IC 13: Drugs for Pain Management and Joint Pain Flashcards
(90 cards)
1
Q
What are the non-selective COX inhibitors?
A
- Irreversible COX inhibitor: Aspirin
- Reversible COX inhibitor: Naproxen, ibuprofen, diclofenac, mefanamic acid
2
Q
What are the COX-2 selective inhibitors?
A
Celecoxib, parecoxib, etoricoxib (reversible)
3
Q
What are the CNS-selective COX inhibitor?
A
Paracetamol (reversible)
4
Q
What are the opioids/narcotic analgesics?
A
Tramadol, codeine, morphine, oxycodone, fentanyl
5
Q
What is the difference between pain and nociception?
A
Pain: unpleasant sensory and emotional experience associated with actual or potential tissue damage
Nociception: detecting and signaling the presence of a noxious stimulus to the CNS
6
Q
How do NSAIDs work?
A
They block phospholipase A2 enzyme which catalyses the release of arachidonic acid from the phospholipid molecule. Therefore, less stimulation of enzymes 15-lipoxygenase, cyclooxygenase and 5-lipoxygenase. There is less production of lipoxins, prostaglandins and leukotrienes.
7
Q
What are some examples of prostanoids?
A
Prostacyclin, classical prostaglandins and thromboxanes
8
Q
How do the various lipid molecules (prostacyclin, prostaglandin and thromboxanes) affect pain and platelet aggregation?
A
Prostacyclin: vasodilatation and inhibit platelet aggregation
Prostaglandin: vasodilatation, vascular permeability and pain
Thromboxanes: vasoconstriction and platelet aggregation
9
Q
How do non-selective NSAIDs exert their anti-inflammatory effect?
A
- Blocks vasodilatation (less heating, redness and swelling)
- Decreases vascular permeability (less swelling)
- Block production of prostaglandins which sensitize the nociceptive fibres to stimulation by other inflammatory mediators
- Analgesic actions in the CNS
- Antipyretic
10
Q
Are non-selective NSAIDs good for mild to moderate pain or severe pain? Why?
A
Mild to moderate pain. NSAIDs block sensitization of the pain and therefore there is an analgesic ceiling (if it gets too painful, patients will still feel the pain)
11
Q
Is aspirin used often as a anti-inflammatory agent? Why?
A
No. Due to adverse effects of aspirin use as a pain killer, it is now over taken by paracetamol
12
Q
What are the adverse effects of aspirin caused by at high doses?
A
Salicylate toxicity
13
Q
What are some adverse effects of aspirin that are present even at low doses?
A
- Gastric intolerance (bleeding and hypersensitivity)
- Tinnitus (ringing in ears)
- Uricosuric (promote excretion of uric acid)
14
Q
What life threatening syndrome is aspirin linked to?
A
Reye’s syndrome:
* Swelling of brain and liver
* Vomiting, personality changes, listlessness, delirium, convulsions, loss of consciousness
* Increased risk if it is taken by children with viral infections
15
Q
What is naproxen often used for?
A
Dysmenorrhoea
16
Q
Why is indometacin strongly anti-inflammatory?
A
Additional steroid-like phospholipase A inhibition
17
Q
What is diclofenac often used as?
A
Use for inflammatory joint disease because of it’s long half-life in synovial (joint) fluid
18
Q
What are the adverse effects of non-selective NSAIDs?
Hint: think of the different body systems
A
- GI: Dyspepsia, nausea, vomiting, ulcer formation and potential haemorrhage risk in chronic users
- Renal: Sodium retention, water retention, peripheral oedema, hypetension, suppression of renin and aldosterone secretion, hyperkalaemia, acute renal failure
- Pseudo-allergic reaction: skin rashes, swelling, itching, nasal congestion, anaphylactic shock
- Asthma: can trigger bronchospasm in suspectible asthmatics
- Bleeding: failure of haemostasis, bruising
19
Q
What drugs constitute the triple whammy?
A
NSAIDs, diuretics, ACEi as they all reduce kidney function and increase risk of acute kidney injury
20
Q
What are the risk factors for NSAID-induced AKI?
