Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

A)

1) SL-77499
2) CAS 81403-80-7 (alfuzosin)
3) CAS 81403-68-1 (alfuzosin hydrochloride)

1) CAS 77883-43-3 (doxazosin mesylate)
2) CAS 74191-85-8 (doxazosin)

1) Wy-21901
2) CAS 26844-12-2 (indoramin)
3) CAS 33124-53-7 (indoramin hydrochloride)

1) SKF-688A
2) CAS 59-96-1 (phenoxybenzamine)
3) CAS 63-92-3 (phenoxybenzamine hydrochloride)

1) CAS 50-60-2 (phentolamine)
2) CAS 73-05-2 (phentolamine hydrochloride)
3) CAS 65-28-1 (phentolamine mesylate)

1) 1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)
2) -4-(2-furanylcarbonyl)piperazine
3) CP 12,299-1
4) Furazosin hydrochloride
5) CAS 19216-56-9 (prazosin)
6) CAS 19237-84-4 (prazosin hydrochloride)

1) CAS 160970-54-7

1) CAS 106133-20-4 (tamsulosin)
2) CAS 106463-17-6 (tamsulosin hydrochloride)

1) Abbott 45975
2) CAS 63590-64-7 (terazosin)
3) CAS 63074-08-8 (terazosin hydrochloride, anhydrous)
4) CAS 70024-40-7 (terazosin hydrochloride, dihydrate)

1) Benzazoline hydrochloride
2) Tolazolinium Chloratum
3) 2-Benzyl-2-imidazoline hydrochloride
4) CAS 59-98-3 (tolazoline)
5) CAS 59-97-2 (tolazoline hydrochloride)

1) B-66256M
2) CAS 34661-75-1

1) BLOCKER, ALPHA-ADRENERGIC

Available Forms Sources

A)

1) ALFUZOSIN (Uroxatral(R)): 10 mg extended-release tablets
2) DOXAZOSIN (Cardura(R)): 1 mg, 2 mg, 4 mg, and 8 mg tablets
3) INDORAMIN: Available in Europe under the trade name Baratol(R) in 25 and 50 mg tablets.
4) PHENOXYBENZAMINE HYDROCHLORIDE (Dibenzyline(R)): 10 mg capsules
5) PHENTOLAMINE MESYLATE (Regitine(R)): 5 mg vial
6) PRAZOSIN (Minipress(R)): 1 mg, 2 mg, and 5 mg capsules
7) SILODOSIN: 4 mg and 8 mg capsules
8) TAMSULOSIN HYDROCHLORIDE (Flomax(R)): 0.4 mg capsules
9) TERAZOSIN (Hytrin(R)): 1 mg, 2 mg, 5 mg, and 10 mg capsules; 1 mg, 2 mg, 5 mg, and 10 mg tablets
10) TOLAZOLINE HYDROCHLORIDE (Priscoline(R)): 25 mg/mL ampuls
11) URAPIDIL is investigational

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Alpha-adrenergic blockers are used for treatment of hypertension, for symptomatic prostatic hypertrophy, and to facilitate treatment of renal stones.
B) PHARMACOLOGY: Alpha-adrenergic blockers block peripheral alpha-adrenergic receptors and cause vasodilation.
C) TOXICOLOGY: Excessive vasodilation causes hypotension and reflex tachycardia. Hypotension is generally not life-threatening.
D) EPIDEMIOLOGY: Exposures to alpha-adrenergic blockers are common. Mild to moderate symptoms occur occasionally, but severe hypotension is rare. Deaths are rare from single-substance ingestions.
E) WITH THERAPEUTIC USE

1) Orthostasis and tachycardia have occurred with therapeutic use.

F) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Orthostatic hypotension, reflex tachycardia, nausea, vomiting, and dizziness are common; syncope and mild sedation may develop.
2) SEVERE TOXICITY: Hypotension, torsades de pointes, agitation, seizures, and priapism have been reported. Hypotension is generally not life-threatening.

0.2.20)

A) Doxazosin, phenoxybenzamine, phentolamine, prazosin, terazosin, and tolazoline are classified as FDA pregnancy category C, and alfuzosin and silodosin are classified as FDA pregnancy category B. In animal studies, teratogenicity or embryotoxicity were not observed with alfuzosin or silodosin. Respiratory depression, decreased neurological tone and mild transient hypotension were seen in an newborn after the mother was treated for pheochromocytoma and given oral phenoxybenzamine at 33 weeks. Dutasteride/tamsulosin combination is categorized as FDA pregnancy category X. Dutasteride can be absorbed through the skin, and pregnant women are warned to avoid handling the soft gelatin capsules to prevent possible absorption due to the potential risk of a fetal anomaly to a male fetus. Dutasteride should not be used or handled by breastfeeding women. Refer to "Dutasteride" document for more information.

Laboratory Monitoring

A)

B)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Hypotension usually responds to IV fluids.

B) MANAGEMENT OF SEVERE TOXICITY

1) Hypotension that does not respond to IV fluids should be treated with adrenergic vasopressors such as phenylephrine or norepinephrine. Intubate patients with significant CNS depression. Treat seizures with benzodiazepines; add propofol or barbiturates if seizures persist or recur.

C) DECONTAMINATION

1) PREHOSPITAL: Prehospital decontamination is NOT recommended because of the risk for seizures.
2) HOSPITAL: Patients who are awake after a significant ingestion should be treated with activated charcoal to limit the potential for symptomatic hypotension. Gastric lavage is not indicated as overdose is rarely life-threatening.

D) AIRWAY MANAGEMENT

1) Airway management is not generally required for alpha adrenergic antagonists poisoning.

E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. 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) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. 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, if seizures continue).

1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

F) ANTIDOTE

1) None.

G) PRIAPISM

1) Priapism may occur with these agents. An immediate urological consult is necessary. Clinical history should include the use of other agents (ie, antihypertensives, antidepressants, illegal agents) that may also be contributing to priapism. In a patient with ischemic priapism the corpora cavernosa are often completely rigid and the patient complains of pain, while nonischemic priapism the corpora are typically tumescent, but not completely rigid and pain is not typical. Aspirate blood from the corpus cavernosum with a fine needle. Blood gas testing of the aspirated blood may be used to distinguish ischemic (typically PO2 less than 30 mmHg, PCO2 greater than 60 mmHg, and pH less than 7.25) and nonischemic priapism. Color duplex ultrasonography may also be useful. If priapism persists after aspiration, inject a sympathomimetic. PHENYLEPHRINE: Dose: Adult: For intracavernous injection, dilute phenylephrine with normal saline for a concentration of 100 to 500 mcg/mL and give 1 mL injections every 3 to 5 minutes for approximately 1 hour (before deciding that treatment is not successful). For children and patients with cardiovascular disease: Use lower concentrations in smaller volumes. NOTE: Treatment is less likely to be effective if done more than 48 hours after the development of priapism. Distal shunting (NOT first-line therapy) should only be considered after a trial of intracavernous injection of sympathomimetics.

H) ENHANCED ELIMINATION

1) Dialysis is not likely to be useful as these agents are highly protein bound.

I) PATIENT DISPOSITION

1) HOME CRITERIA: Unintentional ingestions by children of a single tablet or less can be observed at home; parents should be instructed to watch for dizziness or fainting. All symptomatic patients and those with self-harm ingestions should be sent to a healthcare facility.
2) OBSERVATION CRITERIA: Asymptomatic patients who have ingested an immediate-release formulation can be observed for 6 hours (observe at least 12 hours after overdose with a sustained-release formulation) and cleared if they have normal vital signs and mental status.
3) ADMISSION CRITERIA: Patients with persistent hypotension, seizures, or dysrhythmias should be admitted.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance with patients with severe toxicity or if the diagnosis is not clear.

