Phenoxybenzamin

INHIBITION OF COMPENSATORY VASOCONSTRICTION ALSO EXAGGERATES DEPRESSOR EFFECTS OF OPIOIDS & OTHER AGENTS THAT ACT DIRECTLY TO RELAX VASCULAR SMOOTH MUSCLE.

EXPTL HEMORRHAGIC SHOCK WAS PRODUCED IN 50 DOGS & METABOLIC STATUS WAS ASSESSED. ADRENERGIC BLOCKADE WITH PHENOXYBENZAMINE HAD PROTECTIVE ACTION ON METABOLIC STATUS BUT BLOOD LOSS REQUIRED TO ATTAIN SAME DEGREE OF HYPOTENSION WAS LESS. ADMIN OF PHENOXYBENZAMINE & PROPRANOLOL TOGETHER (COMBINED ADRENERGIC BLOCKADE) GAVE BEST RESULT REGARDING METABOLIC STATUS.

Prior administration of phenoxybenzamine may decrease the pressor response to phenylephrine.

Prior administration of phenoxybenzamine may block the pressor response to methoxamine, possibly resulting in severe hypotension.

For more Interactions (Complete) data for PHENOXYBENZAMINE (11 total), please visit the HSDB record page.

The following adverse effects may occur during treatment with phenoxybenzamine:；* Drowsiness；* Fatigue；* Inhibited ejaculation；* Orthostatic hypotension；* Tachycardia (reflex tachycardia)；* Miosis；* Gastrointestinal irritation；* Nasal congestion；Almost all cases will present with fatigue, nasal stuffiness, and orthostasis. Retrograde ejaculation may also occur, so men taking phenoxybenzamine should receive counsel.

Overdose of phenoxybenzamine may result in a block of the sympathetic nervous system and circulating adrenaline hormones (epinephrine), resulting in postural hypotension presenting with tachycardia (especially postural), dizziness or fainting, lethargy, vomiting, and shock.；According to the FDA drug label, case reports have shown the development of carcinoma associated with long-term treatment; therefore, long-term therapy is not recommended.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Phenoxybenzamine hydrochloride/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=63-92-3]

... RESULTS OF ALPHA-RECEPTOR BLOCKADE INCL MIOSIS, NASAL STUFFINESS, & INHIBITION OF EJACULATION. EFFECTS NOT CLEARLY RELATED TO BLOCKADE ARE LOCAL TISSUE IRRITATION, SEDATION, & GENERALIZED FEELING OF WEAKNESS & TIREDNESS. LOCAL IRRITATION IS ... INVOLVED IN NAUSEA & OCCASIONAL VOMITING THAT MAY FOLLOW LARGE ORAL DOSES, PARTICULARLY IF ADMIN ON AN EMPTY STOMACH.

PHENOXYBENZAMINE ... MAY PRODUCE SLIGHT CONJUNCTIVAL HYPEREMIA ASSOC WITH NASAL STUFFINESS & SLIGHT PTOSIS. IT HAS HAD NO ADVERSE EFFECT IN GLAUCOMA, BUT RATHER HAS OCCASIONALLY BEEN SUSPECTED TO REDUCE INTRAOCULAR PRESSURE SLIGHTLY.

CONTACT DERMATITIS FROM PHENOXYBENZAMINE HYDROCHLORIDE OCCURRED IN A WOMAN LAB TECHNICIAN. CROSS-SENSITIVITY TO RELATED CMPD MAY BE DUE TO THE CHLOROETHYLAMINE MOIETY OF THE MOLECULE. /PHENOXYBENZAMINE HYDROCHLORIDE/

... PHENOXYBENZAMINE ... CAN STIMULATE THE CNS TO CAUSE NAUSEA, VOMITING, HYPERVENTILATION, MOTOR EXCITABILITY, & EVEN CONVULSIONS, PARTICULARLY WHEN A RELATIVELY LARGE DOSE IS RAPIDLY INJECTED IV. IN MAN, A CHARACTERISTIC LOSS OF TIME PERCEPTION MAY OCCUR.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

phenoxybenzamine

Dibenzyline®

Vasodilators

Not Applicable

no-DILI-concern

THREE GROUPS OF 10 MALE & 10 FEMALE A/HE MICE, 6-8 WK OLD, WERE GIVEN 4 IP INJECTIONS ... OF PHENOXYBENZAMINE (FREE BASE) DISSOLVED IN TRICAPRYLIN TO GIVE TOTAL DOSES OF 40, 100 OR 200 MG/KG BODY WT. 24 WK AFTER THE FIRST INJECTION, THE 20, 14 & 7 SURVIVORS IN THE 3 GROUPS, RESPECTIVELY, WERE KILLED, & 9, 9 & 3 HAD LUNG TUMORS, WITH AVG OF 0.45, 0.79 & 0.71 TUMORS/MOUSE. AS CONTROLS, 80 MICE OF EACH SEX RECEIVED 24 WEEKLY INJECTIONS OF TRICAPRYLIN; OF THE 77 MALE & 77 FEMALE SURVIVORS IN EACH GROUP, LUNG TUMORS WERE FOUND IN 28% OF MALES (AVG, 0.24 TUMORS/MOUSE) & 20% OF FEMALES (AVG, 0.20 TUMORS/MOUSE).

