Brainscape's Knowledge GenomeTM

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


See full index

ACEM Primary Written > Anaesthesia: Pharmacology - NSAIDs and paracetamol > Flashcards

Anaesthesia: Pharmacology - NSAIDs and paracetamol Flashcards

1
Q

Are NSAIDs acid or base? What is the exception?

A

All but one are weak organic acids
Nabumetone is the exception (ketone prodrug which is metabolised to acidic active form)

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

What is the main mechanism of action of NSAIDs? What are four other possible mechanisms of action?

A

Inhibit prostaglandin synthesis via COX enzyme inhibition (may be selective or non-selective; all are reversible except aspirin)

Other possible mechanisms of action include inhibition of chemotaxis, decreased IL-1 production, decreased free radicals, interference with calcium-mediated intracellular events

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

Seven effects of aspirin

A

Analgesia
Anti-pyretic
Anti-inflammatory
Decreased sensitivity of vessels to bradykinin and histamine
Affect lymphokine production by T cells
Reverse vasodilation of inflammation
Inhibition of platelet aggregation (except selective COX-2 inhibitors)

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

Describe the pharmacokinetics of NSAIDs

A

Absorption: most are well-absorbed, absorption not impaired by food
Distribution: mostly highly protein-bound (98%, predominantly to albumin), all can be found in synovial fluid after repeated dosing
Metabolism: most highly metabolised, either by phase I and phase II reactions or directly by glucuronidation (phase II), in part by CYP3A or CYP2C families of P450 enzymes in the liver
Excretion: varying degrees of enterohepatic circulation (corresponds with degree of lower GIT irritation), final excretion predominantly renal

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

List eight adverse effects of NSAIDs by organ system

A
  1. CNS: headache, tinnitus, dizziness, rarely aseptic meningitis
  2. CVS: fluid retention, HTN, oedema, rarely MI or CCF
  3. GIT: abdominal pain, dyspepsia, nausea, vomiting, rarely ulcers or bleeding
  4. Haematologic: rarely thrombocytopaenia, neutropenia, aplastic anaemia
  5. Hepatic: deranged LFTs, rarely liver failure
  6. Pulmonary: asthma
  7. Renal: renal insufficiency, renal failure, hyperkalaemia, proteinuria
  8. Skin: rashes (all types), pruritis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the mechanism and duration of action of aspirin?

A

Irreversible non-selective COX inhibitor
Antiplatelet effect lasts 8-10 days (lifespan of platelet)
In other tissues, synthesis of new COX enzymes replaces inactivated enzyme so half-life is 6-12hrs

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

What is aspirin’s chemical name and active metabolite?

A

Acetylsalicylic acid
Active metabolite is salicylate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

pKa of aspirin and salicylate

A

Aspirin 3.5
Salicylate 3.0

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the concept of “gastric trapping” as it relates to aspirin

A

Weak acid, so is predominantly in its unionised form in acidic environment of the stomach: unionised form is more lipophilic enabling absorption
Aspirin ionises in neutral pH of bloodstream to prevent diffusion back into stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where does the majority of aspirin occur and why?

A

In upper GIT
More readily absorbed in stomach due to “gastric trapping” in setting of acidic pH, however greater total absorption in upper GIT due to large surface area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the pharmacokinetics of aspirin

A

Absorption: well absorbed from stomach and upper GIT, peak concentration 1-3hrs
Distribution: rapidly hydrolysed (serum t1/2 = 15mins) to acetic acid and salicylate by esterases in tissue and blood, non-linearly bound to albumin (saturable: free portion increases with increasing drug concentration)
Metabolism: several pathways after hydrolisation including conjugation with glycine to form salicylurate (50%), glucuronidation (20%), saliacyl glucuronide (10%) and gentisic acid (1%), with 15% excreted unchanged
Excretion: renal (increased by alkalinisation of urine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the main clinical uses of aspirin?

A
  1. Antiplatelet effect (low dose): decreased incidence of TIA, unstable angina, coronary artery thrombosis with MI, thrombosis post CABG
  2. Anti-inflammatory
  3. Anti-pyretic
  4. Analgesia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the relationship between longterm aspirin use and risk of colon cancer?

A

Reduced risk of colon cancer with longterm aspirin use

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

What is Reye syndrome?

A

Syndrome of acute noninflammatory encephalitis and fatty degenerative liver failure in children
Occurs post-viral and associated with aspirin use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the symptoms and signs of aspirin overdose

A

Common features: sweating, tinnitus, blurred vision, tachycardia, hyperthermia, hyperventilation, respiratory alkalosis
Severe overdose: metabolic acidosis, seizures, coma, pulmonary oedema, CV collapse, hypokalaemia, GI bleeding, coagulopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the management of aspirin overdose

A

General supportive care (IVT, monitoring)
In massive ingestion: activated charcoal, gastric lavage, whole bowel irrigation, haemodialysis
In moderate ingestion: IV NaHCO3 for urinary alkalinisation to increase excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which two types of NSAIDs do not have antiplatelet activity?

A

Selective COX-2 inhibitors
Nonacetylated salicylates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When are nonacetylated salicylates indicated?

