Salicylates Pharmacological propertis,Untoward Effects and Therapeutic uses

 

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Definition of SALICYLATES

Salicylic acid is Non Steroidal Anti-inflammatory Drugs and a very irritant for internal useand various derivatives have been synthesized to be used systemically . The two mos commonly used preparations are sodium salicylate and aspirin ( acetyl salicylic acid

Pharmacological propertis of Salicylates

1 _ Antipyretic Action : Salicylates reduce the body temperature of febrile patients by influencing the thermoregulatory nuclei of the hypothalamus .

2_ Analgesia : Salicylates relieve dull aching pain of low intensity coming from integumental structures ( as muscles and joints ) rather than from viscera . They are not useful in visceral pain and the significance of this is poorly understood .

3 _ Anti-inflammatory Action : Salicylates exert marked anti-inflammatory activity by inhibiting
cyclooxygenase (PG-synthase) and thereby inhibit the synthesis of
prostaglandins which are involved in inflammatory reaction .
4 _ Cardiovascular System : Therapeutic doses of salicylates produce no significant effectson the heart or blood vessels. Large doses produce peripheral vasodilatationdue to direct action on vascular smooth muscle. In toxic doses they produce direct paralysis of vasomotor center.
5_ Gastrointestinal ract : The ingestion of salicylates may produce epigastric distress , nausea and vomiting

6 _ Urate Excretion : The effects of salicylates on uric acid excretion is dose - dependent. Small doses (1-2 gm / day) inhibit proximal tubular secretion of uric acid . in Large doses (over 5 gm/day) inhibit, in addition, the proximal tubular reabsorption of urates and this effect is of greater magnitude than inhibition of urate secretion ; thus uricosuria ensues .
With intermediate doses (2-4 gm /day ) the two effects .
7 _ Blood : Small dose of salicylates ( 75-150 mg/day by mouth ) produces antiplatelet effect by irreversibly inhibiting platelet cycloxygenase

Pharmacokinetics 

Salicylates are mainly metabolized in the liver and excreted in urineas

Untoward Effects and Toxic Manifestations of Salicylates ( Aspirin)

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1_ Intolerance or Hypersensitivity Aspirin : This occurrs in about 2% of patients, common in middle aged females . It may be manifested in
the form of skin rashes and allergic phenomenon as angioneurotic edema, bronchial asthma , anaphylactic shockor thrombocytopenic purpura . Aspirin is the commonest to cause asthma
and great care should be taken when given to asthmatic individuals ; hypersensitivity reactions are noted in 20-25% of such patients .
Hypersensitivity to aspirin is a contraindication to therapy with any of the NSAIDs . The administration of any one of them could provoke life-threatening anaphylactic shock

2 - Reye's Syndrome : Aspirin when given to children and adolescents with febrile viral illness(chicken pox, viral influenza ) there is a great risk of development of Reye's syndromewhich is hepatic injury and
encephalitis . Paracetamol should be preferredfor such febrile illness .

3 - Acute Salicylate Poisoning :
Acute salicylate intoxication requires immediate hospitalization

4 _ Chronic Salicylate Poisoning ( Salicylism ) : Repeated administration of large doses of salicylates as in rheumatic fever, may produce a condition of mild salicylate poisoning termed "salicylism". it is characterized by neurologica ( headache , dizziness ringing in ears and difficulty in hearing , drowsiness ,
lassitude, mental confusion ) and GIT manifestations ( nausea , vomiting and occasionally diarrhea ) . These signs and symptoms disappear on cessation of therapy

Therapeutic uses of Salicylates

1_ Antipyretic : Salicylates can be used in the symptomatic treatment of fever . The effect is non-specific
and salicylates do not affect the cause of the underlying disease . Dose 0.3 - 1 g orally every 4 hours .

2_ Analgesic : The main therapeutic use of salicylates is the relief of certain types of pain as headache ,
arthritis , dysmenorrhea , neuralgia , mylagia . Dose 0.3 - 1 g orally every 4 hours .
3 _ Antiinflammatory : Sodium salicylate and aspirin are equally effective and an adult daily dose of 5 - 8 g is usually given at intervals in 1 g amounts .
4 _ Antiplatelet : Because of the potent effect of low doses of aspirin on platelet function it is used in treatment or prophylaxis of cerebral and coronary artery thrombosis and postoperative deep vein thrombosis ( 325 mg/day or lower )
5 _ Epidemeological : studies have shown that regular and sustained use of aspirin reduces the risk of cancer colon and cancer rectum by about 50% .

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resources and references

The Dentist’s Drug and Prescription Guide
Mea Weinberg and Stuart J. Froum
Stuart L. Segelnick, Consulting Editor