II. BASIC PHARMACOLOGY OF OCULAR AUTONOMIC DRUGS

Objectives:After listening to the lecture (s), and studying the textbook the student should be able to know pharmacological actions, mechanisms of action, adverse effects and therapeutic used and contraindications of:

- Miotics

- Mydriatics

- Cycloplegics

- Drugs affecting intra-ocular pressure

- Treatment of open and closed angle glaucoma

I. Parasympathetic stimulation (via muscarinic receptors) causes:

1. Conjunctival vasodilatation

2. Contraction of constrictor pupillae muscle causing miosis

3. Contraction of ciliary muscle causing accommodation for near objects

4. Increased lachrymal secretion

5. Stimulation of nicotinic receptors causes twitches of eye lid muscles

Antimuscarinic drugs as atropine causes:

1. Mydriasis

2. Cycloplegia3. Loss of light reflex

4. May increase IOP in susceptible patients

I. Sympathetic stimulation causes:

1. Conjunctival vasoconstriction

2. Contraction of dilator papillae muscle causing mydriasis (α effect)

3. Exophthalmos and widening of palpebral fissure

The ciliary muscle contains β2 adrenoceptors (cause relaxation). Both α- and β- adrenoceptors are present in the blood vessels of the ciliary’s processes. These receptors are important in the regulation of aqueous humour formation.

MIOTICS

1. Drugs that cause constriction of pupil

2. Parasympathetic axons innervate the constrictor muscle of the iris producing miosis.

3. Miosis is seen in a variety of medical conditions and can be caused by drugs

3. Miotics include central miotics and peripheral mioticsCentral miotics:

MORPHINE: stimulates oculomotor nucleus causing miosis

Peripheral miotics include:

1. Cholinomimetic Drugs

I. Cholinesterase as acetylcholine and carbachol

II. Natural cholinomimetic alkaloids as pilocarpine

III. Cholinesterase inhibitors as physostigmine and ecothiopate

2. α-adrenoceptor blockers as phenoxybenzamine

Mydriasis caused by:

1. Disruption of the parasympathetic nerve supply to the eye

2. over activity of the sympathetic nervous system

Madras's is excessive dilation of the pupil due to disease or drugs

Mydriatics

Drugs that cause dilatation of the pupil

1. Sympathomimetics as phenylephrine causes mydriasis without cycloplegia or loss of light reflex

2. Antimuscarinic drugs as atropine, homatropine, cyclopentolate, tropicamide

3. Ganglion blockers cause mydriasis and cyclplegia* The pupil will normally dilate in the dark.

* Usually constricted in the light.

* Mydriatic pupil will remain excessively large, even in A bright environment

* Two types of muscle control the size of the iris, circular muscle, (parasympathetic innervation), and radial muscle (Sympathetic innervations (α1 effect)

* Mydriatics as tropicamide are used in:

1. Pupil examination of the retina and other deep structures of the eye

2. To reduce painful ciliary muscle spasms

Cycloplegia

1. Cycloplegia is the paralysis of the ciliary muscle of the eye resulting in a loss of accommodation.

2. The ciliary's muscle has Muscarinic (parasympathetic) innervations and controls the shape of the lens.

3. Cycloplegic drugs are generally muscarinic receptor blockers. These include atropine, cyclopentolate, homatropine, scopolamine and tropicamide.

4. They are indicated for use in cycloplegic refractions and the treatment of uveitis. Many cycloplegics are also mydriatic (pupil dilating) agents and are used as such during ophthalmoscopic examinations to better visualize the retina.

5. These agents paralyze the ciliary's muscles and cause dilatation of the pupil. They are useful in providing pain relief to patients with corneal abrasions and iritis.

CYCLOPLEGIC DRUGS

Cause paralysis of ciliary muscle, resulting in loss of accommodation, resulting in pupil dilation

Drugs as atropine, homatropine, tropicamide and cyclopentolate are used in cycloplegic refractions and treatment of Uveitis

CYCLOPENTOLATE

Mydriasis obtained in 30-60 minutes and recovery in in 12 hours.

HOMATROPINE 2.5%

Mydriasis is obtained in 40-60 minutes and recovery occurs in 2-3 days. This agent is useful for patients with conditions where the healing period may last a few days.

3. TROPICAMIDE/PHENYLEPHRINE 0.8%/5%

Mydriasis occurs in 20 minutes and recovery occurs in 2-3 hours. This agent is best used for fundoscopic examination when longer term mydriasis is not required.

CAUTION IN USING CYCLOPLEGIC DRUGS??

