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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

• Serious infections caused by aerobic Gram-negative bacteria
• Infections due to mycobacteria, including tuberculosis
• Endocarditis in conjunction with penicillin-related antibiotics

Dosage

Children: Refer to BNF for Children for specific dosing information, as it is determined by weight and age.

Adults: Refer to BNF for specific dosing information, as it varies based on the type and severity of the infection.

Mechanism of action

Kanamycin irreversibly binds to specific proteins and 16S rRNA of the 30S ribosomal subunit. This binding interferes with the decoding site, leading to misreading of mRNA, incorrect amino acid insertion into peptides, and disruption of polysomes into nonfunctional monosomes. This bactericidal action results in the inhibition of protein synthesis in susceptible microorganisms.

Pharmacodynamics

Kanamycin is effective primarily against aerobic Gram-negative bacteria and some mycobacteria, including those causing tuberculosis. It disrupts the integrity of the bacterial cell membrane and inhibits protein synthesis, rendering bacteria unable to grow and replicate. While it can be used for Gram-positive infections, other antibiotics are usually preferred due to their higher potency and lower toxicity.

Pharmacokinetics

Kanamycin is administered parenterally, as it is poorly absorbed from the gastrointestinal tract. It demonstrates a volume of distribution that is primarily extracellular. The drug is primarily eliminated by the kidneys through glomerular filtration, necessitating dose adjustments in patients with renal impairment. Kanamycin's half-life is approximately 2 to 3 hours in individuals with normal renal function.

Contra-indications

• Hypersensitivity to kanamycin or any aminoglycoside antibiotic
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Nephrotoxicity
• Ototoxicity (hearing loss, vestibular toxicity)
• Neuromuscular blockade
• Allergic reactions (skin rash, itching)
• Gastrointestinal disturbances (nausea, vomiting)

Interactions

• Other nephrotoxic drugs (e.g., cisplatin, vancomycin) may increase the risk of renal toxicity
• Neurotoxins may potentiate neuromuscular blockade
• Concurrent use with diuretics (e.g., furosemide) may enhance ototoxicity

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with pre-existing hearing loss
• Adjust dosage in cases of renal impairment
• Ensure adequate hydration to minimize risk of nephrotoxicity

Pregnancy

Kanamycin is classified as category D. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Kanamycin is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Refrigeration may be required for some formulations.

Formulations

• Kanamycin sulfate injection
• Kanamycin oral 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

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Dermatological conditions (e.g., eczema, psoriasis)
• Allergic reactions
• Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Certain cancers (e.g., leukemia, lymphoma)

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in children.

Adults: Refer to the BNF for specific dosing guidelines based on condition and severity.

Mechanism of action

Prednisolone exerts its effects by binding to the glucocorticoid receptor in the cytoplasm, which then translocates to the nucleus. This complex interacts with glucocorticoid response elements in the DNA, leading to the modulation of gene expression. This results in decreased production of pro-inflammatory cytokines, inhibition of immune cell proliferation, and suppression of the inflammatory response.

Pharmacodynamics

Prednisolone demonstrates anti-inflammatory effects by reducing the infiltration of inflammatory cells and inhibiting the release of inflammatory mediators such as prostaglandins and leukotrienes. Its immunosuppressive actions are characterized by the inhibition of T-cell activation and the reduction of antibody production. The drug's effects are dose-dependent and can lead to both therapeutic benefits and potential adverse effects.

Pharmacokinetics

Prednisolone is well absorbed following oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It is extensively metabolized in the liver, primarily by the cytochrome P450 enzyme system, producing active and inactive metabolites. The elimination half-life is approximately 2-3 hours, and the drug is primarily excreted in urine. Factors such as liver function and concurrent medications can affect its metabolism and clearance.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to prednisolone or any of its components
• Live vaccines in immunocompromised patients

Adverse effects

• Increased susceptibility to infections
• Gastrointestinal disturbances
• Weight gain and fluid retention
• Hypertension
• Hyperglycemia
• Osteoporosis
• Mood changes and psychiatric disturbances
• Cushing's syndrome with prolonged use

Interactions

• Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal side effects
• Anticoagulants may have altered effects
• Diuretics may enhance potassium loss
• Vaccines may be less effective in immunosuppressed patients

Precautions

• Use with caution in patients with diabetes mellitus
• Monitor for signs of infection
• Gradual withdrawal is recommended after long-term therapy to avoid adrenal insufficiency
• Use with caution in patients with a history of peptic ulcer disease

Pregnancy

Prednisolone can be used during pregnancy if the benefits outweigh the risks. It is classified as Category C.

Breast-feeding

Prednisolone is excreted in breast milk, and caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Oral solution
• Injection (intravenous and intramuscular)
• Topical formulations (creams and ointments)

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

Aminoglycosides like kanamycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin binds to 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. Kanamycin, an aminoglycoside, acts by inhibiting the synthesis of protein in susceptible microorganisms. It is bactericidal in vitro against Gram-negative bacteria and certain Gram-positive bacteria. 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/ ... 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

Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

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.