What are the clinical applications of quinolone antibiotics?🙌🙌🙌

1. Introduction.

Quinolones have a broad antibacterial spectrum. They are more effective
against Gram-negative bacteria than Gram-positive bacteria. Commonly used quinolone drugs include: ① Ciprofloxacin has the strongest activity against Gram-negative bacteria, especially Pseudomonas aeruginosa. ② Levofloxacin has good activity against most Gram-positive and Gram-negative bacteria. ③ Moxifloxacin has broad-spectrum antibacterial activity, with strong activity against Gram-positive bacteria, anaerobes, Mycobacterium tuberculosis, Legionella, Mycoplasma, and Chlamydia. Levofloxacin and moxifloxacin have bioavailability exceeding 90%. They can be administered sequentially via intravenous and oral administration. They have long half-lives and are generally given once daily. Ciprofloxacin has low oral bioavailability. It has a short half-life and is generally given twice daily or three times daily. Levofloxacin and ciprofloxacin are primarily excreted through the kidneys, so dosage adjustments are necessary for patients with renal insufficiency. Some quinolones (such as gemifloxacin, gatifloxacin, levofloxacin, and moxifloxacin) have high concentrations in lung tissue and exhibit good bactericidal activity against common pathogens in lung tissue. They demonstrate good antibacterial activity and pharmacokinetics in the treatment of community-acquired respiratory infections. Quinolone drugs all share the common structure of pyridoxine. Early quinolone drugs did not contain a fluorine atom in their structure. Later, a fluorine atom was introduced at the 6-position of the quinolone nucleus to enhance its inhibitory effect on DNA gyrase and its penetration into cells, thereby strengthening its antibacterial activity. Therefore, they can be divided into non-fluoroquinolones and fluoroquinolones. Common fluoroquinolones include ciprofloxacin, levofloxacin, and moxifloxacin.

2. Pharmacokinetics.

Fluoroquinolones are well absorbed orally. The oral bioavailability of most fluoroquinolones is close to or greater than 90%. Food generally does not affect the absorption of fluoroquinolones, but it can delay the time to peak absorption. Foods rich in calcium, iron, and magnesium can reduce the bioavailability of the drugs. Fluoroquinolones have a large distribution volume, mostly around 100 L, which is significantly larger than that of aminoglycosides or β-lactam antibiotics. Therefore, fluoroquinolones are widely distributed in tissues and body fluids. Drug concentrations in the lungs, kidneys, prostate, urine, bile, feces, macrophages, and neutrophils are higher than in the blood, but concentrations in cerebrospinal fluid, bone tissue, and prostatic fluid are lower. The drug can also be distributed to the lacrimal glands, salivary glands, genitourinary system, and respiratory mucosa. Drug elimination pathways differ. Pefloxacin is primarily metabolized in the liver and excreted via bile. Ofloxacin, levofloxacin, lomefloxacin, and gatifloxacin are excreted unchanged (over 80%) via the kidneys. For other drugs, both hepatic and renal elimination are equally important. 

3. Antibacterial properties.

Fluoroquinolones are bactericidal drugs. Their bactericidal concentration is 2 to 4 times the microinhibitory concentration (MIC). Third and fourth generation quinolones are broad-spectrum bactericides. Later-developed drugs such as moxifloxacin and gatifloxacin, in addition to retaining good antibacterial activity against Gram-negative bacteria, further enhanced their killing effects on Gram-positive bacteria, Mycobacterium tuberculosis, Legionella, Mycoplasma, and Chlamydia, especially improving their antibacterial activity against anaerobic bacteria such as Bacteroides fragilis, Fusobacterium spp., Peptostreptococcus spp., and anaerobic spore-forming Clostridium spp. Ciprofloxacin still has the strongest killing effect against Pseudomonas aeruginosa.

4. Mechanism of action.

Quinolone drugs target DNA gyrase and topoisomerase IV. They interfere with bacterial chromosome replication and transcription by binding to these enzymes. At low concentrations, they disrupt DNA replication, and at high concentrations, they cause cell death, thus exerting their antibacterial effect. The mechanisms of quinolone drug resistance are multifactorial. These include target site variations caused by chromosomal mutations, decreased bacterial outer membrane permeability or increased drug efflux leading to reduced drug uptake, and overexpression of repair enzymes and target site protective proteins.

5. Clinical applications.

1. Genitourinary tract infections: Ciprofloxacin and ofloxacin are recommended for treating uncomplicated gonococcal urethritis or cervicitis. Escherichia coli generally has a high quinolone resistance rate, therefore, for complicated urinary tract infections, drug sensitivity results should be used as a reference. Ciprofloxacin is the first-line drug for Pseudomonas aeruginosa urethritis.

