Miosis reversal

Dapiprazole acts by blocking die a-adrenergic receptor in smootii muscle and produces miosis through an effect on the dilator muscle of the iris. The drug is used primarily after ophtiialmic examinations to reverse the diagnostic mydriasis (dilation of the pupil). 

Patients who are acutely intoxicated with an opioid usually present with miosis, euphoria, slow breathing and slow heart rate, low blood pressure, and constipation. Seizures may occur with certain agents such as meperidine (Demerol ). It is critically important to monitor patients carefully to avoid cardiac/ respiratory depression and death from an excessive dose of opioids. One strategy is to reverse the intoxication by utilizing naloxone (Narcan ) 0.4 to 2 mg IV every 2 to 3 minutes up to 10 mg. Alternatively, the IM/SC route may be used if IV access is not available. Because naloxone is shorter-acting than most abused opioids, it may need to be readministered at periodic intervals otherwise the patient could lapse into cardiopulmonary arrest after a symptom-free interval of reversed... 

A 36-year-old male heroin addict is seen in the ED because he cannot be aroused from sleep On examination, he has shallow breathing and pinpoint pupils. Naloxone is administered, and the patient wakes up. Which of the opiate receptor subtypes that binds naloxone is responsible for reversing the respiratory depression and miosis ... 

Meperidine (Demerol) [C-ll] [Narcotic Analgesic] Uses Moderate/ severe pain Action Narcotic analgesic Dose Adults. 25-50 mg IV, 50-100 mg IM Peds. 1 mg/kg IV/IM (onset w/in 5 min IV and 10 min IM duration about 2 h) Caution [C, ] Contra Convulsive disorders and acute abdomen Disp Prefilled 1 mL syringes 25, 50, 75, 100 mg/mL various amps and vials oral syrup and tabs SE N/V (may be severe), dizziness, weakness, sedation, miosis, resp d ession, xerostomia (dry mouth) Interactions t CNS depression W/ opiates, sedatives/ hypnotics TCNS stimulation W/amphetamines t risk of tox W7 phenytoin EMS Pt should be receiving O2 prior to administration have resuscitation equipment and naloxone available naloxone can be used as an antidote to reverse resp depression aspirate prior to IM administration inadv tent IV admin of IM doses may cause tach and syncope mix w/ NS to make a 10 mg/mL soln and inj very slowly N/V may be sev e may premedicate w/ an antiemetic... 

X effects W/ carbamazepine, nelfmavir, phenobarbital, phenytoin, primidone, rifampin, ritonavir EMS Use CNS depressants w/ caution concurrent EtOH use can T resp depression, may T QT interval, monitor ECG OD May cause miosis, CNS and resp depression, hypotension, bradycardia, and CV collapse activated charcoal may be effective for PO form naloxone can be used give slowly and only give enough to reverse resp depression... 

Respiratory depression, miosis, hypotension, and coma are signs of morphine overdose. While the IV administration of naloxone reverses the toxic effects of morphine, naloxone has a short duration of action and must be administered repeatedly at 30- to 45minute intervals until morphine is cleared from the body. 

Symptoms of overdose with meperidine are qualitatively different from those of morphine in that seizures rather than sedation are common. Respiratory depression and miosis are present. While naloxone reverses overdose-associated toxicity, its use in patients who have received large, frequent doses of meperidine may precipitate seizures. 

Physostigmine (eserine sulfate) causes miosis and spasm of accommodation it also lowers intraocular pressure and hence can be used in the treatment of wide-angle glaucoma. As it is lipid soluble, it penetrates into the brain rapidly, raises the acetylcholine concentration and, in toxic amounts, may cause cholinergic CNS toxicity, which is characterized by restlessness, insomnia, tremors, confusion, ataxia, convulsions, respiratory depression, and circulatory collapse. These effects are reversed by atropine. 

Muscarinic cholinomimetics mediate contraction of the circular pupillary constrictor muscle and of the ciliary muscle. Contraction of the pupillary constrictor muscle causes miosis, a reduction in pupil size. Miosis is usually present in patients exposed to large systemic or small topical doses of cholinomimetics, especially organophosphate cholinesterase inhibitors. Ciliary muscle contraction causes accommodation of focus for near vision. Marked contraction of the ciliary muscle, which often occurs with cholinesterase inhibitor intoxication, is called cyclospasm. Ciliary muscle contraction also puts tension on the trabecular meshwork, opening its pores and facilitating outflow of the aqueous humor into the canal of Schlemm. Increased outflow reduces intraocular pressure, a very useful result in patients with glaucoma. All of these effects are prevented or reversed by muscarinic blocking drugs such as atropine. 

Actions Actions include generalized cholinergic stimulation, paralysis of motor function (causing breathing difficulties), and convulsions. Isoflurophate produces intense miosis and thus has found therapeutic use. Atropine in high dosage can reverse many of the muscarinic and central effects of isoflurophate. 

Ciguatera is the most famous seafood poisoning prevalent in circumtropical areas (Scheuer 1994). Its effects to human health and economic impacts are serious problems in those areas. The clinical symptoms are diverse. Neurological disturbances are prominent reversal of thermal sensation, called dry ice sensation, is one of the most characteristic symptoms of ciguatera. Other illnesses include joint pain, miosis, erethism, cyanosis, and prostration. 

Adapted from NRC (2003) with permission by the National Academy of Sciences, courtesy of the National Academies Press, Washington DC Mild miosis defined by Johns (1952) as decrease of 1 to 2 mm in pupil diameter reversible within 24 h. 

Dapiprazole was specifically developed for ocular use. After topical instillation it produces miosis and a reduction in lOP. Like thymoxamine, dapiprazole reverses mydriasis by blocking a receptors in the iris dilator muscle. Concentrations ranging from 0.12% to 1.5% significantly reduce pupil size in both normal and glaucomatous eyes. The miotic effect is concentration dependent and can last up to 6 hours after instillation. lOP can be reduced for up to 6 hours. In patients with decreased amplitude of accommodation associated with tro-picamide-induced cycloplegia, dapiprazole may partially increase the accommodative amplitude (Figure 8-5). This restoration of near vision seems to come from a combination of increasing depth of field due to pupillary recovery and an actual increase in accommodative amplitude independent of pupillary size. 

Unlike pilocarpine, dapiprazole appears to be a safe miotic for reversing phenylephrine-induced mydriasis. Moreover, the miosis is maintained long after the phenylephrine effect has dissipated. When instilled according to the manufacturer s recommendation of two drops followed 5 minutes later by two drops, dapiprazole can produce nearly complete reversal of phenylephrine-induced pupillary dilation. Studies reported that a single drop of dapiprazole has a clinical effect equivalent to the multiple-drop regimen. Dapiprazole was shown to increase the recovery rate of adequate pupillary dilation and accommodative function with the use of Paremyd more rapidly in mainly white subjects with light brown irides than in mainly black subjects with dark brown... 

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