BRONQUIDIAZINA C.R

Indications

• Chronic bronchitis
• Asthma
• Bronchiectasis
• Pneumonia
• Respiratory tract infections with productive cough

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Additionally, bromhexine has been shown to inhibit the transmembrane serine protease 2 receptor (TMPRSS2), which plays a crucial role in viral respiratory diseases. This inhibition may help in preventing or treating various respiratory illnesses, including COVID-19, by blocking viral entry into cells.

Pharmacodynamics

Bromhexine thins airway secretions, thus improving breathing and alleviating discomfort associated with thick mucus in the airways. Its action is particularly beneficial in respiratory disorders where mucus obstruction is a significant issue.

Pharmacokinetics

Bromhexine is well absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It is metabolized in the liver, primarily to ambroxol, which is its active metabolite. The elimination half-life of bromhexine is approximately 8 to 12 hours, and it is excreted mainly through urine. The pharmacokinetics can be influenced by factors such as liver function and concurrent medications.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Vomiting
• Diarrhea
• Allergic reactions

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor patients with asthma or bronchospastic conditions

Pregnancy

Bromhexine should be used during pregnancy only if clearly needed and after careful consideration of the potential benefits and risks.

Breast-feeding

Bromhexine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Syrup
• Solution for inhalation

Indications

• Urinary tract infections
• Respiratory tract infections
• Gastrointestinal infections
• Pneumocystis pneumonia
• Toxoplasmosis

Dosage

Children: Refer to the BNF for Children for specific dosing information appropriate for paediatric patients, as doses are typically weight-based and vary by age and condition.

Adults: Refer to the BNF for specific dosing information based on the clinical condition being treated, as dosing may vary depending on the severity of the infection and patient characteristics.

Mechanism of action

Sulfamethoxazole inhibits bacterial dihydrofolic acid synthesis due to its structural similarity to para-aminobenzoic acid (PABA). It competitively inhibits dihydropteroate synthase, the enzyme responsible for converting PABA to dihydrofolic acid. This action prevents the synthesis of tetrahydrofolate, leading to the inhibition of bacterial purine and DNA synthesis, resulting in a bacteriostatic effect.

Pharmacodynamics

Sulfamethoxazole is generally bacteriostatic, inhibiting a crucial step in bacterial folate synthesis. It is typically used in combination with trimethoprim, which inhibits the reduction of dihydrofolic acid to tetrahydrofolate. This combination allows for a synergistic effect, reducing the rate of bacterial resistance development compared to using either drug alone. Care should be taken as sulfamethoxazole can cause hypersensitivity reactions, and it may contribute to folate deficiency, particularly in at-risk populations.

Pharmacokinetics

Sulfamethoxazole is well absorbed following oral administration and is widely distributed in body tissues. It has a moderate half-life, necessitating multiple daily doses for sustained therapeutic effect. The drug is metabolized in the liver and excreted primarily via the kidneys, with some metabolites being active. Its excretion can be influenced by renal function, necessitating dose adjustments in patients with compromised kidney function.

Contra-indications

• Hypersensitivity to sulfamethoxazole or other sulfonamides
• Severe liver impairment
• Severe renal impairment
• History of severe adverse reactions to sulfonamides (e.g., Stevens-Johnson syndrome)

Adverse effects

• Rash
• Nausea
• Vomiting
• Diarrhea
• Hematological reactions (e.g., leukopenia, thrombocytopenia)
• Liver toxicity
• Renal toxicity
• Hemolytic anemia in patients with G6PD deficiency
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Interactions

• Sulfamethoxazole may increase the anticoagulant effect of coumarins
• Concurrent use with other folate antagonists may enhance toxicity
• May interact with methotrexate, increasing the risk of toxicity

Precautions

• Use with caution in patients with a history of hypersensitivity reactions
• Monitor for signs of folate deficiency
• Assess renal and liver function prior to and during treatment
• Discontinue immediately at the first sign of rash or skin reaction

Pregnancy

Sulfamethoxazole is generally not recommended during pregnancy, especially in the first trimester and near term, due to potential risks of teratogenic effects and kernicterus in the newborn.