2. Respiratory system infections: Taking upper respiratory tract infections as an example, moxifloxacin and levofloxacin can be used as empirical treatment options.

3. Intestinal infections and typhoid fever: Quinolones are the first-line empirical treatment.

4. Bone, joint and soft tissue infections: Bone and joint infections can be treated with rifampin in combination with ciprofloxacin and levofloxacin, depending on drug sensitivity results. For skin and soft tissue infections, such as diabetic foot ulcers with a diameter >2 cm or depth involving the fascia, quinolones in combination with other drugs can be used.

5. Other: It can be used as a second-line treatment option for tuberculosis, brucellosis, cholera, etc.

6. Precautions.

Quinolones are not suitable for routine use in children. Quinolones should be avoided in patients under the age of 18. 

Quinolone drugs may cause photosensitivity of the skin (avoid sun exposure during medication), joint lesions, tendinitis, tendon rupture (including various routes of administration, some of which may occur after discontinuation of the drug), and occasionally cause QT interval prolongation on electrocardiogram.

Drugs containing metal ions such as calcium, aluminum, and magnesium, as well as antacids, can chelate with most quinolone drugs when used together, affecting the absorption of quinolone drugs and significantly reducing their bioavailability and blood concentration. Therefore, the timing of medication administration should be staggered according to the specific drugs being used.

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Precautions regarding novel oral anticoagulants.📃📃📃

Atrial fibrillation is a common persistent arrhythmia. It can significantly increase the risk of stroke. Novel oral anticoagulants (NOACs) are widely used in clinical practice for atrial fibrillation anticoagulation due to their superior safety and ease of administration. The four commonly used NOACs are dabigatran, which directly inhibits thrombin, and rivaroxaban, apixaban and edoxaban, which inhibit factor Xa.

Pharmacokinetics of NOACs and the Effect of Antiarrhythmic Drugs (AADs) on Their Anticoagulant Effect.

The selection of NOACs should consider factors such as bioavailability, potential drug interactions along metabolic pathways, elimination half-life, and the presence of antagonists. In the absence of clear indications, reducing or increasing the dose will increase adverse events without increasing safety. Different NOACs have different metabolic characteristics. When used in combination with antiarrhythmic drugs (AADs), attention should be paid to the effect of AADs on NOAC blood concentrations, and appropriate drug selection and dosage adjustments should be made.

**White indicates no drug interactions. Gray indicates no data. Yellow indicates use with caution. Orange indicates low dose (Dabigatran) or reduced dose (Edoxaban). Red indicates contraindication, as it is not recommended due to increased blood drug concentration.

What is the NOAC dosage?

Improper use of NOAC dosage may have adverse consequences for patients with atrial fibrillation. Off-label use of low-dose NOACs increases the risk of stroke. Off-label use of higher-dose NOACs increases the risk of major bleeding. Therefore, correct use of NOACs and minimizing adverse outcomes in patients with atrial fibrillation are crucial.

How to choose between NOACs and warfarin for elderly patients with atrial fibrillation?

For elderly patients with atrial fibrillation, NOAC anticoagulation therapy is preferred. It recommends anticoagulation therapy with dabigatran etexilate, rivaroxaban, or edoxaban. If warfarin is used, the INR should be maintained at 2.0–3.0 or 1.6–2.5 (for patients ≥ 75 years of age or those at high risk of bleeding with a HASBLED score ≥ 3).

Management of Anticoagulation-Related Bleeding:

1. Minor bleeding related to NOACs: Discontinue medication for 12–24 hours if necessary.

2. Moderate to severe bleeding: Consider using blood products, hemodialysis, etc., depending on the anticoagulant used.

3. Life-threatening bleeding: Use specific antagonists (vitamin K, edasuzumab, or andexanet-α, etc.).

Whether or when to resume anticoagulation therapy after bleeding requires careful consideration of the patient's thrombotic and bleeding risks.

Switching between anticoagulants: Switching between different anticoagulants should follow the principle of not affecting the effectiveness of anticoagulation therapy and minimizing the risk of bleeding.

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Is it more appropriate to take metformin before or after meals?😐😐😐

Metformin has a significant hypoglycemic effect. It does not increase the risk of hypoglycemia when used alone. It also has good tolerability and safety, and its price is relatively inexpensive. Therefore, it remains a widely used oral hypoglycemic agent in clinical practice.

The hypoglycemic pharmacological effects of metformin.

1. Inhibition of hepatic glycogen output

Blood glucose is produced in the liver through gluconeogenesis (the conversion of non-carbohydrate substances into glucose). Metformin can reduce hepatic gluconeogenesis, thereby lowering fasting blood glucose levels.

