D. MASTINOR

Indications

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Meningitis
• Gastrointestinal infections
• Endocarditis prophylaxis

Dosage

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

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

Mechanism of action

Ampicillin exerts its antibacterial effects by binding to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. This binding inhibits the transpeptidation reaction, which is crucial for cross-linking peptidoglycan layers in the bacterial cell wall, ultimately leading to cell lysis and death due to osmotic instability.

Pharmacodynamics

The pharmacodynamics of ampicillin involve its time-dependent antibacterial activity, where the efficacy of the drug is related to the duration of time that plasma concentrations are above the minimum inhibitory concentration (MIC) for the target organism. It demonstrates a post-antibiotic effect (PAE), meaning that bacterial growth remains inhibited even after drug levels have fallen below the MIC.

Pharmacokinetics

Ampicillin is well absorbed after oral administration, with a bioavailability of approximately 40-60%. It is widely distributed in body tissues and fluids, including the central nervous system in cases of meningitis. The drug is primarily excreted unchanged in the urine, with renal clearance being a significant route of elimination. The half-life of ampicillin is approximately 1-2 hours in healthy individuals, but it can be prolonged in patients with renal impairment.

Contra-indications

• History of hypersensitivity to penicillins or cephalosporins
• Severe renal impairment (with caution)
• Mononucleosis (risk of rash)

Adverse effects

• Allergic reactions (rash, anaphylaxis)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Hematological reactions (eosinophilia, thrombocytopenia)
• Clostridium difficile-associated diarrhea
• Nephrotoxicity (rare)

Interactions

• Probenecid (increased ampicillin levels)
• Methotrexate (increased toxicity of methotrexate)
• Allopurinol (increased risk of skin rash)
• Anticoagulants (enhanced effect)

Precautions

• Caution in patients with renal impairment
• Use with caution in patients with a history of allergy to other beta-lactam antibiotics
• Monitor for signs of superinfection (especially with prolonged use)

Pregnancy

Ampicillin is classified as category B. It is generally considered safe but should be used only if clearly needed.

Breast-feeding

Ampicillin is excreted in breast milk. It is generally considered safe, but caution is advised due to potential effects on the infant.

Storage

Store below 25 degrees Celsius in a dry place, protected from light. Reconstituted solutions should be refrigerated and used within 7 days.

Formulations

• Capsules (250 mg, 500 mg)
• Oral suspension (125 mg/5 mL, 250 mg/5 mL)
• Injection (500 mg, 1 g, 2 g)

Indications

• Skin and soft tissue infections caused by susceptible Staphylococcus species
• Bone and joint infections (e.g., osteomyelitis) due to Staphylococcus
• Endocarditis prophylaxis in patients with penicillin-sensitive organisms
• Respiratory tract infections caused by susceptible organisms

Dosage

Children: For children, the dosage of cl

Adults: The usual adult dose for cloxacillin is 250 mg to 500 mg every 6 hours, depending on the severity and type of infection. Higher doses may be required for more severe infections.

Mechanism of action

Cloxacillin exerts its antibacterial effects by binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall. This binding inhibits the third and final stage of bacterial cell wall synthesis, leading to cell lysis mediated by bacterial autolytic enzymes such as autolysins. Cloxacillin is particularly effective against strains that produce penicillinase, thus broadening its spectrum of activity compared to penicillin.

Pharmacodynamics

As a semisynthetic penicillin, cloxacillin exhibits bactericidal activity, primarily targeting Gram-positive bacteria. Its action is contingent upon the bacteria being in a multiplying state since penicillins do not affect existing cell walls. Cloxacillin's effectiveness is enhanced against beta-lactamase producing strains, allowing for successful treatment of infections that would otherwise be resistant to standard penicillin.

Pharmacokinetics

Cloxacillin is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. It has a volume of distribution that indicates good tissue penetration, and it is metabolized in the liver. The elimination half-life is approximately 0.5 to 1 hour, with renal excretion being the primary route of elimination for the unchanged drug.

Contra-indications

• History of hypersensitivity to cloxacillin or any other penicillin antibiotics
• Severe renal impairment
• History of allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions (rash, urticaria, anaphylaxis)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Hepatic dysfunction (elevated liver enzymes)
• Renal impairment (nephrotoxicity)
• Hematological reactions (eosinophilia, thrombocytopenia)

Interactions

• Probenecid may increase serum levels of cloxacillin
• Anticoagulants (may increase effect)
• Other antibiotics (may have antagonistic effects)

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of allergic reactions
• Caution in patients with a history of gastrointestinal disease, particularly colitis

Pregnancy

Cloxacillin is generally considered safe to use during pregnancy, but it should only be used when clearly needed.

Breast-feeding

Cloxacillin is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Once reconstituted, it should be stored in the refrigerator and used within a specified time frame as per manufacturer instructions.

Formulations

• Capsules
• Injection (vial for intravenous use)
• Oral suspension

Indications

• Severe infections caused by gram-negative bacteria
• Complicated urinary tract infections
• Bacterial sepsis
• Endocarditis caused by susceptible organisms

Dosage

Children: Dosing in children is also weight-based and varies by indication. Refer to the BNF for Children for specific dosing recommendations.

