Pharmacological Aspects of Immunology 1 Flashcards
1
Q
Discovery of aspirin
- Rev Edmund Stone (1763)
- White willow (Salix alba)
- Used bark to treat fever and joint pain (mostly post-rheumatic fever)
- Felix Hoffman* (Bayer) (1899)
- … acid ‘Aspirin’
A
- Rev Edmund Stone (1763)
- White willow (Salix alba)
- Used bark to treat fever and joint pain (mostly post-rheumatic fever)
- Felix Hoffman* (Bayer) (1899)
- Acetylsalicylic acid ‘Aspirin’
2
Q
NSAIDS
- Large, chemically diverse family of drugs
- Aspirin
- Propionic acid derivatives - e.g. ibuprofen, naproxen
- Arylalkanoic acids – e. g indometacin, diclofenac
- Oxicams - e.g. piroxicam
- Fenamic acids - e.g. mefanamic acid
- Butazones - e.g. phenylbutazon
A
- Large, chemically diverse family of drugs
- Aspirin
- Propionic acid derivatives - e.g. ibuprofen, naproxen
- Arylalkanoic acids – e. g indometacin, diclofenac
- Oxicams - e.g. piroxicam
- Fenamic acids - e.g. mefanamic acid
- Butazones - e.g. phenylbutazon
3
Q
NSAIDS
- Large, chemically diverse family of drugs
- Aspirin
- Propionic acid derivatives - e.g. …, naproxen
- Arylalkanoic acids – e. g indometacin, diclofenac
- Oxicams - e.g. piroxicam
- Fenamic acids - e.g. … acid
- Butazones - e.g. phenylbutazon
A
- Large, chemically diverse family of drugs
- Aspirin
- Propionic acid derivatives - e.g. ibuprofen, naproxen
- Arylalkanoic acids – e. g indometacin, diclofenac
- Oxicams - e.g. piroxicam
- Fenamic acids - e.g. mefanamic acid
- Butazones - e.g. phenylbutazon
4
Q
Eicosanoid pathways
- Where do NSAIDs act? (antagonise which part?)
A
- NSAIDs are non specifc inhibitors of cyclo-oxygenase
5
Q
NSAIDs are non-selective … inhibitors
A
NSAIDs are non-selective COX inhibitors
6
Q
NSAIDs are …-… COX inhibitors
A
NSAIDs are non-selective COX inhibitors
7
Q
NSAID mechanism of action
- All inhibit …
- Three isoforms
- COX-1 - Constitutive expression – all tissues
- Stomach, Kidney, Platelets, Vascular endothelium
- Inhibition → anti-platelet activity, also side effects
- COX-2 – Induced in inflammation (IL-1)
- Injury, infection, neoplasia
- Inhibition → analgesia and anti-inflammatory actions
- COX-3 – CNS only?
- May be relevant to paracetamol
- COX-1 - Constitutive expression – all tissues
A
- All inhibit cyclo-oxygenase
- Three isoforms
- COX-1 - Constitutive expression – all tissues
- Stomach, Kidney, Platelets, Vascular endothelium
- Inhibition → anti-platelet activity, also side effects
- COX-2 – Induced in inflammation (IL-1)
- Injury, infection, neoplasia
- Inhibition → analgesia and anti-inflammatory actions
- COX-3 – CNS only?
- May be relevant to paracetamol
- COX-1 - Constitutive expression – all tissues
8
Q
NSAID mechanism of action
- All inhibit cyclo-oxygenase
- Three isoforms
- COX-1 - Constitutive expression – … tissues
- Stomach, Kidney, Platelets, Vascular endothelium
- Inhibition → anti-… activity, also side effects
- COX-2 – Induced in inflammation (IL-1)
- Injury, infection, neoplasia
- Inhibition → … and anti-inflammatory actions
- COX-3 – CNS only?
- May be relevant to …
- COX-1 - Constitutive expression – … tissues
A
- All inhibit cyclo-oxygenase
- Three isoforms
- COX-1 - Constitutive expression – all tissues
- Stomach, Kidney, Platelets, Vascular endothelium
- Inhibition → anti-platelet activity, also side effects
- COX-2 – Induced in inflammation (IL-1)
- Injury, infection, neoplasia
- Inhibition → analgesia and anti-inflammatory actions
- COX-3 – CNS only?
- May be relevant to paracetamol
- COX-1 - Constitutive expression – all tissues
9
Q
NSAID mechanism of action
- All inhibit cyclo-…
- Three isoforms
- COX-1 - Constitutive expression – all tissues
- Stomach, Kidney, Platelets, Vascular endothelium
- Inhibition → anti-platelet activity, also … effects
- COX-2 – Induced in … (IL-1)
- Injury, infection, neoplasia
- Inhibition → analgesia and anti-inflammatory actions
- COX-3 – … only?
- May be relevant to paracetamol
- COX-1 - Constitutive expression – all tissues
A
- All inhibit cyclo-oxygenase
- Three isoforms
- COX-1 - Constitutive expression – all tissues
- Stomach, Kidney, Platelets, Vascular endothelium
- Inhibition → anti-platelet activity, also side effects
- COX-2 – Induced in inflammation (IL-1)
- Injury, infection, neoplasia
- Inhibition → analgesia and anti-inflammatory actions
- COX-3 – CNS only?
- May be relevant to paracetamol
- COX-1 - Constitutive expression – all tissues
10
Q
COX-1 is expressed where?
A
Constituitvely expressed in all tissues (Stomach, Kidney, Platelets, Vascular endothelium)
11
Q
Inhibition of COX-1 produces …-… activity and also … …
A
Inhibition of COX-1 produces anti-platelet activity and also side effects
12
Q
Inhibition of COX-… produces anti-platelet activity and also side effects
A
Inhibition of COX-1 produces anti-platelet activity and also side effects
13
Q
Inhibition of COX-… - predominant mechanism for analgesia and anti-inflammatory actions
A
Inhibition of COX-2 - predominant mechanism for analgesia and anti-inflammatory actions
14
Q
Inhibition of COX-2 - predominant mechanism for … and anti-… actions
A
Inhibition of COX-2 - predominant mechanism for analgesia and anti-inflammatory actions
15
Q
COX-2 is induced in …
A
inflammation
16
Q
COX-3 is only expressed in the the … (probably)
A
COX-3 is only expressed in the the CNS (probably)
17
Q
COX-3 may be relevant to which drug?
