ocular pharmacology

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Ocular PharmacologyIntroduction of drugs used in Eyes : 

1 Ocular PharmacologyIntroduction of drugs used in Eyes Gyanendra Lamichhane, MD LEI, Bhairahawa

Pharmacodynamics : 

2 Pharmacodynamics It is the biological and therapeutic effect of the drug (mechanism of action) Most drugs act by binding to regulatory macromolecules, usually neurotransmitters or hormone receptors or enzymes If the drug is working at the receptor level, it can be agonist or antagonist If the drug is working at the enzyme level, it can be activator or inhibitor

Pharmacokinetics : 

3 Pharmacokinetics It is the absorption, distribution, metabolism, and excretion of the drug A drug can be delivered to ocular tissue as: Locally: Eye drop Ointment Periocular injection Intraocular injection Systemically: Orally IV

Drug Delivery in Eyes : 

4 Drug Delivery in Eyes Topical Periocular Intraocular Systemic drop ointment gel Soft contact lens Subconj. Subtenon Peribulbar Retrobulbar Intracameral Intravitreal oral intravenous Intramuscular

Factors influencing local drug penetration into ocular tissue : 

5 Factors influencing local drug penetration into ocular tissue Drug concentration and solubility: the higher the concentration the better the penetration e.g pilocarpine 1-4% but limited by reflex tearing Viscosity: addition of methylcellulose and polyvinyl alcohol increases drug penetration by increasing the contact time with the cornea and altering corneal epithelium Lipid solubility: because of the lipid rich environment of the epithelial cell membranes, the higher lipid solubility the more the penetration Amphipathic- epithelium/endothelium----lipophilic stroma---hydrophilic

Factors influencing local drug penetration into ocular tissue : 

6 Factors influencing local drug penetration into ocular tissue Surfactants: the preservatives used in ocular preparations alter cell membrane in the cornea and increase drug permeability e.g. benzylkonium and thiomersal pH: the normal tear pH is 7.4 and if the drug pH is much different, this will cause reflex tearing Drug tonicity: when an alkaloid drug is put in relatively alkaloid medium, the proportion of the uncharged form will increase, thus more penetration Molecular weight and size:

TOPICAL : 

7 TOPICAL Drop (Gutta)- simplest and more convenient mainly for day time use 1 drop=50 microlitre Conjuctival sac capacity=7-13 micro liter so, even 1 drop is more than enough Method hold the skin below the lower eye lid pull it forward slightly INSTALL 1 drop measures to increase drop absorption: -wait 5-10 minutes between drops -compress lacrimal sac -keep lids closed for 5 minutes after instillation

Ointments : 

8 Ointments Increase the contact time of ocular medication to ocular surface thus better effect It has the disadvantage of vision blurring The drug has to be high lipid soluble with some water solubility to have the maximum effect as ointment

Peri-ocular injections : 

9 Peri-ocular injections They reach behind iris-lens diaphragm better than topical application E.g. subconjunctival, subtenon, peribulbar, or retrobulbar This route bypass the conjunctival and corneal epithelium which is good for drugs with low lipid solubility (e.g. penicillins) Also steroid and local anesthetics can be applied this way

Periocular : 

10 Periocular Subconjunctival - To achieve higher concentration Drugs which can’t penetrate cornea due to large size Penetrate via sclera Subtenon— ant. Subtenon– disease ant to the Lens Post Subtenon– disease posterior to the lens Retrobulbar-Optic neuritis Papillitis Posterior uveitis Anesthesia Peribulbar-- anesthesia

Intraocular injections : 

11 Intraocular injections Intracameral or intravitreal E.g. Intracameral acetylcholine (miochol) during cataract surgery Intravitreal antibiotics in cases of endophthalmitis Intravitreal steroid in macular edema Intravitreal Anti-VEGF for DR

Sustained-release devices : 

12 Sustained-release devices These are devices that deliver an adequate supply of medication at a steady-state level E.g. Ocusert delivering pilocarpine Timoptic XE delivering timolol Ganciclovir sustained-release intraocular device Collagen shields

Common ocular drugs : 

13 Common ocular drugs Antibacterials (antibiotics) Antivirals Antifungal Mydriatics and cycloplegics Antiglaucoma Anti-inflammatory agents Ocular Lubricants Ocular diagnostic drugs Local anesthetics Ocular Toxicology Corticosteroids NSAID