Breast-feeding

Sulfamethoxazole is excreted in breast milk; caution is advised when administering to nursing mothers due to potential effects on the nursing infant.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Oral tablets
• Oral suspension
• Injection

Indications

• Urinary tract infections
• Acute exacerbations of chronic bronchitis
• Pneumocystis pneumonia (PCP) prophylaxis
• Bacterial infections in patients with compromised immune systems

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information, as it is based on age and weight.

Adults: Refer to the BNF for specific dosage information as it varies based on the indication and severity of infection.

Mechanism of action

Trimethoprim selectively inhibits dihydrofolate reductase, leading to a decrease in the production of tetrahydrofolate. This inhibition impairs bacterial growth by preventing the synthesis of nucleic acids and ultimately, bacterial cell reproduction.

Pharmacodynamics

Trimethoprim exhibits bactericidal activity against a wide range of gram-positive and gram-negative bacteria. Its antibacterial action is due to the interference with folate metabolism, which is crucial for DNA and RNA synthesis. The drug is particularly effective against Escherichia coli, a common pathogen in urinary tract infections.

Pharmacokinetics

Trimethoprim is well absorbed from the gastrointestinal tract with an oral bioavailability of approximately 90%. It reaches peak plasma concentrations within 1-4 hours. The drug is widely distributed throughout the body and penetrates well into bodily tissues, including the prostate and lungs. Trimethoprim is primarily eliminated via renal excretion, with a half-life of about 8-10 hours. Dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to trimethoprim or any of its excipients
• Severe renal impairment
• Pregnancy (especially in the first trimester) due to potential risk of teratogenic effects

Adverse effects

• Nausea
• Vomiting
• Rash
• Pruritus
• Bone marrow suppression leading to anemia
• Leukopenia
• Thrombocytopenia
• Elevated liver enzymes
• Hyperkalemia
• Elevated creatinine levels

Interactions

• Increased risk of hyperkalemia when used with potassium-sparing diuretics
• May enhance the effects of anticoagulants such as warfarin
• Decreased effectiveness when used with certain anticonvulsants
• May interact with methotrexate, increasing its toxicity

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during treatment
• Use cautiously in patients with a history of folate deficiency
• Consider alternative treatments in patients with known hypersensitivity to sulfonamides

Pregnancy

Trimethoprim is generally avoided during pregnancy, especially in the first trimester due to potential teratogenic effects. It is important to weigh the benefits against the risks before prescribing.

Breast-feeding

Trimethoprim is excreted in breast milk. Caution should be exercised when administering to nursing mothers. Monitor the infant for potential adverse effects.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension
• Injectable solution

Mechanism of action

Inflammation of the airways, increased mucus secretion, and altered mucociliary clearance are the hallmarks of various diseases of the respiratory tract. Mucus clearance is necessary for lung health; bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Recent have studies have demonstrated that bromhexine inhibits the transmembrane serine protease 2 receptor (TMPRSS2) in humans. Activation of TMPRSS2 plays an important role in viral respiratory diseases such as influenza A and Middle East Respiratory Syndrome (MERS). Inhibition of receptor activation and viral entry by bromhexine may be effective in preventing or treating various respiratory illnesses, including COVID-19. In vitro studies have suggested the action of ambroxol (a metabolite of bromhexine) on the angiogensin-converting enzyme receptor 2 (ACE2), prevents entry of the viral envelope-anchored spike glycoprotein of SARS-Cov-2 into alveolar cells or increases the secretion of surfactant, preventing viral entry.

Pharmacodynamics

Bromhexine thins airway secretions, improving breathing and discomfort associated with thick mucus in airways associated with a variety of respiratory conditions.

