1) 0.5, 1, and 2 mg tablets
2) 1 mg/mL injection

1) 2 mg tablet
2) 5 mg/mL injection

1) 50 mg tablet

1) 100 mg tablet
2) 60 mg/2 mL injection

1) 5 mg tablet

1) 2 and 5 mg tablets
2) 5 mg sustained release capsule
3) 2 mg/5 mL elixir

1) 50 mg tablet

1) 10 mg dragees
2) 20 mg/mL injectable
3) 7.5 mg, 10 mg suppositories

1) 2.5 and 5 mg capsules

1) 20 mg tablet
2) 10 mg capsules
3) 10 mg/5mL syrup
4) 10 mg/mL injection

1) 2% cream and powder

1) 1 and 2 mg tablets
2) 0.2 mg/mL injectable

1) 25 mg tablet

1) 5 mg tablet

1) 25 mg tablet

1) 50 mg tablet

1) 2.5 mg tablet

1) 10 mg tablet

1) 5 mg tablet

1) 7.5 and 15 mg tablets

1) 5 mg, 15 mg, 30 mg tablets
2) 0.6 mg/mL injectable
3) 0.75 mg and 1.0 mg suppositories

1) 4 mg or 8 mg extended-release tablets

1) 100 mg tablet

1) 5 mg tablet
2) 5 mg/5 mL syrup

1) 5 mg light yellow film-coated tablet and 10 mg light pink film-coated tablet

1) 1 and 2 mg tablets

1) 0.5, 1, and 2% solutions

1) 2 and 5% solutions

1) 0.5 and 1% solutions

1) 15 mg tablet (0.187 mg alkaloids/tablet)

1) 27 to 33 mg alkaloids/100 mL

1) 0.4 and 0.6 mg tablets
2) 0.05, 0.1, 0.3, 0.4, 0.5, 0.8, and 1 mg/mL injectable
3) 2 mg prefilled automatic injection device
4) 0.5 and 1% ophthalmic ointment
5) 0.5, 1 and 2% ophthalmic solutions
6) 0.2 and 0.5% solution for inhalation

1) 0.125 and 0.15 mg tablets
2) 0.375 mg sustained release capsule
3) 0.125 mg/mL oral drops
4) 0.125 mg/5mL elixir
5) 0.5 mg/mL injectable

1) 0.25 mg tablet

1) 0.3, 0.4, 0.86, and 1 mg/mL injection
2) 0.25% ophthalmic solution
3) 0.25 mg capsule
4) 1.5 mg transdermal patch, designed to release a loading dose followed by a total of 0.5 mg over 72 hours or approximately 5 micrograms/hour. Theoretically, cutting of the patch may disrupt the sustained release mechanism and lead to an immediate release of toxic quantities of scopolamine.

1) 10 mg tablet
2) 5 mg/5 mL oral solution
3) 5 and 10 mg suppository
4) 20 mg/mL injection
5) 6.67 mg/mL oral drops

1) 18 mcg/dose metered dose inhaler (14 gram canister contains 200 inhalations)
2) 500 mcg/vial (0.02%) solution for inhalation

1) 25 mg tablet

1) Atropa belladonna
2) Brugmansia arborea
3) Brugmansia suaveolens
4) Cestrum diurnum
5) Cestrum nocturnum
6) Cestrum parqui
7) Datura metel
8) Datura stramonium
9) Hyoscyamus niger
10) Lantana camara
11) Lycium halimifolium
12) Solandra species

a) Hyperthermia occurs more commonly than hypothermia.

a) ATROPINE/CASE REPORT (CHILD): Temperatures of 34 degrees C and 34.4 degrees C were reported in a 14-year-old boy 1 to 2 hours after a total dose of atropine sulfate 0.8 mg intravenously on 2 separate occasions (Lacouture et al, 1983).

a) ATROPINE/CASE REPORT (ADULT): A 65-year-old man who accidentally ingested approximately 3 mg of atropine subsequently developed facial warmth and flushness, restlessness, hyperactivity, dry tongue and mouth, speech dysphasia, and hypothermia. Blood pressure was 190/100 mmHg and pupils were dilated with hypertonicity of limbs and reflexes. Following treatment with chlorpromazine and paraldehyde, the patient became calm and after 24 hours was fully oriented and relaxed (Wood & Haq, 1971).

a) ATROPINE/CASE REPORT: Three children overdosed with atropine developed anticholinergic effects including tachycardia of 130 to 150 beats/min. The majority of signs and symptoms and rapid pulse rate resolved after 48 hours (Arthurs & Davies, 1980a).
b) ORPHENADRINE/CASE REPORT: A 2-year-old child presented with seizures and a rapid, irregular pulse of approximately 180 beats/min after ingesting 28 orphenadrine tablets. Symptoms resolved several days later following supportive treatment (Stoddart et al, 1968).

a) HOMATROPINE/CASE REPORT (CHILD): An 11-year-old child experienced widely dilated pupils, as well as ataxia, visual hallucinations, flushed face, and dry mouth, after the instillation of homatropine hydrobromide 2% ophthalmic solution, 1 drop in each eye 6 times at 10-minute intervals. Signs and symptoms resolved 24 hours later following supportive treatment (Hoefnagel, 1961).

a) TRANSDERMAL SCOPOLAMINE: Unilateral and bilateral pupillary dilation and impaired visual acuity have been described in patients who accidentally contaminated their eye or contact lenses after using a transdermal scopolamine patch. These effects were transient, gradually improving over 2 to 3 days (Thiele & Riviello, 1995; Rubin et al, 1990; Hughes & Zaloga, 1989; Patterson et al, 1986; Price, 1985; McCrary & Webb, 1982).
b) Leakage from a mask nebulizing salbutamol and ipratropium and exposure to an anti-rash powder containing 2% diphemanil methylsulphate have been implicated in causing unilateral dilated pupils (Silbert & Edis, 1991; Helprin & Clarke, 1986).
c) ATROPINE/CASE REPORT: A 7-year-old child was given aerosolized albuterol with atropine, via a mask, to treat asthma. The mask was slightly angled away from his face, allowing the mist to pass over his left eye. One hour later, the patient developed anisocoria. The atropine was then discontinued from his aerosol treatments, and the anisocoria resolved 40 hours later (Nakagawa et al, 1993).
d) PROPANTHELINE/CASE REPORT: Two women presented with unilateral mydriasis after using propantheline bromide lotion as an antiperspirant and getting some in the affected eye. The dilation disappeared after a few days (Nissen & Nielsen, 1977).
e) SCOPOLAMINE/CASE REPORT: A 55-year-old man developed mydriasis and ocular hypertension that lasted for 6 weeks following occupational exposure to dust of a scopolamine-related test agent (Muttray et al, 1994).

a) ATROPINE/CASE REPORT: Two patients developed unilateral angle closure glaucoma after receiving aerosolized atropine to treat COPD. Both patients were treated with pilocarpine to reduce the pressure, followed by laser iridotomy after stabilization (Berdy et al, 1991).
b) IPRATROPIUM: Bilateral closed-angle glaucoma has been reported in patients receiving ipratropium by nebulization. Use of a tight-fitting mask, properly placed to avoid eye contact, or use of a spacer device has been suggested to avoid absorption of the drug across the cornea (Mulpeter et al, 1992; Packe et al, 1984; Malani et al, 1982) .
c) TIOTROPIUM: A 46-year-old man developed acute closed-angle glaucoma of his right eye approximately 4 hours after touching his eye with the contents of a capsule containing tiotropium. The intraocular pressures of his right and left eye were 42 mmHg and 14 mmHg, respectively, and a gonioscopic exam of his right eye showed narrow iridocorneal angle. Treatment with acetazolamide, pilocarpine 1% eye drops, and mannitol 20% infusion resolved all signs and symptoms within 12 hours (Oksuz et al, 2007).

a) CLIDINIUM: Mild mydriasis and persistent sinus tachycardia were reported in a 24-year-old man following 2 overdose ingestions, separated by 90 minutes, of a combination medication containing chlordiazepoxide 5 mg and clidinium 2.5 mg (amounts ingested per overdose: chlordiazepoxide 50 mg and clidinium 25 mg). With supportive care, the patient recovered and was discharged without sequelae (Richardson & Edwards, 2009).

a) Dry mouth and skin are common adverse anticholinergic effects that are dose-related (Muttray et al, 2012; Gregory et al, 2010; Myers et al, 1997; Boyd et al, 1997; Handerhan, 1994; Boyson, 1988) .