A
- Increasing age (>65)
- Chronic hypertension
- Atherosclerosis
- Pre-existing glomerular disease or renal insufficiency
- Volume depletion
- Use of ACEi or ARB
- Use of triple whammy
21
Q
What patients are more susceptible to bronchospasm when using non-selective NSAIDs?
there are 3
A
Those with asthma, chronic urticaria and nasal polyps
22
Q
What is the difference between COX-1 and COX-2 enzymes?
A
COX-1 = housekeeping
COX-2 = inducible (CNS, kidneys, female reproductive tract, synovium)
23
Q
What are the unwanted effects of COX-2 inhibition?
A
- Renal toxicity due to constitutive expression of both COX-1 and COX-2 in the kidney
- Effects on ovulation, including delayed follicular rupture
- Premature closure of ductus arteriosus in late pregnancy
24
Q
Can selective COX inhibitors be used in pregnancy?
A
Yes but not in third trimester
25
What is the impact of wound healing of COX-2 inhibitors?
COX-2 inhibitors impair wound healing and may exacerbate ulcers.
26
What is the effect of non-selective NSAIDs on thrombosis?
There is a relative increase in TXA2 which favours platelet aggregation and may increase risk of thrombosis
27
Why should there be greater caution when using NSAIDs in elderly or patients with a history of cerebovascular or cardiovascular disease?
NSAIDs except aspirin can increase the risk of heart attack, heart failure and stroke. This is due to the renal effects causing hypertension and the risk of prothrombic effects which together increases the risk of heart attack and stroke.
28
In what patients is the use of NSAIDs contraindicated?
* Severe kidney impairment
* Severe heart failure
* Active GIT ulcer or bleeding
* Bleeding disorders like haemophilia
* Use of systemic corticosteroids or antiplatelet agents/anticoagulants
* Multiple risk factors for NSAID toxicity (e.g. elderly patients with a history of GIT bleeding)
* Third trimester of pregnancy
29
How should NSAIDs be chosen for patients with risk of cardiovascular toxicity?
* Avoid diclofenac and COX-2 selective NSAIDs other than celecoxib
* Use celecoxib or ibuprofen limited to < 5 days
* If cannot use celecoxib, ibuprofen or naproxen, consider paracetamol alone
30
How should NSAIDs be chosen for patients with risk of GI toxicity?
* Avoid non-selective NSAIDs
* Use a COX-2 selective NSAID but with caution
* Consider co-prescribing GI protectant
31
How should NSAIDs be chosen for patients with risk of NSAID related bronchospasm?
* Avoid non-selective NSAIDs
* Use of COX-2 selective NSAID but with caution
32
Should NSAIDs be taken with food?
No as it can reduce absorption rate
33
What is the mechanism of paracetamol?
CNS-selective COX inhibition
34
What are the advantages of paracetamol?
* Good analgesic
* Potent antipyretic
* Spares the GI tract
* Side effects few and uncommon
* Few DDI
35
What are the disadvantages of paracetamol?
* Weak anti-inflammatory
* Toxic doses cause nausea, vomiting and liver damage
* Allergic skin reactions sometimes occur
36
In what patients should paracetamol be used with caution?
Hepatic dysfunction or alcohol abuse
37
What is the amount of paracetamol that constitutes overdose?
>10g per 24 hours is overdose
>4g per 24 hours is increased risk of harm
Lead to liver damage
38
How can paracematol and NSAIDs be administered together?
* Alternating for sustaining antipyretic effect
* Together for stronger analgesic effect
39
What are the issues associated with opioid analgesics?
* Risk of addiction and abuse
* Risk of sedation
* Risk of overdose in respiratory depression
40
Out of the 3 which is anti-inflammatory?
| NSAIDs, paracetamol, opioids
NSAIDs
41
Which opioids are weak opioids and which are strong opioids?
Weak: tramadol, codeine
Strong: morphine, oxycodone and fentanyl
42
What are the adverse effects associated with opioid analgesics?
* GI (constipation, nausea, vomiting)
* Hormonal effects
* Depression
* Respiratory effects
* Overdose and death
* Falls and fracture
* Sedation/drowsiness
* Tolerance, physical dependance, addiction or withdrawal
* Opioid-induced hyperalgesia
43
What are the risk factors for opioid analgesics?
