adrenal glandAdrenaline (epinephrine, abbreviated as A or E) is a hormone secreted by the human body.When people experience certain stimuli (such as excitement, fear, tension, etc.), they secrete this chemicalmaterial, can make people breathe faster (provide a lot of oxygen), heart rate and blood flow faster,Pupillary enlargement, provide more energy for physical activities, and make the reaction faster.Adrenaline is a hormone and neurotransmitter that is released by the adrenal gland.Adrenaline will increase the contractility of the heart and make the heart, liver, muscles and bonesVasodilationAnd skin and mucous membranevasoconstrictionIt is necessary for saving dying people or animals.hisbiosynthesisMainly inmedullaFirst formed in each cellNorepinephrine, and then furtherPhenylethylamine-N-Methyltransferase(phenylethanolamine N-methyl transfer, PNMT) can methylate norepinephrine to form epinephrine.
Drug name
adrenaline
Foreign name
adrenaline,epinephrine,A，E[2]
Alias
Accessory kidney
Prescription medicine or not
yes
Main indications
It can relieve weak heartbeat, decreased blood pressure, dyspnea, etc
Main drug contraindications
Children, the elderly, patients with organic brain damage and pregnant women
Careful use by athletes
yes
Whether included in medical insurance
no
Drug type
hormone
Usage and dosage
Subcutaneous injection or intramuscular injection 0.5 ～ 1mg
This product is（R)-4-(2-(Methylamino）-1-hydroxyethyl]-1,2-Benzenediol, calculated as dry product, including CnineHthirteenNOthreeNot less than 98.5%.
character
This product is white or off whiteCrystallinityPowder, odorless, easy to oxidize and deteriorate in contact with air or sunlight, unstable in neutral or alkaline aqueous solution, weak in saturated aqueous solutionAlkaline reaction。
Take this product, precisely weigh it, addhydrochloric acidThe solution (9 → 200) is dissolved and quantitatively diluted to make a solution containing 20mg per 1mL, which is determined according to the law (general rule 0621), and the specific rotation is - 50.0 ° to - 53.5 °.
identify
1. Take about 2mg of this product, add 2-3 drops of hydrochloric acid solution (9 → 1000) to dissolve it, then add 2mL of water and three drops ofFerric chlorideOne drop of test solution will turn emerald green, and one drop of ammonia test solution will turn purple and finally purple red.
2. Take 10mg of this product, add 2mL of hydrochloric acid solution (9 → 1000) to dissolve it, and then addhydrogen peroxideTest solution10 drops, boiling, blood red.
Check the solution under the specific rotation item, which should be clear and colorless. If it develops color, check it with the same volume of control solution (yellow No. 3Standard colorimetric solutionOr orange red No. 2 standard colorimetric solution 5mL plus 5mL of water) (General Rule 0901, Method 1), shall not be deeper.
Ketone body
Take this product and add hydrochloric acid solution (9 → 2000) to make a solution containing 2.0mg per 1mLUltraviolet visible spectrophotometry(General Rule 0401), measured at the wavelength of 310nm,absorbanceNot more than 0.05.
Test solution: Take about 10mg of this product and place 10mLMeasuring flaskMedium, add 0.1mL hydrochloric acid to dissolve, usemobile phaseDilute to the scale and shake well.
Reference solution: Accurately measure 1mL of the test solution, place it in a 500mL volumetric flask, dilute it with mobile phase to the scale, and shake it up.
Oxidation damage solution: take 50mg of this product, put it into a 50mL measuring bottle, addConcentrated hydrogen peroxide solution1mL, place overnight, add 0.5mL hydrochloric acid, dilute with mobile phase to the scale, and shake up.
