PHARMACOLOGY - Miosis and Mydriasis Flashcards
What are the effects of atropine - anti-muscarinic (2 ocular, 3 systemic)
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
What are the mechanism of pilocarpine? (6)
DIRECT muscaranic agonist - acts on muscarinic / Ach receptor
- MIOSIS - iris sphincter contraction
- ACCOMODATION - ciliary muscle contraction (accomodative spasm)
- REDUCES IOP - ciliary muscle contraction increases tension of scleral spur by pulling is posteriorly and internally –> opening of trabecular meshwork (conventional route)
- MYOPIA - ciliary muscle contraction
- VASCULAR PERMEABILITY - increases so should be avoided in uveitis.
- REVERSAL OF MYDRIASIS - only ones caused by phenylephrine, not atropine.
Which drugs can reverse atropine mydriasis?
Which drugs can reverse phenylephrine mydriasis?
- Pilocarpine, thymoxamine (more effective)
What are the effects of apraclonidine? (3)
- Mydriasis
- Eyelid retraction
- Conjunctival blanching
What is the main ocular side effects of brimonidine / apraclonidine?
After 1 year - allergic conjunctivitis, follicular conjunctivitis
Which drugs are alpha-1 adrenergic agonists?
Which drugs are alpha-2 adrenergic agonists?
Alpha-1 : phenylephrine
Alpha-2: apraclonidine, brimonidine
Which drug relaxes the ciliary body?
Atropine
Which drugs are parasympathetic antagonists?
- Cyclopentolate
- Tropicamide
- Atropine
- Phenothiazine
What is the mechanism of action of phenylephrine?
Non selective alpha agonist
What is the mechanism of action of tropicamide?
It is a muscarinic antagonist - blocks parasympathetic pathway.
what are the side effects of tropicamide?
- precipitates angle closure
- exacerbates ataxic dysarthia
- cerebellar signs
- increases risk of seizure
In what instances are alpha-2-agonists contraindicated? (2)
- Potentiates hypertensive crisis with monoamine oxidase inhibitors
- WIth TCAs, its IOP effect is removed.
What is the effect of muscarinic agonists, example? (3)
Direct - pilocarpine
Indirect - carbachol - inhibits cholinesterase
- Miosis
- Accomodation
- Decreased intraocular pressure
What are the main muscarinic agonists and antagonists?
Musacrinic agonist - pilocarpine, carbachol
Muscarinic antagonist - tropicamide (short acting 6 hours), cyclopentolate (24 hours) atropine (7 days)
What is the order of potency for muscarinic antagonists?
atropine > cyclopentolate > homatropine > tropicamide
What is the mechanism of action of apraclonidine?
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)
What are the ocular side effects of pilocarpine? (8)
- Miosis
- Induced myopia (myopic shift)
- Accomodative spasm
- Conjunctival vascular congestion
- Punctal stenosis
- Cataract formation
- Retinal detachment (causes contraction of ciliary body, pushes everything forward - caution in myopic patients)
- Headaches/brow ache
What is the general actions of adrenergic agonists (4)
- Increase aqueous outflow by stimulating trabecular meshwork
- Ciliary muscle relaxation
- Contraction of Muller’s muscle –> ptosis relief
- Conjunctival vessel constriction
Which drugs are alpha-1 adrenergic agonists?
Which drugs are alpha-2 adrenergic agonists?
Alpha-1 : phenylephrine
Alpha-2: aproclonidine, brimonidine (selective)
What is the mechanism of action of cocaine?
inhibits reuptake of monoamines (adrenaline and noradrenaline) at the synaptic space
Accomodation occurs with parasympathetic or sympathetic control?
parasympathetic control
What is the mechanism of action of brimonidine?
Selective alpha-2 agonist
1. Reduces aqueous production by interfering with adenylyl cyclase
- Increases outflow by stimulating TM adrenergic receptors
- Induces miosis
What are the side effects of brimonidine?
Induces CMO in aphakia, allergic blepharoconjunctivitis,
Contraindicated in heart block and bradycardia
What is an example of an adrenergic antagonist? (2)
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)
What is the mechanism of action of hydroxyamphetamine?
stimulates release of noradrenaline from nerve terminals.
Differentiates between pre and post-ganglionic causes of Horner’s syndrome.
What is the mechanism of action of botolinium toxin?
Inhibits ACh release at the neuromuscular junction.
Important table regarding dilation in Horner’s
What drugs are direct acting parasympathomimetic (ACh receptor agonist)?
What drugs are indirect acting parasympathomimeter (cholinesterase inhibitor)?
- pilocarpine
- physostigmine
alpha 1 agonists vs alpha 2 agonists
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.
Whats the difference between apraclonidine and brimonidine and phenylephrine?
phenylephrine is a synthetic sympathetic agonist that directly acts on alpha receptors
apraclonidine and brimonidine are both selective alpha-2 agonists. Brimonidine causes miosis.
How is adrenaline formed?
From the meythylation of noradrenaline
How is noradrenaline formed?
hydroxylation of tyrosine causes DOPA synthesis which converts to dopamine which coverts to noradrenaline.
What are the main miotic agents? (6)
- Pilocarpine - stimulates ACh muscarinic receptors
- Carbachol - increases ACh release
- Alpha blockers - they paralyse the sphincter dilator muscle (brimonidine)
- Physostigmine - inhibits acetylcholinesterases –> Increased ACh in synaptic cleft.
- Heroine - reduces cortical inhibition of Edinger-Westphal nucleus
- Guanethidine (inhibits noradrenaline release from nerve terminals).
Which mydriatic drug does not inhibit accomodation?
Phenylephrine
Table of mydriatic drops - onset and duration.
Diagram of mydriasis and miosis pupil effects
Which drug can cause rebound miosis?
phenylephrine
What are the side effects of 10% phenylephrine?
Stroke, MI, Cardiac arrest.
