Autonomic Nervous System

The Autonomic Nervous System (ANS) has 2 pathways


1. Sympathetic - fight & flight
2. Parasympathetic - rest & digest

Sympathomimetic Drugs are drugs that mimic the sympathetic nervous system. The chemicals are known as adrenergics. 2 examples of adrenergics are: Phenylephrine and Dipivefrin.

Parasympathomimetic Drugs mimic the parasympathetic nervous system. These chemicals are known as cholinergics. 2 examples of cholinergics are: Scopolamine and Tropicamide.

Phenylephrine

Mechanisms of action:
Stimulates post-synaptic alpha receptors which constricts the dilator muscle, hence causing mydriasis.

Clinical Uses:

Used as an eye drop to dilate the pupil which can be also used as an aid in viewing the fundus in adults. It is often used in combination with tropicamide, an anti-cholinergic drug.

Phenylephrine can also be used in the diagnostic test of horner’s syndrome to determine the site of the neurologic damage.

Phenylephrine is also used to break synaechiae to prevent glaucoma caused by pupil block.

Ocular side effects:

Use of phenylephrine may cause widening of the palpebral aperture and blanching of the conjunctival blood vessels because alpha receptors are also found in those areas.

Systemic effects:

Central Nervous System – Headache, Dizziness

Respiratory System – Respiratory Distress

Cardiovascular System – Bradycardia

Contraindications:

Phenylephrine should not be used in patients with severe hypertension or tachycardia(fast heart rate) or should they be hypersensitive to any of the components in the drugs.

Intraocular Pressure(IOP):

Phenylephrine has little effect on IOP and if safe to be taken in patients with glaucoma

Dipivefrin

Mechanism of Action

Dipivefrin is available as an ophthalmic solution. It causes vasoconstriction, decreased aqueous humor production, and decreases Intra-Ocular Pressure (IOP) of the eye. The Dipivefrin prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine and it is an active agent that stimulates alpha- adrenergic receptors and/or beta-adrenergic receptors increasing aqueous humor outflow with fewer side effects than are associated with conventional epinephrine therapy.

Dipivefrin hydrochloride is converted to epinephrine inside the human eye by enzyme hydrolysis. The liberated epinephrine, which is an adrenergic agonist, appears to exert its action by decreasing aqueous production and by enhancing outflow facility.

Cinical Uses

Dipivefrin hydrochloride is a member of a class of drugs known as prodrugs (substances administered in an inactive form that is then metabolized in the body in vivo into the active compound).

Dipivefrin is used to treat primary open-angle glaucoma by decreasing IOP. It metabolizes in epinephrine and cause constriction of afferent vessels in the ciliary processes via binding to and stimulation of alpha-1 receptor resulting in reduction in aqueous production. Therefore, when aqueous production is lesser than aqueous drainage, IOP decreases.

Ocular Effects

Common ocular side effects are stinging and burning. Corneal vascularization, eyelid ectropion, papillary conjunctivitis, blepharoconjunctivitis, macular edema, corneal toxicity for example dendritic keratitis, punctate keratitis or epitheliopathy, and blurred vision has been reported.
However, some patients treated with Dipivefrin reported discomfort due to photophobia, glare or light sensitivity.

There are cases of follicular conjunctivitis, mydriasis and allergic reactions to Dipivefrin reported infrequently.

Systemic effects

Systemic side effects of using Dipivefrin are slight increases in heart rate and diastolic blood pressure.

Tachycardia, arrhythmias and hypertension have been also reported with ocular administration of epinephrine.

Indications

Dipivefrin hydrochloride ophthalmic solution is indicated as initial therapy for the control of intraocular pressure in chronic open-angle glaucoma. Patients responding inadequately to other anti-glaucoma therapy may respond to addition of Dipivefrin.

According to studies, in controlled and open-label studies of glaucoma, Dipivefrin demonstrated a statistically significant intraocular pressure lowering effect. Patients using Dipivefrin twice daily in studies with mean durations of 76-146 days experienced mean pressure reductions ranging from 20-24%.

Contraindications

Dipivefrin hydrochloride should not be used if patient has a known allergy to Dipivefrin.

Patients with narrow angle glaucoma also should not use Dipivefrin hydrochloride since any dilation of the pupil may increase the risk of the patient of getting an attack of angle-closure glaucoma.

 Aqueous drainage through trabecular meshwork.

During dilation, crystalline lens becomes bigger and pushes iris towards the corneal endothelium,  leading to obstruction of aqueous drainage through trabecular meshwork, therefore IOP increases which may result in angle closure glaucoma.

Compare and Contrast for Phenylephrine and Dipivefrin

Tropicamide

Mechanism of Action
Tropicamide binds to the receptors in the muscles of the eye involved in controlling the pupil size and the shape of the lens (muscarinic receptor M4) and blocks them. Then, it acts by blocking the responses of the iris sphincter muscle to the iris and ciliary muscles to cholinergic stimulation, thus producing pupil dilation and cycloplegia.


