Healit Skin Ointment

Indications

• Ventricular arrhythmias, especially after myocardial infarction
• Local anesthesia for minor surgical procedures
• Pain relief in conditions such as oral ulceration and inflammation

Dosage

Children: Refer to the BNF for Children

Adults: For ventricular arrhythmias, an initial intravenous bolus of 100 mg is given over a few minutes, followed by a continuous infusion of 4 mg/minute for 30 minutes, then reduced to 2 mg/minute for 2 hours, and finally to 1 mg/minute. The total dose should not exceed 3 mg/kg.

Mechanism of action

Lidocaine hydrochloride exerts its effects by blocking voltage-gated sodium channels in neurons, which inhibits the influx of sodium ions during depolarization. This action prevents the generation and conduction of nerve impulses, resulting in local anesthesia. The drug also stabilizes neuronal membranes and decreases the excitability of both peripheral and central nerves.

Pharmacodynamics

The onset of action for lidocaine is rapid, typically occurring within minutes of administration, with a duration of action that can vary based on the route of administration and the presence of additives such as epinephrine. Lidocaine can be used to manage ventricular arrhythmias by decreasing myocardial excitability and conduction velocity, thus stabilizing the cardiac rhythm.

Pharmacokinetics

Lidocaine is well-absorbed when administered intravenously, with peak plasma concentrations occurring shortly after infusion. It is extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP1A2 and CYP3A4, producing active metabolites. The elimination half-life of lidocaine ranges from 1.5 to 2 hours, and it is excreted mainly in urine. Caution is advised in cases of hepatic impairment, as the metabolism of lidocaine may be significantly reduced, leading to increased plasma levels.

Contra-indications

• All grades of atrioventricular block
• Severe myocardial depression
• Sino-atrial disorders

Adverse effects

• Anxiety
• Arrhythmias
• Cardiac arrest
• Circulatory collapse
• Confusion
• Dizziness
• Drowsiness
• Euphoric mood
• Headache
• Hypotension (may lead to cardiac arrest)
• Loss of consciousness
• Methaemoglobinaemia
• Muscle twitching
• Nausea
• Neurological disorders
• Tinnitus
• Tremor
• Blurred vision
• Vomiting

Interactions

• Antiarrhythmics

Precautions

• Acute porphyrias (consider infusion of glucose for its anti-porphyrinogenic effects)
• Congestive cardiac failure (consider lower dose)
• Post cardiac surgery (consider lower dose)
• Monitor serum potassium
• Caution in hepatic impairment (risk of increased exposure)
• Caution in renal impairment (possible accumulation of lidocaine and active metabolites)

Pregnancy

Crosses the placenta but not known to be harmful in animal studies-use if benefit outweighs risk.

Breast-feeding

Present in milk but amount too small to be harmful.

Storage

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

Formulations

• Lidocaine hydrochloride 5 mg per 1 ml solution for injection
• Lidocaine hydrochloride 10 mg per 1 ml solution for injection
• Lidocaine hydrochloride 10% solution for oral use

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

• Topical treatment of superficial skin infections
• Prevention of infections in minor cuts and abrasions
• Conditions caused by susceptible gram-positive bacteria

Dosage

Children: For children, dosing is similar to adults, but refer to BNF for Children for specific recommendations and guidelines.

Adults: For topical application, bacitracin ointment should be applied 1 to 3 times daily to the affected area. Refer to specific guidelines for dosage details.

Mechanism of action

Bacitracin binds to divalent metal ions such as Mn(II), Co(II), Ni(II), Cu(II), or Zn(II). These complexes subsequently bind C55-isoprenyl pyrophosphate, which inhibits the hydrolysis of lipid dolichol pyrophosphate, ultimately blocking cell wall synthesis. Bacitracin also interferes with the incorporation of amino acids and nucleotides into the bacterial cell wall, damages the bacterial plasma membrane, and can oxidatively cleave DNA.

Pharmacodynamics

Bacitracin's pharmacodynamics involve its ability to inhibit bacterial cell wall synthesis and oxidative DNA cleavage. The drug has a short duration of action, necessitating frequent topical applications every 3 to 4 hours. While effective against a range of gram-positive bacteria, the risk of nephrotoxicity when given intramuscularly limits its systemic use.

Pharmacokinetics

Bacitracin is poorly absorbed from the gastrointestinal tract and is primarily administered topically. Systemic absorption can occur if given intramuscularly, leading to potential nephrotoxicity. The drug has a short half-life and requires frequent dosing to maintain effective concentrations at the site of infection.