2. Improve insulin sensitivity

Metformin activates adenosine monophosphate-activated protein kinase (AMPK) in fat and muscle cells. This promotes glucose uptake and utilization, thereby lowering postprandial blood glucose levels.

3. Increase glucagon-like peptide-1 (GLP-1) levels

GLP-1 can stimulate insulin secretion, delay gastric emptying, and reduce glucose absorption. Metformin, on the other hand, can promote GLP-1 secretion by acting directly on intestinal L cells or by regulating gut microbiota.

**Metformin is a potent oral hypoglycemic agent. As a monotherapy, it can reduce glycated hemoglobin (HbA1c) by 1% to 1.5%.

Other effects of metformin besides lowering blood sugar

1. Anti-cancer

People with type II diabetes are more likely to develop breast cancer, endometrial cancer, colorectal cancer, and other cancers. Clinical studies have found that metformin can be used to prevent breast and endometrial cancer in obese individuals. It also can reduce the risk of colorectal polyps developing into colorectal cancer. Metformin can also increase the sensitivity of tumors to chemotherapy drugs.

2. Improve Polycystic Ovary Syndrome (PCOS)

PCOS has a high prevalence among women of reproductive age. Its main manifestations include excessive androgens (acne, hirsutism), menstrual disorders, ovulation disorders, and polycystic ovarian changes. PCOS is also often accompanied by obesity and insulin resistance. Metformin can correct hyperandrogenemia by lowering blood insulin levels. This improves ovarian ovulation and enhances the effectiveness of ovulation induction treatment.

3. The preventive effect of diabetes

Prediabetes includes impaired fasting glucose (≥6.1 to <7.0 mmol/L) and impaired glucose tolerance (2-hour post-glucose load blood glucose ≥7.8 to <11.1 mmol/L). Clinical studies have shown that metformin can effectively reduce the risk of developing type II diabetes in people with prediabetes. In addition, metformin also has potential cardiovascular protective effects.

Dosage of metformin tablets

The minimum recommended dose is 500 mg/day. The optimal effective dose is 2000 mg/day. The maximum dose is 2550 mg/day. Metformin should be started at a low dose and gradually increased to reduce gastrointestinal reactions (such as diarrhea and nausea). Take 2 to 3 times daily, with or immediately after meals. Taking metformin after meals will slow down the absorption rate and reduce the extent of absorption, but it can reduce gastrointestinal reactions.

Dosage of metformin extended-release tablets

The maximum dose of metformin extended-release tablets is 2000 mg/day. Compared with regular tablets, extended-release tablets may have better gastrointestinal tolerability and improve patient medication adherence. Take once daily with dinner. Sustained-release tablets must be swallowed whole; do not crush or chew them. Taking on an empty stomach will reduce absorption by approximately 30%. Take once daily with dinner. Sustained-release tablets must be swallowed whole; do not crush or chew them. Taking on an empty stomach will reduce absorption by approximately 30%.

Dosage of Metformin enteric-coated tablets

The usual daily dose is 1 to 1.5g, with a maximum daily dose not exceeding 2g. Take 2 to 3 times daily, half an hour before meals. The coating of enteric-coated tablets needs to dissolve in the alkaline environment of the intestines. Taking it before meals allows the tablet to quickly enter the intestines, reducing stomach discomfort.

Regularly monitor vitamin B12 levels

Long-term use of metformin can cause vitamin B12 deficiency in patients. Therefore, it is recommended that patients with insufficient vitamin B12 intake or absorption have their vitamin B12 levels monitored annually before starting metformin treatment and after treatment. If deficiency is found, appropriate supplementation should be given, especially for patients with anemia and peripheral neuropathy.

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What is the difference between the expectorants Ambroxol and N-acetylcysteine❔❔❔

The mixture of mucin, sugar, protein, water, etc. secreted by the airway submucosal glands and goblet cells is called airway mucus. It moisturizes the inhaled air and protects the airways. However, multiple pathogenic factors such as infection, oxidative stress, and smoking can cause hypertrophy and proliferation of goblet cells and mucous glands, leading to excessive mucus production. If the patient's airway epithelial cell cilia function is dysfunctional and the airway purification capacity is reduced, it will lead to difficulty in expectoration. Sputum obstruction of the airways can cause or worsen dyspnea. Expectorants can dilute sputum, reduce sputum viscosity, promote airway clearance, and make sputum easier to expel from the body. They effectively improve patients' expectoration. Ambroxol and N-acetylcysteine ​​(NAC) are very widely used expectorants in clinical practice.

Various functions of ambroxol and N-acetylcysteine.

1. Expectorant effect

    Ambroxol: It reduces sputum viscosity by increasing serous fluid secretion. It also enhances ciliary beating, promoting the secretion and release of alveolar surfactant, thereby facilitating sputum excretion.