Chromatographic conditions:Octadecyl silane bonded silica gelbyFiller, withsulphuric acidTetramethylammonium hydrogen solution (take 4.0g tetramethylammonium hydrogen sulfate,Heptane sulfonate sodium1.1g，0.1mol/LDisodium ethylenediamine tetraacetate2mL solution, dissolved with water and diluted to 950mL)-methanol(95:5) (adjust the pH value to 3.5 with 1mol/L sodium hydroxide solution) is the mobile phase, the flow rate is 2mL per minute, the detection wavelength is 205nm, and the injection volume is 20 µ L.
System suitability requirements: system suitability solutionChromatogramIn, there should be two peaks between norepinephrine peak and epinephrine peakUnknown impurityPeak,Theoretical plate numberNot less than 3000 according to the calculation of norepinephrine peakResolutionShould beMeet the requirements.
Determination method: Precisely measure the test solution and control solution, and inject them respectivelyLiquid chromatographRecord the chromatogram.
Limit: if there is impurity peak in the chromatogram of the test solution, single impuritypeak areaIt shall not be greater than the main peak area of the reference solution (0.2%), and the sum of the impurity peak areas shall not be greater than 2.5 times (0.5%) of the main peak area of the reference solution.
Take about 0.15g of this product, precisely weigh it, addGlacial acetic acid10mL, after shaking and dissolving, addcrystal violet1 drop of indicator liquidperchloric acidTitrant(0.1mol/L) titrate to the solutionTurquoise, and use the titration resultBlank testcorrecting.Every 1mL perchloric acid titrant (0.1mol/L) is equivalent to 18.32mg CnineHthirteenOthreeN。
Adrenaline stimulates adrenaline directlyαandβReceptors, by excitationa bronchial tubesmooth muscleβ 2 receptor can alleviateBronchospasm, relax the bronchus, improve the ventilation function, inhibit the release of allergic media, produce the antiasthmatic effect, inhibit the increase of vascular endothelial permeability, promote mucus secretion andCiliary movement, promoteAlveolar type II cellsSynthesis and secretionSurfactant。Simultaneously excite bronchial mucosal vesselsαReceptor, causing excessive contraction of mucosal blood vessels,blood capillaryThe increase of blood pressure may lead to the aggravation of mucosal edema and congestion, and weaken the antiasthmatic effect.CardiovascularβoneReceptor activation canMyocardial contractilityStrengthens, increases heart rate,Cardiac outputIncrease.In addition, there is still an increaseBasal metabolismIt can increase blood sugar and dilate pupils.Its bronchodilator effect is strong and rapid, but relatively short.subcutaneous injection0.25 ～ 0.5mg, effective for 10 ～ 15min, and maintained for 1 ～ 2h.Because ofAdverse reactionsMore. At present, it is rarely used as antiasthmatic treatment in clinical practice, only in severe casesbronchial asthma, especiallyAllergic asthmaApply in case of acute attack.withQuantitative aerosolMethod Inhalation, rightBronchodilationThe effect is weak and short.
Pharmacokinetics
Very little oral absorption.Local digestive tract after oral administrationvasoconstriction, reduce absorption, and the absorption part can be quickly absorbed in the gastrointestinal tractEnzymatic degradationAnd metabolism in liver, unable to reachEffective concentration, so oral administration is invalid.After subcutaneous injection, the effect was obvious 3~5 minutes later, and the effect could be maintained for about 1 hour.Because it can constrict the subcutaneous blood vessels,DurationIt is longer and the absorption is delayed, so it is generally appropriate to inject it subcutaneously.Intramuscular injectionThe absorption is fast and the effect is strong, but it only lasts for 10~30min.Injection administrationAfter that, the blood and tissueCatecholOxymethyltransferase（COMT）AndMonoamine oxidase(MAO) metabolismInactivation，metabolite4-hydroxy-3-MethoxyMandelic acidIt is mainly excreted by urine.