Adverse effects

• Nephrotoxicity (when given intramuscularly)
• Allergic reactions
• Dermatitis
• Local irritation at the application site

Precautions

• Use with caution in patients with renal impairment
• Avoid intramuscular use due to risk of nephrotoxicity
• Monitor for allergic reactions in patients with a history of hypersensitivity to antibiotics

Pregnancy

Bacitracin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data are available regarding its safety in pregnancy.

Breast-feeding

Bacitracin is expected to be excreted in breast milk, caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Topical powder

Indications

• Local anesthesia for surgical and diagnostic procedures
• Management of certain types of arrhythmias
• Topical anesthesia for mucosal surfaces

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Lidocaine acts by diffusing through neural sheaths into the axoplasm, where it is ionized and binds reversibly to sodium ion channels on nerve cell membranes. This binding keeps the channels in an open state, preventing nerve depolarization and thus blocking action potential transmission. This mechanism facilitates its anesthetic effects by aborting pain signal generation and preventing their transmission to the brain.

Pharmacodynamics

Excessive blood levels of lidocaine may lead to changes in cardiac output, total peripheral resistance, and mean arterial pressure. The block of autonomic fibers and the direct depressant effect on the cardiovascular system can cause hypotension when recommended dosages are exceeded. Lidocaine's action on sodium channels affects cardiac myocytes, potentially leading to hypotension, bradycardia, myocardial depression, arrhythmias, or even cardiac arrest.

Pharmacokinetics

Lidocaine is absorbed rapidly and widely distributed throughout the body. It undergoes extensive hepatic metabolism, primarily by cytochrome P450 enzymes, leading to various metabolites. Its elimination half-life is approximately 1.5 to 2 hours, but this can vary based on factors such as hepatic blood flow and enzyme activity.

Contra-indications

• Hypersensitivity to lidocaine or any amide local anesthetics
• Severe degree of heart block
• A history of malignant hyperthermia

Adverse effects

• Hypotension
• Bradycardia
• Myocardial depression
• Cardiac arrhythmias
• CNS stimulation followed by depression
• Dizziness
• Nausea
• Vomiting
• Tinnitus

Interactions

• cimetidine+lidocaine: Moderate (increases exposure)
• cobicistat+lidocaine: Unknown (increases concentration)
• lidocaine+suxamethonium: Unknown (increases effects)
• ciprofloxacin+lidocaine: Unknown (increases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Use with caution in patients with cardiac conditions
• Monitor for signs of systemic toxicity, especially after high doses or rapid administration

Pregnancy

Lidocaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as FDA pregnancy category B.

Breast-feeding

Lidocaine is excreted in breast milk, but at therapeutic doses, it is not expected to cause adverse effects in nursing infants. Monitor infants for any signs of sedation.

Storage

Store at room temperature, away from moisture and heat. Protect from light. Do not freeze.

Formulations

• Lidocaine injection solution
• Lidocaine cream
• Lidocaine gel
• Lidocaine patch

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

• Pneumonia caused by multidrug-resistant gram-negative bacteria
• Septicemia caused by gram-negative bacteria
• Urinary tract infections caused by resistant organisms
• Skin infections caused by resistant gram-negative bacteria

Dosage

Children: Refer to BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to local guidelines or BNF for specific dosing recommendations based on the type and severity of infection.

Mechanism of action

Polymyxin exerts its antibacterial effect by disrupting the integrity of the bacterial cell membrane. It binds to the lipopolysaccharides and phospholipids in the outer membrane of gram-negative bacteria, leading to increased permeability and eventual cell lysis.

Pharmacodynamics

Polymyxin has a bactericidal effect against susceptible gram-negative organisms. Its action is concentration-dependent, with higher concentrations leading to a more significant bactericidal effect. Resistance can occur through modifications in the bacterial cell membrane components that reduce drug binding.

Pharmacokinetics

Polymyxin is poorly absorbed from the gastrointestinal tract and is typically administered parenterally (intravenously or intramuscularly) for systemic infections. It has a volume of distribution that suggests extensive tissue penetration but is primarily eliminated by the kidneys. Half-life varies based on renal function, and dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Respiratory distress
• Nausea
• Vomiting

Interactions

• Increased nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides or cisplatin
• Potential for respiratory depression with neuromuscular blocking agents

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Consider the risk of neurotoxicity, especially with prolonged use

Pregnancy

Polymyxin is classified as category C. Its safety during pregnancy has not been established, thus it should only be used if clearly needed.

