What Is Phentolamine?

M-Hydroxyamine is often used as a substitute for norepinephrine (NA). Suitable for all kinds of early shock. Its effect is weaker and longer lasting than norepinephrine. The general dose does not cause arrhythmia, so myocardial infarction shock can be used.
Meta-hydroxylamine

Drug type: Essential medicines
Drug name: M-hydroxylamine

English name: Metaramino
Chinese alias: Alamin
English alias: Metaraminol Tartrate;

Introduction to m-hydroxylamine compounds

Basic information

Chinese name: metahydroxylamine

Chinese alias: - (1-aminoethyl) -3-hydroxybenzyl alcohol; Alamin; m-phenolamine; m-hydroxyamine tartrate

English name: metaraminol

English alias: Pressonex; Metaradrine; m-Hydroxy norephedrine; Metaraminolum; m-Hydroxypropadrine; Bitartrate; Aramine; Pressonex

CAS number: 54-49-9

Molecular formula: C ₉ H ₁₃ NO ₂

Structural formula:

Molecular weight: 167.20500

Exact mass: 167.009500

PSA: 66.48000

LogP: 1.47310

M-hydroxylamine physicochemical properties

Density: 1.198g / cm ³

Boiling point: 357.9ºC at 760mmHg

Flash point: 170.3ºC ^[1]

Its heavy tartrate is commonly used as a white crystalline powder; it is almost odorless. Soluble in water, slightly soluble in ethanol, insoluble in chloroform or ether. The pH of the 5% aqueous solution is 3.2 to 3.5.

M-hydroxylamine pharmacopoeia standard

[Identification] (1) Take about 5mg of this product, add 2ml of saturated sulfuric acid solution of ammonium molybdate, mix well, and it will be blue. (2) Take about 5mg of this product, add 0.5ml of water to dissolve, add 2 drops of sodium nitrosoferrocyanide test solution, 2 drops of acetone and 0.2g of sodium bicarbonate, and heat in a water bath at 60 ° C for 1 minute. Red purple. (3) Take this product, add water to make a solution containing about 0.1mg per lml, and measure it according to the ultraviolet-visible spectrophotometry (Appendix IV A). It has a maximum absorption at a wavelength of 272nm. (4) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 294).

[Inspection] Take 1.0g of this product, add 20ml of water to dissolve it, and then measure it according to law (Appendix VI H). The pH value should be 3.2 ~ 3.5. Take the appropriate amount of this substance, dissolve and dilute it with water to make a solution containing about 0.4mg per lml as the test solution; take a precise amount and dilute it quantitatively with water to make a solution containing about 1g per lml as a control. Solution. Test according to high performance liquid chromatography (Appendix VD). Octadecylsilane-bonded silica gel was used as a filler; a 0.03% sodium hexanesulfonate solution (pH adjusted to 3.0 with 40% phosphoric acid)-methanol (80:20) was used as a mobile phase; the detection wavelength was 220 nm. The number of theoretical plates should not be less than 5,000 based on the meta-hydroxylamine peak, and the resolution of the meta-hydroxylamine peak and the adjacent impurity peaks should meet the requirements. Take 20 l of the control solution and inject it into the liquid chromatograph to adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 30% of the full scale. Then, 20 l of each of the test solution and the control solution was precisely measured and injected into the liquid chromatograph respectively, and the chromatogram was recorded to three times the peak retention time of the main component. If there is an impurity peak (except for the tartaric acid peak) in the chromatogram of the test solution, the area of a single impurity peak must not be greater than the area of the main peak of the control solution (0.25%), and the sum of the area of each impurity peak must not be more than 4 times the area of the main peak of the control solution ( 1.0%). Take this product after losing weight and dry it at 105 to constant weight, and the weight loss should not exceed 0.5% (Appendix L). The ignition residue shall not exceed 0.1% (Appendix N).

