MIOTICS & MYDRIATICS

Presenter : Dr. ShamikaModerator: Dr. Arun Kumar

Date: 05/02/2016

Muscles of the iris:

•DILATOR PUPILLAE

•Dual nerve supply.•Sympathetic α1 adrenergic are stimulatory while parasympathetic are inhibitory.

• SPHINCTER PUPILLAE

•Dual nerve supply.•Parasympathetic muscarinic are stimulatory while sympathetic are inhibitory.

Miotics Parasympathomimetic drugs

Choliergic drugs.Classified as-1. Directly acting or agonists. Eg-acetylcholine, bethanechol, pilocarpine.2. Indirectly acting or cholinesterase inhibitors.

a. Reversible. Eg- physostigmine, neostigmine, edrophonium.b. Irreversible. Eg- ecothiophate iodide, demecarium, diisopropylfluro phosphate.

3. Dual action: having bothmuscarinic and weak cholinesterase action. Eg- carbachol.

4. Reactivation of acetylcholinesterase: pralidoxime.

• Five types of muscarinic receptors:• The M1 receptors are located in the nervous system.• The M2 receptors are located in the heart, and slow the heart rate and force of contraction.• The M3 receptors are located at the endothelial cells of blood vessels

and cause vasodilatation, lungs causing bronchoconstriction the smooth muscles of the GIT to increase intestinal motility and dilating sphincters, glands to stimulate secretion in salivary glands, detrusor muscle and urothelium of the bladder, causing contraction. They are present in the ciliary muscle and the iris. • The M4 receptors: Postganglionic cholinergic nerves, possible CNS

effects• The M5 receptors: Possible effects on the CNS

Stimulation of the M3 receptors in the eye causes-

1. Contraction of the pupil (miosis) and alters the relationship of the iris with thee lens behind and the anterior chamber angle in front.

2. They contract the longitudinal fibres of the ciliary body and cause opening of the trabecular meshwork and increase the aqueous outflow.

3. They cause contraction of the circular muscles of the ciliary body thus causing the zonules to relax and allow the lens to assume a more spherical shape (accommodation).

Pilocarpine hydrochloride:• It is a parasympathomimetic alkaloid obtained

from the leaves of tropical South American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist.• It was introduced in 1877 for the treatment of

glaucoma.•When applied topically it is largely degraded

in the cornea. Only 3% enters the aqueous. • It is available in 0.12%, 0.25%, 0.5%, 1%, 2%,

3% ,4%, 6%.

•Pilocarpine ocular therapeutic system (ocusert) is available as ocusert P-40 or P-20 or incorporated into soft contact lenses. • Is also available in a polymer vehicle as a gel that

prolongs the duration of action. •The ocusert releases 3 times the dose for 1 hour

and then declines to required value over 6 hours.•Are to be placed in the cul de sac before

sleeping, so that the induced myopia wanes away by morning.

Uses:1. It causes complete miosis on intracameral administration. Used in

cataract sx after lens extraction, in penetrating keratoplasty, iridectomy, etc.

2. 0.12% is used diagnostically to confirm Adie’s tonic pupil. In this condition there is defective parasympathetic innervation to the iris and ciliary body due to post ganglionic denervation. The affected muscles exhibit hypersensitivity to pilocarpine and hence contract, while normal iris does not react to this low concentration.

3. 0.25% to 6% are used in the management of primary open angle glaucoma. It is contraindicated in acute angle closure glaucoma because it cause anterior movement of lens iris diaphragm.

4. As it causes increase in tear secretion and punctal stenosis as side effects, it is used in aqueous tear deficiency (ATD) dry eye. Due to increased salivation and lacrymal secretion it is used in Sjgrens’s syndrome and also for dry eye and xerostomia as an effect of radiation therapy for head and neck cancer.

5. Used to differentiate pharmacological mydriasis from neurological mydriasis. In pharmacological as the receptors are saturated the pupil will remain dilated while in third nerve palsy or Adie’s tonic pupil it will constrict even with very dilute solution.

6. Used to reduce glare in patients with intra ocular lens Implantation.

7. Pilocarpine is used to stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat. It is used to diagnose cystic fibrosis.

Adverse effects:1. Contraction of the ciliary body can cause traction on the pars

plana as well causing retinal tear or rhegmatogenous retinal detachment.

2. Catarctogenesis. 3. Drug induced contraction of the ciliary body causes increased

convexity of the lens and shifts the lens forward. Hence causes induced myopia. This causes brow ache.

4. Reduced vision during night time due to miosis. Reduced field of vision.

5. Higher concentration use causes miotic iris cysts 6. Increased lacrimal secretion and punctal stenosis can cause

epiphora. 7. Increased bleeding during surgery.

8. It causes break down of the blood aqueous barrier hence can cause severe fibrinous iridocyclitis post operative. Hence it is contraindicated in uveitic glaucoma.

9. Posterior synechiae formation.10. It is known to cause idiosyncratic reaction, allergic

reaction, pseudopemphigoid.11. Systemic- salivation, diarrhoea, urinary urgency, vomiting,

bronchospasm, bradycardia, diaphoresis, flushing.12. Succinyl choline should be avoided in patients who have

used these drugs recently.

Acetylcholine Carbachol• Used only intracamerally as

it is not active if used topically. • Available as a powder. Fresh

solution has to be prepared. When given intracamerally it causes miosis in seconds.• Rapidly degraded by

cholinesterases in aqueous. Hence v short acting.

• It is 100 times effective and longer acting than acetylcholine.• Lesser fluctuations in IOP.

Effect last upto 8 hours.• ADR- corneal clouding,

bullous keratopathy, iritis, injection, ciliary spasm, retinal detachment.• Topical- 0.75%, 1.5%, 2.5%,

3%. 3 times a day• Intracameral- 0.01%

Physostigmine Demecarium

•Acetylcholinesterase inhibitor.• Same actions, uses.•Used in patients who fail to

respond to directly acting cholinergic agents.•0.25-0.5% up to 4 times a

day. Eye ointment also available.

• Same as physostigmine.

•Also used for accommodative esotropia. 0.125% once a day for 3-4 weeks. Miosis may interfere.•Prolonged action. Twice

daily usage. Severe ADR.•0.125% twice a day.•Avoid overdosing.

Ecothiophate • Depresses plasma & erythrocyte cholinesterase.• Used in subacute or chronic angle closure glaucoma.• Topical solution is prepared by reconstituting powder

form. Concentrations available are 0.03, 0.06, 0.125 and 0.25%.• Tolerance may develop on chronic use.• As it is an insecticide it is also used for lice infestations of

the eye lashes.

Mydriatics •Mydriatics are agents who dilate the pupil and

cycloplegics are agents which cause paralysis off the ciliary body.• Two classes of mydriatics are available-

1. Adrenergic agonists- adrenaline, cocaine, phenylephrine, hydroxyamphetamine.

They cause pupillary dilatation, increase in aqueous outflow, decreased aqueous formation, and relaxation of ciliary muscles.2. Cholinergic antagonists- tropicamide.Causes mydriasis and cycloplegia.

Adrenaline (epinephrine) Cocaine • Causes mydriasis.• 1:1000 solution used.

Repeated in 5 minutes.•Used for open angle

glaucoma.• Can be used with

procaine and atropine in severe iritis.

• Alkaloid• 2 and 4% solution.• Toxic to corneal

epithelium (hence increased penetration).• Inhibits the action of

amine oxidases and hence reduces the uptake of NE.•Used to diagnose Horner’s

syndrome.

Horner’s syndrome.It is caused due to a lesion in the oculosympathetic pathway. Characterised by ipsilateral miosis, ptosis and anhidrosis.The light reflex is normal in these patients but the pupil is slow to redilate in dim light.

It can be tested pharmacologically as—

Step 1: Instill 2 drops of 4% cocaine in both eyes.It inhibits reuptake of nor epinephrine from the post ganglionic segment. Hence causes mydriasis. But in Horner’s there is no NE. Hence no dilatation.Post cocaine anisocoria of 1mm is diagnostic.Apraclonidine has weak α1 agonistic action. In normal eyes it has little effect on pupil. But in Horner’s syndrome there is supersensitivity and the pupil dilates.

•Step 2: once diagnosis is established, hydroxyamphetamine is used to localise the lesion.•Normal pupil dilates with hydroxyamphetamine. If the Horner’s pupil does not dilate means lesion is in the preganglionic segment. But if it does dilate lesion is in the preganglionic segment.

Phenylephrine hydrochloride•Causes pupil dilatation and conjunctival

vasoconstriction causing blanching.•Action can be reversed by thymoxamine 0.1%.•2.5 and 10% concentrations. 2.5% used most

commonly.•Sufficient mydriasis occurs in 15-30 mins, maximum

dilation in 45-60 mins and remains for 4-6 hours.•Since sphincter pupillae muscles are stronger than

dilator, mydriasis caused by phenylephrine is largely overcome by light reflex.

Phenylephrine hydrochlorideUses •Used mainly for pupil dilation for diagnostic purposes

and in pathological conditions like uveitis, for cycloplegic refraction, before intraocular surgery and in conjunction with miotics.• As an ocular decongestant.•Used to diagnose Horner’s syndrome. In Horner’s

syndrome, phenylephrine 1% solution administered causes mydriasis more than that in the normal eye, because of denervation hypersensitivity.

Adverse effects •Ocular- transient stinging,

blurring, rarely maculopathy in aphakic patients.•Systemic- • Palpitations. • Tachycardia.• Extrasystoles. • Arrhythmias.• Hypertension. • Headache.

• Browache.• Reflex bradycardia• Stroke.•Myocardial infarction.

10% solution contains 5mg of drug per drop. Systemic dose for hypotension is 50-100 micro gram.

Contraindicated in-• Narrow angle glaucoma.• Hypertensives.• Type 1 diabetes mellitus. • Aneurysms.• Cardiac diseases. • Old debilitated patients • Patients on reserpine, TCAs MAO inhibitors or cocaine.• Infants. As it increases BP (dose per unit weight is high)

Hydroxyamphetamine hydrobromide • Indirect acting adrenergic agent.• It releases nor- epinephrine from post ganglionic nerves.•Minimal cycloplegia. •1% concentration equivalent to 2.5% phenylephrine.•25-40 minutes for max dilatation. Lasts 4-6 hours.

Uses-•To dilate the pupil for ocular examination.•To differentiate post ganglionic Horner’s syndrome from pre ganglionic Horner’s syndrome. Post ganglionic lesions fail to dilate.

Tropicamide •Blocks the effect of acetyl choline released. •Causes mydriasis and cycloplegia both.•0.5 or 1% acts within 20-30 minutes and effect lasts for 6-8 hours.•Mydriasis is more pronounced. It prevents pupil constriction in response to indirect ophthalmoscopy and retinal photography. • Independent of iris pigmentation.

Uses and Adverse reactions•Since it has no vasopressor action it can be used safely in cardiac patients.• It is the first choice of mydriatic because it is rapid acting, short acting, and strong intensity of action.•Commonly used as a combination with phenylephrine or hydroxyamphetamine.

Mydriatics and cycloplegics

•Atropine, homatropine, scopolamine and cyclopentolate are cycloplegics that are used in uveitis or acute anterior segment inflammation to reduce the formation of posterior synechiae.•They also reduce the permeability of blood aqueous

barrier and help to reduce inflammation apart from causing cycloplegia. •They can be used as occlusion therapy for amblyopia.

Thank you