a) Hypertension is common and may be delayed in onset.
b) ATROPINE/CASE REPORT: A 65-year-old man who accidentally ingested approximately 3 mg of atropine subsequently developed facial warmth and flushness, restlessness, hyperactivity, dry tongue and mouth, speech dysphasia, and hypothermia. Blood pressure was 190/100 mmHg and pupils were dilated with hypertonicity of limbs and reflexes. Following treatment with chlorpromazine and paraldehyde, the patient became calm and after 24 hours was fully oriented and relaxed (Wood & Haq, 1971).
c) ATROPINE/CASE REPORT: A 36-year-old woman experienced hypertension (150/100 mmHg), tachycardia, visual hallucinations, and confusion after ingesting Indian tonic water. Analysis of the tonic water revealed that it contained substantial quantities of atropine (Boyd et al, 1997).
d) OXYBUTYNIN/CASE REPORT: A 34-year-old woman experienced hypertension and tachycardia after ingesting 100 mg of oxybutynin. Seventy-two hours later, signs resolved with supportive treatment (Banerjee et al, 1991).
e) SCOPOLAMINE-TAINTED HEROIN: Hypertension and tachycardia were reported in several patients following insufflation of scopolamine-tainted heroin (Perrone et al, 1999; Hamilton et al, 1995).

a) Peripheral cutaneous vasodilatation (facial flushing) may occur.
b) ATROPINE/CASE REPORT: A 65-year-old man who accidentally ingested approximately 3 mg of atropine subsequently developed facial warmth and flushness, restlessness, hyperactivity, dry tongue and mouth, speech dysphasia, and hypothermia. Blood pressure was 190/100 mmHg and pupils were dilated with hypertonicity of limbs and reflexes. Following treatment with chlorpromazine and paraldehyde, the patient became calm and after 24 hours was fully oriented and relaxed (Wood & Haq, 1971).
c) DIPHENIDOL/CASE SERIES: A retrospective analysis of diphenidol overdoses reported that facial flushing was a common toxic effect that occurred in 10 of 21 patients following diphenidol overdose ingestions. All patients recovered within 12 hours (Yang & Deng, 1998).
d) HYOSCYAMINE/CASE SERIES: Flushed skin occurred in 5 infants following overdose ingestions of hyoscyamine to treat colic (Myers et al, 1997).

a) DIPHENIDOL/CASE REPORT (CHILD): Hypotension occurred in a 2-year-old child approximately 2 hours after ingesting 225 mg of diphenidol. The child also experienced tachycardia, recurrent seizures, respiratory failure, and deep coma. He subsequently died due to profound shock, despite aggressive supportive measures (Yang & Deng, 1998).

a) Tachycardia is a common anticholinergic effect and may be cyclical and delayed in onset (Joseph et al, 1991; Arthurs & Davies, 1980; Adcock, 1971; Hoefnagel, 1961).
b) HOMATROPINE/CASE REPORT (ADULT): Topical homatropine eyedrops were the implicated cause of tachycardia (160 to 180 beats/min) and syncope in an 84-year-old woman. Attacks of symptoms occurred within 1 hour of instilling the drops (Reid & Fulton, 1989).

a) Tachycardia is a common anticholinergic effect and may be cyclical and delayed in onset (Joseph et al, 1991; Arthurs & Davies, 1980; Adcock, 1971; Hoefnagel, 1961).
b) DIPHENIDOL/CASE SERIES: Tachycardia was reported in 6 children following diphenidol overdose ingestions ranging from 25 mg to 800 mg. In most cases, recovery occurred following supportive care (Yang & Deng, 1998).
c) HYOSCYAMINE/ CASE SERIES: Tachycardia (heart rates ranging from 155 beats/min to 220 beats/min) occurred in 5 infants who were given hyoscyamine sulfate in overdose amounts of 2 to 4 mL (1 dropperful is equivalent to 1 mL or 20 drops) to treat colic. The patients recovered within 24 hours following supportive care (Myers et al, 1997).
d) ATROPINE: Sinus tachycardia was reported in a child and an adult after drinking Indian tonic water. Analysis of a sample of the Indian tonic water showed that it contained substantial quantities of atropine (Boyd et al, 1997).
e) ORPHENADRINE/ CASE REPORT (CHILD): A 2-year-old child presented with seizures and a rapid, irregular pulse of approximately 180 beats/min with associated hypotension (50 systolic) after ingesting 28 orphenadrine tablets. Symptoms resolved several days later following supportive treatment (Stoddart et al, 1968).
f) SCOPOLAMINE-TAINTED HEROIN: Tachycardia and hypertension were reported in several people following insufflation of scopolamine-tainted heroin (Perrone et al, 1999; Hamilton et al, 1995).
g) TIOTROPIUM: A 74-year-old man with a history of COPD, atrial fibrillation, and renal insufficiency who was taking tiotropium 18 mcg daily as part of his medication regimen presented to a hospital with dyspnea and tachycardia (130 beats/min). After hospital admission, he received metoprolol which decreased his heart rate to 80 to 90 beats/min. Twenty-four hours later, he inadvertently received 5 tiotropium 18-mcg capsules via inhalation instead of the prescribed one 18-mcg capsule. Approximately 15 minutes later, the patient's heart rate increased to 160 beats/min. With IV administration of metoprolol and diltiazem, his heart rate returned to the 80s, although it continued to be difficult to control throughout his hospitalization (Gregory et al, 2010).
h) CLIDINIUM: A 24-year-old man developed sinus tachycardia (110 to 125 beats/min) that persisted for 11 hours following 2 overdose ingestions, separated by 90 minutes, of a combination medication containing chlordiazepoxide 5 mg and clidinium 2.5 mg (amounts ingested per overdose: chlordiazepoxide 50 mg and clidinium 25 mg). With supportive care, the patient recovered and was discharged without sequelae (Richardson & Edwards, 2009).

a) ORPHENADRINE/CASE REPORT (CHILD): Wide complex tachycardia unresponsive to lidocaine, precordial thump, and cardioversion were seen in a 3-year-old who may have ingested 1000 to 5000 mg of orphenadrine. IV physostigmine converted the patient to sinus tachycardia (Danze & Langdorf, 1991).
b) Life-threatening dysrhythmias, cardiogenic shock, and cardiorespiratory arrest are rare but may occur (Freedberg et al, 1987).

a) ATROPINE/CASE REPORT: The administration of atropine 1 mg IV paradoxically caused bradycardia in a 49-year-old man with impaired AV conduction immediately after an inferior myocardial infarction (Ng & Nikolic, 1991).
b) BENZTROPINE/CASE REPORT: Similar clinical effects were seen in a patient that had been given benztropine mesylate. The bradycardia disappeared after discontinuation of the drug (Voinov et al, 1992).
c) TRIHEXYPHENIDYL/CASE REPORT: There is 1 reported case where administration of trihexyphenidyl paradoxically caused bradycardia (Blumensohn et al, 1986).

a) Respiratory depression and aspiration may occur in patients with seizures or mental status changes secondary to severe overdose (Stoddart et al, 1968).

a) DIPHENIDOL/CASE REPORT (CHILD): Respiratory failure with cyanosis occurred in a 2-year-old child following a diphenidol overdose ingestion of 225 mg. The patient subsequently died due to profound shock (Yang & Deng, 1998).

a) TRANSDERMAL SCOPOLAMINE: Therapeutic use of transdermal scopolamine patches has been linked to hallucinations, memory loss, disorientation, and agitation in adults (Elias & Abouleish, 1997; Mego et al, 1988; Rozzini et al, 1988) and in children (Lin et al, 2014).
b) BIPERIDEN/CASE REPORT (CHILD): A 15-year-old boy, initially diagnosed with gastroenteritis and receiving prochlorperazine therapy, experienced auditory and visual hallucinations, an altered mental status, disorientation, restlessness, and insomnia after receiving biperiden 5 mg intramuscularly followed by biperiden 2 mg orally 3 times daily for treatment of dystonia caused by the prochlorperazine. Prior to onset of delirium signs and symptoms, the prochlorperazine had been discontinued. With supportive care and discontinuation of biperiden therapy, the patient's delirium resolved and he was discharged approximately 2 days later (Wang et al, 2011).

