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For ophthalmic use during surgery, the standard dose of Acetylcholine Chloride (Miochol-E) typically ranges from 0.5 mL to 2.0 mL of a 1% solution. The solution is instilled gently into the anterior chamber of the eye. In most cases, a volume of 0.5 mL is sufficient to produce satisfactory miosis. The effect is rapid, usually occurring within seconds, and typically lasts for about 10 to 20 minutes. If the surgical procedure requires a longer duration of miosis, the surgeon may administer additional doses or follow with a longer-acting miotic like carbachol.

Safety and effectiveness of Acetylcholine Chloride in pediatric patients have not been established through formal clinical trials. However, it has been used by ophthalmic surgeons in children when the benefits of miosis during surgery outweigh the potential risks. Dosing in children is usually determined by the surgeon based on the size of the anterior chamber and the specific requirements of the procedure, often using the minimum effective volume.

Renal Impairment

Because acetylcholine is rapidly hydrolyzed in the plasma and acts locally in the eye, dosage adjustments for patients with renal impairment are generally not required. However, clinicians should monitor for systemic effects in patients with severe renal failure if multiple doses are used.

Hepatic Impairment

Patients with severe hepatic impairment may have reduced levels of plasma pseudocholinesterase. While this could theoretically slow the metabolism of any systemically absorbed acetylcholine, the clinical impact is usually negligible given the tiny doses used in eye surgery.

Elderly Patients

No specific dosage adjustments are recommended for elderly patients. This population frequently undergoes cataract surgery, and acetylcholine is commonly used in this age group without unique age-related complications, provided cardiovascular status is stable.

Acetylcholine is not a medication that patients self-administer. It is used exclusively in a controlled surgical environment.

• Preparation: The solution must be prepared immediately before use. The dual-chamber vial or the powder and diluent are mixed to create a clear, colorless 1% solution.
• Administration: The surgeon uses a cannula to instill the solution into the anterior chamber, ensuring the solution reaches the iris.
• Storage: The dry powder should be stored at controlled room temperature (15°C to 30°C). Once reconstituted, the solution is unstable and must be used immediately; any unused portion must be discarded.

As this medication is administered by a surgeon during a procedure, missed doses by the patient are not possible. The surgeon will administer the drug as needed based on the real-time requirements of the operation.

Systemic overdose of acetylcholine is extremely rare during ophthalmic use. However, if excessive amounts are absorbed (e.g., through the tear ducts), symptoms of a 'cholinergic crisis' may occur.

• Signs: Profuse sweating, salivation, nausea, vomiting, abdominal cramps, urinary urgency, bradycardia (slow heart rate), and hypotension (low blood pressure).
• Emergency Measures: If systemic toxicity occurs, the primary treatment is the intravenous administration of Atropine sulfate (0.5 mg to 1.0 mg), which acts as a direct antagonist at muscarinic receptors. Supportive care for respiration and blood pressure may also be required.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. In the case of acetylcholine, this guidance applies to the clinical team managing your surgical care.

Because acetylcholine is used locally in the eye, most common side effects are ocular. These may include:

• Temporary Clouding of Vision: Immediately following instillation, the vision may become blurry or cloudy as the pupil constricts and the solution distributes.
• Ocular Hyperemia: Redness of the eye caused by the dilation of small blood vessels in the conjunctiva.
• Corneal Edema: Swelling of the cornea, which may cause a temporary 'hazy' appearance to the eye surface.

• Brow Ache: A dull ache or pressure sensation above the eye or in the forehead area, caused by the sudden and forceful contraction of the iris sphincter and ciliary muscles.
• Accommodative Spasm: A temporary shift in the eye's focus, making it difficult to see distant objects clearly for a short period after the procedure.

Systemic reactions are rare but can occur if the drug enters the systemic circulation through the nasolacrimal duct. These include:

• Bradycardia: A noticeable slowing of the heart rate.
• Hypotension: A drop in blood pressure that may cause lightheadedness.
• Flushing: A sudden feeling of warmth and redness in the face and neck.
• Breathing Difficulties: Bronchoconstriction, which may feel like chest tightness or wheezing.
• Increased Salivation and Sweating: General activation of the exocrine glands.

> Warning: Stop taking Acetylcholine and call your doctor immediately if you experience any of these symptoms after your procedure, as they may indicate a systemic reaction or surgical complication.

• Severe Bradycardia: A heart rate that drops significantly, potentially leading to fainting or cardiac distress.
• Acute Bronchospasm: Sudden, severe difficulty breathing or wheezing, especially in patients with a history of asthma.
• Signs of Anaphylaxis: While extremely rare, symptoms like hives, swelling of the face or throat, and severe dizziness require emergency intervention.
• Persistent Corneal Opacity: If the clouding of the eye does not resolve within the expected post-operative timeframe.