J) PITFALLS

1) Onset of toxicity may be delayed and duration prolonged after overdose with extended-release formulations.

K) PHARMACOKINETICS

1) ALFUZOSIN: About 50% bioavailability, peak concentrations 1 to 2 hours after immediate release and 8 hours after sustained release. Protein binding 80% to 90%, volume of distribution 2.3 L/kg. Extensive hepatic metabolism; 69% fecal elimination and 11% excreted unchanged in the urine. Half-life 10 hours.
2) DOXAZOSIN: About 65% bioavailability, peak concentrations 2 to 3 hours after immediate-release and 8 to 9 hours after extended-release. Protein binding 98%. Extensive hepatic metabolism, 63% fecal and 9% renal elimination. Half-life 22 hours.
3) PRAZOSIN: Well absorbed, peak concentrations 1 to 3 hours. Protein binding greater than 90%, volume of distribution 0.5 L/kg. Hepatic metabolism, primarily excreted in bile and feces, minor (3%) renal elimination as metabolites. Half-life 2 to 4 hours.
4) SILODOSIN: About 32% bioavailability, peak concentration 2.5 hours. Protein binding 97%, volume of distribution 50 L. Extensive hepatic metabolism, about 33% renal and 55% fecal elimination. Half-life 13 hours.
5) TAMSULOSIN: Bioavailability more than 90%, peak concentrations 4 to 8 hours. Protein binding greater than 90%, volume of distribution 0.2 L/kg. Extensive hepatic metabolism, 76% renal excretion (mostly as metabolites) and 21% fecal elimination. Half-life 5 to 7 hours after immediate release, 9 to 15 hours after capsules.
6) TERAZOSIN: Bioavailability 90%, time to peak concentration 1 hour. Protein binding 90%, volume of distribution 25 to 30 L. Extensive hepatic metabolism, about 60% fecal elimination and 40% renal elimination, with only 10% to 20% of this as parent drug. Half-life 9 to 12 hours.

L) DIFFERENTIAL DIAGNOSIS

1) Other vasodilators (eg, nitroglycerine, hydralazine), ACE inhibitors, angiotensin II receptor antagonists

Range Of Toxicity

A)

B)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

1) Orthostasis and tachycardia have occurred with therapeutic use.

F)

1) MILD TO MODERATE TOXICITY: Orthostatic hypotension, reflex tachycardia, nausea, vomiting, and dizziness are common; syncope and mild sedation may develop.
2) SEVERE TOXICITY: Hypotension, torsades de pointes, agitation, seizures, and priapism have been reported. Hypotension is generally not life-threatening.

Vital Signs

3.3.4)

A) HYPOTENSION: Severe hypotension may occur with prazosin, terazosin, and doxazosin overdose (Seak & Lin, 2008; Satar et al, 2005; Lenz et al, 1985).

3.3.5)

A) WITH POISONING/EXPOSURE

1) CASE REPORT/DOXAZOSIN: A 19-year-old woman presented to the ED with hypotension (80/50 mmHg supine), tachycardia (126 bpm), and drowsiness approximately 2 hours after ingesting 60 mg of doxazosin. She recovered over 24 hours with supportive care (Satar et al, 2005).

Heent

3.4.3)

A) MIOSIS: Phenoxybenzamine produces miosis (Prod Info DIBENZYLINE(R) oral capsules, 1999).
B) MYDRIASIS: Phentolamine and tolazoline are mydriatics (Preis & Nonnan, 1987).

Cardiovascular

3.5.2)

A) HYPOTENSIVE EPISODE

1) WITH THERAPEUTIC USE

a) Orthostatic hypotension, resulting in syncope, has been reported with therapeutic use of alpha-adrenergic antagonists and may occur within a few hours following administration (Prod Info UROXATRAL(R) oral extended-release tablets, 2010; Prod Info CARDURA(R) oral tablets, 2009).
b) TERAZOSIN: Postural hypotension has been reported following therapeutic administration of terazosin for benign prostatic hypertrophy (WIlt et al, 2002; Lepor et al, 2000).

2) WITH POISONING/EXPOSURE

a) CASE REPORT: Hypotension (90/60 mmHg upon presentation to the ED) and bradycardia with ST-segment elevation were reported in a 22-year-old man following an overdose ingestion of 10 doxazosin 4 mg tablets. The patient recovered following decontamination and supportive care (Gokel et al, 2000).
b) CASE REPORT: After ingesting 5 tamsulosin (0.4 mg each) tablets, a 78-year-old woman developed headache, dizziness, syncope, orthostatic hypotension (BP 100/50 mmHg while lying and 60/40 in sitting position), and bradycardia (47-50 beats/min). Following supportive care, she recovered without further sequelae (Anand et al, 2005).
c) CASE REPORT: A 19-year-old woman presented to the ED with hypotension (80/50 mmHg supine), tachycardia (126 bpm), and drowsiness approximately 2 hours after ingesting 60 mg of doxazosin (30 2-mg tablets). She recovered over 24 hours with supportive care (Satar et al, 2005).
d) CASE REPORT: A 75-year-old man developed hypotension (73/43 mmHg) and bradycardia (42 bpm) after intentionally ingesting 300 mg of terazosin. The patient completely recovered without sequelae following supportive treatment (Seak & Lin, 2008).
e) CASE REPORT/DOXAZOSIN: A 39-year-old woman developed hypotension, that responded to IV fluids, after intentionally ingesting 70 mg doxazosin, as well as alcohol and an unknown amount of flurazepam (Prod Info CARDURA(R) oral tablets, 2009).

B) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) PRAZOSIN: Moderate tachycardia (140/min) was reported in one overdose of 200 mg in an adult (McClean, 1976).
b) CASE REPORT: A 19-year-old woman presented to the ED with hypotension (80/50 mmHg while lying down), tachycardia (126 bpm), and drowsiness approximately 2 hours after ingesting 60 mg of doxazosin (30 2-mg tablets). An ECG confirmed sinus tachycardia. She recovered over 24 hours with supportive care (Satar et al, 2005).

C) BRADYCARDIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Sinus bradycardia with ST-segment elevation, as demonstrated by an ECG, occurred in a 22-year-old man following an overdose ingestion of doxazosin (total amount ingested was 40 mg). The patient recovered following decontamination and supportive care (Gokel et al, 2000).
b) CASE REPORT: After ingesting 5 tamsulosin (0.4 mg each) tablets, a 78-year-old woman developed headache, dizziness, syncope, orthostatic hypotension (BP 100/50 mmHg while lying and 60/40 in sitting position), and bradycardia (47 to 50 beats/min). An ECG revealed sinus bradycardia with PQ and QTc intervals 0.2 sec and 0.41 sec, respectively. Following supportive care, she recovered without further sequelae (Anand et al, 2005).
c) CASE REPORT: A 75-year-old man developed hypotension (73/43 mmHg) and bradycardia (42 bpm) after intentionally ingesting 300 mg of terazosin. The patient completely recovered without sequelae following supportive treatment (Seak & Lin, 2008).

D) CONGESTIVE HEART FAILURE

1) WITH THERAPEUTIC USE

a) DOXAZOSIN: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a large, randomized, double-blind study conducted to assess whether amlodipine, lisinopril, or doxazosin will reduce the incidence of coronary artery disease when compared with chlorthalidone, has dropped doxazosin from the study due to an approximately 2-fold increase in the incidence of congestive heart failure when compared with chlorthalidone. The patients in the doxazosin group also had a 25% higher incidence of combined cardiovascular disease when compared to patients in the chlorthalidone group (Beevers & Lip, 2000; Miller, 2000; Vidt, 2000). Based on observations from this study, it has been suggested that doxazosin should not be used as monotherapy for management of stage 1 or stage 2 hypertension.

