G. AMOXINOR

Indications

• Bacterial infections
• Urinary tract infections
• Sinusitis
• Uncomplicated community-acquired pneumonia
• Salmonellosis
• Oral infections
• Lyme disease (under expert supervision)
• Acute exacerbation of bronchiectasis
• Anthrax (treatment and post-exposure prophylaxis)

Dosage

Children: 1 month–11 years: 30 mg/kg 3 times a day for 21 days; children 1–4 years: 250 mg 3 times a day; children 5–11 years: 500 mg 3 times a day.

Adults: 500 mg 3 times a day; increased if necessary up to 1 g 3 times a day in severe infections.

Mechanism of action

Amoxicillin works by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, interfering with the transpeptidation process necessary for cell wall integrity.

Pharmacodynamics

Amoxicillin exhibits bactericidal activity against susceptible bacteria. Its action is time-dependent, meaning that its effectiveness is related to the duration of time that the drug concentration remains above the minimum inhibitory concentration (MIC) for the target pathogen.

Pharmacokinetics

Amoxicillin is well absorbed from the gastrointestinal tract, with peak plasma concentrations achieved within 1-2 hours after oral administration. It is widely distributed in body tissues and fluids, and it is excreted primarily via the kidneys. The elimination half-life is approximately 1 hour, and renal impairment may necessitate dosage adjustments.

Adverse effects

• Skin rash
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Allergic reactions (including anaphylaxis)
• Superinfection (due to resistant organisms)

Interactions

• Allopurinol (increases risk of skin rash)

Precautions

• History of penicillin allergy
• Renal impairment (reduce dose)
• Use with caution in patients with mononucleosis

Pregnancy

Use only if clearly needed; no adequate studies in pregnant women.

Breast-feeding

Amoxicillin is excreted in breast milk; use with caution.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Phenoxymethylpenicillin 250mg/5ml oral solution
• Phenoxymethylpenicillin 250 mg tablets

Indications

• Bacterial infections
• Sepsis
• Pneumonia
• Meningitis
• Endocarditis
• Biliary tract infections
• Prostatitis
• Surgical prophylaxis
• Acute diverticulitis
• Leg ulcer infections

Dosage

Adults: 3–5 mg/kg daily in 3 divided doses, or a single daily dose of 5–7 mg/kg adjusted according to serum-gentamicin concentration. For surgical prophylaxis, 1.5 mg/kg administered intraven

Mechanism of action

Gentamicin exerts its antibacterial effects through a multi-phase mechanism. Initially, it binds to negatively charged components of bacterial cell membranes, increasing membrane permeability. Following this, it enters the bacterial cell via energy-dependent transport mechanisms, where it binds to the 30S ribosomal subunit. This binding causes mistranslation of proteins and disrupts membrane integrity, resulting in bacterial cell death. The action is concentration-dependent, leading to rapid bactericidal effects.

Pharmacodynamics

Gentamicin has a rapid onset of action due to its mechanism of disrupting the bacterial cell membrane and inhibiting protein synthesis. Its effectiveness is enhanced by higher concentrations, and it demonstrates a post-antibiotic effect where bacteria remain suppressed even after drug levels fall below the minimum inhibitory concentration. The drug's efficacy is influenced by factors like the bacterial strain and its susceptibility patterns.

Pharmacokinetics

Gentamicin is usually administered intravenously or intramuscularly. It has a volume of distribution of approximately 0.25 L/kg and is not significantly protein-bound. The drug is primarily eliminated via renal excretion, with a half-life of 2 to 3 hours in individuals with normal renal function. Dosing adjustments are necessary in patients with renal impairment to avoid toxicity. Serum levels should be monitored to optimize therapeutic efficacy while minimizing toxicity.

Contra-indications

• Hypersensitivity to gentamicin or any aminoglycoside
• Severe renal impairment
• Pre-existing auditory or vestibular dysfunction

Adverse effects

• Ototoxicity (hearing loss, vertigo, tinnitus)
• Nephrotoxicity
• Neuromuscular blockade
• Allergic reactions (rash, pruritus)
• Injection site reactions

Interactions

• Gentamicin + relugolix: Unknown (increases exposure)
• Gentamicin + other nephrotoxic drugs (e.g., vancomycin, cisplatin): Increased risk of nephrotoxicity
• Gentamicin + neuromuscular blocking agents: Enhanced neuromuscular blockade

Precautions

• Monitor renal function during therapy, especially in patients with pre-existing renal impairment
• Caution in patients with pre-existing hearing loss or vestibular disorders
• Use with caution in pregnant women and during breastfeeding

Pregnancy

Use only if clearly needed and the benefit justifies the risk to the fetus. Limited data on use in pregnancy.

