CLINICAL CASES

1. CLINICAL CASES Chen,Chun-Huang(Alex)

2. Case NO.5 • An elderly woman with arthritis becomes confused about her medications, and start taking 20 aspirin tablet per day instead of her usual eight. Over several days, she become more agitated and confused, and she develops a ringing in her ears, nausea and vomiting. She is brought to the emergency room where she has a temperature of 103。F, abounding pulse of 130, a blood pressure of 95/65 mmHg, and a respiratory rate of 36 breaths per minute. Her skin is flushed and moist, there is a little urine in her bladder. Her lag test reveal a PCO2 of 30mmHg, and a HCO3 of 18 mEq/L.

3. This woman was taking aspirin for its inflammatory effect. What are its other therapeutic uses? • The t1/2 for aspirin is only a half-hour. Why does it take days for the aspirin toxicity to develop?

4. Aspirin • Aspirin or acetylsalicylic acid (acetosal) is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant ("blood-thinning") effect and is used in long-term low-doses to prevent heart attacks.

5. How it works • Aspirin was the first discovered member of the class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs), not all of which are salicylates, though they all have similar effects and a similar action mechanism.

6. Aspirin suppresses the production of prostaglandins and thromboxanes. This happens because cyclooxygenase, an enzyme that participates in the production of prostaglandins and thromboxanes, is irreversibly inhibited when aspirin acetylates it. This makes aspirin different from other NSAIDS , which are reversible inhibitors. • Prostaglandins are local hormones (paracrine) produced in the body and have diverse effects in the body, including but not limited to transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation

7. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are primarily caused by blood clots, and their reduction with the introduction of small amounts of aspirin has been seen to be an effective medical intervention. The side-effect of this is that the ability of the blood in general to clot is reduced, and excessive bleeding may result from the use of aspirin.

8. More recent work has shown that there are at least two different types of cyclooxygenase: COX-1 and COX-2. Aspirin inhibits both of them. Newer NSAID drugs called COX-2 selective inhibitors have been developed that inhibit only COX-2, with the hope for reduction of gastrointestinal side-effects. • However, several of the new COX-2 selective inhibitors have been recently withdrawn, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the arteries in the body express COX-2, and, by selectively inhibiting COX-2, prostaglandins (specifically PGF2) are downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected.

9. Thus, the protective anti-coagulative effect of PGF2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new COX once aspirin has irreversibly inhibited the enzyme, rendering them "useless": an important difference with reversible inhibitors. • Furthermore, aspirin has 2 additional modes of actions, contributing to its strong analgesic, antipyretic and antiinflammatory properties:

10. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria. • It induces the formation of NO-radicals in the body that enable the white blood cells (leukocytes) to fight infections more effectively

11. Anser A • Aspirin, as with many older drugs, has proven to be useful in many conditions. Despite its well-known toxicity it is widely used, since physicians are familiar with its properties. Indications for its use include: 1.Fever 2.Pain (Especially rheumatoid arthritis arthritis, osteoid osteoma, and chronic pain) 4.Migraine 5.Rheumatic fever (drug of choice)

12. 6.Kawasaki's disease (along with IVIG) 7.Pericarditis 8.If 75-81 mg can be used as preventing the heart attack (Myocardial infarction ) and defending the heart disease to send with about of low medicine amount every day A. Myocardial infarction - in patients with risk factors for cardiovascular disease and defending the heart disease to send with about of low medicine amount every day B.Stroke - as secondary prevention (i.e. to prevent recurrence)

13. Contraindications and warnings 1.allergic to aspirin, ibuprofen or naproxen 2.patients with kidney disease, peptic ulcers, mild diabetes, gout or gastritis 3.Taking aspirin with alcohol 4.Children, including teenagers, are discouraged from using aspirin in cold or flu symptoms as this has been linked with Reye's syndrom 5.Patients with hemophilia or other bleeding tendencies 6.patients with hyperthyroidism avoid aspirin because it elevates T4 levels.

14. Common side-effects 1.Gastrointestinal complaints (stomach upset, dyspepsia, heartburn, small blood loss) 2.Frequently, central effects (dizziness, tinnitus, hearing loss, vertigo, centrally 3.mediated vision disturbances, and headaches). 4.Sweating, seen with high doses, independent from antipyretic action 5.Long-term treatment with high doses,the potentially fatal Reye's syndrome may occur 6.chronic renal failure. 7.Skin reactions, angioedema, and bronchospasm 8.Prolonged and more severe bleeding after operations and post-traumatic

15. Dosage • For adults a maximum of 4000 mg per day, spread over at least 4 doses of at most 1000 mg. For children over 12 years old a maximum of 2000 mg, spread over at least 4 doses of at most 500 mg, with at least 4 hours between doses. Overdose • Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, supratherapeutic doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal with a mortality rate of 25%; chronic overdose may be especially severe in children.

16. ANSER B • t1/2 for aspirin is only a half-hour but aspirin can hydrolysis to the salicylate ,than the salicylate metabolism thought for renal. When eat aspirin reach 600mg in whole body aspirin total content, its metabolism way saturation, after increasing low dose of aspirin will cause increase more salicylate concentration in the blood. • The pt taking 20 aspirin tablet per day instead of her usual eight, she increase more dose, so her renal not enough time to metabolism all salicylate, Next day her still use 20 tables aspirins that cause salicylate was accumulate in her BODY ,several days the salicylate was be more maximal dose ,the pt to be affected by poison.( Chronic overdose)

17. Toxicity • The toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass. Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 to 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg.

18. Tinnitus The belly aches hypokalemia Hypoglycemia and disease State that generate heat It is excessive to take a breath dysrhythmia Make the blood pressure and disease Illusion Kidney failure Confused Apoplexy Stupor Death Symptoms

19. Treatment • Initial treatment of an acute overdose includes gastric decontamination of the patient. This is achieved by administering activated charcoal which adsorbs the aspirin in the gastrointestinal tract, charcoal might not be of significant value. • However, most toxicologists will administer additional charcoal if serum salicylate levels are increasing. Because no antidote to salicylate poisoning.

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