* Combination with other CNS depressants
* Other comorbidities
* Renal or hepatic insufficiency
* Age > 65
* Pregnancy
* Personal or family history of substance use disorder
* Already prescribed an opioid
44
What is the antidote for paracetamol overdose?
Acute poisoning: oral activated charcoal and sorbitol
More than 2 hours after: IV n-acetyl-cysteine
45
What is the mechanism that leads to toxicity in paracetamol overdose?
There is depletion of glutathione by paracetamol overdose and therefore the toxic metabolite is not converted an a nontoxic metabolite.
46
What is the difference in the pathophysiology of osteoarthritis, rheumatoid arthritis and gouty arthritis?
OA: wear and tear, progressive and irreversible loss of cartilage
RA: inflammation, swollen inflamed synovial membrane
GA: inflammation, urate cystals that are recognised and attacked by immune cells
47
What are drugs that can be used for OA?
* Pain relief/anti-inflammatory
* Intra-articular hyaluronic acid
48
What are the risk factors for gout?
* Ageing
* Diet
* Hypertension
* Diabetes
* Hyperlipedemia
49
What can cause drug-induced hyperuricaemia?
* Thiazide/loop diuretics
* Low-dose aspirin
* Ciclosporin
50
What is the goal of drug treatment for gout?
1. Relieve acute gouty attack
2. Prevent recurrent gouty episodes
51
What are the drugs used for gout?
* Acute: nonselective NSAIDs, COX2 selective NSAIDs, Glucocorticoids, Colchicine
* Prevention of gout: xanthine oxidase inhibitors
52
What are the MOAs of the drugs for gout?
NSAIDs and corticosteroids: anti-inflammatory and analgesic effect
Colchicine: inhibit leukotriene b4 and prostaglandin production, reduce leucocyte migration into joints
Uric acid synthesis inhibitors (allopurinol, febuxostat): inhibit uric acid synthesis
Uricosuric agents (probenecid): increase uric acid excretion
53
Colchicine relieves pain and inflammation in gout within how many hours?
24 to 36 hours
54
What are the side effects of colchicine?
* Diarrhoea
* Nausea and vomiting
* Abdominal pain
* Muscle weakness
* Unusual bleeding
* Pale lips
* Change in urine amount
55
Are allopurinol and febuxostat competitive or non-competitive inhibitors?
Allopurinol: competitive
Febuxostat: non-competitive
56
What is the therapeutic target for xanthine oxidase inhibitors?
<6.0 mg/dL
57
What are some serious adverse effects that should be noted for allopurinol?
* Allopurinol hypersensitivity syndrome
* SCAR
* Risk factors: renal impairment (CrCl < 60), thiazide therapy, HLA-B *58:01 genotype
58
What are the side effects of xanthine oxidase inhibitors?
* Skin rash
* Nausea and vomiting
* Diarrhea
* Fever
* Sore throat
* Stomach pain
* Dark urine
* Jaundice
59
When is probenecid indicated?
* When allopurinol is contraindicated in tophaceous gout
* In increasingly frequent gout attack
* Start 2-3 weeks after an acute attack
60
What are some precautions when using probenecid?
* Take plenty of fluid to minimise renal stone formation
* Keep urine pH > 6 by administration of alkaline
61
What are the side effects of probenecid?
* Nausea and vomiting
* Painful urination
* Lower back pain
* Allergic reactions
* Rash
62
What is the first line treatment for RA?
synthetic DMARDs
63
What are the drug treatments available for RA?
* Anti-inflammatory: NSAIDs, corticosteroids
* conventional DMARD: methotrexate, sulfasalazine, leflunomid, hydroxychloroquine, ciclosporin
* targetted synthetic DMARD: tofacitinib, baricitinib
* biologic DMARD: anti-TNF mAb, IL-1R antagonist, anti-CTLA4i, anti-CD20, anti-IL6 receptor mAb
64
What is the MOA of methotrexate?
* Increase in extracellular adenosine level and activation of adenosine A2a receptor
* Anti-proliferative effects on T cells and inhibition of macrophage functions
* Decrease in pro-inflammatory cytokines, adhension molecules, chemotaxis and phagocytosis
65
What are the side effects of methotrexate?