E) TORSADES DE POINTES

1) WITH POISONING/EXPOSURE

a) INDORAMIN: Torsade de pointes was reported in two patients following overdose ingestions of indoramin (Nisse et al, 2009).

1) The first patient, a 58-year-old woman, ingested 1500 mg of indoramin and developed seizures approximately 3 hours later. An ECG, obtained 10 hours postingestion, revealed a prolonged QTc interval (650 ms), and she subsequently experienced 5 episodes of torsade de pointes, each episode requiring cardioversion. With supportive care, the patient recovered and was discharged on hospital day 5 with a normal QTc interval (350 ms).
2) The second patient, a 22-year-old woman, presented to the ED with drowsiness 12 hours after ingesting an unknown amount of indoramin. An initial ECG showed a QTc interval of 480 ms. Six hours postadmission, the patient experienced one episode of torsade de pointes. A repeat ECG indicated a QTc interval of 651 ms. With supportive care, the patient's QTc interval decreased to 410 ms by hospital day 2.

Respiratory

3.6.2)

A) CHEYNE-STOKES RESPIRATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT/PRAZOSIN: Cheyne-Stokes breathing was reported in a 72-year-old man 3 hours following an ingestion of 120 mg of prazosin. Mechanical ventilation was required for 18 hours (Lenz et al, 1985).

B) BRONCHOSPASM

1) WITH POISONING/EXPOSURE

a) CASE REPORT/PRAZOSIN: Occupational asthma was reported in a pharmaceutical worker exposed to prazosin intermittently for 3 years. Symptoms were sneezing, dyspnea, and wheezing (Perrin et al, 1990).

Neurologic

3.7.2)

A) SEIZURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT/INDORAMIN: Extreme CNS stimulation and seizures have been noted. Refractory seizures resulting in death were noted in a 43-year-old woman within 7 hours of ingesting 2.5 grams indoramin (Hunter, 1982).
b) CASE REPORT/INDORAMIN: Seizures occurred in a 58-year-old woman approximately 3 hours after ingesting 1500 mg of indoramin. The patient also experienced several episodes of torsade de pointes, requiring cardioversion. With supportive care, the patient recovered and was discharged on hospital day 5 (Nisse et al, 2009).
c) CASE REPORT/DOXAZOSIN: A 32-year-old woman with chronic renal failure, epilepsy, and depression, developed hypotension and a grand-mal seizure, resulting in death, after intentionally ingesting 60 mg doxazosin. Doxazosin blood concentration was 0.9 mcg/mL (normal 0.02 mcg/mL) (Prod Info CARDURA(R) oral tablets, 2009).

B) DIZZINESS

1) WITH THERAPEUTIC USE

a) TERAZOSIN: Headache, dizziness, and asthenia have been reported with therapeutic use of terazosin (WIlt et al, 2002; Lepor et al, 2000; Sperzel et al, 1986).

2) WITH POISONING/EXPOSURE

a) CASE REPORT/TAMSULOSIN: After ingesting 5 tamsulosin (0.4 mg each) tablets, a 78-year-old woman developed headache, dizziness, syncope, orthostatic hypotension (BP 100/50 mmHg while lying and 60/40 in sitting position), and bradycardia (47 to 50 beats/min). Following supportive care, she recovered without further sequelae (Anand et al, 2005).
b) CASE REPORT/TERAZOSIN: Headache and dizziness occurred in a 75-year-old man who intentionally ingested 300 mg of terazosin (Seak & Lin, 2008).

C) SYNCOPE

1) WITH THERAPEUTIC USE

a) Syncope within 30 to 90 minutes of a first dose or change in dose has been reported with prazosin and terazosin. Literature suggests this effect may be minimized by initiating the first increased dose at bedtime (Rosendorff, 1976).

2) WITH POISONING/EXPOSURE

a) CASE REPORT/TAMSULOSIN: After ingesting 5 tamsulosin (0.4 mg each) tablets, a 78-year-old woman developed headache, dizziness, syncope, orthostatic hypotension (BP 100/50 mmHg while lying and 60/40 in sitting position), and bradycardia (47 to 50 beats/min). Following supportive care, she recovered without further sequelae (Anand et al, 2005).

D) HEADACHE

1) WITH POISONING/EXPOSURE

a) CASE REPORT/TAMSULOSIN: After ingesting 5 tamsulosin (0.4 mg each) tablets, a 78-year-old woman developed headache, dizziness, syncope, orthostatic hypotension (BP 100/50 mmHg while lying and 60/40 in sitting position), and bradycardia (47 to 50 beats/min). Following supportive care, she recovered without further sequelae (Anand et al, 2005).
b) CASE REPORT/TERAZOSIN: Headache and dizziness occurred in a 75-year-old man who intentionally ingested 300 mg of terazosin (Seak & Lin, 2008).

E) DROWSY

1) WITH POISONING/EXPOSURE

a) CASE REPORT/DOXAZOSIN: A 19-year-old woman presented to the ED with hypotension (80/50 mmHg while lying down), tachycardia (126 bpm), and drowsiness approximately 2 hours after ingesting 60 mg of doxazosin (30 2-mg tablets). She recovered over 24 hours with supportive care (Satar et al, 2005).
b) CASE REPORT/INFANT: A 6-month-old child became drowsy after inadvertently receiving a crushed 1 mg tablet of immediate-release doxazosin (Prod Info CARDURA(R) oral tablets, 2009).
c) CASE REPORT/PRAZOSIN: A 2-year-old child unintentionally ingested at least 50 mg of prazosin. Symptoms included profound drowsiness and depressed reflexes, although no decrease in blood pressure. Recovery was uneventful (Prod Info Minipress(R) oral capsules, 2009a).

Gastrointestinal

3.8.2)

A) VOMITING

1) WITH POISONING/EXPOSURE

a) Toxic symptoms include severe GI effects with vomiting and diarrhea following large oral doses (Prod Info phentolamine mesylate injection, 1999).

B) PEPTIC ULCER

1) WITH THERAPEUTIC USE

a) Peptic ulcer is frequently exacerbated by these agents (Butt et al, 1986).

C) INCONTINENCE OF FECES

1) WITH THERAPEUTIC USE

a) PRAZOSIN: Prazosin has been associated with a case of fecal incontinence (Holmes et al, 1990).

D) GASTROINTESTINAL HEMORRHAGE

1) WITH THERAPEUTIC USE

a) CASE REPORT/TOLAZOLINE: Tolazoline stimulates gastric H2 receptors and may precipitate gastric hemorrhage. A neonate developed pulmonary hypertension and was treated with intravenous tolazoline 2 mg/kg/hour. Two hours after initiation of tolazoline therapy, the neonate developed voluminous coffee ground gastric secretions (Kuint et al, 1996).

Genitourinary

3.10.2)

A) PRIAPISM

1) WITH THERAPEUTIC USE

a) CASE REPORT/DOXAZOSIN: A 66-year-old man developed priapism approximately 15 days after taking 8 mg of doxazosin (normal dosage regimen was 4 mg daily) for benign prostatic hypertrophy. The patient recovered following surgical intervention and cessation of doxazosin therapy (Avisrror et al, 2000).

2) WITH POISONING/EXPOSURE

a) CASE REPORT/PRAZOSIN: Priapism (painful prolonged erection) was described in a 25-year-old man 24 hours following an overdose ingestion of 150 mg of prazosin (Robbins et al, 1983).

B) URINARY INCONTINENCE

1) WITH THERAPEUTIC USE

a) PRAZOSIN has been associated with a couple of cases of urinary incontinence thought to be due to alpha-adrenoceptor blockage (Kiruluta et al, 1981; Thien et al, 1978) .

Hematologic

3.13.2)

A) LEUKOCYTOSIS

1) WITH THERAPEUTIC USE

a) Mild leukocytosis (leukocytes 14.4 x 10(9)/L, eosinophils 1.4 x 10(9)/L) and a slightly increased erythrocyte sedimentation rate (25 mm/h) occurred in a 56-year-old man 3 days after starting terazosin therapy, 2 mg/day (Hernandez-Cano et al, 1998).

Dermatologic

3.14.2)

A) FLUSHING

1) WITH THERAPEUTIC USE

a) Flushing may occur due to vasodilation of cutaneous vessels (Prod Info UROXATRAL(R) oral extended-release tablets, 2010; Prod Info phentolamine mesylate injection, 1999).

B) ERUPTION

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 56-year-old man developed a generalized erythematous rash with scaling plaques on his trunk and extremities, including palms and soles, 3 days after beginning terazosin therapy (2 mg/day) to treat benign prostatic hyperplasia. Inguinal lymphadenopathy was also noted during medical examination. The patient completely recovered following discontinuation of the terazosin and beginning treatment with oral methylprednisolone (40 mg/day) and emollients (Hernandez-Cano et al, 1998).

Immunologic

3.19.2)

A) ACUTE ALLERGIC REACTION

1) WITH THERAPEUTIC USE

a) CASE REPORT/PRAZOSIN: Urticaria and facial edema were reported in a 70-year-old woman while on prazosin. Sensitivity was verified by prick test (Ruzicka & Ring, 1983).

Reproductive

3.20.1)

A) Doxazosin, phenoxybenzamine, phentolamine, prazosin, terazosin, and tolazoline are classified as FDA pregnancy category C, and alfuzosin and silodosin are classified as FDA pregnancy category B. In animal studies, teratogenicity or embryotoxicity were not observed with alfuzosin or silodosin. Respiratory depression, decreased neurological tone and mild transient hypotension were seen in an newborn after the mother was treated for pheochromocytoma and given oral phenoxybenzamine at 33 weeks. Dutasteride/tamsulosin combination is categorized as FDA pregnancy category X. Dutasteride can be absorbed through the skin, and pregnant women are warned to avoid handling the soft gelatin capsules to prevent possible absorption due to the potential risk of a fetal anomaly to a male fetus. Dutasteride should not be used or handled by breastfeeding women. Refer to "Dutasteride" document for more information.

3.20.2)

A) PLACENTAL BARRIER

1) PHENOXYBENZAMINE - CASE REPORT - A 22-year-old pregnant woman was diagnosed with pheochromocytoma and was given oral phenoxybenzamine (10 mg three times daily) and oral labetalol (100 mg three times daily) at 33 weeks gestation until delivery by cesarean section. The newborn showed respiratory depression, decreased neurological tone, and mild transient hypotension following delivery. At the time of the cesarean section, samples, obtained from the cord blood, maternal blood, and amniotic fluid, were analyzed for phenoxybenzamine. The mean concentrations of phenoxybenzamine, from those samples, were 103.3, 66, and 79.3 ng/mL, respectively, and the fetal-maternal plasma accumulation ratio was 1.6:1, indicating the placental transfer of phenoxybenzamine (Santeiro et al, 1996).

B) LACK OF EFFECT

1) DOXAZOSIN

a) In animal studies, no evidence of fetal harm was observed when pregnant rabbits and rats were administered daily oral doses up to 41 and 20 mg/kg (10 and 4 times the human Cmax and AUC exposure with a 12 mg/day dose), respectively. However, reduced fetal survival was observed in rabbits administered at 82 mg/kg/day. Postnatal development (body weight gain and appearance of anatomical features and reflexes) was delayed in rats administered maternal doses of 40 or 50 mg/kg/day (8 times the human AUC exposure with a 12 mg/day dose). In pregnant rats, doxazosin was found to cross the placenta (Prod Info CARDURA(R) oral tablets, 2013).

2) TAMSULOSIN

a) RATS: Studies in rats receiving tamsulosin in doses of 300 mg/kg a day (AUC exposure in rats approximately 50 times the maximum human exposure using the maximum therapeutic dose) showed no evidence of fetal harm (Prod Info JALYN(R) oral capsules, 2010).
b) RABBITS: In a studies of pregnant female rabbits receiving tamsulosin 50 mg/kg/day showed no evidence of fetal harm (Prod Info JALYN(R) oral capsules, 2010).

C) ANIMAL STUDIES

1) ALFUZOSIN

a) There was no evidence of teratogenicity or embryotoxicity when pregnant rats were given alfuzosin maternal doses up to 1200 times the expected human systemic exposure. Rabbit data was similarly negative at doses approximately 3 times the clinical dose (Prod Info UROXATRAL(R) oral extended-release tablets, 2008).

2) SILODOSIN

a) There was no evidence of teratogenicity or embryotoxicity when pregnant rats were given silodosin during organogenesis at approximately 20 times the maximum recommended human exposure (MRHE). Rabbit data was similarly negative at doses approximately 13 to 25 times the MRHE. Offspring of rats treated during pregnancy and lactation with silodosin (up to 300 mg/kg/day) showed no effects in physical or behavioral development (Prod Info RAPAFLO(TM) oral capsules, 2008).

3) TAMSULOSIN/DUTASTERIDE

a) Dutasteride has demonstrated teratogenicity in developmental toxicity and animal reproduction studies (Prod Info JALYN(R) oral capsules, 2010).
b) Refer to "Dutasteride" document for more information.

3.20.3)

A) PREGNANCY CATEGORY

1) ALFUZOSIN

a) The manufacturer has classified alfuzosin as FDA pregnancy category B (Prod Info UROXATRAL(R) oral extended-release tablets, 2008).

2) DOXAZOSIN

a) The manufacturer has classified doxazosin as FDA pregnancy category C (Prod Info CARDURA(R) oral tablets, 2013).

3) PHENOXYBENZAMINE

a) The manufacturer has classified phenoxybenzamine as FDA pregnancy category C (Prod Info DIBENZYLINE(R) oral capsules, 1999).

4) PHENTOLAMINE

a) The manufacturer has classified phentolamine as FDA pregnancy category C (Prod Info phentolamine mesylate injection, 1999).

5) PRAZOSIN

a) The manufacturer has classified prazosin as FDA pregnancy category C (Prod Info MINIPRESS(R) oral capsules, 2000).

6) SILODOSIN

a) The manufacturer has classified silodosin as FDA pregnancy category B (Prod Info RAPAFLO(TM) oral capsules, 2008).

7) TAMSULOSIN/DUTASTERIDE

a) The manufacturer has classified dutasteride/tamsulosin as FDA pregnancy category X. Dutasteride can be absorbed through the skin, and pregnant women are warned to avoid handling the soft gelatin capsules to prevent possible absorption due to the potential risk of a fetal anomaly to a male fetus (Prod Info JALYN(R) oral capsules, 2010).

8) TERAZOSIN

a) The manufacturer has classified terazosin as FDA pregnancy category C (Prod Info HYTRIN(R) oral capsules, 2005).

9) TOLAZOLINE

a) Tolazoline is classified as FDA pregnancy category C (Prod Info Priscoline(R), 1998).

B) ANIMAL STUDIES

1) ALFUZOSIN

a) Gestation was slightly prolonged in rats receiving alfuzosin doses 12 times higher than expected human exposure levels. There were no apparent sequelae on delivery or labor (Prod Info UROXATRAL(R) oral extended-release tablets, 2008).

2) DOXAZOSIN

a) In animal studies, no evidence of fetal harm was observed when pregnant rabbits and rats were administered daily oral doses up to 41 and 20 mg/kg (10 and 4 times the human Cmax and AUC exposure with a 12 mg/day dose), respectively. However, reduced fetal survival was observed in rabbits administered at 82 mg/kg/day. Postnatal development (body weight gain and appearance of anatomical features and reflexes) was delayed in rats administered maternal doses of 40 or 50 mg/kg/day (8 times the human AUC exposure with a 12 mg/day dose). In pregnant rats, doxazosin was found to cross the placenta (Prod Info CARDURA(R) oral tablets, 2013).

