Drug Effects on the Human Eye Flashcards
Autonomic Nervous System
- Responsible for fuction & protective mechanisms (based on sensory inputs)
- Controls do not require conscious thought to activate/change
- Parasympathetic vs Sympathetic innervation block each other out (only one at a time)
- Depending on the sensory input, the amount of innveration for control mechanisms changes
- Parasympathetic pathway - neurotransmitter: acetylcholine, activates cholinergic receptors on post-synaptic cells
- Sympathetic pathway - neurotransmitter: noradrenaline, adrene receptors on post-synaptic cells
Key Eye Structures
- Acts as a surrogate marker to see how drugs will affect various aspects of the ANS
Key Structures:
Cornea
- protective & transparent tissue at front of the eye
- bristling with noci + mechanoreceptors
- sensory nerve-endings that are sensitive to pressure/pain
- retina (CNS tissue) is non-regenerative so damage must be detected
Lens
- focuses on objects been looked at
- refracts light through itself & allows it to be reflected onto the retina to be sharply focused
- must be able to focus on distant/close objects, changes shape to do so
Iris
- comprised of two different muscles that allows light to enter the eye through the pupil
- control of the iris is due to parasympathetic/sympathetic innervation
Canal of Schlemm
- eyeball maintains it’s shape as it is liquid-filled
- jelly-like vitreous humor & watery aqueous humor that is constantly being drained/replenished
- amounts of aqueous humor results in high hydrostatic pressure - intra-ocular pressure (IOP), if there is too much then pressure can become dangerous & cause blindess
- canal of schlemm can drain this solution - a valve from the eye to bloodstream
Sclera
- whites of the eye, help define structure
- contains small blood vessels
Pupil
- hole in the centre of the iris
- diameter controls how much light can reflect on the retina
- dilated/constricted
Retina
- Critical element of the eye
- Can transduce photons from an object into electrical impulses
- Impulses can that travel along the optic nerve to the visual cortex at the rear of the brain
- Contains two-types of light sensitive nerve endings:
Cone cells - sensitive to different wavelengths of light, give colour vision
Rod cells - sensitive to high-contrast & moving objects
- High density of cone cells in the centre of the macula of the retina
- High density of rod cells in the periphery of the retina, helps with peripheral vision (sensitive movements but not colour descrimination)
- Both nerve fibres extend to optic disc - exit the eye & converge into optic nerve
- Optic disc is also where all the blood vessels (that supply nutrients to the retina) enter the eye
Controlling Pupil Reflex
- Controlling how much light hits the retina is a critical protective mechanism controlled by the ANS
- This influences the muscles in the iris to dilate/constrict
Iris comprises two muscle groups:
- radial dilator controlled by sympathetic innervation
- circular constrictor controlled by parasympathetic innervation
There is a constant dynamic on how much influence parasympathetic & sympathetic innvervation has on the muscle contraction:
- moderate light - average pupil size, balance of innervation
- bright light - constricted pupil (limit light input), P>S
- low light - dilated pupil (maximise light input), P
Focusing on Objects
- Eye must be able to focus on an object, irrespective of it’s distance
- Focusing on objects involves autonomic control (unconcious)
- Parasympathetic innervation of the ciliary muscle allows ‘gel-like’ flexible lens to change shape & hence increase its refractive properites
- Lens is attached to cillary muscle by a number of suspensory ligaments - when cillary muscle is relaxed, suspensory ligaments are taught
- Taught ligaments pull the gel-like lens into a thin shape, which doesn’t refract/bend light much - needed for focusing on distant objects
- If focusing on a close object, parasympathetic innervation contracts the cillary muscle & slackens suspensory ligaments - causes the lens to revert to original shape of ‘fat & round’ which can refract light more
- Accomodation point - the closest distance an object can be for the lens to still focus (limit of how convex the lens can be made)
- Anything closer than the accomodation point will be blurry - point gets more distant as we age, muscles become weaker
Corneal Reflex
- One autonomic protective mechanism - prevents matter entering & damaging the eye (dust etc)
- Surface of the cornea is covered with noci- & mechano-receptors that elicit a powerful response (even for small particles) - blink reflex
- As soon as the cornea is touched, blinking starts along with perfuse eye-watering
- Blinking - sweeps matter out of the eye & spreads secreted lubricants across the surface
- Tears - flushes the matter out of the eye
- Irritation is part of the mechanism
Pupil Diameter Test
- Simply measure the subject’s pupil diameter by holding reference cards by the eyes
- The pupil diameters should be recorded for both the control & treated eye
- Some drugs affect pupil diameter by modulating the functions of the iris muscles
Accomodation Point Test
- Test is performed for each of the eyes seperately
- Device used is a focusing plane that can slide along a ruler to give the closest distance at which the eye can focus on the near-object
- The closest point at which the object is still in sharp focus is the accomodation point
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Ambient Light Reaction Test
- Parasympathetic nervous system protects the retina from potentially blinding light by innervating the iris constrictor muscle to reduce aperture size
- Test is performed by sweeping a pen-light across the subject’s eye to see how quickly the pupil constricts in reaction
Scoring System:
2 - extremely quickly
1 - somewhat slower
0 - no constriction
Corneal Reflex Test
- Test measures how quickly corneal reflex is triggered
- Causes non-damaging corneal irritation - gently touching the cornea with the tip of a cotton wool ball
- Cotton wool minics dust/pollen hitting the cornea
Score how quickly a blink reflex is stimulated in each eye:
2 - very fast blink
1 - slightly sluggish/delayed blink
0 - no blinking at all
Scleral Colour Test
- Measures the changes in colour of the sclera (‘white of the eyes’) - in both control & treated eye
- Small blood vessels in the sclera can vasodilate or vasoconstrict which changes the visible colour of the sclera (‘white of the eyes’)
- Some drugs have colateral effects - cause effects in tissues other than intending target
- Test is completed every 5 mins for 40 mins to see how long the drug has effect on the treated eye
Colour Changes are measured the following score system:
2 - extremely bloodshot
1 - relatively bloodshot
0 - cannot tell?
- 1 - relatively pale
- 2 - extremely pale
- Score of control eye is subtracted from the treated eye to see what effect the drug actually has
Phenylepherine
- Adrene-receptor agonist drug - binds to adrenergic receptors on the post-synaptic cell membrane
- Adrene-receptors would usually be activated by neurotransmitter: neuroadrenaline or hormone: adrenaline - structure of phenylepherine can mimic them
- Sympathomimetric drug - acting like noradrenaline on adrenoceptors in the eye, induces a sympathetic response
- Causes mydrasis (pupil dilation through innervation of the iris muscle)
- Also causes scleral whitening through vasoconstriction (colateral effect)
- Subtle but measureable, dose of phenylepherine deliberately low in practical to limit colateral effects in other areas of the body - increased heart rate etc
- Eye-drop useful for dilating the pupil in advance of funduscopy (examining retina with an opthalmoscope)
Tetracaine
- Local anaesthetic - blocks voltage-gated Na+ channels in sensory nerve axons
- Causes temporary ‘numbing’ of pain & pressure sensation in the area where the drug is applied
- Purpose is to blunt or totally abolish corneal reflex - no blink reflex triggered when stimulus (cotton wool) is present
- Useful for treatment of painful corneal trauma/inflammation (abrasion/burns)
- Also may used in cataract removal/lens replacement surgeries without the need to use a more dangerous, general anaesthetics
- Effects at dose given wears off around 30-40mins, re-dosing may be needed to experience longer effects
Tropicamide
- Abolishes the light reflex
- Acetylcholine receptor antagonist (acting in parasympathetic nervous system) - blocks receptors & stops activation
- Paralyses anything involving parasympathetic innervation, including the constriction of the retina
- Causes cycloplegia (paralysis of ciliary muscle) & paralysis of pupillary constrictor reflex
- Useful for paralysing pupil constrictor in advance of fundoscopy (in conjunction with phenylepherine) - allows retina to be seen clearly at the rear of the eye
- Colateral effects - accomodation distance gets larger as the PNS is responsible for cillary muscle contraction (will be paralysed)
- Patient should be made aware that they may temporarily lose their ability to focus on close objects
- Though it causes contriction, it does not actively cause dilation - dilation seen is down to the body’s own response (sympathetic nervous system not effected)
- Always a dynamic between PNS&SNS, tropicamide just removes the PNS out of the equation - even a small dilation response is visible as it is unnoposed
Pilocarpine
- Acetylcholine receptor agonist drug - binds to & activates receptors of the parasympathetic system of the eye (mimics effects of acytelcholine)
- Opposite effect of when tropicamide is used
- Causes intense & prolonged pupil constriction (miosis) - stimulation of iris constrictor muscle
- Also causes transient vasodilation through release of nitric oxide
- Useful in reducing IOP by opening Canal of Schlemm via pupil constriction - some types of glucoma
- Canal of Schlemm is indirectly attached to iris muscles - when dilator muscle is active, canal can often be pushed shut (raises IOP due to excess aqueous humor)
- In some cases, pilocarpine can be used to offest sudden blindness in patients with narrow angle disorders
- Bloodshot apperance - acetylcholine receptors on small blood vessels in the sclera
- Intracellular cascade (due to receptors being activated), causes nitrous oxide to be produced by vascular endothelial cells & causes the vascular smooth muscle cells to relax (marked vasodilation & reddening of sclera)
- Bloodshot apperance only lasts around 5 mins - nitrous oxide has short half-life, pilocarpine related-effects are short-lived in the blood vessels but are longer in the parasympathetic system (pupil constriction)