Salicylates 化学特性,用途語,生産方法
化学的特性
Aspirin is a weak organic acid and is one of the oldest
known drugs for the relief of fever and pain. Aspirin remains
the standard to which most NSAIDs are compared
for efficacy.
適応症
The salicylates are useful in the treatment of minor
musculoskeletal disorders such as bursitis, synovitis,
tendinitis, myositis, and myalgia.They may also be used
to relieve fever and headache. They can be used in the
treatment of inflammatory disease, such as acute rheumatic
fever, rheumatoid arthritis, osteoarthritis, and certain
rheumatoid variants, such as ankylosing spondylitis,
Reiter’s syndrome, and psoriatic arthritis. However,
other NSAIDs are usually favored for the treatment of
these chronic conditions because of their lower incidence
of GI side effects. Aspirin is used in the treatment
and prophylaxis of myocardial infarction and ischemic
stroke.
作用機序
Aspirin and related salicylates produce their pharmacological
effects predominantly by inhibiting the synthesis
of prostaglandins and to a lesser extent synthesis of the
thromboxanes (implicated in platelet aggregation). The
prostanoids are mediators of inflammatory responses in
many cell types. Aspirin is unique among NSAIDs in
that it irreversibly acetylates COX-1 and COX-2, which
are required for the synthesis of prostanoids from
arachidonic acid. COX-2 is induced during inflammation
and is therefore considered to mediate most inflammatory
responses. Aspirin acetylation of COX-1
permanently inactivates the enzyme, while acetylated
COX-2 is capable of producing 15-HETE. New enzyme
must be synthesized to overcome the effects of aspirin,
which in the case of platelets can take as long as 11 days.
The metabolite of aspirin, salicylic acid, is a reversible
inhibitor of COX. Other NSAIDs have reversible effects
at different sites on COX-1 and on COX-2. In addition,
aspirin interferes with kinin-induced modulation
of the inflammatory response.
臨床応用
Aspirin and related salicylates are the primary treatment
for mild to moderate pain, such as that associated
with headache, joint and muscle pain, and dysmenorrhea.
At higher doses aspirin is an effective analgesic in
rheumatoid arthritis.The analgesic effects
of salicylates are thought to be due to the inhibition
of prostaglandin synthesis in the periphery and to a
less well documented mechanism at cortical areas.
The salicylates are also potent antipyretic agents,
with the exception of diflunisal, which is only weakly active.
Aspirin acts at two distinct but related sites. It decreases
prostaglandin-induced fever in response to pyrogens
and induces a decrease in interleukin-1
modulation of the hypothalamic control of body temperature.
Thus, the hypothalamic control of body temperature
returns, vasodilation occurs, heat dissipates,
and fever decreases. Other uses of aspirin include inhibition
of platelet aggregation via inhibition of thromboxanes,
which has been shown to decrease the incidence
of blood clots, myocardial infarction, and
transient ischemic attacks.
副作用
The most commonly observed side effects associated with the use of salicylates relate to disturbances of the GI tract. Nausea, vomiting, epigastric discomfort, intensification of symptoms of peptic ulcer disease (e.g., dyspepsia
and heartburn), gastric ulcerations, erosive gastritis, and GI hemorrhage occur in individuals on high doses of
aspirin. The incidence of these side effects is more rare at low doses, but a single dose of aspirin can cause GI
distress in 5% of individuals.
薬物相互作用
The salicylates displace a number of drugs from plasma
protein binding sites, thereby leading to potential adverse
effects by these agents. Since aspirin is an over-thecounter
medication, patients may fail to inform the
doctor of their aspirin consumption. Anticoagulants are
potentiated by aspirin by displacement of the anticoagulants
from plasma proteins and the intrinsic anticoagulant
effect of aspirin. Thus, the dosage of drugs
such as coumarin and heparin should be reduced in
patients taking aspirin. A similar effect is observed in
patients taking oral sulfonylureas (Orinase, DiaBeta)
for non–insulin-dependent diabetes or phenytoin
(Dilantin) for seizures. Displacement of the sulfonylureas or phenytoin from plasma binding necessitates a decrease
in dosage to prevent an acute hypoglycemic event
or sedation, respectively.Aspirin enhances the effects of
insulin (leading to hypoglycemia), penicillins and sulfonamides
(increasing acute toxicity), and corticosteroids.
Aspirin increases the hypotensive effects of the cardiac
drug nitroglycerin but decreases the effectiveness of the
loop diuretics. In patients taking methotrexate for cancer
chemotherapy, aspirin may increase retention of the
drug, and severe toxicity may result.
Conversely, certain drugs modify the effectiveness
or side effects of aspirin. Phenobarbital, occasionally
used for seizures, induces liver enzymes that increase the
metabolism and excretion of aspirin, β-adrenoceptor–
blocking drugs, such as propranolol, and decrease the antiinflammatory
effects of aspirin, whereas reserpine decreases
its analgesic effects. Antacids decrease the absorption
of aspirin. Alcohol consumption in combination
with aspirin increases the latter’s ulcerogenic effects.
Salicylates 上流と下流の製品情報
原材料
準備製品