drugs for arthritis Flashcards by natalie fisher

how is inflammation caused?

release of various chemicals at the site of injury including histamine, bradykinin, prostaglandins which are activated by bradykinin

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what is the action of bradykinin?

local vasodilation stimulation of nerve ending causing pain arachidonic acid release - this is precursor to prostaglandins, leuotrienes and thromboxanes

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what is the first step in takling inflammation?

block production of inflammatory mediators → prostaglandins can sensitive afferent C fibres to bradykinin

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how could prostaglandins be inhibited to treat inflammation?

Non -Steroidal Anti Inflammatory drugs (NSAIDs)

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describe the roles of the COX 1 and 2 enzyme in inflammation

COX 1 - always produced - has protective effect, converts arachidonic acid into prostaglandinsCOX 2 - responsible for pain and inflammation - active at site of traum/injury

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how do NSAIDs reduce inflammation?

block COX 1 and 2 - blocks many signs/symptoms of inflammation

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why is it important to block COX 1 and 2 to reduce inflammation?

COX 1 and 2 activate convertion of arachidonic acid to prostaglandins (PGs) PGs increase sensitivity of nociceptors to other stimuli

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name the three pharmacological actions of NSAIDs

antipyretic analgesic - relieves pain ass. with production of PGs anti - inflammatory - reduces oedema, sensitisation of nociceptors and musculoskeletal pain

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what are the side effects of NSAIDs?

in chronic treatment - high dose, prolonged use indigestion diarrhoea nausea/vomiting gastric bleeding and ulceration

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what do NSAIDs inhibit and why does this cause gastric bleeding and ulceration?

PG1 and PG2 → these produce mucus and HCO3 secretion, reduced acid secretion and increased blood flow to stomach

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how can the side effects of NSAIDs be reduced?

develop drugs which only inhibit COX 2 enteric coating of tablets give drugs with protective agent prodrugs

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name 2 drugs which only inhibit COX 2

celecoxib etoricoxib

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name 2 drugs with a protective agent which reduce the side effects of NSAIDs

misoprostol (PGE1 analogue) omeprazole (H+ pump inhibitor)

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name 3 NSAIDs prodrugs

sulindac nabumetone fenbufen

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what is aspirin an example of?

NSAIDs

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what is aspirin effectice for?

mild pain and fever

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name 5 NSAIDS

aspirin
ibuprofen
diclofenac
melexicam
indomethacin

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is paracetamol an NSAID?

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describe the pros and cons of paracetamol

pros - antipyrexic, analgesic

cons - not anti inflammmatory

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how does paracetamol work?

supresses prostaglandin production

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name two drugs which have potential benefits for treating osteoarthritis

strontium ranelate

glucosamine sulphate

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what does strontium ranelate do?

promotes osteoblast differentiation / inhibits osteoclast activity

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name the classes of drugs which are used to treat rheumatoid arthitis

Corticosteriods
immunosupressants
disease modifying anti-rheumatoid drugs (DMARDS)
anticytokines

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describe the actions of glucocorticoids

metabolic effects
anti inflammatory
immunosuppressive

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name 2 Corticosteriods which has mixed gluco and mineralocorticoid actions. what is the duration of action?

prednisolone predisone intermediate 12--36hrs

name 4 Corticosteriods which have just glucocorticoid actions. what is the duration of action?

``` dexamethasone bethamethosone bedomethosone budesonide long 36-55hrs ```

name a Corticosteriods which has mainly mineralocorticoid actions.

fludrocortisone

name 2 short acting Corticosteriods

cortisone hydrocortisone 1-12hrs

name the corticosteroids most likely to be used in rheumatoid arthritis

beclomethosone budesonide prednisolone

describe the mechanism of glucocorticoids in rheumatic arthritis

reduces transcription of pro-inflammatory cytokines (eg. IL-2) reduces circulating lymphocytes inhibits phosphodipase A2 which reduces release of anahioddonic acid thus reducing circulating PGs increase synthesis of anti-iunflammatory proteins (eg. protese inhibitors)

what are DMARDS

disease modifying anti-rheumatoid drugs = group of drugs with unrelated structure

which DMARD is the first drug of choice in RA?

sulfasalazine

what is sulfasalazine a complex of?

salicylate (NSAID) and sulphonamide (antibiotic)

what is the mechanism of action of sulfasazine?

acts by scavenging free radials produced by neutrophils

what are free radicals?

reactive chemicals that kill bacteria - over production destroys surrounding tissue

what does sulfasazine achieve in RA?

causes remission of 'active' RA

what are the side effects of sulfasazine

GI upset headache skin reaction leukopenis (reduced WC count)

what is penicillamine?

a DMARD

how is penicillamine produced?

hydrolysis of penicillin

what is the mechanism of action of penicillamine?

lowers generation of IL-1 and reduces fibroblast proliferation thus reducing immune response

how is penicillamine administered?

oral - takes weeks to work

what are the side effects of penicillamine?