    NAC: Its molecular structure contains sulfhydryl groups, which can break the disulfide bonds between mucin complexes, reduce the viscosity of sputum, and make it easier for patients to cough up sputum.

2. Antioxidant Effect

    Ambroxol: It activates the glutathione system in cells. The synthesis of glutathione in cells will be promoted, which can remove active peroxidation products. It has a destructive effect on oxygen free radicals.

    NAC: Its molecular structure contains sulfhydryl groups. These groups can interact with hypochlorous acid, hydroxyl radicals, hydrogen peroxide and other substances to directly scavenge oxygen free radicals. Binding to glutathione peroxidase reduces the production of lipid peroxides. It can also serve as a precursor for the synthesis of glutathione, thereby maintaining sufficient glutathione levels in lung tissue and protecting cells from damage by cytotoxins.

3. Anti-inflammatory effects

    Ambroxol: It inhibits the release of inflammatory factors such as histamine and leukotrienes by eliminating free radicals, which can effectively inhibit the inflammatory effects of white blood cells and macrophages.

    NAC: It acts as an antioxidant. It inhibits oxidative stress-mediated inflammation. It can reduce the damage of oxidative stress to lung tissue and inhibit airway remodeling. It can also reduce the impact of inflammation on lung function.

4. Antibacterial effect

    Ambroxol: When ambroxol used in combination with antibiotics such as amoxicillin, cefuroxime and erythromycin, it can increase the concentration of these drugs in lung tissue. This will increase the bacterial clearance rate of antibiotics in the lungs, thereby reducing the duration and dosage of antibiotics.

    NAC: It reduces the adhesion of Haemophilus influenzae and Streptococcus pneumoniae to oropharyngeal epithelial cells, making it more difficult for the bacteria to grow in the airways. It also inhibits the replication of influenza virus and respiratory syncytial virus.

5. Other

    NAC: It is used as an antidote for acetaminophen poisoning and hemorrhagic cystitis caused by cyclophosphamide.

Indications for ambroxol and N-acetylcysteine.

1. COPD

    GOLD Guidelines: For patients with COPD not using ICS, routine use of expectorants and antioxidants can reduce the frequency of acute exacerbations of COPD and modestly improve health status.

    NAC: It has strong expectorant, anti-inflammatory, and antioxidant properties. It can reduce sputum viscosity and promote expectoration. It can also improve cough, sputum production, and associated dyspnea in COPD patients. It can also reduce oxidative stress, decrease the frequency of acute exacerbations, and reduce bacterial colonization in the respiratory tract. It improves the patient's quality of life. Therefore, NAC is more suitable for COPD patients than ambroxol.

2. Bronchiectasis

    Various pathogenic factors can lead to increased secretions in the airways of patients with bronchiectasis. The patient's airway clearance will be impaired and causing sputum accumulation. This can lead to airway obstruction and recurrent bacterial infections.

    Guidelines recommend that patients with bronchiectasis who have difficulty expectorating and whose symptoms cannot be controlled by conventional airway clearance can use mucosal active drugs for long-term treatment (> 3 months). The current research results show that bromhexine combined with antibiotics or nebulized NAC can help clear sputum. Ambroxol, the active ingredient in bromhexine, can help improve lung function and shorten hospital stays in patients with bronchiectasis and infection.

3. Idiopathic interstitial pneumonia

    Patients with idiopathic interstitial pneumonia mainly present with dry cough and progressively worsening dyspnea. Conventional expectorants do not seem to be of much use for patients with idiopathic interstitial pneumonia.

    As a glutathione precursor, NAC can increase glutathione levels in the lining fluid of lung epithelial cells, exerting an antioxidant effect. NAC monotherapy has a certain effect on some patients with idiopathic interstitial pneumonia with TOLLIP gene phenotype, and NAC combined with pirfenidone is superior to pirfenidone alone in the treatment of patients with intermediate and late stage idiopathic interstitial pneumonia. Patients already receiving NAC monotherapy can continue maintenance therapy.

4. Bronchial asthma

    There is limited research evidence on the effects of ambroxol and NAC in the treatment of patients with bronchial asthma. Currently, there is insufficient evidence to support the benefit of expectorant therapy in patients with asthma.

5. Acute respiratory distress syndrome

    Currently, there is insufficient evidence to support the use of antioxidants such as NAC in the treatment of acute respiratory distress syndrome. Expectorants are also not recommended as a routine treatment for acute respiratory distress syndrome.

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What are the common combined uses and indications for Calamine lotion?😕😕😕

Calamine lotion is a common skin medication. It is used to treat acute itchy skin conditions such as hives and prickly heat. While it is effective alone, it can also be used in combination with other medications to achieve varying therapeutic effects. The following will describe the efficacy and characteristics of calamine lotion, combined medication regimen and precautions.