Breast-feeding

Gentamicin is excreted in breast milk, exercise caution when administering to breastfeeding mothers. Monitor infant for possible side effects.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Injection solution (various concentrations)
• Ophthalmic solution (0.3% w/v)
• Topical ointment (0.1% w/v)

Indications

• Dyspepsia
• Peptic ulcer disease
• Gastroesophageal reflux disease (GERD)
• Heartburn
• Diarrhea
• Mucosal irritations

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations based on the condition being treated.

Mechanism of action

Aluminum acts as an astringent, causing local shrinkage or constriction of body tissues through osmotic flow of fluids away from the area of application. This mechanism assists in reducing mucous secretions and managing conditions such as peptic ulcers and diarrhea. Additionally, it can help in drying and hardening of tissues when applied topically.

Pharmacodynamics

Aluminum-based antacids work by neutralizing gastric acid, leading to an increase in gastric pH. This action helps to alleviate symptoms associated with excess gastric acid, such as heartburn and discomfort. The astringent properties of aluminum also contribute to its therapeutic effects in managing mucosal irritations and secretions.

Pharmacokinetics

Aluminum is absorbed minimally when taken orally, with a bioavailability of about 0.1 to 0.5%. The majority of aluminum is excreted renally, and its half-life can be prolonged in individuals with renal impairment. Long-term use may lead to accumulation and potential toxicity, particularly impacting bone and neurological health.

Interactions

• aluminiumhydroxide+deferasirox: Severe (decreases exposure)
• aluminiumhydroxide+enteralfeeds: Unknown (increases risk of blocked enteral or nasogastric tubes)
• aluminiumhydroxide+roxadustat: Unknown (decreases exposure)

Pregnancy

Aluminum compounds are generally considered safe in pregnancy when used as directed. However, excessive exposure should be avoided.

Breast-feeding

Aluminum is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• aluminium hydroxide suspension
• aluminium hydroxide tablets

Dosage

Children: Refer to specific formulations and usages, as dosing can vary widely depending on the application and regulatory guidelines.

Adults: Refer to specific formulations and usages, as dosing can vary widely depending on the application and regulatory guidelines.

Mechanism of action

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) act as antioxidants by inhibiting the oxidation of lipids. They scavenge free radicals and donate hydrogen atoms to reactive species, thus stabilizing and preventing oxidative damage to cellular components. This action helps to protect the integrity of cell membranes and prevent the formation of harmful peroxides.

Pharmacodynamics

The pharmacodynamic properties of butylated compounds are primarily related to their antioxidant activity. They exhibit a dose-dependent ability to inhibit lipid peroxidation, which is crucial in protecting cells from oxidative stress. Furthermore, they may modulate certain biochemical pathways involved in cell signaling and apoptosis, although these effects are less well-characterized.

Pharmacokinetics

Butylated compounds are absorbed from the gastrointestinal tract following oral ingestion. They undergo metabolic processing primarily in the liver, where they are conjugated and excreted in urine. The half-life of butylated compounds in humans is variable, influenced by factors such as dosage and individual metabolism. Accumulation in tissues is generally low, but prolonged exposure may lead to higher tissue concentrations.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Potential carcinogenic effects with prolonged exposure

Precautions

• Use with caution in patients with a history of hypersensitivity to butylated compounds
• Avoid prolonged exposure due to potential toxicity

Pregnancy

Limited data available, use only if the benefits outweigh the risks.

Breast-feeding

Unknown, exercise caution and consult a healthcare provider.

Storage

Store in a cool, dry place away from light.

Formulations

• Butylated hydroxytoluene (BHT)
• Butylated hydroxyanisole (BHA)

Indications

• Head lice infestation
• Body lice infestation
• Scabies

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Benzyl alcohol, a component of hydroxytoluene, inhibits lice from closing their respiratory spiracles. This action allows the vehicle to obstruct the spiracles, leading to asphyxiation of the lice.

Pharmacodynamics

The pharmacodynamics of hydroxytoluene involves its local anesthetic properties and its ability to disrupt the respiratory function of certain parasites. It exerts its effects primarily on ectoparasites like lice, leading to their death through suffocation. Its effectiveness is facilitated by its lipophilicity, which allows it to penetrate the cuticle of the lice and interfere with their respiratory system.

Pharmacokinetics

Hydroxytoluene is absorbed through the skin when applied topically. Its pharmacokinetic profile is influenced by its formulation, with variations in absorption rates based on the vehicle used. Once absorbed, it undergoes metabolic processes primarily in the liver, where it may be conjugated and excreted in urine. The elimination half-life and specific metabolic pathways are not well defined, requiring further research for comprehensive understanding.

Pregnancy

Hydroxytoluene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when administering hydroxytoluene during breastfeeding due to limited data on its excretion in human milk.

