Pupil Size and Pharmacology

Question 1

ANS - push pull mechanism in organ

Answer 1

• There is always neutral tone to the dilator and sphincter
• When a light is shone in the eye the parasympathetic nervous system is activated and the sympathetic nervous system inhibited and pupil constricts
• When light is low the sympathetic system is activated and the parasympathetic is inhibited and the pupil enlarges
  The sphincter is stronger than the dilator

Question 2

Sympathetic Stimulation

Answer 2

ACh is used at preganglionic synapse whereas noradrenaline is used as neurotransmitter at long postganglionic axon.

Question 3

Parasympathetic System

Answer 3

ACh is used at both synapses but have different receptor types

Nicotinic Receptors allow fast transfer of the signal and Muscarinic Receptors which are at sphincter allow for different types of actions (constriction)

Question 4

Receptors on the pupil

Answer 4

Dilator (sympathetic):

- Adrenergic 
- Mainly driven by a1 causes contraction of dilator 
- Locally given A2 do not affect pupil size but if given systemically can alter the overall sympathetic tone which will alter pupil size 
- Beta adrenergic receptors have also been identified and are thought to cause relaxation to the dilator muscle 

Sphincter (parasympathetic):

- Mainly M3 muscarinic receptors 
- Some M2 receptors 
- 5 different types found in human body

Stimulated naturally by:
- Acetylcholine for muscarinic receptors
- Adrenaline and noradrenaline for adrenergic receptors
Noradrenaline released locally, adrenaline released adrenal gland (epinephrine)

Question 5

Pharmacology in the synapse

Answer 5

Levels of competition:

- Affinity for the receptor 
- Greater affinity means more likely to bind

Levels of binding:

- Reversible 
- Irreversible --> last longer until receptor is replaced 

Agonist vs Antagonist:
- Agonist - bind and activate
Antagonists bind the receptors but don’t activate

Question 6

Sympathetic Antagonists

Answer 6

Phenylephrine (mixed a1 and a2):dilate pupil in conjunction with muscarinic antagonist as sphincter is stronger

Apraclondine (a2): a2 agonist doesn’t cause mydriasis

Amphetamine increases NA release from the synapse. Increases amount of neurotransmitter that is released at the synapse. Acts as if there is a increased sympathetic stimulus. Pupil Dilation

Cocaine blocks reuptake of NA from the synaptic cleft. More transmitter in synapse to bind with receptors

Question 7

parasympathetic synaptic function

Answer 7

Rather than re uptaking the neurotransmitter it is broken down into its components

Common drugs were through blocking the cholinergic receptor

Question 8

parasympathetic antagonists

Answer 8

Atropine, homatropine, cyclopentolate, tropicamide block parasympathetic function (block the muscarinic receptor)

Pupil dilation

Optometrists typically use tropicamide for mydriasis

Parasympathetic Antagonist can be used to block the muscarinic receptor in the sphincter muscle and cause pupil dilation. These drugs compete with Ach for the receptors but instead of triggering cascade of events nothing happens.

Strength of dilation depends on how well drug competes against Ach

Question 9

parasympathetic agonist

Answer 9

• Constrict pupil

Pilocarpine: increase activation of parasympathetic system but stimulating muscarinic receptors instead od blocking them

Used for angle closure etc.

Question 10

Tropicamide

Answer 10

used for dilation as it causes strong dilation for small duration

Question 11

Tropicamide

Answer 11

used for dilation as it causes strong dilation for small duration

Question 12

Non ocular medication effects on pupil

Answer 12

Nasal Decongestants:

- Adrenergic to cause constriction of arteries and reduced nasal blood flow
- Stimulates a receptors 
- Epinephrin, pseudoephedrine, naphazoline, oxymetazoline, phenylephrine and tetrahydrozoline 
- Often see pupil dilation 
- Ask patients if they have been using any medications 

Anticholinergics are used to treat a variety of disorders:

- Gastrointestinal 
- Asthma
- COPD
- Muscle relaxants 

Affect parasympathetic system and can cause pupil dilation

Antidepressants:

- SSRIs - serotonin stimulates sympathetic nervous system mild dilation 
- Tricyclics have an anti-cholinergic action 

Opioids/Narcotics:

- Miosis (pinpoint pupils) 
- Parasympathetic excess 

Illicit Drugs:

Dilation:

- Cocaine 
- Amphetamines (ecstasy, MDMA)
- Marijuana 
- Hallucinogenic (LSD)

Miosis:
Heroin (parasympathetic excess)