drugs and immune system.txt
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drugs and immune system.txt
which immunisations are live attenuated and who can they not be given to?
not to immunocompromised as they are active organisms
which immunisations are neutralised toxins i.e. PASSIVE
give 3 examples of dead organisms or extracts (active)
hep a and b
HiB (haemophilus influenzae b)
what are the effects of steroids? 2 main categories
how do steroids reduce inflammation?
reduce production of PG, LT, thromboxane, PAF so
reduced cap perm so less oedema
reduced leukocyte infiltraion
reduce histamine release from basophils
what is the mechanism of action of steroids?
bind to intracellular glucocorticoid and mineraocorticoid receptors and also bind to cell surface receptors
regulate gene transciption and expression
e.g. makes lipocortin a phospholipid binding protein which inhibits phospholipoase A2 from converting PL to AA so less PG and PAF made
how long does it take before anti inflame of steroids start? and why?
4-6 hours because DNA and protein synthesis is involved
what are the side effects of steroids?
iatrogenic cushing's syndrome
: BUT NO HIRSUTISM!
due to negative feedback, reduce hypothalamic and pituitary drive to make cortisol and aldosterone so if stop steroids abruptly can get iatrogenic addison's disease as adrenals have atrophied
: salt and water retention - hypertension; hypokalaemia; alkalosis
immune suppression due to thymus involution
osteoporosis due to increased bone catabolism so inc Ca conc
decreased wound healing
due to reduced collagen formation and fibroblast proliferation and inc protein catab
: less glucose uptake and use and increase gluconeogenesis so hyperglycaemia and diabetes
increased protein catabolism
: reduced muscle bulk, wound heal, bruise, thin skin, cardiomyopathy and myopathy
: redistribution of fat with moon face, buffalo hump, supraclavicular fat pads, central adiposity, thin limbs. increased HSL hormone sensitive lipase expression so increased free fatty acids
: depression and psychosis
What is cyclosporin derived from?
what is the mechanism of action of cyclosporin?
it binds cyclophilin in T cells and inhibits calcineurin to reduce IL2 transcription
give 2 uses of cyclosporin?
anti rejection treatment for transplant
2nd line for autoimmune diseases
what are the side effects of cyclosporin
increased urea and creatinine
bit of BM depression
narrow TI so needs TDM (therapeutic drug monitoring)
interacts with hepatic enzyme inducers and inhibitors e.g. ERYTHROMYCIN inhibits cytochrome p450 system so less metabolism of ciclosporin therefore increased toxicity
What is tacrolimus made by?
what is the MOA of tacrolimus?
post T cell receptor activation inhibition of calcineurin so reduced IL2 and other cytokine production
what is tacrolimus used for?
to reduce acute renal allograft rejection
whats the difference between tacrolimus and cyclosporin?
tacrolimus is more potent
and therefore also more toxic and more immunosuppressive so causes more opportunistic infections
what type of drug is azathioprine?
purine anti metabolite
prodrug activated to 6 mercaptopurine
what is the MOA of azathioprine?
aza is converted to a fraudulent purine analogue
inhibits DNA synthesis so reduces proliferation of WBC esp B and T lymphochytes
what is azathioprine used for? 2 main categories and give subcategories
transplant - reduce rejection
autoimmune diseases such as RA, IBD, AIH, MS, pemphigus (skin sores and blisters)
how is azathioprine metabolised?
what drug can increase the toxicity of azathioprine and how?
allopurinol can as it inhibits xanthine oxidase, so less aza is metabolised
what are the side effects of azathioprine?
increased risk tumour especially lymphoma (NHL) and SCC
increase risk infection, pancreatitis
anorexia, N and V
what type of drug is cyclophosphamide?
nitrogen mustard alkylating agent
what is the MOA of cyclophosphamide?
crosslinks DNA and prevents replication
what is cyclophosphamide especially useful for?
B cell suppression
give 3 main uses of cyclophosphamide?
give 3 main SE of cyclophosphamide
pancytopenia - so anaemia, neutropenia so inc infection, thrombocytopenia so bleed
what type of drug is mycophenolate mofetil? and how does it work?
purine anti metabolite to reduce lymphocyte production by reducing DNA synthesis
when is mycophenolate mofetil used?
alternative to azathioprine, if aza toxicity
: PREVENT TRANSPLANT REJECTION - immunosuppression
in which ways is mycophenolate mofetil better than azathioprine?
more specific inhibition of lymphocytes than azathioprine
less BM toxicity
what are the SE of mycophenolate mofetil?
what type of drug is methotrexate?
anti folate drug
what is the MOA of methotrexate?
inhibits dihydrofolate reductase to reduce RNA and DNA synthesis
give 5 uses of methotrexate
what must you give with methotrexate?
how often is methotrexate given?
once a week, orally
what are the side effects of methotrexate? 4
: anaemia, neutropenia
give 2 types of antiTNFa
: receptor blocker
adalimumab or infliximab
: MAb to TNFa
what is antiTNFa used for?
DMARD resistant RA, Ank spond, severe Crohns
what is INF1B used for?
MS - reduce relapse
What is INF1a used for?
in CHRONIC hep B and C to prevent further hepatic damage
what is the MOA of thalidomide?
inhibits TNF synthesis
what is the use of thalidomide?