MULTIMAST DC INTRAMAMMARY SUSPENSION

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
• Pneumonia
• Meningitis
• Syphilis
• Endocarditis
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing for benzylpenicillin is determined by the child's weight and the severity of the infection. Refer to the BNF for Children for specific dosing guidelines.

Adults: The usual adult dose for benzylpenicillin varies based on the type and severity of the infection. It is generally administered via intramuscular or intravenous routes. For severe infections, doses may range from 1 to 4 million units every 4 to 6 hours.

Mechanism of action

Benzylpenicillin exerts its antibacterial effects by inhibiting the synthesis of bacterial cell walls. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the transpeptidation process, which is crucial for cross-linking peptidoglycan layers. This inhibition leads to cell lysis and death of the bacteria.

Pharmacodynamics

Benzylpenicillin demonstrates time-dependent bactericidal activity, meaning its effectiveness is related to the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target bacteria. It has a narrow spectrum of activity, primarily targeting Gram-positive cocci and some Gram-negative rods.

Pharmacokinetics

Benzylpenicillin is typically administered parenterally due to poor oral absorption. It is rapidly distributed throughout the body and can penetrate various tissues, including the central nervous system during inflammation. The drug is primarily eliminated by renal excretion, with a half-life of approximately 30 minutes to 1 hour in healthy individuals. Dosage adjustments may be necessary in patients with renal impairment.

Interactions

• leflunomide+benzylpenicillin: Unknown (increases exposure)
• nitisinone+benzylpenicillin: Unknown (increases exposure)
• teriflunomide+benzylpenicillin: Unknown (increases exposure)

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, as it is a penicillin antibiotic and has a long history of use.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts, but it is not expected to have adverse effects on a nursing infant.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly or stored in a refrigerator and used within a limited time frame.

Formulations

• Benzylpenicillin injection

Indications

• Cough associated with respiratory infections
• Bronchitis
• Other conditions requiring mucus clearance from the respiratory tract

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Hydriodide is believed to act reflexly by irritating the gastric mucosa, which in turn stimulates respiratory tract secretion. This action enhances mucus production, aiding in the expulsion of mucus from the airways.

Pharmacodynamics

The pharmacodynamic effects of hydriodide are largely related to its ability to stimulate secretory glands in the respiratory tract. This leads to increased mucus production, which helps to clear mucus from the airways and alleviates cough symptoms. The irritant effect on the gastric mucosa may also contribute to its efficacy in promoting cough reflex.

Pharmacokinetics

The pharmacokinetics of hydriodide, particularly the absorption, distribution, metabolism, and excretion, are not extensively detailed. However, as an iodine-containing compound, it is expected to be absorbed in the gastrointestinal tract, with the potential for systemic distribution. The metabolism may involve incorporation into thyroid hormones, as iodine is a crucial element in the synthesis of thyroxine. Excretion primarily occurs via the kidneys.

Pregnancy

Hydriodide is not recommended during pregnancy unless clearly needed, as the effects on fetal development are not fully understood.

Breast-feeding

It is not known whether hydriodide is excreted in human milk, caution should be exercised when administering to nursing mothers.

Storage

Store in a tightly closed container, protected from light and moisture, at room temperature.

Formulations

• Hydriodic acid syrup

Dosage

Children: Refer to specific drug monographs for dosing information, as dosing varies by the active ingredient and therapeutic indication.

Adults: Refer to specific drug monographs for dosing information, as dosing varies by the active ingredient and therapeutic indication.

Mechanism of action

Micronisation itself does not alter the inherent mechanism of action of a drug, but it improves the drug's solubility and absorption characteristics. For drugs that are micronised, the enhanced surface area allows for more rapid dissolution in the gastrointestinal tract, which can lead to increased plasma concentrations and improved therapeutic effects.

Pharmacodynamics

The pharmacodynamics of micronised drugs depend on the specific active pharmaceutical ingredient (API) being micronised. Generally, micronisation enhances the bioavailability of drugs that exhibit poor solubility, leading to more effective pharmacological responses at lower doses. This may result in a reduction in side effects and improved patient compliance.

Pharmacokinetics

Micronised drugs typically exhibit altered pharmacokinetic profiles compared to their non-micronised counterparts. The increased surface area and improved solubility facilitate quicker absorption, often resulting in higher peak plasma concentrations and potentially shorter time to peak effect. However, the elimination half-life may remain unchanged, depending on the drug's metabolism and excretion mechanisms.

Adverse effects

• Headache
• Nausea
• Dizziness
• Fatigue
• Gastrointestinal disturbances

Precautions

• Use with caution in patients with a history of hypersensitivity to the drug or its components.
• Monitor for potential allergic reactions.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and after evaluating risks versus benefits.

