Aspirin, Lecture 2

aspirin
Other names ,acetylsalicylic acid,ASA

Is a salicylate.with analgesic,anti-inflammatory and anti-
pyretic action
It also has anti-platelet action
Its available in several combinations
It is generally misused because of ease of availability
It can cause fatal poisoning in children
pharmacology
Aspirin is acetylated salicylate,other salicylates are non
acetylated
Has a molecular weight of 180.16,pka 3.5,its acidic
Mechanism of action-all the actions of aspirin is due to
both the acetyl and the salicylates portion as well as the
salicylates metabolite
Other salicylates activity is due to the salicylates portion
only
Aspirin inhibits cyclo-oxygenenase to decrease the
precursors of PG and thromboxanes from arachidonic acid
ANALGESIA
Analgesia-this is possible through a peripheral action by
blocking pain impulse generation and via a central action
through the hypothalamus
The peripheral action predominates, and may involve
both PG inhibition and also inhibition of the synthesis or
actions of other substances which sensitize pain receptors
to mechanical or chemical stimulation
ANTI-INFLAMMATORY
ACTION
This is through a peripheral action on the infammed tissue
They may inhibit synthesis of PGs
They may inhibit synthesis or actions of other mediators
of the inflammatory response
They may inhibit leukocyte migration or release or action
of lysosomal enzymes or even other aspects of an
immunological response
Anti-pyretic
Acts centrally through the heat regulating center in the
hypothalamus
This produces peripheral vasodilation,resulting in
increased cutaneous blood flow, sweating and heat loss
The central action may involve inhibition of PG synthesis
at the hypothalamus
Anti-platelet activity
This is possible by aspirin donating an acetyl to the
platelet membrane
Aspirin affects platelet function by inhibiting CO
(cyclooxygenase) in platelets preventing the formation of
aggregating agent thromboxanes A2
This is an irreversible process and persists during the life
of that platelet
Aspirin also inhibits formation of platelet aggregation
inhibitor prostacyclin(prostagladin,I2) in blood vessel, this
is a reversible process
Other actions/effects
It has a G.I.T toxicity, this is because the PGs are
cytoprotective
Because it is acidic the gastric effect may be directly an
irritant effect or an erosive effect
absorption
Is rapid and complete after oral adminstration
Food decreases the rate but not extent of absorption
Different formulations may affect the absorption profiles
Enteric coated tablet have a delayed absorption
distribution
It is distributed in breast milk
Peak concentrations of 173-483mcg per ml have been
obtained after 5 to 8 hrs after maternal ingestion
Protein binding
Is bound to albumin but decrease as
 plasma salicylates concentration increases,
 With reduced plasma albumin concentration
 Renal dysfunction
 pregnancy
Biotransformation-Hydrolysed in the GI,liver and blood
to salicylate
Further metabolism is done at the liver

HALF LIFE-----------------15 to 20 mins
Time to peak concentration--------1 to 2hrs with single
dose
Time to steady-state plasma concentration—increases as
daily doses and plasma concentration are increased
With anti-rheumatic doses may take 7 days
Therapeutic plasma concentrations-for analgesia and
antipyretic activity, 25 to 50mcg per ml these are achieved
with single dose
Anti-inflammatory/antirheumatic—150-300mcg per
ml,there is however wide interpatient variability because
of complex kinetics
With large or repeated doses major metabolic pathways
are saturated, small changes in dosage may result in large
changes in plasma concentration
Time to peak effect---may require 2 to 3wks of
continuous therapy
elimination
Primarily renal as free salicylic acid and conjugated
metabolite
Total salicylates excretion does not increase with dose
Excretion of unmetabolised salicylic acid is increased
with dose
Large inter patient variation exist with the elimination
kinetics
Rate of excretion of total salicylates and quantity of free
salicylic acid are increased in alkaline urine and decreased
in acid urine
precautions
Patients sensitive to aspirin or salicylate containing
compound
Asthmatics patients
Allergic diseases
Avoid in children,risk of reyes disease
Avoid use with drugs that increase risk of bleeding
fertility
Salicylates have caused increased numbers of fetal
resorption in animal studies
pregnancy
There is impaired platelet function with risk of
hemorrhage
Delayed onset and increased duration of labour and
increased blood loss
NOTE-avoid analgesics in the last few weeks
With high doses closure of fetus ductus arteriosus in
utero leading to persistent pulmonary hypertension of
newborn
Kernicterus in jaundiced neonates
breastfeeding
Avoid ,risk of reyes syndrome
Use of high doses over time may impair platelet function
and produce hypoprothrombnemia
Renal and hepatic
impairment
Avoid in severe impairment in renal disease and liver
disese
paediatrics
Its is associated with Reyes syndrome especially children
with febrille illness
Serum salicylate concentration must be monitored in

kawasaki disease
geriatrics
Are more susceptible to the toxic effects because of
reduced renal function
Lower doses are recomended

Side effects
Mild and not frequent
Gi irritation
Increased bleeding time
Bronchospasm and skin reactions in allergic patients
contraindication
Children under 16 yrs
Previous or active peptic ulceration
Haemophillia
hypersensitivity
Drug interactions
Prolonged concurrent use with paracetamol may cause
analgesic nephropathy, renal papillary necrosis, end stage
renal disease, or cancer of the kidney or bladder
Urine acidifiers eg,ammonium chloride,ascorbic acid
decrease aspirin excretion this may lead to toxic
concentrations
Adrenocorticoids and glucocoticoids increase salicylate
excretion ,leads to lower levels,reverse or their decrease
would cause salicylism
Read other interactions
With NSAIDS
With alcohol
With urine alkalinizes
With antacids
With anticoagulants
etc
Medical
problems/contraindications
Bleeding ulcers
Haemorrhagic states
Haemophillia
Angioedema,anaphylaxis
Nasal polyps
Thrombocytopenia
Anemia
Gout
Patient monitoring
Hematocrit determinations
Hepatic function
Serum salicylate concentrations
Patient consultation
Care for those allergic to the medication

Pregnancy
Breastfeeding
Use in pediatrics
Use in elderly
Use with other medications eg anticoagulants,anti-
diabetic may cause hypoprothrombinemia
Other medical conditions eg coagulation disorders,platelet
function disorders
dose
Oral-300-900mg every 4to 6hrs,max 4gm daily
By rectum-450-900mg every 4hrs max 3.6gm daily

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aspirin

Other names ,acetylsalicylic acid,ASA

Further metabolism is done at the liver

Serum salicylate concentration must be monitored in

Lower doses are recomended

Care for those allergic to the medication

By rectum-450-900mg every 4hrs max 3.6gm daily

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