What Is Pilocarpine?

Pilocarpine, for the treatment of primary glaucoma, including open-angle and closed-angle glaucoma. After eye drops, the pupil shrinkage effect appears for 10 ~ 30 minutes and maintains for 4 ~ 8 hours; the maximum IOP reduction effect appears within about 75 minutes and maintains for 4 ~ 14 hours; it can relieve or eliminate the symptoms of glaucoma. Compared with physostigmine, pilocarpine is mild and transient, and its aqueous solution is more stable. It can also be used for salivary gland hypofunction. Oral tablets (SALAGEN) can relieve xerostomia.

Drug type: Essential medicines
Drug name: Pilocarpine

English name: Pilocarpine
Chinese alias: Pilocarpine pilocarpine
English alias: Pilocar

Introduction of pilocarpine compounds

Pomegranate base information

Chinese name

Chinese alias: pilocarpine; pilocarpine; 4-[(l-methyl-1H-imidazol-5-yl) methyl] -3-ethyldihydro-2 (3H) -furanone

English name: (+)-pilocarpine

English alias: ocusertp20; PILOCARPINE; 2 (3H) -Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl) methyl]-, (3S-cis)-; pilokarpol; Pilocarpol;

CAS number: 92-13-7

Molecular formula: C ₁₁ H ₁₆ N ₂ O ₂

Molecular weight: 208.25700

Exact mass: 208.12100

PSA: 44.12000

LogP: 1.16180

Physiochemical properties of pilocarpine

Density: 1.22 g / cm ³

Boiling point: 260ºC at 5 MM HG (PARTIALºCONVERSION TO ISOPILºCARPINE)

Flash point: 215ºC

Oily liquid or crystal, MP34 , BP5 260 , refractive index: + 106 ° (C = 2), refractive index: + 100.5 ° (water). pK1 7.15; pK2 12.57 (20 °), soluble in water, ethanol, chloroform, hardly soluble in ether and benzene, hardly soluble in petroleum ether. Incompatible with silver salt, mercury dichloride, iodine, gold salt, tannin, mercury chloride, potassium permanganate, alkali, etc. Hydrochloride: colorless crystal or white crystalline powder, odorless, slightly bitter, easy to deteriorate when exposed to light. MP173.5-174.0 , refractive index: + 77 ° ~ + 83 ° (C = 10), soluble in water (1: 4), ethanol (1:75), insoluble in chloroform and ether, the aqueous solution showed litmus Acidic. Sealed and protected from light. It is incompatible with alkali, iodine, and dichlorophenformin hexane acetate. More than 1% of the solution is incompatible with benzalkonium. Racemate hydrochloride MP 208-209 ° C. MP of this product is 34 , BP5 is 260 , refractive index: + 100.5 ° (H2O). This product is hydrochloride crystal, MP 204-205 . Racemate hydrochloride MP 208-209 ° C.

Pilocarpine Safety Information

Packing level: III

Hazard category: 6.1 (b)

Dangerous Goods Transport Code: UN 1544

Danger category code: R26 / 28

Safety instructions: S25; S45

Dangerous goods mark: T + ^[1]

Pilocarpine Pharmacopoeia Standard

[Identification] (1) Take about 10mg of this product, add 2ml of water to dissolve, add 2 drops of potassium dichromate test solution, 1ml of hydrogen peroxide test solution and 2ml of chloroform, shake, the chloroform layer will become purple . (2) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 472). (3) Identification of nitrate in aqueous solution of this product (Appendix III).

[Inspection] Take 1.0g of this product, dissolve in 20ml of water, and divide into two parts: one drop of methyl red indicator solution should be red, and the other one should be 2 drops of bromophenol blue indicator solution. blue. Clarity and color of the solution take 0.5g of this product, add 10ml of fresh boiling cold water to dissolve, the solution should be clear and colorless; if it is turbid, compare with No. 1 turbidity standard solution (Appendix B), it must not be more concentrated ; If the color is developed, it must not be deeper than the yellow colorimetric standard colorimetric solution (Appendix A, the first method). Take 0.10g of this product, add 5ml of water to dissolve it, add dilute nitric acid to make it acidic, and add a few drops of silver nitrate test solution, no immediate turbidity. For other alkaloids, take 0.2g of this product, dissolve it in 20ml of water, and divide into two parts: one drop of ammonia test solution and a few drops of potassium chromate test solution, no turbidity should occur. Take 10mg of this product easily, add 1ml of sulfuric acid and 0.5ml of nitric acid to dissolve, the solution should be colorless. Take this product for weight loss, and dry it at 105 to constant weight. The weight loss should not exceed 0.5% (Appendix L). The ignition residue shall not exceed 0.1% (Appendix N).