SENSITIZATION TO PHENOXYBENZAMINE WAS PRODUCED IN GUINEA PIGS. CROSS-SENSITIVITY TO RELATED CMPD MAY BE DUE TO THE CHLORETHYLAMINE MOIETY OF THE MOLECULE.

WITHIN 10 SEC OF 50 MG INJECTION OF PHENOXYBENZAMINE IN UNANESTHETIZED NORMAL CALVES & CALVES WITH BRISKET DISEASES THE PULMONARY ARTERY PRESSURE INCR SIGNIFICANTLY REACHING A PEAK IN 30-60 SEC. THERE WAS A TRANSIENT FALL IN ASCENDING AORTA PRESSURE & RISE IN HEART RATE, WHILE CARDIAC OUTPUT & PULMONARY ARTERY WEDGE PRESSURE REMAINED CONSTANT.

GROUPS OF 35 MALE & 35 FEMALE B6C3F1 MICE, 6-8 WK OLD AT START OF THE EXPT, RECEIVED /IP INJECTIONS OF/ 12.5 OR 25 MG/KG BODY WT PHENOXYBENZAMINE HYDROCHLORIDE 3 TIMES A WK, IN PHOSPHATE-BUFFERED SALINE CONTAINING 0.05% POLYSORBATE 80 FOR THE FIRST 10 WK & THEN IN 6% PROPYLENE GLYCOL IN SALINE FOR AN ADDNL 42 WK (1 ML/100 G BODY WT). DUE TO THE DEATH OF ALL HIGH-DOSE MALE MICE, TREATMENT LASTED ONLY 50 WK IN THIS GROUP. A GROUP OF 14 MALE & 16 FEMALE MICE & 1 OF 15 MALES & 15 FEMALES WERE KEPT AS UNTREATED & VEHICLE-TREATED CONTROLS, RESPECTIVELY. ALL SURVIVING MICE WERE KILLED AT 83-85 WK. IN THE HIGH-DOSE GROUP, 17/21 MALES ... & 16/20 FEMALES ... DEVELOPED ABDOMINAL CAVITY (PERITONEAL) SARCOMAS. NO SUCH TUMORS WERE FOUND IN THE LOW-DOSE GROUP (0/30 MALES, 0/33 FEMALES) OR IN CONTROLS. /PHENOXYBENZAMINE HYDROCHLORIDE/

For more Non-Human Toxicity Excerpts (Complete) data for PHENOXYBENZAMINE (9 total), please visit the HSDB record page.

Treatment: Stabilization. Establish adequate respiratory function. Normal tidal volume: 10-15 ml/kg. Endotracheal intubation with assisted ventilation may be required. Gut Decontamination. Emesis induction is indicated unless the patient is comatose, is convulsing, or has no gag reflex. If these are present, endotracheal intubation must be performed with a cuffed endotracheal tube before a large-bore gastric tube is inserted for gastric lavage. ... Activated Charcoal. Adults, 50-100 g; children, 15-30 g in aqueous or sorbital slurry, after emesis is induced or into the gastric tube after lavage. Cathartic. Magnesium sulfate or sodium sulfate; adult, 30 g children, 250 mg/kg. No studies on efficacy are available with this group of drugs. Elimination enhancement. In view of the extensive protein binding and extensive volume of distribution of some drugs of this group, it is unlikely that hemodialysis or peritoneal dialysis would be effective. In any case, no studies exist to demonstrate such efficacy. Most cases are amenable to good supportive therapy. Antidotes. There are no antidotes. /alpha-Adrenergic blockers/

Recommended treatment for phenoxybenzamine overdose includes: treatment of circulatory failure, either by placing the patient in the recumbent position with legs elevated or additional measures if shock is present. The usual pressor agents are not effective; epinephrine should not be used because of the risk of further hypotension. Intravenous administration of levarterenol bitartrate may be useful.

A bioassay of phenoxybenzamine hydrochloride for possible carcinogenicity was conducted by administering the test chemical by ip injection to Sprague-Dawley rats and B6C3F1 mice. ... Groups of 35 rats of each sex were administered phenoxybenzamine hydrochloride at one of two doses, either 5 or 10 mg/kg body weight, 3 days/wk for 52 wk, then observed for an additional 31 or 32 wk. The vehicle used for most of the period of the bioassay was 6% propylene glycol in saline, although other vehicles, including 0.05% polysorbate 80 in saline, were used at the beginning. Controls consisted of groups of 10 vehicle controls and 10 untreated controls of each sex. All surviving rats were killed at 83-85 wk. Groups of 35 mice of each sex were administered phenoxybenzamine hydrochloride at two doses, either 12.5 or 25 mg/kg body weight 3 days/wk for 50 or 52 wk, then observed for an additional 31-33 wk. Controls consisted of groups of 15 males and 15 females which were administered the vehicle (vehicle controls), and groups of 14 males and 16 females which were untreated (untreated controls). All surviving mice were killed at 83-85 wk. ... Under the conditions of this bioassay, phenoxybenzamine hydrochloride was carcinogenic (sarcomagenic) for the peritoneum of both sexes of Sprague-Dawley rats and B6C3F1 mice.

0.00089

CALEPA

3.1

CALEPA