Cyclopentolate

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Cyclopentolate
Cyclopentolate.png
Clinical data
Pregnancy
category
  • C
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administration
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ATC code
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Identifiers
  • (RS)-2-(dimethylamino)ethyl (1-hydroxycyclopentyl)(phenyl)acetate
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Chemical and physical data
Formula C17H25NO3
Molar mass 291.391 g·mol−1
3D model (JSmol)
  • O=C(OCCN(C)C)C(c1ccccc1)C2(O)CCCC2
  • InChI=1S/C17H25NO3/c1-18(2)12-13-21-16(19)15(14-8-4-3-5-9-14)17(20)10-6-7-11-17/h3-5,8-9,15,20H,6-7,10-13H2,1-2H3 Yes check.svgY
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Cyclopentolate is a muscarinic antagonist. [2] It is commonly used as an eye drop during pediatric eye examinations to dilate the eye (mydriatic) and prevent the eye from focusing/accommodating (cycloplegic). Cyclopentolate[ citation needed ] or atropine can also be administered to reverse muscarinic and central nervous system effects of indirect cholinomimetic (anti-AChase) administration.

Contents

It is on the World Health Organization's List of Essential Medicines. [3]

After instillation of cyclopentolate, pupil dilation (mydriasis) typically lasts up to 24 hours, while paralysis of the ciliary muscle (cycloplegia) typically lasts 6-24 hours. [4] During this time, patients may be more light sensitive than normal and may notice close objects blurred (and possibly distant objects blurred, depending on the patient's visual system). Cyclopentolate is often chosen as a milder, shorter-lasting, cycloplegic alternative to atropine, another cycloplegic agent which lasts much longer. Tropicamide is an even shorter-lasting cycloplegic than cyclopentolate, but is less reliable for finding latent hyperopia. Cyclopentolate drops act rapidly to dilate the pupil. [5]

The side and adverse effects of cyclopentolate are similar to the side and adverse effects of other anticholinergic medications. Because of that, extra caution should be taken when prescribing cyclopentolate to patients who are already taking other anticholinergic drugs. A possible ocular (eye-related) side effect is increase in pressure inside the eye, which is of particular concern when there is a predisposition toward or a presence of glaucoma. Other ocular side effects can include burning sensations, discomfort with bright light (photophobia), blurred vision, irritation, inflammation of the eye mucous membranes (conjunctivitis), inflammation of the cornea of the eye (keratitis), and other issues. Nonocular (not eye-related) side and adverse effects can include neuropsychiatric symptoms. [6] like subtle concentration and memory problems, subtle decision-making problems, drowsiness, and more pronounced disorientation to time and place, confusion, disturbances of speech and movement, hyperactivity, restlessness, and seizures. Temporary psychosis [7] can develop that includes hallucinations, particularly when higher doses are used in children or older adults [8] on other anticholinergic medications. [9] Patients with dementia of the Alzheimer's type can experience worsening of their dementia symptoms. Additional side and adverse effects can include skin flushing, skin rashes, gastrointestinal problems, increased heart beat (tachycardia), increased body temperature (hyperpyrexia), blood vessel dilation, urinary retention, dry mouth and reduced sweating, and reduced bronchial secretions. Severe poisoning with cyclopentolate may result in coma, paralysis of breathing, and death. Cyclopentolate derivatives can be used as an antidote for organophosphate poisoning. [10] [11] [12] [13] [14]

Lethality of cyclopentolate has been studied in rodents. The LD50 (the dose at which 50% of animals die from the drug) is approximately 4000 mg/kg in rats and 960 mg/kg in mice. Readily recognizable symptoms of overdose include tachycardia, dizziness, dry mouth, behavioral disturbances, uncoordination, and drowsiness.

Cycloplegia is necessary in cases of suspected latent hyperopia (or "over-focusing") so that an ophthalmologist or optometrist can accurately measure how much a person has to flex their focusing muscle (accommodation) in order to see in the distance and up-close. Correction of latent hyperopia in children can often prevent, or sometimes correct, unwanted eye turns (strabismus), some forms of refractive amblyopia, and may alleviate eye strain or frontal headaches caused by prolonged near-work. Cycloplegia is also helpful in relieving accommodative spasm.

History

Cyclopentolate was first synthesized in 1952 as a chemical analogue of atropine. It was one of several derivatives of an analogue to tropic acid which were tested for pharmacological action "in a search for new and better antispasmodic agents." [15]

Brand names for cyclopentolate include Cyclogyl, Cylate, Mydrilate, and Pentolair. [16]

Pupil dilation (mydriasis) caused by cyclopentolate 1% instilled into both eyes Cyclopentolate 1 percent Pupils.jpg
Pupil dilation (mydriasis) caused by cyclopentolate 1% instilled into both eyes

Related Research Articles

<span class="mw-page-title-main">Atropine</span> Anticholinergic medication used as antidote for nerve agent poisoning

Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle. Eye drops are also available which are used to treat uveitis and early amblyopia. The intravenous solution usually begins working within a minute and lasts half an hour to an hour. Large doses may be required to treat some poisonings.

<span class="mw-page-title-main">Mydriasis</span> Excessive dilation of the pupil

Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drug. It may also be of unknown cause.

<span class="mw-page-title-main">Farsightedness</span> Eye condition in which light is focused behind instead of on the retina

Far-sightedness, also known as long-sightedness, hypermetropia, and hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blur is due to incoming light being focused behind, instead of on, the retina due to insufficient accommodation by the lens. Minor hypermetropia in young patients is usually corrected by their accommodation, without any defects in vision. But, due to this accommodative effort for distant vision, people may complain of eye strain during prolonged reading. If the hypermetropia is high, there will be defective vision for both distance and near. People may also experience accommodative dysfunction, binocular dysfunction, amblyopia, and strabismus. Newborns are almost invariably hypermetropic, but it gradually decreases as the newborn gets older.

Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation. Because of the paralysis of the ciliary muscle, the curvature of the lens can no longer be adjusted to focus on nearby objects. This results in similar problems as those caused by presbyopia, in which the lens has lost elasticity and can also no longer focus on close-by objects. Cycloplegia with accompanying mydriasis is usually due to topical application of muscarinic antagonists such as atropine and cyclopentolate.

Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.

<span class="mw-page-title-main">Pilocarpine</span> Medication used to treat glaucoma and dry mouth

Pilocarpine is a lactone alkaloid originally extracted from plants of the Pilocarpus genus. It is used as a medication to reduce pressure inside the eye and treat dry mouth. As an eye drop it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to constrict the pupil after dilation. However, due to its side effects, it is no longer typically used for long-term management. Onset of effects with the drops is typically within an hour and lasts for up to a day. By mouth it is used for dry mouth as a result of Sjögren syndrome or radiation therapy.

<span class="mw-page-title-main">Prednisolone</span> Corticosteroid medication

Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthritis, dermatitis, eye inflammation, asthma, and multiple sclerosis. It can be taken by mouth, injected into a vein, used topically as a skin cream, or as eye drops. It differs from the similarly named prednisone in having a hydroxyl at the 11th carbon instead of a ketone.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Uveitis</span> Inflammation of the uvea of the eye

Uveitis is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is described anatomically, by the part of the eye affected, as anterior, intermediate or posterior, or panuveitic if all parts are involved. Anterior uveitis (iridocyclitis) is the most common, with the incidence of uveitis overall affecting approximately 1:4500, most commonly those between the ages of 20–60. Symptoms include eye pain, eye redness, floaters and blurred vision, and ophthalmic examination may show dilated ciliary blood vessels and the presence of cells in the anterior chamber. Uveitis may arise spontaneously, have a genetic component, or be associated with an autoimmune disease or infection. While the eye is a relatively protected environment, its immune mechanisms may be overcome resulting in inflammation and tissue destruction associated with T-cell activation.

<span class="mw-page-title-main">Eye examination</span> Series of tests assessing vision and pertaining to the eyes

An eye examination, commonly known as an eye test, is a series of tests performed to assess vision and ability to focus on and discern objects. It also includes other tests and examinations pertaining to the eyes. Eye examinations are primarily performed by an optometrist, ophthalmologist, or an orthoptist. Health care professionals often recommend that all people should have periodic and thorough eye examinations as part of routine primary care, especially since many eye diseases are asymptomatic.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among numerous others, is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, applied to the skin, or as a rectal suppository.

<span class="mw-page-title-main">Eye drop</span> Liquid applied directly to the eye

Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline and sometimes a lubricant are often used as artificial tears to treat dry eyes or simple eye irritation such as itching or redness. Eye drops may also contain one or more medications to treat a wide variety of eye diseases. Depending on the condition being treated, they may contain steroids, antihistamines, sympathomimetics, beta receptor blockers, parasympathomimetics, parasympatholytics, prostaglandins, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, antifungals, or topical anesthetics.

Diphenoxylate/atropine, also known as co-phenotrope, is a combination of the medications diphenoxylate and atropine, used to treat diarrhea. It should not be used in those in whom Clostridioides difficile infection is a concern. It is taken by mouth. Onset is typically within an hour.

<span class="mw-page-title-main">Tropicamide</span> Chemical compound

Tropicamide, sold under the brand name Mydriacyl among others, is a medication used to dilate the pupil and help with examination of the eye. Specifically it is used to help examine the back of the eye. It is applied as eye drops. Effects occur within 40 minutes and last for up to a day.

<span class="mw-page-title-main">4-Hydroxyamphetamine</span> Group of stereoisomers

Hydroxyamphetamine, also known as 4-hydroxyamphetamine or norpholedrine and sold under the brand names Paredrine and Paremyd among others, is a sympathomimetic medication used in eye drops to dilate the pupil for eye examinations.

<span class="mw-page-title-main">Homatropine</span> Medication

Homatropine is an anticholinergic medication that is an antagonist at muscarinic acetylcholine receptors and thus the parasympathetic nervous system. It is used in eye drops as a cycloplegic, and as a mydriatic.

<span class="mw-page-title-main">Dilated fundus examination</span> Method of viewing the interior of the eye

Dilated fundus examination (DFE) is a diagnostic procedure that uses mydriatic eye drops to dilate or enlarge the pupil in order to obtain a better view of the fundus of the eye. Once the pupil is dilated, examiners use ophthalmoscopy to view the eye's interior, which makes it easier to assess the retina, optic nerve head, blood vessels, and other important features. DFE has been found to be a more effective method for evaluating eye health when compared to non-dilated examination, and is the best method of evaluating structures behind the iris. It is frequently performed by ophthalmologists and optometrists as part of an eye examination.

Pseudomyopia occurs when a spasm of the ciliary muscle prevents the eye from focusing in the distance, sometimes intermittently; this is different from myopia which is caused by the eye's shape or other basic anatomy. Pseudomyopia may be either organic, through stimulation of the parasympathetic nervous system, or functional in origin, through eye strain or fatigue of ocular systems. It is common in young adults who have active accommodation, and classically occurs after a change in visual requirements, such as students preparing for an exam, or a change in occupation.

A spasm of accommodation is a condition in which the ciliary muscle of the eye remains in a constant state of contraction. Normal accommodation allows the eye to "accommodate" for near-vision. However, in a state of perpetual contraction, the ciliary muscle cannot relax when viewing distant objects. This causes vision to blur when attempting to view objects from a distance. This may cause pseudomyopia or latent hyperopia.

<span class="mw-page-title-main">Cholinergic blocking drug</span> Drug that block acetylcholine in synapses of cholinergic nervous system

Cholinergic blocking drugs are a group of drugs that block the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and muscarinic receptors.

References

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  2. "Cyclopentolate". Drug Bank. Retrieved June 15, 2012.
  3. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  4. Bartlett JD, Jaanus SD, eds. (2008). "Chapter 9: Cycloplegics. Table 9-1: Mydriatic and Cycloplegic Properties of Anticholinergic Agents". Clinical Ocular Pharmacology (5th ed.). Saint Louis: Butterworth Heinemann - Elsevier. p. 127. ISBN   978-0-7506-7576-5.
  5. "Cyclogyl Eye Drops Medsafe data sheet New Zealand" (PDF). 11 January 2017. Retrieved 3 June 2017.
  6. Derinoz O, Er A (January 2012). "Inability to walk, disequilibrium, incoherent speech, disorientation following the instillation of 1% cyclopentolate eyedrops: case report". Pediatric Emergency Care. 28 (1): 59–60. doi:10.1097/PEC.0b013e3182417a63. PMID   22217890.
  7. Rajappa N, Patra S, Bhalsing S, Lune AA (January 2014). "A case of acute psychosis induced by topical cyclopentolate eye drops in an elderly patient". Medical Journal of Dr. D.Y. Patil University. 7 (1): 68–69. doi: 10.4103/0975-2870.122789 .
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  9. Carpenter WT (October 1967). "Precipitous mental deterioration following cycloplegia with 0.2 percent cyclopentolate HCl". Archives of Ophthalmology. 78 (4): 445–447. doi:10.1001/archopht.1967.00980030447006. PMID   6046837.
  10. Bryant SM, Rhee JW, Thompson TM, Lu JJ, Aks SE (2009). "Parenteral ophthalmic tropicamide or cyclopentolate protects rats from lethal organophosphate poisoning". American Journal of Therapeutics. 16 (3): 231–234. doi:10.1097/MJT.0b013e318182254b. PMID   19454862. S2CID   36599696.
  11. Bauer CR, Trottier MC, Stern L (March 1973). "Systemic cyclopentolate (Cyclogyl) toxicity in the newborn infant". The Journal of Pediatrics. 82 (3): 501–505. doi:10.1016/s0022-3476(73)80134-9. PMID   4698940.
  12. Fitzgerald DA, Hanson RM, West C, Martin F, Brown J, Kilham HA (April 1990). "Seizures associated with 1% cyclopentolate eyedrops". Journal of Paediatrics and Child Health. 26 (2): 106–107. doi:10.1111/j.1440-1754.1990.tb02399.x. PMID   2113819. S2CID   20030473.
  13. Bhatia SS, Vidyashankar C, Sharma RK, Dubey AK (March 2000). "Systemic toxicity with cyclopentolate eye drops". Indian Pediatrics. 37 (3): 329–331. PMID   10750080.
  14. Ozgun U, Demet T, Ozge KA, Zafer D, Murat S, Mehmet Y, Nilgun K (May 2014). "Fatal necrotising enterocolitis due to mydriatic eye drops". Journal of the College of Physicians and Surgeons--Pakistan. 24 (Suppl 2): S147–S149. PMID   24906272.
  15. Treves GR, Testa FC (1952). "Basic Esters and Quaternary Derivatives of β-Hydroxy Acids as Antispasmodics1". Journal of the American Chemical Society. 74 (1): 46–48. doi:10.1021/ja01121a012. ISSN   0002-7863.
  16. "cyclopentolate hydrochloride solution - ophthalmic, Cyclogyl, Cylate, Pentolair" . Retrieved June 15, 2012.

Further reading