COMBIKEL 40 INJECTABLE SOLUTION

Indications

• Bacterial infections caused by susceptible gram-positive organisms
• Pneumonia
• Meningitis
• Syphilis
• Streptococcal infections

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Benzylpenicillinum binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, inhibiting the third and final stage of bacterial cell wall synthesis. This binding leads to weakening of the cell wall and subsequent cell lysis, mediated by bacterial autolytic enzymes. The drug also acts as an immunogen, potentially causing allergic reactions in some individuals.

Pharmacodynamics

Benzylpenicillinum is effective against a variety of gram-positive and some gram-negative bacteria. Its bactericidal action is due to the inhibition of cell wall synthesis through binding to PBPs, which are essential for bacterial growth and division. The drug is stable against certain beta-lactamases, enhancing its efficacy in treating infections caused by resistant strains.

Pharmacokinetics

Benzylpenicillinum is administered parenterally and exhibits rapid distribution in body tissues and fluids. Its half-life is relatively short, necessitating frequent dosing in order to maintain therapeutic levels. The drug is primarily excreted unchanged in the urine, and its pharmacokinetics can be affected by renal function.

Contra-indications

• History of hypersensitivity to penicillins
• Severe renal impairment (without dosage adjustment)
• Mononucleosis (risk of rash)

Adverse effects

• Allergic reactions (including anaphylaxis)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Hematologic reactions (hemolytic anemia, leukopenia, thrombocytopenia)
• Superinfection (due to prolonged use)
• Neurotoxicity (in cases of high doses or renal impairment)

Interactions

• Probenecid (increases penicillin G levels by inhibiting renal excretion)
• Aminoglycosides (synergistic effect against certain bacteria)
• Oral anticoagulants (may enhance effect leading to increased bleeding risk)
• Methotrexate (increased toxicity due to decreased renal clearance)

Precautions

• Use with caution in patients with a history of allergic reactions to other beta-lactam antibiotics
• Monitor renal function, particularly in high-risk patients
• Caution in patients with asthma or hay fever
• Consider potential for superinfection with prolonged therapy

Pregnancy

Penicillin G is generally considered safe during pregnancy, but should be used only if clearly needed.

Breast-feeding

Penicillin G is excreted in breast milk in low concentrations; it is usually considered safe for breastfeeding.

Storage

Store in a cool, dry place away from light. Reconstituted solutions should be stored in the refrigerator and used within 24 hours.

Formulations

• Injectable solution
• Powder for injection

Indications

• Tuberculosis
• Bacterial infections caused by susceptible strains

Dosage

Children: Refer to BNF for Children for specific dosage recommendations based on the child's age and weight.

Adults: Refer to BNF for specific dosage recommendations based on the condition being treated.

Mechanism of action

Dihydrostreptomycin works by binding to the 30S ribosomal subunit of bacteria, inhibiting protein synthesis. This binding disrupts the reading of mRNA, leading to the production of non-functional proteins, ultimately resulting in bacterial cell death. The drug is particularly effective against aerobic bacteria.

Pharmacodynamics

Dihydrostreptomycin demonstrates concentration-dependent bactericidal activity. Its efficacy is influenced by the peak concentration achieved relative to the minimum inhibitory concentration (MIC) for the target bacteria. The drug's activity is enhanced in the presence of oxygen, making it effective against aerobic pathogens.

Pharmacokinetics

Dihydrostreptomycin is poorly absorbed from the gastrointestinal tract and is typically administered parenterally. It has a volume of distribution that is relatively large, indicating tissue binding. The drug is primarily excreted unchanged in the urine. Its half-life is approximately 2 to 3 hours, which necessitates multiple daily dosing to maintain effective therapeutic levels.

Contra-indications

• Hypersensitivity to dihydrostreptomycin or other aminoglycosides
• Severe renal impairment
• Pregnancy (except in specific cases of tuberculosis)

Adverse effects

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

Interactions

• Other ototoxic drugs (e.g., loop diuretics)
• Other nephrotoxic agents (e.g., nonsteroidal anti-inflammatory drugs)
• Neuromuscular blocking agents

Precautions

• Monitor renal function during therapy
• Assess hearing function before and during treatment
• Use with caution in patients with pre-existing hearing loss

Pregnancy

Dihydrostreptomycin should be avoided during pregnancy unless the benefits outweigh the risks, particularly in cases of tuberculosis.

Breast-feeding

Use with caution, as it may be excreted in breast milk and could affect the nursing infant.

Storage

Store in a cool, dry place away from light. Reconstituted solutions should be used promptly or stored in the refrigerator.

Formulations

• Injectable solution

Indications

• Local anesthesia for dental procedures
• Regional anesthesia for minor surgical interventions
• Pain management in specific surgical settings

Dosage

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

Adults: Refer to BNF for specific dosing information based on the procedure and individual patient factors.

Mechanism of action

Procaine primarily acts 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 can bind to N-methyl-D-aspartate (NMDA) receptors, nicotinic acetylcholine receptors, and serotonin receptor-ion channel complexes, contributing to its anesthetic effects. The drug not only decreases permeability to sodium ions but also reduces the resting nerve permeability to potassium ions, ultimately impairing nerve conduction.

Pharmacodynamics

Procaine is effective in providing local anesthesia, particularly in oral surgery. It possesses vasoconstrictive properties, which are beneficial in reducing intraoperative bleeding. As an ester anesthetic, it is hydrolyzed in the plasma by pseudocholinesterase, leading to the formation of para-aminobenzoic acid (PABA), which is then excreted in urine. Its anesthetic onset is rapid, with a duration of action that can be influenced by the use of vasoconstrictors.

Pharmacokinetics

Procaine is rapidly metabolized in the bloodstream by pseudocholinesterase, resulting in a short duration of action. Peak plasma concentrations occur shortly after administration. The drug is mainly excreted as metabolites in the urine. The pharmacokinetic profile may vary based on the route of administration and the presence of vasoconstrictors that can prolong its effects.

Contra-indications

• Hypersensitivity to procaine or any of the components of the formulation
• Severe liver dysfunction
• Severe renal impairment

Adverse effects

• Allergic reactions including anaphylaxis
• Cardiovascular collapse
• CNS effects such as seizures, dizziness, or drowsiness
• Local tissue reactions including irritation or necrosis
• Hypotension

Interactions

• Increased risk of toxicity when used with other local anesthetics
• Caution with use alongside other CNS depressants
• May enhance the effects of neuromuscular blocking agents

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor for signs of systemic toxicity, especially in high doses or when administered rapidly
• Consider potential for infection at the injection site

Pregnancy

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

Breast-feeding

Procaine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Procaine hydrochloride injection
• Procaine topical solution

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.