What Is Captopril?

Captopril is an angiotensin-converting enzyme inhibitor (ACE inhibitor or ACEI) and is used to treat hypertension and certain types of congestive heart failure. As the first ACEI drug, captopril is considered a breakthrough in drug therapy due to its new mechanism of action and revolutionary development process. Captopril was first produced by Bristol-Myers Squibb under the trade name Capoten ^[1] .

Drug Name: Captopril
Alias: Open Broadcom
Main indications: hypotensive

Dosage: 2-3 times a day
Adverse reactions: cough
Main medication contraindications: Disabled for pregnant women

Captopril compounds

Captopril Basic Information

Chinese name: Captopril

Chinese alias: 1-((2S) -2-methyl-3-mercapto-1-oxopropyl) -L-proline; methyl mercaptoproline; (S) -1- (3-mercapto -2-methyl-1-oxopropyl) -L-proline; meproproline; meproproline; captopril; captopril; pliblot; captopril; carved Fuding; Methanoyl; St. Ryan Captopril

English name: captopril

English alias: dilabar; acepress; lopril; sa333; Tensiomin; Capoten; Lopril; Lopirin; SQ-14225

CAS number: 62571-86-2

Molecular formula: C ₉ H ₁₅ NO ₃ S

Structural formula:

Molecular weight: 217.28500

Exact mass: 217.07700

PSA: 96.41000

LogP: 0.56580

Captopril physical and chemical properties

Appearance and properties: white to off-white crystalline powder

Density: 1.272 g / cm ³

Melting point: 104-108 ° C (lit.)

Boiling point: 427ºC at 760 mmHg

Flash point: 212.1ºC

Refractive index: -127.5 ° (C = 1.7, EtOH)

Water solubility: soluble

Stability: stable. Incompatible with strong oxidants.

Storage conditions: Store in a cool, dry place. Store in a closed container.

Captopril safety information

Symbol: GHS07 GHS08

Signal Word: Warning

Hazard statement: H317; H361

Cautionary Statement: P280

Customs code: 2933990090

WGK Germany: 2

Danger category code: R36 / 37/38

Safety instructions: S36 / 37-S37 / 39-S26

RTECS number: UY0550000

Dangerous goods mark: Xi ^[1]

Captopril production method

(1) Obtained from L-proline by isobutene condensation, benzyloxycarbonyl chloride esterification, hydrogen hydrogenation, 3-acetylthio-2-methylpropanoic acid condensation, dicyclohexylamine salt formation, desalting, and hydrolysis.

(2) 1: 230 g of L-proline dissolved in 1 L of water and 400 ml of 5 mol / L sodium hydroxide. Sodium oxide and 340 ml of benzyl chloroformate. After the addition was complete, the mixture was stirred at room temperature for 1 h. The reaction solution was extracted twice with ether and acidified with concentrated hydrochloric acid. The precipitate was filtered and dried to obtain 442 g of N-benzylcarbonyl-L-proline, with a melting point of 78-80 ° C. A solution of 180 g of N-benzylcarbonyl-L-proline dissolved in 300 ml of dichloromethane, 800 ml of liquid isobutylene, and 7.2 ml of concentrated sulfuric acid was shaken in a pressure vessel for 72 h. After decompression, isobutylene was distilled off, and the remaining solution was sequentially washed with 5% sodium carbonate and water, dried over anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to obtain 205 g of N-benzylcarbonyl-L-proline tert-butyl ester. 205 g of N-benzylcarbonyl-L-proline tert-butyl ester was dissolved in 1.

