Aspirin Research Paper
Aspirin
Aspirin is a salicylate, also known as a non steroidal anti-inflammatory drug (NSAID). It is the generic name of acetylsalicylic acid and is used clinically to treat fever, pain and inflammation as it works by preventing the formation of prostaglandin. Prostaglandin is the active agent that is responsible for the sensitisation at the nerve endings. It can be administered orally, rectally or by intravenous route. (6)
Benzene ring Carboxylic acid Ester Alkane
Aspirin has a pKa of 3.49 and a melting point of 138-140 degrees Celsius. Aspirin molecule’s are insoluble in water that is why it must be sold in a solid form, there are no liquid forms of aspirin available. Aspirin is ionised in the stomach. Aspirin is easily hydrolysed as …show more content…
it contains an ester. Esters are prone to be hydrolysed. (7)
Therefore, aspirin is absorbed quickly by the stomach and the ileum through the process of diffusion. It is a prodrug, that is covered into a salicylate considerably within the liver and also in the stomach, the intestinal mucosa and in the blood. Salicylate is known to be the active metabolite responsible for the majority of anti-inflammatory and analgesic effects, however acetylsalicylate is the active moiety for the antiplatelet-aggregating effect. Gastrointestinal intolerance to salicylate detected in some patients has triggered the development of formulations with enteric coating.
Furthermore, a salicylate distributes quickly into the body fluid compartments and binds to albumin in the plasma. As the total plasma salicylate concentration increases, this leads to the unbound fraction increasing also. Salicylate could cross the placental barrier and be released into breast milk.
As mentioned above, due to aspirin being quickly bio transformed into the active metabolite, it has a very short half-life of between 15-20 minutes.
A salicylate, is mainly metabolised by the liver, due to hepatic conjugation with either glucuronic acid or glycine, in which both have different metabolic pathways. The primary pathway is the conjugation with glycine, which is saturable and approximately 90% of salicylate is metabolised through this pathway with low doses of aspirin. When the maximum capacity of this pathway is achieved, the other pathways with a lower clearance become more important. Therefore, the half-life of the salicylate depends on the significant metabolic pathway used at a given concentration, and with increasing dosage, it becomes longer. A salicylate is known to follow nonlinear kinetics at the upper limit of the dosing range. Certain studies report that there is much inter-subject variation with respect to the relative contribution of the dissimilar salicylate metabolic pathways.
Urinary excretion of an unchanged salicylate accounts for 10% of the full elimination of the salicylate. Elimination of a salicylate is the result of glomerular filtration, active proximal tubular secretion through the organic acid transporters and passive tubular reabsorption. Urinary elimination is clearly pH dependent and as the urinary pH rises from 5 to 8. The amount of free ionised salicylate eliminated is increased from 3% of the total salicylate dose to over 80%, due …show more content…
to ions being trapped in the urine. Salicylate metabolites are also excreted in the urine. (2)
Acetylsalicylic acid (ASA) is an anti-rheumatic, analgesic, antipyretic and anti-inflammatory agent. Aspirins mode of action as an anti-inflammatory and anti rheumatic agent may be due to restriction of synthesis and release of prostaglandins. It produces analgesia by virtue of both a peripheral and CNS effect. Acting centrally, it is known to produce analgesia at a hypothalamic site in the brain. The manner of action for this is not known. Aspirin also acts on the hypothalamus to produce antipyresis; as a result of vasodilation and increased peripheral blood flow heat dissipation is increased. Aspirins antipyretic activity may also be connected to inhibition of synthesis and release of prostaglandins. (3)
Indications: Aspirin is used clinically for the treatment of headache, pyrexia, transient musculoskeletal pain and dysmenorrhoea pyrexia. In cases where inflammatory occurs, most physicians would rather anti-inflammatory treatment with another NSAID, which may be better accepted and more convenient for the patient. Aspirin is used progressively for its antiplatelet properties. Aspirin tablets and also dispersible aspirin tablets are acceptable for most purposes as they act rapidly throughout the body. (1)
DOSE
Aspirin dosage varies depending on the indication. For Anti-Inflammatory conditions such as Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis, the adult dose is 3g a day, which will be divided up into different doses. Spondyloarthropathies may require up to 4g per day, again, divided into doses. For cardiac conditions such as Myocardial Infarction, Ischemic Stroke and Angina Pectoris Prophylaxis, an adult dose is 75-325mg orally once a day. For conditions such as fever and pain, an adult dose is 325mg-650mg either orally or rectally every 4 hours as needed, Patients must not exceed 4g a day. The pediatric dose for anti-inflammatory conditions is initially 60-90mg/kg/day orally, divided into equal doses. Maintenance: 80-100 mg/kg/day orally, again, divided into equal doses. Higher dosages, up to 130mg/kg/day, in some cases may be necessary, but do not exceed 5.4 g/day for children ages 2 to 11 years or less than or equal to 25 kg. For children aged 12 years and over or weigh greater than 25 kg, the initial dose is 2.4-3.6g per day orally in equally divided doses. The maintenance dose is 3.6-5.4 g/day orally in equally divided doses. Again, higher dosages may be necessary in some cases. To treat fever and pain the dose is 10-15 mg/kg orally or rectally every 4-6 hours when required, not to exceed 4 g/day for 2-11 year olds. The dose for 12 years or older is 325-650 mg orally or rectally every 4 hours when required, 4g/day must not be exceeded. For cardiac conditions such as Prosthetic Heart Valves - Mechanical Valves is 6-20mg/kg orally once daily for patients aged over one month. (4)
Side Effects
The main side effects reported from taking aspirin are: generally mild and infrequent but high incidence of gastro-intestinal irritation, slight asymptomatic blood loss. Blood disorders have occurred, confusion, tinnitus , bronchospasm and also skin reactions in hypersensitive patients. (1)
Overdose
Common features of salicylate poisoning include sweating, vomiting, tinnitus, vertigo, dehydration, deafness, warm extremities and also an increase respiratory rate and hyperventilation can occur.