[Content determination] Take about 0.2g of this product, weigh it accurately, add 30ml of glacial acetic acid, dissolve it with a little heat, let it cool, according to potentiometric titration (Appendix A), use perchloric acid titration solution (0.1mol / L ) Titrate and correct the results of the titration with a blank test. Per ml of perchloric acid titration solution (0.1 mol / L) is equivalent to 27.13 mg of C11H16N2O2 · HNO3

[Category] miotic drugs.

[Storage] shading and sealed.

Pilocarpine medicine description

Pilocarpine pharmacology

Selective action directly on M choline receptors. It has the most obvious effect on eyes and glands. cause contraction of the pupil, decrease of intraocular pressure, and have the effect of regulating spasm. By activating the M choline receptors of the pupil sphincter, the pupil sphincter is contracted. Anterior chamber angle gap is enlarged due to contraction of the pupil, aqueous humor is easy to return, and intraocular pressure is reduced. Due to the contraction of the ciliary muscle and the relaxation of the suspensory ligament, the refractive power of the lens increases, so the near and clear objects are clear, and the distant objects are blurred, which is called regulating spasm. Increase exocrine gland secretion. It has the most obvious effect on sweat glands and salivary glands, and it can still increase the secretion of tear fluid, gastric fluid, pancreatic fluid, intestinal fluid and mucous cells of the respiratory tract. Causes intestinal smooth muscle excitement, increased muscle tone, and increased bronchial smooth muscle, urethra, bladder and biliary tract muscle tension.

Pilocarpine pharmacokinetics

Pilocarpine has two-phase solubility in water and fat, so its eye drops have good permeability. 1% eye drops have a miotic effect 10 to 30 minutes after the eye drops, lasting for more than 4 to 8 hours. The peak time of the IOP lowering effect is about 75 minutes, which lasts 4 to 14 hours (depending on the concentration). The peak time of the hypotensive effect of the ophthalmic film is 1.5 to 2 hours. Food can reduce the absorption rate and range of pilocarpine. When used to alleviate the symptoms of dry mouth, it takes effect in 20 minutes, the effect of single use lasts 3 to 5 hours, and the continuous use can last more than 10 hours. The elimination half-life of the parent compound is 0.76 to 1.35h. Pilocarpine may be inactivated at the synapses of neurons, and it is also likely to be inactivated in plasma. Pilocarpine and its inactive metabolites are excreted with urine ^[2] .

Pilocarpine drug interactions

1. This product has a synergistic effect when used in combination with beta blockers, carbonic anhydrase inhibitors, alpha and beta adrenergic receptor agonists or hypertonic dehydrating agents.

2. Combining this product with latanoprost can reduce the amount of aqueous humor flowing through the uveal sclera and reduce the effect of lowering intraocular pressure.

3. Combination with local anticholinergic drugs will interfere with the effect of this product. Combination with an appropriate amount of systemic anticholinergic drugs, because the concentration of systemic drugs reaching the eye is very low, usually does not affect the intraocular pressure lowering effect of this product.

Pilocarpine indication

Treatment of primary glaucoma, including open-angle and closed-angle glaucoma. After eye drops, the pupil shrinkage effect appears for 10 ~ 30 minutes and maintains for 4 ~ 8 hours; the maximum IOP reduction effect appears within about 75 minutes and maintains for 4 ~ 14 hours; it can relieve or eliminate the symptoms of glaucoma. Compared with physostigmine, pilocarpine is mild and transient, and its aqueous solution is more stable. It can also be used for salivary gland hypofunction. Oral tablets (SALAGEN) can relieve xerostomia.

