Aspirin & Nsaid

ASPIRIN & ANTI
INFLAMMATORY DRUGS
DR. RAFIA TABASSUM
ASSISTANT PROFESSOR
DEPT: ANAESTHESIOLOGY, SICU & PAIN
MANAGEMENT,
PUMHSW SBA
KEY POINTS
• INTRODUCTION
• PHARMACOKINETICS & DYNAMICS
• MODE OF ACTION
• CLASSIFICATION
• INDICATIONS
• DOSAGE
• CONTRAINDICATIONS
• ADVERSE EFFECTS
• DRUG INTERACTIONS
INTRODUCTION
• Salicylates and other similar agents
exert antipyretic and analgesic effects,
but it is their anti-inflammatory
properties that make them most useful
in the management of disorders in which
pain is related to the intensity of the
inflammatory process.
PHARMACOKINETICS
• Most of the NSAIDs are highly
metabolized, some by phase I followed by
phase II mechanisms and others by direct
glucuronidation (phase II) alone.
• While renal excretion is the most
important route for final elimination,
nearly all undergo varying degrees of
biliary excretion and reabsorption
(enterohepatic circulation).
• Most of the NSAIDs are highly protein-
bound (∼ 98%), usually to albumin.
PHARMACODYNAMICS
• NSAID anti-inflammatory activity is
mediated chiefly through inhibition of
prostaglandin biosynthesis.
• Aspirin irreversibly acetylates and
blocks platelet cyclooxygenase, while
the non-COX-selective NSAIDs are
reversible inhibitors.
MODE OF ACTION
CLASSIFICATION
INDICATIONS & DOSAGE
CONTRAINDICATIONS
• Irritable bowel syndrome
• Peptic ulcer
• Uncontrolled hypertension
• Kidney disease
• Inflammatory bowel disease (Crohn's
disease or ulcerative colitis
• NSAID hypersensitivity reactions,
e.g. aspirin-induced asthma
• In third trimester of pregnancy
ADVERSE EFFECTS
• Central nervous system: Headaches, tinnitus, and
dizziness.
• Cardiovascular: Fluid retention, hypertension, edema,
and rarely, myocardial infarction, and congestive heart
failure.
• Gastrointestinal: Abdominal pain, dysplasia, nausea,
vomiting, and rarely, ulcers or bleeding.
• Hematologic: Rare thrombocytopenia, neutropenia, or
even aplastic anemia.
• Hepatic: Abnormal liver function tests and rare liver
failure.
• Pulmonary: Asthma.
• Skin: Rashes, all types, pruritus.
• Renal: Renal insufficiency, renal failure, hyperkalemia,
and proteinuria.
DRUG INTERACTIONS
ASPIRIN
• Aspirin’s long use and
availability without
prescription diminishes
its glamour compared
with that of the newer
NSAIDs.
• Aspirin is now rarely
used as an anti-
inflammatory
medication and will be
reviewed only in terms
of its anti-platelet
effects (doses of 81–
325 mg once daily).
PHARMACOKINETICS
• Salicylic acid is a simple organic acid with a pKa of
3.0.
• Aspirin (acetylsalicylic acid; ASA) has a pKa of 3.5.
• The salicylates are rapidly absorbed from the
stomach and upper small intestine yielding a peak
plasma salicylate level within 1–2 hours.
• Aspirin is absorbed as such and is rapidly
hydrolyzed (serum halflife 15 minutes) to acetic
acid and salicylate by esterases in tissue and blood.
• Salicylate is nonlinearly bound to albumin.
• Alkalinization of the urine increases the rate of
excretion of free salicylate and its water-soluble
conjugates.
MECHANISMS OF ACTION
• Aspirin irreversibly inhibits platelet
COX so that aspirin’s antiplatelet
effect lasts 8–10 days (the life of the
platelet).
• In other tissues, synthesis of new COX
replaces the inactivated enzyme so that
ordinary doses have a duration of action
of 6–12 hours.
CLINICAL USES
• Aspirin decreases the incidence of
transient ischemic attacks, unstable
angina, coronary artery thrombosis with
myocardial infarction, and thrombosis
after coronary artery bypass grafting.
• Epidemiologic studies suggest that long-
term use of aspirin at low dosage is
associated with a lower incidence of colon
cancer, possibly related to its COX-
inhibiting effects.
Phases of detoxification
• PHASE I catalysed by the cytochrome P-450-
dependent mixed-function oxidase system.
• Phase I reactions (also termed nonsynthetic
reactions) may occur
by oxidation, reduction, hydrolysis, cyclization,
and decyclization,
• Phase II – conjugation metabolites
are conjugated with charged species such
as glutathione (GSH), sulfate, glycine, or glucuronic
acid.
• Phase III – is the processing of glutathione
conjugates to acetylcysteine (mercapturic acid)
conjugates
• The prostaglandins (PG) are a group
of physiologically active lipid compounds having
diverse hormone-like effects,
• They act as autocrine or paracrine factors with their
target cells present in the immediate vicinity of the site
of their secretion.
• Prostaglandins have two
derivatives: prostacyclins and thromboxanes. Prostacyclins
are powerful locally acting vasodilators and inhibit the
aggregation of blood platelets. Through their role in
vasodilation, prostacyclins are also involved
in inflammation. They are synthesized in the walls of blood
vessels and serve the physiological function of preventing
needless clot formation, as well as regulating the
contraction of smooth muscle tissue.[1] Conversely,
thromboxanes (produced by platelet cells)
are vasoconstrictors and facilitate platelet aggregation.
Their name comes from their role in clot formation
(thrombosis).

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ASPIRIN & ANTI

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