PENISTREP 20/25

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

• Lead poisoning
• Mercury poisoning
• Cadmium poisoning
• Hypercalcemia
• Diagnostic aid in certain medical tests

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on the condition and age of the child.

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

Mechanism of action

EDTA2Na acts by chelating divalent and trivalent metal ions through the formation of stable, water-soluble complexes. The chelation process involves the formation of coordinate covalent bonds between the electron-rich donor atoms of EDTA and the metal ions, effectively reducing the bioavailability and toxicity of the metals. This mechanism enhances the renal excretion of the metal complexes, thus decreasing their concentration in the body.

Pharmacodynamics

The pharmacodynamic effects of EDTA2Na are primarily related to its chelating activity, leading to the reduction of metal toxicity and the alleviation of symptoms associated with heavy metal exposure. It can also influence the distribution of certain minerals and trace elements within the body, potentially affecting their physiological functions. However, its use can result in the depletion of essential minerals, necessitating careful monitoring and management during treatment.

Pharmacokinetics

EDTA2Na is administered intravenously or intramuscularly, allowing for rapid systemic distribution. It is not readily absorbed from the gastrointestinal tract, which limits its oral bioavailability. Once in the circulation, EDTA binds to metal ions and is excreted primarily via the kidneys. The half-life of EDTA varies based on the presence of chelated metals, but typically it is eliminated from the body within a few hours following administration. Renal function plays a significant role in the clearance of EDTA and its metal complexes.

Contra-indications

• Hypersensitivity to EDTA or any of its components
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Fever
• Headache
• Thrombocytopenia
• Renal toxicity
• Cardiac arrhythmias

Interactions

• May enhance the effects of anticoagulants, leading to increased bleeding risk
• May interfere with the absorption of essential minerals such as calcium, magnesium, and zinc
• Caution with nephrotoxic agents due to potential additive renal toxicity

Precautions

• Use with caution in patients with renal impairment
• Monitor serum electrolytes, particularly calcium levels, during treatment
• Should not be administered rapidly due to risk of hypotension
• Not recommended for use in children unless supervised by a specialist

Pregnancy

The safety of EDTA in pregnancy has not been established. It should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

EDTA is excreted in breast milk. Caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Intravenous solution
• Intramuscular injection
• Oral tablets

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Preservative in cosmetics
• Preservative in pharmaceuticals
• Preservative in food products

Dosage

Children: Refer to specific product guidelines as dosing varies based on formulation and concentration used.

Adults: Refer to specific product guidelines as dosing varies based on formulation and concentration used.

Mechanism of action

Parabens work by inhibiting the growth of microorganisms through their ability to disrupt the cellular processes of bacteria and fungi. They penetrate the microbial cell membrane and disrupt enzyme and protein functions, leading to cell death. Parabens are known to have low toxicity and are metabolized by the body, subsequently being excreted in urine.

Pharmacodynamics

Parabens demonstrate broad-spectrum antimicrobial activity, making them effective preservatives in various formulations. Their efficacy is influenced by factors such as concentration, pH, and the presence of other ingredients in the formulation. Due to their structural similarity to estrogen, there has been concern regarding their potential endocrine-disrupting effects, although the clinical significance of this is still debated.

Pharmacokinetics

Parabens are readily absorbed through the skin and gastrointestinal tract. Once absorbed, they are rapidly metabolized primarily in the liver. They undergo hydrolysis to form para-hydroxybenzoic acid, which is then conjugated with glucuronic acid and excreted in urine. The half-life of parabens in the human body is relatively short, and they are eliminated rapidly.

Adverse effects

• Allergic reactions, such as skin rashes
• Irritation at the site of application
• Endocrine disruption (in high concentrations)

Precautions

• Use with caution in individuals with known sensitivities or allergies to parabens
• Consider potential endocrine effects with prolonged exposure

Pregnancy

Parabens are generally considered safe in cosmetics and personal care products during pregnancy, although caution is advised due to potential endocrine disruption.

