Toxic Effects on

OCULAR & DERMAL SYSTEM

Drh. Tiara Widyaputri, M.Si

OCULAR SYSTEM
EXPOSURE TO THE EYE AND VISUAL
SYSTEM
Ocular Pharmaco dynamics and Pharmacokinetics
 Toxic chemicals and systemic drugs can affect all parts of the
eye
 Factors determining whether a chemical can reach a
particular ocular site of action include physiochemical
properties of the chemical, concentration and duration of
exposure, and movement across ocular compartments and
barriers.
EXPOSURE TO THE EYE AND VISUAL
SYSTEM
Ocular Pharmaco dynamics and Pharmacokinetics
 The cornea, conjunctiva, and eyelids are often exposed
directly to chemicals, gases, drugs, and particles.
 The avascular cornea is considered the external barrier to the
internal ocular structures.
 Greater systemic absorption occurs through contact with
the vascularized conjunctiva.
 Following systemic exposure to drugs and chemicals by the
oral, inhalation, dermal, or parenteral route, some
ompounds are distributed to all parts o the eye by the blood
in the uveal blood vessels and retinal vessels
EXPOSURE TO THE EYE AND VISUAL
SYSTEM
Ocular Pharmaco dynamics and Pharmacokinetics
 Most chemicals rapidly equilibrate with the extravascular
space of the choroid where they are separated from the
retina and vitreous body by the RPE and endothelial cells of
the retinal capillaries, respectively
 the corneal endothelium —the cells responsible or
maintaining normal hydration and transparency o the corneal
stroma—could be exposed to chemical compounds by the
aqueous humor and limbal capillaries
EXPOSURE TO THE EYE AND VISUAL
SYSTEM
Ocular Pharmaco dynamics and Pharmacokinetics
 The anterior surface of the lens also can be exposed as a
result of its contact with the aqueous humor.
 The most likely retinal target sites following systemic drug
and chemical exposure appear to be the RPE and
photoreceptors, because the endothelial cells of the
choriocapillaris are permeable to proteins smaller than 50 to
70 kDa.
 However, the cells of the RPE are joined on their basolateral
surface by tight junctions that limit the passive penetration of
large molecules into the neural retina.
EXPOSURE TO THE EYE AND VISUAL
SYSTEM
Ocular Pharmaco dynamics and Pharmacokinetics
 Intraocular melanin plays a special role in ocular toxicology.
 First, it is found in several different locations in the eye:
pigmented cells of the iris, ciliary body, RPE, and uveal tract.
 Second, it has a high binding afinity or polycyclic aromatic
hydrocarbons, electrophiles, calcium, and toxic heavy metals
such as aluminum, iron, lead, and mercury.
 Although this initially may play a protective role, the
excessive accumulation, long-term storage, and slow release
of numerous drugs and chemicals from melanin can influence
toxicity.
Ocular absorption and distribution of drugs and
chemicals following the topical route of exposure
Distribution of drugs and chemicals in the anterior and
posterior segments of eye, optic nerve, brain, and other organs
following the systemic route of exposure
Ocular and central visual system sites of action of
selected xenobiotics following systemic exposure
Ocular and central visual system sites of action of
selected xenobiotics following systemic exposure
Common signs and symptoms of visual system
dysfunction
Common signs and symptoms of visual system
dysfunction
Common signs and symptoms of visual system
dysfunction
Common Veterinary Toxins Affecting
the Eyes
TOXINS ASSOCIATED WITH MYDRIASIS
Mydriasis is dilatation of the pupil.
• Antihistamines
• Atropine
• Ivermectin
• Lysergic acid diethylamide (LSD)
• Lead
• Marijuana
• Plants with atropine-like properties (Datura)
• Tricyclic antidepressants
Common Veterinary Toxins Affecting
the Eyes
TOXINS ASSOCIATED WITH MIOSIS
Miosis is contraction of the pupil.
• Carbamates
• Nicotine
• Opiates
• Organophosphorus insecticides
• Physostigmine
Ocular Drug Metabolism
 Metabolism of xenobiotics occurs in all compartments o the
eye by well-known phase I and II xenobiotic- biotransforming
enzymes.
 Drug-metabolizing enzymes that are present in the tears,
iris–ciliary body, choroid, and retina of many different
species are listed in the table below.
 Whereas the activity of these enzymes varies between species
and ocular tissues, the whole lens has low biotransfrmational
activity
Distribution of ocular xenobiotic-biotransforming enzymes
Distribution of ocular xenobiotic-biotransforming enzymes
Decontamination and Detoxification
of the Poisoned Patient
■ In veterinary medicine, the primary treatment for toxicant
exposure should be decontamination and detoxification of
the patient.
■ The goal of decontamination is to inhibit or minimize
further toxicant absorption and to promote excretion or
elimination of the toxicant from the body.
■ Knowledge of the underlying mechanism of action, the
pharmacokinetics (including absorption, distribution,
metabolism, and excretion), and the toxic dose of the
toxicant are imperative in determining appropriate
decontamination and therapy for the patient.
Decontamination and Detoxification
of the Poisoned Patient
■ Decontamination can only be performed within a narrow
window of time for most substances; therefore, it is
important to obtain a thorough history and time since
exposure.
■ Decontamination categories may include ocular, dermal,
inhalation, injection, GI, forced diuresis, and surgical
removal to prevent absorption or enhance elimination of the
toxicant.
Ocular Decontamination
■ If ocular exposure has occurred, thorough evaluation and
appropriate medical care of the eye may be necessary.
■ Proper decontamination is often difficult for the pet owner, as it
requires restraint of the animal.
■ If the product is corrosive, owners should flush the eye at home
with physiological saline (e.g., contact lens solution without any
cleaners, soaps, etc.) or tepid water for 15 –20 minutes prior to
transportation to a veterinarian. This will help maximize
decontamination and secondary injury to the cornea. Immediate
veterinary care is imperative. Owners should be advised to
prevent injury or rubbing of the eye until veterinary attention is
sought. An Elizabethan collar should be used, if available.
Ocular Decontamination
■ If the product is considered a noncorrosive irritant, owners
should flush the eye at home with physiological saline (e.g.,
contact lens solution without any cleaners, soaps, etc.) or
tepid water for 10 –15 minutes. Ophthalmic ointments or
medications should not be used, and the pet should be
monitored carefully for an extended period of time to
prevent iatrogenic corneal abrasion or ulceration from
rubbing the eyes. Owners should be advised to prevent injury
or rubbing of the eye. An Elizabethan collar should be used, if
available. Any change in condition (e.g., blepharospasm, pupil
size change, pruritis, ocular discharge) should prompt
immediate medical attention.