2 L of absolute ethanol, under normal pressure using 10% palladium-carbon as a catalyst, hydrogenation until only a trace amount of carbon dioxide (about 24h) in the hydrogen released. The catalyst was removed by filtration, the filtrate was concentrated at 4.0 kPa, and the residue was distilled under vacuum to obtain L-proline tert-butyl ester, with a boiling point of 50-51 ° C / 133Pa. 5.1g of L-proline tert-butyl ester was dissolved in 40ml of dichloromethane, stirred and cooled in an ice bath. 15 ml of DCC (dicyclohexylcarbodiimide) was added, and immediately a solution of 4.9 g of 3-acetylmercapto-2-methylpropionic acid in 5 ml of dichloromethane was added. After stirring on an ice bath for 15 min, and then at room temperature for 16 h, the precipitate was removed by filtration, and the filtrate was concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate, washed with water to neutrality, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure. The residue was N- (3-acetylmercapto-2-methylpropanoyl) -L-proline tert-butyl ester, which was purified by column chromatography (silica gel-chloroform) to obtain 7.9 g. To a mixed solution of 55 ml of anisole and 110 ml of trifluoroacetic acid, 7.8 g of N- (3-acetylmercapto-2-methylpropanoyl) -L-proline tert-butyl ester was added and left at room temperature for 1 h. The solvent was evaporated under reduced pressure, and the residue was precipitated several times with ether-hexane. The precipitate (6.8g, racemate) was dissolved in 40ml of acetonitrile, and 4.5ml of dicyclohexylamine was added. Only the (S, S) isomer could form a salt with dicyclohexylamine. The crystalline salt was filtered off and boiled in freshly distilled acetonitrile, then cooled to room temperature and filtered to obtain 3.8 g of the (S, S) L-proline derivative of dicyclohexylamine, melting point 187-188 . After recrystallization from propanol, [] D-67 ° (C = 1.4, ethanol). The salt was suspended in a mixed solution of 5% potassium hydrogen sulfate and ethyl acetate. The separated organic layer was washed with water and concentrated to dryness, and the residue was crystallized from ethyl acetate-hexane to obtain optically active (S, S) -N- (3-acetylmercapto-2-D-methylpropionyl). -1-Proline, melting point 83 ~ 85 . 0.85 g of the optically active proline derivative obtained above was dissolved in a 5.5 mol / L ammonia methanol solution and kept at room temperature for 2 h. The solvent was distilled off under reduced pressure, and the residue was dissolved in water. An acid-type ion exchange resin (Dowex 50 (Analytical grade) was chromatographed and the developing solution was water. The effluent that was positive for the thiol test was collected and dried on ice. The residue was crystallized from acetone-hexane to obtain 0.3 g of captopril, with a melting point of 103-104 ° C ^[1] .

Captopril use

Antihypertensive APIs ^[1] .

Captopril safety term

S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.

After accidental contact with eyes, rinse immediately with plenty of water and seek medical advice.

S37 / 39Wear suitable gloves and eye / face protection

Wear appropriate gloves and goggles or a mask.

Captopril risk term

R36 / 37 / 38Irritating to eyes, respiratory system and skin.

Irritation of eyes, respiratory system and skin.

Captopril Pharmacopoeia Standard

Captopril source (name), content (potency)

This product is 1-[(2S) -2-methyl-3-mercapto-1-oxopropyl] -L-proline. Calculated on dry basis, containing C9H15NO3S shall not be less than 97.5%.

Captopril traits

This product is a white or off-white crystalline powder; it has a special smell similar to garlic and has a salty taste.

This product is easily soluble in methanol, ethanol or chloroform, and soluble in water.

Melting point

The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 104-110 ° C.

Specific rotation

Take this product, weigh it accurately, add ethanol to dissolve and quantitatively dilute it to make a solution containing about 20mg per 1ml, and measure it according to law (Appendix VI E of the 2010 Pharmacopoeia Part II). The specific rotation is -126 ° to -132 °.

Captopril identification

(1) Take about 25mg of this product, add 2ml of ethanol to dissolve, add a little sodium nitrite crystals and 10 drops of dilute sulfuric acid, shake, the solution is red.

(2) Take the test solution under the captopril disulfide, dilute with mobile phase to make a solution containing 0.1mg per 1ml as the test solution; take another captopril reference, add An appropriate amount of methanol was dissolved, and then diluted with mobile phase to make a solution containing about 0.1 mg per 1 ml as a reference solution. According to the chromatographic conditions under the captopril disulfide, take 20 l each of the test solution and the reference solution, and inject them into the liquid chromatograph respectively. The retention time of the main peak of the test solution should be the same as the retention time of the main peak of the reference solution. Consistent.

(3) The infrared light absorption spectrum of this product should be consistent with the control spectrum ("Infrared Spectra of Medicine" 96).