Breast-feeding

Parabens are considered safe in breastfeeding, but it is recommended to use products with minimal or no parabens when possible.

Storage

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

Formulations

• Topical creams
• Lotions
• Shampoos
• Conditioners
• Makeup products
• Pharmaceutical preparations

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

Indications

• Used as a binder in tablet formulations
• Film-coating agent for oral dosage forms
• Stabilizer in liquid formulations
• Enhancer of drug solubility and bioavailability

Dosage

Children: Dosage varies depending on formulation, refer to specific product guidelines for details.

Adults: Dosage varies depending on formulation, refer to specific product guidelines for details.

Mechanism of action

PVPK17 works primarily through its hydrophilic properties, which allow it to interact with a variety of compounds, enhancing the solubility of poorly soluble drugs. It forms a gel-like matrix that can facilitate controlled drug release. Additionally, PVPK17 can improve the dispersion of active pharmaceutical ingredients in formulations, ensuring uniformity and stability.

Pharmacodynamics

The pharmacodynamics of PVPK17 is largely related to its role as an excipient rather than having intrinsic pharmacological activity. It aids in the modulation of drug release kinetics, enhancing absorption and therapeutic efficacy by ensuring that active ingredients are delivered adequately to their site of action. Its ability to improve the solubility of drugs can lead to increased plasma concentrations and improved therapeutic outcomes.

Pharmacokinetics

PVPK17 is not typically absorbed systemically when used in pharmaceutical formulations, as it is designed to act locally within the gastrointestinal tract or as a component of topical preparations. It is biocompatible and generally considered non-toxic, with a favorable safety profile. The polymer is metabolized by enzymatic hydrolysis into smaller fragments, which may be further metabolized or excreted by the body, but specific pharmacokinetic parameters are not well-defined due to its primary use as an excipient.

Pregnancy

The effects of pvpk17 during pregnancy are not well-studied. Caution is advised when administering this drug to pregnant women.

Breast-feeding

It is unknown whether pvpk17 is excreted in human milk. Caution is recommended when using this drug while breastfeeding.

Storage

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

Indications

• Surgical procedures
• Injection of medications
• Preparation of sterile pharmaceutical products
• Management of open wounds
• Use in controlled environments such as hospitals and laboratories

Dosage

Children: Refer to specific drug monographs for dosage information as sterile itself is not a pharmacological agent.

Adults: Refer to specific drug monographs for dosage information as sterile itself is not a pharmacological agent.

Mechanism of action

Sterility itself does not have a mechanism of action as it is a state of cleanliness and does not interact with biological systems. However, the methods used to achieve sterility, such as heat or chemical agents, act by denaturing proteins, disrupting cellular structures, or damaging nucleic acids in microorganisms, leading to their inactivation or destruction.

Pharmacodynamics

The pharmacodynamics of sterile techniques primarily involves the prevention of microbial infection and contamination when administering medications. By ensuring that products are sterile, the risk of adverse effects related to infections is minimized. The effectiveness of sterilization methods can be influenced by factors such as temperature, duration of exposure, and the type of microorganisms present.

Pharmacokinetics

As sterility does not pertain to a specific drug, pharmacokinetics is not applicable. However, the pharmacokinetics of a drug will depend on its formulation, route of administration, and the presence of preservatives or stabilizers that may be used alongside sterile preparations.

Pregnancy

Sterile preparations are generally considered safe during pregnancy as they are used to provide hydration, nutrition, or medications in a controlled manner, but specific formulations should be assessed individually.

Breast-feeding

Sterile solutions used for hydration or nutritional support are typically safe during breastfeeding, but any specific additives or medications within the solutions should be evaluated for safety.

Storage

Sterile solutions should be stored in a cool, dry place, protected from light, and should be used before the expiration date. Once opened, they may have specific storage requirements based on the formulation.

Formulations

• Sterile saline solution
• Sterile water for injection
• Sterile dextrose solution
• Sterile electrolyte solutions

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.