Trimethaphan

365.515

365.169

6G8X656T45

DTXSID8043787

C - Cardiovascular system

24.6

3.473

Solid

6.65e-03 g/L

Trimethaphan camsylate injection should be stored at 2-8 deg C, although it is stable for 14 days at up to 25 deg C.

3.74X10-10 mm Hg at 25 deg C (est)

Henry's Law constant = 2.28X10-13 atm-cu m/mole at 25 °C (est)

White crystals or a white, crystalline powder /Trimethaphan camsulate/|Hydroxyl radical reaction rate constant = 4.76X10-11 cu cm/molec-sec at 25 °C (est)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl trimethaphan camsylate on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Trimethaphan camsylate/

Trimethaphan may prolong the effects of neuromuscular blocking agents such as tubocurarine chloride or succinylcholine chloride, especially when large doses of trimethaphan are administered.|Procainamide has an additive hypotensive effect with trimethaphan.|Trimethaphan may have an additive hypotensive effect when administered with anesthetic agents, especially spinal anesthetics. Halothane and trimethaphan have an additive hypotensive effect which is used to therapeutic advantage. In general, the deeper the plane of anesthesia, the smaller the dose of trimethaphan required to produce hypotension; conversely, less anesthetic is required after hypotension has been induced.|When trimethaphan is administered with diuretics or other hypotensive agents, the hypotensive effect of trimethaphan may be increased.|For more Interactions (Complete) data for TRIMETHAPHAN (6 total), please visit the HSDB record page.

Pregnant women are extremely sensitive to ganglionic blocking agents. These drugs cross the placenta, decreasing fetal GI motility and resulting in meconium ileus. In addition, trimethaphan-induced hypotension may have other serious adverse effects on the fetus. For these reasons, trimethaphan should be avoided during pregnancy.|Trimethaphan is contraindicated in patients with anemia, hypovolemia, shock (incipient or frank), asphyxia, respiratory insufficiency, or other conditions in which hypotension may subject the patient to undue risk. The drug may also be contraindicated when fluid and blood replacement are impossible and in patients with glaucoma.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 202 workers (70 of these were female) were potentially exposed to trimethaphan in the US(1).

For the controlled reduction of blood pressure during surgery and in the treatment of hypertensive emergencies.

Arfonad (active ingredient: trimethaphan camsylate) 50 mg/mL ingection, discontinued /Former/|Trimethaphan camsylate is used in hypertensive crises for the immediate reduction of blood pressure in patients in whom such reduction is considered an emergency (hypertensive emergencies). Hypertensive emergencies are those situations requiring immediate blood pressure reduction (not necessarily to normal ranges) to prevent or limit target organ damage. /Former use in the US/|Trimethaphan is also given to anesthetized patients to produce controlled hypotension (and therefore reduce bleeding) in a variety of surgical procedures on the head and neck. /Former use in the US/|/EXPL/ Hexamethonium, trimethaphan, and mecamylamine are ganglionic blockers which can reduce acetylcholine (ACh) release presynaptically. All these agents are capable of protecting mice from diisopropyl fluorophosphate (DFP) intoxication by prolonging the latent period of death or by completely preventing death. Combinations of these agents with 2-pyridine aldoxime methochloride (2-PAM) (50 mg/kg) improved prophylactic action even further. These results indicate that reduction of ACh release presynaptically plus neutralization of organophosphates with 2-PAM could be an effective way to reduce mortality in patients exposed to organophosphorus poisons.|For more Therapeutic Uses (Complete) data for TRIMETHAPHAN (9 total), please visit the HSDB record page.

When trimethaphan is used to produce controlled hypotension during surgery, it should be administered by physicians with proper training in this technique and when adequate facilities, equipment, and personnel are available for close monitoring of circulation and blood pressure. The hypotensive response to trimethaphan is variable and frequent blood pressure determinations and dosage adjustments are essential to maintain proper control.|Trimehaphan camsylate produces numerous adverse effects, primarily due to its nonselective blockade of the autonomic nervous system. Generally, adverse effects are decreased when dosage is reduced or the drug is temporarily discontinued. Trimethaphan may cause urinary retention, orthostatic hypotension, tachycardia, precipitation of angina, anorexia, nausea, vomiting, dry mouth, extreme weakness, restlessness, cycloplegia, urticaria, and itching. The drug prevents surgically induced elevation of blood glucose and decreases serum potassium slightly.|Because trimethaphan causes histamine release, it should be used with caution in patients with allergies. A histamine-type reaction has been reported along the course of the vein used for trimethaphan administration.|Trimethaphan should be used with extreme caution in patients with arteriosclerosis, cardiac disease, hepatic or renal disease, degenerative disease of the CNS, Addison's disease, diabetes mellitus, or those receiving corticosteroids, The drug should also be used cautiously in elderly or debilitated patients and in children.|For more Drug Warnings (Complete) data for TRIMETHAPHAN (11 total), please visit the HSDB record page.