``` rashes stomatitis anorexia taste disturbance fever N&V ```

what should penicillamine not be given with?

gold compound

what are gold compounds and what are they used for?

DMARDS - RA

name 2 gold compounds used in RA

``` sodium aurthiomalate (deep IM) auranofin (oral) ```

what is the mechanism of action of auranofin?

inhibits production of IL-1 and TNF-a | reduces pain and swelling

what are the side effects of gold compounds?

``` skin rashes flu symptoms mouth ulcers blood disorders severe: encephalopathy, peripheral neuropathy ```

what are antimalarial in relation to RA treatment?

DMARD

name 2 antimalarial used in RA treatment

choloquine | hydroxychoroquine

what are the actions of antimalarial in treating RA?

increase pH of intracellular vacuoles which interferes with antigen presenting induces apoptosis in T-lymphocytes

when are antimalarial used in RA treatment?

when other treatments fail

what are the side effects of antimalarial?

N&V dizziness blurring of vision screening needed

What are anticytokine drugs used to treat?

what are anticytokines?

engineered recombinant antibodies - v. expensive so restricted to patient that don't respond to DMARDS

name 3 anticytokines which target TNF

adalimab entenercept infliximab

name 3 anticytokines which target leukocyte receptors

rituximab abatacept natalizumab

what is the mechanism of action of tocilizumab

blocks IL-6 receptors which disrupts immune signalling

what other drug can anticytokines be given with?

methotrexate (an immunosuppressant)

name 5 immunosuppressant's used to treat RA

``` ciclosporin azathioprine methotrexate leflunomide cyclophosphamide ```

why is immunosuppression useful in RA?

RA is an autoimmune disease

what is the mechanism of action of ciclosporin?

inhibits IL-2 gene transcription | reduces t-cell proliferation

how is ciclosporin administered?

poorly absorbed orally - special formulations

what are the side effects of ciclosporin?

``` accumulation in high conc. in some tissues nephrotoxicity hepatotoxicity hypertension N&V, gum hypertrophy, GI probs ```

in what phase of the immune response does azathioprine target cells?

induction phase thus depresses cell and antibody mediated immune reactions

what is the mechanism of action of azathioprine?

cytotoxic - interferes with purine metabolism thus reducing DNA synthesis

what is the main specific effect of azathioprine in treating RA?

suppression of bone marrow which reduces RBC and WBC production

what is methotrexate and what does it treat?

immunosuppressant - RA

what is the mechanism of action of methotrexate?

folic acid antagonist - inhibits DNA synthesis blocks growth and differentiation of rapidly dividing cells inhibits T-cell activation

what are the side effects of methotrexate?

poss. blood abnormalities liver cirrhosis folate def.

what is leflunomide and what does it treat?

immunosuppressant - RA

what is the mechanisms of action of leflunomide?

inhibits pyrimidine synthesis | specific inhibitor of activated T cells

how is leflunomide administered and how long does it last?

orally - long t half life (14-18 days)

what are the side effects of leflunomide?

diahorroea alopecia increased liver enzymes - risk of hepatotoxicity

what is cyclophosphamide and what does it treat?

immunosuppressant- RA

what is the mechanism of action of cyclophosphamide?

increases cross linking of DNA

cyclophosphamide is a PRODRUG when administered orally where is it activated and into which other drugs?

liver | phoshoramide mustard & acrolein

what can occur when administering acrolein and how is this avoided?

haemorrhagic cystitis | large volume of fluid given

drugs for arthritis Flashcards

(77 cards)