Charki.psb

Mydriatics

Cycloplegics

Miotics

(Optometrist)

NERVE SUPPLYDilator Pupillae & Sphincter Pupillae

Acetylcholine receptors: muscarinic and nicotinic

• A number of drugs target acetylcholine receptors, blockade of these receptors is associated with anticholinergic (parasympatholytic) effect, while stimulation causes activation of cholinergic (parasympathomimetic) effects.

Receptors Muscarine & Nicotinic

Muscarinic Cholinergic Receptors:A toxin with neurologic effects, first isolated from Amanita muscaria (fly agaric) and also present in some species of Hebeloma and Inocybe.

The quaternary trimethylammonium salt of 2-methyl-3-hydroxy-5-(aminomethyl)tetrahydrofuran, it is a cholinergic substance whose pharmacologic effects resemble those of acetylcholine and postganglionic parasympathetic stimulation (cardiac inhibition, vasodilation, salivation, lacrimation, bronchoconstriction, gastrointestinal stimulation).

Nicotinic Cholinergic Receptors :• Relating to the stimulating action of acetylcholine and other nicotine-like agents on

autonomic ganglia, adrenal medulla, and the motor end-plate of striated muscle..

Cholinergic:- It means Relating to nerve cells or fibers that employ acetylcholine as their neurotransmitter..

Receptors Muscarine (Vs) Nicotinic1) Nicotinic acetyle choline receptors are ligand gated ion channels, where as

mucarinic Ach receptors are G-proteins coupled receptors system.

2) Nicotine is a agonist/ muscarine( a toxin produced by certain mushrooms) is a agonist.

3) Action of nicotine is fast(1-2msec)/action of muscarinic is slow (100-250msec).

4) In case of nicotinic Ach receptor, subtypes based on different sub-unit composition. muscle and neuronal classification/ in case of muscarinic receptor at least 5 receptors subtype have been described by molecular cloning.

5) In case of nicotinic receptor agonist effects blocked by tubocuranine/ in case of muscarinic receptor agonist effects blocked by atropine.

6) Nicotinic receptor found at neuro muscular junction of skeletal muscle, on the post ganglion neurons of the parasympathetic nervous system and on many neurons on the brain(hypothalamus)/muscarinc receptor found at neuromuscular junction of cardiac and smooth muscle as well as on glands and on the post ganglionic neurons of the sympathetic nervous system..

NEURON &Neuromuscular Junction

Sympathetic & Parasympathetic

Direct & indirect acting Parasympathomimetic

Miotics• Miotics are drugs that cause constriction of pupil.• These are used in t he management of glaucoma’s and the

treatment of esotropias and accommodation insufficiency.

• Types: – Pilocarpine– Carbachol– Phospholine iodide– Physostigmine sulphate

1. Pilocarpine• It is direct acting Parasympathomimetic drug, which duplicates

the muscarine effects of acetylcholine, but has no nicotinic effects.• (Acetylcholine is an organic chemical that functions in the brain

and body, as a neurotransmitter—a chemical released by nerve cells to send signals to other cells)

• Pilocarpine stimulates secretory glands and smooth muscles, but has no effect on striated muscles.

• Pilocarpine Nitrate, a sterile ophthalmic solution is available as 1%, 2%, 4% Drops

• Pilocarpine is effective in the treatment of glaucoma by improving the facility of outflow (by contraction of ciliary muscle) and by decreasing aqueous secretion.

• Onset of miosis occurs with in 10-30 Minutes and• Lasts for 4-8 Hrs following topical application.

• Control of IOP in Angle Closure Glaucoma

• Emergency relief of Mydriasis in an acutely glaucomatous situation

• To reverse mydriasis caused by a cycloplegic agent

• In the treatment of accommodative strabismus

• Controversial role in the treatment of hyphema.

• After cataract extraction in cases of ICCE

Pilocarpine Indications and Usage

Pilocarpine Contra-Indications and Warnings

Contraindications: Hypersensitivity to its components Anterior Uveitis

Warnings:• Readily absorbed systemically on topical application.• Excessive application may elicit toxicity symptoms

(Salivation, lacrimation, sweating, nausea, vomiting, and diarrhea, bronchiolar spasm and pulmonary edema can occur)

Precautions:• Pilocarpine has been reported to cause retinal

detachment in individuals with pre-existing retinal diseases or predisposed to retinal tears. Safety and effectiveness in children have not been established.