3.20.4)

A) DOXAZOSIN

1) When a 37-year-old breastfeeding woman was administered 2 oral doses of doxazosin 4 mg approximately 24 hours apart, it resulted in an AUC (0 to 18 hours) of 52 and 525 mg/L.hr in the milk and plasma, respectively. Given the milk/plasma AUC ratio of 0.1, the average doxazosin concentration in milk (over the study period) of 2.93 mcg/L, and an average infant milk intake of 0.15 L/kg/day, an absolute infant dose of 0.044 mcg/kg/day was calculated, which corresponded to an estimated relative infant dose of 0.06%. When the maximum relative infant dose of 4.15 mcg/L was used, an absolute infant dose of 0.062 mcg/kg/day was calculated, which corresponded to a relative infant dose of 0.09%. Since these values are below the generally accepted cutoff of 10% for predicting safety during breastfeeding, it was concluded that maternal doxazosin therapy may be compatible with breastfeeding following a thorough risk-benefit analysis (Jensen et al, 2013). Exercise caution when administering this drug to a breastfeeding woman (Prod Info CARDURA(R) oral tablets, 2013).

B) DUTASTERIDE/TAMSULOSIN

1) It is not known if dutasteride/tamsulosin is excreted in human milk, and the potential for adverse effects in the nursing infant from exposure to the drug are unknown. Dutasteride/tamsulosin should not be used or handled by breastfeeding women (Prod Info JALYN(R) oral capsules, 2010).

C) ANIMAL STUDIES

1) DOXAZOSIN

a) Animal studies have also shown that doxazosin accumulates in the breast milk of lactating rats at approximately 20 times the maternal plasma concentration. Exercise caution when administering this drug to a breastfeeding woman (Prod Info CARDURA(R) oral tablets, 2013).

2) SILODOSIN

a) Offspring of rats treated during pregnancy and lactation with silodosin (up to 300 mg/kg/day) showed no effects in physical or behavioral development (Prod Info RAPAFLO(TM) oral capsules, 2008).

3.20.5)

A) ANIMAL STUDIES

1) DUTASTERIDE/TAMSULOSIN: Impaired fertility has been reported in male rats exposed to dutasteride or tamsulosin, and female rats have had reduced litter sizes and fetal body weights, along with increased embryo resorption and feminization of male fetuses (Prod Info JALYN(R) oral capsules, 2010).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Obtain an ECG and monitor renal function and serum electrolytes in hypotensive patients.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with persistent hypotension, seizures, or dysrhythmias should be admitted.

6.3.1.2) HOME CRITERIA/ORAL

A) Unintentional ingestions by children of a single tablet or less can be observed at home; parents should be instructed to watch for dizziness or fainting. All symptomatic patients and those with self-harm ingestions should be sent to a healthcare facility.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a poison center or medical toxicologist for assistance with patients with severe toxicity or if the diagnosis is not clear.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Asymptomatic patients who have ingested an immediate-release formulation can be observed for 6 hours (observe at least 12 hours after overdose with a sustained-release formulation) and cleared if they have normal vital signs and mental status.

Monitoring

A)

B)

Oral Exposure

6.5.1)

A) No pre-hospital decontamination is recommended because of the risk for seizures.

6.5.2)

A) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

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.

2) CHARCOAL DOSE

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).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Obtain an ECG and monitor renal function and serum electrolytes in hypotensive patients.

B) HYPOTENSIVE EPISODE

1) Administer 10 to 20 mL/kg of isotonic IV fluids and place in Trendelenburg position. In theory, agents with beta adrenergic activity such as epinephrine or dopamine may worsen hypotension induced by alpha-adrenergic antagonists. If hypotension is unresponsive to IV fluids, agents with alpha adrenergic effects such as phenylephrine or norepinephrine may be preferred.
2) PHENYLEPHRINE

a) MILD OR MODERATE HYPOTENSION

1) INTRAVENOUS: ADULT: Usual dose: 0.2 mg; range: 0.1 mg to 0.5 mg. Maximum initial dose is 0.5 mg. A 0.5 mg IV dose can elevate the blood pressure for approximately 15 min (Prod Info phenylephrine HCl subcutaneous injection, intramuscular injection, intravenous injection, 2011). PEDIATRIC: Usual bolus dose: 5 to 20 mcg/kg IV repeated every 10 to 15 min as needed (Taketomo et al, 1997).

b) CONTINUOUS INFUSION

1) PREPARATION: Add 10 mg (1 mL of a 1% solution) to 500 mL of normal saline or dextrose 5% in water to produce a final concentration of 0.2 mg/mL.
2) ADULT DOSE: To raise blood pressure rapidly; start an initial infusion of 100 to 180 mcg/min until blood pressure stabilizes; then reduce infusion to 40 to 60 mcg/min titrated to desired effect. If necessary, additional doses in increments of 10 mg or more may be added to the infusion solution and the rate of flow titrated to the desired effect (Prod Info phenylephrine HCl subcutaneous injection, intramuscular injection, intravenous injection, 2011).
3) PEDIATRIC DOSE: Intravenous infusion should begin at 0.1 to 0.5 mcg/kg/min; titrate to the desired effect (Taketomo et al, 1997).

c) ADVERSE EFFECTS

1) Headache, reflex bradycardia, excitability, restlessness and rarely dysrhythmias may develop (Prod Info phenylephrine HCl subcutaneous injection, intramuscular injection, intravenous injection, 2011).

3) NOREPINEPHRINE

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

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

C) VENTRICULAR ARRHYTHMIA

1) SUMMARY: Tachycardia is common. Specific alpha-adrenergic agonists such as norepinephrine are preferred for the treatment of hypotension because agents with combined alpha- and beta-agonist effects may worsen tachycardia and further increase myocardial oxygen demand.

a) Profound reflex tachycardia may occur. PHENTOLAMINE and TOLAZOLINE are more frequently associated with ventricular dysrhythmias which may respond to lidocaine or procainamide.

2) LIDOCAINE

a) LIDOCAINE/DOSE

1) 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.

a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).

2) 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).

b) LIDOCAINE/MAJOR ADVERSE REACTIONS

1) 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).

c) LIDOCAINE/MONITORING PARAMETERS

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

3) PROCAINAMIDE

a) PROCAINAMIDE/ADULT LOADING DOSE

1) 20 to 50 milligrams/minute IV until dysrhythmia is suppressed or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%), or a total dose of 17 milligrams/kilogram is given (1.2 grams for a 70 kilogram person) (Neumar et al, 2010).
2) ALTERNATIVE DOSING: 100 mg every 5 minutes until dysrhythmia is controlled, or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%) or 17 mg/kg have been given (Neumar et al, 2010).
3) MAXIMUM DOSE: 17 milligrams/kilogram (Neumar et al, 2010).

b) PROCAINAMIDE/CONTROLLED INFUSION

1) In conscious patients, procainamide should be administered as a controlled infusion (20 milligrams/minute) because of the risk of QT prolongation and its hypotensive effects (Link et al, 2015)

c) PROCAINAMIDE/ADULT MAINTENANCE DOSE

1) 1 to 4 milligrams/minute via an intravenous infusion (Neumar et al, 2010).

d) PROCAINAMIDE/PEDIATRIC LOADING DOSE

1) 15 milligrams/kilogram IV/Intraosseously over 30 to 60 minutes; discontinue if hypotension develops or the QRS widens by 50% (Kleinman et al, 2010).

e) PROCAINAMIDE/PEDIATRIC MAINTENANCE DOSE

1) Initiate at 20 mcg/kg/minute and increase in 10 mcg/kg/minute increments every 15 to 30 minutes until desired effect is achieved; up to 80 mcg/kg/minute (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).

f) PROCAINAMIDE/PEDIATRIC MAXIMUM DOSE

1) 2 grams/day (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).

g) MONITORING PARAMETERS

1) ECG, blood pressure, and blood concentrations (Prod Info procainamide HCl IV, IM injection solution, 2011). Procainamide can produce hypotension and QT prolongation (Link et al, 2015).

h) AVOID

1) Avoid in patients with QT prolongation and CHF (Neumar et al, 2010).

