Mydriatic Agents PDF

Mydriatic Agents Part 1 - Introduction Manveer Seyan BSc(Hons) MCOptom Mydriatics Lecture Outline; what is mydriasis? how is pupillary size controlled? what are mydriatic agents? how do they work (mode of action)? when do we use them? different types of mydriatic agents adverse react...

Mydriatic Agents Part 1 - Introduction Manveer Seyan BSc(Hons) MCOptom Mydriatics Lecture Outline; what is mydriasis? how is pupillary size controlled? what are mydriatic agents? how do they work (mode of action)? when do we use them? different types of mydriatic agents adverse reactions and contra-indications to mydriasis what must an Optometrist do? communication, pre-tests, gaining consent, advice Mydriatics What is mydriasis; Mydriasis: the maximum dilation of the pupil with abolition of the light reflex Mydriatics What controls the pupil size? (Innervation of the iris); The pupillary diameter (or iris size) is controlled by two muscles; Sphincter Pupillae: primarily controlled by the parasympathetic nervous system Dilator Pupillae: primarily controlled by the sympathetic nervous system N.B. the dilator pupillae is weaker than the sphincter pupillae Mydriasis: contraction of the dilator accompanied by the relaxation of the sphincter Miosis: contraction of the sphincter accompanied by the relaxation of the dilator Mydriatics Parasympathetic - Innervation of the iris; Parasympathetic Sphincter Pupillae muscle (IIIn) system supplies Parasympathetic Lacrimal gland (VIIn) system also supplies Levator palpebral superioris (IIIn) Parasympathetic neurotransmitter Acetylcholine Mydriatics Parasympathetic system; pre-ganglionic: division of the IIIN: nerve fibres travel from the midbrain → EW nucleus → ciliary Neurones involved ganglion post-ganglionic: long and short fibres pre-ganglionic: acetylcholine Neurotransmitter post-ganglionic: acetylcholine Neurotransmitter Muscarinic: ciliary muscle, sphincter and lacrimal gland receptors Nicotinic: skeletal muscle Mydriatics Sympathetic - Innervation of the iris; Sympathetic system Dilator Pupillae muscle (α1) supplies throughout the body: lacrimal gland, Sympathetic system Muller’s muscle also supplies receptors alpha (α1 & α2), beta (β1 & β2) acetylcholine (sweat glands and adrenal Sympathetic medulla) neurotransmitter noradrenaline (norepinephrine) elsewhere Mydriatics Sympathetic pathway; pre-ganglionic: originates from the hypothalmus → emerges from the spinal cord, cervical and upper Neurones involved thoracic segments (long fibres) post-ganglionic: long fibres pre-ganglionic: acetylcholine Neurotransmitter post-ganglionic: noradrenaline Neurotransmitter α1&2 (α1 excitatory and α2 inhibitory) receptors β1&2 (β1 excitatory and β2 inhibitory) Mydriatics Neurone Receptor Theory and Drug Action (recap); Mydriatics Anti-muscarinic drugs – how do they work?; the sphincter pupillae is largely responsible for pupil miosis and is innervated by acetylcholine acetylcholine has an affinity for (synaptic) muscarinic receptors by blocking muscarinic receptors, anti-muscarinic drugs stop the sphincter pupillae from constricting (competitive acetylcholine antagonists) effectivity of the drug depends on: the receptor’s affinity for the drug the concentration of the drug in the tissue fluid surrounding the receptor Mydriatics Anti-muscarinic drugs – their effects; Mydriasis: better fundus examination possible can cause aberrations and photophobia Cycloplegia: unwanted side-effect caused by relaxation of the ciliary muscle Reduced tear secretion: can cause dry eyes (lacrimal gland inhibition) Mydriatics Sympathomimetic drugs – how do they work?; the dilator pupillae is innervated by noradrenaline noradrenaline has an affinity for α-receptors (mainly α1) sympathomimetic drugs are noradrenaline agonists N.B. the dilator pupillae is weaker than the sphincter pupillae effectivity of the drug depends on: the receptor’s affinity for the drug the concentration of the drug in the tissue fluid surrounding the receptor Mydriatics Sympathomimetic drugs – their effects; Mydriasis: better fundus examination possible can cause aberrations and photophobia Cycloplegia: no significant cycloplegia reported Other effects: can cause watery eyes (lacrimal gland excitatory) can cause widening of the palpebral aperture Mydriatics What makes a “good” mydriatic?; rapid onset of action adequate duration of mydriasis abolition of the light reflex no stinging on administration no cycloplegia (not always possible) no effect on refraction no local or systemic toxicity no adverse reactions stable Mydriatics When do Optometrists use mydriatics?; Symptoms: recent onset of flashes and floaters unexplained vision loss History: recent blunt trauma Clinical signs: retinal disturbances or macular changes inadequate fundus view – small pupils/ media opacities Other risk factors: diabetes high myopia Mydriatics When do Ophthalmologists use mydriatics?; As per Optometrists, plus… essentially, every patient Before treatments: prior to LASER (posterior segment) uveitis corneal abrasions cataract surgery Mydriatic Agents Part 2 – Theory, Contra-indications and Communication Manveer Seyan BSc(Hons) MCOptom Mydriatics Systemic side-effects of sympathomimetic Contraindications of sympathomimetic drugs (common); drugs ; dry mouth Should be avoided in patients with: hypertension heart disease cardiac arrythmias cardiac arrythmias & tachyarrythmia tachycardia & palpitations hypertension myocardial infarction taking beta-blockers vision disorders aneurysms headaches advanced arteriosclerosis stomach cramps thyrotoxicosis nausea asthma long-standing insulin dependence taking monoamine oxidase inhibitors (MAOIs) or tri-cyclic anti- depressants Mydriatics Ocular side effects to sympathomimetic agents; allergic conjunctivitis – with sympathomimetic drugs ocular discomfort & stinging superficial punctate keratitis vision disorders – aberrations (accommodation not usually affected) photophobia peri-orbital pallor (children) Mydriatics Side-effects of Atropine (anti-muscarinic); Mydriatics Systemic side-effects of anti- Contraindications of anti-muscarinic muscarinic drugs (common); drugs ; dry mouth & skin Should be avoided in patients with: flushing gastrointestinal problems increased body temperature Myasthenia Gravis tachycardia & palpitations prostatic enlargement CNS effects – ataxia & severe ulcerative colitis hallucinations bladder problems dizziness & drowsiness severe hepatic impairment dyspepsia angle-closure glaucoma urinary disorders tachyarrythmias vision disorders Interactions: the effects of anti-muscarinic drugs can be enhanced by the concomitant administration of other drugs (with mild anti-muscarinic properties e.g. anti- histamines) Mydriatics Contraindications to mydriatic agents; known hypersensitivity to drug or component in the preparation soft contact lenses patients with symptoms suggestive of acute or chronic closed-angle glaucoma (CAG) red eyes eye ache blurred vision & haloes around lights (corneal oedema?) symptoms more common in the evening patients with diagnosed CAG patients with narrow anterior chamber angles (increased risk of CAG) Mydriatics Acute angle-closure glaucoma; an acute condition in which the IOP is rapidly elevated caused by the partial (or complete) closure of the irido-corneal angle by the iris pupillary block due to pupil dilation is the most common cause of angle closure the iris comes into contact with the lens and obstructs the aqueous outflow pressure builds up in the posterior chamber resulting in the bowing of the peripheral iris anteriorly (iris bombé) subsequent apposition of the peripheral iris to the trabecular meshwork prevents drainage of the aqueous humour Mydriatics Risk of inducing acute angle-closure glaucoma; risk of pupillary block is 1:10,000 some studies show that the risk associated with tropicamide is minimal higher risk with cyclopentolate higher risk with hyperopic patients higher risk with patients over 60 years of age higher risk with patients who have shallow AC depth Mydriatics What must an Optometrist do before instilling mydriatic eye drops; determine the need for mydriasis decide on an appropriate mydriatic and concentration assess the patients anterior-chamber (van-Herricks technique) measure IOPs before dilation assess the risk of an adverse reaction (taking in to account any previous history) discuss all of the above with the patient instill the mydriatic and record the dose, time of instillation, batch number (BN) and expiry (EXP) on the patient’s record card record any clinical findings Mydriatics What advice must an Optometrist give prior to instilling mydriatic eye drops; the purpose of mydriasis how long the drops will take to work and the duration of mydriasis discuss expected side-effects stinging on instillation photophobia (protection from sunlight) blurred near vision (and possibly distance too) discuss unexpected side-effects possibility of AACG any other advice – e.g. avoid driving, operating heavy machinery etc. Only instill the mydriatic if the patient consents to the above Mydriatics What must an Optometrist do after instilling mydriatic eye drops; re-assess the patients anterior-chamber (van-Herricks technique) re-measure IOPs after dilation there often is a slight increase in IOPs following mydriasis if IOPs rise > 5mmHg → monitor IOPs every 15 minutes if IOPs con nue to rise → refer to Eye Casualty IOPs may rise when patient is mid-dilated (a few hours) after leaving the practice advise patient of the signs and symptoms of AACG advise patient to return or attend Eye Casualty issue an information leaflet/ written information Mydriatics College of Optometrist’s Information Leaflet; available to all College members available in printed form available as a PDF Good written advice should include: practice contact details the mydriatic name and concentration time of instillation and number of drops what not to do what the potential adverse reactions are and what to do in an emergency Mydriatic Agents Part 3 - Mydriatic Preparations Manveer Seyan BSc(Hons) MCOptom Mydriatics Tropicamide Hydrochloride (anti-muscarinic); POM: for use and supply by all Optometrists a synthetic (soluble) white crystalline powder stings on instillation (less than Cyclopentolate) light reflex abolished provides mild cycloplegia (Tropicamide 1%) ciliary tone not completely abolished most commonly used mydriatic by Optometrists Mydriatics Tropicamide Hydrochloride; Administration: topically (by Optometrists) Contraindications: hypersensitivity to Tropicamide or any other component patients with suspected (or confirmed) narrow anterior chamber angles (risk of AACG) pregnancy? Ocular adverse drug reactions: blurry vision, glare & photophobia conjunctival hyperaemia & oedema raised IOPs Mydriatics Tropicamide Hydrochloride; Cautions: exercise caution in very young children (particular new-borns: use 0.5% conc.) dark (pigmented) irides are more resistant to pupillary dilation and care needs to be taken to avoid over-dosage risk of inducing AACG – anterior chamber depth should be assessed before instillation patients should avoid driving for at least 2 hours after instillation Sensitivity: less toxicity reported (with 0.5%) than Cyclopentolate systemic side-effects of anti-muscarinics Mydriatics Tropicamide Hydrochloride; Availability: 0.5% & 1.0% strength Minims store below 25⁰C protect from sunlight (can be hydrolysed by light) Dose (for mydriasis): adults and children (over 12 years old) one drop of 0.5% for children or patients with pale irides one drop of 1.0% for patients with dark irides or diabetes for cycloplegia one drop (1.0%) → second drop 5 minutes later Onset: mydriasis: 5-10 minutes (duration: several hours) cycloplegia: after 30 minutes (duration: 4 - 6 hours) https://pubmed.ncbi.nlm.nih.gov/1015526/ - Effective degree of mydriasis with phenylephrine and tropicamide. L Levine. 1976 Mydriatics Cyclopentolate Hydrochloride (anti-muscarinic); POM: for use and supply by all Optometrists a synthetic (soluble) white crystalline powder stings on instillation provides longer mydriasis than Tropicamide light reflex fully abolished not commonly used as a mydriatic due to (unwanted) cycloplegia Mydriatics Cyclopentolate Hydrochloride; Administration: topically (by Optometrists) Contraindications: hypersensitivity to Cyclopentolate or any other component patients with suspected (or confirmed) narrow anterior chamber angles (risk of AACG) pregnancy? Ocular adverse drug reactions: blurry vision, glare & photophobia conjunctival hyperaemia & oedema raised IOPs Mydriatics Cyclopentolate Hydrochloride; Cautions: exercise caution in very young children or other high-risk patients e.g. the elderly dark (pigmented) irides are more resistant to pupillary dilation and care needs to be taken to avoid over-dosage systemic absorption may be reduced by compressing the lacrimal sac at the medial canthus during and (for 3-4 minutes) after instillation patients should avoid driving for up to 24 hours after instillation Sensitivity: more toxicity reported than Tropicamide systemic side-effects of anti-muscarinics Mydriatics Cyclopentolate Hydrochloride; Adverse drug reactions Adverse drug reactions in children (Frequency not known): (Frequency not known): allergic conjunctivitis allergic conjunctivitis blurry vision blurry vision cardiac arrythmias & abdominal distension palpitations abnormal behaviour dry mouth & flushing cardio-respiratory distress gastrointestinal disorders psychotic disorder urinary disorders vomiting NB. Systemic side-effects can occur – more likely in children and the elderly Mydriatics Cyclopentolate Hydrochloride; Availability: 0.5% & 1.0% strength Minims store below 25⁰C protect from sunlight (can be hydrolysed by light) Dose (for mydriasis): adults and children (over 12 years old) one drop of 0.5% (may be repeated after 5 minutes) is usually sufficient Onset: mydriasis: 5-10 minutes (duration 24 - 48 hours) cycloplegia: max cycloplegia after 30 (duration up to 24 hours) https://pubmed.ncbi.nlm.nih.gov/27274191/ - Time of maximum cycloplegia after instillation of cyclopentolate 1% in children with brown irises. S Laojaroenwanit et al. 2016 Mydriatics Phenylephrine Hydrochloride (sympathomimetic); P: for use and supply by all Optometrists a synthetic (soluble) white crystalline powder some stinging on instillation minimal effect on accommodation less potent than Tropicamide light reflex not completely abolished not as commonly used as a mydriatic (compared to Tropicamide) Mydriatics Phenylephrine Hydrochloride; Contraindications: hypersensitivity to Phenylephrine or any other component patients with suspected (or confirmed) narrow anterior chamber angles (risk of AACG) patients with cardiac disease, hypertension, aneurysms, asthma, thyrotoxicosis, long-standing insulin dependence pregnancy? Ocular adverse drug reactions: blurry vision, glare & photophobia conjunctival allergic reaction & punctate keratitis raised IOPs eyelid retraction Mydriatics Phenylephrine Hydrochloride; Cautions: exercise caution in very young children and the elderly – avoid using 10% Phenylephrine due to the risk of systemic toxicity risk of inducing AACG – anterior chamber depth should be assessed before instillation corneal clouding may occur if (10%) instilled when the corneal epithelium is damaged patients should avoid driving for at least 2 hours after instillation Sensitivity: may reverse the action of anti-hypertensives (potentially fatal) interacts with MAOIs, try-cyclic anti-depressants and quinidine (increased risk of cardiovascular events) Mydriatics Phenylephrine Hydrochloride; Availability: 2.5% & 10.0% strength Minims store below 25⁰C protect from sunlight (can be hydrolysed by light) Dose (for mydriasis): adults and children (over 3 months old) one drop of 2.5% (repeat only once an hour later if required) 10% is contraindicated in children and patients over (increased risk of systemic toxicity) Onset: mydriasis: up to 30 minutes (duration: 12 - 24 hours) https://pubmed.ncbi.nlm.nih.gov/1015526/ - Effective degree of mydriasis with phenylephrine and tropicamide. L Levine. 1976 Mydriatics Summary; Action Mydriatic Agent Usage Mydriatic Agent Strongest Cyclopentolate 1.0% Most Tropicamide 1.0% or 0.5% common Cyclopentolate 0.5% Tropicamide & Phenylephrine 2.5% Tropicamide 1.0% Cyclopentolate 0.5% Tropicamide 0.5% Phenylephrine 10.0% Phenylephrine 10.0% Cyclopentolate 0.5% & Phenylephrine 2.5% Weakest Phenylephrine 2.5% Least Phenylephrine 2.5% common Mydriatics Summary – what must Optometrists do; determine the need for mydriasis decide on an appropriate mydriatic and concentration assess the anterior chamber angle and measure IOPs assess the possible risk of an adverse reaction discuss the all of the above with the patient and obtain consent instill the mydriatic and record the dose, batch number, expiry and time of instillation record any clinical findings & carry out post-dilation checks (IOPs) advise patient of the signs and symptoms of AACG issue an information leaflet with emergency advice Mydriatics Further Reading; Kanski J, (2015) Clinical Ophthalmology – A Systematic Approach. (Eighth Edition) Vale, J, Cox, B (1999) Drugs and the Eye. Third Edition. Butterworth- Heinemann Bartlett, JD and Jaanus, SD. (2008) – Clinical Ocular Pharmacology (Fifth Edition) British National Formulary: https://bnf.nice.org.uk/drugs/ College of Optometrists Formulary: https://www.college- optometrists.org/guidance/optometrists-formulary.html