Captopril inspection

Captopril disulfide

Protect from light. Take this product, weigh it accurately, add mobile phase to dissolve and quantitatively dilute it to make a solution containing about 0.5mg per 1ml, as a test solution (provisional new); also take captopril disulfide reference, Precisely weigh, add appropriate amount of methanol to dissolve, then quantitatively dilute with mobile phase to make a solution containing about 5g per 1ml, as a reference solution; then take captopril and captopril disulfide reference substance, add methanol Dissolve in proper amount, and dilute with mobile phase to make a mixed solution containing about 0.1mg and 15g per 1ml, as a system suitability test solution. Tested according to high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 edition), using octadecylsilane bonded silica as a filler; 0.01mol / L sodium dihydrogen phosphate solution-methanol-acetonitrile (70: 25: 5) (Use phosphoric acid to adjust pH to 3.0) as mobile phase; detection wavelength is 215nm; column temperature is 40 ° C. Take 50l of the system suitability test solution and inject it into the liquid chromatograph. The resolution between the Captopril peak and the Captopril disulfide peak should be greater than 4.0. Take 50l of the reference solution and inject it into the liquid chromatograph to adjust the detection sensitivity so that the peak height of the captopril disulfide chromatographic peak is about 50% of the full range; and then accurately measure each of the test solution and the reference solution. 50l, separately injected into the liquid chromatograph, record the chromatogram; if the chromatogram of the test solution solution has chromatographic peaks consistent with the retention time of captopril disulfide, calculate the peak area according to the external standard method, and it must not exceed 1.0 %.

Sulfate

Take 1.0g of this product and check it according to law (Appendix B of Part Two of the Pharmacopoeia of 2010 Edition). It must not be more concentrated (0.05%) than the control solution made from 5.0ml of standard potassium sulfate solution.

Loss on drying

Take this product, use phosphorus pentoxide as a desiccant, and dry under reduced pressure at 60 ° C to constant weight, and the weight loss should not exceed 0.5% (Appendix L of the second edition of the Pharmacopoeia of 2010 Edition).

Residue on ignition

Take 2.0g of this product and inspect it according to law (Appendix N of Part Two of the Pharmacopoeia of 2010 Edition). The residual residue shall not exceed 0.1%.

Heavy metal

Take the remaining residue under the burning residue, add 1ml of nitric acid, evaporate to dry up until the nitrogen oxide vapor is removed, add 2ml of hydrochloric acid, evaporate to dry in a water bath, add 5ml of water, evaporate to dry, add 15ml of water and acetate buffer solution (pH 3.5) 4ml, dissolve at a slight temperature, add water to make 50ml, shake well, divide 25ml, and check according to law (Appendix H of the second edition of the Pharmacopoeia of 2010 Edition H first method), containing no more than 20 parts per million.

Zinc salt

Take 25ml of the remaining solution under the above heavy metal, put it in a 50ml Nass colorimetric tube, add 4ml of hydrochloric acid solution (1 2) and 3ml of potassium ferrocyanide test solution, add water to the mark, and shake well. If turbidity occurs, and Standard zinc solution [precisely weigh 44mg of zinc sulfate (ZnSO4 · 7H2O), put it in a 100ml measuring flask, add water to dissolve and dilute to the mark, shake well, take 10ml precisely, place in another 100ml measuring bottle, and dilute to the mark with water. Shake well. Each 1ml is equivalent to 10g of Zn] 3.0ml control solution, it must not be more concentrated (0.003%).

Captopril determination

Take about 0.3g of this product, accurately weigh, add 100ml of water, shake to dissolve, add 10ml of dilute sulfuric acid, then add 1.0g of potassium iodide and 2ml of starch indicator solution, titrate with potassium iodate titration solution (0.01667mol / L), until The solution was micro-blue (no fading for 30 seconds) and the results of the titration were corrected with a blank test. Each 1ml of potassium iodate titration solution (0.01667mol / L) is equivalent to 21.73mg of C9H15NO3S ^[2] .

Captopril Categories

Angiotensin transferase inhibitor.

Captopril storage

Shaded and sealed.

Captopril

(1) Captopril (2) Compound Captopril

Captopril Drug Analysis

Method Name: Captopril API-Determination of Captopril-Redox Titration

Molecular structure diagram ^[3]

Scope of application: This method uses the titration method to determine the content of captopril in the captopril drug substance.

This method is applicable to Captopril APIs.

Principle of the method: Dilute sulfuric acid, add potassium iodide and starch indicator solution after test solution is dissolved in water, titrate with potassium iodate titration solution until the solution is slightly blue, and correct the titration result with blank test. According to the amount of titrant used, Calculate the content of captopril.

Reagent:

Potassium iodide

2. Potassium iodate titration solution (0.01667mol / L)

3. Dilute sulfuric acid

4. Starch indicator liquid

equipment:

Sample preparation:

1. Potassium iodate titration solution (0.01667mol / L)

Preparation: Take the benchmark potassium iodate, dry it at 105 to constant weight, accurately weigh 3.5667g, place it in a 1000mL measuring bottle, add an appropriate amount of water to dissolve and dilute to the mark, and shake to obtain.

