Immunosuppression: drugs Flashcards
Short-acting corticosteroids
Hydrocortisone (cortisol, the natural corticosteroid) Prednisone, prednisolone
Triamcinolone
Medium-term action corticosteroid (24-48h)
Dexamethasone
Longer-term action corticosteroid (>48hrs)
Prednisone
Short acting corticosteroid. (<24hrs)
Prodrug, metabolised to prednisolone
Prednisolone
Short acting corticosteroid
Infliximab
Uses?
Monoclonal antibody, binds (sequesters) TNF-alpha
Crohn’s disease, Rheumatoid arthritis
Adalimumab
Uses?
Monoclonal antibody, binds (sequesters) TNF-alpha
Crohn’s disease, Rheumatoid arthritis
Etanercept
Binds (sequesters) TNF-alpha, not strictly a monoclonal antibody
An artificial construct of the receptor for TNF-alpha fused to an antibody Fc domain
Omalizumab
Uses?
Monoclonal antibody, binds IgE
IgE-mediated asthma
Alemtuzamab
Uses?
Monoclonal antibody
Binds CD52 leading to destruction of B and T cells by cell-based immunity.
Thus acquired immunity is ‘reset’ to a naive state. Patients still have functioning innate immune system, do not suffer hugely increased rate of infection.
B-cell chronic lymphocytic leukaemia (CLL) Multiple sclerosis (still in trials)
Zileuton
Inhibitor of 5-lipoxygenase
(inhibits production of leukotrienes)
Treatment of asthma, other respiratory diseases e.g COPD
Zafirlukast
Leukotriene D4 and E4 receptor antagonist
Treatment of asthma, other respiratory diseases e.g COPD
Cromolyn sodium
Inhibits release of inflammatory mediators from mast cells
Treatment of asthma, other respiratory diseases e.g COPD
Salbutamol
B2 selective adrenergic agonist
(Bronchodilator, also inhibits release of inflammatory mediators from mast cells)
Short acting
Treatment of asthma, other respiratory diseases e.g COPD
Salmeterol
B2 selective adrenergic agonist
(Bronchodilator, also inhibits release of inflammatory mediators from mast cells)
Longer acting than salbutamol
Treatment of asthma, other respiratory diseases e.g COPD
Ipratropium
Muscarinic antagonist.
Asthma, also used in COPD
Theophylline
Phosphodiesterase inhibitor
A methylxanthine
Treatment of asthma, other respiratory diseases e.g COPD. Causes direct bronchodilation.
Inhibits degranulation of mast cells
Drugs used to treat rheumatoid arthritis
NSAIDS
Disease modifying anti-rheumatoid drugs (DMARDS)
- Methotrexate
- gold compounds
- Sulfasalazine,
- Penicillamine
- Chloroquine
Glucocorticoids: may be used systemically or topically
Antibodies against cytokines e.g Infliximab, Adalimumab against TNF-α
Methotrexate
Inhibits folic acid synthesis
Sulfasalazine
Interferes with lymphocytes
Penicilllamine
Metabolite of penicillin
Inhibits T lymphocyte proliferation
Chloroquine
Inhibits T lymphocyte proliferation.
Also antimalarial
Transplantation and immunosuppression
Systemic corticosteroids: effective but long term treatment with high doses necessary to prevent rejection - NB side effects.
Cyclophosphamide Alemtuzumab Cyclosporin, Tacrolimus Sirolimus (rapamycin) Basiliximab Azathioprine, mycophenolate
Cyclophosphamide
Uses?
Alkylates DNA: adds an alkyl group to guanosine, preventing DNA replication- causes apoptosis of rapidly dividing cells.
Inhibits B, T cell proliferation
Prodrug- metabolised in liver to active compound, a nitrogen mustard alkylating agent.
Used for aggressive short term treatment of severe autoimmune diseases, also in cancer chemotherapy
Numerous side effects: hair loss, haemorrhagic cystitis, infertility.
Cyclosporin
Calcineurin inhibitor
Inhibits secretion of IL2
Inhibits T cell proliferation & mobilisation
Tacrolimus
Calcineurin inhibitor
Inhibits secretion of IL2
Inhibits T cell proliferation & mobilisation.
Sirolimus
Inhibits mTOR
Blocks late activation of T and B cells
Basiliximab
Antibody against IL-2 receptor
Blocks late activation of T cells
Azathioprine
Inhibits guanosine synthesis, and thus DNA synthesis. Prevents B, T cell proliferation
Effects limited mainly to B, T cells because other cell types possess an alternative salvage pathway for guanosine synthesis.
Mycophenolate
Inhibits guanosine synthesis, and thus DNA synthesis. Prevents B, T cell proliferation
Effects limited mainly to B, T cells because other cell types possess an alternative salvage pathway for guanosine synthesis.
Hydrocortisone
= cortisol, the natural corticosteroid.
A glucocorticoid
COPD
Treatment
Lung disease
- reduced airflow
- inflamed airways
- different inflammatory cell profile to asthma
Treatment:
- cromolyn sodium, zileuton, zafirlukast, salbutamol, salmeterol, ipratropium, theophylline (as asthma)
Inhaled glucocorticoids are NOT effective.
- basis of resistance is unclear
- may relate to high levels of oxidative stress within lungs of COPD patients, many of whom are smokers
oxidation products formed may interfere with normal effects of glucocorticoids.
Asthma
Treatment
A chronic inflammatory disease affecting the lungs. Characterised by:
- variable airflow
- airway hyper-responsiveness to various stimuli
- episodic bronchoconstriction
Treatment:
- inhaled glucocorticoids: reduce production of acute inflammatory mediators, & cytokins, homing of T cells to the lungs, prevent dendritic cell maturation
- cromolyn sodium
- zileuton, zafirlukast
- salbutamol, salmeterol
- ipratropium
- Theophylline
Calcineurin
Inhibitors?
A Ca2+ dependent serine-threonine phosphatase.
Dephosphorylates NF-AT (nuclear factor- activated T cells)
Dephosphorylated NF-AT translocated to the nucleus and causes upregulation of IL-2, which is important for T cell proliferation.
Inhibition of calcineurin (e.g cyclosporin, tacrolimus) therefore inhibits mobilisation of T cells.
