HIPRACILLIN RETARD INJ

Indications

• Tuberculosis, resistant to other treatment
• Brucellosis (as an adjunct to doxycycline)
• Severe gram-negative infections (specific cases)

Dosage

Adults: For tuberculosis: 15 mg/kg daily (maximum 1 g per dose), reduce in those under 50 kg and over 40 years. For other infections: 3 mg/kg daily in 3 divided doses, increased if necessary up

Mechanism of action

Streptomycin enters bacterial cells through a three-phase process. Initially, it binds electrostatically to negatively charged components of bacterial cell membranes, increasing permeability and allowing entry. This is followed by energy-dependent transport into the cytoplasm where it binds to the 30S ribosomal subunit, causing mistranslation of proteins and disrupting membrane integrity. The resultant damage leads to concentration-dependent bactericidal effects, including immediate and delayed actions due to impaired protein synthesis.

Pharmacodynamics

Streptomycin has a narrow spectrum of activity, effective against susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, and certain strains of gram-negative bacilli and gram-positive cocci. Resistance has reduced its effectiveness against many pathogens, and it is not effective against Pseudomonas aeruginosa. The drug's therapeutic index is narrow, necessitating close monitoring for toxic effects, particularly nephrotoxicity and ototoxicity.

Pharmacokinetics

Streptomycin is administered parenterally due to poor oral absorption. After intramuscular injection, it achieves peak plasma concentrations within 1-2 hours. It is distributed widely in body tissues and fluids, but does not penetrate well into the central nervous system. The drug is primarily eliminated unchanged by the kidneys, necessitating dosage adjustments in renal impairment. The half-life is approximately 2-3 hours in individuals with normal renal function.

Contra-indications

• Hypersensitivity to streptomycin or other aminoglycosides
• Myasthenia gravis (due to risk of neuromuscular blockade)
• Pregnancy (especially in the second and third trimesters due to risk of auditory or vestibular nerve damage)

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Nausea
• Vomiting
• Diarrhea
• Electrolyte imbalance
• Blood disorders
• Confusion
• Paraesthesia
• Drowsiness
• Respiratory disorders
• Hearing loss
• Vestibular dysfunction

Interactions

• Other nephrotoxic drugs (e.g., vancomycin, furosemide)
• Neuromuscular blocking agents
• Other ototoxic agents

Precautions

• Caution in renal impairment due to increased risk of nephrotoxicity and ototoxicity
• Monitor renal function and auditory function before and during treatment
• Use with caution in patients with existing hearing loss

Pregnancy

There is a risk of auditory or vestibular nerve damage in the infant when aminoglycosides, including streptomycin, are used during the second and third trimesters of pregnancy.

Breast-feeding

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

Storage

Store below 25°C, protect from light, and keep out of reach of children.

Formulations

• Streptomycin sulfate injection (various concentrations)
• Streptomycin for inhalation (nebulized form)
• Streptomycin oral solution

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Acute pain
• Dysmenorrhea
• Postoperative pain
• Gout

Dosage

Children: Refer to the BNF for Children for detailed pediatric dosing information.

Adults: Refer to the specific clinical guidelines or BNF for appropriate dosing recommendations based on the condition being treated.

Mechanism of action

Lasting acts primarily by inhibiting cyclooxygenase (COX) enzymes, which are essential for the conversion of arachidonic acid to prostaglandins. Prostaglandins are mediators of inflammation and pain. By inhibiting COX, Lasting decreases the production of these inflammatory substances, leading to reduced pain and inflammation.

Pharmacodynamics

The pharmacodynamics of Lasting involve its ability to modulate the pain threshold and reduce inflammatory responses. The onset of action can vary depending on the formulation, but analgesic effects are usually experienced within several hours of administration. The anti-inflammatory effects are due to the inhibition of prostaglandin synthesis, which is critical in the inflammatory pathway.

Pharmacokinetics

Lasting is absorbed relatively quickly from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 3 hours post-administration. The drug is metabolized in the liver, primarily by CYP enzymes, and its metabolites are excreted mainly through the kidneys. The half-life of the drug can vary, but it is typically around 1 to 3 hours, necessitating multiple doses for sustained effect.