Breast-feeding

It is not known if polymyxin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Polymyxin B sulfate injection
• Polymyxin E (colistin) inhalation solution
• Topical formulations

Mechanism of action

Bacitracin binds to a divalent metal ion such as Mn(II), Co(II), Ni(II), Cu(II), or Zn(II). These complexes bind C₅₅-isoprenyl pyrophosphate, preventing the hydrolysis of a lipid dolichol pyrophosphate, which finally inhibits cell wall synthesis. Bacitracin metal complexes also bind and oxidatively cleave DNA. Bacitracin interferes with bacterial cell wall synthesis by blocking the function of the lipid carrier molecule that transfers cell wall subunits across the cell membrane. It is active against many gram positive bacteria including staphylococci, streptococci (particularly group A streptococci), corynebacteria, and clostridia. It is also active against Actinomyces, Treponema pallidum and some gram negative species such as Neisseria and Haemophilus influenzae, although most Gram-negative organisms are resistant. . Bacitracin may be bactericidal or bacteriostatic in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Bacitracin inhibits bacterial cell wall synthesis by preventing the incorporation of amino acids and nucleotides into the cell wall. The drug probably interferes with the final dephosphorylation step in the phospholipid carrier cycle and in this manner bacitracin prevents the transfer of the mucopeptide to the growing cell wall. Bacitracin also damages the bacterial plasma membrane and is active against protoplasts. Bacitracin is a polypeptide antibiotic active against Gram-positive bacterial strains. Its mechanism of action postulates disturbing the cell wall synthesis by inhibiting dephosphorylation of the lipid carrier. We have discovered that bacitracin induces degradation of nucleic acids, being particularly active against RNA. In the examination of the nucleolytic activity of bacitracin several model RNA and DNA oligomers were used. The oligomers were labeled at their 5' ends with (32)P radioisotope and following treatment with bacitracin the cleavage sites and efficiency were determined. Bacitracin induces degradation of RNA at guanosine residues, preferentially in single-stranded RNA regions. Bacitracin is also able to degrade DNA to some extent but comparable effects to those observed with RNA require its 10-fold higher concentration. The sites of degradation in DNA are very infrequent and preferentially occur near cytidine residues. Free radicals are not involved in the reaction, and which probably proceeds via a hydrolytic mechanism. The phosphate groups at the cleavage sites are present at the 3' ends of RNA products and at the 5' ends of DNA fragments. Importantly, the presence of EDTA does not influence RNA degradation but completely inhibits the degradation of DNA. For DNA degradation divalent metal ions like Mg(2+), Mn(2+) or Zn(2+) are absolutely necessary. The ability of bacitracin to degrade nucleic acids via a hydrolytic mechanism was a surprising observation, and it is of interest whether these properties can contribute to its mechanisms of action during antibiotic treatment.

Pharmacodynamics

Bacitracin is a mixture of polypeptides that prevent the formation of the bacterial cell wall and oxidatively cleave DNA. It has a short duration of action as it must be given every 3 to 4 hours topically. Bacitracin is nephrotoxic when given intramuscularly and may lead to renal failure.

Mechanism of action

Lidocaine is a local anesthetic of the amide type. It is used to provide local anesthesia by nerve blockade at various sites in the body. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions. The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization. As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential. This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place. In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system. After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction. Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+ channels may be involved in several diseases of muscle and nerve, including familial myotonias and neuropathic pain syndromes. Systemic local anesthetics have been shown to have clinical efficacy against myotonias and some forms of neuropathic pain, so we sought to develop an in vitro model to examine the cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro by the sucrose-gap method, peptide alpha-toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na+ channel inactivation, induced repetitively firing compound action potentials (CAPs) superimposed on a plateau depolarization lasting several seconds. The initial spike of the CAP was unaffected, but the plateau and repetitive firing were strongly suppressed by 5-30 uM lidocaine. Lidocaine caused a rapid, concentration-dependent decay of the plateau, quantitatively consistent with blockade of open Na(+) channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 uM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 hr, showing that lidocaine had not caused dissociation of channel-bound alpha-toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the "abnormal" features of action potentials caused by non-inactivating Na+ channels without affecting the normal spike component. Lidocaine controls ventricular arrhythmias by suppressing automaticity in the His-Purkinje system and by suppressing spontaneous depolarization of the ventricles during diastole. These effects occur at lidocaine concentrations that do not suppress automaticity of the sinoatrial (SA) node. At therapeutic plasma concentrations, lidocaine has little effect on atrioventricular (AV) node conduction and His-Purkinje conduction in the normal heart. Specialized conducting tissues of the atria are less sensitive to the effects of lidocaine than are those of ventricular tissues. Lidocaine has a variable effect on the effective refractory period (ERP) of the AV node; the drug shortens the ERP and the action potential duration of the His-Purkinje system. Lidocaine does not appear to affect excitability of normal cardiac tissue. Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydroly

Pharmacodynamics

Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded. In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction. Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse. Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base. As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection. The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection. Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation. This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels.

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.