Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MSS > MSS24 Non-opioid Analgesics > Flashcards

MSS24 Non-opioid Analgesics Flashcards

1
Q

Non-opioid analgesics

A
  1. Paracetamol / Acetaminophen
  2. NSAIDs
    - traditional NSAIDs
    - selective COX-2 inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Paracetamol

A
  1. Analgesic effect
    - -> Mild to Moderate pain preferred
  2. Therapeutically safe
    - -> minor allergic reactions, skin rash
  3. Liver +/- Kidney damage
    - -> only at toxic dose
    - -> normally metabolised by **CYP450 to **NAPQI (toxic intermediate)
    - -> then conjugated with ***glutathione (GSH)
    - -> non-toxic metabolite
  • GSH depletion (fasting/malnutrition) / CYP enzyme induction (heavy alcohol consumption)
  • -> driven to generate toxic metabolite
  • -> liver cell death
  • Risk reduced by treatment with ***N-acetylcysteine (another antioxidant substitute)
    4. Lack of anti-inflammatory effect

Acetaminophen-induced asthma:

  • -> taking paracetamol > once a month
  • -> higher risk of asthma
  • -> used up glutathione (antioxidants)
  • -> ***oxidative stress in lungs
  • -> precipitate asthma in children
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

NSAIDs

A

Inhibit activity of cyclooxygenase (COX)
—> ↓ ***Prostanoids production

  1. Anti-inflammatory effect —> ***↓ Vasodilatation and vascular permeability —> ↓ oedema, swelling and redness
  2. Analgesic effect —> ***↓ Sensitisation of pain nerve endings —> ↓ low to moderate pain arisen from integumental structures
  3. Anti-pyretic effect —> ***↓ Set-point of the hypothalamic thermoregulatory centre —> relieve fever
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Immune response and How to ensure immune response continue

A

Pathogens

  • -> bind to receptors on surface of Macrophage / Dendritic cells
  • -> Pro-inflammatory cytokines (IL-1, TNFα)
  • -> ***Vasodilatation + ↑ Vascular permeability + Expression of adhesion molecules (attract WBC)
  • -> ↑ Blood flow in post-capillary venule

Trigger:

  1. Complement cascade
    - spasmogen (causing contraction of smooth muscle)
    - chemotaxis
    - phagocytosis
    - lysis of bacteria
    - releases ***Histamine
  2. Plasma fibrinogen move into tissue
  3. Factor 12a move into tissue
    - Coagulation cascade
    - Fibrinolytic cascade
    - Kinin cascade –> ***Bradykinin
    - -> ↑ vascular permeability
    - -> spasmogen
    - -> pain
    - -> generates Eicosanoids (NSAID target), Nitric oxide
    - -> vasodilatation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Prostanoids

A
  1. Prostaglandins
    - PGE2 in macrophages
    - PGD2 in mast cells
  2. Prostacyclin
    - PGI2 in endothelial cells
  3. Thromboxane
    - TXA2 in platelets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Synthesis of prostanoids in inflammation

A

Cell membrane phospholipid
—(Phospholipase A2)—>
Arachidonic acid
1. —(Lipoxygenase)—> Leukotriene
2. —(COX-1: GI, platelets, kidneys)—> Prostanoid (TXA2 in platelet)
3. —(COX-2: inflammatory sites)—> Prostanoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

***Role of prostanoids in inflammation

A
  1. ***Dilate precapillary arterioles
    - -> ↑ blood flow
    - -> Redness (紅)
  2. Cause greater ↑ permeability of postcapillary venules induced by Histamine + Bradykinin (enhance effects of histamine, bradykinin)
    - -> Swelling (腫)
  3. Potentiate pain production by Bradykinin
    - -> Pain (痛)
  4. Affect hypothalamic thermoregulatory centre
    - -> Fever (熱)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

***Mechanism of NSAID

A

Inhibit COX-1, COX-2
–> ↓ formation of prostanoids

  1. ↓ Vasodilatation + ↓ Vascular permeability
    - -> ↓ edema, swelling, redness (anti-inflammatory effect)
  2. ↓ Sensitization of pain nerve endings
    - -> ↓ **low to moderate pain arisen from **integumental (cutaneous) structures (analgesic effect) (NOT effective in visceral pain)
  3. ↓ Set-point of hypothalamic thermoregulatory centre
    - -> relieve fever (antipyretic effect)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

