DIARIV SUSPENSION

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

• Dry eye conditions
• Anterior uveitis
• Cycloplegia

Dosage

Children: For children aged 3 months to 1 year, apply 1 drop once daily or on alternate days, adjusted according to response. For children aged 2 to 17 years

Adults: Apply 1 drop to the affected eye 3–4 times daily as directed, adjusting frequency based on clinical response.

Mechanism of action

Homatropine hydrobromide works by blocking the action of acetylcholine at muscarinic receptors in the iris sphincter and ciliary body. This antagonism leads to dilation of the pupil (mydriasis) and paralysis of the ciliary muscle (cycloplegia), resulting in decreased eye accommodation. It also reduces secretions from mucous membranes, which can help alleviate symptoms associated with dry eye.

Pharmacodynamics

The pharmacodynamic effects of homatropine hydrobromide are characterized by its ability to induce mydriasis and cycloplegia, which are crucial for diagnostic procedures in ophthalmology. Its anti-secretory properties also contribute to its therapeutic effects in treating dry eye conditions. The onset of action occurs within 30 to 60 minutes after administration, with peak effects typically lasting up to 24 hours.

Pharmacokinetics

Homatropine hydrobromide is administered topically as eye drops, leading to localized effects with minimal systemic absorption. Its bioavailability through the ocular route is influenced by factors such as corneal permeability and the formulation of the eye drops. The metabolism and excretion pathways are not extensively documented, but the drug is expected to undergo hepatic metabolism, with metabolites likely excreted renally. Systemic absorption may lead to side effects, particularly in sensitive populations such as children and the elderly.

Adverse effects

• Eye discomfort
• Eye redness
• Abdominal distension (in children)
• Behavioural abnormalities (in children)
• Cardiac arrhythmias
• Respiratory distress (in children)
• Conjunctivitis
• Constipation
• Dry mouth
• Oedema (on prolonged administration)
• Flushing
• Gastrointestinal disorders
• Hyperaemia (on prolonged administration)
• Mydriasis
• Palpitations
• Psychotic disorders (in children)
• Staggering
• Urinary disorders
• Vomiting

Precautions

• Use caution in children and the elderly due to potential for systemic side effects.
• Preservative-free formulations are preferred for frequent and chronic application.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. The effects on a nursing infant are unknown.

Storage

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

Formulations

• Homatropine hydrobromide 0.5% eye drops
• Homatropine hydrobromide 1% eye drops

Indications

• Amebiasis
• Amoebic dysentery
• Intestinal protozoal infections

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored to the pediatric population.

Adults: Refer to professional guidelines for specific dosing recommendations, as these may vary based on the severity of the infection and patient response.

Mechanism of action

Diiodohydroxyquinoline acts by disrupting the metabolic processes of the protozoa. It is believed to interfere with the function of the cell membrane and inhibit the enzymes involved in the metabolism of the parasites, ultimately leading to their death. Its iodine content may also contribute to its antimicrobial activity.

Pharmacodynamics

The pharmacodynamic profile of diiodohydroxyquinoline includes its ability to reduce the viability of Entamoeba histolytica and other protozoan pathogens. It exerts its effects through both direct cytotoxicity to the parasites and by impeding their metabolic functions, which is crucial for their survival and replication.

Pharmacokinetics

Diiodohydroxyquinoline is absorbed from the gastrointestinal tract following oral administration. It is distributed throughout the body, with a particular affinity for the intestinal lumen where it exerts its therapeutic effects. The drug undergoes hepatic metabolism and is primarily excreted in the feces, with a lesser extent through urine. Its half-life is variable, depending on the individual's metabolic rate and liver function.

Adverse effects

• Gastrointestinal disturbances
• Mild liver enzyme elevations
• Skin rashes
• Headaches

Precautions

• Use with caution in patients with hepatic impairment
• Monitor liver function periodically during treatment

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus, as there are no adequate and well-controlled studies in pregnant women.

Breast-feeding

It is not known if diiodohydroxyquinoline is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a tightly closed container at room temperature, away from moisture and heat.

Formulations

• Tablets

Indications

• Mydriasis for ophthalmic examination
• Cycloplegia for refractive error assessment
• Treatment of uveitis and iritis

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and condition.

Adults: For mydriasis, 1-2 drops of 2% or 5% solution may be instilled in the affected eye(s) as needed, up to 3 times a day.

Mechanism of action

Homatropine works by blocking the action of acetylcholine on muscarinic receptors in the iris sphincter muscle and the ciliary body. This results in dilation of the pupil (mydriasis) and paralysis of the ciliary muscle (cycloplegia), leading to reduced accommodation and facilitating diagnostic procedures in the eye.

Pharmacodynamics

The anticholinergic effects of homatropine lead to increased intraocular pressure due to the relaxation of the ciliary muscle and the dilation of the pupil. This can be particularly useful in certain ocular conditions but may also pose risks in patients with narrow-angle glaucoma. The onset of mydriatic effect typically occurs within 30 minutes and can last for several hours.

Pharmacokinetics

Homatropine is rapidly absorbed following ocular administration. Its effects can be prolonged due to its binding to ocular tissues. The drug is metabolized in the liver and excreted in the urine. The half-life of homatropine is variable but generally, its effects persist for a few hours after administration.

Interactions

• clozapine+homatropine: Unknown (additive effect)
• antipsychotics, second generation+homatropine: Unknown (additive effect)

Pregnancy

The safety of homatropine during pregnancy has not been established. Use with caution and only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Homatropine is excreted in breast milk. Caution is recommended when administering to nursing mothers.

Storage

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

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.