Breast-feeding

Consult a healthcare provider before use, as it is not known whether the drug is excreted in breast milk.

Storage

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

Formulations

• Micronised powder for oral administration
• Micronised capsules

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

• Bacterial infections
• Pneumonia
• Skin and soft tissue infections
• Otitis media
• Sinusitis
• Endocarditis prophylaxis

Dosage

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

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Penethamate exerts its antibacterial effects by binding to penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding inhibits the transpeptidation enzyme that is crucial for cross-linking peptidoglycan layers, resulting in the disruption of cell wall synthesis. Consequently, the bacteria become susceptible to osmotic pressure and undergo lysis.

Pharmacodynamics

Penethamate is bactericidal, meaning it kills bacteria rather than merely inhibiting their growth. The drug's efficacy is enhanced in actively dividing bacteria, where the inhibition of cell wall synthesis leads to rapid bacterial death. The spectrum of activity includes many strains of Streptococcus, Staphylococcus, and some Enterobacteriaceae, although resistance may develop with prolonged use.

Pharmacokinetics

Penethamate is absorbed well from the gastrointestinal tract and reaches peak plasma concentrations within 1 to 2 hours after administration. It is distributed widely throughout body tissues and fluids, including the respiratory tract and soft tissues. The drug is metabolized in the liver and excreted primarily via the kidneys. The half-life of penethamate is approximately 1 to 2 hours, necessitating multiple doses to maintain effective concentrations.

Contra-indications

• Known hypersensitivity to penethamate or any component of the formulation
• Severe liver impairment
• Active peptic ulcer disease

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Rash
• Headache
• Dizziness
• Allergic reactions including anaphylaxis

Interactions

• May enhance the effects of anticoagulants
• Potential interaction with other CNS depressants
• Antacids may reduce absorption

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of hypersensitivity reactions
• Consider renal function prior to use

Pregnancy

Use during pregnancy only if clearly needed. Animal studies have shown adverse effects, and there are no well-controlled studies in pregnant women.

Breast-feeding

Caution is advised when administered to breastfeeding mothers. It is not known whether penethamate is excreted in human milk.

Storage

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

Formulations

• Oral tablets
• Injectable solution

Indications

• Bacterial infections
• Pneumonia
• Streptococcal infections
• Syphilis
• Meningitis
• Endocarditis
• Skin infections

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on the type of penicillin and indication.

Adults: Refer to the BNF for specific dosing recommendations based on the type of penicillin and indication.

Mechanism of action

Penicillin targets penicillin-binding proteins (PBPs) located inside the bacterial cell wall. By binding to these proteins, penicillin disrupts the transpeptidation process, which is essential for cell wall structural integrity. This results in weakened cell walls, causing osmotic instability and ultimately leading to cell lysis and death.

Pharmacodynamics

Penicillin exhibits bactericidal activity, meaning that it kills bacteria rather than merely inhibiting their growth. Its effectiveness is generally dependent on the growth phase of the bacteria, as it is most active against actively dividing cells. The spectrum of activity varies among different penicillins, with some being more effective against specific bacterial strains.

Pharmacokinetics

Penicillin is primarily absorbed in the gastrointestinal tract, with its bioavailability varying depending on the specific type of penicillin. It is primarily excreted by the kidneys, with a half-life that typically ranges from 30 minutes to 2 hours, depending on the formulation. Dosage adjustments may be necessary in patients with renal impairment to prevent accumulation and toxicity.

Contra-indications

• History of hypersensitivity to penicillins
• Severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions such as rash, urticaria, and anaphylaxis
• Gastrointestinal disturbances including nausea, vomiting, and diarrhea
• Superinfection due to alteration of normal flora
• Hematologic reactions such as leukopenia, thrombocytopenia

Interactions

• valproate+penicillins: Severe (increases risk of adverse effects)
• allopurinol+penicillins: Unknown (increases risk of skin rash)
• leflunomide+penicillins: Unknown (increases exposure)
• nitisinone+penicillins: Unknown (increases exposure)
• penicillins+phenindione: Unknown (increases risk of bleeding events)
• teriflunomide+penicillins: Unknown (increases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of allergic reactions
• Consider alternative therapy in patients with a history of severe allergies

Pregnancy

Penicillins are generally considered safe to use during pregnancy; however, consult local guidelines and assess benefits versus risks.

Breast-feeding

Penicillins are excreted in breast milk in small amounts; generally considered safe, but monitor infant for possible effects.