Antibacterials( antibiotics) : 

14 Antibacterials( antibiotics) Penicillins Cephalosporins Sulfonamides Tetracyclines Chloramphenicol Aminoglycosides Fluoroquinolones Vancomycin macrolides

Antibiotics : 

15 Antibiotics Used topically in prophylaxis (pre and postoperatively) and treatment of ocular bacterial infections. Used orally for the treatment of preseptal cellulitis e.g. amoxycillin with clavulonate, cefaclor Used intravenously for the treatment of orbital cellulitis e.g. gentamicin, cephalosporin, vancomycin, flagyl Can be injected intravitrally for the treatment of endophthalmitis

Slide 16: 

16 Specific antibiotic for almost each organisms Sulfonamiodes- Chlamydial infections like TRACHOMA INCLUSION CONJUNCTIVITIS TOXOPLAMOSIS Bacterial cell wall syntheis inhibitors- Penicillin Cephalosporins I) first generation- gm + cocci eg cephazolone ii) second generation —Gm – ve and antistaphylococcal— cefuroxime iii) Third generation– Gm –ve bacilli --ceftriaxones

Slide 17: 

17 Side effects- allergic reaction neutropenia thrombocytopenia Amino glycosides mainly against gm negative bacilli Bacterial protein synthesis inhibitors Gentamycin—0.3% eye drop Tobramycin- Pseudomonas 1% eye drop Neomycin—0.3-0.5% eye drop

Slide 18: 

18 Tetracycline Inhibit protein synthesis active against both gm+ and gm -, some fungi and Chlamydia Chloromphenicol Broad spectrum ,bacteriostatic, gm+/gm-, Chlamydia 0.5% Eye drop, ointment COMMONLY KNOWN AS JUKE MALAM

Antibiotics : 

19 Antibiotics Trachoma can be treated by topical and systemic tetracycline or erythromycin, or systemic azithromycin. Bacterial keratitis (bacterial corneal ulcers) can be treated by topical fortified penicillins, cephalosporins, aminoglycosides, vancomycin, or fluoroquinolones. Bacterial conjunctivitis is usually self limited but topical erythromycin, aminoglycosides, fluoroquinolones, or chloramphenicol can be used

Antivirals : 

20 Antivirals Acyclovir 3% oinment 5 times-10-14 days 800mg oral 5 times 10-14 days intravenous for Herpes zoster retinitis Others Idoxuridine Vidarabine Cytarabine Triflurothymidine Gancyclovir INDICATIONS HZ keratitis Viral uveitis

Slide 21: 

21 VIRAL DENTRITIC ULCER

CMV Retinitis : 

22 CMV Retinitis

ANTIFUNGAL : 

23 ANTIFUNGAL INDICATIONS Fungal corneal ulcer Fungal retinitis/ Endophthalmitis Commonly used drugs are Polyenes damage cell membrane of susceptible fungi e.g. amphotericin B, natamycin, nystatin side effect: nephrotoxicity Imidazoles increase fungal cell membrane permeability e.g. miconazole, ketoconazole,fluconazile Flucytocine act by inhibiting DNA synthesis

Slide 24: 

24

Mydriatics and cycloplegics : 

25 Mydriatics and cycloplegics Dilate the pupil, ciliary muscle paralysis CLASSIFICATION Short acting- Tropicamide (4-6 hours) Intermediate- homatropine ( 24 hours) Long acting- atropine (2 weeks) Indications corneal ulcer uveitis cycloplegic refraction

Antiglaucoma drugs : 

26 Antiglaucoma drugs Beta blockers- Selective – betaxolol Non selective- timolol reduces aqueous humour production Reduces IOP Side effect systemic bradycardia, Sweating anxiety ocular Irritaion Frontal headache Iris cyst Follicular conjuctivitis

Slide 27: 

27 Carbonic anhydrase inhibitors Systemic topical acetazoamide Dorzolamide brinzolamide Mechanism of action---- reduce aqueous humour formation Side effect Paresthesiae Frequent urination GI disturbances Hypokalamia

Slide 28: 

28 Hyperosmotic agent--- iv mannitol when IOP is very high 60-70 Prostaglandins Latanoprost (0.005% eye drop) increased aqueous out flow Reduced IOP Side effect– conjunctival redness, iris and periocular pigmentation hypertrichosis, darkening of iris

Slide 29: 

29

Slide 30: 

