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Scandinavian Formulas
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800-688-2276 |
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Products Intro: |
Product Name:Salicylates
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| Salicylates Basic information |
Product Name: | Salicylates | Synonyms: | Salicylates | CAS: | | MF: | | MW: | 0 | EINECS: | | Product Categories: | | Mol File: | Mol File | |
| Salicylates Chemical Properties |
| Salicylates Usage And Synthesis |
Chemical Properties | 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. | Indications | 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. | Mechanism of action | 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. | Clinical Use | 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. | Side effects | 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. | Drug interactions | 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. | Metabolism | Aspirin itself is an acid with a pKa of 3.5 and is relatively
insoluble in water, while its sodium or calcium
salts have enhanced solubility.Aspirin and related salicylates
are rapidly absorbed upon oral administration,
with most absorption occurring in the small intestine.
The pH of the stomach, a secondary site of drug absorption,
along with the gastric emptying time of the
stomach, determines the rate of absorption of the drug.
Thus, food, which alters gastric emptying time and possibly
the pH of the stomach, will alter absorption of the
drug. Buffering of the drug decreases irritation in the
stomach, increases drug solubility, and therefore may
increase the rapidity of absorption. Enteric-coated aspirin
tablets have a variable rate of dissolution depending
on the preparation but are somewhat useful for prevention
of stomach ulceration and gastric distress.
Absorption of aspirin from rectal suppositories is
slower and more variable than from oral administration.
The peak plasma concentration of aspirin occurs 1
to 2 hours following oral administration. Aspirin is immediately
hydrolyzed by various esterases in the stomach
and in the liver to acetate and salicylic acid. Salicylic
acid is glucuronidated, conjugated to glycine to form
salicyluric acid (the major metabolic pathway), oxidized
to gentisic acid (a minor metabolic pathway), or remains
free as salicylic acid, which is secreted in the
proximal tubule of the kidney. Diflunisal (Dolobid) differs
from other salicylates in that it is not metabolized
to salicylic acid but is rapidly glucuronidated. The conjugated
metabolites of salicylates are inactive.
Salicylic acid is highly plasma protein bound, an effect
that alters the pharmacokinetics of other drugs taken in
combination with aspirin. Salicylates passively diffuse to
all tissues, including breast milk, fetal tissues, and the
CNS.They tend to accumulate, since increases in dose decrease
renal clearance and prolong the half-life of the
drug. Clearance at high doses (>2–4 g/day) is via zero order
kinetics, and the half-life can approach 15 hours.At
lower doses (600–1000 mg/day), clearance depends on
the concentration of glucuronide or glycine available for
conjugation and is a first-order process (half-life of approximately
3–6 hours). However, renal clearance is highly dependent on the pH of the urine; the higher the
pH of the urine, the greater the clearance of the drug.
Alkalinization of the urine is used to increase clearance
of the salicylates in the case of toxicity or overdose. |
| Salicylates Preparation Products And Raw materials |
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