Dilute sulfuric acid

Take 57mL of sulfuric acid and dilute to 1000mL with water.

3. Starch indicator liquid

Take 0.5g of soluble starch, add 5mL of water and stir well, then slowly pour into 100mL of boiling water. Stir with the addition, continue to boil for 2 minutes, let cool, and pour the supernatant liquid.

Operation steps: Precisely weigh about 0.3g of the test sample, add 100mL of water, shake to dissolve, add 10mL of dilute sulfuric acid, add 1.0g of potassium iodide and 2mL of starch indicator solution, and titrate with potassium iodate titrant (0.01667mol / L) , Until the solution is micro-blue (hold for 30 seconds without discoloration), and the results of the titration are corrected with a blank test. Each 1mL of potassium iodate titer (0.01667mol / L) is equivalent to 21.73mg of C9H15NO3S.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards ^[4] .

Captopril Drug Description

Captopril classification

Circulatory Drugs> Cardiovascular Dilatation Drugs> Angiotensin Transferase Inhibitors

Captopril dosage form

1. Tablets: 12.5mg, 25mg, 50mg, 100mg each;

2. Compound tablets: Each tablet contains captopril 10mg, hydrochlorothiazide 6mg.

3. Injection: 25mg (1ml), 50mg (2ml).

Captopril pharmacological effects

It is a synthetic non-peptide angiotensin converting enzyme (ACEI) inhibitor, mainly acting on the renin-angiotensin-aldosterone system (RAAS system)

Captopril System). Inhibits angiotensin-converting enzyme (ACEI) of the RAAS system, prevents angiotensin conversion or angiotensin , and can inhibit aldosterone secretion and reduce water and sodium retention. It has obvious antihypertensive effect on many types of hypertension and can improve cardiac function in patients with congestive heart failure. The antihypertensive effect of hypertension with different renin types is high renin and normal renin type; the low blood pressure of low renin type is also obvious after adding diuretics. Its antihypertensive mechanism is to inhibit angiotensin-converting enzyme activity, reduce angiotensin level, and relax small arteries. This product has a light to medium intensity antihypertensive effect, which can reduce peripheral vascular resistance and increase renal blood flow without reflex heart rate acceleration. This product can reduce blood pressure through the following mechanisms: inhibit angiotensin converting enzyme, reduce angiotensin I to AngII and reduce vasodilation; at the same time reduce aldosterone secretion to facilitate sodium excretion; specific renal vasodilation also enhances sodium excretion Effect; because of inhibiting the hydrolysis of bradykinin, reducing the inactivation of bradykinin; in addition, it can also inhibit the formation of local angiotensin I in vascular tissues and myocardium. Can improve heart function in patients with heart failure.

Captopril pharmacokinetics

1. Tablet system: oral absorption is rapid, it takes effect in about 15 minutes, the blood concentration reaches a peak in 1 hour, and it is widely distributed. It can pass through the placenta and migrate into milk. Bioavailability is 60%, protein binding rate is about 30%, T1 / 2 is 4h, and the effect is maintained for 6-8h. Increasing the dose can prolong the duration of action, while

Captopril Does not enhance the antihypertensive effect. Metabolized in the liver, metabolites and prototype drugs are excreted from the urine.

2. Injection: This product has a rapid onset of injection. 25% to 30% of this product is bound to proteins in the blood circulation. The half-life is less than 3 hours, and drug retention occurs when renal function is impaired. The antihypertensive effect is progressive, reaching the maximum therapeutic effect in a few weeks. It is metabolized into disulfide and the like in the liver. This product is excreted by the kidney, about 40% to 50% is excreted in its original form, and the rest are metabolites, which can be removed during hemodialysis. This product cannot cross the blood-brain barrier. This product can be secreted through milk and through the placenta.

Captopril indication

It is used to treat various types of hypertension, especially refractory hypertension that is ineffective for other antihypertensive drugs. Combination with diuretics can enhance the efficacy, and it has a better effect on those with high plasma renin activity. It is also used for acute and chronic congestive heart failure, and it is more effective when combined with heart-strengthening agents or diuretics.