The risk of angle closure glaucoma should not prevent the generalist from using these agents for diagnosis and treatment. Caution is advised in patients over 70, patients with a past history of glaucoma or those with a shallow anterior chamber. An easy way to define the depth of the anterior chamber is to simply shine a light across the cornea. Patients with a shallow chamber will show a shadow on the distal side.

Mydriatics and cycloplegics should be used with some care when patients exhibit narrow angles. Complications can occur, but are not common, and can be dealt with should an emergency occur. Side effects will be blurred vision and photobia, and driving immediately after dilation or cycloplegia is not recommended.

What is glaucoma?

1. Glaucoma is actually a group of eye diseases that lead to damage of the optic nerve which can then lead to vision loss and the possibility of blindness.

2. Optic nerve damage usually occurs in the presence of high intraocular pressure; however, it can occur with normal or even below-normal eye pressure.

3. Glaucoma is not a disease that is limited to the elderly. The condition can also appear in children and young adults

4. Symptoms or signs of glaucoma are often absent in the earliest stages of the disease. Tragically, impaired vision is sometimes the first sign of glaucoma. In other instances, symptoms and signs of glaucoma may include eye pain, clouded or haloed vision, red eyes, headaches, and nausea

GLAUCOMA

* Disease of the eye that damage the optic nerve

* Can cause blindness

* Not limited to the elderly but can appear in children and young adults

* Glaucoma may occur when the natural fluids of the eye are impeded from draining properly causing elevated IOP which may damage the optic nerve

* Symptoms or signs of glaucoma are often absent in the earliest stages of the disease. Impaired vision is sometimes the first sign of glaucoma. Others may include eye pain, clouded vision, red eyes, headaches and nausea.

* Frequent, routine eye examinations are the best way to detect glaucoma. Ophthalmologist will:

1. Test the eye’s drainage angle (Gonioscopy)

2. Evaluate the optic nerve (Ophthalmoscopy)

3. Measure the eye pressure (Tonometry)

4. Test the visual field of each eye (Perometry)

The information from these examinations is compared at regular intervals to determine if glaucoma has progressed over time. Regular check-ups play an important role in the early detection of glaucoma.

Glaucoma is often asymptomatic for an extended period of time making routine eye examinations extremely important.

DIFFERENT FORMS OF GLAUCOMA

1. OPEN ANGLE GLAUCOMA

1. The most common form of the disease (95% of cases). 2. Occurs when the angle between the cornea and the iris where fluid is supposed to drain from the eye is open, but the fluid drains too slowly.

2. Has no symptoms at first.

3. Progressive disease characterized by optic nerve damage.

4. High eye pressure is the most significant risk factor 5. The pressure in the eye builds up gradually. At some point, side vision (peripheral vision) is lost and without treatment, total blindness will occur.

2. CLOSED-ANGLE GLAUCOMA

1. Occurs when the drainage angle is blocked by part of the iris and fluid cannot drain from the eye 2. Comes in two forms: chronic or acute

Acute closed-angle glaucomaA medical emergency that must be treated immediately or blindness can result in one or two days. This happens when the normal flow of aqueous humor between the iris and the lens suddenly becomes blocked.

Symptoms may include severe pain, nausea, vomiting, and blurred vision. When the patient looks at a light source they may also see colored halos around the lights.

Chronic closed-angle glaucoma progresses slowly and can produce damage without symptoms, similar to open-angle glaucoma.

3. Congenital glaucoma: 1. Incorrect or incomplete development of the eye's drainage canals during the prenatal period.

2. A condition where babies are born with defects that prevent the normal drainage of fluid from the eye.

4. Low-tension or normal-tension glaucoma:

1. Optic nerve is damaged even though intraocular pressure is consistently within a normal range.

2. Occurs in people with normal eye pressure who have optic nerve damage and experience narrowed side vision. 3. Lowering eye pressure at least 30 percent through medicines slows the disease in some people.

5. Secondary glaucoma:

Occurs as a result of eye injury, inflammation, or tumor or in advanced cases of cataracts or diabetes.

TREATMENT OF GLAUCOMA:

* No cure for glaucoma

* Treatments of glaucoma fall into two groups: medication and surgery

Disadvantages of drugs include:

A) Possibility of side effects

B) Medication may become ineffective over time

* If IOP cannot be managed by medications or eye drops alone, surgery may be recommended.

The surgical goal:

I. Drain the IO fluid by expanding the existing drainage area

II. Creating a new outlet for the fluids to drain through

Some patients may experience a slight stinging sensation following the glaucoma surgical procedure, local anesthetics are used diminish any patient discomfort.

After surgical procedure, some patients may experience blurred vision or irritation, but these effects are short-lived and normal activities can be resumed the next day.