[Content determination] Take about 0.1g of this product, weigh it accurately, place it in an iodine bottle, dissolve it with 40ml of water, add 40ml of bromine titration solution (0.05mol / L), and then add 8ml of hydrochloric acid. Minutes, pay attention to the micro-opening stopper, add 8ml potassium iodide test solution, immediately stopper, shake, rinse the stopper and bottleneck of the iodine bottle with a small amount of water, add 1ml of chloroform, shake, and use sodium thiosulfate titration solution ( (0.1 mol / L) titration. At the near end, add the starch indicator solution, continue the titration until the blue color disappears, and correct the result of the titration with a blank test. Each 1 ml of bromine titration solution (0.05 mol / L) is equivalent to 5.288 mg of C ₉ H ₁₃ NO ₂ · C ₄ H ₆ O ₆ .

[Category] a adrenergic receptor agonist.

[Storage] shading and sealed.

M-hydroxylamine drug description

M-hydroxylamines

Circulatory Drugs> Cardiopulmonary resuscitation and anti-shock drugs

M-hydroxylamine dosage form

Injection: 10 mg (1 ml) each (corresponding to 19 mg of m-hydroxytartrate), 50 mg (5 ml) (corresponding to 95 mg of m-hydroxytartrate).

M-hydroxylamine pharmacology

M-Hydroxyamine is an alpha-adrenergic receptor agonist. It works mainly by directly stimulating alpha receptors, and can promote the release of norepinephrine from sympathetic nerve endings, and can also stimulate cardiac beta 1 receptors. Its epinephrine-like action causes blood vessels to constrict and increase blood pressure, but the effect is weaker and longer-lasting than norepinephrine; it can enhance myocardial contractility, increase blood flow to the brain, kidneys and coronary arteries, and increase heart rate in patients with hypotension and shock The amount of blood discharged; the contraction of renal blood vessels is weak, so it rarely causes symptoms of renal failure such as oliguria and anuria.

M-hydroxylamine pharmacokinetics

It can be absorbed orally, but the effective dose is too large, and the effect is slow, so it is administered by injection. Intramuscular injection takes 10 minutes to take effect. Subcutaneous injection is effective for 5-20 minutes, and the effect lasts for about 1 hour. Intravenous injection is effective for 1 to 2 minutes, and the effect lasts for 20 minutes. It is mainly metabolized by the liver. Most of the metabolites are excreted by bile and urine. Acidified urine can increase the excretion of the original drug.

M-hydroxylamine indication

For neurological shock, anaphylactic shock, toxic shock, cardiogenic shock, brain injury shock and hypotension during surgery. The general dose does not cause arrhythmia, so it can be used for myocardial infarction shock.

M-hydroxylamine contraindications

General anaesthesia with chloroform, halothane, and cyclopropane, or those who have used monoamine oxidase inhibitors within two weeks, are contraindicated.

M-hydroxylamine dosage

1. Each time 10 20mg, once every 30 60min; children each time 0.04 0.2mg / kg.

2. Intravenous infusion: 10 to 40 mg each time after adding 5% glucose injection or 0.9% sodium chloride injection to dilute (0.06 to 0.12 g / L), infusion at a rate of 20 to 30 drops per minute, or according to the condition and The reaction adjusts the drip rate and dosage. Extreme amount 100mg each time (0.2 0.4mg per minute); children 0.4mg / kg each time.

M-hydroxylamine considerations

1. (1) hyperthyroidism; (2) hypertension; (3) congestive heart failure; (4) diabetes.

2. Meta-hydroxylamine is not a substitute for supplementing blood volume. Before using meta-hydroxylamine, the hypovolemia should be corrected before using meta-hydroxylamine.

3. The route of administration is suitable for intravenous injection, and larger veins should be selected to avoid the use of small veins in the extremities, especially for patients with peripheral vascular disease, diabetes or hypercoagulable blood; caution should be taken when using intravenous medication. Make the liquid leak. Intramuscular or subcutaneous injections can easily cause tissue necrosis, so the injection site should be carefully selected to avoid use in areas with poor blood circulation.

