ACEZYME TABLETS

Indications

• Pain and inflammation in rheumatoid arthritis
• Pain and inflammation in osteoarthritis
• Pain and inflammation in ankylosing spondylitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: The recommended dose for adults is 100 mg twice daily.

Mechanism of action

Aceclofenac acts by inhibiting the cyclooxygenase (COX) enzymes, specifically COX-2, leading to a decrease in the synthesis of prostaglandins. This results in an anti-inflammatory effect, pain relief, and reduction in swelling. The pathway involves the blockade of the arachidonic acid pathway, which is vital for the production of pro-inflammatory mediators.

Pharmacodynamics

Aceclofenac exhibits anti-inflammatory, analgesic, and antipyretic properties. By inhibiting COX-2, it reduces inflammation and pain while sparing COX-1, which helps maintain gastric mucosal integrity, thereby potentially lowering the risk of gastrointestinal side effects compared to other NSAIDs. However, it still poses risks such as gastrointestinal bleeding, renal impairment, and cardiovascular events.

Pharmacokinetics

Aceclofenac is well-absorbed after oral administration, with peak plasma concentrations occurring approximately 1-2 hours post-dose. It is extensively metabolized in the liver, primarily via glucuronidation, with its metabolites being excreted through urine. The half-life of aceclofenac is about 4 hours, necessitating twice-daily dosing for effective pain management. The drug's clearance may be reduced in patients with hepatic impairment.

Contra-indications

• Active bleeding
• Active gastrointestinal bleeding
• History of hypersensitivity to aspirin or any other NSAID
• Severe renal impairment
• Severe hepatic impairment

Adverse effects

• Constipation
• Vomiting
• Anaemia
• Angioedema
• Depression
• Drowsiness
• Dyspnoea
• Fatigue
• Haemolytic anaemia
• Headache
• Heart failure
• Hepatic disorders
• Hyperkalaemia
• Hypertension
• Inflammatory bowel disease
• Leg cramps
• Nephrotic syndrome
• Neutropenia
• Oedema
• Palpitations
• Pancreatitis
• Paraesthesia
• Respiratory disorders
• Severe cutaneous adverse reactions (SCARs)
• Sleep disorders
• Taste altered
• Thrombocytopenia
• Tinnitus
• Tremor
• Vasculitis
• Vertigo
• Visual impairment
• Weight increased

Interactions

• Increased risk of gastrointestinal side effects when combined with low-dose aspirin
• Alcohol increases risk of gastrointestinal hemorrhage
• NSAIDs may exacerbate symptoms in asthma patients

Precautions

• Use with caution in elderly patients and those at risk of gastrointestinal ulceration
• Patients with serious rheumatic diseases may become dependent on NSAIDs
• Consider gastroprotective treatment for at-risk patients

Pregnancy

Most manufacturers advise avoiding the use of NSAIDs during pregnancy unless the potential benefit outweighs the risk, particularly during the third trimester due to risks associated with fetal ductus arteriosus closure.

Breast-feeding

Use with caution during breastfeeding.

Storage

Store in a cool, dry place away from light.

Formulations

• Oral tablets

Indications

• Osteoarthritis
• Sinusitis
• Postoperative inflammation
• Wound healing
• Digestive disorders

Dosage

Children: Refer to specific product guidelines for paediatric doses, as bromelain usage in children should be approached with caution and under medical supervision.

Adults: Refer to specific product guidelines for dosing, as bromelain is available in various formulations. Doses may range widely based on the indication and formulation.

Mechanism of action

Bromelain acts by breaking down proteins into smaller peptides and amino acids, which aids in digestion. It also has anti-inflammatory effects by inhibiting the activity of pro-inflammatory mediators, including bradykinin and prostaglandins. Additionally, bromelain may enhance the absorption of certain antibiotics and improve the bioavailability of other therapeutic agents.

Pharmacodynamics

Bromelain exhibits anti-inflammatory and analgesic properties, which are beneficial in reducing swelling, bruising, and pain. Its proteolytic activity can promote the degradation of fibrin, a protein involved in blood clotting, thereby assisting in the reduction of inflammation and promoting healing. Its effects on the immune system also contribute to its therapeutic potential.

Pharmacokinetics

Bromelain is absorbed in the gastrointestinal tract, with its bioavailability influenced by the presence of food. Its systemic effects may vary based on the formulation and dosage. The elimination of bromelain occurs primarily through the renal pathway, and its half-life is not well established due to variations in individual metabolism and formulation.

Adverse effects

• Gastrointestinal disturbances (nausea, diarrhea, abdominal pain)
• Allergic reactions (skin rash, itching, anaphylaxis in sensitive individuals)
• Increased bleeding risk (due to its fibrinolytic activity)

Interactions

• Anticoagulants (increased risk of bleeding)
• Antiplatelet drugs (may enhance effects)
• Antibiotics (may enhance absorption and effects)

Precautions

• Use with caution in individuals with a history of allergies to pineapples or other bromelain sources
• Caution in patients with bleeding disorders or those undergoing surgery

Pregnancy

There is insufficient reliable information regarding the safety of bromelain during pregnancy. It should be used with caution and only if clearly needed.

Breast-feeding

Limited information is available; consult a healthcare provider before use.