ANTIGLAUCOMA DRUGS:

1. CARBONIC ANHYDRASE INHIBITORS

* The first-line agents * Should be used immediately during the initial intervention

* They reduce bicarbonate production in the ciliary epithelium and so decrease aqueous formation

Acetazolamide is an example: 1. Reduce the rate of aqueous humour formation by direct inhibition of CA enzyme on secretory ciliary epithelium causing a reduction in IOP

2. Effects seen in about an hour. They peak in 4 hours

Contraindications include:

. Documented hypersensitivity

. Hepatic disease

. Severe renal disease

. Adrenocortical insufficiency

. Severe pulmonary obstruction

2. BETA ADRENERGIC BLOCKERS

May lower IOP by suppressing aqueous humour production and probably NOT through any effect on the pupil

TIMOLOLReduces elevated and normal IOP by reducing aqueous humour production or possibly the outflow

Contraindications include:1. Documented hypersensitivity2. Bronchial asthma3. Sinus bradycardia4. Second and third degree AV block5. Severe chronic obstructive pulmonary disease6. Cardiogenic shock

CARTEOLOL. Non selective beta blocker. Has mild intrinsic sympathomimetic activity. Has fewer cardiac and lipid profile adverse effects. Reduces IOP via reduction of aqueous formation

LEVOBETAXOLOL. Selective β1 blocker with little or no effect on β2

3. ALPHA-ADRENERGIC AGONISTS

Used as adjunct agents to further decrease IOP secondary to their effect on aqueous humour production

APRACLONIDINE. Selective α2 agonist. Suppress aqueous production. Reduces IOP elevated or normal, whether or not accompanied by glaucoma . Have minimal CV effects

4. CORTICOSTEROIDSReduce ocular inflammation so providing symptomatic relief and augment the effects of other medications

5. OPHTHALMIC AGENTS (MIOTICS)

These agents will pull the peripheral iris tissue away from the trabecular meshwork helping to eliminate obstructed aqueous humour flow

Ineffective during the initial period due to the ischaemic paralysis of the iris

Should be used after the immediate management and the initial reduction of the IOP

PILOCARPINEContraindicated include:. Documented hypersensitivity. Acute inflammatory disease of the anterior chamber

6. HYPEROSMOTICS

Drugs that increase serum osmolarity and cause a fluid shift from the eye into the vascular space. The subsequent osmotic diuresis reduces IOP

Glycerine

Used to interrupt acute attacks

Contraindications include:. Documented hypersensitivity. Acute pulmonary edema. Severe dehydration, anuria

MANITOL

. Osmotic diuretic

. Reduces IOP when cannot be lowered by other mechanisms

. Contraindicated in progressive renal damage and progressive heart failure

7. Prostaglandin analogues:

Topical medications that help lower intraocular pressure by increasing uveoscleral outflow (outflow through the soft tissues of the front of the eye [iris and ciliary body]). This type of medication includes latanoprost (Xalatan).

Drug therapy of primary open angle glaucoma (chronic simple glaucoma)

Miotics (pilocarpine, physostigmine, ecothiopate: act mainly by increasing aqueous outflow

Sympathomimetics: have an immediate effect decreasing aqueous production and increase aqueous outflow as Dipivefrin

B-adrenoceptor blockers: decrease aqueous humour production and may increase outflow facility. They have the advantage of not affecting either the pupil size or aaccomodation as timolol and befenolol

Oral agents as CA inhibitors: lower IOP by decreasing aqueous humour production as acetazolamide

Drug therapy of acute angle closure (congestive) glaucoma

Drugs are used to control IOP prior to surgery

Dehydrating agents as IV infusion of hypertonic solution of mannito or oral glycerol

Oral acetazolamide

Topical miotics as pilocarpine eye drops

Analgesics : pethidine or morphine to control pain

Several factors that can put a person "at risk" for developing glaucoma:

Family history of glaucoma - There is a 20 percent chance of developing glaucoma of a parent had it, and 50 percent chance if a sibling has it.

Age - If the person is 65 to 79 years of age, there is a 3 percent chance of developing glaucoma. If the person is 80 years of age or older, there is a 14 percent of developing glaucoma.

Medical conditions, such as morning headaches, diabetes, lupus, Crohn's disease, rheumatoid arthritis, myopia (nearsightedness), and high blood pressure

Use of topical steroid (prednisone or cortisone) medications

Race - Blacks are three to four times more likely than Caucasians to develop glaucoma. Asians and Eskimos are more likely to develop glaucoma than Caucasians.

Abnormally high intraocular pressure

Previous eye injuries

Recurrent blurry vision

Pain around the eyes after watching TV or leaving a dark theater

Seeing a rainbow - hued halos around lights at night

END OF THE LECTURE