Paracetamol Flashcards
NON-STEROIDAL
ANTIINFLAMMATORY DRUGS
Treat ?
NON-STEROIDAL
ANTIINFLAMMATORY DRUGS
* Treat
NON-STEROIDAL
ANTIINFLAMMATORY DRUGS MOA?
↓ production of prostaglandins → ↓inflammation, relieve pain,
↓fever
Classes of NSAIDs?
- Irreversible COX inhibitors (Aspirin)
- Reversible COX inhibitors (non-aspirin NSAIDs)
A) Non-selective COX inhibitors (e.g. Ibuprofen)
B) Selective COX-2 inhibitors (e.g. Celecoxib)
Irreversible COX inhibitors MAO?
(antiplatelet): (-) COX-1 in platelets → ↓production of thromboxane
A2 (platelet activator) → (-) platelet production of new COX-1; new
platelets → COX-1 enzymes → ↑bleeding time (w/o affecting PT)
Aspirin ?
Aspirin (acetylsalicylic acid; ASA)
* Irreversible inhibitor of COX-1 & COX-2
* Taken orally
MOA (anti-inflammatory)?
in liver; metabolised into salicylate (anti-
inflammatory; no antiplatelet effect); (-) COX-2 →↓prostaglandin
production → ↓inflammation, pain, fever.
Irreversible COX inhibitors I?
I: headaches, musculoskeletal pain; short term Tx of chronic pain (e.g.
osteoarthritis, rheumatoid arthritis)
Irreversible COX inhibitors CI?
CI: aspirin-associated hypersensitivity, bleeding GI ulcers, hemolytic
anemia, hemophilia, hemorrhoids, lactation, UC, asthma, chronic diarrhea
Irreversible COX inhibitors A/E?
AE: angioedema, bronchospasm, GI ulceration/bleeding, hepatotoxicity,
hearing loss, platelet aggregation inhibition, pulmonary edema (non-
cardiogenic)
Reversible COX inhibitors types?
Non-selective COX inhibitors &
Non-selective COX inhibitors
Ibuprofen, diclofenac, flurbiprofen, indomethacin, ketoprofen, naproxen,
lornoxicam, piroxicam, mefenamic acid, ketorolac, phenazone (antipyrine)
✻All taken orally (ketorolac, ibuprofen also parenterally; indomethacin
(rectal susp.), ketorolac (eye drops), phenazone (ear drops only)
Non-selective COX inhibitors MOA?
MOA: reversibly (-) COX-1 (→ ↓production of thromboxane A2 → (-)
platelet aggregation; transient) & COX-2 (→↓prostaglandin production →
↓inflammation, pain, fever)
✻Same indications as aspirin
Ibuprofen?
Ibuprofen
I: Analgesia, inflammation (high dose required for anti-inflammatory
action), ductus arteriosus in premature new-born infants (IV prep.)
CI: hypersensitivity to aspirin/other NSAIDs, active peptic ulceration,
pregnancy (3rd trim.), proctitis/haemorrhoids (suppositories)
AE: epigastric pain, heartburn, dizziness, nausea, rash, tinnitus
Kinetics: A=rapid (85%) reduced by food; bioav. 80-100%; onset 30-60
min; duration 4-6 hr, D=90-99% protein-bound, M=rapidly in liver by
CYP2C9; CYP2C19 substrate, E= t1/2 2-4 hr (adults); 1.6 hr (child 0.25-1 yr)
Naproxen ?
I: Analgesia & inflammation in rheumatic disease, gout, dysmenorrhea
CI: hypersensitivity to aspirin/other NSAIDs, active peptic ulceration,
pregnancy (3rd trim.), proctitis/haemorrhoids
AE: epigastric pain, peptic ulceration, headache, dizziness, rash, tinnitus,
nephrotoxicity, hepatic dysfunction
Kinetics: A= rapid oral; bioav. 95%; onset 30-60 min; duration <12 hr,
D=99% protein-bound, M=in liver via conjugation, E= t1/2 12-15 hr; 95% in
urine as metabolites
Diclofenac
I: pain & inflammation in rheumatic disease, gout
CI: hypersensitivity to aspirin/other NSAIDs, active peptic ulceration,
pregnancy (3rd trim.), proctitis/haemorrhoids (suppositories)
AE: epigastric pain, peptic ulceration, headache, dizziness, rash, tinnitus,
nephrotoxicity, hepatic dysfunction
Kinetics: A=absolute bioav. 55%, D=diffuses into/out of synovial fluid; 99%
protein-bound, M=in liver via glucuronidation, E= t1/2 12-15 hr; in bile
Indomethacin
I: pain & inflammation in rheumatological disorders
CI: hypersensitivity to aspirin/other NSAIDs, active peptic ulceration,
pregnancy (3rd trim.), proctitis/haemorrhoids (suppositories)
AE: as for diclofenac (more than diclofenac on GI), dizziness, drowsiness,
headaches, retinal disturbances (prolonged use)
Kinetics: A= bioav. 100%; onset 30 min; duration 4-6 hr, D=99% protein-
bound, M=in liver, E= t1/2 4.5 hr; 60% in urine; >33% in feces
Ketorolac ?