Pilocarpine (Adverse-Reaction and Dosage)

Adverse-Reaction: Visual blurring due to miosisAccommodative spasmPoor Dark adaptiation caused by the failure of the pupil to dilate in reduced illumination .Conjunctival hyperemia.

Miotics have been reported to cause lens opacities in suseptible individuals after prolonged use.

Allergic blepharo-conjunctivitis,\Ocular pseudopemphoigoidCorneal epitheliall staining and vascularizationAtypical band keratopathy Iris hyperemiaEpithelial cyst

Dosage and Administration:• To aid in emergency Miosis, 1 to 2 drops of one of the higher

concentraitons should be used.• In reverse mydriasis used depends up on the cycloplegic used.• The drops are used bd(every day) – qid (quater in die (four

times a day) in the treatment of angle closure glaucoma.

2. Carbachol•It is cholinergic prepared as a sterile topical ophthalmic solution•Carbachol is a direct acting parasympathomimetic that is sometimes used when allergy or resistance to Pilocarpine develops.•Unlike pilocarpine, carbachol has both NICOTINIC and MUSCARINE actions.•it is available as 0.75% to 3% Drops

Clinical Pharmacology : It is a cholinergic (parasympathomimetic) agent.Carbachol has a double action, it not only stimulates the motor

end plate of the muscle cell, as do all cholinesterase, but it also partially inhibits cholinesterase.

***Cholinesterase inhibitors are used to reduce the action of cholinesterase, thereby making more acetylcholine available to nerve cells in the brain.***

Cholinesterase : Cholinesterase or choline esterase, which serve as neurotransmitters.Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic

neurotransmitters, such as breaking acetylcholine into choline and acetic acid.These reactions are necessary to allow a cholinergic neuron to return to its resting

state after activation (For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase).

The main type for that purpose is acetylcholinesterase (also called choline esterase or erythrocyte cholinesterase)

it is found mainly in chemical synapses and red blood cell membranes.

Cholinesterase

Carbachol Indications and Contraindications

Indications: For lowering IOP in the Glaucoma

Contraindications:• Miotics are contraindicated where constriction is

undesirable such as acute iritis.• Patient showing hypersensitivity to any component to this

preparation.

Warnings:• Topical only not for injection• Carbachol should be used with caution in the presence of corneal

abrasion to avoid excessive penetration that can be produce systemic toxicity and in patients with acute cardiac failure, bronchial asthma, active peptic ulcer, hyperthyroidism, gastrointestinal spasm, urinary tract obstruction and Parkinson's disease. • As with all Miotics retinal detachment has been reported when used in

certain susceptible individuals

Carbachol Precautions & Adverse Reaction & Dosage

Precautions: Avoid over dosage The miosis usually causes difficulty in dark adaptation Patient should be advised to exercise caution in night driving and other hazardous

occupations in poor light

Adverse reactions:• This preparation is cable of producing systemic symptoms of a

cholinesterase inhibitor even when the epithelium is intact.• Transient ciliary and Conjunctival injection, headache and ciliary

spasm with resultant temporary decrease of visual acuity may occur. • Salivation, syncope, cardiac arrhythmia, gastrointestinal cramping,

vomiting, asthama and diarrhoea may occur..• Patient showing hypersensitivity to any component to this preparation.

Dosage and Administraion:• It is administrated 3 to 4 times per day

It is available in the following concentrations: 0.03 %, 0.06%, 0.125%, 0.25%

it is a long acting cholinesterase inhibitor for topical use that enhances the effect of endogenously liberated acetylcholine of iris, ciliary muscle and other parasympatheticallly innervated structured of the eye.

**** Cholinesterase inhibitors are used to reduce the action of cholinesterase, thereby making more acetylcholine available to nerve cells in the brain.

It thereby causes miosis, increase in facility of aqueous humor, fall in intra ocular pressure and potentiation of accommodation.

Indications and Uses:IN glaucoma-Chronic open angle glaucoma, sub-acute or chronic angle closeure glaucoma after iridectormy or where surgery is refused or contraindicated.