Acetylcholine is intended for short-term, acute use during surgery. There are no documented long-term side effects associated with a single intraocular administration. However, repeated exposure in experimental settings has been linked to changes in receptor sensitivity (downregulation), though this is not clinically relevant for surgical patients.

There are currently no FDA black box warnings for Acetylcholine Chloride. It is considered safe for its intended ophthalmic use when administered by trained surgical professionals.

Report any unusual symptoms to your healthcare provider. If you notice persistent changes in your vision or heart rate after surgery, ensure your surgical team is informed immediately.

Acetylcholine is a potent biological molecule. Its clinical use is strictly limited to ophthalmic surgery. It should never be self-administered or used for any purpose other than that prescribed by an ophthalmologist. Patients with a history of severe allergies should be monitored closely, as the chloride salt or the diluent may cause reactions in sensitive individuals.

No FDA black box warnings for Acetylcholine.

• Allergic Reactions / Anaphylaxis Risk: While rare, hypersensitivity to acetylcholine chloride can occur. Surgeons should be prepared to manage acute allergic reactions, including anaphylaxis, with epinephrine and antihistamines.
• Cardiovascular Risk: Patients with pre-existing heart conditions, such as bradycardia, heart block, or recent myocardial infarction, should be monitored closely. Systemic absorption of acetylcholine can exacerbate these conditions by further slowing the heart rate.
• Respiratory Risk: Acetylcholine can cause bronchoconstriction. Patients with asthma or chronic obstructive pulmonary disease (COPD) are at a higher risk of respiratory distress if the drug is absorbed systemically.
• Gastrointestinal and Urinary Precautions: In rare cases of systemic absorption, the drug may increase gastric acid secretion and bladder tone, which could be problematic for patients with peptic ulcers or urinary tract obstructions.

During surgery, the patient's vital signs—including heart rate, oxygen saturation, and blood pressure—are continuously monitored by the anesthesia team. Post-operatively, the surgeon will monitor:

• Intraocular Pressure (IOP): Miotics can sometimes cause a temporary rise in eye pressure.
• Corneal Clarity: To ensure no lasting damage to the corneal endothelium occurred during administration.
• Pupillary Response: To confirm the miosis is reversing as expected or that the pupil remains stable if that was the surgical goal.

Patients should not drive or operate machinery immediately following eye surgery. Acetylcholine causes miosis (small pupils), which significantly reduces the amount of light entering the eye and can impair night vision and depth perception. Furthermore, the surgical procedure itself usually requires the eye to be patched or blurred by other medications.

There is no direct interaction between alcohol and intraocular acetylcholine. However, patients are generally advised to avoid alcohol before and immediately after surgery to ensure proper healing and to avoid interactions with sedative medications used during the procedure.

Acetylcholine is a single-use surgical agent. There is no 'discontinuation' or tapering process for the patient. The effects wear off naturally as the drug is metabolized by the body's enzymes within minutes to an hour.

> Important: Discuss all your medical conditions, especially asthma or heart problems, with your healthcare provider before starting any procedure involving Acetylcholine.

While acetylcholine is used locally, certain drugs can interfere with its action or increase the risk of toxicity:

• Topical Anticholinergics (e.g., Atropine, Cyclopentolate): These drugs block the muscarinic receptors that acetylcholine needs to bind to. Using them simultaneously will neutralize the effect of acetylcholine, preventing miosis.

• Cholinesterase Inhibitors (e.g., Neostigmine, Physostigmine): These medications inhibit the enzyme that breaks down acetylcholine. If a patient is taking these systemically or using them topically, the effect of Acetylcholine Chloride may be significantly prolonged and the risk of systemic toxicity increases.
• Beta-Blockers (e.g., Timolol, Metoprolol): Systemic absorption of acetylcholine in a patient already taking beta-blockers can lead to additive bradycardia (dangerously slow heart rate).

• Digoxin: Like acetylcholine, digoxin can slow the heart rate via the vagus nerve. Combined systemic effects could lead to heart rhythm issues.
• Pilocarpine: Another cholinergic agonist. While not contraindicated, using multiple miotics can increase the risk of ocular side effects like brow ache and increased eye pressure.

There are no known food interactions with intraocularly administered acetylcholine. Because the drug is used during surgery, patients are typically under 'NPO' (nothing by mouth) orders, which precludes food interactions during the window of drug activity.

• Cholinergic Herbs: Supplements with theoretical cholinergic activity (such as Huperzine A) could potentially enhance the effects of acetylcholine, though the clinical significance of this for a one-time ophthalmic dose is likely low.

Acetylcholine is not known to interfere with common laboratory blood or urine tests. Its extremely short half-life ensures it is cleared from the system long before most post-operative lab work would be conducted.

For each major interaction, the mechanism involves either competitive binding at the muscarinic receptor (anticholinergics) or interference with the metabolic pathway (cholinesterase inhibitors). The management strategy for surgeons is to ensure a thorough medication reconciliation is performed prior to surgery.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially any eye drops you use for glaucoma.

