LONG P.S

Indications

• Rheumatic fever prevention
• Syphilis treatment
• Streptococcal infections
• Bacterial endocarditis prophylaxis

Dosage

Children: For children, the recommended dose for rheumatic fever prophylaxis is 600,000 units for those weighing less than 27 kg, and 1.2 million units for those weighing 27 kg or more, administered every 3 to 4 weeks.

Adults: The usual adult dose for the treatment of syphilis is a single intramuscular injection of 2.4 million units. For rheumatic fever prophylaxis, the recommended dose is 1.2 million units every 3 to 4 weeks.

Mechanism of action

Benzathine exerts its antibacterial effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) within the bacterial cell wall, leading to cell lysis and death. This mechanism is effective against a wide range of gram-positive bacteria, particularly Streptococcus species.

Pharmacodynamics

The pharmacodynamics of benzathine penicillin involves the drug's ability to maintain therapeutic concentrations in the body for an extended period. The prolonged release from the injection site allows for sustained antibacterial activity, making it effective in treating infections such as rheumatic fever and syphilis. The drug is particularly effective against organisms that are sensitive to penicillin.

Pharmacokinetics

Benzathine is administered intramuscularly, where it is slowly absorbed into the bloodstream. The peak plasma concentrations occur within 12 to 24 hours after administration, with a half-life that can extend up to several days, depending on the dosage and individual patient factors. It is primarily excreted by the kidneys. Due to its long-acting nature, benzathine is suitable for single-dose treatment regimens in certain infections.

Contra-indications

• Hypersensitivity to benzathine or any component of the formulation
• Severe allergies to other penicillins or beta-lactam antibiotics

Adverse effects

• Allergic reactions, including anaphylaxis
• Rash
• Fever
• Angioedema
• Nausea
• Vomiting
• Diarrhea
• Superinfection with prolonged use

Interactions

• May have reduced efficacy when administered concurrently with bacteriostatic antibiotics such as tetracyclines
• Probenecid may increase the serum concentrations of benzathine

Precautions

• Use with caution in patients with a history of allergies or asthma
• Monitor for signs of anaphylaxis during and after administration
• Evaluate renal function in patients receiving high doses or prolonged therapy

Pregnancy

Benzathine is classified as category B. Animal studies have shown no harm; however, adequate and well-controlled studies in pregnant women are lacking.

Breast-feeding

Benzathine is excreted in breast milk. Caution is recommended when administering to breastfeeding mothers.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Benzathine benzylpenicillin injection
• Benzathine penicillin G suspension

Indications

• Severe bacterial infections
• Sepsis
• Pneumonia
• Urinary tract infections
• Intra-abdominal infections
• Skin and soft tissue infections

Dosage

Children: Refer to paediatric dosing guidelines in established drug reference texts or formularies for recommendations based on age, weight, and clinical condition.

Adults: Refer to established clinical guidelines or drug formularies for specific dosing regimens based on the type and severity of infection, renal function, and patient factors.

Mechanism of action

Dihystreptomycin exerts its antibacterial effect by binding to the 30S ribosomal subunit of bacterial ribosomes. This binding interferes with the initiation complex of protein synthesis, leading to misreading of mRNA and ultimately resulting in the production of non-functional or toxic proteins. This mechanism contributes to its bactericidal activity, particularly against rapidly dividing bacteria.

Pharmacodynamics

The pharmacodynamics of dihystreptomycin involve its capacity to inhibit bacterial protein synthesis, which is crucial for bacterial growth and replication. Dihystreptomycin demonstrates concentration-dependent killing, where higher concentrations lead to more significant bacterial death. Its activity is enhanced in an alkaline environment, and it is generally more effective against aerobic bacteria due to its uptake mechanisms.

Pharmacokinetics

Dihystreptomycin is typically administered parenterally, as it is poorly absorbed from the gastrointestinal tract. After administration, it distributes widely in extracellular fluid and achieves therapeutic concentrations in various tissues. The drug is primarily eliminated by the kidneys through glomerular filtration, and monitoring of renal function is essential during treatment to avoid toxicity. The half-life of dihystreptomycin can vary, particularly in patients with renal impairment.

Contra-indications

• Hypersensitivity to dihystreptomycin or any component of the formulation
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Ototoxicity, including hearing loss and tinnitus
• Nephrotoxicity
• Neuromuscular blockade
• Allergic reactions, including rash and anaphylaxis
• Gastrointestinal disturbances, including nausea and vomiting

Interactions

• Other nephrotoxic agents, which may increase the risk of renal impairment
• Other ototoxic medications, which may enhance the risk of hearing loss
• Neuromuscular blocking agents, which may have additive effects leading to respiratory depression

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
• Caution in patients with a history of neuromuscular disorders

Pregnancy

Dihystreptomycin is classified as a category D drug. There is evidence of risk to the human fetus, but the potential benefits may warrant use in pregnant women despite potential risks.

Breast-feeding

It is unknown whether dihystreptomycin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Injectable solution
• Powder for reconstitution

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

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.