MYDRIATIC & MIOTIC EFFECT OF DRUGS ON RABBIT'S EYE.

Object To study the mydriatic & miotic effect of topically applied drugs on rabbit's eye. Experimental Animal: Rabbit - (2.5 Kg in wt.) Experimental Requirement; - Torch, Scale (6 small), Cotton, Hair aesthesiometer, Scissors, Dropper, Rabbit holder (cage) Drugs : Normal saline 0.9% Pilocarpine 1-2% Ephedrine 4% Atropine 0.5-1% Phenylepherine 5% Xylocaine 0.5% Principle Local action of a large number of drugs in an eye can be achieved without systematic effect by the application of drugs as eye drops or eye ointment. Most of these drugs belong to antimicrobial, autonomic or local anaesthetic groups. The eye is supplied both by sympathetic & parasympathetic nerves. The iris has two types of muscles 1. Dilator pupillae (radial muscle) 2. Sphincter pupillae (circular muscle) Circular muscle has parasympathetic supply while radial muscle has sympathetic supply. The cilliary muscle is also supplied by parasympathetic nerves & when it contracts, the cilliary body move inwards & forwards. Because of this the lens bulges forwards & eye is accommodated for near vision. The opposite effect is produced by the relaxation of cilliary muscles resulting in paralysis of accommodation (cycloplegia). When the pupil dilates the iris folds back near the opening of the canal of schlemn & the drainage of aquous humour is decreased thereby increasing intraocular pressure and constriction of pupil by opposite action that will increase drainage & reduce intra ocular tension. Topically applied drugs can affect the eye by changing conjunctival congestion, pupillary size, corneal sensitivity & intra ocular pressure. However the effect of drugs on Pupillary size, Light Reflex (L.R.) & Corneal Reflex (C.R) can be studied easily. 1. Pupillary size- Can be measured by placing a transparent plastic scale in front of the eye, as close as possible. 2. LR- Elicited by directing the light of a torch towards the pupil from back. The positive response shows constriction of pupil. 3. Corneal Reflex- Sensitivity of cornea is tested by touching cornea gently with a fine cotton wick/hair aesthesiometer from the side & not from the front of the eye.Positive response show blinking of the eyelids. Physostigmine is a reversible cholenestrase inhibitor which increases the endogenous acetylcholine, this inturn stimulates the circular muscle of iris to produce pupillary constriction without producing loss of light reflex & corneal reflex.

Ephedrine & Phenylephrine- Stimulate the radial muscle of the iris, this produces dilatation of pupil without any effect on light reflex & corneal reflex. Atropine- An antimuscarinic agent, block the effect of endogenously released. ACh in the circular muscle of the iris. This also causes stimulation of ciliary muscle. This produces mydriasis & spasm of accommodation leading to cycloplegia but without producing loss of corneal reflex. Ciliary muscle is present in the eye mainly supplied by parasympathetic nerves & weak sympathetic supply. This is responsible for accommodation. Anticholinergic drugs eg. atropine causes paralysis of ciliary muscle, tightening of suspensory ligaments, the lens is flattened & focal length increases. Eye is fixed for far vision known as 'paralysis of accomodation' or cycloplegia EXPERIMENTAL SET UP (PROCEDURE) One rabbit is used to study the action of one drug. Different rabbits are required to study the action of various drugs. Their eye lashes are trimmed with scissors, as they interfere with elicitation of corneal reflex/conjunctival reflex. Place a rabbit in the rabbit holder box. Keeping its head outside. Observe size of the pupil, LR & CR in both the eyes [examine the LR by holding the torch in front of the eye moving light beam to & fro (from back to front), examine the corneal reflex by touching side of the cornea with horse hair aesthesiometer or cotton wick. One eye of the rabbit is used (RE) as 'control' for the experiment. Instill few drops of normal saline in right eye & atropine(Drug) in left eye (test eye). Record the pupillary size, LR & CR after 10 mins of drug instillation & tabulate the observation Repeat the test with other drugs (pilocarpine, ephedrine etc) OBSERVATION TABLE Drugs Size of Pupil(mm) Light Reflex Corneal Reflex Remarks (inference) Pilocarpine 2% RE LE RE LE RE LE Miotic response is seen causing constriction of pupil, no effect on LR/ CR. could be a Parasympatho-mimatic drug. BABABABABABA 5552PPPPPPPP Atropine 1% 5 5 5 10 P P P Ab P P P p Mydriatic effect is seen i.e. (dilatation of pupil) no change in CR LR is lost. So possibility of parasympa-tholytic drug Ephedrine 4% 5 5 10 P P P P P P P P P Mydriatic effect is seen. CR and LR both remain unaffected. Hence, possibility of a sympathomimetic drug. B- Before drug instillation - P- Present A- After the drug instillation - Ab- Absent Definitions Mydriatics: These are the drugs which causes dilation of the pupil. Miotics: These are the drugs, which produce constriction of the pupil.

