FLUCORDAY LIQUID GEL

Indications

• Mild to moderate pain
• Fever
• Headaches
• Muscle aches
• Arthritis
• Backaches
• Toothaches
• Colds

Dosage

Adults: For adults, the typical dosage is 500 mg to 1 g every 4 to 6 hours, with a maximum daily limit of 4 g. In cases of intravenous administration, the dosage is 15 mg/kg every

Mechanism of action

Paracetamol is thought to exert its analgesic effects by inhibiting cyclo-oxygenase (COX) enzymes, specifically COX-1 and COX-2, which are involved in the synthesis of prostaglandins responsible for pain sensation. Unlike most NSAIDs, paracetamol does not exhibit peripheral anti-inflammatory effects. Its antipyretic action is believed to result from direct action on heat-regulating centers in the brain, leading to peripheral vasodilation and sweating.

Pharmacodynamics

Paracetamol has been shown to have both antipyretic and analgesic effects, lacking any significant anti-inflammatory activity. It does not interfere with platelet aggregation or disrupt hemostasis, making it a safer option for individuals at risk of bleeding. Allergic reactions to paracetamol are rare. The drug does not affect uric acid secretion or acid-base balance when used at recommended doses.

Pharmacokinetics

Paracetamol is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 30 to 60 minutes after oral administration. It is primarily metabolized in the liver via conjugation with glucuronide and sulfate, with a minor pathway involving cytochrome P450 enzymes. The elimination half-life ranges from 1 to 4 hours, with renal excretion of metabolites as the primary route of elimination.

Adverse effects

• Nausea and vomiting
• Liver injury
• Renal damage
• Hypersensitivity reactions
• Flushing
• Hypotension
• Anorectal erythema
• Angioedema
• Agranulocytosis
• Thrombocytopenia
• Leukopenia
• Severe cutaneous adverse reactions (SCARs)

Interactions

• Increased risk of methaemoglobinaemia with topical prilocaine
• Increased risk of methaemoglobinaemia with topical anaesthetics
• Increased anticoagulant effect with coumarins
• Increased risk of hepatotoxicity with imatinib
• Decreased exposure with rifampicin
• Decreased exposure with pitolisant

Precautions

• Monitor patients with liver disease or heavy alcohol use for increased risk of hepatotoxicity
• Adjust doses in patients taking enzyme-inducing antiepileptic medications
• Use caution in patients with renal impairment
• Clinical judgement is required for dose adjustment in weight-based dosing

Pregnancy

Paracetamol is generally considered safe to use during pregnancy for pain and fever relief, but should be used at the lowest effective dose for the shortest duration necessary.

Breast-feeding

Paracetamol is excreted in breast milk in small amounts and is considered safe for use while breastfeeding.

Storage

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

Formulations

• Oral tablets (500 mg)
• Oral suspension (120 mg/5 mL, 500 mg/5 mL)
• Rectal suppositories (various strengths)
• Intravenous infusion (various strengths)

Indications

• Cough due to common cold
• Cough due to bronchitis
• Cough due to other upper respiratory tract infections

Dosage

Children: Refer to BNF for Children for appropriate dosing recommendations based on age and weight.

Adults: Refer to specific product guidance or clinical guidelines for dosing, as it can vary by formulation and indication.

Mechanism of action

Dextromethorphan acts primarily on the central nervous system, specifically targeting the cough center in the medulla oblongata. It is an NMDA receptor antagonist and also inhibits the reuptake of serotonin, contributing to its cough-suppressing effects. By modulating the activity of neurons in the brain responsible for triggering the cough reflex, it effectively reduces the urge to cough.

Pharmacodynamics

Dextromethorphan exhibits a nonlinear pharmacokinetic profile, with effects observed at therapeutic doses that primarily involve central nervous system activity. It does not act on opioid receptors in a manner that would typically lead to respiratory depression or analgesia, making it unique among cough suppressants. The peak effect usually occurs within 1-2 hours after oral administration.

Pharmacokinetics

After oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism in the liver, primarily by cytochrome P450 2D6 to form its active metabolite, dextrorphan. The elimination half-life varies depending on individual metabolic rates, but it generally ranges from 3 to 6 hours. Renal impairment may affect the clearance of dextromethorphan and its metabolites.

Contra-indications

• Hypersensitivity to dextromethorphan or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe respiratory insufficiency
• Cough due to emphysema or chronic bronchitis

Adverse effects

• Dizziness
• Drowsiness
• Nausea
• Vomiting
• Constipation
• Confusion
• Hallucinations
• Nervousness
• Rash

Interactions

• Increased risk of serotonin syndrome when used with other serotonergic drugs
• Potentially enhanced CNS depressant effects when used with alcohol, benzodiazepines, or other CNS depressants
• May interact with drugs affecting hepatic metabolism such as CYP2D6 inhibitors

Precautions

• Caution in patients with a history of substance abuse
• Use with caution in patients with hepatic impairment
• Not recommended for use in children under 4 years of age
• Monitor for signs of serotonin syndrome when used with other serotonergic agents

Pregnancy

Dextromethorphan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on its safety in pregnancy is limited.