Storage

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

Indications

• Cancer (various types)
• Rheumatoid arthritis
• Multiple sclerosis
• Inflammatory bowel disease
• Psoriasis
• Hypercholesterolemia
• Infectious diseases (e.g., COVID-19)

Dosage

Children: Refer to the BNF for Children for paediatric dosing information, as it varies based on the specific monoclonal antibody and the condition being treated.

Adults: Refer to the specific monoclonal antibody product information for adult dosage, as it varies based on indication and specific agent used.

Mechanism of action

Monoclonal antibodies work by binding to specific proteins on the surface of cells. This binding can block the activity of certain proteins, mark cells for destruction by the immune system, or deliver cytotoxic agents directly to target cells. The mechanism of action varies depending on the specific monoclonal antibody but often involves modulation of immune response, inhibition of cell proliferation, and induction of apoptotic pathways.

Pharmacodynamics

The pharmacodynamics of monoclonal antibodies is primarily characterized by their specificity and affinity for targeted antigens. This leads to a variety of effects, including neutralization of pathogens, blockade of receptor-ligand interactions, and antibody-dependent cellular cytotoxicity. The clinical effects depend on the disease being treated and the specific antibody's action, such as inducing tumor regression in cancer or reducing inflammation in autoimmune diseases.

Pharmacokinetics

Monoclonal antibodies typically have a long half-life, allowing for less frequent dosing. They are generally administered intravenously or subcutaneously, with absorption and distribution influenced by the antibody's size and charge. The elimination occurs primarily through proteolytic degradation and intracellular recycling. Factors such as patient-specific variables, including immunogenicity and the presence of antibodies against the monoclonal antibody, can impact pharmacokinetics.

Interactions

• abatacept+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anakinra+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anthracyclines+monoclonalantibodies: Severe (increases risk of cardiotoxicity)
• filgotinib+monoclonalantibodies: Severe (increases risk of immunosuppression)
• monoclonalantibodies+fingolimod: Severe (increases risk of generalised infection (possibly life-threatening))
• normal immunoglobulin+monoclonalantibodies: Severe (affects effects)
• monoclonalantibodies+ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+vemurafenib: Severe (increases risk of hepatotoxicity)
• monoclonalantibodies+aminophylline: Moderate (decreases exposure)

Indications

• Cardiovascular health
• Menopausal symptom relief
• Bone health
• Cholesterol management
• Potential cancer risk reduction

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate dosage.

Adults: Refer to specific product guidelines or consult a healthcare professional for appropriate dosage.

Mechanism of action

Soybeans contain isoflavones, which are phytoestrogens that can mimic the effects of estrogen in the body. They exert their effects primarily through binding to estrogen receptors and modulating gene expression related to estrogen-responsive pathways. This interaction can influence various physiological processes, including bone density, lipid metabolism, and hormonal balance.

Pharmacodynamics

The pharmacodynamics of soybeans are attributed to their content of isoflavones, notably genistein and daidzein. These compounds may exhibit antioxidant properties, modulate lipid profiles by lowering LDL cholesterol, and influence bone metabolism. Additionally, the anti-inflammatory effects of soy isoflavones may contribute to cardiovascular benefits. The bioactive compounds in soybeans can also have protective effects against certain cancers, particularly hormone-sensitive types, by interfering with cancer cell growth and proliferation.

Pharmacokinetics

Isoflavones are absorbed in the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 3 hours after ingestion. The bioavailability of isoflavones can be influenced by factors such as food matrix, gut microbiota, and individual metabolism. Soy isoflavones undergo extensive metabolism in the liver, resulting in various metabolites, some of which may exhibit different biological activities. The elimination half-life of isoflavones can vary widely, depending on individual factors and the form in which soy is consumed.

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Nausea
• Diarrhea
• Flatulence

Precautions

• Use with caution in individuals with a known allergy to soy products.
• Monitor for potential interactions with anticoagulants, as soybean contains vitamin K.

Pregnancy

Soybean is generally considered safe during pregnancy when consumed in food amounts. However, high doses or supplements should be avoided due to potential hormonal effects.

Breast-feeding

Soybean is likely safe in food amounts during breastfeeding, but high doses or supplements should be approached with caution.

Storage

Store in a cool, dry place, away from direct sunlight. Keep tightly closed to avoid moisture.

Formulations

• Whole soybeans
• Soy flour
• Soy protein isolate
• Soy milk
• Soy oil
• Soy lecithin

Indications

• Muscle spasticity
• Anxiety disorders
• Sedation prior to surgical procedures
• Management of muscle pain or discomfort

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in paediatric patients. Doses are typically adjusted according to age and weight.

Adults: Refer to relevant clinical guidelines or the BNF for specific dosing information. Dosage may vary based on condition being treated and patient response.

Mechanism of action

Span acts as a positive allosteric modulator of the GABA-A receptor. By binding to this receptor, Span enhances the inhibitory effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system. This leads to increased neuronal hyperpolarization, resulting in muscle relaxation and sedation.

Pharmacodynamics

The pharmacodynamic properties of Span are characterized by its ability to induce muscle relaxation, sedation, and anxiolytic effects. The onset of action may vary depending on the route of administration, with intravenous administration producing effects more rapidly than oral forms. The therapeutic effects are generally dose-dependent, with higher doses yielding more pronounced muscle relaxant and sedative effects.

Pharmacokinetics

Span is well-absorbed when administered orally, with peak plasma concentrations typically occurring within 1 to 3 hours. It is metabolized primarily in the liver via cytochrome P450 enzymes, particularly CYP3A4. The elimination half-life can vary significantly among individuals, often ranging from 6 to 12 hours, depending on dosing and individual metabolism. The drug is excreted mainly in urine as metabolites.

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution, as it is not known if this drug is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat.

Mechanism of action

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action. The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Amoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.

Pharmacodynamics

Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis. Amoxicillin has a long duration of action as it is usually given twice daily. Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity. Patients should be counselled regarding the risk of anaphylaxis, _Clostridium difficile_ infections, and bacterial resistance.

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Mechanism of action

Aluminum Acetate is an astringent. An astrignent is a chemical that tends to shrink or constrict body tissues, usually locally after topical medicinal application. The shrinkage or constriction is through osmotic flow of water (or other fluids) away from the area where the astringent was applied. Astringent medicines cause shrinkage of mucous membranes or exposed tissues and are often used internally to check discharge of blood serum or mucous secretions. This can happen with a sore throat, hemorrhages, diarrhea, or with peptic ulcers. Externally applied astringents, which cause mild coagulation of skin proteins, dry, harden, and protect the skin. Acne sufferers are often advised to use astringents if they have oily skin. Astringents also help heal stretch marks and other scars. Mild astringent solutions are used in the relief of such minor skin irritations as those resulting from superficial cuts, allergies, insect bites, or fungal infections such as athlete's foot. Excessive dietary aluminum has been proposed to be a factor contributing to several neurological disorders in humans. Six 8-week-old female Swiss Webster mice were fed for 10 wk purified diets containing 100 (control), 500 or 1000 ug aluminum/g diet. Brain and liver lipid peroxidation was determined by evaluating the production of 2-thiobarbituric acid reactive substances in brain and liver homogenates in the presence or absence of 50 uM ferrous iron. 2-Thiobarbituric acid reactive substances production in the absence of iron in brain homogenates from mice fed the 1000 ug/g diet was higher (30%) than that in the 100 ug/g control group (3.1 vs 2.4 nmol 2-thiobarbituric acid reactive substances/mg protein). The addition of ferrous iron increased 2-thiobarbituric acid reactive substances production in brain homogenates from all 3 dietary groups. The iron induced 2-thiobarbituric acid reactive substances production was 26% higher in the 1000 ug/g brain homogenates than in the 100 ug/g group (4.9 vs 3.9 nmol 2-thiobarbituric acid reactive substances/mg protein). Brain 2-thiobarbituric acid reactive substances production in the presence and absence of iron was similar between the 100 and 500 ug/g aluminum groups. 2-Thiobarbituric acid reactive substances production in liver homogenates measured either with or without iron was similar for the 3 groups. These results show that, in mice, dietary aluminum intoxication leads to increased brain 2-thiobarbituric acid reactive substance production, suggesting that enhanced lipid peroxidation may be one possible mechanism underlying the neurological damage associated with increased tissue aluminum. Evidence is presented indicating that dementias are associated with a relative insufficiency of magnesium in the brain. Such insufficiency may be attributable to low intake or retention of magnesium; high intake of a neurotoxic metal, such as aluminum, which inhibits activity of magnesium requiring enzymes; or impaired transport of magnesium and/or enhanced transport of the neurotoxic metal into brain tissue. It is proposed that Alzheimer's disease involves a defective transport process, characterized by both an abnormally high incorporation of aluminum and an abnormally low incorporation that an altered serum protein contributes to the progression of Alzheimer's disease by having a greater affinity for aluminum than for magnesium, in contrast to the normal protein, which binds magnesium better than aluminum. The altered protein crosses the blood-brain barrier more efficiently than the normal protein and competes with the normal protein in binding to brain neurons. Binding of the altered protein to the target neurons would both facilitate aluminum uptake and impede magnesium uptake. Evidence suggests that albumin is the serum protein that is altered. Aluminum is established as a neurotoxin, although the basis for its toxicity is unknown. It recently has been shown to alter the function of the blood-brain barrier, which regulates ex

Mechanism of action

Benzyl alcohol inhibits lice from closing their respiratory spiracles, allowing the vehicle to obstruct the spiracles and causing the lice to asphyxiate.