Non-steroidal anti-inflammatory drugs

(NSAIDs)and Paracetamol
Both are Prostaglandin synthesis inhibitors
Non-steroidal anti-inflammatory drugs (NSAIDs)
• Group of chemically compounds have the fallowing effects :-
• anti-inflammatory.
• Antipyretic.
• Analgesic actions.
• Antiplatelet action.
• Widely used for mild pain (e.g. musculoskeletal disease, headache, ),
inflammatory disorders (especially musculoskeletal, Arthritis) and
postoperative analgesia and decreases thrombosis.
Paracetamol It has analgesic and antipyretic properties similar to NSAID but
dose not have any anti-inflammatory activity, So it dose not belong to NSAID
Paracetamol consider a weak inhibitor of prostaglandin synthesis.
 Mechanisms of Action
• Arachidonic acid ( part of cell membrane) release
during cellular damage and by aid cyclooxygenase
(COX) enzyme converted to prostaglandin which
is responsible of inflammatory symptom.
• Agents that inhibit COX enzyme reduce
prostaglandin release a called Prostaglandin
synthesis inhibitors and will control fever,
inflammation, pain, and thrombosis.
 COX enzyme is 2 types COX-1 and COX-2, have differing
distribution in tissue.
• COX-1 are widely distributed through out the body,
including the CNS ,gut and platelets.
• COX-2 produced in response to inflammation.
SO :- Prostaglandin synthesis inhibitors( NSAIDs )
Classified into
• Non selective COX inhibitors :- inhibit both types of
enzyme ( aspirin , metfenamic acid, diclofenac
,indomethacin ,ibuprofen)
• selective COX-2 inhibitors : inhibit COX type 2
(acetaminophen [paracetamol], ) .
 Pharmacokinetics
• A. Absorption
All COX inhibitors are well absorbed after oral administration
and all will typically achieve their peak blood concentrations
in less than 3 hours.
• B. Distribution
Their lipid solubility allows them to readily permeate the
blood– brain barrier to produce a central analgesia and
antipyresis,
• C. Biotransformation
Most COX inhibitors undergo hepatic biotransformation. The
agent with the most notable metabolite is acetaminophen
which may produce hepatic failure.
• D. Excretion
Nearly all COX inhibitors are excreted in urine after
biotransformation.
• Effects on Organ Systems
No specific effect other than therapeutic actions mention
before.
• General Side effects:-
GIT disturbance, e.g. nausea, discomfort, diarrhea, bleeding
and ulceration because the loss of protective effect of
prostaglandin on stomach mucosa.
The selective COX-2 inhibitors are associated with a lower risk
GIT disturbance than non-selective NSAIDs.
• Renal impairment may occur with both
selective and non-selective NSAIDs; specially
with prolong period of usage.
• Respiratory system :- exacerbate asthma
• others, e.g. fluid retention, hyperkalemia and
rarely hepatotoxicity
 Aspirin
• Group of non-selective NSAIDs derived from salicylic acid i
• Have anti-inflammatory and antipyretic effects; they inhibit both central and
peripheral synthesis of prostaglandins. They are also used as antiplatelet drugs.
Effects on platelets are irreversible, lasting until new platelets are synthesized (7–
10 days).
• Used for
• mild-to-moderate pain,
• pyrexia.
• Rheumatoid arthritis
• peripheral and coronary artery disease.
• Contraindicated
• children < 16 years because of the risk of Reye’s syndrome.
• patients with peptic ulcer disease
• coagulation disorders or taking anticoagulant drugs.
• Asthma
• Renal impairment.
• ● Dosage:
• ◗ analgesia: 300–900 mg orally 4–6-hourly, up to a total of 4 g daily.
• ◗ secondary prevention of thrombotic cerebrovascular or CVS disease: 75–100 mg
orally .
•
 Diclofenac sodium (Voltarine).
• NSAID, non-selective COX inhibitors commonly used for postoperative
analgesia, reducing opioid requirements and for musculoskeletal pain and
renal colic.
• half-life is 1–2 h. 60% excreted via urine, the rest passing into the bowel.
• ● Dosage:
• ◗ 1 mg/kg (up to 75 mg) via deep IM and IV injection .
• ◗ 75–150 mg/day orally in divided doses
• ● Side effects:
• as for NSAIDs.
• Should be used with caution in renal impairment and asthma.
• Muscle damage after IM injection has been reported.
• Sterile abscesses have occurred after superficial injection
• Should be used with caution in renal
impairment and asthma.
• Muscle damage after IM injection has been
reported.
• Sterile abscesses have occurred after
superficial injection.
 Selective COX-2 inhibitors
Peroxicam (feldin)
Meloxicam (mobic)
• New drugs selectively inhibit COX-2 enzyme and
spare COX-1 enzyme that why called Selective
COX-2 inhibitors
• Have effective anti-inflammatory ,analgesia, but
with fewer side effects than the NSAIDs. their use
is associated with an increased risk of
cardiovascular thromboembolic events as side
effect.
 Ketorolac
• NSAID, for short-term postoperative analgesia.
Has a marked analgesic effect with little anti-
inflammatory effect. Maximal plasma levels
occur within 60 min of IM injection and 5 min of
IV injection, with half-life of 5–6 h.
• Dose Orally 10 mg four times aday
• 15 -30mg IV or IM four times aday
• Specifically, ketorolac does not cause respiratory
depression, sedation, or nausea and vomiting.
Paracetamol ( acetaminophen)
• Analgesic selective COX-2 inhibitors drug,
• Inhibits central prostaglandin synthesis and has a central antipyretic action have
minimal peripheral anti-inflammatory effects.
• Does not cause gastric irritation or affect platelet adhesion.
• Used in isolation to treat minor pain, and postoperative analgesia.
• Rapidly absorbed after oral intake , with peak plasma levels within 60 min. Half-life
is about 2 h.
• Paracetamol has fewer side effects than theNSAIDs, and can be used in (asthma,
peptic ulcers, bleeding diathesis).
• ● Dosage:
• ◗ 0.5–1.0 g orally/rectally 4-hourly, up to 4 g maximum daily.
• ◗ an iv preparation 1 g 4–6-hourly up to 4 g daily.
• Available in combination with other analgesics, e.g. codeine, tramadol.
• ● Side effects:
• nausea, vomiting, rashes.
• Paracetamol poisoning, is rare lethal condition accrue with very large dose if
>150 mg/kg is lead to hepatic failure.
•