D) TORSADES DE POINTES

1) SUMMARY

a) Withdraw the causative agent. Hemodynamically unstable patients with Torsades de pointes (TdP) require electrical cardioversion. Emergent treatment with magnesium (first-line agent) or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia). Correct hypoxia, if present (Drew et al, 2010; Neumar et al, 2010; Keren et al, 1981; Smith & Gallagher, 1980).
b) Polymorphic VT associated with acquired long QT syndrome may be treated with IV magnesium. Overdrive pacing or isoproterenol may be successful in terminating TdP, particularly when accompanied by bradycardia or if TdP appears to be precipitated by pauses in rhythm (Neumar et al, 2010). In patients with polymorphic VT with a normal QT interval, magnesium is unlikely to be effective (Link et al, 2015).

2) MAGNESIUM SULFATE

a) Magnesium is recommended (first-line agent) for the prevention and treatment of drug-induced torsades de pointes (TdP) even if the serum magnesium concentration is normal. QTc intervals greater than 500 milliseconds after a potential drug overdose may correlate with the development of TdP (Charlton et al, 2010; Drew et al, 2010). ADULT DOSE: No clearly established guidelines exist; an optimal dosing regimen has not been established. Administer 1 to 2 grams diluted in 10 milliliters D5W IV/IO over 15 minutes (Neumar et al, 2010). Followed if needed by a second 2 gram bolus and an infusion of 0.5 to 1 gram (4 to 8 mEq) per hour in patients not responding to the initial bolus or with recurrence of dysrhythmias (American Heart Association, 2005; Perticone et al, 1997). Rate of infusion may be increased if dysrhythmias recur. For persistent refractory dysrhythmias, a continuous infusion of up to 3 to 10 milligrams/minute in adults may be given (Charlton et al, 2010).
b) PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes up to 2 g (Charlton et al, 2010).
c) PRECAUTIONS: Use with caution in patients with renal insufficiency.
d) MAJOR ADVERSE EFFECTS: High doses may cause hypotension, respiratory depression, and CNS toxicity (Neumar et al, 2010). Toxicity may be observed at magnesium levels of 3.5 to 4.0 mEq/L or greater (Charlton et al, 2010).
e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium concentrations (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009).

3) OVERDRIVE PACING

a) Institute electrical overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated. Rates of 100 to 120 beats per minute may terminate torsades (American Heart Association, 2005). Pacing can be used to suppress self-limited runs of TdP that may progress to unstable or refractory TdP, or for override refractory, persistent TdP before the potential development of ventricular fibrillation (Charlton et al, 2010). In a case series overdrive pacing was successful in terminating TdP associated with bradycardia and drug-induced QT prolongation (Neumar et al, 2010).

4) POTASSIUM REPLETION

a) Potassium supplementation, even if serum potassium is normal, has been recommended by many experts (Charlton et al, 2010; American Heart Association, 2005). Supplementation to supratherapeutic potassium concentrations of 4.5 to 5 mmol/L has been suggested, although there is little evidence to determine the optimal range in dysrhythmia (Drew et al, 2010; Charlton et al, 2010).

5) ISOPROTERENOL

a) Isoproterenol has been successful in aborting torsades de pointes that was resistant to magnesium therapy in a patient in whom transvenous overdrive pacing was not an option (Charlton et al, 2010) and has been successfully used to treat torsades de pointes associated with bradycardia and drug induced QT prolongation (Keren et al, 1981; Neumar et al, 2010). Isoproterenol may have a limited role in pharmacologic overdrive pacing in select patients with drug-induced torsades de pointes and acquired long QT syndrome (Charlton et al, 2010; Neumar et al, 2010). Isoproterenol should be avoided in patients with polymorphic VT associated with familial long QT syndrome (Neumar et al, 2010).
b) DOSE: ADULT: 2 to 10 micrograms/minute via a continuous monitored intravenous infusion; titrate to heart rate and rhythm response (Neumar et al, 2010).
c) PRECAUTIONS: Correct hypovolemia before using; contraindicated in patients with acute cardiac ischemia (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

1) Contraindicated in patients with preexisting dysrhythmias; tachycardia or heart block due to digitalis toxicity; ventricular dysrhythmias that require inotropic therapy; and angina. Use with caution in patients with coronary insufficiency (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

d) MAJOR ADVERSE EFFECTS: Tachycardia, cardiac dysrhythmias, palpitations, hypotension or hypertension, nervousness, headache, dizziness, and dyspnea (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respirations and central venous pressure to guide volume replacement (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

6) OTHER DRUGS

a) Mexiletine, verapamil, propranolol, and labetalol have also been used to treat TdP, but results have been inconsistent (Khan & Gowda, 2004).

7) AVOID

a) Avoid class Ia antidysrhythmics (eg, quinidine, disopyramide, procainamide, aprindine), class Ic (eg, flecainide, encainide, propafenone) and most class III antidysrhythmics (eg, N-acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with TdP.

E) SEIZURE

1) SUMMARY

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).

2) DIAZEPAM

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 .

3) NO INTRAVENOUS ACCESS

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).

4) LORAZEPAM

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, 2009; Chin et al, 2008).

5) PHENOBARBITAL

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).

6) OTHER AGENTS

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):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

7) RECURRING SEIZURES

a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:

1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)

b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

F) PRIAPISM

1) SUMMARY

a) Priapism may occur with these agents.

2) GUIDELINE ON THE MANAGEMENT OF PRIAPISM

a) The following American Urological Association Guideline has been developed to evaluate and treat priapism (Montague et al, 2003):

1) Ischemic priapism is characterized by little or no cavernous blood flow and abnormal cavernous blood gases (hypoxic, hypercarbic and acidotic).

a) CLINICAL HISTORY: A clear history can determine the most effective treatment and should include the following:

1) Duration of erection.
2) Degree of pain (ischemic priapism is painful; nonischemic is not painful).
3) Use of drug(s) associated with priapism (eg, antihypertensives, anticoagulants, antidepressants, illegal agents).
4) Underlying disease (eg, sickle cell) or trauma.

b) LABORATORY ANALYSIS: CBC, reticulocyte count, hemoglobin electrophoresis to rule out acute infection or underlying disease, psychoactive medication screening, and urine toxicology.
c) PHYSICAL EXAMINATION: In a patient with ischemic priapism the corpora cavernosa are often completely rigid and painful while nonischemic priapism the corpora are typically tumescent, but not completely rigid, and is usually not painful.
d) DIAGNOSTIC STUDIES: Blood gas testing and color duplex ultrasonography are the most reliable methods to distinguish between ischemic and nonischemic priapism.

