PHARMACOLOGY - Miosis and Mydriasis

Question 1

What are the effects of atropine - anti-muscarinic (2 ocular, 3 systemic)

Answer 1

Ocular
1. mydriasis via iris sphincter muscle paralysis
2. cycloplegia via ciliary body paralysis

Systemic
3. Sedatory effect
4. Delays gastric emptying
5. Reduces sweating

Question 2

What are the mechanism of pilocarpine? (6)

Answer 2

DIRECT muscaranic agonist - acts on muscarinic / Ach receptor

1. MIOSIS - iris sphincter contraction
2. ACCOMODATION - ciliary muscle contraction (accomodative spasm)
3. REDUCES IOP - ciliary muscle contraction increases tension of scleral spur by pulling is posteriorly and internally –> opening of trabecular meshwork (conventional route)
4. MYOPIA - ciliary muscle contraction
5. VASCULAR PERMEABILITY - increases so should be avoided in uveitis.
6. REVERSAL OF MYDRIASIS - only ones caused by phenylephrine, not atropine.

Question 3

Which drugs can reverse atropine mydriasis?

Which drugs can reverse phenylephrine mydriasis?

Answer 3

2. Pilocarpine, thymoxamine (more effective)

Question 4

What are the effects of apraclonidine? (3)

Answer 4

1. Mydriasis
2. Eyelid retraction
3. Conjunctival blanching

Question 5

What is the main ocular side effects of brimonidine / apraclonidine?

Answer 5

After 1 year - allergic conjunctivitis, follicular conjunctivitis

Question 6

Which drugs are alpha-1 adrenergic agonists?

Which drugs are alpha-2 adrenergic agonists?

Answer 6

Alpha-1 : phenylephrine
Alpha-2: apraclonidine, brimonidine

Question 7

Which drug relaxes the ciliary body?

Answer 7

Atropine

Question 8

Which drugs are parasympathetic antagonists?

Answer 8

1. Cyclopentolate
2. Tropicamide
3. Atropine
4. Phenothiazine

Question 9

What is the mechanism of action of phenylephrine?

Answer 9

Non selective alpha agonist

Question 10

What is the mechanism of action of tropicamide?

Answer 10

It is a muscarinic antagonist - blocks parasympathetic pathway.

Question 11

what are the side effects of tropicamide?

Answer 11

1. precipitates angle closure
2. exacerbates ataxic dysarthia
3. cerebellar signs
4. increases risk of seizure

Question 12

In what instances are alpha-2-agonists contraindicated? (2)

Answer 12

1. Potentiates hypertensive crisis with monoamine oxidase inhibitors
2. WIth TCAs, its IOP effect is removed.

Question 13

What is the effect of muscarinic agonists, example? (3)

Answer 13

Direct - pilocarpine
Indirect - carbachol - inhibits cholinesterase

1. Miosis
2. Accomodation
3. Decreased intraocular pressure

Question 14

What are the main muscarinic agonists and antagonists?

Answer 14

Musacrinic agonist - pilocarpine, carbachol

Muscarinic antagonist - tropicamide (short acting 6 hours), cyclopentolate (24 hours) atropine (7 days)

Question 15

What is the order of potency for muscarinic antagonists?

Answer 15

atropine > cyclopentolate > homatropine > tropicamide

Question 16

What is the mechanism of action of apraclonidine?

Answer 16

alpha-2-adrenergic agonist (partial) –> potent systemic anti-hypertensive –> causes mydriasis

Acts on the presynaptic nerve endings and are inhibitory –> prevent further release of neurotransmitter

Has very little alpha-1 activity (use in Horners)

Question 17

What are the ocular side effects of pilocarpine? (8)

Answer 17

1. Miosis
2. Induced myopia (myopic shift)
3. Accomodative spasm
4. Conjunctival vascular congestion
5. Punctal stenosis
6. Cataract formation
7. Retinal detachment (causes contraction of ciliary body, pushes everything forward - caution in myopic patients)
8. Headaches/brow ache

Question 18

What is the general actions of adrenergic agonists (4)

Answer 18

1. Increase aqueous outflow by stimulating trabecular meshwork
2. Ciliary muscle relaxation
3. Contraction of Muller’s muscle –> ptosis relief
4. Conjunctival vessel constriction

Question 19

Which drugs are alpha-1 adrenergic agonists?

