Drugs Flashcards
1
Q
What is biological therapy?
A
- Prod by means of bio processes involving recombinant DNA technology
- Includes…monoclonal antibodies, receptor constructs, signaling proteins
- Highly specific, have an effector function and must have some part of their structure that withstands immediate breakdown
2
Q
4 Anti-TNF antibodies
A
- Infliximab - chimeric TNF antibody; need methotrexate at same time to prevent antibodies against mouse portion
- Etanercept - 2 human p75 TNF receptors +Fc that bind and inhibit free TNF
- Adalimumab - humanized TNF antibody; subQ injection every 2 wks
- Golimumab- fully human TNF antibody
- Certolizumab pegol - human Fab + polyethylene glycol (PEG inc half-life)
- **Side effects= inc opportunistic infection (esp TB - reoccurrence of latent TB), worsening lung disease, CHF, demyelination, drug-induced lupus, injection site rxn
3
Q
Anakinra and Anakinumab
A
Anti- IL-1
- Anakinra - recombinant IL-1 receptor antagonist; less effective but safer
- Anakinumab- IL-1 antibody
4
Q
Tocilizumab
A
- antibody against IL-6 receptor (IL-6 leads to neovascularization and panes formation in RA)
5
Q
3 Anti IL-17/23 Drugs
A
- Ustekinumab - human antibody; targets p40 subunit of IL-12 and IL-23; for psoriasis
- Secukinumab- against IL-17R; also for psoriasis and ankylosing spondylitis
- Brodalumab - against IL-17A; leads to eventual TRAF6—> NF-kB —> pro-inflammatory transcription; for psoriasis and ankylosing spondylitis
6
Q
Abatacept
A
- Targets T cells
- extracellular CTLA4 fused to IgG1 heavy constant region; competes w/ CD28 to down-regulate T cell activation
- **Risk of upper respiratory infection
7
Q
3 Antibodies that Target B Cells
A
- Rituximab - chimeric antibody against CD20 (on mature naive B cells but not plasma cells; so mainly dec APC actions and cytokines production)
- Depletes autoantibodies, dec APC by B cells, dec B cell cytokine exp and T cell co-activaiton, CD20+ T cell depletion
- Epratuzumab- targets CD22 on B cells
- Belimumab - targets BLys (B cell proliferation and differentiation)
8
Q
Natalizumab
A
- antibody against alpha4beta1 intern (specific for lymphocyte migration to CNS and intestinal parenchyma); used for MS
- No longer on market
9
Q
Anti-Malarials (3)
A
- Hydroxylchloroquine, Chloroquine, Quinacrine
- Least toxic and slow; usually good for early/mild disease
- Mechanism- weak base so conc in acidic lysosomes —> interrupt MHC class II presentation —> less lymphocyte stimulation (also prevent thrombosis, help w/ glucose tolerance, lower LDL)
- Side effects - RETINAL TOXICITY (check baseline then yearly after 5 yr) **most common in chloroquine
10
Q
Anti-Metabolites (2)
A
- Methotrexate
- Dose escalation
- Mechanism - dec purine synthesis (inhibit dihydrofolate reductase) AND at low dose…inc AICAR —> adenosine —> inhibitor of neutrophils and anti-inflammatory
- Side effects - inc risk of infection, nausea, photosensitive, lymphoma risk, teratogenic, renal
- Monitor CBCs, Cr and LFTs
- Leflunomide
- No dose escalation
- Mechanism - dec pyrimidine synthesis (inhibit dihydrorotate dehydrogenase)
- Similar to methotrexate but only FDA approved for RA
- Also should not use if pregnant
11
Q
Transplant Meds (3)
A
- AZA —> 6-MP
- Mechanism- inhibit purine synthesis
- Caution- if use w/ purine analogue (allopurinol for gout) OR if thiopurine S methyltransferase deficiency
- Side effects - GI, lymphoma risk, rash
- Use if liver issues b/c less toxicity than others
- Cyclosporine/Tacrolimus
- Mechanism - inhibit calcineurin (phosphatase) in T cell signal pathway (less IL-2 transcription)
- Side effects- renal; gout; inc K+, neuropathy or tremors
- Monitor - levels of drug + CBCs, LFTs, Cr
- Mycophenolate Mofetil (MMF)
- Prodrug —> mycophenolic acid
- Mechanism - inhibit purine synthesis (inhibit inosine monophosphate dehydrogenase)
- Side Effects - GI, inc infection, PML, cytopenia, liver toxicity
12
Q
Cyclophosphamide
A
- LOTS OF TOXICITIES so used if severe lupus, vasculitis, connective tissue disease
- Mechanism - prodrug activated cp450 enzyme —> phosphoramide mustard which alkylates DNA and crosslinks it DNA to break it and dec DNA synthesis and apoptosis
- Toxicity - GI, alopecia, hepatotoxic, infections, bone marrow suppression, inc risk of bladder cancer, lymphoma or leukemia
- May put on prophylaxis
- Infertility - premature ovarian failure and azoospermia BUT safe in pregnancy
13
Q
Sulfasalazine
A
- Use in early mild disease
- Less clear mechanism
- Much less toxic but also less effective
- Side effects - GI, rash, headache, neutropenia, azoospermia (reversible if stop drug); safe in pregnancy
14
Q
Physio Cortisol
A
- Prod by adrenal cortex via hydroxylation of cortisone
- Stress —> CRH from hypothalamus —> ACTH from pituitary —> cortisol from adrenal cortex
- Only 10% bio active (rest bound to globulin or albumin)
15
Q
Glucocorticoid Mechanism
A
- Glucocorticoids are synthetic cortisol; act on same receptors
- Crosses cell membrane —> binds receptors in cytoplasm (receptor made of heat shock protein which becomes displaced on binding) —> conformational change —> translocation into nucleus —> promotes or inhibits transcription of certain genes
- Inc synthesis of lipocortin (inhibits phospholipase A2
- Inhibit synthesis of cytokines like TNFalpha
- Crosses cell membrane —> binds receptors in cytoplasm (receptor made of heat shock protein which becomes displaced on binding) —> conformational change —> translocation into nucleus —> promotes or inhibits transcription of certain genes
- Immune Effects
- Dec clearance - helps inc platelet count if platelet bound by antibodies
- Dec adhesion molecules/dec endothelial permeability —> less neutrophil migration to site (seen as higher neutrophil count in blood)
- Levels of basophils, eosinophils, lymphocytes and monocytes all dec in blood