Cycloplegic: These are the drugs, which cause loss of the accommodation by casing paralysis of the ciliary muscle. Discussion (Effect of Drugs) Pilocarpine : Is a parasympathomimetic drug. It acts directly. It causes contraction (++) of circular muscle of the iris & leads to decrease in size of pupil (constriction of pupil). Physostigine (Eserine): Is indirectly acting drug it is anticholineterase agent. It decreases the metabolism of ACh. Hence increase the concentration of ACh locally. Thus, causes miosis. (same as parasympathomimetics). Adrenaline /Ephedrine These are sympathomimetic drugs they cause contraction of radial muscle (++) (Ephedrine act indirectly by releasing Adr / NA & causes mydriasis. The light reflex & corneal reflex are not affected by these drugs. Atropine: It is a parasympatholytic drug. It causes paralysis of circular muscles by blocking muscarinic receptors which release ACh. Thus, causing predomination of sympthetic action. There is unopposed action on radial muscles this produces mydriasis and there is loss of accomodation (cycloplegia) & light reflex, due to action on cilliary ganglion. Advantages of the Experiment 1. To study the effects of drugs on ANS (eye) 2. Also to screen the drugs for surface anaesthesia. Clinical relevance 1. Miotic effect of physostigmine is useful in glaucoma as drainage of aquous humor is facilitated resulting into decrease in I.O.P. 2. Short acting mydriatic effect of phenylepherine is used in fundoscopy, where topical anticholinergic (mydiatrics) are avoided. 3. Topical effect of xylocaine is used to produce surface anaesthesia for minor local surgery eg. Foreign body removal, symptomatic relief of corneal/ conjunctival irritation. 4. Atropine is used for fundoscopy & to provide rest to the iris, e.g. in iritis 5. To counteract the mydriatic & cycloplegic effect miotics are used. Miotic effect of phystostigmine is used in glaucoma as the drainage of aquous humor is facilitated & decrease in I.O.P occurs Phenylepherine is short acting and not causing cycloplegia. Hence, often preferred over atropine and its substitutes specially in elderly. MYDRIATIC AND MIOTICS (VIVA-VOCE QUESTIONS) Q. 1 What are mydriatics? Name some mydriatic agents

Ans. Those drugs which cause dilatation of pupil, are called mydratics. The commonly used mydriatics are a. Atropine - Having slow and long lasting action. b. Homatropine - less potent than atropine short duration of action c. Cyclopentolate, tropicamide. d. Sympathomimetics ephedrine, adrenaline, phenylepherine. Q. 2 Discuss the mechanism of mydriasis, what do you understand by Active mydrasis and Passive mydriasis ? Ans. There are two types of muscles present in the iris a) Dilator pupillae or radial muscle, is supplied by both and and receptors innervated by sympathetic nerves. b) Sphinctor pupillae or circular muscle, it is having muscarinic cholinergic receptor innervated by parasympathetic nerves. Topical instillation of sympathemimetic in the eye causes stimulation of radial muscle of iris and causes mydriasis because there is constriction of muscle, it is called 'active mydriasis' this is not associated with cycloplegia. When anti cholinergic drugs, like atropine instilled locally in the eye it causes paralysis of circular muscle of the iris and there is unopposed action of dilator pupillae or radial muscles. This causes dilation of pupil this is called 'passive mydriasis' because it is caused by paralysis of muscle. This is associated with cycloplegia. Q. 3 What is cycloplegia? Ans : Mydriasis caused by atropine is associated with paralysis of circular muscle. This produces tightening of the suspensory ligament, resulting in flattening of lens with a consequent increase in the focal length of the lens. Thus, the individual is able to see things clearly only at a long distance due to fixing of lens for far vision. He is unable to constrict the pupil due to paralysis of circular muscle for viewing of near objects or in response to bright light (photophobia) this phenomenon is known as loss of accomodation or cycloplegia. Q.4 Name some drugs which produces mydriasis with cycloplegia? Ans. Sympathomimetics, viz. adrenaline, phenylepherine, cyclopentolete (less cycloplegia). Q. 5 Name mydriatic agent which preferred in children? Ans. Atropine and homatropine. Q.6 Name mydriate agent in elderly Ans Phenylepherine, tropicamide, sympathomimetics. Q. 7 Why atropine is not preferred in elderly? Ans. Because of aging process elderly have shallow anterior chamber of eye. So, when we use atropine it causes mydriasis with cycloplegia it may precipitate glaucoma. Also it may cause systemic adverse effects, e.g retention of urine. Q. 8 Why atropine substitue are preferred over atropine? Ans. Mydriasis caused by atropine is long lasting. Also it causes cycloplegia. Some times it may cause severe adverse effects if absorbs systemically specially, in children. So, atropine substitutes are