Dosage

Children: Dosage information for pediatric patients should be derived from specific product guidelines or the BNF for Children, as it varies widely based on the formulation and indication.

Adults: Dosage information for phthalyl derivatives is specific to the formulation and intended use. Refer to product-specific guidelines for appropriate dosing.

Mechanism of action

Phthalyl compounds may act via different mechanisms based on their specific applications. Generally, they can influence cellular pathways, potentially interacting with enzymes or receptors involved in metabolic processes. Specific mechanisms can vary widely among different phthalyl derivatives.

Pharmacodynamics

The pharmacodynamics of phthalyl compounds can vary significantly depending on the specific derivative and its intended use. Some phthalyl derivatives may exhibit effects such as inhibition or activation of metabolic pathways, modulation of enzyme activity, or interaction with neurotransmitter systems. The pharmacological profile is determined by the specific chemical structure and the biological target.

Pharmacokinetics

Pharmacokinetics of phthalyl compounds also vary based on the specific derivative. Generally, factors such as absorption, distribution, metabolism, and excretion are influenced by the chemical properties of the compound. Phthalyl derivatives may exhibit variable bioavailability, half-life, and routes of elimination, depending on their formulation and route of administration.

Pregnancy

Phthalyl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data are available on its safety.

Breast-feeding

It is not known whether phthalyl is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Indications

• Bacterial infections
• Urinary tract infections
• Respiratory tract infections
• Certain gastrointestinal infections

Dosage

Children: Refer to the BNF for Children

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated and individual patient factors.

Mechanism of action

Sulfathiazole acts as a structural analog of p-aminobenzoic acid (PABA) and competitively inhibits the enzyme dihydropteroate synthase. This enzyme catalyzes the formation of dihydropteroic acid from PABA and pteridine, an essential step in the biosynthesis of tetrahydrofolic acid in bacteria. By interfering with this process, sulfathiazole reduces the synthesis of dihydrofolate and consequently tetrahydrofolate, impairing the bacteria's ability to produce nucleic acids and proteins, which are vital for growth and replication.

Pharmacodynamics

Sulfathiazole exhibits bacteriostatic properties, meaning it inhibits bacterial growth rather than killing bacteria directly. Its effectiveness may be decreased in the presence of body fluids such as blood or pus, which can interfere with its action. The drug demonstrates synergistic effects when used in conjunction with other agents that inhibit later stages of folic acid synthesis, such as trimethoprim and pyrimethamine.

Pharmacokinetics

Sulfathiazole is absorbed from the gastrointestinal tract and is distributed throughout the body. It is metabolized in the liver and excreted primarily through the kidneys. The half-life of the drug is influenced by various factors, including the patient's renal function. Dosage adjustments may be necessary in cases of renal impairment to avoid accumulation and toxicity.

Contra-indications

• Hypersensitivity to sulfathiazole or other sulfonamides
• Severe renal impairment
• Porphyria

Adverse effects

• Rash
• Nausea
• Vomiting
• Diarrhea
• Hematological reactions (e.g., agranulocytosis, thrombocytopenia)
• Hepatotoxicity
• Renal impairment
• Crystalluria

Interactions

• May enhance the effects of anticoagulants, such as warfarin
• May inhibit the metabolism of phenytoin
• Concurrent use with methotrexate may increase toxicity
• May interact with oral hypoglycemic agents

Precautions

• Monitor renal function during therapy
• Use cautiously in patients with G6PD deficiency
• Caution in pregnancy and lactation
• Avoid use in patients with severe allergies or asthma

Pregnancy

Sulfathiazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is advisable to consult a healthcare professional.

Breast-feeding

Sulfathiazole is excreted in breast milk; caution is advised when administered to a nursing mother.

Storage

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

Formulations

• Oral tablets
• Injectable solution

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.

Mechanism of action

Sulfonamides are usually bacteriostatic in action. Sulfonamides interfere with the utilization of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid (the reduced form of folic acid) cofactors in susceptible bacteria. Sulfonamides are structural analogs of PABA and appear to interfere with PABA utilization by competitively inhibiting the enzyme dihydropteroate synthase, which catalyzes the formation of dihydropteroic acid (a precursor of tetrahydrofolic acid) from PABA and pteridine; however, other mechanism(s) affecting the biosynthetic pathway also may be involved. Compounds such as pyrimethamine and trimethoprim, which block later stages in the synthesis of folic acid, act synergistically with sulfonamides. Only microorganisms that synthesize their own folic acid are inhibited by sulfonamides; animal cells and bacteria which are capable of utilizing folic acid precursors or preformed folic acid are not affected by these drugs. The antibacterial activity of the sulfonamides is reportedly decreased in the presence of blood or purulent body exudates. /Sulfonamides/ The sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit an enzymatic step (dihydropterate synthetase) during which PABA is incorporated into the synthesis of dihydrofolic acid (folic acid). Because dihydrofolate synthesis is reduced, the levels of tetrahydrofolate (folinic acid) formed from dihydrofolate diminish. Tetrahydrofolate is an essential component of the coenzymes responsible for single carbon metabolism in cells. Acting as antimetabolites to PABA, sulfonamides eventually block, in a complex fashion, several enzymes. These enzymes include those needed for the biogenesis of purine bases; for the transfer of desoxyuridine to thymidine; and for the biosynthesis of methionine, glycine, and formylmethionyl-transfer-RNA. This results in suppression of protein synthesis, impairment of metabolic processes, and inhibition of growth and multiplication of those organisms that cannot use preformed folate. The effect is bacteriostatic, although a bactericidal action is evident at the high concentrations that may be found in urine.