4. Immediately before use should be diluted with 0.9% sodium chloride injection or 5% glucose injection. After preparation, it should be used up within 24 hours. Do not add other drugs that are difficult to dissolve in acidic solutions or have contraindications to compatibility.

5. Long-term use can produce accumulation, so that blood pressure is still high after stopping the drug. If the blood pressure rise is not obvious after taking the drug, you must observe more than 10min before deciding whether to increase the dose, so as not to rashly increase the blood pressure and cause it to rise too high.

6. Continuous use in a short period of time, due to the decrease in the amount of norepinephrine in the vesicle, the efficacy gradually weakens, resulting in rapid tolerance.

7. When the drug is stopped, the dose should be gradually reduced. If the drug is stopped suddenly, hypotension may occur again.

8. Excessive manifestations are convulsions, severe hypertension, severe arrhythmia, headache, dizziness, nervousness, tremor, palpitations, and chest compressions. At this time, the drug should be discontinued and observed. Those with high blood pressure can use 5-10mg phentol Intravenous injection can be repeated if necessary.

9. In the process of using m-hydroxylamine, it can be combined with vasodilators (such as phentolamine and isoproterenol) to prevent adverse reactions.

M-hydroxylamine adverse reactions

Headache, dizziness, tremor, nausea, and vomiting are common; arrhythmias are rare, and pulmonary edema, sudden cardiac arrest, and ischemic necrosis of the local tissue are caused by excessive pressure. M-Hydroxyamine has an accumulation effect. If the blood pressure does not rise significantly after administration, it must be observed for more than 10 minutes before deciding whether to increase the dose, so as not to rashly increase the dose to increase the blood pressure too high. Continuous use can cause rapid tolerance.

Inter-hydroxylamine drug interactions

1. Combination of halothane, cyclopropane and other halogen anesthetics can induce arrhythmia. The addition of m-hydroxylamine to digitalis patients is more likely to induce arrhythmia.

2. Combined with monoamine oxidase inhibitors, the boosting effect is increased.

3. Combined with guanethidine and reserpine, the latter can increase the sensitivity to the pressure-boosting effect of m-hydroxylamine.

4. Combined with -receptor blocking drugs, including phenothiazine drugs, can block the effect of -receptor of meta-hydroxylamine, while retaining the effect of -receptor, make the blood vessels dilate and lower blood pressure.

5. Oxytocin or ergometrine can increase the pressure-boosting effect of m-hydroxylamine, and should be used with caution.

6. Can not be compatible with basic drugs to prevent decomposition of m-hydroxylamine.

M-hydroxylamine

Injection: 1ml: 10mg, 5ml: 50mg

Meta hydroxylamine Expert Reviews

M-hydroxylamine injection

Drug Name

Common name: m-Hydroxyamine bitartrate injection

English name: Metaraminol Bitartrate Injection

Chinese Pinyin: Chongjiushisuan Jianqiang'an Zhusheye

The chemical name of this product is: (-)- (1-aminoethyl) -3-hydroxybenzyl alcohol tartrate.

Molecular formula: C ₉ H ₁₃ NO ₂ · C ₄ H ₆ O ₆

Molecular weight: 317.29

[Character]

This product is a colorless clear liquid.

[Pharmacology and Toxicology]

This product mainly acts on the a receptor, which directly excites the a receptor. It has a weaker but longer-lasting effect than norepinephrine, and its cardiovascular effect is similar to that of norepinephrine. It can constrict blood vessels and continuously increase systolic and diastolic blood pressure. It can also increase myocardial contractility. Normal human cardiac output does not change much, but it can increase cardiac output in shock patients. Excitation of heart rate is not very significant, rarely causes arrhythmia, and has no central nervous excitability. Because of its reliable pressure-increasing effect and longer maintenance time, it rarely causes reactions such as palpitations or decreased urine output. During continuous administration, because this product indirectly replaces the transmitter in the adrenergic nerve vesicles, it can reduce the transmitter and reduce the internal effects. Therefore, the drug cannot be stopped suddenly to avoid hypotension rebound.

Pharmacokinetics

The human pharmacokinetic parameters of this product have not been studied. After intramuscular injection for 10 minutes or subcutaneous injection for 5 to 20 minutes, blood pressure increases for about 1 hour; intravenous injection for 1 to 2 minutes takes effect for about 20 minutes. It is not destroyed by monoamine oxidase and has a longer effect. It is mainly metabolized in the liver, and the metabolites are mostly excreted through bile and urine.

[Indications]

Prevention and treatment of acute hypotension during spinal block anesthesia; Adjuvant symptomatic treatment for hypotension caused by bleeding, drug allergy, surgical complications, and brain trauma or brain tumor combined with shock; Can also be used for heart Hypotension caused by septic shock or sepsis.

Dosage

1. Adult dosage

Intramuscular or subcutaneous injection: 2 10mg / time (based on m-hydroxylamine), because the biggest effect is not immediately apparent, the initial dose effect should be observed for at least 10 minutes before repeated medication;

Intravenous injection, the initial amount of 0.5 to 5mg, and then intravenously for severe shock;

Intravenous infusion, add 15-100mg of m-hydroxylamine to 5% glucose solution or 500ml of sodium chloride injection, and adjust the drip rate to maintain proper blood pressure.

Adults should take 100 mg once (0.3 to 0.4 mg per minute).

2. Pediatric dosage

Intramuscular or subcutaneous injection: 0.1mg / kg for severe shock;

Intravenous infusion of 0.4 mg / kg or body surface area of 12 mg / m, diluted with sodium chloride injection to a solution containing 1 mg of m-hydroxylamine per 25 ml, the drip rate is to maintain a proper blood pressure level.

It should be used up within 24 hours after preparation. Do not add other drugs that are difficult to dissolve in the acidic solution for contraindication.

Adverse reactions

1. Arrhythmias, the incidence varies with dosage and patient sensitivity.

2. Too fast or too fast a booster response can cause acute pulmonary edema, arrhythmia, and cardiac arrest.

3 Excessive manifestations are convulsions, severe hypertension, and severe arrhythmias. At this time, the drug should be discontinued and observed. Those with high blood pressure can use 5 to 10 mg of phentolamine intravenously and can be repeated if necessary.

4 The drip of the medicinal solution during intravenous infusion can cause severe local contraction of blood vessels, leading to tissue necrosis and erosion or redness and swelling to form abscesses.

5. Hypotension may occur when long-term use is stopped suddenly.

Precautions

1. Hyperthyroidism, hypertension, coronary heart disease, congestive heart failure, diabetic patients and those with a history of malaria should be used with caution.

2. Hypovolemia should be corrected before using this product.

3 This product has an accumulation effect. If the blood pressure does not rise significantly after taking the drug, you must observe more than 10 minutes before deciding whether to increase the dose, so as not to rashly increase the blood pressure and cause it to rise too high.

4 When the drug is administered, a relatively large intravenous injection should be used, and the spillage of the drug solution should be avoided.

5. Continuous application in a short period of time, rapid tolerance appears, the effect will gradually weaken.

[Medication for pregnant and lactating women]

still uncertain.

medicine interactions

1. Combined with cyclopropane, halothane, or other halogenated hydroxyl anesthetics, it is easy to cause arrhythmia.

2. Used in combination with monoamine oxidase inhibitors to increase the boosting effect and cause severe hypertension.

3 Combination with digitalis or other epinephrine drugs can cause ectopic heart rhythm.

4 It is not advisable to co-inject with alkaline drugs, as it can cause decomposition of this product ^[7] .

[Drug overdose]

Overdose, high blood pressure can be intravenously injected with phentolamine 5 ~ 10mg.

specification

(1) 1ml: 10mg m-hydroxylamine (equivalent to 19 mg of m-hydroxylamine tartrate)

(2) 5ml: 50mg m-hydroxylamine (equivalent to 95 mg of m-hydroxyl tartrate)

Storage

Protected from light and sealed.