1. Calamine lotion + nystatin

Pharmacology of combined medication: Calamine lotion combined with nystatin can fully exert the anti-inflammatory, astringent and antipruritic effects of calamine on perianal eczema. It can reduce tissue redness, swelling and exudate. It can also protect the local skin. Nystatin can effectively inhibit the growth and reproduction of fungi. The combination of the two is effective in treating perianal eczema.

Instructions for use: Grind 6 nystatin tablets (dosage is 500,000 units/tablet) into powder and add them to 100 ml of calamine lotion. Shake well before use. Dip a cotton swab in the medicine and apply it gently and evenly to the affected area. After applying the medication, keep the patient's buttocks exposed as much as possible. Apply 4-6 times daily. Before applying the medicine, remove any remaining medicine on the skin and then apply the medicine. Keep the patient in the side-lying position to avoid local pressure.

2. Calamine lotion + clindamycin

Pharmacology of combined medication: Calamine lotion has astringent properties and neutralizes acidic skin secretions. Clindamycin has strong effects against both Gram-positive and Gram-negative bacteria. In addition, it is equally sensitive to non-spore-forming bacteria among anaerobic bacteria. Clindamycin powder is readily soluble in water and has some efficacy in treating acne vulgaris when mixed with calamine lotion and applied topically.

Instructions for use: Add an appropriate amount of clindamycin powder to every 100ml of calamine lotion and mix well before applying topically. Apply topically six to eight times daily for a seven-day course of treatment, generally requiring two to three courses. If the patient does not improve after three courses, discontinue use immediately and seek alternative treatment options.

3. Calamine lotion + prednisone acetate

Pharmacology of combined medication: Calamine has astringent and antipruritic properties. It is effective in treating skin oozing, rashes and itching, etc. Prednisone acetate has anti-infective, anti-allergic, and immunosuppressive properties. Adding prednisone acetate to calamine lotion can enhance the anti-allergic effect and quickly relieve skin allergy symptoms. The combined use of the two drugs can have a certain effect on children's rash, skin flushing, blisters and other symptoms caused by allergies to dressings or adhesive tapes.

Instructions for use: Dissolve 50mg of prednisone acetate completely in 1000ml of calamine lotion and apply it externally once every 6 hours. Use normal saline to remove residual medicine on the child before each application.

4. Calamine lotion + Hydrocortisone butyrate cream

Pharmacology of combined medication: Hydrocortisone butyrate cream binds strongly to steroid receptors. However, its systemic effects are weak. Combining it with calamine lotion can effectively enhance its astringent, anti-inflammatory, and antipruritic properties. This combination is particularly effective in treating infantile eczema. However, infants have a thin skin barrier and high permeability, so corticosteroids can easily penetrate into the body. Therefore, topical medications containing hydrocortisone butyrate are not recommended for long-term use in infants. If the patient experiences poor efficacy after using the drug for three days, the drug should be discontinued immediately. In addition, the combined use of calamine lotion and hydrocortisone butyrate cream for exudative rashes is contraindicated.

Instructions for use: First, apply an appropriate amount of hydrocortisone butyrate cream to the affected area and gently massage for a while. Use once in the morning and evening for five days before discontinuing. Discontinue hydrocortisone butyrate cream and then use calamine lotion. Shake the lotion well and apply to the affected area twice a day, allowing it to dry naturally.

5. Calamine lotion + Loratadine

Pharmacology of combined medication: Calamine lotion was applied to cover the local mucous membranes of the buttocks lesions. It effectively promotes the regeneration of the buttocks mucosal tissue, restoring and maintaining the physiological barrier function of the mucosa. It promotes healing of mucous membranes and accelerates scab formation on the skin. It also has excellent anti-inflammatory and antipruritic properties. Calamine lotion combined with loratadine has a stronger anti-allergic effect. It can effectively relieve the discomfort caused by diaper rash in children.

Instructions for use: Grind three loratadine tablets into a powder and mix thoroughly with calamine lotion. Use a sterile cotton swab to evenly apply the mixture to the affected area from the inside out. Apply once with each diaper change.

6. Calamine lotion + Zinc oxide ointment

Pharmacology of combined medication: Zinc oxide has protective, astringent, and antiseptic properties on wounds. Calamine lotion also has protective, antipruritic, antiseptic, and astringent properties. The combined of these two drugs can enhance wound protection and antibacterial effects. It can also accelerate the improvement of diaper rash.

Instructions for use: Apply zinc oxide ointment evenly to the affected area on the buttocks three times daily, washing the skin after two hours. After changing the diaper, apply calamine lotion three times daily for a seven-day course of treatment.