Acetylcholine Chloride must NEVER be used in the following circumstances:

1. 1Known Hypersensitivity: If a patient has a documented severe allergy to acetylcholine chloride or any component of the formulation.
2. 2When Miosis is Undesirable: In certain ocular conditions, such as acute iritis (inflammation of the iris) or other inflammatory conditions where constricting the pupil could lead to the formation of synechiae (adhesions between the iris and lens).

Conditions requiring a careful risk-benefit analysis include:

• Asthma: Due to the risk of bronchoconstriction if systemic absorption occurs.
• Bradycardia or Heart Block: Due to the risk of further slowing the heart rate.
• Peptic Ulcer Disease: As cholinergic stimulation increases gastric acid secretion.
• Hyperthyroidism: Cholinergic agents can occasionally trigger atrial fibrillation in hyperthyroid patients.
• Urinary Tract Obstruction: As the drug may increase the pressure of the bladder contraction against an obstruction.

Patients who are sensitive to other cholinergic esters (such as methacholine or carbachol) may exhibit cross-sensitivity to acetylcholine. While not a strict contraindication, healthcare providers should proceed with extreme caution in these individuals.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of asthma or heart disease, before prescribing or administering Acetylcholine.

Acetylcholine is classified under FDA Pregnancy Category C. This means that animal reproduction studies have not been conducted, and it is not known whether acetylcholine can cause fetal harm when administered to a pregnant woman. Because acetylcholine is a naturally occurring substance and is rapidly destroyed by plasma esterases, the risk to the fetus from a small intraocular dose is likely very low. However, it should be used during pregnancy only if clearly needed and if the potential benefit outweighs the risk.

It is not known whether acetylcholine chloride is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to forgo the drug, taking into account the importance of the drug to the mother. Given its half-life of seconds, the likelihood of it reaching breast milk in active form is extremely remote.

As noted in the dosage section, safety and effectiveness in pediatric patients have not been formally established. While it is used in pediatric ophthalmic surgery, surgeons must exercise caution and use the smallest effective dose to avoid potential systemic effects in smaller children.

No overall differences in safety or effectiveness have been observed between elderly and younger patients. Acetylcholine is used frequently in the geriatric population, as this group undergoes the majority of cataract surgeries. The primary concern in this population is the presence of comorbid cardiovascular disease, which requires careful monitoring for bradycardia during administration.

Specific studies in patients with renal impairment have not been conducted. However, since the drug is metabolized by plasma esterases and not primarily cleared by the kidneys in its active form, renal impairment is not expected to significantly alter the drug's clinical effect or safety profile.

Patients with severe liver disease may have lower levels of pseudocholinesterase, the enzyme responsible for breaking down acetylcholine in the blood. This could theoretically prolong the systemic effects of the drug if absorption occurs. Surgeons should be aware of this possibility in patients with end-stage liver disease.

> Important: Special populations require individualized medical assessment. Always inform your surgical team if you are pregnant, nursing, or have chronic kidney or liver issues.

Acetylcholine is the natural neurotransmitter for cholinergic neurons. In the eye, it acts as a potent miotic by stimulating the muscarinic receptors of the iris sphincter muscle. This stimulation causes the muscle to contract, which pulls the iris inward and constricts the pupil. It also acts on the ciliary muscle, which can lead to a spasm of accommodation. At the molecular level, it is a non-selective agonist, meaning it binds to both muscarinic (M1-M5) and nicotinic (Nm, Nn) receptors, though its surgical use targets the M3 receptors in the ocular tissue.

• Onset of Action: Nearly instantaneous (within seconds of application to the iris).
• Duration of Action: Short-lived, typically lasting 10 to 20 minutes.
• Dose-Response: There is a clear dose-response relationship up to the point of receptor saturation; however, in clinical practice, a 1% concentration is standardized to ensure complete miosis in most patients.

| Parameter | Value |

|---|---|

| Bioavailability | Negligible (systemic); 100% (local intraocular) |

| Protein Binding | Minimal |

| Half-life | < 1 minute (due to rapid hydrolysis) |

| Tmax | Immediate (seconds) |

| Metabolism | Rapidly hydrolyzed by Acetylcholinesterase and Pseudocholinesterase |

| Excretion | As metabolites (Choline/Acetic Acid) via Renal/Recycling |

• Molecular Formula: C7H16ClNO2
• Molecular Weight: 181.66 g/mol
• Solubility: Highly soluble in water.
• Structure: A quaternary ammonium cation with an ester linkage. It consists of an ethane chain with an ester group and a trimethylammonium group.

Acetylcholine is classified as a Direct-Acting Cholinergic Agonist. Within the therapeutic area of ophthalmology, it is categorized as a Miotic. It is related to other cholinergic agents like Carbachol and Pilocarpine, though it is much shorter-acting than both.