Which drugs are alpha-2 adrenergic agonists?

Answer 19

Alpha-1 : phenylephrine
Alpha-2: aproclonidine, brimonidine (selective)

Question 20

What is the mechanism of action of cocaine?

Answer 20

inhibits reuptake of monoamines (adrenaline and noradrenaline) at the synaptic space

Question 21

Accomodation occurs with parasympathetic or sympathetic control?

Answer 21

parasympathetic control

Question 22

What is the mechanism of action of brimonidine?

Answer 22

Selective alpha-2 agonist
1. Reduces aqueous production by interfering with adenylyl cyclase

2. Increases outflow by stimulating TM adrenergic receptors
3. Induces miosis

Question 23

What are the side effects of brimonidine?

Answer 23

Induces CMO in aphakia, allergic blepharoconjunctivitis,

Contraindicated in heart block and bradycardia

Question 24

What is an example of an adrenergic antagonist? (2)

Answer 24

Beta blockers - timolol (block beta adrenergic receptors)

Guanethidine - inhibits release of noradrenaline from nerve terminals (inhibits mullers muscle to lead to a narrow palpebral fissure)

Question 25

What is the mechanism of action of hydroxyamphetamine?

Answer 25

stimulates release of noradrenaline from nerve terminals. Differentiates between pre and post-ganglionic causes of Horner's syndrome.

Question 26

What is the mechanism of action of botolinium toxin?

Answer 26

Inhibits ACh release at the neuromuscular junction.

Question 27

Important table regarding dilation in Horner's

Answer 27

Question 28

What drugs are direct acting parasympathomimetic (ACh receptor agonist)? What drugs are indirect acting parasympathomimeter (cholinesterase inhibitor)?

Answer 28

1. pilocarpine 2. physostigmine

Question 29

alpha 1 agonists vs alpha 2 agonists

Answer 29

Alpha-1 agonists are excitatory, principally causing smooth muscle contraction, as in the contraction of the dilator pupillae muscle. This dilatation causes an early rise in IOP. Alpha-2 agonists occur mainly on the presynaptic nerve endings and are inhibitory as they prevent further release of neurotransmitter. Alpha-2 agonists such as clonidine cause a reduction in IOP and this is thought to be mediated centrally by the stimulation of the medullopontine sympathetic nerve and by reducing aqueous production locally. Apraclonidine is a partial alpha-2 agonist; it has very little alpha-1 activity.

Question 30

Whats the difference between apraclonidine and brimonidine and phenylephrine?

Answer 30

phenylephrine is a synthetic sympathetic agonist that directly acts on alpha receptors apraclonidine and brimonidine are both selective alpha-2 agonists. Brimonidine causes miosis.

Question 31

How is adrenaline formed?

Answer 31

From the meythylation of noradrenaline

Question 32

How is noradrenaline formed?

Answer 32

hydroxylation of tyrosine causes DOPA synthesis which converts to dopamine which coverts to noradrenaline.

Question 33

What are the main miotic agents? (6)

Answer 33

1. Pilocarpine - stimulates ACh muscarinic receptors 2. Carbachol - increases ACh release 3. Alpha blockers - they paralyse the sphincter dilator muscle (brimonidine) 4. Physostigmine - inhibits acetylcholinesterases --> Increased ACh in synaptic cleft. 5. Heroine - reduces cortical inhibition of Edinger-Westphal nucleus 6. Guanethidine (inhibits noradrenaline release from nerve terminals).

Question 34

Which mydriatic drug does not inhibit accomodation?

Answer 34

Phenylephrine

Question 35

Table of mydriatic drops - onset and duration.

Answer 35

Question 36

Diagram of mydriasis and miosis pupil effects

Answer 36

Question 37

Which drug can cause rebound miosis?

Answer 37

phenylephrine

Question 38

What are the side effects of 10% phenylephrine?

Answer 38

Stroke, MI, Cardiac arrest.