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How to distinguish respiratory acidosis, metabolic acidosis, respiratory alkalosis and metabolic alkalosis?😕😕😕

Arterial blood gas analysis is the main diagnostic method for distinguishing
respiratory acidosis, metabolic acidosis, respiratory alkalosis and metabolic alkalosis. Arterial blood gas analysis can be simply divided into three steps. The first step is to determine whether the patient has acidosis or alkalosis. The second step is to determine whether the acidosis or alkalosis is respiratory or metabolic. The third step is to determine whether the patient has respiratory acidosis or respiratory alkalosis due to respiratory factors alone or metabolic factors.

The specific method of arterial blood gas analysis is as follows:

Step 1: Check the patient's pH. A normal pH is 7.4 ± 0.05. If the patient is acidotic, the pH should be ≤ 7.35. If the patient is alkalotic, the pH should be ≥ 7.45.

Step 2:  Observe the direction of changes in the patient's pH and PCO₂. If the acidosis or alkalosis is metabolic, pH and PCO₂ will change in the same direction (an increase in pH will increase PCO₂, or a decrease in pH will decrease PCO₂). If the acidosis or alkalosis is respiratory, pH and PCO₂  will change in opposite directions.

Step 3: If respiratory acidosis or alkalosis is present, observe the ratio of changes in the patient's pH to PCO₂. A normal PCO₂ is 40 ± 5 mmHg. In simple respiratory acidosis or alkalosis, for every 10 mmHg change in PCO₂, the pH value changes in the opposite direction by 0.08 ± 0.02. For example, if a patient has a PCO₂ of 40 mmHg and a pH of 7.4, a decrease in their PCO₂ by 10 mmHg to 30 mmHg would increase their pH by 0.08 to 7.48. A decrease in their PCO₂ by 20 mmHg to 60 mmHg would decrease their pH by 0.16 to 7.24.

If the changes in pH and PCO₂ do not conform to this ratio, it indicates that the patient also has a second factor (metabolic factor). In this case, the medical staff should compare the patient's theoretical pH value with the actual pH value. If the actual pH value is lower than the theoretical pH value, it indicates that metabolic acidosis is also present. Conversely, if the actual pH value is higher than the theoretical pH value, it indicates that metabolic alkalosis is also present. It should be noted that the pH value calculated according to the formula can fluctuate by ± 0.02.

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An introduction to pembrolizumab (Keytruda®) and its common usage and dosage.👀👀👀

Pembrolizumab is a monoclonal antibody. It is a programmed death receptor-1 (PD-1) blocker. The PD-1 receptor expressed by T cells binds to its ligands PD-L1 and PD-L2, thereby inhibiting T cell proliferation and cytokine production. PD-1 ligands are upregulated in some tumor cells. Signaling in this pathway can help inhibit active T cell immune surveillance of tumors. Pembrolizumab can bind to the PD-1 receptor. Blocking the binding of PD-1 to PD-L1 and PD-L2 will relieve the suppression of immune responses mediated by the PD-1 pathway. Therefore, the growth of tumor cells will also be inhibited. Pembrolizumab can be used clinically to treat a variety of cancers.

Common Pediatric Usage and Dosage of Pembrolizumab:

