5.1 - Analgesics - Non-Narcotic

Question 1

Analgesics

Answer 1

• Non-narcotic

* Narcotic

Question 2

Non-narcotic

Answer 2

• Nociceptive
  
  • Somatic
  • Visceral

Question 3

Narcotic

Answer 3

Psychogenic/ Affective

Question 3

Para-amino Phenols

Answer 3

• Phenacitin

* Paracetamol

Question 3

– Active form: Paracetamol
– ✖️ used anymore
   - ⬆️ risk of Urinary Tract Cancer
   - ⬆️ risk of acute renal failure
   - methemoglobinemia

Answer 3

Phenacitin

Question 4

– Weak inhibitor of PG synthesis

Answer 4

Paracetamol

Question 5

Paracetamol aka:

Answer 5

– Acetaminophen
– APAP
– Acetyl-p-aminophenol

Question 6

Uses: PARACETAMOL

— Safe to give during pregnancy/ lactation

Answer 6

• Analgesic
- Mgt of MILD pain
- 1st line: Mgt if Osteoarthritis
• Antipyretic

Question 7

S/E: PARACETAMOL

Answer 7

• Mild transaminitis
• SJS-TEN
— SJS: 10% TEN: >30%

Question 8

Toxicity: PARACETAMOL

Answer 8

• Hepatic necrosis

- > 150mg/ kg/ day

Question 9

Maximum Daily Dose: PARACETAMOL

Answer 9

Nmt 4 mg

Question 10

Metabolism: PARACETAMOL

Answer 10

• Glucuronidation (65%)
• Sulfation (30%)
• Oxidation (5%)
 – CYP1A2
  – NAPQI

Question 11

NSAIDs

— All are WEAK organic acids ✖️ Nabumetone

Answer 11

MOA: Inhibition of COX

Question 12

2 Types of COX

Answer 12

• COX 1

* COX 2

Question 13

– Constitutive enzyme
– produced by most cells as part of their function
– synthesis of PGs with maintenance functions
- cytoprotection
- vasodilation

Answer 13

COX 1

Question 14

– Inducible Enzyme
– found in immune cells
– Produced in the setting of inflammation

Answer 14

COX 2

Question 15

‼️‼️‼️

In ENDOTHELIAL cells, COX 2 is constitutive

Answer 15

– synthesis of PGI2 & PGE 2

- Anti-agreggants

Question 16

NSAIDs

Answer 16

– Nonselective COX inhibitors

– Selective/ Specifix COX2 Inhibitors

Question 17

Non-narcotic

Answer 17

• Para-amino phenols

* NSAIDs

Question 18

Nonselective COX Inhibitors

Answer 18

• ASA & Salicylates
• Pyrazole Derivatives
• Pyrrole alkanoic acid derivative
• Indole derivatives
• Fenamates
• Oxicam Derivatives
• Phenyl acetic acid derivatives
• Propionic Acid derivatives

Question 19

ASA & Salicylates

Answer 19

• Pharmacokinetics
• Pharmacodynamics
• S/E

Question 20

Pharmacokinetics

Answer 20

• Absorption

* Excretion

Question 21

Absorption

Answer 21

– Stomach

– Upper part of the SI

Question 22

Elimination

Answer 22

– < 600 mg/ day (1st order)

– > 600 mg/ day (zero order)

Question 23

Pharmacodynamics

Answer 23

* Analgesic * Anti-inflammatory * Anti-pyretic * Antiplatelet * Anticancer

Question 24

Analgesic | — NMT 600 mg/ day

Answer 24

* Peripheral: ✖️PG synthesis | * Central: ✖️ Pain perception in the subcortical sites

Question 25

Anti-inflammatory | — 3.2-4 g/ day

Answer 25

– ✖️ PG synthesis | – ✖️Chemotaxis — cell movement

Question 26

Anti-pyretic — 0.3-2.4 g/ day — 0.3-1.2 g/ day

Answer 26

– ✖️ of response to endogenous pyrogens (interleukin 1) — Central – induces cutaneous vasodilation — Peripheral

Question 27

Antiplatelet | — NMT 325 mg/ day

Answer 27

– Irreversible acetylation (inhibition) of COX in platelets — TXA2 synthesis – ⬇️ dose = ⬆️ Antiplatelet effect

Question 28

Anticancer | — Potential

Answer 28

Reduction of colonic polyps

Question 29

S/E

Answer 29

* GI S/E * Renal * Effdct on serum urate level * CNS Effects * Hypersensitivity reactions * Reye's Syndrome

Question 30

S/E: NON SELECTIVE COX

Answer 30

* GI Intolerance | * Gastritis

Question 31

– Hyperacidity/ dyspepsia – ✖️ mucosal injury – Prevention: Intake of NSAIDs after a FULL meal

Answer 31

GI Intolerance

Question 32

``` – ✔️ mucosal injury – Prevention: - PPIs - H2 blockers - Misoprostol ```

Answer 32

Gastritis

Question 33

Risk Factors: NSAID-INDUCED GASTRITIS

Answer 33

- Advanced Age - ⬆️ dose NSAIDs - Multiple NSAID use - History of PUD - Concomittant use of Corticosteroids - Critical illness

Question 34

Renal S/E: ALL NSAIDs

Answer 34

⬇️ GFR = reversible | — afferent arteriole - constriction

Question 35

‼️‼️‼️

Answer 35

* * NSAIDs nay predisppse pts with pre-existing renal disease to acute rena failure * * NSAIDs ⬇️⬇️ the effects of Diuretics

Question 36

Effect on serum urate level | — C/I: Gout

Answer 36

``` • Aspirin – < 2 g/ day: Hyperuricemia • Salicylates – > 4 g/ day: Uricosurin • Tolmetin ```

Question 37

CNS S/E

Answer 37

* Serum Level | * Clinical Manifestation

Question 38

50-80 mg/ dL

Answer 38

``` • Salicylism - tinnitus - ⬇️ hearing - vertigo • Respiratory ALKALOSIS • Hyperventilation ```

Question 39

80-110 mg/ dL

Answer 39

* Metabolic ACIDOSIS * Hyperthermia * Dehydration

Question 40

110-160 mg/ dL

Answer 40

Hypoprothrombinemia | Bleeding

Question 41

> 160 mg/ dL

Answer 41

Respiratory/ Renal Failure

Question 42

Hypersensitivity Rxn: ALL NSAIDs

Answer 42

NSAID-induced bronchial asthma

Question 43

Reye's Syndrome

Answer 43

• ASA + suring/ after a recent viral infection - hepatic failure - encephalopathy

Question 44

Pyrazolone Derivatives — Anti inflammatory — Analgesic

Answer 44

* PhenylbutazONE * DipyrONE * SulfinoyrazONE

Question 45

– ✖️ NSAID – Uricosuric — tx of gout

Answer 45

Sulfinpyrazone

Question 46

A/E: PYRAZOLONE DERIVATIVES

Answer 46

* Hematotoxocities | * Nephrotoxicities

Question 47

Hematotoxicities

Answer 47

* Agranulocytosis * Aplastic anemia * Theombocytopenia