Contraindications: Active Uveal inflammationMost cases of angle closure glaucoma due to the possiblity of incresing angle block.Hypersensitivity to the active or inactive ingredients.

3. Phospholine iodide

ADVERSE REACTIONS:- Stinging, burning, lacrimation, lid muscle twitching, conjunctival and ciliary

redness, browache, induced myopia with visual blurring may occur.

Iris cysts may form and, if treatment is continued, may enlarge and obscure vision. This occurrence is more frequent in children.

Prolonged use may cause Conjunctival thickening, obstruction of nasolacrimal canals.

Lens opacities, paradoxical increase in intraocular pressure.

Dosage and Administration: Early chronic glaucoma, 0.03% instilled twice a day. Refrigerated aqueous solution

shows a drop in potency within four weeks.

Adverse Reaction & Dosage

4. Physostigmine Sulphate•It is an alkaloid obtained from the seeds of physosigmine venenosum.•It is an indirectly acting parasympathomimetic agent.•It is available as a solution 0.25%, 0.5% and an ointment containing 2 % of the drug.•It is a reversible anticholine–esterase.•The mechanism of action involves inhibition of choline esterase with consequent accumulation of acetylcholine a the neuromuscular junctions.

Indications: It can be used in conjunction with pilocarpine in the

treatment of acute glaucoma and angle closure glaucoma and in diagnosis and treatment of myasthenia gravis.

4. Physostigmine Sulphate•Contra-indications: •Predisposing to Retinal Detachment and Hypersensitivity to the Drug •Adverse Reactions: •Twitching (Sudden muscle Spasm)•Irritation•Allerginc Reaction •Depigmentaiton of the lid •Skin has been noted in some patient with the use as an ointmentDosage and Administration:

It is administered every 4 to 6 hours.

Mydriatics

Mydriatics

•Mydriatics are drugs that cause dilation of pupil (No cycloplegic effect)

•Phenylephrine Hydrochloride: •It is available in 5% and 10%•it is primarily a direct acting drug that stimulates the alpha-receptors of those structures innervated by the post ganglionic sympathetic nerve fibers.•It also causes blanching of the conjunctival vessels•It is a mydriatic with no cycloplegic effect

Phenylephrine Hydrochloride-Indications

•Indications and Uses:•Although the mydriasis produced by 2.5% phenylephrine alone is generally adequate for detailed examination of the retinal periphery, it is often sufficient for viewing the posterior pole.

•Mydriasis produced is not accompanied by cycloplegia

•It is a fast acting mydriatic.

•One drop of 2.5% phenylephrine causing >5mmhg rise in IOP has been used as a provoctive test for diagnosis of angle closure glaucoma.

•It is used in diagnosis of ptosis of Horner's Syndrome as it responds to the instillation of 0.125 % phenylephrine drops.

•The diagnosis of Horner's syndrome can also be established as 1.0% phenylephrine causes dilation of a horner’s pupil but not of a normal pupil

Posterior Pole & Horner’s Syndrome

Nerve Pathway & Muscles

Phenylephrine-Contra Indications•Contraindications:•Angle Closure glaucoma (ACG)•Hypertensive patients: phenylephrine is a powerful vasoconstrictor and is absorbed systemically when applied topically to the eye.•10% phenylephrine is contraindicated in infants.•In patients receiving reserpine, guanethidine and tricyclic antidepressants phenylephrine is contraindicated because of their increased susceptibility to vasoconstriction action.•In eyes where corneal epithelium is denuded it may cause corneal clouding.•Persons with a known hypersensitivity to any component.

Phenylephrine-Adverse Effects•Ophthalmic: •Mild Stinging (Pricking Pain (Needle)) on initial instillation•Rebound(Move back or Return) conjunctival congestion on prolonged use•Rebound miosis may occur in some elderly patients•Subsequent instillation my produce les mydriasis (elder patients)

•Systemic:(The Major difficulty in using this drug is the possibility of inducing systemic HYPERTENSION, TACHYCARDIA, HEADACH OR BROWACHE may occur.•Episodes of myocardial infraction(little serious) and arrhythmias in eolderly patients are reported.