* Nausea and vomiting
* Mouth and GI ulcers
* Hair thinning
* Leukopenia
* Hepatic fibrosis
* Pneumonitis
66
What can be given with methotrexate to reduce the side effects?
* Folic acid or folinic acid given 12-24 hours after methotrexate
67
What leads to methotrexate toxicity?
Inhibition of dihydrofolate reductase and depletion of N5, N10 - methylene- FH4
68
What is the rescue therapy for methotrexate toxicity?
Folinic acid or folinate
69
What are the side effects of sulfasalazine?
* Nausea, vomiting
* Headache
* Rash
* Haemolytic anemia
* Neutropenia
* Reversible infertility in men
70
What is the MOA of leflunomide?
* Inhibits dihydroorotate dehydrogenase
* Decrease in pyrimidine synthesis and growth arrest at G1 phase
* Inhibit T cell proliferation and B cell autoantibody production
* Inhibits NF-KB activation pro-inflammatory pathway
71
What are the side effects of leflunomide?
* Diarrhoea
* Elevation of liver enzymes
* Alopecia
* Weight gain
* Teratogenic
72
What is the MOA of chloroquine and hydroxychloroquine?
* Anti-inflammatory agents
* Reduced MHC class II expression and antigen-presentation
* Reduced TNF-alpha and IL-1 and cartilage resorption
* Antioxidant activity
73
What are the side effects of chloroquine and hydroxychloroquine?
* Nausea and vomiting
* Stomach pain
* Dizziness
* Hair loss
* Ocular toxicity
74
What is the place in therapy for targetted synthetic DMARDs?
* Combined with methotrexate for moderate to severe RA
* Monotherapy in cases of intolerance to methotrexate
* Methotrexate and multiple bDMARD-refractory active RA
* Tofacitinib approved for psoriatic arthritis
75
What is the place in therapy for targetted synthetic DMARDs?
* Combined with methotrexate for moderate to severe RA
* Monotherapy in cases of intolerance to methotrexate
* Methotrexate and multiple bDMARD-refractory active RA
* Tofacitinib approved for psoriatic arthritis
76
What is the MOA of ts DMARDs?
* Janus kinase pathway inhibitor
* Blocks cytokine production by blocking JAK/STAT-activation of gene transcription
77
What are the adverse effects of tsDMARDs?
* Cytopenia including neutrophils, lymphocytes, platelets and NK cells
* Immunosuppression resulting opportunistic infections
* Anemia
* Hyperlipidemia: increase total, LDL and HDL cholesterol and triglycerides
78
Can tsDMARDs be combined with biological DMARDs?
No
79
What is the binding target for anti-TNF biologics?
* Infliximab, adalimumab, golimumab: TNF-alpha
* Etanercept: TNF-alpha and lymphotoxin-alpha
80
Which of the TNF biologics have a extra short half-life?
Etanercept with a half life of 70 hours
81
What are the biological DMARDs?
Infliximab, adalimumab, golimumab, etanercept, anakinra, tocilizumab, abatacept, rituximab
82
What is the place in therapy of TNF blockers?
* For RA patients who do not respond well with sDMARD therapies
* In combination with MTX for optimal effects
83
What are the side effects of TNF blockers?
* Respiratory infection and skin infection
* Increased risk of lymphoma
* Optic neuritis
* Exacerbation of multiple sclerosis
* Leukopenia
* Aplastic anemia
84
What are the contraindications of TNF blockers?
Live vaccination, hepatitis B
85
What are the monitoring parameters for TNF blockers?
Screen for latent or active TB
86
Can allopurinol and probenecid be given for an acute gouty attack?
No. Because they have a greater risk of worsening ongoing acute gouty attacks and kidney stones
87
Which drug for gout is not as effective until 24-36 hours after onset of gout attack?
Colchicine
88
Should allopurinol be combined with colchicine or an NSAID during onset of treatment?
Yes. As allopurinol will cause more urate to move out of joints and this can precipitate an acute gouty attack
89
What is the first line DMARD for RA?
Methotrexate
90
Which drugs cannot be combined for RA?
bDMARDs cannot be used with tsDMARDs