Application
This productDirect actionEuadrenergicα、βReceptors that produce intense, rapid and transient excitationsαandβType effect, on the heartβone-The excitation of receptors can enhance the myocardial contractility and speed up the heart rate,Myocardial oxygen consumptionIncrease.Simultaneously act on vascular smooth muscleβtwo-ReceptorVasodilation, lower aroundvascular resistance And decreasediastolic pressure。excitementβtwo-Receptors can relax bronchial smooth muscle, expand bronchi and relieve bronchospasm;yesα-Excited receptors can make skin, mucosal blood vessels and visceral small blood vessels shrink.Clinically, it is mainly used forCardiac arrest, bronchial asthmaAnaphylactic shock, can also treat urticariaHay feverandnasal mucosaorGingival bleeding。
Physiological function
Adrenaline generally increases the contractility of the heart, dilates the blood vessels of the heart, liver and bones, and narrows the blood vessels of the skin and mucosa.In medicine, adrenaline is used to stimulate the heart when the heart stops, orasthmaThe trachea is dilated when.It shrinks the blood vessels of skin, mucosa and viscera (such as kidney);yescoronary arteryandskeletal muscleVascular dilation.Because it can directly act onCoronary vesselCauses vasodilation and improves blood supply to the heart.It can stimulate the heart to contract blood vessels and relax bronchial smooth muscle, which can alleviate weak heartbeat, decreased blood pressuredyspneaAnd other symptoms.Adrenergic stimulationαandβTwo types of receptors, producing strongerαType andβType effect.
The heart acts on the heart muscleConduction systemandSinoatrial nodeOfβoneReceptors, EnhancedMyocardial contractility, accelerate conduction, accelerate heart rate, and improve myocardialExcitability。The effect on isolated myocardium is characterized by accelerationContractilityThe rate of development (positive shrinkage effect).
clinical application
It is used for the rescue of cardiac arrest and anaphylactic shock, as well as otherAllergic disease(e.g. bronchial asthmaUrticaria）Treatment.And gameanestheticCombined use is beneficial to local hemostasis and prolongation of efficacy.
indication
1. Early adrenaline solution eye drops are used to treat primaryOpen angle glaucomaandsecondaryOpen angle typeglaucoma, its dropIntraocular pressureThe mechanism is not completely clear, and is considered to reduceAqueous humorSecretion is related to the improvement of aqueous humor flow coefficient.AdrenergicTreatment indexLow, the effect of lowering intraocular pressure is proportional to its concentration, but the increase of the concentration is accompanied by the increase of side effects caused by systemic absorption, so it has rarely been used solely for the treatment of glaucoma.
2. Pupil dilation: often used to dilate pupilscocaineandatropineTo form a mydriasis mixture to maximize the mydriasis effect to resistSynechia iridis, for treatmentirisInflammation andOcular traumaEtc.It can also be used together with miotic agent in the treatment of glaucoma to prevent posterior synechia of iris andPupillary sphincterSpasm andPupillary block, reduce the side effects of long-term pupil contraction.
3. Vasoconstruction effect: use its vasoconstriction effect, and use solution eye drops for contractionBulbar conjunctivaBlood vessels, which can identify ballsConjunctival congestionAndCiliary hyperemiaAnd scleral congestion;Intraoperative or preoperative application of external eye surgery can reduce bleeding in the surgical field, but it is ineffective for larger blood vessels;Local anestheticAdd a small amount of adrenaline toextra-inningThe action time of anesthetics and reducing the amount of local anesthetics can also reduce their systemic absorption.
contraindication
1. It can temporarily aggravate the symptoms of rigidity and tremor.
1. Commonly used to rescue anaphylactic shock, such aspenicillinAllergic shock.Because it can excite the heart muscle, raise blood pressure and relax bronchial smooth muscle, it can alleviate the symptoms of anaphylactic shock such as weak heartbeat, decreased blood pressure and dyspnea.Subcutaneous injection orIntramuscular injection0.5~1mg, also can be used for 0.1~0.5mg slow intravenous injection (Isotonic brineDilute it to 10mL). If the curative effect is not good, it can be changed to 4~8mg intravenous drip (dissolved in 5% glucose solution 500~1000mL).