Pilocarpine usage and dosage

1. Chronic glaucoma, 0.5% to 4% solution 1 drop at a time, 1 to 4 times a day.

2. During acute exacerbation of acute angle-closure glaucoma, 1 drop of 1% to 2% solution, one drop every 5 to 10 minutes, and one drop every 1 to 3 hours after 3 to 6 times, until the intraocular pressure drops. (Note: The contralateral eye drops every 6 to 8 hours to prevent the onset of angle-closure glaucoma in the contralateral eye).

3. Mydriasis: Antimydriatic effect, 1% solution eye drops 1 to 2 or 3 times; congenital glaucoma atrial incision or external trabeculotomy, 1% solution, general eye drops 1 or 2 times ; Before iris resection, 2% solution, 1 drop at a time.

Medicine for pregnant and lactating women: The safety of this product for pregnant and lactating women has not been determined, so it should be used with caution.

Medication for children: Children should use this product with caution, because children with light weight and easily overdose can cause systemic poisoning ^[3] .

Pilocarpine adverse reactions

(1) Pupil shrinkage and adjustment of convulsions can occur after medication, which can reduce vision, produce temporary myopia, and can cause eye pain, eyebrow arch pain and other symptoms.

(2) Long-term use can cause ankylosing pupil reduction, posterior iris adhesion, iris cyst, cataract, and deepening of myopia.

(3) Frequent eye contact can cause systemic toxic reactions due to excessive absorption, such as sweating, salivation, nausea, vomiting, bronchospasm and pulmonary edema.

Eye reactions usually occur early in the treatment and disappear during the treatment. Elderly and opaque lens suffer from vision loss in poorly lit situations. There are rare reports of retinal detachment after the use of a migraine.

Pilocarpine contraindications

It is contraindicated in elderly patients with cataract, retinal detachment, acute conjunctivitis and keratitis, acute iritis, bronchial asthma, gastric ulcer and other patients.

Pilocarpine notes

1. Pupil shrinkage often causes difficulty in dark adaptation. Patients who need to drive at night or engage in dangerous occupations with poor lighting should be advised to be especially careful.

2. Check your intraocular pressure regularly. If there is a change in vision, check the vision, visual field, tonometry, and angle of the room, etc., and change the medication and treatment plan according to the change of the condition.

3. To avoid systemic adverse reactions caused by excessive absorption, compress the lacrimal sac with your fingers for 1 to 2 minutes after eye drops.

4. If you take it by accident, you need to induce vomiting or gastric lavage; if there is a systemic toxic reaction caused by excessive absorption, atropine anticholinergics should be used for anti-treatment.

Pilocarpine poisoning

Pilocarpine (Pilocarpine) is an M-choline receptor agonist, which directly activates the M-choline receptor and shrinks the pupil; it also has the effects of contracting smooth muscle, sweating, salivation, etc. After absorption, the effect is wide and complex, with many side effects. Clinically, it is only used for local eye drops to treat glaucoma. When dropping the eye, the internal constriction should be compressed to prevent the medicinal solution from flowing into the nasal cavity and absorbing it, causing systemic M cholinergic effects. The produced cholinergic effects of M can be countered by atropine.

Pilocarpine preparation

Eye drops: 1%; 2%. Tablet (ASLAGEN): 5mg per tablet. Injection: 2mg (1ml) each.

^[4-7] Zhang Ye, editor. Acute poisoning [M]. Xi'an: Fourth Military Medical University Press, 2008: 112.

Pilocarpine expert review

Pilocarpine is often used in neurology for some patients with myopathy and more for ophthalmology. Pilocarpine is a post-holiday pseudocholine drug that can directly excite M cholinergic receptors and contract the pupil sphincter. Mydriasis occurs in 10 to 30 minutes and is maintained for 4 to 8 hours. Anterior chamber angle gap is enlarged due to contraction of the pupil, aqueous humor is easy to circulate, and intraocular pressure is decreased. The maximum IOP lowering effect occurred in about 75 minutes and maintained for 4 to 14 hours. Pilocarpine has many side effects after absorption, and is highly toxic. It is clinically limited to eye drops. It is mainly used for the treatment of chronic simple glaucoma, angle-closure glaucoma, antagonizing pupil dilation, regulatory esotropia, anterior chamber hemorrhage, etc. It is used to combat the mydriatic effect of atropine ^[2] .