Transcript Case 5

CLINICAL CASES
Chen,Chun-Huang(Alex)
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.
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?
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.
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.
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
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 sideeffect 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.
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.
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:
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
Anser A
Aspirin, as with many older drugs, has proven to
be useful in many conditions. Despite its wellknown 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)
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)
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.
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
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.
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)
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.
Symptoms
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
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.