***Adverse effect of NSAID

A
  1. GI disturbance (dyspepsia, diarrhoea/constipation, NV)
    - chronic user –> gastric damage (haemorrhage, ulceration)
    - due to inhibition of prostaglandin production in GI tract
    - -> ***↓ gastric mucus secretion
    - -> ↑ gastric acid secretion
    - -> CI in gastric ulcer patient
  2. Prolonged bleeding (esp. Aspirin)
    - due to inhibition of TXA2 production in platelets
    - -> ↓ platelet aggregation
  3. Renal insufficiency
    - due to inhibition of prostanoids production in kidneys
    - -> impair regulation of ***renal blood flow (minor role, major role: RAAS system –> CVS patient, renal patient more susceptible)
    - reversible in susceptible patients at therapeutic doses
    - irreversible analgesic-associated nephropathy in chronic user
  4. Skin reactions (rashes, urticaria/hives, photosensitivity)
  5. Liver disorder (less common)
  6. Bronchospasm (less common)
    - due to leukotriene production in airway
    - -> can give 5-Lipoxygenase inhibitor (Zileuton) / Leukotriene antagonist (Montelukast)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Aspirin

A
  • **Irreversible inhibition of COX (other NSAID: reversible)
  • -> ↓ TXA2 production in platelets
  • -> inhibition of platelet activation persist for 8-10 days (lifetime of platelet) (since platelets incapable of synthesizing new COX)
  • -> antiplatelet effect for 8-10 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

***Precaution of NSAID

A
  1. Elderly (↑ age, ↑ risk)
  2. Pregnancy (esp. close to terms e.g. >32 weeks –> impaired fetal circulation and ↑ risk of postpartum haemorrhage)
  3. Pre-existing condition (**gastric ulcer, **renal disease, cirrhosis, asthma)
  4. Current medication
    - Anticoagulants (heparin / warfarin) –> **prolonged bleeding
    - ACE inhibitor –> both causes **    hyperkalemia –> arrhythmia
    - **Protein-bound drugs (warfarin, sulfonylureas) –> NSAID highly protein bound –> displace other drugs
    - Anti-inflammatory **    glucocorticoid (↑ risk of gastric bleeding)
  5. Combination with OTC NSAIDs (aspirin, naproxen, ibuprofen, ketoprofen)
  6. Surgical treatment
    - discontinue NSAID for period of 5x t1/2 prior
    - Aspirin: > 2 weeks prior since its effect determined by platelet turnover rate (irreversible inhibition of COX) rather than t1/2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

***Classification of tNSAIDs

A
  1. Salicylate
    - Aspirin (metabolised in body to give free salicylate) —> COX-1 selective
    - Diflunisal
  2. Propionic acids
    - Ibuprofen
    - Naproxen
  3. Acetic acids
    - Indomethacin —> COX-1 selective
    - Sulindac
  4. Oxicams
    - Piroxicam
  5. Fenamates
    - Meclofenamic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Salicylate toxicity

A

0-50 mg/dL:

  • anti-inflammatory
  • anti-pyretic
  • anti-platelet
  • analgesic
  • ***uricosuric (↑ excretion of uric acid)

Complications:

  • gastric intolerance
  • bleeding
  • hypersensitivity

> 50 mg/dL: Intoxication

Mild salicylism
50-80:
- tinnitus (ringing in ears), central hyperventilation

Moderate
80-110:
- fever, dehydration, metabolic acidosis

Severe
110-160:
- vascular collapse, coma, ***hypoprothrombinemia

Lethal
>160:
- renal + respiratory failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

***Precautions with salicylates

A
  1. Children with viral illness fever
    - ***Reye’s syndromes –> brain, liver damage (unknown mechanism)
  2. Pre-existing conditions
    - Compromised cardiac function
    - -> Salicylate: **direct vasodilator effect + **↑ retention of Na, water
    - -> ↑ cardiac output, workload
    - -> **congestive heart failure, pulmonary edema
    - **    Hypoprothrombinemia / **Vit K deficiency
    - **    Gout (Gout flare)
  3. Current medications
    - ***Uricosuric agents (Probenecid / Sulfinpyrazone)
    - Penicillin (block its active transport in proximal tubule)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Aspirin

