CENTRE-NEOVITAL

Indications

• Bacterial infections (e.g. Chlamydia, Rickettsia, Mycoplasma)
• Acne
• Prophylaxis of asymptomatic meningococcal carrier state (not recommended)

Dosage

Adults: For adult patients, the typical dosage of oxytetracycline for susceptible infections is 100 mg twice daily for 5 days. For other conditions, such as acne, the dosage may be 500 mg twice daily, usually for a duration of 6 to 12 weeks, with the possibility of repeating the course intermittently.

Mechanism of action

Oxytetracycline exerts its antibacterial effects by binding to the 30S ribosomal subunit of bacteria, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. This action prevents the synthesis of proteins essential for bacterial growth and replication, leading to the bacteriostatic effect of the drug.

Pharmacodynamics

The pharmacodynamics of oxytetracycline involve its ability to inhibit bacterial protein synthesis, which is critical for the growth and reproduction of bacteria. The drug demonstrates a broad spectrum of activity against both Gram-positive and Gram-negative organisms, as well as some atypical pathogens. Its effectiveness can be influenced by the presence of tetracycline resistance mechanisms in certain bacterial strains.

Pharmacokinetics

Oxytetracycline is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours after oral administration. It has a relatively long half-life of about 8-10 hours, allowing for twice-daily dosing. The drug is widely distributed in body tissues and fluids, including the liver, kidneys, and lungs, but is less effective in central nervous system infections due to limited penetration. It is primarily excreted via urine, and dosage adjustments may be necessary in patients with renal impairment.

Contra-indications

• Children under 12 years due to deposition in growing bone and teeth, causing staining and occasionally dental hypoplasia

Adverse effects

• Gastrointestinal disturbances
• Photosensitivity
• Dental discoloration
• Hepatotoxicity
• Renal impairment
• Skin reactions including rash and urticaria
• Ataxia
• Hearing impairment
• Colitis
• Systemic lupus erythematosus exacerbation

Interactions

• Antacids and supplements containing calcium, magnesium, or iron may reduce absorption
• Oral contraceptives may be less effective
• Other tetracyclines
• Warfarin (may increase anticoagulant effect)

Precautions

• Use with caution in patients with renal impairment
• Monitor for hepatic toxicity in long-term use
• Patients should be advised to avoid excessive sunlight exposure
• Discontinue if systemic lupus erythematosus develops or worsens

Pregnancy

Oxytetracycline is contraindicated during pregnancy due to potential harm to fetal development, particularly affecting bone and dental health.

Breast-feeding

Use with caution; oxytetracycline is excreted in breast milk and may affect the infant's dental health.

Storage

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

Formulations

• Oxytetracycline 250 mg tablets
• Oxytetracycline oral suspension
• Oxytetracycline oral solution

Indications

• Bowel sterilization before surgery
• Hepatic coma
• Topical infections caused by susceptible organisms

Dosage

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

Adults: By mouth: 1 g every 1 hour for 4 hours, then 1 g every 4 hours for 2–3 days. For hepatic coma: Up to 4 g daily in divided doses usually for 5–7 days.

Mechanism of action

Neomycin sulfate binds to the 30S ribosomal subunit of bacteria, leading to the misreading of mRNA and the inhibition of protein synthesis. This disrupts the production of essential proteins needed for bacterial growth and function, ultimately resulting in cell death.

Pharmacodynamics

Neomycin demonstrates bactericidal activity against susceptible bacteria. Its efficacy is enhanced in alkaline environments, which is why it is often used in combination with other agents for surgical prophylaxis. The drug is primarily effective against a range of gram-negative organisms, including Escherichia coli and Klebsiella species, but also has some activity against gram-positive organisms.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract, and its systemic absorption is minimal when administered orally. In cases of systemic use, such as intramuscular or intravenous administration, neomycin is distributed widely in the body but is primarily excreted unchanged in the urine. The elimination half-life varies but is generally around 2 to 3 hours in individuals with normal renal function. Monitoring of serum concentrations is essential to prevent toxicity, especially in patients with renal impairment.

Adverse effects

• neurotoxicity
• ototoxicity
• nephrotoxicity
• allergic reactions
• skin rashes
• hearing loss

Interactions

• other nephrotoxic drugs
• loop diuretics
• neuromuscular blocking agents

Precautions

• monitor renal function
• use cautiously in patients with hearing impairment
• avoid concurrent use with other ototoxic medications
• ensure adequate hydration

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use caution; neomycin can be absorbed systemically and may affect the nursing infant.

Storage

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

Formulations

• oral tablets
• topical ointments
• injectable solutions

Indications

• Bacterial infections caused by aerobic organisms
• Topical treatment of skin infections

Mechanism of action

Neomycin binds to specific proteins and 16S rRNA within the 30S ribosomal subunit of susceptible bacteria. This binding interferes with the decoding site, causing misreading of mRNA and leading to the incorporation of incorrect amino acids into polypeptides. As a result, nonfunctional or toxic peptides are produced, and polysomes are disrupted into nonfunctional monosomes. Neomycin's bactericidal action is characterized by its ability to irreversibly bind to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Pharmacodynamics

Neomycin is primarily active against aerobic bacteria and is not effective against fungi, viruses, or most anaerobic bacteria. It mediates its bactericidal effects by inhibiting protein synthesis, which suppresses bacterial growth and survival. Following oral administration, neomycin exhibits a duration of bactericidal activity lasting between 48 to 72 hours. It is particularly useful in treating infections caused by strains of E. coli and Klebsiella, and it also acts to reduce colonic bacterial populations in patients with hepatic coma.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract when taken orally, which limits its systemic availability and enhances its utility in targeting colonic bacteria. It is generally not used parenterally due to its potential for nephrotoxicity and ototoxicity. The duration of action following oral administration can last from 48 to 72 hours, and it is primarily excreted unchanged in the urine. Caution should be exercised when using neomycin in patients with renal impairment, as the risk of toxicity increases.

