Paracetamol

Question 1

NON-STEROIDAL
ANTIINFLAMMATORY DRUGS
Treat ?

Answer 1

NON-STEROIDAL
ANTIINFLAMMATORY DRUGS
* Treat

Question 2

NON-STEROIDAL
ANTIINFLAMMATORY DRUGS MOA?

Answer 2

↓ production of prostaglandins → ↓inflammation, relieve pain,
↓fever

Question 3

Classes of NSAIDs?

Answer 3

1. Irreversible COX inhibitors (Aspirin)
2. Reversible COX inhibitors (non-aspirin NSAIDs)
   A) Non-selective COX inhibitors (e.g. Ibuprofen)
   B) Selective COX-2 inhibitors (e.g. Celecoxib)

Question 4

Irreversible COX inhibitors MAO?

Answer 4

(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)

Question 5

Aspirin ?

Answer 5

Aspirin (acetylsalicylic acid; ASA)
* Irreversible inhibitor of COX-1 & COX-2
* Taken orally

Question 6

MOA (anti-inflammatory)?

Answer 6

in liver; metabolised into salicylate (anti-
inflammatory; no antiplatelet effect); (-) COX-2 →↓prostaglandin
production → ↓inflammation, pain, fever.

Question 7

Irreversible COX inhibitors I?

Answer 7

I: headaches, musculoskeletal pain; short term Tx of chronic pain (e.g.
osteoarthritis, rheumatoid arthritis)

Question 8

Irreversible COX inhibitors CI?

Answer 8

CI: aspirin-associated hypersensitivity, bleeding GI ulcers, hemolytic
anemia, hemophilia, hemorrhoids, lactation, UC, asthma, chronic diarrhea

Question 9

Irreversible COX inhibitors A/E?

Answer 9

AE: angioedema, bronchospasm, GI ulceration/bleeding, hepatotoxicity,
hearing loss, platelet aggregation inhibition, pulmonary edema (non-
cardiogenic)

Question 10

Reversible COX inhibitors types?

Answer 10

Non-selective COX inhibitors &

Question 11

Non-selective COX inhibitors

Answer 11

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)

Question 12

Non-selective COX inhibitors MOA?

Answer 12

MOA: reversibly (-) COX-1 (→ ↓production of thromboxane A2 → (-)
platelet aggregation; transient) & COX-2 (→↓prostaglandin production →
↓inflammation, pain, fever)
✻Same indications as aspirin

Question 13

Ibuprofen?

Answer 13

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)

Question 14

Naproxen ?

Answer 14

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

Question 15

Diclofenac

Answer 15

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

Question 16

Indomethacin

Answer 16

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

Question 17

Ketorolac ?

Answer 17

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

Question 18

Lornoxicam ?

Answer 18

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?

Question 19

Meloxicam

Answer 19

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

Question 20

Mefenamic acid

Answer 20

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

Question 21

Reversible COX inhibitors types?

Answer 21

Selective COX-2 inhibitors &

Question 22

Selective COX-2 inhibitors:

Answer 22

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

Question 23

Celecoxib

Answer 23

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

Question 24

Etoricoxib

Answer 24

I: osteoarthritis, rheumatoid arthritis, gouty arthritis, primary
dysmenorrhea
CI: As for celecoxib
AE: dizziness, headache, palpitations, bronchospasm, gastritis, SJS, tinnitus
Parecoxib
I: preoperative pain

Question 25

PARACETAMOL?

Answer 25

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

Answer 26

CI: severe hepatic or renal disease
DI: oral anticoagulants
AE: neutropenia, thrombocytopenia, hepatotoxicity, nephrotoxicity