preferred over atropine. Q. 9 Can cocaine is used for opthalmic purpose? Ans. Cocaine is a local anaesthetic agent causes mydriasis due to a receptor action. It is not used for this action purpose because it causes corneal necrosis. Also it is a drug of abuse and leads to strong psychological dependence. It also stimulate CNS Other systemic effects are seen like rise in BP, tachycardia, etc. Q. 10 Enumerate the therapeutic uses of mydriatics ? Ans (a) For the refraction and others ophthalmic examinations like retinoscopy fundoscopy. (b) To break adhesion between iris and cornea or iris and lens, used alternatively with miotics. (c) In inflammatory conditions of eye to relieve pain. C/I of mydriatics Glaucoma Q. 11 What are miotics? Name some miotic agents. Ans. Those drugs which cause constriction of pupil are called miotics. Commonly used miotics are : Pilocarpine occusert Phystostigmine, neostingmine Carbachol a- adrenergic antagonist. Adrenergeric neuron blockers Demcarium is the longest acting miotic but not used clinically because it accelerate the development of cataract. Pilocarpene (occusert) is available now as (long DDS). Q. 12 What is the mechanism of action of miotics? Ans. Topical instillation of parasympathomimetic drug in the eye stimulates circular Muscle of the iris and causes miosis. Q. 13 What is glaucoma? Name drugs used in glaucoma Ans. Increase in I.O.T. is known as glaucoma (>19mm Hg). In Acute narrow angle. Glaucoma. 1. Timolol topical b - blocker 2. Miotics pilocarpine 3. Hypertonic mannitol 4. Acetazolamide In chronic angle glaucoma 1. b- Blocker Timolol 2. Miotics 3. a - adrenergic agonist Dipivefrine 4. Acetazolamide Mechanism of Action of drugs used in glaucoma Miotics Increase the tone of cilliary muscle and sphinctor pupilae thus facilitate the flow of aq. humour. But short acting so fluctuation in I.O.T is common. b blockers no fluctuation/ no change in size of pupil, no induced myopia, no headache but causes systemic adverse effects e.g. bronchospasm; bradycardia, CHF specially, in elderly. a - adr agonist increase aq outflow, increase aq formation e.g. Dipivefrine is a prodrug of adrenaline, longer and consistent action used as adjuvant to miotics or b blockers.

Betaxolol b1 selective antagonist, less effective and few adverse effects. Q. 14. What are the advantages and disadvantages of b blockers used in glaucoma? Ans. Discussed in mechanism of action. Q. 15 Name the drug which produces miosis by central action? Ans: Morphine Q. 16 Will morphine produce miosis when applied locally in the eye? Ans. No, because morphine causes miosis due to its action on E.P nucleus of 3rd cranial nerve which is its central action. Morphine does not have local miotic action. Q. 17 Enumerate therapeutic uses of miotics? Miotics are used in the treatment of glaucoma Alternatively with mydratics, they are used to prevent adhesions or to break adhesion in iritis. To counteract the mydriatic effect of atropine and others.