a) CASE REPORT (OCULAR): Disorientation, asthenia, drowsiness, verbosity with incoherent speech, and light delirium occurred 195 minutes after 12 drops of an eye preparation, containing atropine 12 mg, phenylephrine 24 mg, and scopolamine 3 mg, were instilled over 1.5 hours in a 67-year-old woman (Kortabarria et al, 1990).
b) SCOPOLAMINE-TAINTED HEROIN: Agitation, hallucinations, paranoia, and combativeness were reported in several people following insufflation of scopolamine-contaminated heroin. The patients recovered following benzodiazepine administration (Perrone et al, 1999) and physostigmine administration (Hamilton et al, 1995).
c) SCOPOLAMINE/CASE REPORT: A 55-year-old man developed delirium and subsequent toxic encephalopathy following occupational exposure to a scopolamine-related substance. The delirium regressed within 1 day without treatment; however there was only partial regression of the encephalopathy over the following 3 years (Muttray et al, 1994).
d) SCOPOLAMINE/CASE REPORT: Toxic psychosis from overdosage of Sominex(R) (containing scopolamine) occurred in a 27-year-old man following ingestion of 10 to 30 tablets. The patient developed symptoms of agitation, pressured speech, flushing, hyperpyrexia, mydriasis, and blurred vision. Confusion and disorientation with visual hallucinations were also observed. Psychotic behavior existed beyond the toxic phase, possibly unmasking an underlying schizophrenia. Signs and symptoms disappeared within 24 to 36 hours. Similar symptoms were reported in a second patient following ingestion of scopolamine in large amounts over a period of 3 days (Bernstein & Leff, 1967).
e) TROPICAMIDE/CASE REPORT: A 22-year-old heroin addict, enrolled in a methadone replacement program, presented with palpitations. Vital signs revealed hypertension (160/90 mmHg) and tachycardia (120 beats/minute). Mydriasis and xerostomia were noted, and the patient was agitated, reporting visual and auditory hallucinations. Treatment with diazepam resulted in resolution of signs and symptoms. Interview of the patient revealed a 2-year history of intravenously injecting tropicamide 1% ophthalmic solution in order to attenuate signs and symptoms of opiate withdrawal. Initially, the patient administered an approximate dose of 0.5 g of tropicamide; however, it was discovered that increasing the dose up to 1 g resulted in visual and auditory hallucinations. Following several months of use, the patient experienced tropicamide dependence and progressively increased the dose up to 1.5 g, resulting in more severe anticholinergic effects. Administration of heroin or methadone immediately following tropicamide administration reportedly reduced the anticholinergic effects. At the time of presentation, the patient had been injecting up to 1.5 g tropicamide daily and using up to 0.5 g of heroin approximately once a week (Spagnolo et al, 2013).

a) Hallucinations are usually visual (Fisher, 1991).

a) Evidence of retrograde amnesia is often noted following the administration of atropine sulfate and homatropine ophthalmic drops in children (Barker & Soloman, 1990).
b) SCOPOLAMINE/CASE STUDY: A group of 20 healthy male volunteers, who took 1.2 mg of scopolamine, were found to have impairment of immediate free recall. However, their mental rotation skills were unimpaired by cholinergic blockade (Rusted, 1988).

a) SCOPOLAMINE/CASE REPORT: A 42-year-old man experienced delirium, hallucinations, dilated pupils, tachycardia, and retrograde amnesia following possible scopolamine poisoning. Signs and symptoms resolved 24 hours later (Brizer & Manning, 1982).
b) SCOPOLAMINE: Following scopolamine exposure, 3 cases of transient global amnesia (TGA) occurred, which is characterized by an abrupt deficit in memory for recent events usually associated with retrograde amnesia (Ardila & Moreno, 1991).

a) ATROPINE/CASE REPORT (CHILD): A 3-month-old infant was hospitalized with generalized tonic-clonic seizures, tachycardia, mydriasis, and fever. Signs began 1.5 hours after atropine sulphate 1% ointment was instilled in his eyes to facilitate ophthalmologic examination. Neostigmine (0.12 mg IV) and diazepam were used to control signs, which subsequently resolved (Joseph et al, 1991).
b) CYCLOPENTOLATE/CASE REPORT (CHILD): Seizures, facial flushing, and tachycardia occurred following instillation of cyclopentolate 1%, 1 drop in each eye, in a 4.5-year-old child with cerebral palsy and paraplegia without an epileptic focus (Fitzgerald et al, 1990).
c) KETAMINE AND ATROPINE: Two patients developed generalized clonic seizures after receiving ketamine and atropine intramuscularly as preoperative medications (Burmeister-Rother et al, 1993).

a) CASE REPORT (INFANT): An 18-month-old infant experienced seizures, along with hyperpyrexia and pupil dilation, several hours after swallowing 23 Debendox(R) tablets. Each delayed-release tablet contained dicyclomine hydrochloride 10 mg, doxylamine succinate 10 mg, and pyridoxine hydrochloride 10 mg. The patient suffered cardiac and respiratory arrest following treatment with diazepam and paraldehyde (Meadow & Leeson, 1974).
b) ATROPINE/CASE REPORT(CHILD): A 3-year-old child developed an exacerbation of akinetic seizures after the administration of atropine sulfate 1% eye drops, 1 drop in each eye twice daily for 4 days. Prior to receiving the eye drops, the patient experienced only 2 seizures in a 3-month period. Twenty-four hours after initiating therapy with the eye drops, the patient began to have an increase in seizures. Overall, the patient had a total of 92 akinetic seizures in 7 days (Wright, 1992).
c) DIPHENIDOL/CASE SERIES: Seizures were reported in 4 children following diphenidol overdose ingestions with doses ranging from 175 to 800 mg. One child, who presented with recurrent seizures, hypotension, respiratory failure, and coma, died 2 days later (Yang & Deng, 1998).
d) TROPENOL ESTER/CASE REPORT: A 40-year-old chemical worker experienced impaired coordination, drowsiness, and a generalized tonic-clonic seizure following suspected occupational dermal exposure to tropenol ester, a precursor to tiotropium bromide. The patient also developed mydriasis, photophobia, and a dry mouth. With supportive care, the patient recovered (Muttray et al, 2012).

a) BENZTROPINE: Acute dystonic reactions following recommended doses of benztropine, especially in children, have been reported (Howrie et al, 1986).
b) TRIHEXYPHENIDYL/CASE SERIES: Trihexyphenidyl was used to treat 5 adult patients for focal or segmental dystonia; all 5 developed chorea. Doses ranged from 15 to 60 mg/day, and an association was found between advanced patient age and a lower dose causing chorea (Nomoto et al, 1987).

a) BIPERIDEN AND TRIHEXYPHENIDYL: Two cases of dyskinesias occurred in patients following ingestions of biperiden and trihexyphenidyl, which resolved with the removal of the medications (Linazasoro, 1994).
b) TRIHEXYPHENIDYL: Orobuccal dyskinesias occurred in a 60-year-old man 3 to 4 days after initiating therapy with trihexyphenidyl, 2 mg twice daily, for the treatment of Parkinson disease. The dyskinesia resolved after discontinuation of the medication (Hauser & Olanow, 1993).

a) SCOPOLAMINECASE REPORT: An 83-year-old woman presented to the emergency department with a decreased level of consciousness (Glasgow Coma Scale score of 8), and intermittent myoclonus after ingesting a single 10-mg dose of scopolamine instead of the prescribed butylscopolamine 10 mg three times daily. Vital signs demonstrated hypertension (167/82 mmHg), tachycardia (127 beats/min) and hyperthermia (38 degrees C). Bilateral mydriasis that was unresponsive to light, and a tetrapyramidal syndrome with myoclonus of the left leg and hypertonia of the extremities were also noted. Following administration of a pyridostigmine infusion and supportive care, the patient gradually improved and was discharged a few days later with baseline mild cognitive deficit (Van de Velde et al, 2015).