Breast-feeding

Dextromethorphan is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Syrup
• Tablets
• Capsules
• Lozenges

Indications

• Nasal congestion due to colds
• Allergic rhinitis
• Sinusitis
• Eustachian tube dysfunction

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines, as doses can vary based on the formulation used and the condition being treated.

Mechanism of action

Pseudoephedrine primarily acts as an agonist at alpha-adrenergic receptors, leading to vasoconstriction of the nasal mucosa. This reduces blood flow and swelling, thereby alleviating nasal congestion. Additionally, it has some beta-adrenergic receptor activity, which may contribute to its overall effects.

Pharmacodynamics

The pharmacodynamic effects of pseudoephedrine include vasoconstriction, which results in decreased blood flow to the nasal mucosa. This leads to reduced edema and congestion. Pseudoephedrine may also have a mild stimulating effect on the central nervous system due to its structural similarity to amphetamines, although this effect is typically less pronounced than with other sympathomimetics.

Pharmacokinetics

Pseudoephedrine is well-absorbed orally, with peak plasma concentrations occurring approximately 1 to 2 hours after administration. It has a half-life of about 5 to 8 hours. Pseudoephedrine is metabolized in the liver, primarily by the cytochrome P450 system, and is excreted in the urine. The elimination half-life can be prolonged in individuals with renal impairment.

Contra-indications

• Hypersensitivity to pseudoephedrine or any component of the formulation
• Severe hypertension
• Severe coronary artery disease
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment

Adverse effects

• Insomnia
• Nervousness
• Dizziness
• Increased blood pressure
• Tachycardia
• Dry mouth
• Nausea

Interactions

• Monoamine oxidase inhibitors (MAOIs) may increase the hypertensive effects of pseudoephedrine
• Other sympathomimetic drugs may enhance the effects and side effects
• Antihypertensive medications may have reduced effectiveness

Precautions

• Use with caution in patients with hypertension, diabetes, thyroid disease, or prostatic hypertrophy
• Monitoring of blood pressure is advisable in patients with cardiovascular disease
• Caution in patients with a history of seizures

Pregnancy

Pseudoephedrine is categorized as a pregnancy category C drug. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Pseudoephedrine is excreted in breast milk. Caution is advised, and it should be used only if necessary.

Storage

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

Formulations

• Oral tablets
• Extended-release tablets
• Liquid formulations

Mechanism of action

According to its FDA labeling, acetaminophen's exact mechanism of action has not been fully established - despite this, it is often categorized alongside NSAIDs (non-steroidal anti-inflammatory drugs) due to its ability to inhibit the cyclo-oxygenase (COX) pathways. It is thought to exert central actions which ultimately lead to the alleviation of pain symptoms. One theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclo-oxygenase, COX-1 and COX-2, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for eliciting pain sensations. Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX indirectly. Studies also suggest that acetaminophen selectively blocks a variant type of the COX enzyme that is unique from the known variants COX-1 and COX-2. This enzyme has been referred to as _COX-3_. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat. The exact mechanism of action of this drug is not fully understood at this time, but future research may contribute to deeper knowledge. Although further investigation is warranted, the active metabolite of acetaminophen (AM404) was shown to interact with several molecular targets, including the Ca_v3.2 calcium channel, the cannabinoid CB1 receptors, TRPV1 receptors, and Na_v1.8 and Na_v1.7 channels. Acetaminophen produces analgesia and antipyresis by a mechanism similar to that of salicylates. Unlike salicylates, however, acetaminophen does not have uricosuric activity. There is some evidence that acetaminophen has weak anti-inflammatory activity in some nonrheumatoid conditions (e.g., in patients who have had oral surgery). ... Acetaminophen lowers body temperature in patients with fever but rarely lowers normal body temperature. The drug acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. The effects of acetaminophen on cyclooxygenase activity have not been fully determined. Acetaminophen is a weak, reversible, isoform-nonspecific cyclooxygenase inhibitor at dosages of 1 g daily. The inhibitory effect of acetaminophen on cyclooxygenase-1 is limited, and the drug does not inhibit platelet function. Therapeutic doses of acetaminophen appear to have little effect on cardiovascular and respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing. Acetaminophen (N-acetyl-p-aminophenol (APAP)) is the most common antipyretic/analgesic medicine worldwide. If APAP is overdosed, its metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI), causes liver damage. However, epidemiological evidence has associated previous use of therapeutic APAP doses with the risk of chronic obstructive pulmonary disease (COPD) and asthma. The transient receptor potential ankyrin-1 (TRPA1) channel is expressed by peptidergic primary sensory neurons. Because NAPQI, like other TRPA1 activators, is an electrophilic molecule, /the researchers/ hypothesized that APAP, via NAPQI, stimulates TRPA1, thus causing airway neurogenic inflammation. NAPQI selectively excites human recombinant and native (neuroblastoma cells) TRPA1. TRPA1 activation by NAPQI releases proinflammatory neuropeptides (substance P and calcitonin gene-related peptide) from sensory nerve terminals in rodent airways, thereby causing neurogenic edema and neutrophilia. Single or repeated administration of therapeutic (15-60 mg/kg) APAP doses to mice produces detectable levels of NAPQI in the lung, and increases neutrophil numbers, myeloperoxidase

Pharmacodynamics

Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the _salicylate_ drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses. Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation. Allergic reactions are rare occurrences following acetaminophen use.