Captopril contraindications

1. Patients with renal insufficiency and severe autoimmune diseases are disabled.

2. Pregnant women, lactating women, and those with allergies are forbidden.

3. Patients with neutropenia and agranulocytosis are disabled.

4. Prohibited in patients with bilateral renal artery stenosis or similar lesions, patients with a history of hypotension, severe aortic stenosis or obstructive cardiomyopathy.

Captop use

2-3 times a day, if you still cannot control your blood pressure satisfactorily, you can take thiazide diuretics such as HCT25mg once a day. In the future, the dose of diuretics can be gradually increased every 1-2 weeks to achieve a satisfactory antihypertensive effect.

Heart failure: the initial dose of 25mg, 3 times a day, the dose increased to 50mg, after 3 times a day, should be taken for 2 weeks to observe the effect. Usually 50-100mg, 3 times a day.

For patients who have recently taken a large number of diuretics, who are in low sodium / hypovolemia, and whose blood pressure is normal or low, the initial dose should be 6.25mg-12.5mg, 3 times a day. It will be gradually increased to the usual amount after testing.

Captopril adverse reactions

1. Central nervous system: fainting, headache, dizziness, paresthesia, insomnia and fatigue, caused by hypotension, especially in the absence of sodium or blood volume

Captopril Full time.

2. Cardiovascular system: palpitations, mild increase in heart rate, hypotension during the first dose, dizziness, etc.

3. Gastrointestinal tract: taste disorder, nausea, vomiting, diarrhea, abdominal pain, constipation, dry mouth, dull taste, loss of appetite, salty or golden odor in the mouth, weight loss, etc.

4, blood system: neutropenia, granulocytes, and various types of cells. Appears 3 to 12 weeks after the start of treatment, and is most significant in 10 to 30 days. It lasts for 2 weeks after stopping treatment.

5, allergic reactions: serum sickness-like reactions, joint pain and skin damage.

6. Kidney: Urine ketones, renal dysfunction, nephrotic syndrome, glomerulonephritis, etc. Proteinuria, which usually occurs within 8 months of treatment, gradually decreases within 6 months, and the course of treatment is not affected.

7, skin: rash (often occurred within 4 weeks of treatment), urticaria, maculopapular rash, angioedema, and photosensitivity. Disappeared after reduction, withdrawal or antihistamine administration, 7% to 10% with increased eosinophils or positive antinuclear antibodies

8. Other: positive anti-nuclear antibody test, cough, etc.

Captopril drug interactions

1. This product can increase blood potassium concentration, which may cause high blood potassium. Caution should be exercised when combined with spironolactone, ampicillin and other potassium-sparing diuretics.

2, combined with potassium-containing drugs, can cause excessive blood potassium.

3, combined with prostaglandin synthesis inhibitors such as indomethacin, can reduce the effect of this product.

4. It is forbidden to use it in combination with other drugs that may change immune function, such as procainamide, ventricaine, hydralazine, probenecid and acebutrolol.

5. This product can reduce the resistance of nitrate drugs.

6. Combined with antipsychotic drugs such as tricyclic antidepressants to enhance their antihypertensive effect and cause the risk of orthostatic hypotension.

7. Combined with corticosteroids to reduce antihypertensive effect.

8. Co-administration with other vasodilator drugs may cause hypotension.

9. Use with diuretics to enhance the antihypertensive effect, but it should be avoided to cause severe hypotension, so the original diuretics should be discontinued or reduced.

10. Combined with other antihypertensive drugs, the antihypertensive effect is enhanced; it has an additive effect with drugs that cause renin release or affect sympathetic activity: it has a less than additive effect with b blockers.

Captopril precautions

1. Patients who are allergic to this product and have leukopenia are disabled.

2, renal insufficiency, elderly patients, pregnant women, nursing mothers with caution.

3. When angioedema is found (such as swelling of the face, eyes, tongue, throat, limbs, swallowing or breathing difficulties, hoarseness), the drug should be stopped immediately. The presence of angioedema of the tongue, glottis, or throat can cause obstruction of the trachea, leading to death. Immediate subcutaneous injection of epinephrine and other drugs should be used for emergency treatment. Angioedema of the face, oral mucosa, lips, and extremities usually disappears after drug withdrawal. If necessary, medication should also be used.

4. During the period of medication, the white blood cell count, urine red blood cells and protein, and serum electrolytes should be checked regularly. If the white blood cell count is too low when using this product, you can resume using this product. Patients with severe autoimmune diseases (especially systemic lupus erythematosus) are prone to agranulocytosis when taking this product.