30 stimulus Phospholipase A2 Lipoxygenases Leukotrines Steroids NSAIDS

Corticosteroids : 

31 Corticosteroids CLASSIFICATION Short acting hydrocortisone, cortisone, prednisolone Intermediate acting Trimcinolone, Fluprednisolone Long acting Dexamethasone ,betamethasone

Indications : 

32 Indications Topical allergic conjunctivitis, scleritis, uveitis, allergic keratitis after intraocular and extra ocular surgeries Systemic (pathology behind the LENS) Posterior uveitis Optic neuritis corneal graft rejection NEVER GIVE STEROID IF YOU ARE SUSPECTING ACTIVE INFECTION

ALLERGIC CONJUNCTIVITIS : 

33 ALLERGIC CONJUNCTIVITIS

Slide 34: 

34 SCLERITIS

Slide 35: 

35 ANTERIOR UVEITIS

Slide 36: 

36

Slide 37: 

37 Side effects OCULAR glaucoma cataract activation of infection delayed wound healing

Slide 38: 

38 NORMAL CUPPED DISC ENLARGED CUP

Slide 39: 

39 SYSTEMIC Peptic ulcer Hypertension Increased blood sugar Osteoporosis Mental changes Activation of tuberculosis and other infections

Pre-requisite : 

40 Pre-requisite BP Blood sugar Mantoux TC,DC,ESR CXR

NSAIDS : 

41 NSAIDS Topical use flurbiprofen indomethacine ketorolac Indications episcleritis and scleritis uveitis CME PRE operatively to maintain dilation of the pupil

Ocular Lubricants : 

42 Ocular Lubricants Indication ocular irritations in various diseases Dry eyes Commonly available commercial tear substitutes REFRESH TEARS TEAR PLUS MOISOL OCCUWET DUDROP

Ocular diagnostic drugs : 

43 Ocular diagnostic drugs Fluorescein dye Available as drops or strips Uses: stain corneal abrasions, applanation tonometry, detecting wound leak, NLD obstruction, fluorescein angiography Caution: stains soft contact lens Fluorescein drops can be contaminated by Pseudomonas sp.

Ocular diagnostic drugs : 

44 Ocular diagnostic drugs Rose bengal stain Stains devitalized epithelium Uses: severe dry eye, herpetic keratitis

Local anesthetics : 

45 Local anesthetics topical E.g. propacaine, tetracaine Uses: applanation tonometry, goniscopy, removal of corneal foreign bodies, removal of sutures, examination of patients who cannot open eyes because of pain Adverse effects: toxic to corneal epithelium, allergic reaction rarely

Local anesthetics : 

46 Local anesthetics Orbital infiltration peribulbar or retrobulbar cause anesthesia and akinesia for intraocular surgery e.g. lidocaine, bupivacaine

Ocular toxicology : 

47 Ocular toxicology

Complications of topical administration : 

48 Complications of topical administration Mechanical injury from the bottle e.g. corneal abrasion Pigmentation: epinephrine- adrenochrome Ocular damage: e.g. topical anesthetics, benzylkonium Hypersensitivity: e.g. atropine, neomycin, gentamicin Systemic effect: topical phenylephrine can increase BP

Amiodarone : 

49 Amiodarone A cardiac arrhythmia drug Causes optic neuropathy (mild decreased vision, visual field defects, bilateral optic disc swelling) Also causes corneal vortex keratopathy (corneal verticillata) which is whorl-shaped pigmented deposits in the corneal epithelium

Digitalis : 

50 Digitalis A cardiac failure drug Causes chromatopsia (objects appear yellow) with overdose

Chloroquines : 

51 Chloroquines E.g. chloroquine, hydroxychloroquine Used in malaria, rheumatoid arthritis, SLE Cause vortex keratopathy (corneal verticillata) which is usually asymptomatic but can present with glare and photophobia Also cause retinopathy (bull’s eye maculopathy)

Chorpromazine : 

52 Chorpromazine A psychiatric drug Causes corneal punctate epithelial opacities, lens surface opacities Rarely symptomatic Reversible with drug discontinuation

Thioridazine : 

53 Thioridazine A psychiatric drug Causes a pigmentary retinopathy after high dosage

Ethambutol : 

54 Ethambutol An anti-TB drug Causes a dose-related optic neuropathy Usually reversible but occasionally permanent visual damage might occur

Thank you : 

55 Thank you Any question?

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