a) ATROPINE/CASE REPORT (INFANT): A 5-week-old infant, through a dosing error, was given atropine 3.2 mg /kg body weight as treatment for colic. Twelve hours later, he lapsed into a coma. Signs resolved within 48 hours with supportive treatment (Pickford et al, 1991).
b) ATROPINE/CASE REPORT: A 55-year-old woman became comatose after administration of a compounded ergotamine tartrate and caffeine suppository that inadvertently contained 25 mg of atropine sulfate instead of 0.25 mg atropine sulfate (Hadzija & Shrewsbury, 1997).
c) CASE REPORT (CHILD - OCULAR): A 6-year-old child presented with coma, agitation, dilated pupils, dry skin and mouth, and tachycardia. Signs and symptoms appeared 1 hour after instillation, 2 drops in each eye, of ophthalmic solution containing atropine sulfate 2%, scopolamine bromhydrate 0.5%, and phenylephrine hydrochloride 4%. The patient regained cognitive functions 16 hours later with physostigmine treatment (Nadal et al, 1987).
d) DIPHENIDOL/CASE REPORT (CHILD): A 2-year-old child ingested 225 mg of diphenidol (15 mg/kg) and developed tachycardia, hypotension, recurrent seizures, respiratory failure, and coma. The onset of symptoms occurred 2 hours after the overdose ingestion. Despite aggressive supportive care, the patient died 2 days later due to profound shock (Yang & Deng, 1998).

a) OXYBUTYNIN: Night terrors have been reported in children and adults following therapeutic administration of oxybutynin. Cessation of oxybutynin therapy resulted in complete recovery (Valsecia et al, 1998).

a) In a study of 372 elderly people (older than 60 years of age), 30 (9.2%) anticholinergic drug users and 297 nonusers were evaluated to determine the potential of anticholinergic drugs as a cause of nondegenerative mild cognitive impairment. Drug users had significantly poorer simple reaction time, attention, immediate and delayed visuospatial memory, narrative recall, verbal fluency, and object naming and visuospatial construction compared with the nonusers. Twenty-four (80%) of 30 drug users met the criteria for mild cognitive impairment compared with 35% of the nonusers. The 2 highly significant predictors of mild cognitive impairment were anticholinergic drug use (odds ratio 5.12; 1.94 to 13.51; P=0.001) and age (1.09; 1.06 to 1.13, P<0.001). At 8-year follow-up, no difference in dementia rates between drug users (16%) and nonusers (14%) was observed (Ancelin et al, 2006).

a) SCOPOLAMINE/CASE REPORT: An 83-year-old woman presented to the emergency department with a decreased level of consciousness (Glasgow Coma Scale score of 8), and intermittent myoclonus after ingesting a single 10-mg dose of scopolamine instead of the prescribed butylscopolamine 10 mg three times daily. Vital signs demonstrated hypertension (167/82 mmHg), tachycardia (127 beats/min) and hyperthermia (38 degrees C). Bilateral mydriasis that was unresponsive to light, and a tetrapyramidal syndrome with myoclonus of the left leg and hypertonia of the extremities were also noted. Following administration of a pyridostigmine infusion and supportive care, the patient gradually improved and was discharged a few days later with baseline mild cognitive deficit (Van de Velde et al, 2015).

a) Decreased gastric motility and diminished bowel sounds commonly occur with anticholinergic toxicity (Fahy et al, 1989; Freedberg et al, 1987; Goldfrank et al, 1982).
b) BENZTROPINE/CASE REPORT: Esophageal atony and dilatation and distention of the colon occurred in a 51-year-old man following ingestion of thiothixene, 10 mg 3 times daily, and benztropine, 2 mg twice daily. Effects resolved 2 days after discontinuation of the medications (Woodring et al, 1993).
c) There have been reported cases of paralytic ileus developing in patients following the oral or intravenous administration of atropine, mesoridazine, or benztropine mesylate (Beards et al, 1994; Van Meurs et al, 1992; Beatson, 1982; Wade & Ellenor, 1980) .
d) IPRATROPIUM BROMIDE/CASE REPORT: A case of paralytic ileus following the use of nebulized ipratropium bromide has been described. The patient recovered several days after discontinuation of the drug (Markus, 1990).

a) TROPICAMIDE/CASE REPORT: Severe weight loss (15 kg in one year) was reported in two patients (37-year-old and 38-year-old men), with a history of heroin use, after intravenously injecting 1% tropicamide ophthalmic solution with heroin several times daily. The patients reported that administration of tropicamide resulted in an increase and prolongation of heroin's effect, and the desire to use heroin decreased. In addition to the weight loss, the patients also experienced hallucinations, blurred vision, dissociation, and impaired concentration. Both patients gradually recovered following cessation of tropicamide administration and treatment with buprenorphine and naloxone for opioid withdrawal symptoms (Bozkurt et al, 2015).

a) Urinary retention is another common anticholinergic effect (Gregory et al, 2010; Hamilton et al, 1995; Larkin, 1991; Worth et al, 1983; Goldfrank et al, 1982).

a) ATROPINE/CASE REPORT: A 65-year-old man who accidentally ingested approximately 3 mg of atropine subsequently developed facial warmth and flushing, restlessness, hyperactivity, dry tongue and mouth, speech dysphasia, and hypothermia. Blood pressure was 190/100 mmHg and pupils were dilated with hypertonicity of limbs and reflexes. Following treatment with chlorpromazine and paraldehyde the patient became calm and after 24 hours the patient was fully oriented and relaxed (Wood & Haq, 1971).

a) TRANSDERMAL SCOPOLAMINE/CASE REPORT: Dermal hypersensitivity has been reported in a woman using a transdermal scopolamine device after 3 months of daily usage (Trozak, 1985).

a) ATROPINE/CASE REPORT: A case of anaphylaxis has been reported secondary to intravenous atropine given preoperatively (Aguilera et al, 1988).
b) HYOSCINE AND DIPHENHYDRAMINE/CASE REPORT (IV): A case of anaphylactic shock was reported following IV administration of hyoscine butylbromide and diphenhydramine. The patient developed severe respiratory distress and cardiovascular collapse (Watanabe et al, 1994).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info DuoDote(R) intramuscular injection solution, 2011).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info LIBRAX(R) oral capsules, 2009).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info Atrovent(R) nasal spray, 2011; Prod Info ATROVENT(R) HFA oral inhalation aerosol, 2010; Prod Info ipratropium bromide 0.02% inhalation solution, 2007).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) Among 1690 pregnancies, the incidence of skeletal and limb malformations, cardiac defects, and oral cleft did not differ between infants exposed to dicyclomine and those who were not (Morelock et al, 1982). Congenital malformation rates also were similar among 1593 infants exposed to dicyclomine during the first trimester, even when controlling for confounding factors (Shapiro et al, 1977).

a) RATS, RABBITS: Animal studies revealed no evidence of structural alterations in rats or rabbits administered aclidinium bromide at doses 15 and 20 times the recommended human daily dose (RHDD), respectively, during organogenesis (Prod Info TUDORZA(TM) PRESSAIR(TM) oral inhalation powder, 2012).

a) RATS: In animal studies, no congenital anomalies or teratogenic effects were observed in rats administered oral doses of either 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide during 2 successive matings. A slight decrease in the number of pups surviving during lactation was observed in rats receiving the highest dose during the first mating. A slight decrease in the number of pregnant females as well as the number of pups surviving until weaning was observed during the second mating (Prod Info LIBRAX(R) oral capsules, 2009).
b) RATS: In animal studies, there was no evidence of congenital anomalies in rats administered chlordiazepoxide hydrochloride 10, 20 or 80 mg/kg/day followed by breeding. In a similar study, rats administered chlordiazepoxide hydrochloride 100 mg/kg/day experienced a significant decrease in fertilization rate and decreased body weight and viability of offspring. Major skeletal defects were observed in 1 neonate from both the first and second mating receiving chlordiazepoxide hydrochloride 100 mg/kg/day. During 2 reproduction studies in rats administered clidinium bromide 2.5 and 10 mg/kg/day, respectively, there was no incidence of congenital anomalies or teratogenic effects (Prod Info LIBRAX(R) oral capsules, 2009).

a) MICE, RABBITS: In mice and rabbit studies, no oral dose-related teratogenicity was observed at doses up to 75 mg/kg/day in mice, up to 27 mg/kg/day in rabbits, or at subcutaneous doses up to 4.5 mg/kg/day in rabbits. In mice treated with 75 mg/kg/day, increased resorptions and a decrease in live fetuses were observed. Cleft palate was observed in 1 fetus at doses of 15, 45, and 75 mg/kg/day. In rabbits, incomplete ossified sternebrae (retardation of bone development) was reported in rabbits treated with subcutaneous doses of 4.5 mg/kg/day. Oral doses of 30 mg/kg/day resulted in decreased body weight of the dams and delayed ear opening of the pups (Prod Info TOVIAZ(TM) extended-release oral tablets, 2008).

a) No evidence of teratogenic effects was seen in animals when pregnant females were administered 18,000 and 270 times the maximum recommended human daily inhalation dose on a body surface area basis when delivered orally or via intramuscular injection, respectively (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016).
b) In animal studies, there were no reports of teratogenic effects (Prod Info glycopyrrolate oral tablets, 2015; Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015) with glycopyrrolate doses up to 1400 times the maximum recommended human dose (MRHD). No effects on perinatal or postnatal development were reported in animals following administration of glycopyrrolate doses up to 1100 times the MRHD (Prod Info CUVPOSA(R) oral solution, 2015; Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015).
c) In animal studies, there were no teratogenic effects to the fetus at dietary or intramuscular doses up to 320 times the maximum recommended daily human dose of 2 mg on a mg/m(2) basis. Glycopyrrolate does not appear to affect fetal heart rate or fetal heart rate variability; however, dietary administration of glycopyrrolate resulted in decreased offspring survival in a dose related manner (Prod Info glycopyrrolate intravenous injection, 2014).

a) During animal studies, no effects on perinatal or postnatal development were reported with indacaterol doses up to 110 times the maximum recommended human dose (MRHD) or with glycopyrrolate at doses up to 1100 times the MRHD. There were also no reports of teratogenicity with indacaterol at doses up to 770 times the MRHD or glycopyrrolate at doses up to 1400 times the MRHD (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) RATS, RABBITS: Following inhalation administration, glycopyrronium did not appear to have any teratogenic effects in rats or rabbits (Prod Info Enurev Breezhaler oral inhalation powder capsules, 2012).

a) MICE, RATS, RABBITS: Animal reproduction studies did not result in teratogenic effects in mice, rats, or rabbits given oral ipratropium bromide doses of 10, 1,000, and 125 mg/kg (approximately 160, 32,000, and 8,000 times the maximum recommended daily intranasal dose (MRDID) in adults on a mg/m(2) basis), respectively. In a similar inhalation reproduction study, rats and rabbits given ipratropium bromide doses of 1.5 and 1.8 mg/kg, respectively (approximately 50 and 120 times, respectively, the MRDID in adults on a mg/m(2) basis) showed no evidence of teratogenicity. Although rats treated with oral doses of ipratropium bromide 90 mg/kg (approximately 2,900 times the MRDID in adults on a mg/m(2) basis) and above resulted in embryotoxicity as resorption increased, this effect is not considered to be relevant to human use due to the difference in administration route as well as the large doses consumed (Prod Info Atrovent(R) nasal spray, 2011; Prod Info ipratropium bromide 0.02% inhalation solution, 2007).
b) MICE, RATS, RABBITS: Animal reproduction studies did not result in teratogenic effects in mice, rats, or rabbits given oral ipratropium bromide doses approximately 200, 40,000, and 10,000 times the maximum recommended human daily inhalation dose (MRHDID) in adults on a mg/m(2) basis, respectively. Although rats treated with oral doses of ipratropium bromide approximately 3,600 times the MRHDID in adults on a mg/m(2) basis resulted in embryotoxicity as resorption increased, this effect is not considered to be relevant to human use due to the difference in administration route as well as the large doses consumed (Prod Info ATROVENT(R) HFA oral inhalation aerosol, 2010).

a) MICE, RATS, HAMSTERS, RABBITS: Studies conducted in rodents (mice, rats, and hamsters) and rabbits have shown no evidence of teratogenic effects associated with the use of oxybutynin during pregnancy (Prod Info DITROPAN XL(R) oral extended release tablets, 2008; Prod Info DITROPAN(R) oral tablets, syrup, 2008; Prod Info OXYTROL(TM) transdermal patch, 2006). In 1 animal study, there was no evidence of harm to the fetus in rats and rabbits receiving subcutaneous oxybutynin doses up to 25 mg/kg (approximately 50 times the human exposure) and doses up to 0.4 mg/kg (approximately 1 time the human exposure), respectively (Prod Info GELNIQUE(R)10% topical gel, 2009).

a) In animal studies, there was no evidence of structural alterations at maternal tiotropium inhalation doses up to 790 and 8 times the recommended human daily dose on a mg/m(2) basis (Prod Info SPIRIVA(R) HANDIHALER(R) oral inhalation powder, 2015).

a) MICE: There were no anomalies or malformations observed at maternal oral doses up to 14 times the human exposure (20 mg/kg/day) in mice. When pregnant mice were given oral doses 30 to 40 mg/kg/day, there was an increased incidence of fetal abnormalities including cleft palate, digital abnormalities, intraabdominal hemorrhage, and various skeletal abnormalities, primarily reduced ossification). At these doses, the AUC values were 20- to 25-fold higher compared with humans (Prod Info DETROL(R) oral tablets, 2008).
b) RABBITS: There was no evidence of teratogenicity at maternal subcutaneous doses of 0.8 mg/kg/day in rabbits. This dose achieved an AUC of 100 mcg x hour/L which is 3-fold higher than that resulting from the human dose (Prod Info DETROL(R) oral tablets, 2008).

a) RATS, RABBITS: No teratogenic effects were found in rats administered umeclidinium at maternal inhaled doses up to 278 mcg/kg/day and rabbits administered umeclidinium at maternal subQ does up to 180 mcg/kg/day (approximately 50 and 200 times, respectively, the maximum recommended human daily inhaled dose [MRHDID] in adults on a AUC basis. No effects on perinatal and postnatal development were observed in rats following maternal administration at subQ doses up to 180 mcg/kg/day (approximately 80 times the MRHDID in adults on an AUC basis) (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) LACK OF EFFECT: RATS: Administration in rats of the single agent umeclidinium at inhaled doses up to 278 mcg/kg/day (approximately 50 times the maximum recommended human daily inhalation dose (MRHDID) on an AUC basis) revealed no evidence of teratogenicity (Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013).
b) LACK OF EFFECT: RABBITS: Teratogenic effects were not observed in rabbits administered umeclidinium subQ maternal doses up to 180 mcg/kg/day (approximately 200 times the MRHDID on an AUC basis). However, in single agent studies of vilanterol, fetal skeletal variations, including decreased or absent ossification in cervical vertebral centrum and metacarpals, were observed in rabbits administered vilanterol at inhaled doses of 5740 mcg/kg/day or subQ doses of 300 mcg/kg/day (approximately 450 times the MRHDID in adults on an AUC basis) (Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013).

1) Atropine (Prod Info ATREZA(TM) oral tablets, 2005)
2) Atropine/pralidoxime chloride (Prod Info DuoDote(R) intramuscular injection solution, 2011)
3) Benztropine mesylate (Prod Info COGENTIN(R) injection, 2005)
4) Biperiden hydrochloride (Prod Info AKINETON(R) oral tablets, 2001)
5) Clidinium bromide (Prod Info LIBRAX(R) oral capsules, 2009)
6) Glycopyrrolate (Prod Info Glycopyrrolate intramuscular injection, intravenous injection, 2009; Prod Info CUVPOSA oral solution, 2010)
7) Glycopyrrolate/formoterol fumarate (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016)
8) Glycopyrronium (Prod Info Enurev Breezhaler oral inhalation powder capsules, 2012)
9) Hyoscyamine sulfate (Prod Info SYMAX(TM) DUOTAB biphasic oral tablets, 2006)
10) Ipratropium bromide (Prod Info Atrovent(R) nasal spray, 2011; Prod Info ATROVENT(R) HFA oral inhalation aerosol, 2010; Prod Info ipratropium bromide 0.02% inhalation solution, 2007)
11) Methscopolamine bromide (Prod Info methscopolamine bromide oral tablets, 2006)
12) Orphenadrine citrate (Prod Info NORFLEX(TM) extended-release oral tablets, injection, 2006)
13) Propantheline bromide (Prod Info PRO-BANTHINE(R) oral tablets, 2006)
14) Scopolamine hydrobromide (Prod Info SCOPACE(TM) oral tablets, 2007)

a) At the time of this review, no data were available to assess the potential effects of this agent during pregnancy in humans (Prod Info SPIRIVA(R) HANDIHALER(R) oral inhalation powder, 2015; Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014).

a) At the time of this review, no data were available to assess the potential effects of this agent during pregnancy in humans (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014)

1) Aclidinium bromide (Prod Info TUDORZA(TM) PRESSAIR(TM) oral inhalation powder, 2012)
2) Atropine (Prod Info ATREZA(TM) oral tablets, 2005)
3) Atropine/pralidoxime chloride (Prod Info DuoDote(R) intramuscular injection solution, 2011)
4) Albuterol sulfate/ipratropium bromide (Prod Info Combivent(R) oral inhalation aerosol, 2010)
5) Belladonna alkaloids (atropine sulfate, hyoscyamine sulfate, and scopolamine hydrobromide)/phenobarbital (Prod Info DONNATAL(R) oral tablets, 2012; Prod Info DONNATAL(R) ELIXIR oral solution, 2011; Prod Info DONNATAL EXTENTABS(R) oral extended release tablets, 2007)
6) Belladonna extract/opium alkaloids (Prod Info Belladonna & Opium rectal suppositories, 2005)
7) Biperiden hydrochloride (Prod Info AKINETON(R) oral tablets, 2001)
8) Fesoterodine fumarate (Prod Info TOVIAZ(TM) extended-release oral tablets, 2008)
9) Glycopyrrolate (oral form only) (Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015)
10) Glycopyrrolate/formoterol fumarate (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016)
11) Glycopyrrolate/indacaterol (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015)
12) Hyoscyamine sulfate (Prod Info SYMAX(TM) DUOTAB biphasic oral tablets, 2006)
13) Methscopolamine bromide (Prod Info methscopolamine bromide oral tablets, 2006)
14) Olodaterol/tiotropium bromide (Prod Info STIOLTO(TM) RESPIMAT(R) oral inhalation spray, 2015)
15) Orphenadrine citrate (Prod Info NORFLEX(TM) extended-release oral tablets, injection, 2006)
16) Propantheline bromide (Prod Info PRO-BANTHINE(R) oral tablets, 2006)
17) Scopolamine hydrobromide (Prod Info SCOPACE(TM) oral tablets, 2007).
18) Tiotropium bromide (Prod Info SPIRIVA(R) HANDIHALER(R) oral inhalation powder, 2015; Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014)
19) Tolterodine tartrate (Prod Info DETROL(R) oral tablets, 2008)
20) Umeclidinium (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014).
21) Umeclidinium and vilanterol (Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013)

1) Dicyclomine hydrochloride (Prod Info BENTYL(R) oral capsules, oral tablets, oral syrup, intramuscular injection, 2011)
2) Glycopyrrolate (IV form only) (Prod Info glycopyrrolate intravenous injection, 2014)
3) Ipratropium bromide (Prod Info Atrovent(R) nasal spray, 2011; Prod Info ATROVENT(R) HFA oral inhalation aerosol, 2010; Prod Info ipratropium bromide 0.02% inhalation solution, 2007)
4) Mepenzolate bromide (Prod Info CANTIL(R) oral tablet, 2003)
5) Oxybutynin (Prod Info GELNIQUE(R)10% topical gel, 2009; Prod Info DITROPAN XL(R) oral extended release tablets, 2008; Prod Info DITROPAN(R) oral tablets, syrup, 2008; Prod Info OXYTROL(TM) transdermal patch, 2006)

a) Use during pregnancy only if the potential maternal benefit outweighs the potential fetal risk (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) Administer during pregnancy only if the benefit justifies the risk to the fetus (Prod Info STIOLTO(TM) RESPIMAT(R) oral inhalation spray, 2015).

a) No well-controlled trials have investigated the effects of glycopyrrolate/formoterol fumarate on labor. Since beta-2 agonists such as glycopyrrolate/formoterol fumarate can interfere with uterine contractions, the drug should be used during labor only if the potential benefits justify the potential risk (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016).

a) Restrict use during labor to only those cases where the benefit clearly outweighs the risk (Prod Info STIOLTO(TM) RESPIMAT(R) oral inhalation spray, 2015).

a) In epidemiologic studies of pregnant women with products containing dicyclomine (40 mg/day), an increased risk of fetal abnormalities has not been demonstrated during the first trimester. Studies using the recommended dose of 80 to 160 mg/day have not been performed (Prod Info BENTYL(R) oral capsules, oral tablets, oral syrup, intramuscular injection, 2011).
b) No increased risk of birth defects associated with the use of dicyclomine was found in a meta-analysis and a prospective cohort study of pregnant women using dicyclomine during the first trimester (relative risk: 1.04; 95% confidence interval: 0.82-1.30) (Magee et al, 2002). No increased risk of fetal anomaly was observed in epidemiologic studies with dicyclomine (Eskenazi & Bracken, 1985; Aselton et al, 1984; McCredie et al, 1984; Mitchell et al, 1983; Morelock et al, 1982; Rothman et al, 1979; Shapiro et al, 1977).

a) In single-dose studies in humans, very small amounts of glycopyrrolate crossed the placental barrier (Prod Info ROBINUL(R) Injection, 2005).

a) RATS, RABBITS: Administration of aclidinium bromide 1400 and 2300 times the recommended human daily dose (RHDD) resulted in incidences of additional liver lobes and decreased fetal body weights, respectively, amongst Himalayan rabbits. Maternal toxicity was also reported amongst rats administered inhaled aclidinium bromide doses greater than or equal to 0.2 mg/kg/day (Prod Info TUDORZA(TM) PRESSAIR(TM) oral inhalation powder, 2012).

a) RATS, RABBITS: In rats and rabbits, there was no evidence of impaired fertility or fetal harm at maternal doses up to 33 times the maximum recommended human dose based on 160 mg/day (3 mg/kg) (Prod Info BENTYL(R) oral capsules, oral tablets, oral syrup, intramuscular injection, 2011).

a) No effects on perinatal or postnatal development were reported in animals following administration of glycopyrrolate doses at approximately 1100 times the maximum recommended human dose (Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015).

a) During animal studies, no effects on perinatal or postnatal development were reported with indacaterol doses up to 110 times the maximum recommended human dose (MRHD) or with glycopyrrolate at doses up to 1100 times the MRHD. There were also no reports of teratogenicity with indacaterol at doses up to 770 times the MRHD or glycopyrrolate at doses up to 1400 times the MRHD (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) RATS, RABBITS: In rats and rabbits, no evidence of impaired fertility or harm to the fetus has been shown at maternal doses up to 30 times the human dose based on a 50 kg weight (Prod Info CANTIL(R) oral tablet, 2003).

a) Fetal resorption, litter loss, decreases in number of live pups at birth and mean pup weights, and delayed pup sexual maturation were reported at maternal tiotropium inhalation doses 45 times the recommended human daily dose (RHDD). These effects were not noted at inhalation doses 4 and 80 times the RHDD, while postimplantation loss was observed at an inhalation dose approximately 360 times the RHDD based on mg/m(2) (Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014).

a) MICE: Maternal oral doses 30 to 40 mg/kg/day were shown to be embryolethal and reduce fetal weight in mice. At these doses, the AUC values were 20- to 25-fold higher compared with humans (Prod Info DETROL(R) oral tablets, 2008).
b) RABBITS: There was no evidence of embryotoxicity at maternal subcutaneous doses of 0.8 mg/kg/day in rabbits. This dose achieved an AUC of 100 mcg x hour/L which is 3-fold higher than that resulting from the human dose (Prod Info DETROL(R) oral tablets, 2008).

a) RATS: There were no observed effects on peri- or postnatal development in rats administered umeclidinium at subQ doses up to 180 mcg/kg/day (approximately 80 times the maximum recommended human daily inhalation dose (MRHDID) in adults) (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014; Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013).

a) It is not known whether glycopyrrolate is excreted into human breast milk (Prod Info CUVPOSA(R) oral solution, 2015; Prod Info glycopyrrolate oral tablets, 2015; Prod Info glycopyrrolate intravenous injection, 2014). However, the highly polar quaternary ammonium group of glycopyrrolate limits its passage across lipid membranes (Prod Info CUVPOSA oral solution, 2010; Prod Info Glycopyrrolate intramuscular injection, intravenous injection, 2009)
b) Discontinue treatment or discontinue nursing taking into account the importance of the drug to the mother (Prod Info glycopyrrolate oral tablets, 2015; Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015).

a) It is unknown whether glycopyrronium bromide is excreted in human milk; however, glycopyrronium bromide and its metabolites are excreted in the milk of lactating rats (Prod Info Enurev Breezhaler oral inhalation powder capsules, 2012).

a) At the time of this review, no data were available to assess the potential effects of exposure to the following anticholinergic agents during lactation in humans or animals:

a) At the time of this review, no data were available to assess the potential effects of exposures to this agent during lactation in humans (Prod Info SPIRIVA(R) HANDIHALER(R) oral inhalation powder, 2015; Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014).

