MEGA STREP 400 LA (Injection)

Indications

• Mild to moderate susceptible infections
• Throat infections
• Otitis media
• Cellulitis
• Pneumonia
• Meningitis
• Meningococcal disease
• Endocarditis (in combination with other antibacterials)

Dosage

Children: For children weighing up to 40 kg: 80 mg/kg every 8 hours, increased if necessary to 80 mg/kg every 6 hours for more severe infections. For children weighing 40 kg and above: 3.2 g every 6-8 hours, increased if necessary. Neonates (up to 7 days): 25 mg/kg every 12 hours, increased if necessary to 25 mg/kg every 8 hours. Neonates (7 to 28 days): 25 mg/kg every 8 hours, increased if necessary to 50 mg/kg every 8 hours for severe infections.

Adults: For adults, the usual dose is 3.2 g every 6 hours for severe infections; for less severe infections, 1.2 g every 6 hours may be sufficient. Dosing frequency can be adjusted based on the severity of the infection.

Mechanism of action

Benzylpenicillin sodium inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis and death in susceptible bacteria.

Pharmacodynamics

Benzylpenicillin sodium demonstrates bactericidal activity against Gram-positive bacteria and some Gram-negative bacteria. Its efficacy is influenced by the bacterial growth phase, with maximum activity observed during active cell division.

Pharmacokinetics

Benzylpenicillin sodium is administered via intramuscular or intravenous routes. It has a short half-life, requiring frequent dosing. The drug is primarily eliminated by renal excretion, necessitating dose adjustments in patients with renal impairment.

Adverse effects

• Eosinophilia
• Hypokalaemia
• Thrombophlebitis
• Cholestatic jaundice

Precautions

• High doses may lead to hypernatraemia due to sodium content.
• Caution in hepatic impairment.
• Caution in renal impairment; adjustment needed based on estimated glomerular filtration rate.

Pregnancy

Not known to be harmful.

Breast-feeding

Trace amounts in milk, but appropriate to use.

Storage

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

Formulations

• Intramuscular injection
• Slow intravenous injection
• Intravenous infusion

Indications

• Bacterial infections caused by susceptible organisms
• Pneumonia
• Meningitis
• Endocarditis
• Sepsis
• Skin and soft tissue infections
• Bone and joint infections

Dosage

Children: Refer to the BNF

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

Mechanism of action

Benzylpenicillin exerts its bactericidal effect by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding inhibits the third and final stage of bacterial cell wall synthesis. The weakened cell wall ultimately leads to cell lysis, which is mediated by bacterial autolytic enzymes. The action of benzylpenicillin is dependent on its ability to reach and bind to these PBPs, which include transpeptidases, carboxypeptidases, and endopeptidases.

Pharmacodynamics

Benzylpenicillin is particularly effective against gram-positive bacteria and has activity against some gram-negative organisms as well. Its bactericidal nature is attributed to the inhibition of cell wall synthesis, which disrupts the structural integrity of the bacterial cell. Benzylpenicillin remains stable against hydrolysis by various beta-lactamases, including penicillinases and extended-spectrum beta-lactamases, enhancing its efficacy in treating infections caused by resistant strains.

Pharmacokinetics

Benzylpenicillin is administered via parenteral routes due to its poor oral bioavailability. It is widely distributed throughout the body, including the central nervous system, especially in the presence of inflammation. The drug is primarily eliminated by the kidneys through glomerular filtration and tubular secretion, with a half-life of approximately 30 minutes to 1 hour in healthy adults. Dosing may need adjustment in patients with renal impairment.

Contra-indications

• Hypersensitivity to benzylpenicillin or any other penicillins
• History of severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions including rash, pruritus, and anaphylaxis
• Gastrointestinal disturbances such as nausea, vomiting, and diarrhea
• Hematologic effects including leukopenia, thrombocytopenia, and hemolytic anemia
• Renal toxicity in cases of high doses or prolonged use

Interactions

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

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of anaphylaxis during initial doses
• Consider alternative therapy in patients with a history of severe penicillin allergy

Pregnancy

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

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts and is considered safe for use during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Reconstituted solutions should be used promptly or stored in a refrigerator and used within 24 hours.

Formulations

• Benzylpenicillin sodium
• Benzylpenicillin potassium

Indications

• Tuberculosis
• Bacterial infections caused by susceptible strains of Mycobacteria
• Severe infections caused by Gram-negative bacteria

Dosage

Children: Refer to BNF for Children for appropriate pediatric dosing recommendations.

Adults: Refer to BNF for specific dosing guidance, as it may vary based on the indication and patient condition.

Mechanism of action

Dihydrostreptomycin binds to the 30S ribosomal subunit of bacteria, interfering with the initiation complex and causing misreading of the mRNA. This action leads to the production of nonfunctional proteins and ultimately results in bacterial cell death.

Pharmacodynamics

Dihydrostreptomycin exhibits concentration-dependent bactericidal activity against a variety of Gram-negative and some Gram-positive bacteria. Its efficacy is influenced by the peak concentration achieved relative to the minimum inhibitory concentration (MIC) of the organism.

Pharmacokinetics

Dihydrostreptomycin is administered parenterally due to poor oral absorption. It is widely distributed in body tissues and fluids, but does not penetrate well into the central nervous system. The drug is primarily eliminated by renal excretion, and its half-life can be prolonged in patients with renal impairment.

Contra-indications

• Hypersensitivity to dihydrostreptomycin or other aminoglycosides
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Ototoxicity, including hearing loss and vestibular dysfunction
• Nephrotoxicity, particularly with high doses or prolonged therapy
• Neuromuscular blockade
• Allergic reactions, including rash and anaphylaxis

Interactions

• Increased risk of nephrotoxicity with other nephrotoxic agents such as vancomycin, amphotericin B, and non-steroidal anti-inflammatory drugs (NSAIDs)
• Potentially enhanced neuromuscular blockade with neuromuscular blockers

Precautions

• Use with caution in patients with pre-existing renal impairment
• Monitor renal function regularly during therapy
• Assess hearing function prior to and during treatment

Pregnancy

Dihydrostreptomycin is categorized as a category D drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dihydrostreptomycin is excreted in breast milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Injection solution

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

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin G 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 penicillin G interferes with an autolysin inhibitor. 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/

Pharmacodynamics

Penicillin G is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Penicillin G has <i>in vitro</i> activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.

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.