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Allergic reactions
• Diarrhea
• Nausea
• Vomiting

Interactions

• neomycin+digoxin: Unknown (decreases absorption)
• neomycin+sorafenib: Unknown (decreases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Evaluate hearing function in long-term use

Pregnancy

Neomycin is classified as category D; it should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Neomycin is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Eye drops
• Oral tablets

Indications

• Vitamin A deficiency
• Night blindness
• Impaired wound healing
• Epithelial disorders

Dosage

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

Adults: Refer to BNF for specific adult dosing information.

Mechanism of action

Retinol is converted in the retina to 11-cis-retinal, which is crucial for the conversion of light into neural signals necessary for vision. It binds to opsin in rhodopsin, facilitating the isomerization to all-trans-retinal upon exposure to light, thus triggering visual signaling. Additionally, retinol interacts with retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) as transcription factors, modulating gene expression related to cellular differentiation and growth.

Pharmacodynamics

Vitamin A is effective in treating Vitamin A deficiency, which can lead to vision impairment and other health issues. It plays a critical role in various biological processes including vision, cellular differentiation, reproduction, and immune system function. Its deficiency can cause symptoms such as night blindness and impaired wound healing, while adequate levels support growth and development.

Pharmacokinetics

Retinol is absorbed from the gastrointestinal tract and stored in the liver, where it can be mobilized as needed. It undergoes metabolism primarily in the liver, where it is converted to retinal and retinoic acid, the active forms of Vitamin A. The elimination half-life varies, but retinol is generally excreted in urine and bile. The bioavailability can be affected by dietary fat intake.

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Fatigue
• Irritability
• Dry skin
• Peeling of skin
• Itching
• Blurred vision

Precautions

• Use with caution in patients with liver disease due to potential hepatotoxicity.
• Monitor for signs of vitamin A toxicity, especially in patients on high doses or prolonged therapy.
• Caution in patients with a history of alcohol abuse, as it may exacerbate liver conditions.

Pregnancy

Retinol should be used with caution during pregnancy due to the risk of teratogenic effects. High doses of vitamin A can lead to fetal malformations.

Breast-feeding

Retinol is generally considered safe during breastfeeding, but excessive intake should be avoided to prevent potential adverse effects on the infant.

Storage

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

Formulations

• Capsules
• Tablets
• Oral solutions
• Topical preparations

Mechanism of action

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation. 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/ A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy. ... 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/

Pharmacodynamics

Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. Neomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.

Mechanism of action

Vision:Vitamin A (all-<i>trans</i> retinol) is converted in the retina to the 11-<i>cis</i>-isomer of retinaldehyde or 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-<i>cis</i>-retinal, while attached to opsin in rhodopsin is isomerized to all-<i>trans</i>-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-<i>trans</i>-retinal is then released from opsin and reduced to all-<i>trans</i>-retinol. All-<i>trans</i>-retinol is isomerized to 11-<i>cis</i>-retinol in the dark, and then oxidized to 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-<i>cis</i> retinal rapidly. Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted. Topical vitamin A can reverse the impairment of wound healing seen in patients receiving corticosteroids, perhaps by restoring the normal inflammatory reaction in the wound. The possibility has been suggested that systemic vitamin A could inhibit the anti-inflammatory effect of systemic corticosteroids. Retinol arrested proliferation of cultured neuroblastoma cells at concentrations of 50 um. A correlation existed between inhibition of growth and inhibition of ornithine decarboxylase in both neuroblastoma cells and glioma cells with retinol. In rats exptl-hypervitaminosis A has been shown ... to produce severe damage of the retina, mainly in the pigment epithelium according to electron microscopy. Alcohol dehydrogenase activity was shown to disappear in the pigment epithelium and visual cells ... . /The authors/ have shown that in an experimental cell culture system consisting of carcinogen-treated 10T1/2 cells, both retinoids and all dietary carotenoids examined can reversibly inhibit neoplastic transformation in the post-initiation phase of carcinogenesis. This activity strongly correlates with their ability to increase gap junctional intercellular communication by up-regulating the expression of the gene CX43 (connexin43). Connexins comprise the structural unit of gap junctions, organelles which allow direct transfer of signals, nutrients and waste products between contacting cells. CX43 is the most widely expressed member of the gap junction family of genes, and we have demonstrated that its expression is strongly down-regulated in human cancers and in several premalignant conditions. When several human tumour cell lines were genetically engineered to conditionally express CX43 under the influence of a tetracycline promoter, their neoplastic phenotype was strongly attenuated. Specifically, induced cells were inhibited from growing in an anchorage-independent manner and, additionally, growth as xenografts in immunocompromised animals was also strongly attenuated. Growth inhibition in suspension was associated both with increased G(1) cell-cycle arrest and with increased apoptosis. /The authors/ propose a model whereby junctional communication allows the transfer of growth inhibitory signals from normal to neoplastic cells and that retinoids and carotenoids, by increasing signal transfer, act to prevent cancer.

Pharmacodynamics

Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-<i>trans</i> retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system.