Trimethaphan is indicated for production of controlled hypotension during surgery to reduce bleeding into the surgical field and also for rapid reduction of blood pressure in the treatment of hypertensive emergencies, especially in patients with acute dissecting aneurysm, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension.

Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage. (See all compounds classified as Adjuvants, Anesthesia.)|Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. (See all compounds classified as Ganglionic Blockers.)|Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses. (See all compounds classified as Nicotinic Antagonists.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

Trimethaphan crosses the placenta. The drug may be metabolized by pseudocholinesterase and is filtered and actively secreted by the kidneys.|Animal studies indicate that trimethaphan camsylate is erratically and incompletely absorbed after oral administration.

Trimethaphan is a ganglionic blocking agent prevents stimulation of postsynaptic receptors by competing with acetylcholine for these receptor sites. Additional effects may include direct peripheral vasodilation and release of histamine. Trimethaphan's hypotensive effect is due to reduction in sympathetic tone and vasodilation, and is primarily postural.|Trimethaphan blocks transmission of impulses at both sympathetic and parasympathetic ganglia by competing with acetylcholine for cholinergic receptors at the autonomic ganglia and by stabilizing the postsynaptic membranes against the actions of acetylcholine released from presynaptic nerve endings. In addition, trimethaphan may also have direct peripheral vasodilator effects and cause the release of histamine. Through its blockade of sympathetic ganglia, trimethaphan causes vasodilation, increased peripheral blood flow, and decreased blood pressure.|Ganglionic blockers such as trimethaphan inhibit impulse transmission down both the postganglionic sympathetic and parasympathetic nerves, decreasing vascular tone, cardiac output, and blood pressure.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... Group 1 patients (n = 7) received a single intravenous injection of trimethaphan, 0.5 mg/kg, while awake and again during stable halothane-nitrous oxide anesthesia. Group 2 patients (n = 6) were pretreated with intravenous H1 (chlorpheniramine, 0.1 mg/kg) and H2 (cimetidine, 4 mg/kg) receptor antagonists administered 15 min before trimethaphan, 0.5 mg/kg, in the awake and anesthetized states. In Group 3 (n = 6), the effects of infusion of trimethaphan, 3 mg/min for 15 min, were studied during halothane-nitrous oxide anesthesia. In Group 1, bolus doses of trimethaphan were associated with maximal increases in serum histamine from 0.56 +/- 0.14 to 2.56 +/- 0.35 ng/mL (p < 0.01) and from 0.60 +/- 0.11 to 2.58 +/- 0.33 ng/mL (p < 0.01) 2 min after drug administration in the awake and anesthetized states, respectively; there were also clinical manifestations of histamine release. Mean arterial pressure decreased maximally after 5 min in the awake (from 92.0 +/- 3.4 to 69.9 +/- 2.2 mm Hg; p < 0.01) and anesthetized (from 82.6 +/- 3.7 to 57.3 +/- 2.5 mmHg; p < 0.01) states, and was associated with increases in cardiac output and heart rate; stroke volume increased in the awake state only.|/HUMAN EXPOSURE STUDIES/ Urinary excretion of renal tubular cell enzymes, N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) was evaluated to elucidate the renal cell damage before, during and after the induced hypotension with trimetaphan (TMP) ... under halothane-nitrous oxide-oxygen anesthesia in patients undergoing neurosurgery. ... Urinary excretion of / NAG and gamma-GTP/ in TMP group tended to increase, but its increases were not statistically significant. ... According to the general opinions, degree in stray of renal tubular cell enzyme into urine is thought to parallel with the injury of renal tubular cells. ...|/HUMAN EXPOSURE STUDIES/ In two groups of patients undergoing induced hypotension with sodium nitroprusside or trimetaphan blood concentrations of lactate, pyruvate and standard bicarbonate did not differ significantly between the groups. In the nine patients who received trimetaphan there was a progressive, but statistically non-significant, decrease in mean lactate. ...|/SIGNS AND SYMPTOMS/ Large doses of trimethaphan camsylate in the management of hypertension have caused apnea and respiratory arrest. Respiration must be monitored closely, especially if large doses of the drug are given. /Trimethaphan camsylate/|For more Human Toxicity Excerpts (Complete) data for TRIMETHAPHAN (7 total), please visit the HSDB record page.

Thimethaphan

Arfonad /Trimehtaphan camsylate/ /Discontinued/|Parenteral: Concentrate for injections, for IV infusion only: 50 mg/mL Arfonad (with sodium acetate), (Roche). /Trimethaphan camsylate/

Discontinued /Arfonad (active ingredient: trimethaphan camsylate)/