PEN ROL

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

• Pain management
• Vaccination
• Antibiotic therapy
• Hormonal therapies
• Anesthesia
• Nutritional support
• Chemotherapy

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as it requires careful consideration of weight and age.

Adults: Refer to specific drug guidelines for adult dosing, as it varies widely depending on the medication and clinical condition.

Mechanism of action

The mechanism of action of injected drugs varies widely based on the specific medication being administered. Generally, injected drugs enter the bloodstream directly, allowing them to circulate rapidly throughout the body. For instance, antibiotics may work by inhibiting bacterial cell wall synthesis, while analgesics may modulate pain pathways in the central nervous system. Each drug has unique pathways through which it achieves its therapeutic effects.

Pharmacodynamics

Pharmacodynamics refers to the effects of drugs on the body and their mechanisms of action. For injectable medications, effects can be immediate or delayed, depending on the drug's formulation and route of administration. Factors influencing pharmacodynamics include receptor affinity, drug concentration, and the presence of other substances that may enhance or inhibit the drug's effects. For example, some injectable drugs may require specific receptors to exert their effects, while others may have a broader range of action.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of injected drugs. After administration, drugs are rapidly absorbed into the bloodstream, leading to quick therapeutic effects. The distribution depends on factors such as blood flow, tissue permeability, and protein binding. Drugs are metabolized primarily in the liver and excreted through the kidneys or bile. The pharmacokinetic profile can vary widely based on the drug's chemical nature, dosage, and individual patient factors.

Pregnancy

Safety during pregnancy depends on the specific injection and its active ingredients. It is essential to consult a healthcare professional for guidance.

Breast-feeding

The safety of injections during breastfeeding varies by the specific medication. It is recommended to seek advice from a healthcare provider.

Storage

Store injections as per manufacturer's guidelines, usually in a cool, dry place away from direct sunlight. Some may require refrigeration.

Indications

• Preservative in cosmetics
• Preservative in pharmaceutical formulations
• Antimicrobial agent in food products

Dosage

Children: Refer to specific product guidelines for dosing information, as methylparaben is primarily used as a preservative rather than a therapeutic agent.

Adults: Refer to specific product guidelines for dosing information, as methylparaben is primarily used as a preservative rather than a therapeutic agent.

Mechanism of action

The mechanism of cytotoxic action of parabens, including methylparaben, may be linked to mitochondrial failure. This is dependent on the induction of membrane permeability transition, which is accompanied by mitochondrial depolarization and depletion of cellular ATP through the uncoupling of oxidative phosphorylation.

Pharmacodynamics

Methylparaben exhibits antimicrobial activity against a range of bacteria and fungi. Its effectiveness as a preservative is attributed to its ability to disrupt microbial cell membranes and inhibit essential metabolic processes, ensuring the stability and safety of various formulations.

Pharmacokinetics

Methylparaben is absorbed following topical application and is metabolized by hydrolysis to p-hydroxybenzoic acid, which is then excreted in urine. The pharmacokinetics may vary based on the route of administration and formulation. Studies suggest a relatively low systemic absorption when used in topical applications.

Pregnancy

There is limited data on the use of methylparaben in pregnancy. It should be used only if clearly needed and the benefits outweigh any potential risks.

Breast-feeding

Methylparaben is excreted in breast milk. Caution is advised when using products containing methylparaben while breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Keep container tightly closed.

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

• Rheumatoid arthritis
• Atopic dermatitis
• Psoriatic arthritis
• Ulcerative colitis

Dosage

Children: Refer to the BNF for Children for dosing information in pediatric patients.

Adults: Refer to the prescribing information for specific dosing guidelines based on the condition being treated.

Mechanism of action

Upto exerts its therapeutic effects by selectively inhibiting Janus kinase 1 (JAK1). This inhibition prevents the phosphorylation and activation of signal transducer and activator of transcription (STAT) proteins, which are crucial for the signaling of numerous pro-inflammatory cytokines. Consequently, the reduced activity of these pathways leads to decreased inflammation and immune response.

Pharmacodynamics

The pharmacodynamics of Upto are characterized by its ability to inhibit the JAK-STAT signaling pathway, leading to a decrease in the production of inflammatory mediators. This results in reduced symptoms of inflammation, such as pain and swelling, and improved clinical outcomes in patients with autoimmune diseases. The onset of action can vary, with some patients reporting improvements within weeks of starting therapy.

Pharmacokinetics

Upto is rapidly absorbed following oral administration, with peak plasma concentrations typically reached within a few hours. It undergoes extensive metabolism primarily via the cytochrome P450 system, particularly CYP3A4. The elimination half-life is approximately 10 hours, allowing for once-daily dosing. Upto is excreted mainly through urine and feces, with a significant portion of the drug being eliminated unchanged.

Contra-indications

• Hypersensitivity to the active substance or any of the excipients
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness
• Fatigue
• Allergic reactions including rash and itching

Interactions

• May interact with other central nervous system depressants, increasing sedation
• Potential interactions with drugs metabolized by the liver
• May affect the pharmacodynamics of anticoagulants

Precautions

• Use with caution in patients with hepatic or renal impairment
• Monitor for signs of sedation or respiratory depression
• Consider potential for abuse and dependence

Pregnancy

Limited data is available. Use only if clearly needed and the benefits justify the risks to the fetus.

Breast-feeding

Excreted in breast milk. Use with caution and consider alternative treatments.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solution

Mechanism of action

...The mechanism of cytotoxic action of parabens may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation.

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.