•Stability:•One other disadvantage is relatively short shelf life as once the bottle is opened Phenylephrine rapidly oxidizes, which makes it less effective.

Phenylephrine - Dosage•Dosage and Administration: •Topically 1 or 2 Drops into the Conjunctiva of each eye for refraction, in conjunction with some cycloplegic of choice.

•Maximum dilation with phenylephrine alone occurs within 15-60 mins

•The pupil size returns to normal within 4-6 hours.

•Initial instillation of a Topical Anaesthtic before phenylephrine prevent st the Stinging caused by phenylephrine and enhances pupillary dilation.

•Premature infants:•In premature infants for dilation, 2.5% phenylephrien is used in conujunciton with 0.2% cyclopentolate or 0.5% tropicamide.

Mydriatics&

Cycloplegics

Mydriatics and Cycloplegics

Cycloplegics are drugs that cause Paralysis of ciliary muscles, i.e., cause relaxation of accommodation.

•Various Types: • Atropine Sulphate• Homatropine Hydrobromide• Cyclopentolate Hydrochloride• Tropicamide

ACCOMMODATIVE EYE

ACCOMMODATIVE RELAXED EYE

Atropine Sulphate•Atropine Sulphate: •It is a anti-cholinergic prepared as a sterile topical ophthalmic solution and ointment supplied in three strengths •0.5%, 1%, and 3%•IM (Intramuscular ) injections are available as 0.3, 0.4, 0.6 mg/ml preparations

•Mechanism of Action:•Atropine sulphate is a naturally occurring that acts directly on the muscarine receptors of structure innervated by the post- ganglionic parasympathetic fibers.•It does not reduce liberation(dismissal) of acetylcholine, but tissues are rendered (Cause to become) sensitive to it.•It is the competitive inhibitor of the muscarine action of acetylcholine and is the strongest of the drug available for cycloplegic purposes •It causes mydriasis and cycloplegic by paralyzing sphincter Pupillae and ciliary muscle respectively.

Nerve Pathway & Muscles

Anti-Cholinergic Action of ATROPINE

Atropine-Indications•Indications: •It is used for mydriasis and cycloplegia(in young patients in which accommodation is very active)•Pupillary dilation in inflammatory conditions of the iris (to prevent pain, release synechiae and give rest to inflamed tissue)•In ciliary block glaucoma•It is used to prevent undue vagal response in tensilon test.•Amblyopia therapy (penalization)•In cases of accommodative spasm•Pre and post operatively in many intra-ocular surgeries. •Contra indications:•Primary glaucoma or a tendency towards glaucoma e.g. Narrow anterior chamber angle.•Hypersensitivity to any component of this preparation.

Atropine-Precautions & Reactions•Precautions: •Not use in Children- Due to Systemic absorption(Lacrymal Sac) •Compress lacrimal Sac for One Minute-for Stop Systemic absroption

•Adverse Reactions:•LOCAL: Allergic(lids&Conjunctiva), Redness and Crusty flaking of the eyelid margins, dryness and wrinkling of the skin around the eyelids and injected bulbar conjunctiva with some watery discharge. Blurred vision and photophobia are consequent to the cycloplegic and mydriatic effect of atropine

•SYSTAMIC : Dryness of skin and mouth, tachyocardia, irritability or delirium, flushing of face, skin rash, abdominal distension in infants and hyperpyrexia may occur in children. Severe reaction are manifest by hypotension with progressive respiratory depression. The elderly are more susceptible to anti-cholinergic toxicity like cognitive impairment and delirium.

Atropine-Dosage and Administration

•Dosage and Administration:•Because of a long duration of its effect and delay in the onset of action it is not routinely used for office procedures.

CHILDREN: For refraction, administer 1% ointment to each eye, thrice daily for three days prior to examination.

HOMATROPINE HYDROBROMIDE

•Homatropine Hydrobromide: •Homatropine 2% sterile ophthalmic solution was the first anit-cholinergic to be developed specifically as an alternative to atropine. •It is a synthetic anti-cholinergic agent that directly blocks the muscarinic action of acetylcholine, causing mydriasis and cycloplegia. •Its effect generally lasts longer than those of either cyclopentolate or Tropicamide but it is not necessarily more effective. •Homatropine is therefore not commonly used as diagnostic agent, however its relatively long lasting effect makes it valuable in the treatment of anterior ocular inflammations such as iritis.

•Indications and Usage:•As a moderately long acting mydriatic and cycloplegic agent for cycloplegic refraction and in the treatment of inflammatory condition of the uveal tract. •It is inferior to atropine for penalization therapy of amblyopia.

HOMATROPINE HYDROBROMIDE

•Contraindications: •In Persons with a tendency of occludable angles.•It should not be used in patients who have shown allergy to atropine.

Patient Warning: Patient should be advised not to drive or engage in other hazardous activities while pupils are dilated. Caution also in pregnant and lactating mothers.

Adverse Reaction:• similar to atropine but much less in frequency.•Prolonged use may produce local irritation characterized by follicular conjunctivitis, vascular congestion, edema, exudate and an eczematous dermatitis.

•Dosage and Administration:•For refraction instill one or two drops topically in the eye(s).•May be repeated in 5 to 10 minutes if necessary.

Cyclopentolate Hydrochloride•Cyclopentolate Hydrochloride: •Cyclopentolate 1% is an anti-cholinergic prepared as a sterile ophthalmic solution.•Also available as 0.5% and 2% solution.

•Indications:•Cyclopentolate is an effective anti-muscarinic agent and the cycloplegic of choice for children under age 12 and for youths between 12 and 20 when latent hyperopia or accommodative esotropia is suspected.•Its cycloplegic efficacy is greater than homatropine.•Also used for pre and post-operative states when mydriasis is required and when a short acting mydriatic cycloplegic is needed in the therapy of iridocyclitis.•Unlike atropine and homatropine onset of maximum cycloplegia approximates the onset of maximum mydriasis.

•It can also be used in patient with central lenticular changes, if they feel better with mydriasis, till the patient is ready for surgery.

Cyclopentolate Hydrochloride•Contraindications: •Angle Closure glaucoma and in patients with hypersensitivity to the drug.•Cyclopentolate is also not recommended for children with emotional problems since it can have marked central nervous system effects that may be increase in susceptible youngsters. •Adverse reaction:•Local: increased intra ocular pressure, blurred vision, and photophobia•Systemic: psychotic reactions, behavioral disturbances, seizures, disorientation and cardio-respiratory collapse in children have been reported.•Dryness of the mouth , tachycardia, headache or allergic reaction may occur.•Because toxic reactions occur with multiple installations of 1% solution, the smallest does should be used•Management of over dosage in life threatening toxicity includes slow injection of Physostigmine intravenously

Cyclopentolate HydrochlorideDosage & Administration

•Dosage and Administration:One drop followed by second drop in 5 Minutes or as desired by the physician complete recovery usually occurs in 24 hours.

Tropicamide•Tropicamide: •It is one of the most commonly used anti-cholinergic mydriatic because of tis powerful mydriatic effects, rapid onnset of action and low incidence of side effects.•Ti is available as 0.5% or 1% eye drops•Tropicamide acts by blocking muscarinic acetylcholine receptors.•The stronger preparation (1%) also paralyses accommodation.•The 0.5% strength may be useful in producing mydriasis with only slight cycloplegia.

•Indications and usage:•For mydriasis and cycloplegia, for diagnostic procedures and when a short acting mydriatic is needed for some pre and post –operative stages.•Unlike atropine, homatropine and cyclopentolate, pupillary dilation with tropicamide is less dependent on iris pigmentation.•For premature infants a combinations of 2.5%phynylephrine and 0.5% tropicamide is recommended because the latter alone fails to dilate adequately.

Tropicamide•Contra indications:•Contraindicated in angel closure glaucoma and in persons showing hypersensitivity to any component of this preparation.

•Precautions:•In the elderly and others where increased intra-ocular pressure may be encountered, Mydriatics and Cycloplegics should be used with caution.•This preparation may cause CNS disturbances that may be dangerous in infants and children.

•Adverse Reactions:•Local: Stinging sensation•Systemic: Rarely in children, confusion or hyperactivity may occur. •Dosage and administration:•One or two drops of 1% solution in each eye 2 to 3 times at 5 minutes intervals or as directed by the physician.

Onset & Recovery of Cycloplegics