5. Strictly restricted sodium diet or dialysis, the first dose is prone to sudden and severe hypotension.

6, when used in patients with renin-type hypertension, the dose should not be too large, so as not to reduce excessive blood pressure.

7, it is best to take medicine 1 hour before meals, because food can reduce the absorption of this product.

8. Angioedema occurs when using this product. This product should be stopped and rapid subcutaneous injection of 1: 1000 epinephrine 0.3 0.5ml

9. This product can increase blood urea nitrogen and creatinine concentrations, which are usually temporary. It is easy to appear after renal disease or long-term severe hypertension and blood pressure drops rapidly, occasionally serum liver enzymes may increase; may increase blood potassium, and maintain potassium Diuretics should be used with special attention to check potassium.

10. Use this product with caution in the following situations: autoimmune diseases such as severe systemic lupus erythematosus, at this time the chance of white blood cells or granulocytes is increased; bone marrow suppression; insufficient blood supply to the cerebral or coronary arteries, which may be due to lower blood pressure Increased ischemia; Hyperkalemia; Renal dysfunction caused an increase in blood potassium, decreased white blood cells and granulocytes, and retained the product; Aortic stenosis, which may reduce coronary perfusion at this time;

11. Patients with poor renal function should take a small dose or reduce the number of doses, and slowly increase; stop taking diuretics one week before using this product. If you need to use diuretics at the same time, it is recommended to use furosemide instead of thiazines. When the blood urea nitrogen and creatinine increase, reduce the amount of this product or stop diuretics at the same time.

12. If proteinuria gradually increases when using this product, suspend this product or reduce the dosage.

Medication for pregnant and lactating women

(1) This product can pass through the placenta.

(2) This product can be drained into milk, and its concentration is about 1% of the blood concentration of the mother. Therefore, the application of lactating women must be weighed against the pros and cons.

(3) ACEI absorption by pregnant women can affect fetal development and even cause fetal death. Pregnant women are prohibited.

Medication for children

It has been reported that the use of this product in infants can cause excessive and long-term reduction of blood pressure with oliguria and convulsions, so the application of this product is limited to those who have failed in other antihypertensive treatments.

Medication for elderly patients

The elderly are more sensitive to the antihypertensive effect, and the dosage of this product must be reduced.

Captopril overdose

Overdose can cause hypotension, and should be discontinued immediately and expanded to correct. In adults, it can also be removed by hemodialysis.

Captopril poisoning

Captopril (captopril, captopril, Kefuding, SQ-14225) is an angiotensin converting enzyme inhibitor, which can effectively antagonize the conversion of angiotensin I to angiotensin II and lower blood pressure. Used to treat hypertension. Oral absorption is rapid (more than 75%), peaks at 1 to 1.5 hours, lasts 6 to 12 hours, and the half-life is about 4 hours. It is mainly excreted by the kidneys. Oral 12.5-50mg, 2-3 / d, 450mg / d. This medicine mainly damages the cardiovascular system, respiratory system, kidney, blood system and causes allergic reactions.

Clinical manifestation

Adverse reaction

Dizziness, dizziness, low blood pressure, dry cough, nasal congestion, rash, and gastrointestinal disorders.

2. Poisoning performance

(1) Cardiovascular system performance: low blood pressure, bradycardia, and atrioventricular block.

(2) Respiratory system performance: cough, dyspnea, bronchospasm, rhinitis, and laryngeal edema.

(3) Urinary system performance: proteinuria, hematuria, acute renal insufficiency.

(4) Blood system performance: white blood cells, granulocytopenia, and thrombocytopenia.

(5) Other system manifestations: angioedema, hyperkalemia, hypermagnesemia, can cause arrhythmia and cause death.

treatment

The main points of treatment for captopril poisoning are:

1. Patients with adverse drug reactions should stop taking the drug immediately. Those who take large oral doses should promptly induce vomiting, gastric lavage, and infusion to accelerate drug excretion.

2. Hypotension occurs, blood volume should be replenished, hyponatremia should be corrected, and booster drugs such as dopamine should be given at the same time.

3. Those with hyperkalemia use intravenous drip of 100 200ml of 5% sodium bicarbonate solution, or 100ml of 25% 50% glucose solution intravenously, 500ml of 10% glucose solution, and add 1% insulin with 3 4g glucose. , Intravenous drip.

