ASCO-30 410MG TABLET

Indications

• Mild to moderate pain relief
• Fever reduction
• Management of inflammatory conditions such as rheumatoid arthritis and osteoarthritis
• Prevention of cardiovascular events in patients with a history of myocardial infarction or stroke
• Management of acute coronary syndrome

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as this may differ significantly from adult dosing.

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on the indication and patient factors.

Mechanism of action

Aspirin works primarily by irreversibly inhibiting cyclooxygenase (COX-1 and COX-2) enzymes, leading to a decrease in the synthesis of prostaglandins and thromboxanes. This results in reduced inflammation, pain, and fever. The inhibition of COX-1 also reduces platelet aggregation by decreasing thromboxane A2 production, which is crucial for platelet activation and aggregation.

Pharmacodynamics

The analgesic effects of aspirin are attributed to its ability to inhibit the generation of prostaglandins, which mediate pain and inflammation. In addition to its pain-relieving and anti-inflammatory effects, aspirin's antiplatelet action is significant in the context of cardiovascular health, as it reduces the risk of thrombus formation in blood vessels.

Pharmacokinetics

Aspirin is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after oral administration. It is extensively metabolized in the liver, primarily via hydrolysis to salicylic acid, which has its own therapeutic effects. The elimination half-life varies depending on the dose, ranging from 15 to 20 minutes for aspirin and several hours for salicylic acid. Aspirin and its metabolites are excreted primarily in the urine.

Contra-indications

• Active gastrointestinal bleeding
• History of peptic ulcer disease
• Severe renal impairment
• Severe hepatic impairment
• Hypersensitivity to acetylsalicylic acid or other NSAIDs
• Children and teenagers with viral infections (risk of Reye's syndrome)

Adverse effects

• Gastrointestinal irritation and bleeding
• Nausea and vomiting
• Dyspepsia
• Allergic reactions such as rash or asthma exacerbation
• Tinnitus (ringing in the ears)
• Renal impairment
• Hepatic dysfunction

Interactions

• Increased risk of gastrointestinal bleeding with other NSAIDs or anticoagulants
• Enhanced effects of anticoagulants (e.g., warfarin, heparin)
• Reduced effectiveness of antihypertensive drugs (e.g., ACE inhibitors)
• Increased risk of renal impairment with diuretics
• Potential interaction with methotrexate, leading to increased toxicity

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in long-term use or in patients with renal impairment
• Assess the risk of bleeding before surgery or dental procedures
• Caution in patients with asthma or nasal polyps due to potential hypersensitivity reactions
• Consider the potential for Reye's syndrome in children and adolescents

Pregnancy

Use during pregnancy is generally not recommended, particularly in the third trimester, due to the risk of adverse effects on the fetus and complications during delivery.

Breast-feeding

Acetylsalicylic acid is excreted in breast milk; caution is advised if used while breastfeeding.

Storage

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

Formulations

• Tablets
• Enteric-coated tablets
• Effervescent tablets
• Suppositories
• Oral suspension

Indications

• Management of apnea of prematurity
• Enhancement of alertness and cognitive performance
• Relief of headaches, particularly when combined with analgesics
• Enhancement of physical performance in sports

Dosage

Children: For infants, particularly for apnea of prematurity

Adults: The usual adult dose for alertness enhancement is 100 to 200 mg, taken as needed. For the management of apnea of prematurity, doses may vary and should be determined by a healthcare professional.

Mechanism of action

Caffeine acts primarily as an antagonist of adenosine receptors, inhibiting the action of adenosine, which normally promotes sleep and relaxation. This antagonism leads to increased neuronal firing and the release of neurotransmitters such as dopamine and norepinephrine. Caffeine also inhibits phosphodiesterase enzymes, enhancing levels of cyclic AMP and cyclic GMP, which are important for various cellular functions. Additionally, in the context of respiratory function, caffeine stimulates the respiratory centers in the central nervous system, enhancing ventilation.

Pharmacodynamics

Caffeine stimulates the central nervous system, increasing alertness and reducing fatigue. It relaxes smooth muscles, increases cardiac muscle contraction, and can enhance physical performance. Caffeine also promotes gastric acid secretion and gastrointestinal motility, and it exhibits mild diuretic properties. Its effects can lead to restlessness and agitation in some individuals, particularly at higher doses.

Pharmacokinetics

Caffeine is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 30 to 120 minutes after ingestion. It is distributed widely throughout body tissues, readily crossing the blood-brain barrier. Caffeine is metabolized primarily in the liver by cytochrome P450 1A2, producing three primary metabolites: paraxanthine, theobromine, and theophylline. The elimination half-life varies significantly among individuals, influenced by factors such as age, liver function, pregnancy, and the use of certain medications. It is primarily excreted in urine.

Adverse effects

• Restlessness
• Agitation
• Insomnia
• Increased heart rate
• Nausea
• Gastrointestinal discomfort
• Headaches

Interactions

• caffeinecitrate+adenosine: Unknown (decreases efficacy)
• caffeinecitrate+antiarrhythmics: Unknown (decreases efficacy)

Precautions

• Use cautiously in patients with a history of anxiety disorders, insomnia, or cardiac arrhythmias.
• Monitor caffeine intake in individuals with certain medical conditions, such as hypertension.

Pregnancy

Caffeine crosses the placenta; excessive intake during pregnancy may be associated with adverse outcomes. It is generally recommended to limit caffeine consumption.

Breast-feeding

Caffeine is excreted in breast milk; moderate consumption is considered safe, but excessive intake may affect the infant's sleep and behavior.

Storage

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

Formulations

• Tablets
• Oral solutions
• Injectable preparations
• Caffeine citrate

Mechanism of action

The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows: **General and cellular actions** Caffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism. Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP. This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol. **Respiratory** The exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others. The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm. **Central nervous system** Caffeine demonstrates antagonism of all 4 adenosine receptor subtypes (A1, A2a, A2b, A3) in the central nervous system. Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the A2a receptor. **Renal system** Caffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion. **Cardiovascular system** Adenosine receptor antagonism at the A1 receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by 5 to 10 mmHg when it is not taken regularly, versus no effect in those who consume it regularly. The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain. Caffeine competitively inhibits phosphodiesterase, the enzyme that degrades cyclic 3',5'-adenosine monophosphate (AMP). Increased levels of intracellular cyclic AMP mediate most of caffeine's pharmacologic actions. Caffeine stimulates all levels of the CNS... Caffeine's cortical effects are milder and of shorter duration than those of amphetamines. In slightly larger doses, caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. Caffeine constricts cerebral vasculature. In contrast, the drug directly dilates peripheral blood vessels...

Pharmacodynamics

Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance. Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.