2. Rescue cardiac arrest;It can be used for accidentsDrug poisoningorCardiac blockCardiac arrest caused by other reasons, 0.25-0.5mgIntracardiac injectionAt the same time, perform heart massage, artificial respiration and correctionAcidemia。This product can also be used for cardiac arrest caused by electric shockElectric defibrillatororlidocaineAnd so on.
3. Treatment of bronchial asthma: the effect is rapid but not lasting.Subcutaneous injection of 0.25-0.5mg will take effect in 3-5 minutes, but it can only last for 1 hour.If necessary, the injection can be repeated once.
4. Combined use with local anesthetics: add a small amount (about 1:200000~500000) to local anesthetics (such asprocaine）It can reduce the absorption of local anesthetics, prolong their efficacy and reduce their toxicityside reactionIt can also reduce bleeding at the operation site.
5. Stop nasal mucosa andGingival bleeding: Fill the bleeding place with gauze soaked with (1:20000-1:1000) solution.
6. Cure urticaria, hay fever, serum reaction, etc.: inject 0.2-0.5ml 1:1000 solution subcutaneously, and inject the above dose once more when necessary.
Common quantity0.25mg-1mg is injected subcutaneously or intramuscularly once.
（1）Cardiac arrestUse 0.5 mg~1.0 mg, or 0.01~0.02 mg/kg adrenaline for injectionnormal saline10mL diluted for intravenous injection or leftApex of heartInject directly into the skin, and use the medicine again after five minutes according to the condition, and cooperateCardiac compression, artificial respiration, acidemia correction and other auxiliary measures.
(2) Subcutaneous injection of 0.25-0.5mg for bronchial asthma can be repeated if necessary.
(3) Hypodermic injection or intramuscular injection of 0.3mg~0.5mg (0.1% injection of 0.3mL~0.5mL) for allergic diseases.When used for anaphylactic shock, 0.1mg~0.5mg of the product can also be diluted slowly with normal salineIntravenous bolusOr take 4mg~8mg of the product and add it into 500ml~1000ml normal salineIntravenous drip。
(4) In combination with local anesthetics, add a small amount (about 1 ∶ 500 000~200 000) into the local anesthetics (procaine), with the total amount not exceeding 0.3 mg.
(5) Local mucous membrane hemostasis: Soak gauze in the solution (1 ∶ 20 000 ～ 1 000) to fill the bleeding area.
2. Eye reaction: temporary tingling or burning sensation, tears, eyebrow arch pain, headacheallergy、Scleritis；Long term application may cause eyelid, conjunctiva and corneaMelanin deposition、Corneal edemaEtc.
Drug interaction
1. Digitalis drugs or general anesthetics can increase the myocardialsusceptibility。The combination of this product and the above drugs can cause arrhythmia, even ventricular fibrillation.
3. AndNitratesDrug combination can lead to hypotension, and the resistance of nitratesangina pectorisThe effect is weakened.
4. AndephedrineCombined use, for the surroundingarterioleContractionSynergy, causing a sharp rise in blood pressure, which can cause arrhythmia in patients with asthma.Not suitable for use.
5. AndHypoglycemic drugsCombined use can reduce the hypoglycemic effect of the latter.
6、β-Receptor blockerAntagonisticbronchiectasiaIt should be carefully used together to enhance its vasoconstrictor effect.
8. AndGuanethidine、reserpineWhen used together, the effect of this product is enhanced, causing hypertension and tachycardia, while the antihypertensive effect of guanethidine and reserpine is weakened.
10. AndAlpha blockerCombined use can cause severe hypotension.Quick acting vasodilators andαReceptor blockers can resist the intense pressor effect caused by large doses of the product.
11. Shock caused by procaine may cause ventricular fibrillation if it is rescued with this product.
12. Use chloroformChloroethaneandHalothaneThis product is forbidden during anesthesia.In order to avoid the acute elevation of myocardium and serious arrhythmia.