Indications	Usual dose for adults	Usual dose for children
Melanoma	For the treatment of unresectable or metastatic melanoma that has failed first-line therapy   200 mg once every three weeks or 400 mg once every six weeks until disease progression or unacceptable toxicity, or up to 12 months.	For adjuvant treatment of melanoma in children 12 years and older.   2 mg/kg every 3 weeks, up to 200 mg. Until disease progression, unacceptable toxicity, or up to 12 months.
Non-small cell lung cancer (NSCLC)	It is used as a first-line monotherapy for locally advanced or metastatic non-small cell lung cancer with negative epidermal growth factor receptor (EGFR) gene mutation and negative anaplastic lymphoma kinase (ALK) as assessed by PD-L1 tumor proportion score (TPS) ≥ 1%. It is used in combination with carboplatin and paclitaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer.   The recommended dose for monotherapy or combination chemotherapy is 200 mg once every three weeks or 400 mg once every six weeks.   Monotherapy or combination chemotherapy: until disease progression or unacceptable toxicity, or up to 24 months.   Adjuvant monotherapy: until disease progression or unacceptable toxicity, or up to 12 months.   For resectable non-small cell lung cancer, if it is given on the same day as chemotherapy, it should be given before chemotherapy. Neoadjuvant combination chemotherapy for 12 weeks or until disease progression that precludes radical surgery or unacceptable toxicity, followed by pembrolizumab as a single-agent adjuvant therapy after surgery for 39 weeks or until disease recurrence or unacceptable toxicity.
Esophageal cancer	Pembrolizumab is used in combination with fluorouracil and platinum chemotherapy for the first-line treatment of patients with locally advanced, unresectable or metastatic esophageal or gastroesophageal junction cancer. Pembrolizumab can also be used to treat patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (CPS ≥ 10) and who have failed previous first-line systemic therapy.   The recommended dose for monotherapy or in combination with chemotherapy is 200 mg once every three weeks or 400 mg once every six weeks until disease progression or unacceptable toxicity, or up to 24 months. If pembrolizumab is administered on the same day as chemotherapy, it should be administered before chemotherapy.
Classical Hodgkin's lymphoma (cHL)	Recommended monotherapy dose: 200 mg once every three weeks or 400 mg once every six weeks until disease progression or unacceptable toxicity, or up to 24 months. (For patients with cHL, an additional 400 mg dose is recommended every six weeks.)	2 mg/kg once every 3 weeks, up to a maximum of 200 mg, until disease progression or unacceptable toxicity, or up to 24 months.
Primary mediastinal large B-cell lymphoma (PMBCL)	Recommended monotherapy dose: 200 mg once every three weeks or 400 mg once every six weeks until disease progression or unacceptable toxicity, or up to 24 months. (For adult patients with PMBCL, an additional 400 mg dose is recommended every six weeks.)	2 mg/kg once every 3 weeks, up to a maximum of 200 mg, until disease progression or unacceptable toxicity, or up to 24 months.
Urothelial carcinoma	Pembrolizumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. Pembrolizumab is indicated for the treatment of patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are not eligible or who choose not to undergo cystectomy.   Recommended dose: 200 mg every three weeks or 400 mg every six weeks until persistent or recurrent high-risk urothelial carcinoma, disease progression, or unacceptable toxicity, or up to 24 months.
High-microsatellite instability/mismatch repair deficiency cancer	Recommended monotherapy dose: 200 mg once every three weeks or 400 mg once every six weeks until disease progression or unacceptable toxicity, or up to 24 months.	2 mg/kg once every 3 weeks, up to a maximum of 200 mg, until disease progression or unacceptable toxicity, or up to 24 months.
Gastric cancer	Pembrolizumab can be used as first-line treatment for patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.   Pembrolizumab should be given before trastuzumab and chemotherapy. The dose is 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.
Cervical cancer	Pembrolizumab can be used with or without bevacizumab for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥ 1).   Pembrolizumab should be given before bevacizumab. The dose is 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.
Hepatocellular carcinoma (HCC)	Pembrolizumab is used to treat hepatocellular carcinoma in patients who have received prior sorafenib or oxaliplatin-containing chemotherapy.   Recommended dose for monotherapy: 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.
Merkel cell carcinoma (MCC)	Pembrolizumab is used to treat adult patients with recurrent locally advanced or metastatic Merkel cell carcinoma.   Recommended dose: 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.	Pembrolizumab is used to treat pediatric patients with Merkel cell carcinoma.   2 mg/kg once every 3 weeks, up to a maximum of 200 mg, until disease progression or unacceptable toxicity, or up to 24 months.
Renal cell carcinoma (RCC)	Pembrolizumab is indicated as first-line treatment for adult patients with advanced renal cell carcinoma. Adjuvant treatment for patients with renal cell carcinoma who are at intermediate or high risk of recurrence after nephrectomy or nephrectomy and resection of metastatic disease   200 mg every three weeks or 400 mg every six weeks.   Combined with oral axitinib (5 mg twice a day) or lenvatinib (20 mg once a day). When pembrolizumab is used in combination with axitinib, it may be considered to increase the dose of axitinib above the initial dose of 5 mg at intervals of six weeks or longer.   Duration of monotherapy: until disease progression or unacceptable toxicity or up to 12 months.   Duration of Combination Therapy: Until disease progression or unacceptable toxicity or Pembrolizumab is given for up to 24 months.
Endometrial cancer	Pembrolizumab combined with lenvatinib can be used in patients with non-MSI-H pMMR advanced endometrial cancer who have disease progression after prior systemic therapy and are not suitable for curative surgery or radiotherapy: 200 mg once every three weeks or 400 mg once every six weeks, combined with lenvatinib 20 mg once daily, until disease progression or unacceptable toxicity or pembrolizumab for up to 24 months.   Monotherapy can be used to treat patients with MSI-H/dMMR advanced endometrial cancer who have disease progression after prior systemic therapy and are not candidates for curative surgery or radiation therapy in any setting: 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.
High tumor mutation burden cancer	Pembrolizumab is indicated for the treatment of adult patients with unresectable or metastatic solid tumors with high tumor mutational burden (TMB-H, ≥10 mutations/megabase/Mb) who have progressed after prior therapy and have no satisfactory alternative treatment options.   Recommended dose for monotherapy: 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.	Pembrolizumab can be used to treat pediatric cancers with high tumor mutation burden.   Recommended dose: 2 mg/kg once every 3 weeks, up to a maximum of 200 mg, until disease progression or unacceptable toxicity, or up to 24 months.
Cutaneous squamous cell carcinoma (cSCC)	Pembrolizumab can be used to treat patients with recurrent or metastatic cSCC or locally advanced cSCC that is not curable with surgery or radiation therapy.   Recommended dose for monotherapy: 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity or up to 24 months.
Triple-negative breast cancer (TNBC)	Pembrolizumab can be used in combination with neoadjuvant chemotherapy and continued as an adjuvant pembrolizumab monotherapy after surgery in patients with early-stage, high-risk TNBC whose tumors express PD-L1 (CPS ≥ 20) as assessed by a well-validated test.   In neoadjuvant therapy, patients should receive pembrolizumab 200 mg every three weeks for eight times or 400 mg every six weeks for four times, or until disease progression precluding radical surgery or unacceptable toxicity, followed by adjuvant pembrolizumab monotherapy. In adjuvant monotherapy, pembrolizumab is given at 200 mg every three weeks for nine times or 400 mg every six weeks for five times, or until disease relapse or unacceptable toxicity.   If patients have disease progression that precludes radical surgery or experience intolerable pembrolizumab-related toxicity during neoadjuvant therapy, they should not continue to receive adjuvant pembrolizumab monotherapy.

