B/28. NSAIDs, except acetylsalicylic acid. Non-opioid and adjuvant analgesics. Drugs used for treatment of gout. Treatment strategy of pain.

Question 1

drugs need to know in this topic

Answer 1

Ibuprofen

Indomethacin

Naproxen

Diclofenac

Metamizole

Ketoprofen

Phenylbutazone

Meloxicam

Paracetamol

Celecoxib

Question 2

Ibuprofen

Answer 2

1. Analgesic use in children (widely-used)
2. Used to induce ductus arteriosus closure

Question 3

Indomethacin

Answer 3

1. Control of acute gout
2. Used to induce ductus arteriosus closure
3. Potential bone marrow suppression – thrombocytopenia, agranulocytosis

Question 4

Naproxen

Answer 4

1. Management of dysmenorrhea – menstrual cramps (the drug induces uterine relaxation)
2. Control of acute gout
3. Long serum T1/2

Question 5

Diclofenac

Answer 5

1. Topical/oral
2. Accumulates in synovial fluid – widely used in pain of musculoskeletal origin (ex. back pain, disc herniation, osteoarthritis)
3. Potential prothrombotic risk
4. Prescription-only drug

Question 6

Metamizole

Answer 6

∙Strong analgesic and antipyretic
∙safe GI profile
∙relaxes smooth muscles
∙alleviate visceral pains
∙limited use due to hemotologic side effect(agranulocytosis)

Question 7

Ketoprofen

Answer 7

inhibit LOX enzyme (leukotrienes ↓)

Question 8

Phenylbutazone

Answer 8

1. Potent anti-inflammatory effect
2. Severe adverse effects – aplastic anemia (continuous use is limited for up to 1 week; withdrawn from market in some
   countries)

Question 9

Meloxicam

Answer 9

1. Inhibitory effect: COX-2 > COX-1
2. Widely used to treat arthritis (rheumatic diseases, osteoarthritis)

Question 10

Paracetamol

Answer 10

1. effective analgesic, especially when administered i.v., useful in a broad range of clinical conditions.
2. Antipyretic
3. Analgesic
4. No anti-inflammatory effect
5. Hepatotoxicity due to acetaminophen overdose → leading to NAPQI build-up.

Question 11

Celecoxib

Answer 11

1. Selective, reversible inhibition of COX-2 enzyme
2. Not more effective than the non-selective COX inhibitors
3. Oral
4. Hepatic metabolism
5. Analgesic
6. Anti-pyretic
7. Anti-inflammatory

Question 12

Non-opioid and adjuvant analgesics

Answer 12

Mechanism of action
1. Analgesic and antipyretic effects (equivalent to ASA) – due to inhibition of cyclooxygenases in the CNS
2. No inhibition of COX in peripheral tissues – lacks significant anti-inflammatory effects
3. No antiplatelet effects
Indications
1. Analgesic and antipyretic agent
2. Aspirin substitute; mainly in children with viral infection or those with aspirin
hypersensitivity (acetaminophen does not carry risk to develop Reye syndrome)
Pharmacokinetics
1. Oral
2. Hepatic metabolism
3. T1/2 2-3 h’
Side effects
*Acetaminophen is safe at therapeutic doses of < 4 g/day (adult weight)
1. Hepatotoxicity → nausea, vomiting, abdominal pain, and ultimately acute liver failure due to centrilobular necrosis (acetaminophen overdose is
the #1 cause of acute liver failure in western countries)
2. Chronic use of ethanol enhances liver toxicity via induction of P45066
3. Patients with pre-existing liver disease are at higher risk to develop acute liver failure
4. Management of toxicity → N-Acetylcysteine (supplies SH groups), preferably within 12 hours of overdose

Question 13

Management of acute gout attack

Answer 13

goal of treatment is to reduce inflammatory reaction

NSAID’s :Indomethacin, naproxen, sulindac

Corticosteroids: Prednisone

Colchicin

1. Acute gout – high doses required (use is limited due to severe diarrhea)
2. Chronic gout – low doses

Question 14

Management of chronic gout

Answer 14

Allopurinol

Rasburicase