Storage

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

Formulations

• Oral tablets
• Capsules
• Powder

Indications

• Chronic venous insufficiency
• Varicose veins
• Hemorrhoids
• Peripheral vascular disorders

Dosage

Children: Refer to BNF for Children for specific dosing recommendations.

Adults: Refer to BNF for specific dosing recommendations.

Mechanism of action

Rutoside exerts its effects through multiple mechanisms, including the enhancement of antioxidant enzyme activity, activation of the Nrf2/HO-1 pathway, and elevation of glutathione levels. It also reduces malondialdehyde levels and inhibits pro-inflammatory cytokines such as IL-1β, IL-6, and TGF-β1. Furthermore, rutoside demonstrates anti-apoptotic properties by inhibiting free radicals and various caspases, while promoting the expression of anti-apoptotic proteins like Bcl-2.

Pharmacodynamics

Rutoside displays significant antioxidant activity, contributing to the reduction of oxidative stress. Its anti-inflammatory effects help mitigate tissue damage in conditions associated with chronic inflammation. The compound's ability to inhibit apoptosis in cells suggests a potential role in protecting tissues from damage induced by toxic substances or stress.

Pharmacokinetics

The pharmacokinetics of rutoside indicate that it is well-absorbed and metabolized in the body, though specific absorption rates and bioavailability details are not fully characterized. It is known to be distributed in various tissues, where it can exert its effects. The elimination half-life and specific metabolic pathways for rutoside require further investigation, though it is generally processed through hepatic metabolism.

Adverse effects

• Gastrointestinal disturbances
• Headache
• Allergic reactions

Precautions

• Use with caution in patients with known allergies to flavonoids
• Monitor for potential interactions with anticoagulants

Pregnancy

There is limited data on the safety of rutoside during pregnancy. Use only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Rutoside is excreted in breast milk. Exercise caution and consult a healthcare professional before use during breastfeeding.

Storage

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

Formulations

• Tablets
• Capsules
• Powder for oral solution

Indications

• Pancreatic insufficiency
• Malabsorption syndromes
• Cystic fibrosis
• Chronic pancreatitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored to paediatric patients.

Adults: Refer to the prescribing information or BNF for specific dosing guidelines based on the condition being treated and the formulation used.

Mechanism of action

Trypsin acts by cleaving peptide bonds in proteins, particularly at the carboxyl side of lysine and arginine residues. This enzymatic activity is essential for protein digestion, leading to the conversion of proteins into smaller peptides and free amino acids, which can be readily absorbed by the intestinal mucosa. The activation of trypsinogen to trypsin is catalyzed by the enzyme enteropeptidase, which is secreted by the intestinal mucosa.

Pharmacodynamics

The pharmacodynamic effects of trypsin are primarily related to its role in protein digestion. It aids in the breakdown of complex protein structures into smaller peptides, which enhances nutrient absorption. Additionally, trypsin may influence various physiological processes by modulating protein signaling pathways, although these effects are less well-characterized compared to its digestive role.

Pharmacokinetics

Trypsin is typically administered exogenously in a proteolytic enzyme supplement form, particularly for conditions associated with pancreatic insufficiency. When taken orally, it is subject to degradation in the gastrointestinal tract; hence, it is often encapsulated to protect it from gastric acid. Its absorption is generally poor, and any systemic effects are limited due to rapid inactivation in the systemic circulation. Clinical studies indicate that trypsin may be absorbed in small amounts, but its primary use remains local to the gastrointestinal tract.

Contra-indications

• Hypersensitivity to trypsin or any of its components
• Active gastrointestinal bleeding
• Severe renal impairment
• History of pancreatitis

Adverse effects

• Gastrointestinal disturbances such as nausea, vomiting, and diarrhea
• Allergic reactions including rash and urticaria
• Increased risk of bleeding
• Local irritation at the site of administration

Interactions

• Anticoagulants may have enhanced effects when used with trypsin due to its proteolytic activity
• Corticosteroids may interfere with the action of trypsin
• Other proteolytic enzymes may have additive effects

Precautions

• Use with caution in patients with a history of allergies
• Monitor for signs of bleeding in patients with clotting disorders
• Evaluate renal function before initiating therapy
• Caution in patients with a history of gastrointestinal disorders

Pregnancy

There are no well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

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

Formulations

• Enteric-coated tablets
• Capsules
• Powder for reconstitution

Mechanism of action

Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL-6 is thought to be mediated by diclofenac converted from aceclofenac. Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes. In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CD62L), which is a cell adhesion molecule expressed on lymphocytes. Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL-1 production and activity. The chrondroprotective effects are generated by 4'-hydroxyaceclofenac which suppresses IL-1 mediated production of promatrix metalloproteinase-1 and metalloproteinase-3 and interferes with the release of proteoglycan from chrondrocytes.

Pharmacodynamics

Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM. Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF). It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects.

Mechanism of action

A 2022 review of Rutin focused on its protective effects on the heart, liver, and kidneys against various chemical and natural toxins. The antioxidant effects involve enhancement of various antioxidant enzymes, Nrf2/HO-1 pathway activation, Glutathione (GSH) elevation, and malondialdehyde (MDA) reduction. The anti-inflammatory effects involve inhibition of IL-1β, IL-6, TGF-β1, COX-2, iNOS, TLR4, and XO. The antiapoptotic effects involve inhibition of free radicals, caspase-3/-7/-9, hsp70, HMGB1, and p53, and elevation of antiapoptotic protein Bcl-2.