13. AndIsoproterenol、Norepinephrine(Triple solution) or quadruple solution composed of atropine can be used for cardiac resuscitation with good effect.
14. When used in combination with gray pressure sensitivity, it has a synergistic vasodilation effect and an enhanced excitatory effect on the heart.
15. AndPhenothiazinesThe combination of drugs can lead to severe shock.
16. Andthyroid hormoneWhen used together, it can significantly increase blood pressure and induce cardiovascular accidents.
17、DiureticsendBlood volumeWhen the blood sodium is reduced, the pressor effect of the product can be weakened.
matters needing attention
1. (1) In the case of insufficient circulating capacity or hypotension caused by phenothiazines, the use of epinephrine may lead to further decrease of blood pressure, so it should be used with caution;
(2) Coronary artery disease.
2. Effects of drugs on the elderly:Sympathomimetic drugThe effect of is more sensitive.
(2) Adrenaline can passPlacental barrier, causing fetal hypoxia, relaxing uterine smooth muscle and prolongingSecond stage of laborLarge dosage can weaken uterine contraction, so it is not recommended to use it during delivery;
（3）Cesarean sectionAdrenaline is used to maintain blood pressure during anesthesia, which can accelerate the heartbeat of the fetus. When the maternal blood pressure exceeds 17.3/10.7kPa (130/80mmHg), it should not be used.
4. Effect of drugs on lactation: not clear
5. Effect of drugs on test value or diagnosis: blood glucose and serum when adrenaline is appliedlactic acidThe level may rise.
6. Check or monitor before, after and during medication: use adrenalineinjectionPay close attention to blood pressure, heart rate andRhythmChange, it is necessary to apply it for many timesBlood glucose measurementChange.Long term or excessive use may causeDrug resistanceThe effect can be recovered after several days of drug withdrawal.
7. Adrenaline injection with a concentration of 1 ∶ 1000 (1mL/mL) is used for intracardiac orintravenous injectionIt must be diluted before.It can cause severe contraction of blood vesselsTissue necrosisTherefore, intra-arterial injection is not recommended.
8. Repeated administration at the same site can lead to tissue necrosis, and the injection site must be rotated.
9. When used in anaphylactic shock, it is effective due to the increased permeability of its blood vesselsInsufficient blood volume, blood volume must be supplemented at the same time.
10. Adrenaline can be decomposed and discolored in the presence of oxides, alkalis, light and heat, and its aqueous solution will become red when exposed to air and light, so it is not suitable for use.
11. The drug dosage must be strictly controlled during use, and the intravenous injection should be diluted and slowly administered.
13. Digitalis drugs can increase the sensitivity of myocardium to adrenaline, soDigitalizationPatients should be careful when applying epinephrine to their eyes.
15. ExcesssignFor: anxiety, red skinChest pain、shiver, convulsions, blood pressure changes, arrhythmia, nausea, vomiting, pale and cold skin, etc.
16. Attention should be paid when the following reactions persist: headache, anxiety, irritability, insomnia, pale face, fear, tremor, dizzinesshyperhidrosisAbnormal fast heartbeat or heavy feeling.
Overdose
Misuse of excessive adrenaline may cause nausea, vomiting, pale complexion, tachycardia, chest compressionVentricular premature beat, blood pressure risemuscle tremor , unsteady gait, shiveringfeverSweating, mydriasis, wheezing breathing, convulsion, etc.When blood pressure rises sharply, there is pulsatile headache.Children with severe diseases often have pulmonary edema, ventricular fibrillationcerebral hemorrhage, coma, heart andRespiratory centerParalysis.
Poisoning rescue
Adrenergic inhibitionBlocker, which can quickly reduce blood pressure and prevent arrhythmia. The commonly used ones are:
1、Benzylamine0.52mg/kg, 250mL of normal saline, intravenous drip.