A
paracetamol
18
Q
Indications for NSAID therapy
- …-term management of pain (and fever)
- As … analgesics (orally and topically)
- mechanical pain of all types
- minor trauma
- headaches, dental pain
- dysmenorrhoea
- As … analgesics (orally, parenterally, rectally)
- peri-operative pain
- ureteric colic
A
- Short-term management of pain (and fever)
- As mild analgesics (orally and topically)
- mechanical pain of all types
- minor trauma
- headaches, dental pain
- dysmenorrhoea
- As potent analgesics (orally, parenterally, rectally)
- peri-operative pain
- ureteric colic
19
Q
Indications for NSAID therapy
- Short-term management of pain (and …)
- As mild … (orally and topically)
- … pain of all types
- minor trauma
- headaches, dental pain
- dysmenorrhoea
- As potent … (orally, parenterally, rectally)
- peri-operative pain
- ureteric …
A
- Short-term management of pain (and fever)
- As mild analgesics (orally and topically)
- mechanical pain of all types
- minor trauma
- headaches, dental pain
- dysmenorrhoea
- As potent analgesics (orally, parenterally, rectally)
- peri-operative pain
- ureteric colic
20
Q
Indications for NSAID therapy
- mainly painkiller, but - As anti-inflammatories (?)
- in g..
- Inflammatory … eg ankylosing spondylitis, rheumatoid arthritis
- mainly painkiller, but - As anti-inflammatories (?)
A
- mainly painkiller, but - As anti-inflammatories (?)
- gout
- Inflammatory arthritis eg ankylosing spondylitis, rheumatoid arthritis
- mainly painkiller, but - As anti-inflammatories (?)
21
Q
Indications for NSAID therapy
- mainly …, but - As anti-… (?)
- gout
- Inflammatory arthritis eg ankylosing spondylitis, rheumatoid arthritis
- mainly …, but - As anti-… (?)
A
- mainly painkiller, but - As anti-inflammatories (?)
- gout
- Inflammatory arthritis eg ankylosing spondylitis, rheumatoid arthritis
- mainly painkiller, but - As anti-inflammatories (?)
22
Q
What % of people use non-prescription NSAIDS?
A
20-30%
23
Q
What % experience serious side-effects from NSAIDS?
A
1-2%
24
Q
How many million’scriptios/year in UK of NSAIDS?
A
25 million
25
Q
How many hospital admissions and deaths from NSAIDs? (yearly)
A
12,000 admissions, 2600 deaths
26
Q
Aspirin
- Use for pain and inflammation limited by
- … toxicity
- … – mechanism obscure, usually reversible
- … syndrome (fulminant hepatic failure in children)
- Anti-platelet effect
- Primary and secondary prevention eg stroke and MI
- Treatment of acute MI and stroke
A
- Use for pain and inflammation limited by
- GI toxicity
- Tinnitus – mechanism obscure, usually reversible
- Reye’s syndrome (fulminant hepatic failure in children)
- Anti-platelet effect
- Primary and secondary prevention eg stroke and MI
- Treatment of acute MI and stroke
27
Q
Aspirin
- Use for pain and inflammation limited by
- GI toxicity
- Tinnitus – mechanism obscure, usually …
- Reye’s syndrome (fulminant hepatic failure in children)
- Anti-… effect
- Primary and secondary prevention eg … and MI
- Treatment of acute MI and …
A
- Use for pain and inflammation limited by
- GI toxicity
- Tinnitus – mechanism obscure, usually reversible
- Reye’s syndrome (fulminant hepatic failure in children)
- Anti-platelet effect
- Primary and secondary prevention eg stroke and MI
- Treatment of acute MI and stroke
28
Q
What is Reye’s syndrome?
A
fulminant hepatic failure in children
29
Q
What is aspirin mainly used for?
A
primary and secondary prevention e.g. stroke and MI, also treatment of acute MI and stroke (anti-platelet effect)
30
Q
What can aspirin cause? (3 things)
A
- GI toxicity
- Tinnitus - mechanism obscure, usually reversible
- Reye’s syndrome (fulminant hepatic failure in children)
*
31
Q
NSAID GI toxicity
- In the GI tract … E2 and I2
- … acid production
- … mucus production
- … blood supply
- NSAID inhibition in stomach and duodenum
- Irritation
- … (gastric 15-30%, duodenal 10%)
- Bleeding
- Similar effect in the colon
- Colitis – esp with local preps e.g. rectal diclofenac
A
- In the GI tract prostaglandins E2 and I2
- Decrease acid production
- Increase mucus production
- Increase blood supply
- NSAID inhibition in stomach and duodenum
- Irritation
- Ulcers (gastric 15-30%, duodenal 10%)
- Bleeding
- Similar effect in the colon
- Colitis – esp with local preps e.g. rectal diclofenac
32
Q
NSAID GI toxicity
- In the GI tract prostaglandins … and I2
- Decrease … production
- Increase … production
- Increase … supply
- NSAID inhibition in stomach and duodenum
- Irritation
- Ulcers (gastric 15-30%, duodenal 10%)
- Bleeding
- Similar effect in the colon
- Colitis – esp with local preps e.g. rectal diclofenac
A
- In the GI tract prostaglandins E2 and I2
- Decrease acid production
- Increase mucus production
- Increase blood supply
- NSAID inhibition in stomach and duodenum
- Irritation
- Ulcers (gastric 15-30%, duodenal 10%)
- Bleeding
- Similar effect in the colon
- Colitis – esp with local preps e.g. rectal diclofenac
33
Q
NSAID GI toxicity
- In the GI tract prostaglandins E2 and …
- Decrease acid production
- Increase mucus production
- Increase blood supply
- NSAID inhibition in stomach and duodenum
- Irritation
- Ulcers (gastric 15-30%, duodenal 10%)
- …
- Similar effect in the colon
- … – esp with local preps e.g. rectal diclofenac
A
- In the GI tract prostaglandins E2 and I2
- Decrease acid production
- Increase mucus production
- Increase blood supply
- NSAID inhibition in stomach and duodenum
- Irritation
- Ulcers (gastric 15-30%, duodenal 10%)
- Bleeding
- Similar effect in the colon
- Colitis – esp with local preps e.g. rectal diclofenac
34
Q
NSAIDS have what affect on prostaglandins? (GI tract prostaglandins E2 and I2)
A
They inhibit them in stomach and duodenum leading to irritation, ulcers (gastric 15-30%, duodenal 10%) and bleeding
35
Q
NSAIDS inhibit GI tract prostaglandins E2 and I2 in stomach and duodenum leading to … (3 things)
A
NSAIDS inhibit GI tract prostaglandins E2 and I2 in stomach and duodenum leading to irritation, ulcers (gastric 15-30%, duodenal 10%) and bleeding
36
Q
NSAID GI toxicity
- … GI …
- Relative Risk 4.7 all users
- Azapropazone = 23.4
- Piroxicam = 18.0
- Small differences between others…
- Biggest risk factor for GI bleed = previous GI bleed
- Also
- Age
- … disease (e.g.rheumatoid disease)
- Steroids
A
-
Upper GI bleeding
- Relative Risk 4.7 all users
- Azapropazone = 23.4
- Piroxicam = 18.0
- Small differences between others…
- Biggest risk factor for GI bleed = previous GI bleed
- Also
- Age
- Chronic disease (e.g.rheumatoid disease)
- Steroids
37
Q
NSAID GI toxicity
- Upper GI bleeding
- Relative Risk 4.7 all users
- Azapropazone = 23.4
- Piroxicam = 18.0
- Small differences between others…
- Biggest risk factor for GI bleed = …
- Also
- …
- Chronic disease (e.g.rheumatoid disease)
- …
A
- Upper GI bleeding
- Relative Risk 4.7 all users
- Azapropazone = 23.4
- Piroxicam = 18.0
- Small differences between others…
- Biggest risk factor for GI bleed = previous GI bleed
- Also
- Age
- Chronic disease (e.g.rheumatoid disease)
- Steroids
38
Q
What is the relative risk for upper GI bleeding for NSAID users?
