SPASMOLAR TABLETS

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

• Acute poisoning
• Drug overdose
• Gastrointestinal decontamination

Dosage

Children: Refer to specific pediatric dosing recommendations based on the child's weight and the clinical situation.

Adults: Refer to specific guidelines depending on the type of poisoning and the clinical scenario.

Mechanism of action

Activated charcoal works through a process called adsorption, where toxins and drugs adhere to the surface of the charcoal particles due to electrostatic attractions and Van der Waals forces. This prevents the absorption of these substances in the gastrointestinal tract, allowing them to be excreted from the body.

Pharmacodynamics

The pharmacodynamic effects of activated charcoal are related to its ability to bind a wide range of substances. The efficacy of activated charcoal varies depending on the type and amount of the toxin or drug ingested, as well as the time elapsed since ingestion. Generally, activated charcoal is most effective when administered within one hour of ingestion of a toxic substance.

Pharmacokinetics

Activated charcoal is not absorbed by the gastrointestinal tract; instead, it remains in the gut, where it binds to ingested substances and promotes their elimination via feces. Its effects are dose-dependent, and it is typically administered as a single dose, although multiple doses may be considered in certain cases of severe poisoning.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Aspiration pneumonia (if inhaled)
• Electrolyte imbalances

Precautions

• Use with caution in patients with gastrointestinal obstruction
• Monitor for potential aspiration in patients with reduced consciousness
• Consider electrolyte levels in patients with significant diarrhea or vomiting

Pregnancy

Activated charcoal is generally considered safe for use in pregnancy, but consult a healthcare professional before use.

Breast-feeding

Activated charcoal is excreted in breast milk, use with caution and consult a healthcare professional.

Storage

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

Formulations

• Activated charcoal powder
• Activated charcoal capsules
• Activated charcoal tablets

Indications

• Irritable bowel syndrome
• Peptic ulcer disease
• Gastritis
• Other gastrointestinal spasmodic conditions

Dosage

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

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Clidinium inhibits muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites primarily by inhibiting the M1 muscarinic receptors.

Pharmacodynamics

Clidinium has a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract, which helps to relieve symptoms associated with gastrointestinal disorders.

Pharmacokinetics

Clidinium is absorbed from the gastrointestinal tract, with its effects lasting several hours. The metabolism and elimination pathways involve hepatic metabolism, although specific details regarding half-life and excretion are not provided.

Contra-indications

• Hypersensitivity to clidinium or any of its components
• Glaucoma
• Myasthenia gravis
• Severe ulcerative colitis
• Tachyarrhythmias

Adverse effects

• Dry mouth
• Constipation
• Blurred vision
• Dizziness
• Nausea
• Urinary retention

Interactions

• May enhance the effects of other anticholinergic drugs
• Use with caution in patients taking other medications that may cause anticholinergic side effects

Precautions

• Use with caution in patients with a history of urinary retention
• Monitor for signs of gastrointestinal obstruction
• Caution in elderly patients due to increased sensitivity to anticholinergic effects

Pregnancy

Clidinium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider for individual assessment.

Breast-feeding

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

Storage

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

Formulations

• Tablets

Indications

• Irritable bowel syndrome
• Functional gastrointestinal disorders
• Spasm of the gastrointestinal tract

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines.

Adults: Typically, dicyclomine is administered in doses of 20-40 mg orally, taken 4 times daily, or 10-20 mg by intramuscular injection. Dicyclomine should not be given intravenously.

Mechanism of action

Dicyclomine exerts its effects through direct antimuscarinic activity at M1, M2, and M3 receptors, along with non-competitive antagonism of bradykinin and histamine. This results in a relaxation of smooth muscle, particularly in the ileum, leading to decreased contractions and alleviation of spasms. Its major action is a non-specific direct relaxant effect on smooth muscle rather than a competitive antagonism of acetylcholine.

Pharmacodynamics

Dicyclomine is classified as an anticholinergic drug, which is effective in relaxing smooth muscle in the intestines. Its onset of action provides symptomatic relief in conditions characterized by gastrointestinal spasm and discomfort. The drug is typically dosed multiple times throughout the day, reflecting its moderate duration of action.

Pharmacokinetics

Dicyclomine is absorbed after oral administration, with peak plasma concentrations usually occurring within 1 to 2 hours. It undergoes hepatic metabolism, and its metabolites are excreted primarily in the urine. The half-life of dicyclomine varies but is generally around 1-2 hours, which supports the need for multiple daily dosing.

Contra-indications

• Glaucoma
• Myasthenia gravis
• Severe ulcerative colitis
• Obstructive uropathy
• Severe hepatic impairment

Adverse effects

• Dry mouth
• Dizziness
• Drowsiness
• Nausea
• Constipation
• Blurred vision
• Tachycardia

Interactions

• Other anticholinergic drugs may increase the risk of side effects
• CNS depressants may enhance drowsiness
• Antacids may affect absorption

Precautions

• Use with caution in patients with urinary retention
• May exacerbate existing gastrointestinal obstruction
• Caution in elderly patients due to increased sensitivity to anticholinergics
• Monitor for signs of overdose, especially in children

Pregnancy

Dicyclomine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult healthcare professionals for guidance.

Breast-feeding

Dicyclomine may pass into breast milk. Caution is advised when administered to nursing women.

Storage

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

Formulations

• Oral tablet (20 mg, 40 mg)
• Injectable solution (10 mg/2 mL, 20 mg/2 mL)

Indications

• Dry skin
• Skin irritation
• Eczema
• Dermatitis
• Cosmetic applications as a moisturizer and thickening agent

Dosage

Children: Refer to specific product guidelines as dosing can vary based on formulation and intended use.

Adults: Refer to specific product guidelines as dosing can vary based on formulation and intended use.

Mechanism of action

Dimethicone works by forming a protective layer on the skin, which helps to seal in moisture and protect the skin from irritants. Its anti-foaming properties are due to its ability to reduce surface tension, allowing gas bubbles to coalesce and escape more easily, thus diminishing the formation of foam in solutions.

Pharmacodynamics

Dimethicone exhibits emollient properties, which means it can soften and soothe the skin. It acts by creating a barrier that prevents transepidermal water loss, thereby enhancing hydration. Its non-irritating nature makes it suitable for sensitive skin, and it does not clog pores, making it a preferred choice in many dermatological preparations.

Pharmacokinetics

Dimethicone is not absorbed systemically; it remains on the skin surface and does not penetrate into the deeper layers of the skin. This characteristic makes it effective as a topical agent. Because it is not metabolized or excreted by the body, its pharmacokinetic profile is primarily focused on its local effects rather than systemic absorption.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal discomfort

Precautions

• Use with caution in patients with a history of allergic reactions to silicone-based compounds
• Monitor for any signs of adverse reactions during treatment

Pregnancy

Dimethicone is generally considered safe for use during pregnancy, as it is not absorbed systemically.

Breast-feeding

Dimethicone is considered safe for use during breastfeeding, as it is not absorbed and is unlikely to affect breastfed infants.

Storage

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

Formulations

• Topical creams
• Lotions
• Ointments
• Oral suspensions

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

Inhibits muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites primarily by inhibiting the M1 muscarinic receptors.

Pharmacodynamics

Clidinium is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract.

Mechanism of action

Dicyclomine achieves its action partially through direct antimuscarinic activity of the M1, M3, and M2 receptors; and partially through antagonism of bradykinin and histamine. Dicyclomine non-competitively inhibits the action of bradykinin and histamine, resulting in direct action on the smooth muscle, and decreased strength of contractions seen in spasms of the ileum. ...MAJOR ACTION APPEARS TO BE NONSPECIFIC DIRECT RELAXANT ACTION ON SMOOTH MUSLCE RATHER THAN COMPETITIVE ANTAGONISM OF ACH.

Pharmacodynamics

Dicyclomine is an anticholinergic drug used to relax the smooth muscles of the intestines. It's duration of action is not especially long as it is usually taken 4 times daily with individual doses of 20-40mg orally or 10-20mg by intramuscular injection. Dicyclomine should not be administered intravenously.