Adults: Dosage varies significantly based on the infection severity and type, renal function, and the specific bacterial susceptibility. Refer to clinical guidelines or the BNF for precise dosing.

Mechanism of action

Gram works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit of the bacteria, causing misreading of the mRNA and ultimately preventing the synthesis of essential proteins necessary for bacterial growth and replication.

Pharmacodynamics

The pharmacodynamics of Gram include its bactericidal activity against susceptible bacteria. The drug shows concentration-dependent killing, meaning that higher drug concentrations correlate with greater bactericidal effects. The post-antibiotic effect is noted, where bacterial growth is inhibited even after the drug concentration falls below the minimum inhibitory concentration (MIC).

Pharmacokinetics

Gram is usually administered parenterally (intravenously or intramuscularly), and its absorption can vary based on the route of administration. It is distributed widely in body fluids and tissues, although it does not penetrate well into the central nervous system. The drug is primarily eliminated through the kidneys, and its half-life may be prolonged in patients with renal impairment. Monitoring of drug levels may be necessary to avoid toxicity.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Allergic reactions
• Rash
• Renal dysfunction

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Assess for potential allergic reactions

Pregnancy

Use only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Use with caution, as it may be excreted in breast milk. Consult with a healthcare provider.

Storage

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

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

Indications

• Constipation
• Dry skin
• Skin irritation

Dosage

Children: Refer to specific guidelines and prescribing information for paediatric dosing.

Adults: Refer to specific guidelines and prescribing information for adult dosing.

Mechanism of action

Paraffin acts as a lubricating agent in the gastrointestinal tract. It coats the stool and the intestinal walls, which helps to ease the passage of feces by reducing friction. This action promotes bowel movements and alleviates constipation. When used topically, it forms a barrier on the skin, which helps to retain moisture and protect against irritants.

Pharmacodynamics

Paraffin has a low viscosity and surface tension, which allows it to spread easily over surfaces. Its lubricating properties facilitate the movement of stool through the intestines, while its emollient properties help in maintaining skin hydration and barrier function. The onset of action for oral administration typically occurs within 6 to 8 hours, making it effective in treating occasional constipation.

Pharmacokinetics

Paraffin is not absorbed systemically when ingested; it remains in the gastrointestinal tract and is excreted unchanged in the feces. After oral administration, it acts locally in the intestines without significant systemic effects. When used topically, it remains on the skin surface and does not penetrate deeply, providing a protective layer without altering systemic pharmacokinetics.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Lipid pneumonia (when aspirated)
• Electrolyte imbalances

Precautions

• Use with caution in patients with gastrointestinal obstruction
• Avoid in patients with a history of aspiration
• Monitor for signs of dehydration with prolonged use

Pregnancy

Use only if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Paraffin can be excreted in breast milk, use with caution.

Storage

Store at room temperature away from moisture and heat.

Formulations

• Liquid paraffin
• Soft paraffin (for topical use)

Dosage

Children: Refer to specific product information for dosing guidelines.

Adults: Refer to specific product information for dosing guidelines.

Pregnancy

Consult a healthcare professional before use. The effects of Soft during pregnancy are not well-documented.

Breast-feeding

Consult a healthcare professional before use. The safety of Soft during breastfeeding is not well-established.

Storage

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

Dosage

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

Adults: Refer to the specific BNF guidelines for dosing information as it may vary based on the condition being treated.

Mechanism of action

The mechanism of action for White involves its interaction with specific biological pathways, leading to the desired pharmacological effects. The precise pathways may include modulation of receptor activity or alteration of enzyme function, although specific details are not provided.

Pharmacodynamics

Pharmacodynamics of White includes its effects on the body, including therapeutic effects and potential side effects. As a compound, it may exert its influence on multiple physiological systems, which can lead to changes in symptoms or disease progression.

Pharmacokinetics

Pharmacokinetics of White involves its absorption, distribution, metabolism, and excretion. Understanding these parameters can help predict how the drug behaves in the body, including onset of action and duration of effect. Detailed pharmacokinetic data is not specified.

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cloxacillin interferes with an autolysin inhibitor. ...ITS ANTIBACTERIAL SPECTRUM AGAINST GRAM-POSITIVE BACTERIA IS LIKE THAT OF PENICILLIN EXCEPT IT IS BROADER BY MARGIN OF THOSE STRAINS OR SPECIES THAT PRODUCE PENICILLINASE. ...IT IS LESS ACTIVE THAN PENICILLIN G AGAINST NON-PENICILLINASE-PRODUCING BACTERIA, ESPECIALLY STREPTOCOCCI. /CLOXACILLIN MONOHYDRATE/ SINCE PENICILLIN HAS NO EFFECT ON EXISTING CELL WALLS, BACTERIA MUST BE MULTIPLYING FOR BACTERIAL ACTION OF PENICILLIN TO BE MANIFEST. /PENICILLINS/ 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/ Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/ TOLERANCE DEVELOPED TO MULTIPLE DOSING. /PENICILLINS/

Pharmacodynamics

Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin is for use against staphylococci that produce beta-lactamase.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.