4. Acute renal insufficiency can be treated with hemodialysis or peritoneal dialysis.

5. In patients with leukocytes, granulocytes, and thrombocytopenia, whole blood and platelets are injected intravenously after stopping the drug. If necessary, use Fegerastine (G-CSF) or Hematocrit (GM-CSF).

6. Bronchial spasm and laryngeal edema should be given immediately.

7. Other symptomatic treatments ^[5] .

Captopril new uses

1. Cirrhosis and ascites

The renin-angiotensin-aldosterone system in most patients with cirrhosis and ascites is often active. Increased vascular tone and vitality can cause renal artery contraction, which may be one of the mechanisms of hepatorenal syndrome. Captopril has the effect of selectively dilating blood vessels. After using this drug, as the systemic arterial pressure decreases, liver blood flow also decreases.

2, myocardial infarction

Captopril can reduce the mean arterial pressure and increase the rate of nonradioactive heart rate. Captopril can prevent ventricular dilatation. After myocardial infarction, myocardial contraction and diastolic dysfunction, ventricular dilatation, increased blood pressure, and rapid heart rhythm, clinical studies have shown that captopril can reduce mean arterial pressure and increase non-reflective heart rate. Prevention of degree and degree heart failure has a very good effect.

3. Idiopathic edema

Mimcan reported a woman with idiopathic edema who took captopril 50 mg 3 times per day, increased sodium and water excretion, edema subsided, switched to placebo after 2 weeks, edema recurred, and then used card After 4 weeks of topril, the edema subsided without recurrence. It has been reported that the application of captopril for the treatment of interstitial edema has achieved good results.

4, Raynaud's disease

Mivazuki has treated Raynaud's disease with captopril. After application, the symptoms such as paleness of the fingers and toes improved rapidly, and the effect of continuous medication for several months was very satisfactory. In addition to inhibiting the production of angiotensin , the involvement of bradykinin also has a certain relationship. Due to the decrease of angiotensin and the increase of bradykinin, the blood vessels dilate, and the terminal vascular resistance decreases, which improves the microcirculation of the fingers and toes.

5, vascular scleroderma

Lopoz-ovejero reported two patients with vascular scleroderma with necrosis. After using captopril, the persistent ulcers were cured, which was also related to the improvement of peripheral microcirculation.

6, cerebral vasospasm and migraine

It is reported that captopril can be used to treat migraine. Generally, the pain can be quickly relieved after medication. Therefore, it can be used as a routine medicine in the acute attack of migraine. However, some people have used this product to treat cerebral vasospasm diseases. Whether it can reduce the incidence of subarachnoid hemorrhage or cerebral artery rupture remains to be confirmed.

7, rheumatoid arthritis

Recent studies have found that captopril has an immunosuppressive effect, which can partially suppress the B lymphocyte effect: this effect can be transmitted by effector T lymphocytes and has nothing to do with prostaglandins. In addition, captopril and D-penicillamine have similar molecular structures with a thiol group. Captopril seems to have a vasodilator effect, so some people have used Captopril for rheumatoid arthritis, and the results are relatively satisfactory. Martin selected 15 patients with rheumatoid arthritis with significant improvement in clinical symptoms and biochemical indicators.

Captopril adverse reactions-cough

Captopril has documented adverse reactions that cause cough. The incidence of dry or severe cough is 0.7% to 6%.

There are currently three explanations for the mechanism of captopril-induced cough: weaken bradykinin catabolism and accumulate in the blood, thereby acting on the bronchi, causing bronchoconstriction, spasm, mucosal congestion and edema, and increased secretion through vagal reflex And a refractory cough appears. This cough occurs in the upper respiratory tract, and vagal nerve fiber cells may play a mediating role, and may also be related to the increased sensitivity of secondary pharyngeal stimulatory receptors. It may affect the inactivation of certain inflammatory mediators, such as histamine and prostaglandins, which increase the concentration of these substances and accumulate in the lungs. After reaching a certain level, they can stimulate cough receptors and cause cough.

Captopril-induced cough has the following characteristics: 1. It only occurs in people who are sensitive to this medicine, and it does not occur in people who are not sensitive; 2. It has nothing to do with the dose, and can occur in small amounts; 3. People with asthma Cough is more likely to occur when taking this medicine, and it is often mistaken for asthma to be aggravated and ignored, so it should be carefully identified when taking it.

