phenylephrine, dilates the pupil, no cycloplegia. Dilation lasts for 3-4 hrs.

Cocaine, prevents re uptake of nor epinephrine thus causing pupil dilation.)rare use)

This group of medication just dilate the pupil NOT affect in CB Not do cycloplegia = paralysis of CB

It is short action about 3-4 hours

Anticholinergic drugs

Indirect way that stimulation the sympathetic similar to sympathatomimic

blocks acetylcholine action.

Atropine, cycloplegia and mydriatic. Lasts 10 days.

Homatropine, 2-4 days.

Cyclopentolate, 24hrs.

This medication do dilated of pupil and DO cycloplegia

So, this medication do:

Mydriasis

Loss of accommodation

This medication Not use for examination in clinic it is use for theraputic

comparison of actions of major cycloplegics

mydriasis cycloplegia duration

Atropine 30 min 1 hr 14 dayshomatropine 10-30 min 30-90 min 6hr-4 daysscopolamine 40 min 40 min 24 hrcyclopentolate 15-30 min 15-45 min 24 hrtropicamide 20-30 min 20-25 min 4-6 hr

Tropicamide shortest>>> use in surgery like glucoma surgery

Systemic side effect

مع االختبار وقت لك يصير ايش stressتذكروا

dry mucus membrane

urinary retention

tachycardia

Confusion especially in children

اهله تنبهين فالزم

Cholinergic drugs

Rare use in clinic use in glucoma

causes pupillary constriction

acetylcholine, used in surgery

carbachole, pilocarpine. Both are used in glaucoma management.

Side effects: salivation, diarrhea, nausea. Bronchial spasm.

Anti inflammatory drugsSteroids,)common use) suppress inflammatory cells and stabilizes intracellular and lysosomal membranes.

Most of it use topical some time use injected like in diabetic reitnopathy some time use oral like optic neuritis

Cortisone

prednisone

dexamethasone

Fluromethilone

Antihistamines mainly in allergy

Livostin, “levocabastine”

cromolyn Na. mast cell stabilirization

Alomide “lodoxamide tromethamide”

NSAID patents cant use steroid use it like glucoma the steroid increase glucoma

inhibits cyclo-oxygenase reducing production of prostaglandins

fluriprofen “ocufen”

diclofenac “voltaren”

ketorolac “acular”

Topical anti infections agentsAntibacterial.

Antiviral , e.g. acyclovir , trifluridine, idoxuridine

Acyclovir common use not drop it is onitment other name )zophirax or zophyrax)

السبلنق من متاكده ماني

antifungal, e.g. amphotericin B, natamycin, fluconazole

Not drops , not use topical

Antiglaucoma drugsEither increase daring or decrease production

1.Beta blockers;

decreases aqueous production. No effect on the pupil .

timolole,)common)

betoxolole “betoptic”

Levobunalole “levobunalole”

ContraindicationsContraindicationsasthma, pulmonary disease, heart failure, asthma, pulmonary disease, heart failure, arrhythmiasarrhythmias..

Side effectsSide effects;;local: redness, SPK, burninglocal: redness, SPK, burning..

2 .ParasympathomimeticsIncrease outflow this not good in ACG becz the angle close not driange

pilocarpine, carbachole.Increase aqueous outflow.

3 .Alpha agonists use in past not nowepinephrine, dipinephrine “propine”it acts by decreasing aqueous production and increasing outflow.

Aproclonidine “iopidine”hyperemic and recurrent inflammation this drug now not use

, Brimonidine “Alphagan”, both act by decreasing aqueous production

4.prostaglandin analogs act mainly by increase outflow

Latanoprost “Xalatan”. It increases outflow.

Very effective in lowering IOP.

Problems: very expensive, hyperpigmentation of iris , uveitis.

Increase eye lashes

5 .Carbonic anhydrase inhibitors topical , oral , IV

dorzolamide “Trusopt”

ساليد اهمOcular toxicity form

Toxic optic neuropathy becz direct toxic to optic nerve may lead to blidnessethambutoleisoniazidemethanoleSulfonamide

Toxic cataractSteroids common one also produce glucomalong acting mioticsanticholestrole agents

Corneal keratopathyChloroquine anti malaria and use in RATamoxifen use in Brest cancerAmiodarone cardiac medication

Chloroquine/ Hydroxychloroquine

1 )used for treatment of malaria, rheumatoid arthritis, SLE, sarcoid

2 )bind to melanin, build up in RPE leads to toxicity affect retina and lead to blidness

3 )effects are dose dependant-hydroxychloroquine 400 mg/day or less generally

safe

4 )toxic effects )>100 grams total chloroquine dose)

-retinopathy )bull’s eye)

More use >>>> toxic affect

The End

بالتوفيق