AUROMIDE PLUS EYE DROPS

Indications

• Nasal congestion
• Hypotension (particularly in acute settings)
• Vasopressor support during anesthesia

Dosage

Children: Refer to the BNF for Children for specific dosing information, as it varies based on age and indication.

Adults: For the treatment of hypotension, the recommended initial dose is 0.16–0.33 mL/minute as an intravenous infusion, adjusted according to blood pressure response. For nasal congestion, 0.25 to 0.5 mL of the 0.5% solution may be applied topically.

Mechanism of action

Phenylephrine primarily acts as a selective agonist for α1-adrenergic receptors. Activation of these receptors results in vasoconstriction of blood vessels, leading to increased systemic vascular resistance and blood pressure. It does not significantly stimulate β-adrenergic receptors, which makes it less effective at increasing heart rate compared to other sympathomimetics.

Pharmacodynamics

Phenylephrine's pharmacodynamic effects include increased peripheral vascular resistance and blood pressure due to its vasoconstrictive action. Its decongestant effects arise from vasoconstriction of nasal mucosal blood vessels, reducing swelling and congestion. The duration of action is dose-dependent and can vary based on the route of administration.

Pharmacokinetics

Phenylephrine is absorbed after oral administration but has a significant first-pass metabolism, which reduces its bioavailability. It is metabolized primarily in the liver and has a half-life of about 2.5 to 3 hours. The drug is excreted in urine, primarily as metabolites. The onset of action varies with the route of administration, with intravenous administration providing the most rapid effect.

Adverse effects

• Hypertension
• Reflex bradycardia
• Headache
• Nausea
• Vomiting
• Palpitations

Precautions

• Use with caution in patients with hypertension
• Monitor blood pressure frequently
• Use during pregnancy only if potential benefit outweighs risk

Pregnancy

Manufacturer advises use if potential benefit outweighs risk-may reduce placental perfusion and induce fetal bradycardia.

Storage

Store at room temperature, protect from light.

Formulations

• Phenylephrine hydrochloride 2.5mg tablets
• Phenylephrine hydrochloride 5mg tablets
• Phenylephrine hydrochloride 10mg tablets
• Phenylephrine hydrochloride solution for injection

Indications

• Mydriasis for ocular fundus examination
• Cycloplegia in diagnostic and therapeutic procedures
• Adjunct in the management of anterior uveitis

Dosage

Adults: For adults, the typical dosage is to instill one to two drops of tropicamide 1% eye drops into the conjunctival sac 15 to 30 minutes before the

Mechanism of action

Tropicamide binds to muscarinic acetylcholine receptors, particularly the M3 subtype, which are involved in controlling smooth muscle function in the eye. By inhibiting these receptors, tropicamide relaxes the sphincter pupillae muscle leading to pupil dilation (mydriasis) and prevents the ciliary muscle from contracting, thus inhibiting accommodation. This action diminishes the parasympathetic influence, allowing sympathetic responses to prevail.

Pharmacodynamics

As an anticholinergic drug, tropicamide works by blocking muscarinic receptors to induce mydriasis and cycloplegia. Mydriasis typically occurs within 10 to 15 minutes after administration, with optimal effects observed at around 25 to 30 minutes. The duration of mydriasis is generally four to eight hours but can extend up to 24 hours in some individuals. The cycloplegic effect is also noted within 20 minutes, lasting four to 10 hours. Tropicamide may elevate intraocular pressure, although serious systemic adverse effects are rare with its ophthalmic use.

Pharmacokinetics

Tropicamide is administered topically as eye drops, allowing rapid absorption through the ocular surface. The drug undergoes minimal systemic absorption, which limits systemic side effects. It has a relatively short half-life and is primarily eliminated through the liver metabolism and renal excretion of its metabolites. The pharmacokinetic profile supports its use as a short-acting mydriatic agent.

Contra-indications

• Hypersensitivity to tropicamide or any excipients
• Concomitant use of ocular formulations containing mercury-based preservatives
• Preterm neonates

Adverse effects

• Eye erythema
• Eye irritation (especially with prolonged administration)
• Eye pain
• Headache
• Hypotension
• Nausea
• Syncope
• Blurred vision
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Clozapine: Unknown additive effect
• Second-generation antipsychotics: Unknown additive effect

Precautions

• Caution in patients with hypersensitivity to other anticholinergics
• Use with caution in patients with narrow-angle glaucoma
• Monitor for elevation of intraocular pressure

Pregnancy

Manufacturer advises caution due to limited data on safety during pregnancy.

Breast-feeding

Manufacturer advises avoiding use unless no suitable alternative is available due to limited information.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Tropicamide 1% eye drops (Mydriacyl, Alcon Eye Care UK Ltd)
• Tropicamide 1% unit dose eye drops (Minims, 0.5ml)

Indications

• Ophthalmic preservative
• Topical antiseptic

Dosage

Children: Refer to specific formulation guidelines, as dosages may vary based on the application and concentration of chlorobutanol in the product.