The onset of cough is hidden and usually takes a few days to appear. Therefore, there have been reports of cases delayed for several months, with dry cough, no sputum, and exacerbation at night. Doctors checked that most of the organic lesions could not be found, and they would be relieved quickly after stopping the medicine, but the cough would still recur after taking the medicine. This kind of cough is generally not harmful to patients. The cough of people with heart and lung disease is easy to be confused with this type of cough. Therefore, patients who take captopril should have a cough that may worsen with the original cough. For adverse drug reactions, the doctor should be consulted to change the drug. For cough caused by captopril, immediate withdrawal is the best measure. Generally, symptoms will be significantly reduced or disappeared within two weeks after the withdrawal. If you don't want to stop the drug, you can use histamine antagonists, such as promethazine (phenagen), to combat cough caused by captopril, which has achieved good results. The specific usage is that on the basis of not stopping captopril, take 12.5 mg of promethazine before going to bed at night and observe it for 1 week. If it is effective, the cough symptoms gradually decrease or disappear from the 4th day after taking the medicine. After the cough disappears, continue the treatment for 7 to 10 days before stopping the medicine. If there is no improvement in cough symptoms after taking the drug for 1 week, it means that promethazine is not effective. At this time, captopril should be stopped and the type of antihypertensive drugs should be adjusted.

Angiotensin converting enzyme inhibitor (ACEI) is a commonly used class of antihypertensive drugs, and its representative drug is captopril. But because many patients cannot tolerate the cough caused by it, they have to stop using it. Iron has been reported to be effective in the treatment of ACEI-induced cough, and 58 cases were selected in this article to verify this result. The 58 patients with hypertension met the WHO diagnostic criteria for hypertension in 1999. There were 24 males and 34 females with an average age of 51.34 years. The dry cough occurred within 7 to 20 days after taking captopril, which was obvious in the period before bedtime. The dry cough disappeared within 1 week after captopril was stopped. Among them, 31 patients had no active anti-inflammatory and antitussive treatment before discontinuing captopril. Fifty-eight patients took captopril again while taking ferrous sulfate 300 mg / day, divided into three meals, and judged the efficacy after 10 days. Cough completely disappeared in 18 cases, significantly reduced in 29 cases, and ineffective in 11 cases, with a total effective rate of 81%. Two patients had epigastric discomfort, but did not stop taking the drug. ACEI is a commonly used drug in the treatment of hypertension, heart failure and reversion of left ventricular hypertrophy. ACEI-induced cough is 5% to 30%. It is more common in women, and dry cough is the main cause. The reason may be that ACEI induces nitric oxide synthase, which increases the production of nitric oxide, and the increased nitric oxide stimulates the airway mucosa and causes cough. Iron is an inhibitor of nitric oxide synthase, which relieves dry cough.

In addition, Compound Licorice Tablets and Huanglian Jiedu Tablets also have a therapeutic effect on cough caused by captopril.

Captopril expert review

Captopril Captopril controls blood pressure by dilating blood vessels, is safe and effective for mild and moderate hypertension, and is listed as a first-line treatment. Its advantage is that it has both anti-congestive heart failure and can eliminate the original left Ventricular hypertrophy slows down the development of renal failure. When hypertension is associated with congestive heart failure and left ventricular hypertrophy, captopril is listed as the first choice. The starting dose is 25 to 50 mg per day, and the total effective rate is 95%. In the domestic affiliated hospital of Guiyang Medical College, 36 patients with hypertension were treated with captopril. After the first dose of 25 mg, blood pressure began to decrease 15 minutes later, and the blood pressure decreased significantly in 2 hours, and returned to the basic level in 10 hours; 150 mg per day for 4 weeks. The treatment results were markedly effective in 27 cases and effective in 4 cases. The total effective rate was 86.1%. After 5 cases of ineffective administration of hydrochlorothiazide, 2 cases were markedly effective and 2 cases were effective. The total effective rate increased to 97.2%. Captopril can dilate static and arterial, reduce heart load, block progressive ventricular dilatation in chronic heart failure, prevent potassium and magnesium deficiency and reperfusion arrhythmia, thereby reducing sudden death. Clinical comparison studies have shown that although captopril and hydralazine can achieve the same degree of hemodynamic improvement at 400 mg per day, the actual survival rate after 1 year of treatment is higher than the former, 81% and 51%, respectively. After treatment with Captopril for 22 patients with refractory congestive heart failure, Shanghai Changning District Central Hospital followed up for a few months. The clinical effect was satisfactory. Increased by 30%, stroke volume increased by 35%, pulmonary capillary wedge pressure decreased by 40%, and peripheral vascular resistance decreased by 32% ^[6] .