A

For anti-inflammatory effects where COX inhibition is undesirable (e.g. in asthma, bleeding tendency, renal failure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Four classes of NSAIDs

A
  1. Irreversible non-selective COX inhibitor (aspirin)
  2. Nonacetylated salicylates
  3. COX-2 selective inhibitors
  4. Non-selective COX inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Give two examples of COX-2 selective inhibitors

A

Celecoxib
Meloxicam

21
Q

Give four examples of non-selective COX inhibitors

A

Diclofenac
Ibuprofen
Indomethacin
Naproxen

22
Q

What is the advantage of COX-2 selective inhibitors over non-selective inhibitors?

A

Same anti-inflammatory and analgesia effects with less gastric effects

23
Q

Which NSAID interacts with warfarin?

A

Celecoxib

24
Q

Which non-selective COX inhibitor is “relatively” non-selective?

A

Diclofenac

25
Q

What is the half-life of ibuprofen?

A

2hrs

26
Q

At what dose range does ibuprofen have anti-inflammatory effects?

A

Analgesia in lowers doses
Anti-inflammatory at higher doses >2400mg/day

27
Q

What is the effect of concomitant administration of ibuprofen and aspirin?

A

Ibuprofen antagonises aspirin’s irreversible platelet COX inhibition

28
Q

What are three other mechanisms of action of indomethacin besides COX inhibition?

A

May also inhibit phospholipase A and C, decreased neutrophil migration, and decreased T- and B-cell proliferation

29
Q

What NSAIDs are used for PDA closure?

A

Ibuprofen
Indomethacin

30
Q

Three specific adverse effects of indomethacin

A

Pancreatitis
Renal papillary necrosis
CNS effects: headache, confusion, depression

31
Q

What is the difference in the pharmacokinetics of naproxen in women vs men?

A

Higher free fraction in women

32
Q

What is the relative incidence of ibuprofen compared with aspirin, and of naproxen compared with ibuprofen?

A

Ibuprofen: less GI irritation than aspirin
Naproxen: incidence of GI bleeding low but double that of aspirin

33
Q

What is the urinary excretion of unchanged ibuprofen?

A

<1%

34
Q

Which NSAID is least likely to cause gastric upset?

A

Ibuprofen

35
Q

What is the mechanism of action of paracetamol?

A

Unclear: has antipyretic and analgesic but not anti-inflammatory effects
Weak COX-1 and COX-2 inhibitor in peripheral tissues

36
Q

Describe the pharmacokinetics of paracetamol

A

Absorption: rapidly and completely absorbed, rate of absorption related to rate of gastric emptying, peak concentration 30-60mins
Distribution: poorly bound to plasma proteins, VD 1L/kg, t1/2 2-3hrs (increased in toxicity or hepatic impairment)
Metabolism: 80% via sulfation or glucuronidation to nontoxic metabolites, 10% undergoes phase I hydroxylation to form intermediate metabolite NAPQI which is then either conjugated to glutathione to form nontoxic metabolite or when this pathway is exhausted forms further hepatotoxic metabolites
Excretion: urine (<5% unchanged)

37
Q

Describe the adverse effects of paracetamol (not in overdose)

A

Mild reversible LFT derangement
Dizziness, excitement, disorientation in larger doses
Renal damage in absence of hepatic damage
Rarely haemolytic anaemia, methaemoglobinaemia

37
Q

What dose of paracetamol may be fatal?

A

15g

38
Q

What acute ingestion of paracetamol (in children and adults) is considered potentially toxic?

A

> 150-200mg/kg in children
7g in adults

39
Q

What daily dose of paracetamol is sufficient to produce LFT derangement?

A

4g/day

40
Q

What paracetamol level at 4hrs post ingestion indicates risk of liver injury?

A

> 150mg/L

41
Q

What is the initial presentation seen with acute paracetamol overdose? How does this progress?

A

Usually asymptomatic initially, may have minor GI upset (nausea, vomiting)
After 24-36hrs: evidence of liver injury (transaminitis, hypoprothrombinaemia)
May progress to fulminant hepatic failure: metabolic acidosis, hypoglycaemia, encephalopathy, death

42
Q

How is paracetamol overdose managed? Within what timeframe should it be given?

A

N-acetylcysteine acts as a glutathione substitute to bind toxic NAPQI and prevent its accumulation
Should be given with 8-10hrs of ingestion

43
Q

What pattern of hepatic damage is seen with paracetamol overdose?

A

Centrilobular necrosis

44
Q

Describe the mechanism of action of tramadol

A

Centrally acting synthetic analgesic structurally related to opioids, but acting on both opioid and nonopioid receptors
Also increases 5HT release and inhibits reuptake of 5HT and NA

45
Q

What is the effect of naloxone on tramadol?

A

Tramadol only 30% antagonised by naloxone (suggests other receptors involved in mechanism of action)

46
Q

How is tramadol metabolised?

A

Via CYP2D6

47
Q

Describe four features of tramadol toxicity

A

Seizures
Serotonin syndrome
Nausea
Dizziness

ACEM Primary Written (160 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions