PROMETHAZINE-PLUS 5MG/125MG SYRUP

Indications

• Allergic conditions such as hay fever
• Motion sickness
• Nausea and vomiting
• Sedation
• Insomnia associated with urticaria
• Pruritus

Dosage

Children: Child 2–4 years: 5 mg twice daily, alternatively 5–15 mg once daily, dose to be taken at night. Child 5–9 years: 5–10 mg twice daily, alternatively 10–25 mg once daily, dose to be taken at night. Child 10–17 years: 10–20 mg 2–3 times a day, alternatively 25 mg once daily, dose to be taken

Adults: 10–20 mg 2–3 times a day, alternatively 25 mg once daily, dose to be taken at night.

Mechanism of action

Promethazine hydrochloride works by antagonizing H1 histamine receptors, which inhibits the actions of histamine, a chemical involved in allergic reactions. Additionally, it has anticholinergic effects, which can help in reducing nausea and motion sickness by affecting the vestibular system.

Pharmacodynamics

Promethazine exhibits sedative, antiemetic, and antihistaminic properties. The sedative effects are due to its ability to cross the blood-brain barrier and block central H1 receptors, while the antiemetic effects are mediated through its action on the chemoreceptor trigger zone and vestibular pathways. The anticholinergic activity contributes to its effectiveness in controlling motion sickness.

Pharmacokinetics

Promethazine is well absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours. It has a long half-life of approximately 10-19 hours, allowing for once or twice daily dosing in most indications. The drug is extensively metabolized in the liver, primarily through cytochrome P450 enzymes, and eliminated mainly via urine. It is also noted for its potential for accumulation in patients with impaired hepatic function.

Contra-indications

• Hypersensitivity to promethazine or any of its components
• Patients with a history of angle-closure glaucoma
• Patients with severe respiratory depression
• Children under 2 years of age (unlicensed use for sedation)

Adverse effects

• Drowsiness
• Dizziness
• Blurred vision
• Dry mouth
• Nausea
• Urinary retention
• Paradoxical excitability in children
• Agranulocytosis
• Seizures
• Insomnia
• Skin reactions
• Leukopenia
• Anxiety
• Restlessness
• Fatigue
• Photosensitivity reaction

Interactions

• Increased sedative effects when used with alcohol or other CNS depressants
• Anticholinergic effects may be enhanced when used with other anticholinergic agents
• May interact with other antihistamines, increasing the risk of side effects

Precautions

• Use with caution in elderly patients due to increased susceptibility to anticholinergic side effects
• May cause sedation; caution patients about performing tasks requiring alertness (e.g., driving)
• Monitor for increased effects in combination with other sedatives
• Not suitable for long-term use in children under 2 years of age without specialist advice

Pregnancy

Most manufacturers advise avoidance during pregnancy; however, no evidence of teratogenicity has been established. Use in late pregnancy may lead to adverse effects in neonates.

Breast-feeding

Most antihistamines are excreted in breast milk; while not known to be harmful, manufacturers typically advise against use during breastfeeding.

Storage

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

Formulations

• Tablets: 10 mg, 25 mg
• Oral solution: 5 mg/5 mL
• Injection: 25 mg/mL

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

• Allergic reactions
• Nausea and vomiting
• Motion sickness
• Sedation
• Anxiety and tension

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Promethazine functions as a competitive antagonist of histamine H1 receptors, which diminishes the effects of histamine in allergic reactions. It also antagonizes post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors. This multifaceted action is responsible for its sedative properties, utility in anxiety and tension, as well as its effectiveness in controlling nausea and vomiting.

Pharmacodynamics

Promethazine exhibits its antihistaminic effects by blocking H1 receptors, leading to reduced allergic response, sedation, and antiemetic effects. The sedative effects typically last between 4 to 6 hours, although they can extend up to 12 hours. Caution is advised regarding potential CNS and respiratory depression, as well as a reduced seizure threshold and possible bone marrow suppression.

Pharmacokinetics

Promethazine is absorbed from the gastrointestinal tract and has a variable bioavailability. It is extensively metabolized in the liver, primarily via the cytochrome P450 enzyme system, and has a long half-life, which contributes to its prolonged effects. The drug is excreted primarily in urine as metabolites. Its pharmacokinetic profile can be influenced by factors such as age and liver function.

Contra-indications

• Hypersensitivity to promethazine or any of its components.
• Children under 2 years of age due to the risk of severe respiratory depression.
• Comatose states or patients with severe central nervous system depression.

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation
• Confusion
• Extrapyramidal symptoms
• Severe respiratory depression
• Hypotension

Interactions

• Increased sedation with alcohol and CNS depressants.
• May enhance the effects of other antihistamines.
• Concomitant use with monoamine oxidase inhibitors (MAOIs) may increase the risk of severe side effects.

Precautions

• Use with caution in patients with asthma, cardiovascular disease, or glaucoma.
• Monitor for signs of respiratory depression, particularly in pediatric and elderly patients.
• Caution advised when driving or operating machinery due to sedative effects.

Pregnancy

Promethazine is classified as category C. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

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

Formulations

• Tablets
• Syrup
• Injection

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.

Mechanism of action

Promethazine is a an antagonist of histamine H1, post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors. The antihistamine action is used to treat allergic reactions. Antagonism of muscarinic and NMDA receptors contribute to its use as a sleep aid, as well as for anxiety and tension. Antagonism of histamine H1, muscarinic, and dopamine receptors in the medullary vomiting center make promethazine useful in the treatment of nausea and vomiting. Promethazine is a phenothiazine derivative with potent sedative properties. Although the drug can produce either CNS stimulation or CNS depression, CNS depression manifested by sedation is more common with therapeutic doses of promethazine. The precise mechanism of the CNS effects of the drug is not known. Although it has been reported that the drug has slight antitussive activity, this may result from its anticholinergic and CNS depressant effects. In therapeutic doses, promethazine appears to have no substantial effect on the cardiovascular system. Although rapid IV administration of promethazine may produce a transient fall in blood pressure, blood pressure usually is maintained or slightly elevated when the drug is given slowly. Promethazine hydrochloride is a phenothiazine derivative which possesses antihistaminic, sedative, antimotion-sickness, antiemetic, and anticholinergic effects. Promethazine is a competitive H1 receptor antagonist, but does not block the release of histamine. Structural differences from the neuroleptic phenothiazines result in its relative lack (1/10 that of chlorpromazine) of dopamine antagonist properties. The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/ For more Mechanism of Action (Complete) data for Promethazine (18 total), please visit the HSDB record page.

Pharmacodynamics

Promethazine is is a histamine H1 antagonist that can be used for it's ability to induce sedation, reduce pain, and treat allergic reactions. Promethazine's effects generally last 4-6h but can last up to 12h. Patients should be counselled regarding CNS and respiratory depression, reduce seizure threshold, and bone marrow depression.