A
Relative Risk 4.7 all users
39
Q
NSAID GI toxicity
- Upper GI bleeding
- Relative Risk 4.7 all users
- Azapropazone = 23.4
- Piroxicam = 18.0
- Small differences between others…
- Biggest risk factor for GI bleed = previous GI bleed
- Also
- Age
- Chronic disease (e.g.rheumatoid disease)
- Steroids
A
- Upper GI bleeding
- Relative Risk 4.7 all users
- Azapropazone = 23.4
- Piroxicam = 18.0
- Small differences between others…
- Biggest risk factor for GI bleed = previous GI bleed
- Also
- Age
- Chronic disease (e.g.rheumatoid disease)
- Steroids
40
Q
What is the biggest risk factor for GI bleed?
A
previous GI bleed
41
Q
What contributes to risk of NSAID GI toxicity? (3)
A
42
Q
NSAID nephrotoxicity
- Primarily related to changes in glomerular blood flow
- Decreased … … …
- … retention
- Hyperkalaemia
- Papillary …
- Acute renal failure 0.5-1%
- Avoid or dose adjust in renal …
- Avoid in patients likely to develop renal …
A
- Primarily related to changes in glomerular blood flow
- Decreased glomerular filtration rate
- Sodium retention
- Hyperkalaemia
- Papillary necrosis
- Acute renal failure 0.5-1%
- Avoid or dose adjust in renal failure
- Avoid in patients likely to develop renal failure
43
Q
NSAID nephrotoxicity
- Primarily related to changes in glomerular blood flow
- … glomerular filtration rate
- Sodium retention
- Hyper…
- Papillary necrosis
- Acute renal failure …-…%
- Avoid or dose adjust in renal failure
- Avoid in patients likely to develop renal failure
A
- Primarily related to changes in glomerular blood flow
- Decreased glomerular filtration rate
- Sodium retention
- Hyperkalaemia
- Papillary necrosis
- Acute renal failure 0.5-1%
- Avoid or dose adjust in renal failure
- Avoid in patients likely to develop renal failure
44
Q
Acute renal failure in …-…% of people using NSAID
A
Acute renal failure in 0.5-1% of people using NSAID
45
Q
In those with renal failure/likely to develop it, can you use NSAIDS?
A
Avoid or dose adjust in renal failure and avoid in patients likely to develop it
46
Q
Asthma and asprin
- About …% of asthmatics experience bronchospasm following NSAID – perhaps because of … acid is shunted down the 5LPO pathway when COX is inhibited
A
- About 10% of asthmatics experience bronchospasm following NSAID – perhaps because of arachidonic acid is shunted down the 5LPO pathway when COX is inhibited
47
Q
Asthma and asprin
- About 10% of asthmatics experience … following NSAID – perhaps because of arachidonic acid is shunted down the 5LPO pathway when … is inhibited
A
- About 10% of asthmatics experience bronchospasm following NSAID – perhaps because of arachidonic acid is shunted down the 5LPO pathway when COX is inhibited
48
Q
What % of astmatics experience bronchospasm following NSAID?
A
10%
49
Q
Preventing NSAID toxicity
- Is an NSAID the answer (paracetamol, opioids, COX2 inhibitor, non-pharmacological?)
- Consider risk factors eg age, renal impairment, previous peptic ulcer disease
- Avoid or dose adjust in … …
- Consider co-administration of … with proton pump inhibitor
A
- Is an NSAID the answer (paracetamol, opioids, COX2 inhibitor, non-pharmacological?)
- Consider risk factors eg age, renal impairment, previous peptic ulcer disease
- Avoid or dose adjust in renal impairment
- Consider co-administration of gastroprotection with proton pump inhibitor
50
Q
Preventing NSAID toxicity
- Is an NSAID the answer (…, opioids, COX2 inhibitor, non-pharmacological?)
- Consider … …
- Avoid or dose adjust in renal impairment
- Consider co-administration of gastroprotection with … … inhibitor
A
- Is an NSAID the answer (paracetamol, opioids, COX2 inhibitor, non-pharmacological?)