Mechanism of action

Sulfamethoxazole is a sulfonamide that inhibits bacterial dihydrofolic acid synthesis due to its structural similarity to an endogenous substrate, para-aminobenzoic acid (PABA). Most bacteria meet their need for folic acid by synthesizing it from PABA, as opposed to Animalia that require exogenous folic acid sources. Sulfamethoxazole competitively inhibits dihydropteroate synthase, the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid. Inhibition of this pathway prevents the synthesis of tetrahydrofolate and, ultimately, the synthesis of bacterial purines and DNA, resulting in a bacteriostatic effect. Sulfonamides are usually bacteriostatic in action. Sulfonamides interfere with the utilization of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid (the reduced form of folic acid) cofactors in susceptible bacteria. Sulfonamides are structural analogs of PABA and appear to interfere with PABA utilization by competitively inhibiting the enzyme dihydropteroate synthase, which catalyzes the formation of dihydropteroic acid (a precursor of tetrahydrofolic acid) from PABA and pteridine; however, other mechanism(s) affecting the biosynthetic pathway also may be involved. Compounds such as pyrimethamine and trimethoprim, which block later stages in the synthesis of folic acid, act synergistically with sulfonamides. Only microorganisms that synthesize their own folic acid are inhibited by sulfonamides; animal cells and bacteria which are capable of utilizing folic acid precursors or preformed folic acid are not affected by these drugs. The antibacterial activity of the sulfonamides is reportedly decreased in the presence of blood or purulent body exudates. /Sulfonamides/ /Sulfonamides inhibit bacterial growth by preventing para-aminobenzoic acid (PABA) from being incorporated/ into dihydropteroic acid, the immediate precursor of folic acid. Sensitive microorganisms are those that must synthesize their own folic acid; bacteria that can utilize preformed folate are not affected. Bacteriostasis induced by sulfonamides is counteracted by PABA competitively. Sulfonamides do not affect mammalian cells by this mechanism, since they require preformed folic acid and cannot synthesize it. /Sulfonamides/ Sulfonamides are broad-spectrum, bacteriostatic anti-infectives. They are structural analogs of para-aminobenzoic acid and competively inhibit a bacterial enzyme, dihydropteroate synthetase, that is responsible for incorporation of para-aminobenzoic acid into dihydrofolic acid. This blocks the synthesis of dihydrofolic acid and decreases the amount of metabolically active tetrahydrofolic acid, a cofactor for the synthesis of purines, thymidine, and DNA. /Sulfonamides/ The hydroxylamine and nitroso metabolites formed by N4-oxidation of sulfonamides are thought to be involved in the pathogenesis of idiosyncratic reactions to this class of drugs. Idiosyncratic reactions to sulfonamides are characterized by multisystemic toxicity, including hepatitis, nephritis, dermatitis, and blood dyscrasias (aplastic anemia, agranulocytosis). Previously it has been shown that cytochrome p-450 in the liver metabolizes sulfamethoxazole to its hydroxylamine metabolite. In this paper the N4-oxidation of sulfamethoxazole by activated monocytes and neutrophils (human and canine) to form sulfamethoxazole hydroxylamine and nitrosulfamethoxazole is reported. The presumed nitroso intermediate was not detected. Purified myeloperoxidase and prostaglandin H synthase were also capable of mediating the oxidation of sulfamethoxazole. The present studies suggest that myeloperoxidase is responsible for the observed oxidation by phagocytic cells. Oxidation by neutrophils may play a role in agranulocytosis, and oxidation by monocytes may facilitate antigen presentation. Extrahepatic bioactivation of sulfonamides by peroxidases in phagocytic cells and other tissues may be important in determining the range of adverse reactions to sulfonamides

Pharmacodynamics

Sulfamethoxazole is a bacteriostatic sulfonamide antibiotic that inhibits a critical step in bacterial folate synthesis. It is generally given in combination with [trimethoprim], a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either trimethoprim or sulfamethoxazole alone, as together they inhibit sequential steps in the bacterial folate synthesis pathway. Sulfonamides, including sulfamethoxazole, have been implicated in hypersensitivity reactions - these agents should be discontinued at the first sign of a developing rash, as this may signal the start of a more severe reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Sulfamethoxazole treatment may contribute to folate deficiency and should therefore be used with caution in patients at a higher risk of developing a deficiency. Hemolysis has been observed in patients with glucose-6-phosphate dehydrogenase deficiency who are using sulfamethoxazole/trimethoprim.