Storage

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

Formulations

• Oral tablets
• Oral suspension
• Intravenous injection
• Intramuscular injection

Indications

• Local anesthesia for dental procedures
• Regional anesthesia
• Minor surgical procedures

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Procaine acts mainly by inhibiting sodium influx through voltage-gated sodium channels in the neuronal cell membrane of peripheral nerves. This inhibition prevents the generation of action potentials, thereby blocking signal conduction. Additionally, procaine has been shown to bind to and inhibit the function of N-methyl-D-aspartate (NMDA) receptors, nicotinic acetylcholine receptors, and the serotonin receptor-ion channel complex. It also reduces the permeability of resting nerve membranes to potassium ions.

Pharmacodynamics

As an anesthetic agent, procaine is indicated for producing local or regional anesthesia, particularly during dental procedures. Its unique property of vasoconstriction helps minimize bleeding. The anesthetic action develops progressively, leading to an increased threshold for electrical excitability, a decline in the rate of rise of action potentials, and a decreased probability of nerve impulse propagation.

Pharmacokinetics

Procaine is metabolized by the enzyme pseudocholinesterase in the plasma, undergoing hydrolysis to form para-aminobenzoic acid (PABA), which is subsequently excreted by the kidneys in urine. The pharmacokinetics of procaine involve a rapid onset of action but also a relatively short duration, necessitating careful consideration of dosing during procedures.

Adverse effects

• Allergic reactions
• Hypotension
• Dizziness
• Nausea
• Vomiting
• Tachycardia
• Sedation

Interactions

• Increased risk of CNS toxicity with other local anesthetics
• Enhanced hypotensive effects with antihypertensive agents
• Potential interaction with anticholinesterase agents

Precautions

• Use with caution in patients with known hypersensitivity to procaine or other local anesthetics
• Caution in patients with pre-existing cardiovascular or neurological conditions
• Careful administration in elderly patients or those with compromised liver or kidney function

Pregnancy

Procaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines.

Breast-feeding

Caution is advised when administering procaine to breastfeeding mothers due to potential excretion in breast milk.

Storage

Store at room temperature, protected from light and moisture. Ensure the vial is sealed when not in use.

Formulations

• Procaine hydrochloride injection

Mechanism of action

... Believed to act reflexly by irritating the gastric mucosa, which in turn, stimulates resp tract secretion. /Hydriodic acid syrup/

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

Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex. LOCAL ANESTHETICS BLOCK CONDUCTION BY DECREASING OR PREVENTING THE LARGE TRANSIENT INCREASE IN THE PERMEABILITY OF EXCITABLE MEMBRANES TO SODIUM IONS THAT NORMALLY IS PRODUCED BY A SLIGHT DEPOLARIZATION OF THE MEMBRANE. /LOCAL ANESTHETIC/ LOCAL ANESTHETICS BLOCK CONDUCTION IN NERVE PERHAPS BY COMPETING WITH CALCIUM @ SOME SITE THAT CONTROLS PERMEABILITY OF MEMBRANE. ... LOCAL ANESTHETICS ALSO REDUCE PERMEABILITY OF RESTING NERVE TO POTASSIUM AS WELL AS TO SODIUM IONS. /LOCAL ANESTHETICS/ AS THE ANESTHETIC ACTION PROGRESSIVELY DEVELOPS IN A NERVE, THE THRESHOLD FOR ELECTRICAL EXCITABILITY GRADUALLY INCREASES, THE RATE OF RISE OF THE ACTION POTENTIAL DECLINES, IMPULSE CONDUCTION SLOWS, & THE SAFETY FACTOR FOR CONDUCTION DECREASES; THESE FACTORS DECREASE THE PROBABILITY OF PROPAGATION OF THE ACTION POTENTIAL, AND NERVE CONDUCTION FAILS. /LOCAL ANESTHETICS/ POSTSYNAPTIC ACTION ... END-PLATE CURRENT IS MUCH PROLONGED BY PROCAINE. SIMILARLY, WHEN ... ADDED TO FLUID PERFUSING GANGLION, PREGANGLIONIC STIMULATION FAILS TO ELICIT POSTGANGLIONIC DISCHARGES & GANGLION CELLS BECOME INSENSITIVE TO STIMULATION BY ACETYLCHOLINE. IN ADDITION TO BLOCKING CONDITIONS IN NERVE AXONS IN THE PERIPHERAL NERVOUS SYSTEM, LOCAL ANESTHETICS INTERFERE WITH THE FUNCTION OF ALL ORGANS IN WHICH CONDUCTION OR TRANSMISSION OF IMPULSES OCCURS. ... EFFECTS ON ... CNS, THE AUTONOMIC GANGLIA, THE NEUROMUSCULAR JUNCTION, & ALL FORMS OF MUSCLE. /LOCAL ANESTHETICS/

Pharmacodynamics

Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine.