Drugs And Arthritis Flashcards
Celecoxib is an example of a COX2 inhibitor, true or false
True
Influximab, etenercept and rituximab are examples of anticytokines, true or false
True
The enzyme COX2 produces prostaglandins that are involved in the production of mucous, true or false
False
Sulfasalazine is an example of a DMARD, true or false
True
Methotrexate is a cytotoxic folic acid agonist, true or false
False
Paracetamol has no antipyretic effect, but does have analgesic and anti inflammatory, true or false
False
Side effects of steroid include:
- Osteoporosis
- Decreased risk of infection
- Suppression of normal steroid synthesis due to excessive negative feedback which may precipitate acute adrenal failure
1 and 3
NSAIDs have pyretic actions, true or false
False
NSAIDs have analgesic actions, true or false
True
Misoprostol is a synthetic PG given alongside NSAIDs, true or false
True
NSAIDs have anti inflammatory actions by increasing vasodilation and increasing permeability of venules, true or false
False
What does ‘itis’ mean?
Inflammation
Which disease affects synovial joints?
Osteoarthritis
Where does osteoarthritis commonly occur
Knee, shoulder, wrist, ankle, finger
What is secreted by the synovium and is responsible for the breakdown of collagen
Matrix metalloprotinases
Obesity, gender (female), age (>40), previous joint injury and genetics are all risk factors for which disease?
Osteoarthritis
Which disease causes joint inflammation, especially in the synovial membrane, tendon sheath and bursae
Rheumatoid arthritis
What causes the following symptoms?
Swollen joints, morning stiffness (>30mins), pain
Rheumatoid arthritis
Which disease affects joints bilaterally
Rheumatoid arthritis
Which disease is an autoimmune disorder, antibodies are produced against the cartilage causing it to breakdown
Rheumatoid arthritis
Which disease is 3 times more common in women
Rheumatoid arthritis
RA affects joints, but where else can it effect
Other tissues, salivary glands, heart
What is an eicosanoid and consists of 20 carbon atoms
Arachnid onion acid
What is arachidonic acid derived from
Linoleic acid (found in veg oils, nut oils and butter)
What does phospholipase A2 (PLA2) do?
Strips arachidonic acid away from the cell membrane
What strips arachidonic acid away from the cell membrane
Phospholipase A2
Arachidonic acid is a sub straight for which enzyme
COX
COX causes arachidonic acid to be broken down into what?
Prostaglandins, thromboxanes, macrophages
When arachidonic acid is broken down by COX it potentials the effects of histamine and bradykinin - what does this do?
Increases permeability of venules - leading to oedema
Increases sensitivity of C fibres (chronic dull pain)
Which COX enzyme is expressed in most tissues all the time?
COX1
Which COX enzyme protects GI mucosa
COX 1
Which COX enzyme controls renal blood flow?
COX1
Which COX enzyme is found in inflammatory cells, induced by injury, infection and cytokines
COX2
Which COX enzyme produces inflammatory mediators
COX2
What catalyses the reaction: arachidonic acid –> PGs and Txs
All COX enzymes
Where is COX3 found?
The CNS of some species
What inhibits the COX enzymes, decreasing production of PGs, decreasing production of inflammatory mediators and decreasing inflammation
NSAIDs
True or false, meloxicam is an NSAID
True
What type of drug is indomethacin
NSAID
What are NSAIDs derived from
Salaclic acid
Which NSAID is derived from propyonic acid
Ibuprofen
True or false, NSAIDs have antipyretic, analgesic and anti inflammatory effects
True
How do NSAIDs have an analgesic effect?
Reduce the sensitivity of neurons to bradykinin
NSAIDs are effective against pain of what origin?
Muscular/skeletal
How do NSAIDs have an antipyretic effect?
Inhibit the actions of prostaglandins on the hypothalamus
Which drugs only suppress the signs and symptoms of inflammation
NSAIDs
Which drug inhibits NFkB expression, decreasing transcription of genes for inflammatory mediators
Aspirin
Which drugs may induce asthma attack in asthmatics, cause angioedema, urticaria or rhinitis?
NSAIDs
Who are NSAIDs contraindicated for?
Elderly
Patients with cardiac disease/hypertension
Which NSAID has COX2 selectivity
Meloxicam
COX2 inhibitory NSAIDs; celecoxib and etoricoxib are used mainly in which patients
Patients at high risk of serious GI side effects, but little CV risk
What are the common side effects of COX2 inhibitory NSAIDs celecoxib and etoricoxib
Headache, dizziness, skin rash, peripheral oedema
Is paracetamol an NSAID
No
Why is misoprostol given alongside NSAIDs
Preserves the mucous lining of the GI tract by increasing production of mucous and blocking the acid pump
What are some side effects of misoprostol
Diarrhoea
Vaginal bleeding
Is misoprostol indicated for pregnant women?
No, it stimulates uterine contractions
What can be given as an alternative to misoprostol (synthetic prostaglandin) alongside NSAIDs?
Proton pump inhibitor eg. Omeprazole
Can aspirin be used in patients who are taking warfarin
No, aspirin displaces the warfarin bound to plasma cells, therefore potentials warfarins anticoagulant activity
Does paracetamol have an anti inflammatory effect
No
What is a toxic dose of paracetamol?
10-15g
What disease might a patient be taking strontium ranelate for
Osteoarthritis
What does the drug strontium ranelate do?
Promote osteoblast differentiation/inhibit osteoclast activity
Why is strontium ranelate restricted to the treatment of severe osteoarthritis?
It increases risk of MI and thrombotic events
What do osteoclasts do?
Strip calcium from the bone
Where are glucocorticoids naturally produced in the body?
Adrenal cortex
What pain relief is recommended for rheumatoid arthritis?
NSAIDs or opioid analgesics
What hormone is released from the hypothalamus during steroid synthesis
Corticotropin releasing hormone
Which hormone is released from the anterior pituitary and acts on the adrenal cortex during steroid synthesis
Adrenocorticotropin hormone
Which two steroids are naturally produced by the adrenal cortex
Cortisone
Hydrocortisone
Which natural steroid only shows mineralocorticoid actions
Aldosterone
Hydrocortisone and cortisone are natural steroids, do they exhibit glucocorticoid actions, mineralocorticoid actions or both
Both
Overstimulation of mineralocorticoid receptors by cortisone/hydrocortisone would cause
Severe hypertension
Hydrocortisone/cortisone have mineralocorticoid properties, these can be inactivated by enzymes in MC sensitive tissues, where might these be found
Kidney
Which synthetic steroid has mainly mineralocorticoid actions
Fludrocortisone
Which steroid, with mainly mineralocorticoid activity, might be used to treat Addison’s disease
Fludrocortisone
What type of steroid activity does Fludrocortisone have
Mineralocorticoid
Dexamethasone, betamethasone, beclomethasone and budesonide are all steroids with which type of activity
Glucocorticoid
Which two steroids exhibit mixed glucocorticoid and mineralocorticoid activity
Prednisolone
Prednisone
Prednisone and prednisolone and steroids which have which type of activity
Mixed glucocorticoid and mineralocorticoid activity
Which two steroids are short acting
Cortisone
Hydrocortisone
How would you administer cortisone
Twice daily cream or intra-Articular injection
How is hydrocortisone administered
Twice daily cream
Intra articular injection
Which steroid is intermediate acting?
Prednisolone
What is the duration of action of prednisolone
Intermediate acting
How is prednisolone administered
Daily oral or intra articular injection
Which steroid is long acting
Dexamethasone
What is the route of administration of Dexamethasone
Intra articular injection every 3-21 days
True or false, steroids are lipid soluble
True
What has anti inflammatory and immunosuppressant actions in rheumatoid arthritis
Glucocorticoids
Glucocorticoids have immunosuppressant actions in rheumatoid arthritis, how?
Decrease transcription do cytokines (eg. IL-2)
Glucocorticoids have anti inflammatory actions in rheumatoid arthritis, how?
Increase synthesis of anti inflammatory proteins (eg. Protease inhibitors)
Which glucocorticoids are used in the treatment of asthma and arthritis
Beclomethasone
Budesonide
Prednisolone
True or false, hypotension a cushingoid feature is a common side effect of oral corticosteroids
False, hypertension is a cushingoid feature
Which of the following is not a cushingoid feature seen as a result of taking oral corticosteroids
Buffalo hump Increased abdo fat
Muscle wastage Moon face
Osteoporosis Good wound healing
Poor wound healing Increased infection risk
Good wound healing
How can you reduce the side effects associated with oral corticosteroids
Choose a different route of admin to decrease systemic concerntration
Eg. Topical
Why must patients who have been taking steroid treatment not stop suddenly
Synthetic steroids inhibit natural production of steroids, could cause Addison’s crisis
Sulfasalazine, penicillamine and aurothiomalate are all types of what drugs
DMARDs disease modifying anti rheumatoid drugs
Which drug is the common 1st drug of choice DMARD in the uk
Sulfasalazine
What is the route of administration of sulfasalazine
Enteric coated tablet
Which DMARD causes the side effects GI upset, headache, skin reactions and leukopenia
Sulfasalazine
Which DMARD is a complex of salicylate (NSAID) and sulphonamide (abx)
Sulfasalazine
How does the DMARD sulfasalazine work
Scavengers free radicals (which cause damage to joints) produced by neutrophils
How is the DMARD penicillamine administered
Orally
When is the peak plasma concerntration of the DMARD penicillamine
1-2 hours
Can penicillamine be used in conjunction with sodium aurothiomalate
No, cannot be used with gold compounds as it is a metal chelator, it combines with the metal and reduces its activity
Which DMARD produces the following side effects
Rashes, stomatitis, anorexia, taste disturbances, fever, n&v
Penicillamine
Which DMARD works by decreasing IL-1 generation, decreasing fibroblast proliferation and decreasing the immune response
Penicillamine
How is the DMARD sodium aurothiomalate administered
Deep IM injection
How is the DMARD auranofin administered
Orally
What are the serious side effects associated with the use of gold compounds for treating rheumatoid arthritis
Encephalopathy
Peripheral neuropathy
Hepatitis
How long does it take for the effects of aurothiomalate to work
3-4 months
Which DMARD is often used when other treatments fail
Anti malarials (chloroquine/hydroxychloroquine)
Which DMARDs have side effects which include n&v, dizziness and blurring of vision
Chloroquine/hydroxychloroquine
How long does it take for the therapeutic effects of chloroquine to work in rheumatoid arthritis
About 1 month
Anticytokines are proteins, how does this effect their administration
Cannot be given orally, as they would be digested
How are anticytokine drugs administered
Sub cut or IV injection
Which patients is he use of anticytokine drugs restricted to in rheumatoid arthritis
Those who don’t respond well to other DMARDs
Which DMARDs are engineered recombinant antibodies
Anticytokine drugs
What type of drugs are the following; etenercept, infliximab, abatacept, adalimumab, natalizumab
Anti cytokines
How to the anticytokine drugs rutiximab, abatacept and natalizumab work
Target leukocyte receptors disrupting the immune signalling
Which anticytokine drugs target TNF
Adalimumab, etenercept, infliximab,
Which DMARDs can be given with methotrexate
Anti cytokines
Which DMARDs may cause the development of latent disease, for example TB, hep B, herpes zoster
Anticytokines
True or false, rheumatoid arthritis is an autoimmune disorder
True
Which drug is a potent immunosuppressant but has no effect on acute inflammation
Ciclosporin
Which immunosuppressant given to people with RA inhibits IL-2 gene transcription, decreasing T cell proliferation
Ciclosporin
How does the immunosuppressant ciclosporin work
Inhibits IL-2 gene transcription, decreasing T cell proliferation
Would ciclosporin be administered orally
No, it is poorly absorbed orally; capsules or oral solutions
Which drug can cause; nephrotoxicity, hepatotoxicity, hypertension, n&v, gum hypertrophy, GI problems
Ciclosporin
Why can ciclosporin cause toxic effects in the kidneys and liver
It accumulates in high concentration in tissues
Which immunosuppressant is cytotoxic, interfering with purine metabolism which decreases DNA synthesis
Azathioprine
Which phase of the immune response does azathioprine work at
The induction phase
What is the main specific effect of the drug azathioprine
Suppression of bone marrow
How does methotrexate work
Folic acid antagonist, which inhibits DNA synthesis
Which cells does methotrexate target
Blocks the growth and differentiation of rapidly dividing cells
Which drug is often prescribed with a DMARD
Methotrexate
Should methotrexate be used in pregnancy
No, can cause folate deficiency
Which immunosuppressant is a specific inhibitor of activated T cells
Leflunomide
What is the route of administration of leflunomide
Oral, long half life
Which immunosuppressant has side effects including, diarrhoea, alopecia, increase in liver enzymes (risk of hepatotoxicity)
Leflunomide
Which drugs side effects include blood dyscrasias (abnormalities) and liver cirrhosis and folate deficiency
Methotrexate
When is cyclophosphamide used to treat RA
When all other therapies have failed
Which immunosuppressant used to treat RA is a pro drug
Cyclophosphamide
When the immunosuppressant cyclophosphamide is administered orally it is activated in the liver to what
Phosphoramide mustard and acrolein
The pro drug cyclophosphamide is activated in the liver to phosphoramide mustard and acrolein, what can acrolein caus
Haemorrhagic cystitis (bleeding from the kidney) can be prevented by administering with very large volumes of fluid
True or false, glucocorticosteroids and other immunosuppressants increase the risk of infection and increase risk of cancer
True
In the treatment of RA how effective is hydroxychloroquine, and what else might this drug be used for
50% effective, antimalarial
What type of drug is etenercept, how is it usually administered
Anticytokine, subcut Twice a week
