Aspirin about

No drugs have been a more faithful companion to man throughout his history than salicylates, the forebears of aspirin. About 3,500 years ago the Ebers Papyrus recommended the application of a decoction of leaves of myrtle to the abdomen and back to get rid of rheumatic pains. Hippocrates championed the juices of the poplar tree and willow bark to treat fever and labor pains. These plants and trees are abimdant in compounds derived from salicylic acid, which gets its name from them (in Latin salix is a willow tree). For thousands of years on all continents they have helped to... 

Half-life. Plasma half-life, aspirin about 17 minutes, salicylic acid dose-dependent (2 to 4 hours after doses of less than 3 g, increasing to about 19 hours after large doses). 

Volume of Distribution. Aspirin about 0.15 litre/kg, salicylic acid about 0.1 to 0.2 litre/kg (dose-dependent). 

Therefore, the pharmacy should order 490 bottles of aspirin about 2.5 (1200/ 490), times per year (about every 20 weeks). 

The following is an alternative method of purifying the crude aspirin. Dissolve the solid in about 30 ml. of hot alcohol and pour the solution into about 75 ml. of warm water if a sohd separates at this point, warm the mixture until solution is complete and then allow the clear solution to cool slowly. Beautiful needle-like crystals will separate. The yield is 13 g. The air-dried crude product may also be recrystallised from benzene or from ether - light petroleum (b.p. 40-60°). 

Although extraordinary in its powers, aspirin is also more dangerous than commonly believed. Only about 15 g can be fatal to a small child, and aspirin can cause stomach bleeding and allergic reactions in long-term users. Even more serious is a condition called Reye s syndrome, a potentially fatal reaction to aspirin sometimes seen in children recovering from the flu. As a result of these problems, numerous other NSAIDs have been developed in the last several decades, most notably ibuprofen and naproxen. 

Sample mixture. A suitable sample mixture is obtained by weighing out accurately about 0.601 g of aspirin, 0.076 g of phenacetin and 0.092 g of caffeine. Dissolve the mixture in 10 mL absolute ethanol, add 10 mL of 0.5M ammonium formate solution and dilute to lOOmL with de-ionised water. 

Procedure. Inject 1 fiL of the sample solution and obtain a chromatogram. Under the above conditions the compounds are separated in about 3 minutes, the elution sequence being (1) aspirin (2) phenacetin (3) caffeine. Measure peak areas with an integrator and normalise the peak area for each compound (i.e. express each peak area as a percentage of the total peak area). Compare these results with the known composition of the mixture discrepancies arise because of different detector response to the same amount of each substance. 

Aspirin sensitive asthma, affecting about 10% of all asthmatics, is a nonallergic response to aspirin and other agents that inhibit cyclooxygenase-1. Mechanistically, the most likely reasons are lack of bronchoprotective prostaglandin E2 and shunting of arachidonic acid into the leukotriene pathway. 

AIA runs a characteristic clinical course [9]. It is more frequent in women than men, and is unusual in children, beginning in adulthood, on average at the age of 30 years. Rhinorrhea and nasal congestion are usually the first symptoms, subsequently complicated by polyposis. Asthma and aspirin hypersensitivity develop 2-15 years later. Once developed, aspirin intolerance remains through life, although sporadic disappearance of intolerance has been reported. Asthma, characterized by blood and nasal eosinophilia, rims a protracted course despite avoidance of analgesics. In about half the patients, the course of asthma is severe, necessitating use of systemic corticosteroids. 

When the CAST collaborative group performed a meta-analysis of 1ST, CAST, and MAST-I, the trend seen in CAST and 1ST toward a beneficial effect of aspirin on the rate of death or dependency reached the threshold for statistical significance. Early aspirin therapy (160-300 mg/day) conferred an absolute reduction in the rate of recurrent ischemic stroke by 0.7% (7 per 1000 patients treated) (p < 0.001) and reduced the rate of death or dependency by 1.3% (13 per 1000 patients treated) (2p = 0.007). Aspirin caused about 2 hemorrhagic strokes among every 1000 patients treated, but prevented about 11 other strokes or deaths in hospital. 

In 1ST and CAST not all patients underwent brain imaging with CT before randomization. It was estimated that about 800 of the 40,000 included subjects in fact had ICH on subsequent imaging. The investigators found no indication in either trial that aspirin treatment led to a deterioration in clinical condition, leading the CAST group to suggest that the hazard of aspirin use in these patients cannot be large (Fig. 7.3). 

Acute Aspirin Therapy for AF-associated Stroke A combined analysis of the 1ST and CAST trials indicated a 21% RRR (95% Cl —5 to 41) in the frequency of early recurrent stroke associated with acute aspirin therapy compared to placebo in patients with AF. No difference in early mortality or sICH was found. This finding was largely driven by the relatively large (about 25% RRR) benefit observed in the unblinded 1ST, compared to the smaller benefit (5% RRR) observed in the double-blinded CAST. 

Aspirin reduces the risk of death or developing MI by about 50% (compared to no antiplatelet therapy) in patients with NSTE ACS.29 Therefore, aspirin remains the cornerstone of early treatment for all ACS. Dosing of aspirin for NSTE ACS is the same as that for STE ACS (Table 5-2). Aspirin is continued indefinitely. 

There is a rough correlation between the hardnesses and the cohesive energies of molecular crystals as shown by Roberts et al. (1995). These authors studied crystals of 11 pharmaceutical compounds and found a linear correlation between their hardnesses and their cohesive energies. However, the data scatter substantially. The hardnesses range from about 1.0 (aspirin), through 5.0 (sucrose), to 10.0 (anthracene) kg/mm2. 

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