1) Ischemic finding: Blood aspirated from the corpus cavernosum is hypoxic and appears dark, and on blood gas testing typically has a PO2 of less than 30 mmHg and a PCO2 of greater than 60 mmHg and a pH of less than 7.25.
2) Nonischemic finding: Blood is generally well oxygenated and appears bright red. Cavernosal blood gases are similar to normal arterial blood gas findings.
3) Color Duplex Ultrasonography: Ischemic patient: Little or no blood flow in the cavernosal arteries.
4) Penile Arteriography: An adjunctive study that has been mostly replaced by ultrasonography; it is often used only as part of an embolization procedure.

e) TREATMENT: Ischemic priapism: Initial treatment usually includes therapeutic aspiration (with or without irrigation) followed by intracavernous injection of sympathomimetics (agents frequently used: epinephrine, norepinephrine, phenylephrine, ephedrine and metaraminol) as needed. Of these agents, resolution of ischemic effects occurred in 81% treated with epinephrine, 70% with metaraminol, 43% with norepinephrine and 65% with phenylephrine. To minimize adverse events, phenylephrine is an alpha1-selective adrenergic agonist is often selected because it produces no indirect neurotransmitter releasing action. Repeat sympathomimetic injection prior to considering surgical intervention.

1) PHENYLEPHRINE: Dose: Adult: For intracavernous injection, dilute phenylephrine with normal saline for a concentration of 100 to 500 mcg/mL and 1 mL injections every 3 to 5 minutes for approximately 1 hour (before deciding that treatment is not successful). For children and patients with cardiovascular disease: Use lower concentrations in smaller volumes. NOTE: Treatment is less likely to be effective if done more than 48 hours after the development of priapism.
2) DISTAL SHUNTING (NOT first -line therapy): Inserting a surgical shunt should ONLY be considered after a trial of intracavernous injection of sympathomimetics. A caveroglanular (corporoglanular) shunt is the preferred method to avoid complications.

Enhanced Elimination

A)

1) Dialysis is not likely to be useful as these agents are highly protein bound.

Abstracts

Case Reports

A)

1) PRAZOSIN: One case of a 19-year-old man who ingested 200 mg in an apparent suicide attempt has been reported. One and one-half hours postingestion, his BP was 110/80 mmHg with a heart rate of 110/minute.

a) The patient was observed following emesis and kept supine for 36 hours. The patient was conscious and oriented; however, after 6 hours the pulse rate increased to 140/minute with a BP minimum of 95/60. No serious effects were noted and BP and heart rate returned to normal after 36 hours (McClean, 1976).

Range Of Toxicity

Summary

A)

B)

Therapeutic Dose

7.2.1)

A) SPECIFIC SUBSTANCE

1) ALFUZOSIN

a) For the treatment of benign prostatic hyperplasia, the recommended dose is 10 mg orally once daily, taken immediately after the same meal each day (Prod Info UROXATRAL(R) oral extended-release tablets, 2010).

2) DOXAZOSIN

a) BENIGN PROSTATIC HYPERPLASIA (BPH): The recommended initial adult dose is 1 mg orally once daily. The dose may be increased up to a maximum dose of 8 mg once daily, depending on the patient's clinical response to the medication. The recommended titration interval is 1 to 2 weeks (Prod Info CARDURA(R) oral tablets, 2009).
b) HYPERTENSION: The recommended initial adult dose is 1 mg orally once daily. The dose may be increased up to a maximum of 16 mg once daily, depending on the patient's clinical response to the medication (Prod Info CARDURA(R) oral tablets, 2009).

3) PHENOXYBENZAMINE

a) Initially 10 mg orally twice a day. Dosage should be increased every other day, usually to 20 to 40 mg twice a day or three times a day until an optimal dosage is obtained as judged by blood pressure control (Prod Info DIBENZYLINE(R) oral capsules, 1999).

4) PHENTOLAMINE

a) Preoperative reduction of elevated blood pressure, 5 mg IV or IM 1 or 2 hours before surgery and repeated if necessary (Prod Info phentolamine mesylate injection, 1999).
b) For control of hypertension during surgery, 5 mg is administered IV as indicated (Prod Info phentolamine mesylate injection, 1999).
c) For severe hypertension caused by agents with alpha adrenergic agonist effects: 5 to 15 mg IV bolus repeated as needed (U.S. Departement of Health and Human Services, National Institutes of Health, and National Heart, Lung, and Blood Institute, 2004). CONTINUOUS INFUSION: 1 mg/hr, adjusted hourly to stabilize blood pressure. Prepared by adding 60 mg of phentolamine mesylate to 100 mL of 0.9% sodium chloride injection; 12 to 52 mg/hr has been used in case reports (McMillian et al, 2011).
d) For prevention of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine, 10 mg of phentolamine is added to each liter of solution containing norepinephrine (Prod Info phentolamine mesylate injection, 1999).
e) For treatment of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine, 5 to 10 mg of phentolamine in 10 mL of saline is injected, within 12 hours, into the area of extravasation (Prod Info phentolamine mesylate injection, 1999).
f) For diagnosis of pheochromocytoma, 5 mg is administered IV or IM (Prod Info phentolamine mesylate injection, 1999).

5) PRAZOSIN

a) Begin with 1 mg orally 2 to 3 times daily, and may be increased up to 20 mg daily, given in divided doses (Prod Info Minipress(R) oral capsules, 2009).

6) SILODOSIN

a) For treatment of benign prostatic hyperplasia, the recommended adult dose is 8 mg orally once daily with food. The dose may be reduced to 4 mg once daily in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min) (Prod Info RAPAFLO(R) oral capsule, 2009).

7) TAMSULOSIN

a) For the treatment of benign prostatic hyperplasia (BPH), the recommended adult dose is 0.4 mg orally once daily. If the patient's clinically unresponsive to the medication after 2 to 4 weeks of dosing, the dose may be increased to 0.8 mg once daily (Prod Info Flomax(R) oral capsules, 2011).

8) TERAZOSIN

a) BPH: The recommended initial adult dose is 1 mg orally once daily at bedtime. The dose may be increased to 2 mg, 5 mg, or 10 mg once daily, depending on the patient's clinical response to the medication. The maximum dose is 20 mg once daily (Prod Info HYTRIN(R) oral tablets, 2009).
b) HYPERTENSION: The recommended initial adult dose is 1 mg orally once daily at bedtime. The usual dosage regimen is 1 to 5 mg once daily, up to a maximum of 20 mg once daily (Prod Info HYTRIN(R) oral tablets, 2009).

7.2.2)

A) SPECIFIC SUBSTANCE

1) ALFUZOSIN

a) Alfuzosin is not indicated for use in the pediatric population (Prod Info UROXATRAL(R) oral extended-release tablets, 2010).

2) DOXAZOSIN

a) According to the manufacturer, the safety and effectiveness in the pediatric population have not been established (Prod Info CARDURA(R) oral tablets, 2009).
b) HYPERTENSION: Based on a report from National High Blood Pressure Education Program (NHBPEP) Working Group on Children and Adolescents, the initial recommended dose is 1 mg orally once daily; MAXIMUM 4 mg/day orally (NoneListed, 2004).

3) PHENOXYBENZAMINE

a) According to the manufacturer, safety and effectiveness in the pediatric population have not been established (Prod Info DIBENZYLINE(R) oral capsules, 1999).