- Consider risk factors eg age, renal impairment, previous peptic ulcer disease
- Avoid or dose adjust in renal impairment
- Consider co-administration of gastroprotection with proton pump inhibitor
51
Q
Which NSAID? – non-selective NSAIDS
A
- Proably the four NSAIDS I’d recommend you know are these
- Ibuprofen available over the counter is demonstrably the least associated with side-effects
- Naproxen is similar but probably slightly more prone to side-effects
- The most widely prescribed NSAID for more severe short term analgesis is probably diclofenac – often referred to by its trade name
- Indomethacin may be slightly more potent again and is generally reserved for specialist use in diseases like gout where marked inflammation ispresent
52
Q
Which NSAID? - non-selective NSAIDS
- Proably the four NSAIDS I’d recommend you know are these
- … available over the counter is demonstrably the least associated with side-effects
- … is similar but probably slightly more prone to side-effects
- The most widely prescribed NSAID for more severe short term analgesis is probably … – often referred to by its trade name
- … may be slightly more potent again and is generally reserved for specialist use in diseases like gout where marked inflammation ispresent
A
- Proably the four NSAIDS I’d recommend you know are these
- Ibuprofen available over the counter is demonstrably the least associated with side-effects
- Naproxen is similar but probably slightly more prone to side-effects
- The most widely prescribed NSAID for more severe short term analgesis is probably diclofenac – often referred to by its trade name
- Indomethacin may be slightly more potent again and is generally reserved for specialist use in diseases like gout where marked inflammation ispresent
53
Q
Which NSAID? - non-selective NSAIDS
- Proably the four NSAIDS I’d recommend you know are these
- … available over the counter is demonstrably the least associated with side-effects
- … is similar but probably slightly more prone to side-effects
- The most widely prescribed NSAID for more … … term analgesis is probably diclofenac – often referred to by its trade name
- Indomethacin may be slightly more potent again and is generally reserved for specialist use in diseases like … where marked inflammation ispresent
A
- Proably the four NSAIDS I’d recommend you know are these
- Ibuprofen available over the counter is demonstrably the least associated with side-effects
- Naproxen is similar but probably slightly more prone to side-effects
- The most widely prescribed NSAID for more severe short term analgesis is probably diclofenac – often referred to by its trade name
- Indomethacin may be slightly more potent again and is generally reserved for specialist use in diseases like gout where marked inflammation ispresent
54
Q
How many different NSAIDS licensed in the UK?
A
- 27 different NSAIDs licensed in the UK, some over the counter
- Toxicity generally increases with analgesic potency
55
Q
NSAID Toxicity generally increases with analgesic …
A
potency
56
Q
Paracetamol (acetaminophen)
- Not classically a member of the … group
- Minimal anti-… effects, but good analgesic/ anti-pyretic
- Very well-tolerated with almost no contraindications
- Mechanism of action is …
- Doesn’t bind COX1 or 2; weak inhibitor of prostoglandin
- May inhibit COX3 (CNS only) but relevance controversial
- Dangerous in overdose
A
- Not classically a member of the NSAID group
- Minimal anti-inflammatory effects, but good analgesic/ anti-pyretic
- Very well-tolerated with almost no contraindications
- Mechanism of action is controversial
- Doesn’t bind COX1 or 2; weak inhibitor of prostoglandin
- May inhibit COX3 (CNS only) but relevance controversial
- Dangerous in overdose
57
Q
Paracetamol (acetaminophen)
- Not classically a member of the … group
- Minimal anti-inflammatory effects, but good …/ anti-pyretic
- … well-tolerated with almost no contraindications
- Mechanism of action is controversial
- Doesn’t bind COX1 or 2; weak inhibitor of prostoglandin
- May inhibit COX3 (CNS only) but relevance controversial
- Dangerous in …
A
- Not classically a member of the NSAID group
- Minimal anti-inflammatory effects, but good analgesic/ anti-pyretic
- Very well-tolerated with almost no contraindications
- Mechanism of action is controversial
- Doesn’t bind COX1 or 2; weak inhibitor of prostoglandin
- May inhibit COX3 (CNS only) but relevance controversial
- Dangerous in overdose
58
Q
Paracetamol (acetaminophen)
- Not classically a member of the NSAID group
- Minimal anti-inflammatory effects, but good analgesic/ anti-…
- Very well-tolerated with almost no …
- Mechanism of action is controversial
- Doesn’t bind … or … ; weak inhibitor of …
- May inhibit … (CNS only) but relevance controversial
- Dangerous in overdose
A
- Not classically a member of the NSAID group
- Minimal anti-inflammatory effects, but good analgesic/ anti-pyretic
- Very well-tolerated with almost no contraindications
- Mechanism of action is controversial
- Doesn’t bind COX1 or 2; weak inhibitor of prostaglandin
- May inhibit COX3 (CNS only) but relevance controversial
- Dangerous in overdose
59
Q
Paracetamol (acetaminophen)
- What are its effects?
- Is it well tolerated?
A
- Minimal anti-inflammatory effects, but good analgesic/ anti-pyretic
- Very well-tolerated with almost no contraindications
60
Q
Paracetamol metabolism
A
61
Q
Paracetamol metabolism
- In overdose, can go from managing paracetamol that is taken to having saturation pathway with production of NAPQI - problem with this is that it is hepatotoxic and causes delayed hepatic … - classic overdose story = present when?
- Overdose is much … common now
A
- In overdose, can go from managing paracetamol that is taken to having saturation pathway with production of NAPQI - problem with this is that it is hepatotoxic and causes delayed hepatic necrosis - classic overdose story = present late (maybe days later) and too late to do anything, potential liver transplant
- Overdose is much less common now - harder to get lots of packs in one go
62
Q
Production of NAPQI leads to what? (paracetamol metabolism)
A
hepatic necrosis - typically present a few days later when it is too late
63
Q
Paracetamol metabolism
- What is used in paracetamol poisoning?
A
- N-acetylcysteine (glutathione precursor)
64
Q
What is used in paracetamol poisoning?
A
N-acetylcysteine (glutathione precursor)
65
Q
Selective COX-2 Inhibitors
- Selective inhibition of COX-2 in vitro and in vivo
- Anti-… and … in humans
- Objective evidence of selectivity (GI, platelets) at > anti-inflammatory doses
- … efficacy (not superior) to non-selective NSAIDs in
- Acute pain
- Dysmenorrhoea
- Inflammatory joint disease
- Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect
- Currently only recommended in high-risk patients and after cardiovascular risk assessment
A
- Selective inhibition of COX-2 in vitro and in vivo
- Anti-inflammatory and analgesic in humans
- Objective evidence of selectivity (GI, platelets) at > anti-inflammatory doses
- Comparable efficacy (not superior) to non-selective NSAIDs in
- Acute pain
- Dysmenorrhoea
- Inflammatory joint disease
- Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect
- Currently only recommended in high-risk patients and after cardiovascular risk assessment
66
Q
Selective COX-2 Inhibitors
- Selective inhibition of COX-2 in vitro and in vivo
- Anti-inflammatory and analgesic in humans
- Objective evidence of selectivity (GI, platelets) at > anti-inflammatory doses
- Comparable efficacy (not superior) to non-selective NSAIDs in
- Acute pain
- Dysmenorrhoea
- Inflammatory joint disease
- Controversy due to apparent increased risk of … – but may have been a result of absence of …-… effect
- Currently only recommended in …-risk patients and after … risk assessment
A
- Selective inhibition of COX-2 in vitro and in vivo
- Anti-inflammatory and analgesic in humans
- Objective evidence of selectivity (GI, platelets) at > anti-inflammatory doses
- Comparable efficacy (not superior) to non-selective NSAIDs in
- Acute pain
- Dysmenorrhoea
- Inflammatory joint disease
- Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect
- Currently only recommended in high-risk patients and after cardiovascular risk assessment
67
Q
Selective COX-2 Inhibitors
- Selective inhibition of COX-2 in vitro and in vivo
- Anti-inflammatory and analgesic in humans
- Objective evidence of selectivity (GI, platelets) at > anti-inflammatory doses
- Comparable efficacy (not superior) to non-selective NSAIDs in
- … pain
- Dys…
- … … disease
- Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect
- Currently only recommended in high-risk patients and after cardiovascular risk assessment
A
- Selective inhibition of COX-2 in vitro and in vivo
- Anti-inflammatory and analgesic in humans
- Objective evidence of selectivity (GI, platelets) at > anti-inflammatory doses
- Comparable efficacy (not superior) to non-selective NSAIDs in
- Acute pain
- Dysmenorrhoea
- Inflammatory joint disease
- Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect
- Currently only recommended in high-risk patients and after cardiovascular risk assessment
68
Q
Selective COX-2 Inhibitors
- Are they superior to non-selective NSAIDs in
- Acute pain
- Dysmenorrhoea
- Inflammatory joint disease
A
- NO - Comparable efficacy (not superior)
69
Q
Why was there controversy with Selective COX-2 inhibitors?
A
- Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect
- Currently only recommended in high-risk patients and after cardiovascular risk assessment
70
Q
Coxibs – GI side-effects
- Which had the highest rate of GI side effects?
A
- Population based retrospective study
- 1.3 million people aged 66 years or older in Ontario
- 365,000 (28%) had a prescription for an NSAID
- NSAIDs had highest rate
71
Q
Corticosteroids
- … (hydrocortisone) – predominant endogenous glucocorticoid
- Carbohydrate and protein …
- Fluid and electrolyte ,,, (mineralocorticoid effects)
- Lipid …
- Psychological effects
- Bone metabolism
- Profound modulator of immune response
A
-
Cortisol (hydrocortisone) – predominant endogenous glucocorticoid
- Carbohydrate and protein metabolism
- Fluid and electrolyte balance (mineralocorticoid effects)
- Lipid metabolism
- Psychological effects
- Bone metabolism
- Profound modulator of immune response
72
Q
Corticosteroids
- Cortisol (…) – predominant endogenous glucocorticoid
- Carbohydrate and protein metabolism
- Fluid and electrolyte balance (mineralocorticoid effects)
- Lipid metabolism
- … effects
- … metabolism
- Profound modulator of … response
A
- Cortisol (hydrocortisone) – predominant endogenous glucocorticoid
- Carbohydrate and protein metabolism
- Fluid and electrolyte balance (mineralocorticoid effects)
- Lipid metabolism
- Psychological effects
- Bone metabolism
- Profound modulator of immune response
73
Q
Corticosteroids - predominant endogenous glucocorticoid = …
A
Cortisol (hydrocortisone)
74
Q
… are the most profound global modulator of the immune response
A
Corticosteroids are the most profound global modulator of the immune response
75
Q
Corticosteroids
- Steroids … immune activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the innate immune system.
- Their onset of action is … and they must be taken regularly
A
- Steroids reduce immune activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the innate immune system.
- Their onset of action is delayed and they must be taken regularly
76
Q
Corticosteroids
- Steroids reduce … activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the … … system. Their onset of action is delayed and they must be taken …
A
- Steroids reduce immune activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the innate immune system. Their onset of action is delayed and they must be taken regularly
77
Q
Immunomodulation by steroids
- Cell …
- Lymphopenia, monocytopenia (redistribution)
- Neutrophilia and impaired phagocyte migration
- Cell …
- T cell hyporesponsiveness
- Inhibited B cell maturation
- Decreased IL1, IL6 and TNFa production (monocytes)
- Widespread inhibition of Th1 and Th2 cytokines
- Inhibition of COX - prostaglandins
- Impaired phagocyte killing
- ↓collagenases, elastases etc
- … effect
- Immunoglobulin levels
- Complement
A
- Cell trafficking
- Lymphopenia, monocytopenia (redistribution)
- Neutrophilia and impaired phagocyte migration
- Cell function
- T cell hyporesponsiveness
- Inhibited B cell maturation
- Decreased IL1, IL6 and TNFa production (monocytes)
- Widespread inhibition of Th1 and Th2 cytokines
- Inhibition of COX - prostaglandins
- Impaired phagocyte killing
- ↓collagenases, elastases etc
-
Don’t effect
- Immunoglobulin levels
- Complement
78
Q
Immunomodulation by steroids
- Cell trafficking
- Lymphopenia, monocytopenia (redistribution)
- Neutrophilia and impaired … migration
- Cell function
- T cell …responsiveness
- … B cell maturation
- … IL1, IL6 and TNFa production (monocytes)
- Widespread inhibition of Th1 and Th2 cytokines
- Inhibition of … - prostaglandins
- … phagocyte killing
- ↓collagenases, elastases etc
- Don’t effect
- Immunoglobulin levels
- Complement
A
- Cell trafficking
- Lymphopenia, monocytopenia (redistribution)
- Neutrophilia and impaired phagocyte migration
- Cell function
- T cell hyporesponsiveness
- Inhibited B cell maturation
- Decreased IL1, IL6 and TNFa production (monocytes)