In majority of cases, some degree of acid-base disturbances exist. A mixed respiratory alkalosis and metabolic acidosis with either normal or high arterial pH (normal or decreased hydrogen ion conc.) is usual in adults and children ages 4 years or over. In children aged under 4 years, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Increased acidity in the blood, may increase salicylate transfer across the blood brain barrier.
(8)
Patient counseling
Patients must feel comfortable with taking their medication in order for them to comply and take their medication correctly. Aspirin has many interactions that patients must be aware of. Some of these include:
Alcohol can increase risk of GI ulceration and prolong bleeding time.
Antacids, corticosteroids and urinary alkalinizers can decrease aspirin levels. Carbonic anhydrase inhibitors, such as methotrexate and valproic acid can however increase levels of these drugs.
Heparin, oral anticoagulants may increase risk of bleeding.
Insulin, sulfonylureas Aspirin, when taking more than 2g per day may potentiate glucose lowering. Probenecid, sulfinpyrazone may decrease uricosuric effect. (5)
Aspirin is a salicylate, also known as a non steroidal anti-inflammatory drug (NSAID). It is the generic name of acetylsalicylic acid and is used clinically to treat fever, pain and inflammation as it works by preventing the formation of prostaglandin. Prostaglandin is the active agent that is responsible for the sensitisation at the nerve endings. It can be administered orally, rectally or by intravenous route. (6)
Benzene ring Carboxylic acid Ester Alkane
Aspirin has a pKa of 3.49 and a melting point of 138-140 degrees Celsius. Aspirin molecule’s are insoluble in water that is why it must be sold in a solid form, there are no liquid forms of aspirin available. Aspirin is ionised in the stomach. Aspirin is easily hydrolysed as …show more content…
it contains an ester. Esters are prone to be hydrolysed. (7)
Therefore, aspirin is absorbed quickly by the stomach and the ileum through the process of diffusion. It is a prodrug, that is covered into a salicylate considerably within the liver and also in the stomach, the intestinal mucosa and in the blood. Salicylate is known to be the active metabolite responsible for the majority of anti-inflammatory and analgesic effects, however acetylsalicylate is the active moiety for the antiplatelet-aggregating effect. Gastrointestinal intolerance to salicylate detected in some patients has triggered the development of formulations with enteric coating.
Furthermore, a salicylate distributes quickly into the body fluid compartments and binds to albumin in the plasma. As the total plasma salicylate concentration increases, this leads to the unbound fraction increasing also. Salicylate could cross the placental barrier and be released into breast milk.
As mentioned above, due to aspirin being quickly bio transformed into the active metabolite, it has a very short half-life of between 15-20 minutes.
A salicylate, is mainly metabolised by the liver, due to hepatic conjugation with either glucuronic acid or glycine, in which both have different metabolic pathways. The primary pathway is the conjugation with glycine, which is saturable and approximately 90% of salicylate is metabolised through this pathway with low doses of aspirin. When the maximum capacity of this pathway is achieved, the other pathways with a lower clearance become more important. Therefore, the half-life of the salicylate depends on the significant metabolic pathway used at a given concentration, and with increasing dosage, it becomes longer. A salicylate is known to follow nonlinear kinetics at the upper limit of the dosing range. Certain studies report that there is much inter-subject variation with respect to the relative contribution of the dissimilar salicylate metabolic pathways.
Urinary excretion of an unchanged salicylate accounts for 10% of the full elimination of the salicylate. Elimination of a salicylate is the result of glomerular filtration, active proximal tubular secretion through the organic acid transporters and passive tubular reabsorption. Urinary elimination is clearly pH dependent and as the urinary pH rises from 5 to 8. The amount of free ionised salicylate eliminated is increased from 3% of the total salicylate dose to over 80%, due …show more content…
to ions being trapped in the urine. Salicylate metabolites are also excreted in the urine. (2)
Acetylsalicylic acid (ASA) is an anti-rheumatic, analgesic, antipyretic and anti-inflammatory agent. Aspirins mode of action as an anti-inflammatory and anti rheumatic agent may be due to restriction of synthesis and release of prostaglandins. It produces analgesia by virtue of both a peripheral and CNS effect. Acting centrally, it is known to produce analgesia at a hypothalamic site in the brain. The manner of action for this is not known. Aspirin also acts on the hypothalamus to produce antipyresis; as a result of vasodilation and increased peripheral blood flow heat dissipation is increased. Aspirins antipyretic activity may also be connected to inhibition of synthesis and release of prostaglandins. (3)
Indications: Aspirin is used clinically for the treatment of headache, pyrexia, transient musculoskeletal pain and dysmenorrhoea pyrexia. In cases where inflammatory occurs, most physicians would rather anti-inflammatory treatment with another NSAID, which may be better accepted and more convenient for the patient. Aspirin is used progressively for its antiplatelet properties. Aspirin tablets and also dispersible aspirin tablets are acceptable for most purposes as they act rapidly throughout the body. (1)
DOSE
Aspirin dosage varies depending on the indication. For Anti-Inflammatory conditions such as Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis, the adult dose is 3g a day, which will be divided up into different doses. Spondyloarthropathies may require up to 4g per day, again, divided into doses. For cardiac conditions such as Myocardial Infarction, Ischemic Stroke and Angina Pectoris Prophylaxis, an adult dose is 75-325mg orally once a day. For conditions such as fever and pain, an adult dose is 325mg-650mg either orally or rectally every 4 hours as needed, Patients must not exceed 4g a day. The pediatric dose for anti-inflammatory conditions is initially 60-90mg/kg/day orally, divided into equal doses. Maintenance: 80-100 mg/kg/day orally, again, divided into equal doses. Higher dosages, up to 130mg/kg/day, in some cases may be necessary, but do not exceed 5.4 g/day for children ages 2 to 11 years or less than or equal to 25 kg. For children aged 12 years and over or weigh greater than 25 kg, the initial dose is 2.4-3.6g per day orally in equally divided doses. The maintenance dose is 3.6-5.4 g/day orally in equally divided doses. Again, higher dosages may be necessary in some cases. To treat fever and pain the dose is 10-15 mg/kg orally or rectally every 4-6 hours when required, not to exceed 4 g/day for 2-11 year olds. The dose for 12 years or older is 325-650 mg orally or rectally every 4 hours when required, 4g/day must not be exceeded. For cardiac conditions such as Prosthetic Heart Valves - Mechanical Valves is 6-20mg/kg orally once daily for patients aged over one month. (4)
Side Effects
The main side effects reported from taking aspirin are: generally mild and infrequent but high incidence of gastro-intestinal irritation, slight asymptomatic blood loss. Blood disorders have occurred, confusion, tinnitus , bronchospasm and also skin reactions in hypersensitive patients. (1)
Overdose
Common features of salicylate poisoning include sweating, vomiting, tinnitus, vertigo, dehydration, deafness, warm extremities and also an increase respiratory rate and hyperventilation can occur.
In majority of cases, some degree of acid-base disturbances exist. A mixed respiratory alkalosis and metabolic acidosis with either normal or high arterial pH (normal or decreased hydrogen ion conc.) is usual in adults and children ages 4 years or over. In children aged under 4 years, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Increased acidity in the blood, may increase salicylate transfer across the blood brain barrier.
(8)
Patient counseling
Patients must feel comfortable with taking their medication in order for them to comply and take their medication correctly. Aspirin has many interactions that patients must be aware of. Some of these include:
Alcohol can increase risk of GI ulceration and prolong bleeding time.
Antacids, corticosteroids and urinary alkalinizers can decrease aspirin levels. Carbonic anhydrase inhibitors, such as methotrexate and valproic acid can however increase levels of these drugs.
Heparin, oral anticoagulants may increase risk of bleeding.
Insulin, sulfonylureas Aspirin, when taking more than 2g per day may potentiate glucose lowering. Probenecid, sulfinpyrazone may decrease uricosuric effect. (5)