a) Exercise caution when administering umeclidinium to pregnant women. At the time of this review, no data were available to assess the potential effect of exposure to this agent during lactation in humans (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) At the time of this review, no data were available to assess the potential effect of exposure to this combination or with the individual components during lactation in humans (Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013).

a) Use caution when administering to lactating women (Prod Info STIOLTO(TM) RESPIMAT(R) oral inhalation spray, 2015).

a) Lactation studies with aclidinium bromide have not been conducted and the effects, if any, on a breastfeeding infant are unknown. Animal studies have shown that aclidinium bromide is excreted in the milk of lactating rats and has resulted in decreased pup weight. Because many drugs are excreted into human milk, the manufacturer recommends using caution when administering aclidinium bromide to a lactating woman (Prod Info TUDORZA(TM) PRESSAIR(TM) oral inhalation powder, 2012).

a) Dicyclomine has been shown to be excreted in human milk and is contraindicated in nursing mothers (Prod Info BENTYL(R) oral capsules, oral tablets, oral syrup, intramuscular injection, 2011).

a) It is unknown whether glycopyrrolate is excreted into human breast milk. Discontinue nursing or discontinue glycopyrrolate, taking into account the importance of the drug to the mother (Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015).

a) It is not known whether glycopyrrolate/formoterol fumarate is excreted in human milk, although it has been detected in the milk of lactating rats. Therefore, caution should be exercised when glycopyrrolate/formoterol fumarate is administered to lactating women (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016).

a) It is unknown whether glycopyrrolate/indacaterol or the individual components are excreted into human breast milk. Discontinue treatment or discontinue nursing, taking into account the importance of the drug to the mother (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) Hyoscyamine is excreted in human milk (Prod Info SYMAX(TM) DUOTAB biphasic oral tablets, 2006).

a) RATS: Aclidinium bromide lactation studies have not yet been conducted in humans. In animal studies, administration of aclidinium bromide approximately 5 times the recommended human daily dose to rats during the lactation period resulted in decreased pup weight (Prod Info TUDORZA(TM) PRESSAIR(TM) oral inhalation powder, 2012).

a) Glycopyrrolate has been detected in the milk of lactating animals with concentrations reaching up to 10-fold higher in the milk than that of the mother (Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015).

a) Formoterol fumarate, one of the active ingredients of this drug, was detected in the milk of lactating rats (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016).

a) During animal studies, indacaterol was detected in the milk of lactating animals. Glycopyrrolate was also detected in the milk of lactating animals with concentrations reaching up to 10-fold higher in the milk than that of the mother (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) RATS: Glycopyrronium bromide and its metabolites are excreted in the milk of lactating rats. Glycopyrronium concentrations were up to 10-fold higher in the milk than in the blood of the female rats (Prod Info Enurev Breezhaler oral inhalation powder capsules, 2012).

a) RATS: In animal studies, tiotropium has been shown to be excreted in the milk of lactating rats (Prod Info SPIRIVA(R) HANDIHALER(R) oral inhalation powder, 2015; Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014).

a) MICE: Immediate-release tolterodine is excreted into the milk of lactating mice. Offspring of female mice treated with tolterodine 20 mg/kg/day during the lactation period had slightly reduced body weight gain. However, the weight was regained during the maturation phase (Prod Info DETROL(R) oral tablets, 2008).

a) RATS: In a rat study, subQ administration of umeclidinium at approximately 25 times the maximum recommended human inhaled daily dose in adults resulted in a measurable amount of umeclidinium in 2 nursing pups, which may indicate transfer of umeclidinium in milk (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014; Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013).

1) Atropine (Prod Info ATREZA(TM) oral tablets, 2005)
2) Atropine/pralidoxime chloride (Prod Info DuoDote(R) intramuscular injection solution, 2011)
3) Benztropine mesylate (Prod Info COGENTIN(R) injection, 2005)
4) Biperiden hydrochloride (Prod Info AKINETON(R) oral tablets, 2001)
5) Hyoscyamine (Prod Info SYMAX(TM) DUOTAB biphasic oral tablets, 2006)
6) Ipratropium bromide (Prod Info Atrovent(R) nasal spray, 2011; Prod Info ATROVENT(R) HFA oral inhalation aerosol, 2010; Prod Info ipratropium bromide 0.02% inhalation solution, 2007)
7) Mepenzolate bromide (Prod Info CANTIL(R) oral tablet, 2003)
8) Methscopolamine bromide (Prod Info methscopolamine bromide oral tablets, 2006)
9) Olodaterol/tiotropium bromide (Prod Info STIOLTO(TM) RESPIMAT(R) oral inhalation spray, 2015)
10) Orphenadrine citrate (Prod Info NORFLEX(TM) extended-release oral tablets, injection, 2006)
11) Propantheline bromide (Prod Info PRO-BANTHINE(R) oral tablets, 2006)
12) Scopolamine hydrobromide (Prod Info SCOPACE(TM) oral tablets, 2007)
13) Tiotropium bromide (Prod Info SPIRIVA(R) HANDIHALER(R) oral inhalation powder, 2015; Prod Info SPIRIVA(R) RESPIMAT(R) oral inhalation spray, 2014)
14) Umeclidinium (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014)

a) ATROPINE/PRALIDOXIME CHLORIDE
b) ACLIDINIUM BROMIDE
c) GLYCOPYRROLATE
d) GLYCOPYRROLATE/INDACATEROL
e) IPRATROPIUM BROMIDE
f) TIOTROPIUM BROMIDE

a) DICYCLOMINE
b) GLYCOPYRROLATE
c) GLYCOPYRROLATE
d) GLYCOPYRRONIUM
e) OXYBUTYNIN
f) TOLTERODINE TARTRATE
g) UMECLIDINIUM

a) No treatment related increases in tumors were reported during a 2-year inhalation study of glycopyrrolate in Wistar rats at doses up to 170 times the maximum recommended human dose (MHRD). There was no evidence of tumorigenicity with doses up to 125.1 mg/kg/day(Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) No long-term studies have been conducted in animals with the glycopyrrolate and formoterol fumarate combination or with glycopyrrolate alone (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016)

a) Institute continuous cardiac monitoring and follow ECG in patients with persistent tachycardia, hemodynamic instability, seizures or severe mental status changes.

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) A diagnostic trial with physostigmine (see physostigmine dosing below) may be initiated without waiting for laboratory confirmation. Reversal within minutes of coma, arrhythmias, hallucinations, and other findings can be expected if the diagnosis is correct and the patient has not suffered anoxia or other insult or ingested a combination preparation. Avoid in cases where tricyclic antidepressants may also be involved, or in patients with cardiac conduction defects suggestive of tricyclic antidepressant overdose (QRS widening).

a) Physostigmine is indicated to reverse the CNS effects caused by clinical or toxic dosages of agents capable of producing anticholinergic syndrome; however, long lasting reversal of anticholinergic signs and symptoms is generally not achieved because of the relatively short duration of action of physostigmine (45 to 60 minutes) (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008). It is most often used diagnostically to distinguish anticholinergic delirium from other causes of altered mental status (Frascogna, 2007; Shannon, 1998).
b) Physostigmine should not be used in patients with suspected tricyclic antidepressant overdose, or an ECG suggestive of tricyclic antidepressant overdose (eg, QRS widening). In the setting of tricyclic antidepressant overdose, use of physostigmine has precipitated seizures and intractable cardiac arrest (Stewart, 1979; Newton, 1975; Pentel & Peterson, 1980; Frascogna, 2007).

a) ADULT: BOLUS: 2 mg IV at slow controlled rate, no more than 1 mg/min. May repeat doses at intervals of 10 to 30 min, if severe symptoms recur (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008). INFUSION: For patients with prolonged anticholinergic delirium, a continuous infusion of physostigmine may be considered. Starting dose is 2 mg/hr, titrate to effect (Eyer et al, 2008)
b) CHILD: 0.02 mg/kg by slow IV injection, at a rate no more than 0.5 mg/minute. Repeat dosage at 5 to 10 minute intervals as long as the toxic effect persists and there is no sign of cholinergic effects. MAXIMUM DOSAGE: 2 mg total (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
c) AVAILABILITY: Physostigmine salicylate is available in 2 mL ampules, each mL containing 1 mg of physostigmine salicylate in a vehicle containing sodium metabisulfite 0.1%, benzyl alcohol 2%, and water (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).