4) PHENTOLAMINE

a) For preoperative reduction of elevated blood pressure, 1 mg administered IV or IM 1 to 2 hours before surgery. The dose may be repeated as needed (Prod Info phentolamine mesylate injection, 1999).
b) For control of hypertension during surgery, 1 mg administered IV as indicated (Prod Info phentolamine mesylate injection, 1999).
c) Diagnosis of pheochromocytoma: For IV administration, 1 mg is dissolved in 1 mL of sterile water and injected. For IM administration, 3 mg is dissolved in 1 mL of sterile water and injected. Blood pressure response is recorded to determine a positive diagnosis of pheochromocytoma. A positive response, suggestive of pheochromocytoma, is indicated when the systolic and diastolic blood pressure is reduced to more than 35 mmHg and 25 mmHg, respectively (Prod Info phentolamine mesylate injection, 1999).
d) HYPERTENSIVE CRISIS: 0.05 to 0.1 milligram/kilogram/dose (maximum of 5 milligrams per dose) intravenously every 5 minutes until hypertension is controlled, then every 2 to 4 hours as needed (Singh et al, 2012; Koch-Weser, 1974).
e) HYPERTENSIVE CRISIS ASSOCIATED WITH PHEOCHROMOCYTOMA: 1 mg IV during surgery and repeated if necessary (Prod Info phentolamine mesylate injection, 1999; Stringel et al, 1980).
f) VASOPRESSOR EXTRAVASATION: Inject a 0.5 to 1 mg/mL solution (5 to 10 mg in 10 mL of normal saline) of phentolamine subcutaneously into the affected area. Inject 0.2 to 1 mL at a time into extravasated area until entire site is infiltrated. Replace needle with each injection. Usual total amount needed is 1 to 5 mL, depending on the size of the infiltrate, but a higher amount may be needed. Should be injected into area of extravasation within 12 hours. May be repeated if necessary (Thigpen, 2007; Prod Info phentolamine mesylate injection, 1999; Hill, 1991; Siwy & Sadove, 1987; MacCara, 1983).

5) PRAZOSIN

a) According to the manufacturer, safety and effectiveness in the pediatric population have not been established (Prod Info Minipress(R) oral capsules, 2009).
b) HYPERTENSION: Based on a report from National High Blood Pressure Education Program (NHBPEP) Working Group on Children and Adolescents, the initial recommended oral dose is 0.05 to 0.1 mg/kg/day, in three divided doses; MAXIMUM 0.5 mg/kg/day, in three divided doses (NoneListed, 2004).

6) SILODOSIN

a) Silodosin is not indicated for use in pediatric patients. Safety and efficacy have not been established (Prod Info RAPAFLO(R) oral capsule, 2009).

7) TAMSULOSIN

a) The safety and effectiveness in the pediatric population have not been established (Prod Info Flomax(R) oral capsules, 2011).

8) TERAZOSIN

a) According to the manufacturer, the safety and effectiveness in the pediatric population have not been established (Prod Info HYTRIN(R) oral tablets, 2009).
b) HYPERTENSION: Based on a report from National High Blood Pressure Education Program (NHBPEP) Working Group on Children and Adolescents, the initial recommended dose is 1 mg orally once daily; MAXIMUM 20 mg/day orally (NoneListed, 2004).

Minimum Lethal Exposure

A)

Maximum Tolerated Exposure

A)

1) DOXAZOSIN

a) CASE REPORT: A 39-year-old woman developed hypotension, that responded to IV fluids, after intentionally ingesting 70 mg doxazosin, as well as alcohol and an unknown amount of flurazepam (Prod Info CARDURA(R) oral tablets, 2009).
b) CASE REPORT: A 19-year-old woman developed hypotension (80/50 mmHg supine), tachycardia (126 bpm), and drowsiness after ingesting 60 mg of doxazosin; she recovered with supportive care (Satar et al, 2005).

2) INDORAMIN

a) CASE REPORT: A 58-year-old woman experienced seizures and torsade de pointes following an overdose ingestion of 1500 mg indoramin. The patient recovered following supportive care (Nisse et al, 2009).

3) PHENTOLAMINE

a) Administration of 440 mg in one day to a 47-year-old man resulted in palpitations and sweating (Prod Info, 1982).

4) PRAZOSIN

a) Unintentional ingestion of at least 50 mg in a 2-year-old child produced profound drowsiness and depressed reflexes (Prod Info Minipress(R) oral capsules, 2009)
b) Approximately 200 mg was ingested by a 19-year-old male, with only a slight decrease in blood pressure (McClean, 1976).

5) TAMSULOSIN

a) CASE REPORT: After ingesting 5 tamsulosin (0.4 mg each) tablets, a 78-year-old woman developed headache, dizziness, syncope, orthostatic hypotension (BP 100/50 mmHg while lying and 60/40 in sitting position), and bradycardia (47-50 beats/min). Following supportive care, she recovered without further sequelae (Anand et al, 2005).

6) TERAZOSIN

a) CASE REPORT: A 75-year-old man developed hypotension (73/43 mmHg) and bradycardia (42 bpm) after intentionally ingesting 300 mg of terazosin. The patient completely recovered without sequelae following supportive treatment (Seak & Lin, 2008).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) SPECIFIC SUBSTANCE

a) DOXAZOSIN

1) CASE REPORT: A 32-year-old woman, with chronic renal failure, epilepsy, and depression, developed hypotension and grand-mal seizures, resulting in death, after intentionally ingesting 60 mg doxazosin. Her blood doxazosin level was 0.9 mcg/mL (normal 0.02 mcg/mL) (Prod Info CARDURA(R) oral tablets, 2009).

b) PRAZOSIN

1) A prazosin serum level of 2350 nanomoles/liter occurred 3 hours after an ingestion of 80 mg of prazosin in a 75-year-old man, who had a baseline blood pressure of 160/90 mmHg. On admission, he was drowsy.

a) A systolic blood pressure of 90 mmHg, with a regular sinus rhythm of 82 beats/ minute, developed 30 minutes after admission. The patient's blood pressure returned to baseline within 18 hours after receiving good supportive care (Rygnestad & Dale, 1983).

c) PHENOXYBENZAMINE

1) Respiratory depression, decreased neurological tone, and mild transient hypotension occurred in a newborn whose mother had ingested phenoxybenzamine and labetalol during her third trimester of pregnancy. The mean phenoxybenzamine concentrations from the cord blood, maternal blood, and amniotic fluid were 103.3, 66, and 79.3 ng/mL, respectively, indicating placental transfer of phenoxybenzamine from the mother to the infant (Santeiro et al, 1996).

Toxicity Information

7.7.1)

A) PHENOXYBENZAMINE HYDROCHLORIDE

1) LD50- (ORAL)RAT:

a) 2000 mg/kg (Prod Info, 1986)

B) PHENTOLAMINE

1) LD50- (ORAL)MOUSE:

a) 1000 mg/kg (Prod Info, 1985)

2) LD50- (ORAL)RAT:

a) 1250 mg/kg (Prod Info, 1985)

C) TOLAZOLINE HYDROCHLORIDE

1) LD50- (ORAL)MOUSE:

a) 400 mg/kg (Prod Info, 1985a)

2) LD50- (ORAL)RAT:

a) 1200 mg/kg (Prod Info, 1985a)

Pharmacology Toxicology

Pharmacologic Mechanism

A)

1.  Phentolamine = nonselective competitive
                   alpha antagonist
                   (alpha 1, alpha 2)
2.  Tolazoline = nonselective alpha antagonist
                 (alpha 1, alpha 2)
3.  Phenoxybenzamine = nonselective,
                       noncompetitive alpha
                       antagonist
4.  Prazosin, terazosin & doxazosin = Alpha 1
                                       selective
                                       antagonist
5.  Indoramin = Alpha 1 selective antagonist
6.  Urapidil = Alpha 1 selective antagonist

B)

C)

D)

E)

1) These include sympathomimetic effects as well as histamine-like response in gastrointestinal stimulation and vasodilation.

F)

1) Prazosin has been shown to cause a significant reduction in total peripheral resistance without any concomitant increase in cardiac output or heart rate.

G)

Toxicologic Mechanism

A)

Physicochemical

Physical Characteristics

A)

B)

C)

D)

Molecular Weight

A)

B)

C)

D)

Animal Toxicology

References

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FeedBack

ALPHA-ADRENERGIC BLOCKERS

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Genitourinary

Hematologic

Dermatologic

Immunologic

Reproductive

Monitoring Parameters Levels

Life Support

Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Toxicity Information

Pharmacologic Mechanism

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

General Bibliography