No dose adjustment is required for patients with mild hepatic impairment, mild or moderate renal impairment, and the elderly.

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An introduction to Nivolumab (Opdivo®) and its common usage and dosage.(Part 2)👀👀👀

The introduction to Nivolumab (Opdivo®) Part. 2. Nivolumab is recommended for the treatment of a variety of malignancies in children aged 12 years and older.

Common Pediatric Usage and Dosage of Nivolumab:

Recommended dose of nivolumab monotherapy:

Indications	Dosage	Duration
Unresectable or metastatic melanoma	For pediatric patients weighing ≥40 kg: Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	Patients were treated until disease progression or unacceptable toxicity.
	For pediatric patients weighing ≥40 kg: Once every two weeks, 3 mg/kg each time, intravenous infusion over 30 minutes. or Once every four weeks, 6 mg/kg each time, intravenous infusion over 30 minutes.
Adjuvant therapy for melanoma	For pediatric patients weighing ≥40 kg: Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	Patients were treated until disease progression or unacceptable toxicity, but not longer than one year.
	For pediatric patients weighing ≥40 kg: Once every two weeks, 3 mg/kg each time, intravenous infusion over 30 minutes. or Once every four weeks, 6 mg/kg each time, intravenous infusion over 30 minutes.
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer	For pediatric patients weighing ≥40 kg: Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	Patients were treated until disease progression or unacceptable toxicity.
	For pediatric patients weighing ≥40 kg: Once every two weeks, 3 mg/kg each time, intravenous infusion over 30 minutes.

Recommended doses of nivolumab when used in combination with other drugs:

Indications	Dosage	Duration
Unresectable or metastatic melanoma	Once every three weeks, 1 mg/kg each time, intravenous infusion over 30 minutes, combined with ipilimumab 3 mg/kg.	Combination therapy with ipilimumab. Use up to four times or until unacceptable toxicity occurs, whichever comes first.
	For pediatric patients weighing ≥40 kg: Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes. Combined treatment with ipilimumab 3 mg/kg.	After completing 4 combination treatments, single-agent therapy was used until disease progression or unacceptable toxicity occurred.
	For pediatric patients weighing ≥40 kg: Once every two weeks, 3 mg/kg each time, intravenous infusion over 30 minutes. or Once every four weeks, 6 mg/kg each time, intravenous infusion over 30 minutes.
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer	Once every three weeks, 3 mg/kg each time, intravenous infusion over 30 minutes, combined with ipilimumab 1 mg/kg.	Combined treatment with ipilimumab for four doses.
	Pediatric patients 12 years and older weighing ≥40 kg: Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes. Combined treatment with ipilimumab 1 mg/kg.	After completing 4 combination treatments, single-agent therapy was used until disease progression or unacceptable toxicity occurred.
	Pediatric patients 12 years and older weighing ≥40 kg: Once every two weeks, 3 mg/kg each time, intravenous infusion over 30 minutes. Combined treatment with ipilimumab 1 mg/kg.

Preparation method of Nivolumab injection.

Nivolumab is generally diluted with 0.9% sodium chloride injection or 5% glucose injection to prepare an infusion solution with a concentration of 1 mg/ml to 10 mg/ml.

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