I: short-term management of moderate postoperative pain
CI: duration >5 days, chronic pain, hypersensitivity to NSAIDs, PUD
AE: dizziness, drowsiness, headaches, GI pain, nausea, dyspepsia,
somnolence
Kinetics: A= bioav. 80-100%; onset 10 min IM, 30-60 min PO; duration 4-6
hr, D=99% protein-bound, M=in liver, E= t1/2 2-6 hr; dialysable; 91% in
urine; 6% in feces
Lornoxicam ?
I: short-term treatment of mild to moderate pain, osteoarthritis,
rheumatoid arthritis
CI: GI bleeding, coagulation disorders, children <18 yrs, known
hypersensitivity to NSAIDs, active peptic ulceration
AE: dizziness, insomnia, migraines, gastritis, N&V, dyspepsia, somnolence,
gastro-esophageal reflux
Kinetics: E= t1/2 3-4 hr?
Meloxicam
I: painful osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute
sciatica
CI: GI bleeding/perforation/ulceration, IBD, heart failure, known
hypersensitivity to NSAIDs
AE: light-headedness, dizziness, insomnia, headache, gastritis,
bronchospasm, rash, renal failure
Kinetics: E= t1/2 20 hr
Mefenamic acid
I: post-traumatic conditions, dysmenorrhea
CI: GI bleeding/perforation/ulceration, IBD, heart failure, known
hypersensitivity to NSAIDs
AE: light-headedness, dizziness, insomnia, headache, gastritis,
bronchospasm, rash, renal failure
Kinetics: A= bioav. Extensive; onset rapid, D=↑protein-bound, M=in liver
via oxidation/conjugation, E= t1/2 2 hr; dialysable; 66% urine; 20-25% feces
Reversible COX inhibitors types?
Selective COX-2 inhibitors &
Selective COX-2 inhibitors:
Celecoxib, etoricoxib, parecoxib, meloxicam
MOA: selectively (-) COX-2 → ↓prostaglandins synthesis → ↓pain +
inflammation
* ↓risk of peptic ulceration; ↓risk of renal failure (or other AE of
NSAIDs); ↑risk of heart attacks, strokes and thrombosis by a relative ↑
in thromboxane
Celecoxib
I: symptomatic treatment of inflammation & pain in osteoarthritis and
rheumatoid arthritis; pain after dental surgery
CI: hypersensitivity to sulphonamides, severe renal/hepatic impairment,
asthma, allergy to NSAIDs, risk to cardiovascular disease, pregnancy
AE: dyspepsia, abd. pain, diarrhea, N&V, flatulence, SJS
Kinetics: A= bioav. undetermined, D=97% protein-bound, M=in liver via
CYP2C9, E= t1/2 11 hr; inactive metabolites in urine and feces
Etoricoxib
I: osteoarthritis, rheumatoid arthritis, gouty arthritis, primary
dysmenorrhea
CI: As for celecoxib
AE: dizziness, headache, palpitations, bronchospasm, gastritis, SJS, tinnitus
Parecoxib
I: preoperative pain
PARACETAMOL?
Administered orally, rectally or IV
MOA: reversibly (-) COX-1 & COX-2 on hypothalamus → ↓prostaglandins
synthesis in CNS → ↓pain + fever
I: fever, mild to moderate pain (e.g. myalgia, headache), post-operative
pain
* Can be co-administered with ibuprofen or morphine (for severe post-
operative pain)
* First-line treatment for children with fever or pain
CI: severe hepatic or renal disease
DI: oral anticoagulants
AE: neutropenia, thrombocytopenia, hepatotoxicity, nephrotoxicity