Clinical Uses

Tropicamide is given to patient in form of eye drops to dilate the pupil and relax the lens so that eye examinations such as cycloplegic refraction and fundus examination of the eye. Tropicamide may also be used before and after eye surgery. The preparation (1% in 3ml) acts in 15-30 minutes, and the duration of activity is approximately 3-8 hours.


Ocular Effects

Tropicamide produces dilation of the pupil and paralysis of the ciliary muscle (cycloplegia) which prevents the eye from accommodating for near vision.

Some adverse ocular effects associated with the use of tropicamide include transient stinging, blurred vision, photophobia, superficial punctate keratitis and increased intra-ocular pressure.


Systemic Effects

Some adverse systemic effects associated with the use of tropicamide include dryness of the mouth, tachycardia (very fast heart rate), headache, allergic reactions, nausea, vomiting, pallor (paleness), central nervous system disturbances and muscle rigidity. Psychotic reactions, behavioral disturbances, and vasomotor or cardio-respiratory collapse in children have been reported with the use of tropicamide.


Indications and Contraindications

Indication: When mydriasis and cycloplegia of rapid onset and brief duration are required.

Contraindications: Patients with angle-closure glaucoma or narrow angles where mydriasis may precipitate attack of angle-closure glaucoma must not use tropicamide. Patients with allergies to tropicamide or any ingredient in the formulation must not use tropicamide.


Intra-Ocular Pressure (IOP)

Use of tropicamide can result in increase of IOP of users with open angle glaucoma. It is caused by a reduction in aqueous outflow, resulting in imbalance between aqueous drainage and production. Thus, aqueous accumulates in eye, increasing IOP.

The risk of inducing acute glaucoma following mydriasis with tropicamide alone is estimated to be about 0.3%, excluding those with history of glaucoma and shallow anterior chamber angles. This is because it is moderately selective for M4 receptors and the muscarinic receptors in the trabecular meshwork are mostly M2 and M3. Mydriasis with tropicamide alone is SAFE even in people with chronic glaucoma.

Clinical Routine

Clinical routine

Prior to dilation, it is important to:
1) Estimate angle of anterior chamber
The below picture showcases the difference between a close and open anterior chamber.

3 Tests, namely the Penlight Shadow Test, Van Herick’s Technique and Gonioscopy are used to estimate if the angle is closed or open.

Penlight Shadow test

A simple test using a penlight helps determine the risk for acute closed-angle glaucoma. A beam of light is directed from the side of the face toward the patient's iris. If no shadow appears on the nose, then most likely the angle is wide enough to dilate.

Van Herick technique

The Van Herick Technique is a slit-lamp estimation of the angle depth. First set the slit beam to very bright and thin. Then offset the beam temporally to the slit lamp oculars. Illuminate the temporal sclera and bring the slit lamp beam slowly towards the cornea until the anterior chamber is first identified. The thickness of the cornea is compared to the depth of the peripheral anterior chamber. If the anterior chamber depth is as deep as the cornea is thick then the angle is presumed to be wide open. If there is only a slit of aqueous then the angle is estimated to be dangerously narrow.

Gonioscopy

Gonio lenses permit observation of the anterior chamber angle by eliminating the cornea as a refracting surface. This is done by placing a concave surface against the cornea, thus allowing visualization of the angle using obliquely inclined mirrors.

2. Performing IOP check (Tonometry) before and after dilation to ensure patient’s IOP wasn’t affected. Carrying out Tonometry before dilation ensures the early detection of any possible glaucoma cases.

3.Have an appropriate Miotic available should dilation be too traumatic for the patient and the examiner has to constrict the pupil back.

4. Perform History Taking to rule out any allergies to any mydriatics or drugs, possible glaucoma cases.

Clinical routine

History Taking

When performing history taking, special attention should be paid to below points.

• Episodes of angle closure?

Does patient have any earlier incidences of angle closure?

• Any known allergy to drug

Is there any drug the patient is allergic to?

• Pressence of Glaucoma which is presently treated with Miotics

Is the patient actually diagnosed with Glaucoma and then currently prescribed with Miotics?

• Systemic Drugs Medication

Is the patient currently on any systemic drug medication? E.g drugs for diabetes.

• Systemic Diseases/ Health Condition

Is the patient suffering from any systemic diseases e.g Diabetes / What is his current health condition? (Healthy , sick etc)

Signs and Symptoms of Acute Angle Closure Glaucoma

Symptoms:

Blurry Vision

Nausea + Vomiting

Pain

Signs:

Ciliary Flush

Elevated IOP

Fixed Semi-Dilated Pupil

Corneal Edema

Contraindications

• Narrow or Closed Anterior Chamber Angle

• Iris Supported Intra Ocular Lens

• History suggesting Angle Closure Glaucoma

General Clinical Routine

Credits

Benjamin Chua-0941860
Tan Si Rui-0941563
Yeo Jie Shun-0941170
Eddie Tan-0900564
Jerial Tan-0959948
Cliff Tan-0941831
Loh Yuan Yi-0941253
Rong Qiang-0941633
Lim Tao Chin-0941336