-
which immunisations are live attenuated and who can they not be given to?
- BCG
- Oral polio
- Yellow fever
- MMR
- 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)
- influenza
- pneomococcus
-
what are the effects of steroids? 2 main categories
- anti inflammatory
- immunosuppressive
-
how do steroids reduce inflammation?
- reduce production of PG, LT, thromboxane, PAF so
- reduced vasodilation
- reduced cap perm so less oedema
- reduced leukocyte infiltraion
- reduce bronchoconstriction
- reduce pain
- 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
- mineralocorticoid effects: 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
- easy bruising
- due to reduced collagen formation and fibroblast proliferation and inc protein catab
- carbohydrate metabolism: 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
- fats: 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
- CNS: depression and psychosis
-
What is cyclosporin derived from?
fungus norway
-
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
- hypertension
- hirsutism
- gum hypertrophy
- peptic ulcer
- 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?
bacteria
-
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?
xanthine oxidase
-
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?
- BM toxicity
- 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?
- lymphoma
- BM transplantation
- autoimmune diseases
-
give 3 main SE of cyclophosphamide
- haemorrhagic cystitis
- pancytopenia - so anaemia, neutropenia so inc infection, thrombocytopenia so bleed
- cardiotoxicity
-
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
- only use: PREVENT TRANSPLANT REJECTION - immunosuppression
-
in which ways is mycophenolate mofetil better than azathioprine?
- more specific inhibition of lymphocytes than azathioprine
- less BM toxicity
- less infection
-
what are the SE of mycophenolate mofetil?
- BM toxicity
- tumour development
-
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
- RA
- Ank spond
- Crohns
- Psoriatic arthritis
- ALL
-
what must you give with methotrexate?
folate supplements
-
how often is methotrexate given?
once a week, orally
-
what are the side effects of methotrexate? 4
- BM suppression: anaemia, neutropenia
- PULM FIBROSIS
- hepatitis
- teratogenic
-
give 2 types of antiTNFa
- etanercept: 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?
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