A
  • low cost
  • long history of safety
  • most commonly used for reducing pain
  • recently consider as CVS drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Diflunisal

A
  • ***lack of antipyretic effect (big molecule: cannot go through BBB, cannot affect CNS)
  • more potent than aspirin
  • ***no salicylate intoxication
17
Q

Comparions of different tNSAIDs

A

Difference in therapeutics / SE due to COX1/2 inhibition

  1. Salicylate:
    Good:
    - low cost, long history of safety (Aspirin)
    - less GI irritation (Diflunisal, compared to Aspirin)
    Bad:
    - upper GI disturbance (Aspirin)
    - ***no antipyretic effect (Diflunisal)
  2. Propionic acid:
    Good:
    - low toxicity (Ibuprofen, Naproxen)
3. Acetic acid:
Good:
- longer t1/2 (Sulindac)
Bad:
- upper GI disturbance (Indomethacin)
- very potent, ***greater toxicity due to other COX-independent actions (Indomethacin)
  1. Oxicams:
    Good:
    - longer t1/2 (Piroxicam)
  2. Fenamates:
    Meclofenamic acid: NA
18
Q

COX-1 vs COX-2

A 
COX-1:
Constitutive (Physiological functions)
- GI tract
- platelet
- kidneys

COX-2:
Inducible (NOT normally present)
- inflammatory sites

19
Q

Selective COX-2 inhibitor

A
  1. Celecoxib
  2. Rofecoxib
    - -> low IC50 for COX-2 (low dose can achieve 50% inhibition of COX-2)
  • Anti-inflammatory, Analgesic, Antipyretic effects
  • ***↓ GI adverse effects
  • ***NO effect on platelet
  • ***renal insufficiency (COX-2 constitutively active in kidneys in susceptible patients)
  • ***CVS thrombotic events?
20
Q

Selectivity of tNSAID compared to Aspirin

A
  • Aspirin: COX-1 selective –> good for antiplatelet effect
  • Diflunisal: ↑ COX-2 selectivity
  • Ibuprofen: ↑ COX-2 selectivity
  • Naproxen: ↑ COX-2 selectivity
21
Q

CVS thrombotic events relating to selective COX-2 inhibitor

A

Normally:
COX-1
–> Prostacyclin PGI2 in endothelial cells
–> inhibit adhesion + activation of platelet
–> balance / antagonise effect of TXA2 (also by COX-1)
–> balance in intact blood vessel (no blood clot form)

Some patients with concurrent condition

  • -> insufficient COX-1
  • -> induced COX-2
  • -> if COX-2 inhibited
  • -> less PGI2 to prevent adhesion (PGI2 can also be produced by COX-2)
  • -> ***TXA2 effect dominate
  • -> adhesion, activation, aggregation
  • -> thrombotic events
22
Q

NSAID with higher selectivity for COX-2 than COX-1

A

tNSAID: Naproxen, Diclofenac
Selective COX-2 inhibitor: Celecoxib, Rofecoxib

–> ALL contain black box warning

23
Q

Choice of NSAIDs

A
  1. ***Efficacy
    - ibuprofen, naproxen, diflunisal more effective than aspirin for anti-inflammatory
  2. Safety
    - ↓ GI complications with ↑ selectivity towards COX-2
    - ***Balance CV risk vs GI risk:
    - -> low GI, low CV risk: tNSAID
    - -> low GI, high CV risk: Naproxen + PPI
    - -> high GI, high CV risk: Naproxen / COX-2 + PPI
    - -> high GI, low CV risk: selective COX-2 inhibitor + PPI
  3. ***Cost-effectiveness
    - celecoxib more expensive than aspirin
  4. Individual differences
    - age, hypersensitivity to aspirin, medications, concurrent illness
    - -> initiate with ***low dose + therapeutic trial of 1-2 week
  5. ***Avoid combinations of NSAIDs
    - additive adverse effects

MSS (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions