biologics clinical Flashcards
MOA of methotrexate
dihydrofolate reductase inhibitor, alters pyrimidine and purine biosynthesis
C/I with methotrexate
- infection - severe renal impairment - hepatic impairment - bone marrow suppression - immunodeficiency - pregnancy/breastfeeding - older patients
use of methotrexate in clinic
- low dose for immunosuppression - once a week - should only be prescribed in 2.5mg - alert card! - can be co prescribed with folic acid 5mg - Missed doses can be taken within 2 days with once weekly preparations
monitoring requirements for methotrexate
- baseline: FBC, LFT, urea, electrolytes, renal function- monitoring: LFT, renal function, FBC 1-2 weeks until stable then every 2-3 months
cautions with methotrexate
- surgery - renal impairment - diarrhoea - ascites - peptic ulcer - not had chicken pox
methotrexate side effects
- bone marrow suppression - GI toxicity - liver toxicity - pulmonary toxicity - skin reactions
MOA of leflunomide
affects de novo pyrimidine biosynthesis - particularly in activated lymphocytes due to increased demand
C/I in leflunomide
- hepatic impairment - severe immunodeficiency - severe infection - severe hyponatraemia - moderate renal impairment - pregnancy/breastfeeding
leflunomide use in clinic
100mg OD for 3 days then decrease to 10-20mg OD- Loading dose can cause side effects - Effect starts 4-6 weeks after taking and an improve 4-6 months after starting - Long half-life - 1-4 weeks - Monitoring after discontinuation is required
wash out procedure for leflunomide
□ Stop treatment □ Give cholestyramine 8mg TDS or activated charcoal 50g QDS Treat for 11 days
monitoring requirements for leflunomide
□ LFTs, FBCs, BP Every 2 weeks for the first 6 months and then every 8 weeks
cautions with leflunomide
- Administration with hemotoxic or hepatotoxic drugs - History of TB - Bone marrow suppression - leucopenia, anaemia, thrombocytopaenia
side effects of leflunomide
- hepatic impairment - bone marrow suppression - leucopenia - anaemia - thrombocytopaenia - hypertension - GI irritation - alopecia - skin reactions - dizziness
MOA of ciclosporin
calcineurin inhibitor
C/I for ciclosporin
abnormal renal function malignancy uncontrolled hypertension uncontrolled infection
cautions with ciclosporin
- Elderly (reduced renal and hepatic) - Gout - Hepatic impairment (main mechanism of metabolism)
use of leflunomide in clinic
- IBD, transplants, psoriasis, atopic dermatitis and RA - Oral solution should be mixed with orange/apple juice immediately before administration- BD - branded
monitoring requirements for ciclosporin
○ Renal function ○ Hepatic function ○ BP ○ Lipids ○ Electrolytes - potassium/magnesium Uric acid
side effects of leflunomide
- fatigue, convulsions, muscle cramps, hyperlipidaemia/glycaemia/tension/kalaemia, hypomagnesaemia
toxic side effects of leflunomide
headache, tremor, hypertension, Hirsutism, ○ Renal impairment
anti-tnf therapy example
infliximab
IL6 receptor inhibitor example
tocilizumab
anti b cell example
rituximab
anti t cell example
abatacept
jak inhibitor example
tofacitinib
C/I with anti-tnf therapy
- hypersensitivity - severe infection/TB- mod - sev heart failure
C/I with jak inhibitors
- surgery/immobilisation - MI- HF- malignancy - age - obesity
monitoring for biologics
before - FBC, eGFR, Cr, LFT, hep B during - every 6 months - FBC, LFT, renal
use of anti-tnf in clinic
- RA, crohns, psoriasis - IV over 2 hours plus 1 hr monitoring - antihistamine pre treatment (or SC)- once a week - blood disorder/TB symptoms report
cautions with anti-tnf
- infection - demyelinating disease - malignancy - mild HF - elderly
jak inhibitors side effects
- increased infection risk - hypersensitivity reactions - URTI - headache - pain
serious side effects of jak inhibitors
- new or worsening heart failure- delayed hypersensitivity- haematological reactions- demyelinating disorders- hepatobiliary events- malignancies- serious infusion reactions