- Widespread inhibition of Th1 and Th2 cytokines
- Inhibition of COX - prostaglandins
- Impaired phagocyte killing
- ↓collagenases, elastases etc
- Don’t effect
- Immunoglobulin levels
- Complement
79
Q
Immunomodulation by steroids
- What do steroids not effect? (2)
A
- Immunoglobulin levels
- Complement
80
Q
Immunomodulation by steroids
- Cell trafficking
- Lymphopenia, monocytopenia (redistribution)
- …philia and impaired phagocyte migration
- Cell function
- … cell hyporesponsiveness
- Inhibited … cell maturation
- Decreased IL1, IL6 and TNFa production (monocytes)
- Widespread … of Th1 and Th2 cytokines
- Inhibition of COX - …
- Impaired phagocyte …
- ↓collagenases, elastases etc
- Don’t effect
- Immunoglobulin levels
- Complement
A
- Cell trafficking
- Lymphopenia, monocytopenia (redistribution)
- Neutrophilia and impaired phagocyte migration
- Cell function
- T cell hyporesponsiveness
- Inhibited B cell maturation
- Decreased IL1, IL6 and TNFa production (monocytes)
- Widespread inhibition of Th1 and Th2 cytokines
- Inhibition of COX - prostaglandins
- Impaired phagocyte killing
- ↓collagenases, elastases etc
- Don’t effect
- Immunoglobulin levels
- Complement
81
Q
Clinical use of corticosteroids
- To suppress … of all kinds, particularly in … disease but also in … therapy
- Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, … arthritis, systemic lupus … etc etc
- Replacement therapy in hypoadrenalism
- Myriad preparations, and also routes
- Systemic (oral and parenteral)
- Topical (skin, joint injections, inhaled, enteric coated, rectal)
A
- To suppress inflammation of all kinds, particularly in acute disease but also in maintenance therapy
- Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, rheumatoid arthritis, systemic lupus erythematosis etc etc
- Replacement therapy in hypoadrenalism
- Myriad preparations, and also routes
- Systemic (oral and parenteral)
- Topical (skin, joint injections, inhaled, enteric coated, rectal)
82
Q
Clinical use of corticosteroids
- To suppress inflammation of all kinds, particularly in acute disease but also in maintenance therapy
- Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, rheumatoid arthritis, systemic lupus erythematosis etc etc
- Replacement therapy in hypoadrenalism
- … preparations, and also routes
- … (oral and parenteral)
- … (skin, joint injections, inhaled, enteric coated, rectal)
A
- To suppress inflammation of all kinds, particularly in acute disease but also in maintenance therapy
- Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, rheumatoid arthritis, systemic lupus erythematosis etc etc
- Replacement therapy in hypoadrenalism
-
Myriad preparations, and also routes
- Systemic (oral and parenteral)
- Topical (skin, joint injections, inhaled, enteric coated, rectal)
83
Q
Clinical use of corticosteroids
- To suppress inflammation of all kinds, particularly in acute disease but also in maintenance …
- Asthma, … / UC, Eczema, Multiple …, Sarcoid, allergy, rheumatoid arthritis, systemic lupus … etc etc
- Replacement therapy in …adrenalism
- Myriad preparations, and also routes
- Systemic (oral and …)
- Topical (skin, joint injections, inhaled, enteric coated, rectal)
A
- To suppress inflammation of all kinds, particularly in acute disease but also in maintenance therapy
- Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, rheumatoid arthritis, systemic lupus erythematosis etc etc
- Replacement therapy in hypoadrenalism
- Myriad preparations, and also routes
- Systemic (oral and parenteral)
- Topical (skin, joint injections, inhaled, enteric coated, rectal)
84
Q
Corticosteroids as drugs
- Five you should know about… (list)
A
85
Q
Corticosteroids as drugs
- Fill in the table
A
86
Q
Corticosteroids as drugs
- Fill in the table
A
87
Q
Corticosteroids as drugs
- Fill in the table
A
88
Q
Corticosteroids as drugs
- Fill in the table
A
89
Q
Side-effects of steroid therapy
- Predictable from steroid actions
- Early
- Weight …
- … intolerance
- … change
- … of ACTH release
- Later
- Proximal muscle …
- Osteoporosis
- Skin changes
- Body shape changes
- Hypertension
- Cataracts
- Adrenal …
- Early
A
- Predictable from steroid actions
- Early
- Weight gain
- Glucose intolerance
- Mood change
- Suppression of ACTH release
- Later
- Proximal muscle weakness
- Osteoporosis
- Skin changes
- Body shape changes
- Hypertension
- Cataracts
- Adrenal suppression
- Early
90
Q
Side-effects of steroid therapy
- Predictable from steroid actions
- Early
- Weight gain
- Glucose intolerance
- Mood change
- Suppression of … release
- Later
- Proximal muscle weakness
- Osteo…
- Skin changes
- Body … changes
- …tension
- Cataracts
- … suppression
- Early
A
- Predictable from steroid actions
- Early
- Weight gain
- Glucose intolerance
- Mood change
- Suppression of ACTH release
- Later
- Proximal muscle weakness
- Osteoporosis
- Skin changes
- Body shape changes
- Hypertension
- Cataracts
- Adrenal suppression
- Early
91
Q
Prednisolone
- Prednisolone is a type of medicine known as a …
- … potency
- Good lipid solubility
- Anti-…
- Oral steroid, also available as enemas
A
- Prednisolone is a type of medicine known as a corticosteroid or steroid.
- Medium potency
- Good lipid solubility
- Anti-inflammatory
- Oral steroid, also available as enemas
92
Q
Prednisolone
- Prednisolone is a type of medicine known as a corticosteroid or steroid.
- Medium potency
- … lipid solubility
- Anti-inflammatory
- … steroid, also available as …
A
- Prednisolone is a type of medicine known as a corticosteroid or steroid.
- Medium potency
- Good lipid solubility
- Anti-inflammatory
- Oral steroid, also available as enemas
93
Q
Hydrocortisone
- Hydrocortisone is a steroid (corticosteroid) medicine
- … potency
- … lipid solubility
- … therapy for hypoadrenalism, occasionaly also used for treatment in some indications
- Skin topically, also injections into joint
A
- Hydrocortisone is a steroid (corticosteroid) medicine
- Low potency
- Good lipid solubility
- Replacement therapy for hypoadrenalism, occasionaly also used for treatment in some indications
- Skin topically, also injections into joint
94
Q
Hydrocortisone
- Hydrocortisone is a steroid (corticosteroid) medicine
- … potency
- Good lipid solubility
- Replacement therapy for …, occasionaly also used for … in some indications
- … topically, also injections into …
A
- Hydrocortisone is a steroid (corticosteroid) medicine
- Low potency
- Good lipid solubility
- Replacement therapy for hypoadrenalism, occasionaly also used for treatment in some indications
- Skin topically, also injections into joint
95
Q
Beclomethasone
- Beclometasone is a type of medicine known as a corticosteroid (or steroid).
- … potency
- … lipid solubility
- … Inhaler for asthma
- Topically in Crohn’s
A
- Beclometasone is a type of medicine known as a corticosteroid (or steroid).
- Medium potency
- Poor lipid solubility
- Brown Inhaler for asthma
- Topically in Crohn’s
96
Q
Beclomethasone
- Beclometasone is a type of medicine known as a corticosteroid (or steroid).
- … potency
- Poor lipid solubility
- Brown Inhaler for …
- Topically in …
A
- Beclometasone is a type of medicine known as a corticosteroid (or steroid).
- Medium potency
- Poor lipid solubility
- Brown Inhaler for asthma
- Topically in Crohn’s
97
Q
Dexamethasone
- Dexamethasone is a corticosteroid
- … potency - IV and oral
- … lipid solubility
- Cerebral …
A
- Dexamethasone is a corticosteroid
- High potency - IV and oral
- Good lipid solubility
- Cerebral oedema
98
Q
Dexamethasone
- Dexamethasone is a corticosteroid
- High potency - … and oral
- Good lipid solubility
- … oedema
A
- Dexamethasone is a corticosteroid
- High potency - IV and oral
- Good lipid solubility
- Cerebral oedema
99
Q
Dexamethasone
- Dexamethasone is a corticosteroid
- High potency - IV and …
- … lipid solubility
- Cerebral oedema
A
- Dexamethasone is a corticosteroid
- High potency - IV and oral
- Good lipid solubility
- Cerebral oedema
100
Q
Triaminiclone
- Triamcinolone is a corticosteroid - typically used for … and …
- High potency
- Poor lipid solubility
A
- Triamcinolone is a corticosteroid - typically used for skin and joints
- High potency
- Poor lipid solubility
101
Q
Triaminiclone
- Triamcinolone is a corticosteroid - typically used for skin and joints
- … potency
- … lipid solubility
A
- Triamcinolone is a corticosteroid - typically used for skin and joints
- High potency
- Poor lipid solubility
102
Q
Adrenal suppression during corticosteroid therapy
- High-dose exogenous corticosteroids suppress endogenous production within …
- After prolonged therapy, the adrenal cortex begins to … and endogenous production takes some time to recover upon cessation
- Abrupt withdrawal below … dose reduces ability to deal with physiological stress – eg infection – and may precipitate an adrenal crisis
- Steroid warning card
- Tail dose slowly
- Increase dose during acute illness and prior to surgery
A
- High-dose exogenous corticosteroids suppress endogenous production within 1 week
- After prolonged therapy, the adrenal cortex begins to atrophy and endogenous production takes some time to recover upon cessation
- Abrupt withdrawal below replacement dose reduces ability to deal with physiological stress – eg infection – and may precipitate an adrenal crisis
- Steroid warning card
- Tail dose slowly
- Increase dose during acute illness and prior to surgery
103
Q
Adrenal suppression during corticosteroid therapy
- High-dose exogenous corticosteroids … endogenous production within 1 week
- After prolonged therapy, the adrenal cortex begins to atrophy and endogenous production takes some time to recover upon cessation
- Abrupt withdrawal below replacement dose reduces ability to deal with … stress – eg infection – and may precipitate an adrenal crisis
- Steroid … card
- Tail dose …
- … dose during … illness and prior to surgery
A
- High-dose exogenous corticosteroids suppress endogenous production within 1 week
- After prolonged therapy, the adrenal cortex begins to atrophy and endogenous production takes some time to recover upon cessation
- Abrupt withdrawal below replacement dose reduces ability to deal with physiological stress – eg infection – and may precipitate an adrenal crisis
- Steroid warning card
- Tail dose slowly
- Increase dose during acute illness and prior to surgery
104
Q
High-dose exogenous corticosteroids suppress … production within 1 week
A
High-dose exogenous corticosteroids suppress endogenous production within 1 week (After prolonged therapy, the adrenal cortex begins to atrophy and endogenous production takes some time to recover upon cessation)
105
Q
What are the side effects of steroid therapy? (Early (4) vs late (7))
A
- Early
- Weight gain
- Glucose intolerance
- Mood change
- Suppression of ACTH release
- Later
- Proximal muscle weakness
- Osteoporosis
- Skin changes
- Body shape changes
- Hypertension
- Cataracts
- Adrenal suppression
106
Q
Risk of infection - Corticosteroids
- Risk is related to … …
- Early risk - … defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- Intracellular pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
A
- Risk is related to cumulative dose
- Early risk - Phagocytic defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- Intracellular pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
107
Q
Risk of infection - Corticosteroids
- Risk is related to cumulative dose
- Early risk - Phagocytic defects
- … infection – S. aureus, enteric bacteria etc
- … infection – candida, aspergillus
- Later risk - Cell … defects
- Intracellular pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
A
- Risk is related to cumulative dose
- Early risk - Phagocytic defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- Intracellular pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
108
Q
Risk of infection - Corticosteroids
- Risk is related to cumulative dose
- Early risk - … defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- … pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
A
- Risk is related to cumulative dose
- Early risk - Phagocytic defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- Intracellular pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
109
Q
Risk of infection - Corticosteroids
- Risk is related to … dose
- Early risk - Phagocytic defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- Intracellular pathogens
- …
- Varicella
- …
- Pneumocystis
A
- Risk is related to cumulative dose
- Early risk - Phagocytic defects
- Bacterial infection – S. aureus, enteric bacteria etc
- Fungal infection – candida, aspergillus
- Later risk - Cell mediated defects
- Intracellular pathogens
- TB
- Varicella
- Listeria
- Pneumocystis
110
Q
Disease-modifying anti-rheumatic drugs (DMARDS)
- A diverse group of drugs that target the … …
- Derive name from use in … …, but also used in transplantation and myriad other autoimmune and inflammatory disorders; also sometimes (in higher doses) for … …
- To be distinguished from:
- NSAIDS: despite name, not disease-modifying
- …: the idea of DMARDS is that they’re ‘…-sparing’
- Biologics: newer class of drugs resembling naturally-occurring molecules
A
- A diverse group of drugs that target the immune system
- Derive name from use in rheumatoid arthritis, but also used in transplantation and myriad other autoimmune and inflammatory disorders; also sometimes (in higher doses) for cancer chemotherapy
- To be distinguished from:
- NSAIDS: despite name, not disease-modifying
- Steroids: the idea of DMARDS is that they’re ‘steroid-sparing’
- Biologics: newer class of drugs resembling naturally-occurring molecules
111
Q
Disease-modifying anti-rheumatic drugs (DMARDS)
- A diverse group of drugs that target the immune system
- Derive name from use in rheumatoid arthritis, but also used in … and … other autoimmune and inflammatory disorders; also sometimes (in higher doses) for cancer chemotherapy
- To be distinguished from:
- …: despite name, not disease-modifying
- Steroids: the idea of DMARDS is that they’re ‘steroid-sparing’
- …: newer class of drugs resembling naturally-occurring molecules
A
- A diverse group of drugs that target the immune system
- Derive name from use in rheumatoid arthritis, but also used in transplantation and myriad other autoimmune and inflammatory disorders; also sometimes (in higher doses) for cancer chemotherapy
- To be distinguished from:
- NSAIDS: despite name, not disease-modifying
- Steroids: the idea of DMARDS is that they’re ‘steroid-sparing’
- Biologics: newer class of drugs resembling naturally-occurring molecules
112
Q
DMARDS are a diverse group of drugs that target the … …
A
DMARDS are a diverse group of drugs that target the immune system
113
Q
Methotrexate
- Competitive inhibitor of … … (DHR), therefore anti-folate action
- Folate needed for purine synthesis in DNA
- This reduces T cell activity, and also (in higher doses) tumour synthesis
- Main indications
- Rheumatoid arthritis
- P…
- … disease
- Main toxicities
- Hepatotoxicity
- L..
- Pulmonary …
- Teratogenic
- NOTE … dosing; errors have caused major toxicity
A
- Competitive inhibitor of dihydrofolate reductase (DHR), therefore anti-folate action
- Folate needed for purine synthesis in DNA
- This reduces T cell activity, and also (in higher doses) tumour synthesis
- Main indications
- Rheumatoid arthritis
- Psoriasis
- Crohns disease
- Main toxicities
- Hepatotoxicity
- Leucopenia
- Pulmonary fibrosis
- Teratogenic
- NOTE weekly dosing; errors have caused major toxicity
114
Q
Methotrexate
- … inhibitor of dihydrofolate reductase (DHR), therefore anti-folate action
- Folate needed for … synthesis in DNA
- This … T cell activity, and also (in higher doses) tumour synthesis
- Main indications
- Rheumatoid arthritis
- Psoriasis
- Crohns disease
- Main toxicities
- H…
- Leucopenia
- Pulmonary fibrosis
- T…
- NOTE weekly dosing; errors have caused major toxicity
A
- Competitive inhibitor of dihydrofolate reductase (DHR), therefore anti-folate action
- Folate needed for purine synthesis in DNA
- This reduces T cell activity, and also (in higher doses) tumour synthesis
- Main indications
- Rheumatoid arthritis
- Psoriasis
- Crohns disease
- Main toxicities
- Hepatotoxicity
- Leucopenia
- Pulmonary fibrosis
- Teratogenic
- NOTE weekly dosing; errors have caused major toxicity
115
Q
How often is methotrexate taken?
A
weekly dosing - errors have caused major toxicity
116
Q
Methotrexate is a competitive inhibitor of what?
A
- DHR (Dihydrofolate reductase) - therefore anti-folate action - folate is needed for purine synthesis in DNA.
- This reduces T cell activity, and also (in higher doses) tumour synthesis
117
Q
Methotrexate … T cell activity, and also (in higher doses) tumour …
A
Methotrexate reduces T cell activity, and also (in higher doses) tumour synthesis
118
Q
What are the 3 main indications of methotrexate?
A
- Rheumatoid arthritis
- Psoriasis
- Crohns disease
119
Q
Main toxicities of methotrexate (4)
A
- Hepatotoxicity
- Leucopenia
- Pulmonary fibrosis
- Teratogenic
120
Q
Azathioprine
- Inhibits … S methyltransferase (TPMT), so also inhibits … synthesis
- Similar indications to …; more widely used in transplantation compared to it
- Toxicities similar to …; GI upset very common when starting
A
- Inhibits thiopurine S methyltransferase (TPMT), so also inhibits purine synthesis
- Similar indications to methotrexate; more widely used in transplantation compared to methotrexate
- Toxicities similar to methotrexate; GI upset very common when starting
121
Q
Azathioprine
- Inhibits thiopurine S methyltransferase (TPMT), so also inhibits purine …
- Similar indications to methotrexate; more widely used in … compared to methotrexate
- Toxicities similar to methotrexate; … upset very common when starting
A
- Inhibits thiopurine S methyltransferase (TPMT), so also inhibits purine synthesis
- Similar indications to methotrexate; more widely used in transplantation compared to methotrexate
- Toxicities similar to methotrexate; GI upset very common when starting
122
Q
Ciclosporin
- Inhibits …, which in turn reduces T lymphocyte activity
- Similar indications to aza/ metho, but used more in … and transplantation
- Main toxicities
- Nephrotoxic
- Hepatotoxic
- Gum hyperplasia
- Hirsuitism
- Note tacrolimus (newer formulation) is easier to take, and available for … use
A
- Inhibits calcineurin, which in turn reduces T lymphocyte activity
- Similar indications to aza/ metho, but used more in Dermatology and transplantation
- Main toxicities
- Nephrotoxic
- Hepatotoxic
- Gum hyperplasia
- Hirsuitism
- Note tacrolimus (newer formulation) is easier to take, and available for topical use (esp eczema)
123
Q
Ciclosporin
- Inhibits calcineurin, which in turn … T lymphocyte activity
- Similar indications to aza/ metho, but used more in Dermatology and …
- Main toxicities
- Nephrotoxic
- Hepatotoxic
- Gum hyperplasia
- Hirsuitism
- Note … (newer formulation) is easier to take, and available for topical use (esp eczema)
A
- Inhibits calcineurin, which in turn reduces T lymphocyte activity
- Similar indications to aza/ metho, but used more in Dermatology and transplantation
- Main toxicities
- Nephrotoxic
- Hepatotoxic
- Gum hyperplasia
- Hirsuitism
- Note tacrolimus (newer formulation) is easier to take, and available for topical use (esp eczema)
124
Q
Main toxicities of Ciclosporin (4)
A
- Nephrotoxic
- Hepatotoxic
- Gum hyperplasia
- Hirsuitism
125
Q
Tacrolimus (newer formulation of ciclosporin) is easier to take, and available for … use (esp …)
A
Tacrolimus (newer formulation of ciclosporin) is easier to take, and available for topical use (esp eczema)
126
Q
Ciclosporin inhibits what?
A
calcineurin - which in turn reduces T lymphocyte activity
127
Q
Ciclosporin has similar indications to azathioprine / methotrexate, but used more in … and …
A
Ciclosporin has similar indications to azathioprine / methotrexate, but used more in dermatology and transplantation