Adults: Refer to specific formulation guidelines, as dosages may vary based on the application and concentration of chlorobutanol in the product.

Mechanism of action

As a detergent, chlorobutanol disrupts the lipid structure of the cell membrane, increasing cell permeability and leading to cell lysis. It induces conjunctival and corneal cell toxicity by causing cell retraction and cessation of normal cytokine production, cell movement, and mitotic activity. Additionally, it inhibits oxygen utilization by the cornea, increasing susceptibility to infections.

Pharmacodynamics

Chlorobutanol exhibits antimicrobial activity and has been shown to inhibit platelet aggregation through mechanisms that may involve the arachidonic acid pathway. It reduces thromboxane B2 formation and affects cytosolic free calcium and ATP release, indicating a potential antiplatelet effect. The compound also demonstrates a negative inotropic effect on myocardial cells and has been shown to cause toxicity in corneal epithelial cells at higher concentrations.

Pharmacokinetics

The pharmacokinetics of chlorobutanol, including its absorption, distribution, metabolism, and excretion, are not extensively characterized in the literature. Given its use as a preservative in ophthalmic preparations, it is presumed to have localized effects with minimal systemic absorption. Further studies may be necessary to fully elucidate its pharmacokinetic profile.

Adverse effects

• Conjunctival toxicity
• Corneal cell toxicity
• Cell retraction
• Cessation of normal cytokine activity
• Impaired cell movement
• Decreased mitotic activity
• Increased susceptibility to infection

Precautions

• Use with caution in patients with known hypersensitivity to chlorobutanol or related compounds
• Monitor for signs of ocular irritation or toxicity during use

Pregnancy

Chlorobutanol should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, as safety in pregnancy has not been established.

Breast-feeding

Caution is advised when using chlorobutanol during breastfeeding, as it is unclear if it passes into breast milk.

Storage

Store in a tightly closed container at room temperature, away from light and moisture.

Formulations

• Ophthalmic solutions
• Topical preparations

Indications

• Hypotension in surgical settings
• Nasal decongestion
• Mydriasis for ophthalmic procedures
• Management of shock states

Dosage

Adults: For intravenous administration, initial doses typically range from 100 to 500 micrograms, repeated as necessary, with careful monitoring of blood pressure. For nasal decongestion, phenylephrine is commonly administered as a 10 mg oral dose every

Mechanism of action

Phenylephrine exerts its effects primarily through agonism of alpha-1 adrenergic receptors, which results in vasoconstriction and mydriasis. The stimulation of these receptors inhibits the production of cyclic adenosine-3',5'-monophosphate (cAMP) by inhibiting adenyl cyclase, leading to increased peripheral vascular resistance and elevated blood pressure. Additionally, phenylephrine indirectly promotes the release of norepinephrine from storage sites, further enhancing its vasoconstrictive effects.

Pharmacodynamics

Phenylephrine causes an increase in blood pressure and local vasoconstriction. Its ophthalmic formulations can induce mydriasis for 3-8 hours, while intravenous administration has a rapid onset with an effective half-life of about 5 minutes and an elimination half-life of approximately 2.5 hours. Caution is advised regarding potential side effects such as hypertension, arrhythmias, and rebound miosis with ophthalmic use, and bradycardia, allergic reactions, and tissue damage with intravenous use.

Pharmacokinetics

Phenylephrine is rapidly absorbed following intravenous administration, leading to a quick elevation in blood pressure. The drug undergoes metabolism primarily in the liver and is eliminated through urine. The pharmacokinetic profile indicates a short effective half-life which necessitates frequent dosing in continuous infusion settings for maintaining blood pressure levels.

Contra-indications

• Severe hypertension
• Hypersensitivity to phenylephrine
• Severe coronary artery disease
• Narrow-angle glaucoma

Adverse effects

• Hypertension
• Reflex bradycardia
• Arrhythmias
• Headache
• Dizziness
• Nausea
• Vomiting
• Local irritation (ophthalmic use)

Interactions

• MAO inhibitors may enhance the hypertensive effect
• Tricyclic antidepressants may increase the pressor response
• Concurrent use with oxytocic drugs may increase the risk of hypertension
• Can interact with other sympathomimetics

Precautions

• Use with caution in patients with hypertension, hyperthyroidism, or diabetes mellitus
• Monitor blood pressure regularly during treatment
• Caution in patients with cardiovascular disease
• Use with caution in elderly patients

Pregnancy

Phenylephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available.

Breast-feeding

It is not known whether phenylephrine is excreted in human milk. Caution is advised when administered to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Ophthalmic solution
• Injectable solution
• Oral tablet

Mechanism of action

Muscarinic acetylcholine receptors are involved in numerous ocular functions. The M₃ subtype is predominantly expressed by smooth muscle cells of the sphincter pupillae, which is a circular muscle of the iris, and ciliary muscles. In response to light or binding of acetylcholine, M₃ receptor signalling leads to contraction of the sphincter pupillae and pupil constriction. Contraction of the ciliary muscle via M₃ receptor signalling also leads to accommodation, adjusting the lens for near vision. The eye is also innervated by parasympathetic nerves: ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction. Tropicamide is a non-selective muscarinic antagonist that binds to all subtypes of muscarinic receptors. By binding to muscarinic receptors, tropicamide relaxes the pupillary sphincter muscle and causes pupil dilation. By blocking the muscarinic receptors of the ciliary body, tropicamide also prevents accommodation. Like other muscarinic antagonists, tropicamide inhibits the parasympathetic drive, allowing the sympathetic nervous system responses to dominate. Tropicamide is thought to ameliorate sialorrhea by blocking M₄ receptors expressed on salivary glands and reducing hypersalivation.

Pharmacodynamics

Tropicamide is an anticholinergic drug and that works by non‐selectively blocking muscarinic receptors to cause mydriasis and cycloplegia. It relaxes the pupillary sphincter to dilate the pupil. The onset of tropicamide‐induced mydriasis is about 10 to 15 minutes, with optimal effect occurring 25 to 30 minutes post-administration. Mydriasis caused by tropicamide wears off within four to eight hours, but it was seen up to 24 hours in some individuals. Tropicamide hinders accommodation by causing the contraction of the ciliary muscle. The cycloplegic effect occurs within 20 to minutes following administration, with a duration of action of four to 10 hours. Tropicamide can elevate intraocular pressure. The ophthalmic use of tropicamide is not typically associated with serious systemic adverse events. One randomized pilot study showed that oral tropicamide alleviated perceived symptoms of sialorrhea in patients with Parkinson's Disease: anticholinergics are believed to restore the dopaminergic to cholinergic activity imbalance in neurodegenerative diseases. Similarly in one case report, tropicamide administered via ophthalmic solution relieved clozapine-induced sialorrhea. Interestingly, in rodent models, tropicamide suppressed drug-induced tremulous jaw movements which are often used as a model of parkinsonian tremor: the significance of this finding requires further investigations.

Mechanism of action

As a detergent, chlorobutanol disrupts the lipid structure of the cell membrane and increases the cell permeability, leading to cell lysis. It induces conjunctival and corneal cell toxicity via causing cell retraction and cessation of normal cytokines, cell movement, and mitotic activity. It disrupts the barrier and transport properties of the corneal epithelium as well as inhibits the utilization of oxygen by the cornea. Chlorobutanol also inhibits oxygen use by the cornea, which increases susceptibility to infection.

Pharmacodynamics

Chlorobutanol is a detergent preservative with a broad spectrum of antimicrobial activity. _In vitro_, chlorobutanol demonstrated to inhibit platelet aggregation and release via unknown mechanisms. A study proposes that the antiplatelet effect of chlorobutanol may occur from inhibition of the arachidonic acid pathway. It attenuated thromboxane B2 formation, elevation of cytosolic free calcium, and ATP release, and additionally exhibited a significant inhibitory activity toward several aggregation inducers in a time- and concentration-dependent manner. Chlorobutanol may exert a direct negative inotropic effect on myocardial cells to isometric tension produced by the heart. Chlorobutanol was shown to induce conjunctival and corneal cell toxicity _in vitro_: at a concentration of 0.1%, Cbl caused near depletion of the squamous layer while degeneration of corneal epithelial cells, generation of conspicuous membranous blebs, cytoplasmic swelling, and occasional breaks in the external cell membrane were observed at a concentration of 0.5%.

Mechanism of action

Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia. Phenylephrine acts predominantly by a direct effect on alpha-adrenergic receptors. In therapeutic doses, the drug has no substantial stimulant effect on the beta-adrenergic receptors of the heart (beta1-adrenergic receptors) but substantial activation of these receptors may occur when larger doses are given. Phenylephrine does not stimulate beta-adrenergic receptors of the bronchi or peripheral blood vessels (beta2-adrenergic receptors). It is believed that alpha-adrenergic effects result from the inhibition of the production of cyclic adenosine-3',5'-monophosphate (cAMP) by inhibition of the enzyme adenyl cyclase, whereas beta-adrenergic effects result from stimulation of adenyl cyclase activity. Phenylephrine also has an indirect effect by releasing norepinephrine from its storage sites.

Pharmacodynamics

Phenylephrine is an alpha-1 adrenergic agonist that raises blood pressure, dilates the pupils, and causes local vasoconstriction. Ophthalmic formulations of phenylephrine act for 3-8 hours while intravenous solutions have an effective half life of 5 minutes and an elimination half life of 2.5 hours. Patients taking ophthalmic formulations of phenylephrine should be counselled about the risk of arrhythmia, hypertension, and rebound miosis. Patients taking an intravenous formulation should be counselled regarding the risk of bradycardia, allergic reactions, extravasation causing necrosis or tissue sloughing, and the concomitant use of oxytocic drugs.