What is Demecarium?
Demecarium bromide is an indirect-acting parasympathomimetic agent, meaning it acts by prolonging the effect of acetylcholine, a neurotransmitter in the parasympathetic nervous system. Specifically, it functions as a potent and long-acting cholinesterase inhibitor, preventing the breakdown of acetylcholine. In the context of ophthalmic medicine, this leads to intense miosis (pupil constriction) and contraction of the ciliary muscle. These actions facilitate the outflow of aqueous humor from the eye, a critical function for lowering intraocular pressure (IOP). Demecarium, previously available for humans under the brand name Humorsol, is no longer commercially manufactured but can be obtained through compounding pharmacies for specialized use.
Historical and Current Uses
Treatment of Open-Angle Glaucoma
For human patients, Demecarium (as Humorsol) was prescribed to treat open-angle glaucoma that was not adequately managed by shorter-acting miotics. By constricting the pupil and contracting the ciliary muscle, it would mechanically open the iridocorneal angle, allowing for increased aqueous humor drainage and thus reducing IOP. Its long duration of action was a significant benefit, often requiring only once or twice daily dosing. However, it is no longer the first-line treatment for glaucoma due to the availability of newer, often better-tolerated, medications.
Management of Accommodative Esotropia
Accommodative esotropia, or convergent strabismus, is a condition where the eyes cross due to an excessive focusing effort. Demecarium was historically used in children to manage this condition. The medication's effect of causing ciliary muscle contraction helped correct the focusing imbalance that led to the eye-crossing. The dosage for this condition was carefully managed and often followed by a reduction in frequency as the patient's condition stabilized.
Veterinary Applications for Glaucoma
Today, Demecarium's most common application is in veterinary medicine, primarily for dogs and sometimes rabbits.
- Preventive treatment: In cases of primary glaucoma, which is often a breed-related hereditary condition, Demecarium is frequently used in the non-affected eye to delay the onset of the condition. In conjunction with a topical corticosteroid, it can significantly prolong the time before glaucoma develops in the healthy eye.
- Management of active glaucoma: While not always the most effective option for acute glaucoma emergencies, it is sometimes used to help manage the condition.
- Dosage frequency: Its long-acting nature means it can be administered less frequently, typically once or twice a day, which can be beneficial for managing chronic conditions in pets.
Because no veterinary formulations are commercially available, the medication must be obtained from a compounding pharmacy under a veterinarian's prescription.
Mechanism of Action
Demecarium's pharmacological effect stems from its ability to inhibit cholinesterase enzymes, specifically both acetylcholinesterase and pseudocholinesterase. This inhibition prevents the rapid breakdown of acetylcholine, allowing this neurotransmitter to accumulate at cholinergic nerve endings.
In the eye, the accumulated acetylcholine leads to:
- Miosis: Contraction of the iris sphincter muscle, leading to pupil constriction.
- Ciliary Muscle Contraction: Spasm of the ciliary muscle, affecting the accommodation reflex and potentially causing near-sightedness.
This ciliary muscle contraction pulls on the trabecular meshwork, physically opening the outflow pathways for the aqueous humor. The resulting increased drainage lowers the intraocular pressure. The sustained inhibition of cholinesterase by Demecarium gives it its characteristic long-lasting effect, with pressure reduction lasting for one to several days.
Comparison of Demecarium and Pilocarpine
Demecarium and pilocarpine are both parasympathomimetic agents used to treat glaucoma, but they differ in several key respects:
| Feature | Demecarium (Indirect-acting) | Pilocarpine (Direct-acting) |
|---|---|---|
| Mechanism | Inhibits cholinesterase enzymes, leading to acetylcholine accumulation. | Directly stimulates muscarinic receptors. |
| Duration of Action | Long-acting, with effects lasting up to 48 hours in dogs, requiring less frequent dosing. | Shorter-acting, requiring more frequent administration to maintain its effect. |
| Availability | Not commercially available in the U.S. for human use; obtained via compounding pharmacies for veterinary use. | More readily available and widely used in veterinary and human medicine. |
| Effectiveness in Dogs | Sometimes used for managing glaucoma in dogs, and effectively used for prevention in the unaffected eye. | The most commonly used parasympathomimetic to treat primary glaucoma in dogs. |
| Tolerance | May be more irritating to the eye and has a higher risk of systemic side effects. | Better tolerated in some patients, though still associated with side effects like headache. |
Potential Side Effects and Risks
Like any potent medication, Demecarium can cause adverse effects, both ocular and systemic. Handlers of the medication, particularly if pregnant, should exercise caution.
Ocular Side Effects:
- Burning, stinging, and irritation upon application.
- Redness and tearing of the eyes.
- Decrease in pupil size (miosis), leading to decreased vision in poor light.
- Headache or brow ache due to ciliary muscle spasm.
- Induced nearsightedness (myopia).
- Iris cysts, especially in children, which typically resolve upon discontinuation.
- Rarely, retinal detachment, which can cause blindness.
Systemic Side Effects (rare):
- Nausea, vomiting, and abdominal cramps.
- Diarrhea and increased salivation.
- Excessive sweating.
- Muscle weakness and difficulty breathing.
- Cardiac irregularities, such as irregular heartbeat.
Conclusion
Demecarium is a long-acting cholinesterase inhibitor with a rich history in ophthalmic medicine, having been used to treat both human glaucoma and accommodative esotropia. While its branded form, Humorsol, is no longer available for human use, it remains a valuable tool in veterinary medicine for the long-term management and prevention of glaucoma in dogs. Its use, however, requires careful consideration of its potential side effects and availability exclusively through compounding pharmacies. The decision to use Demecarium in a veterinary setting should always be made in close consultation with a licensed veterinarian, weighing its benefits against the risks for the individual animal. For further pharmacological details, you can consult DrugBank.