Adverse effects

• Drowsiness
• Dizziness
• Headache
• Nausea
• Dry mouth
• Constipation

Interactions

• CNS depressants may enhance sedative effects
• Alcohol may increase drowsiness and dizziness
• Antihistamines may have additive effects

Precautions

• Use with caution in patients with hepatic impairment
• May cause sedation; caution when driving or operating machinery
• Monitor for signs of dependence with long-term use

Pregnancy

Use only if clearly needed and the benefits outweigh the risks, as safety in pregnancy has not been established.

Breast-feeding

Use with caution; may pass into breast milk and affect the infant.

Storage

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

Mechanism of action

The specific mechanism of action for Long is not detailed in the provided information. However, based on its chemical structure, it may interact with specific neurotransmitter systems or cellular pathways to exert its effects, potentially acting through receptor modulation or enzyme inhibition.

Pharmacodynamics

Pharmacodynamics of Long is not explicitly outlined. Generally, pharmacodynamics refers to the relationship between drug concentration and its therapeutic effect. This includes understanding the drug's efficacy, potency, and side effects, which are influenced by its action on the body’s biological systems.

Pharmacokinetics

Pharmacokinetics details such as absorption, distribution, metabolism, and excretion of Long are not specified. Typically, these parameters help in understanding how the drug behaves in the body over time, influencing dosing regimens and therapeutic decisions.

Pregnancy

Consult the prescribing information, as safety during pregnancy has not been established.

Breast-feeding

Consult the prescribing information, as it is not known whether this drug is excreted in human milk.

Storage

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

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

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. The primary intracellular site of action of the aminoglycosides is the 30 S ribosomal subunit, which consists of 21 proteins and a single 16 S molecule of RNA. at least three of these proteins and perhaps the 16 S ribosomal RNA as well contribute to the streptomycin binding site, and alterations of these molecules markedly affect the binding and subsequent action of streptomycin. For example, a single amino acid substitution of asparagine for lysine at position 42 of one ribosomal protein (S12) prevents binding of the drug; the resultant mutant is totally resistant to streptomycin. Another mutant, in which glutamine is the amino acid at this position, is dependent on streptomycin. During protein synthesis, the ribosome selects aminoacyl-transfer RNAs with anticodons matching the messenger RNA codon present in the A site of the small ribosomal subunit. The aminoglycoside antibiotic streptomycin disrupts decoding by binding close to the site of codon recognition. Here we use X-ray crystallography to define the impact of streptomycin on the decoding site of the Thermus thermophilus 30S ribosomal subunit in complexes with cognate or near-cognate anticodon stem-loop analogues and messenger RNA. Our crystal structures display a significant local distortion of 16S ribosomal RNA induced by streptomycin, including the crucial bases A1492 and A1493 that participate directly in codon recognition. Consistent with kinetic data, we observe that streptomycin stabilizes the near-cognate anticodon stem-loop analogue complex, while destabilizing the cognate anticodon stem-loop analogue complex. These data reveal ho

Pharmacodynamics

Although streptomycin originally had broad gram-negative and gram-positive coverage, its spectrum of activity has been significantly narrowed due to antibiotic resistance. Streptomycins current spectrum of activity includes susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis, H. ducreyi, H. influenza, K. pneumoniae pneumonia, E.coli, Proteus, A. aerogenes, K. pneumoniae, Enterococcus faecalis, Streptococcus viridans, Enterococcus faecalis, and Gram-negative bacillary bacteremia. Streptomycin is not reliably active against pseudomonas aeruginosa. Similar to other aminoglycosides, streptomycin is considered to have a narrow therapeutic index. Characteristic toxicities of streptomycin include nephrotoxicity and ototoxicity. Patients should be carefully monitored for early signs of hearing loss and vestibular dysfunction in order to prevent permanent damage to sensorineural cells. Neuromuscular blockade has also been rarely reported.