a) Relative contraindications to the use of physostigmine are asthma, gangrene, diabetes, cardiovascular disease, intestinal or urogenital tract mechanical obstruction, peripheral vascular disease, cardiac conduction defects, atrioventricular block, and in patients receiving choline esters and depolarizing neuromuscular blocking agents (decamethonium, succinylcholine). It may cause anaphylactic symptoms and life-threatening or less severe asthmatic episodes in patients with sulfite sensitivity (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
b) Too rapid IV administration of physostigmine has resulted in bradycardia, hypersalivation leading to respiratory difficulties, and possible seizures (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).

a) Atropine should be available to reverse life-threatening physostigmine-induced, toxic cholinergic effects (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008; Frascogna, 2007). Atropine may be given at half the dose of previously given physostigmine dose (Daunderer, 1980).

a) A retrospective study was conducted to compare the efficacy and safety of physostigmine with benzodiazepines for treatment of agitation and delirium associated with anticholinergic poisoning. Physostigmine controlled agitation and reversed delirium in 96% and 87% of the patients (n=45), respectively, as compared with benzodiazepine-controlled agitation in 24% of the patients (n=26). Benzodiazepines were completely ineffective in reversing delirium.

a) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
b) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

a) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

a) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) If patient is severely agitated, sedate with IV benzodiazepines.

a) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).

a) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
b) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).

a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.

a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).

a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).

a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).

a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).

a) Osmotic diuretic used in the management of rhabdomyolysis and myoglobinuria (Zimmerman & Shen, 2013).

a) ADULT: TEST DOSE: (for patients with marked oliguria or those with inadequate renal function) 0.2 g/kg IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase within 2 to 3 hours. The patient should be reevaluated if there is inadequate response following the second test dose (Prod Info MANNITOL intravenous injection, 2009). TREATMENT DOSE: 50 to 100 g IV as a 15% to 25% solution may be used. The rate should be adjusted to maintain urinary output at 30 to 50 mL/hour (Prod Info mannitol IV injection, urologic irrigation, 2006) OR 300 to 400 mg/kg or up to 100 g IV administered as a single dose (Prod Info MANNITOL intravenous injection, 2009).
b) PEDIATRIC: Dosing has not been established in patients less than 12 years of age(Prod Info Mannitol intravenous injection, 2009). TEST DOSE (for patients with marked oliguria or those with inadequate renal function): 0.2 g/kg or 6 g/m(2) body surface area IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase; TREATMENT DOSE: 0.25 to 2 g/kg or 60 g/m(2) body surface area IV as a 15% to 20% solution over 2 to 6 hours; do not repeat dose for persistent oliguria (Prod Info MANNITOL intravenous injection, 2009).

a) Fluid and electrolyte imbalance, in particular sodium and potassium; expansion of the extracellular fluid volume leading to pulmonary edema or CHF exacerbations(Prod Info MANNITOL intravenous injection, 2009).

a) Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia; do not add to whole blood for transfusions(Prod Info Mannitol intravenous injection, 2009); enhanced neuromuscular blockade observed with tubocurarine(Miller et al, 1976).

a) Renal function, urine output, fluid balance, serum potassium, serum sodium, and serum osmolality (Prod Info Mannitol intravenous injection, 2009).

a) ADULT DOSE/ADMINISTRATION - Prepare a solution containing 10 milligrams esmolol per milliliter of a compatible intravenous solution (Prod Info Brevibloc(R), esmolol hydrochloride, 1998).
b) PEDIATRIC DOSE/ADMINISTRATION - Safety and effectiveness of esmolol has not been established in children (Prod Info Brevibloc(R), esmolol hydrochloride, 1998).

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) INTRAOPERATIVE MEDICATION
b) PEPTIC ULCER
c) PREANESTHETIC MEDICATION
d) REVERSAL OF NEUROMUSCULAR BLOCKADE

a) The recommended dose is 1 capsule (15.6 mcg glycopyrrolate) by inhalation twice daily at the same time every day. Use of more than 1 capsule twice daily not recommended (Prod Info SEEBRI(TM) NEOHALER(R) oral inhalation powder, 2015).

a) INITIAL: The recommended dose is 0.02 mg/kg ORALLY 3 times daily (Prod Info CUVPOSA(R) oral solution, 2015).
b) TITRATION: Dose may be titrated in increments of 0.02 mg/kg every 5 to 7 days. MAX dose, 0.1 mg/kg 3 times daily not exceeding 1.5 to 3 mg per dose (Prod Info CUVPOSA(R) oral solution, 2015)

a) The recommended initial dosage is 1 mg ORALLY 3 times daily. Maintenance dose, 1 mg ORALLY twice daily or 2 mg ORALLY 2 to 3 times daily; MAX dose, 8 mg/day (Prod Info glycopyrrolate oral tablets, 2015).

a) Safety and effectiveness have not been established in pediatric patients (Prod Info TUDORZA(TM) PRESSAIR(TM) oral inhalation powder, 2012).

a) BRADYCARDIA (PALS GUIDELINES)
b) ORGANOPHOSPHATE OR CARBAMATE POISONING:
c) PREMEDICATION, ANESTHESIA INDUCTION OR KETAMINE SEDATION
d) PREMEDICATION, RAPID SEQUENCE INTUBATION

a) ELIXIR: Dosed every 4 to 6 hours based on body weight (Prod Info DONNATAL(R) ELIXIR oral solution, 2011).

a) 9 mcg/kg or 250 mcg/m(2) daily in 3 to 4 divided doses (Prod Info Cogentin(R) injection, benztropine, 1996)

a) The manufacturer states that benztropine should not be used in children less than 3 years of age (Prod Info Cogentin(R) injection, benztropine, 1996).
b) Benztropine may be of value in children of any age in treating drug-induced acute dystonic reactions that are resistant to diphenhydramine. The recommended dose is 1 to 2 mg IV or IM; additional oral doses may be necessary in some patients (Dahiya & Noronha, 1984).

a) Safety and efficacy have not been established in pediatric patients (Prod Info BENTYL(R) oral capsules, oral tablets, oral syrup, intramuscular injection, 2011)

a) INJECTION
b) ORAL INHALATION
c) ORAL SOLUTION
d) ORAL TABLETS:

a) Safety and effectiveness have not been established in pediatric patients (Prod Info BEVESPI AEROSPHERE(TM) inhalation aerosol powder, 2016).

a) Safety and effectiveness have not been established in pediatric patients (Prod Info UTIBRON(TM) NEOHALER(R) oral inhalation powder, 2015).

a) Safety and efficacy have not been established in pediatric patients (Prod Info Enurev Breezhaler oral inhalation powder capsules, 2012).

a) Safety and efficacy have not been established (Prod Info STIOLTO(TM) RESPIMAT(R) oral inhalation spray, 2015)

a) Safety and effectiveness have not been established in pediatric patients (Prod Info ANTUROL topical gel, 2011).

a) ASTHMA
b) CHRONIC OBSTRUCTIVE PULMONARY DISEASE

a) Safety and effectiveness have not been established in pediatric patients (Prod Info INCRUSE(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) Safety and effectiveness have not been established in pediatric patients (Prod Info ANORO(TM) ELLIPTA(TM) oral inhalation powder, 2013).

1) Following acute poisonings, the lowest ingested dose of scopolamine producing life-threatening symptoms was 2 to 4 mg in a study of 115 patients (Hooper et al, 1979). A 0.45-mg dose has caused toxic psychosis (Goldfrank et al, 1982).
2) CASE REPORT: An 83-year-old woman presented to the emergency department with a decreased level of consciousness (Glasgow Coma Scale score of 8), and intermittent myoclonus after ingesting a single 10-mg dose of scopolamine instead of the prescribed butylscopolamine 10 mg three times daily. Vital signs demonstrated hypertension (167/82 mmHg), tachycardia (127 beats/min) and hyperthermia (38 degrees C). Bilateral mydriasis that was unresponsive to light, and a tetrapyramidal syndrome with myoclonus of the left leg and hypertonia of the extremities were also noted. Following administration of a pyridostigmine infusion and supportive care, the patient gradually improved and was discharged a few days later with baseline mild cognitive deficit (Van de Velde et al, 2015).

a) ATROPINE
b) BENZTROPINE
c) DICYCLOMINE
d) ORPHENADRINE
e) SCOPOLAMINE
f) TRIHEXYPHENIDYL HYDROCHLORIDE

a) 94 mg/kg (Prod Info Poison Control Monograph, Cogentin(R). benztropine, 1984)

a) 1001 to 2010 mg/kg

a) 1667 to 4000 mg/kg