Anti-inflammatories Flashcards
What is COPD treated with?
β2 agonists
muscarinic antagonists
Corticosteroids
How is asthma characterised?
Shortness of breath, wheezing
Inflammation of airways
Bronchial hyper-reactivity
Reversible airway obstruction
Associated with over-active Th2 cells which activate interleukins and IgE which activate eosinophils and mast cells
Polymorphisms in β2 adrenoreceptors
What are some common asthma treatments?
Salbutamol
Steroids
Beta blockers
How is early phase allergic asthma characterised?
Reversible airway obstruction and inflammation
How is late phase allergic asthma characterised?
Mast cells in the lower respiratory tract being activated, releasing cytokines. This leads to leukocyte infiltration, causing inflammation
How is allergic rhinitis characterised?
Allergen activates mast cells in nasal mucosa
Nasal congestion
Where are histamine and prostaglandins released from?
Mast cells
What physiological effects do mast cell activation have?
Bronchoconstriction and increased vascular permeability from prostaglandins
Nerve endings stimulated for coughing
Decreased lung elasticity from mucus and increased collagen
What mechanism do NSAIDs have?
Cyclo-oxygenase inhibitors. Prevents prostaglandin and thromboxane production
What effects do NSAIDs have?
Decreases vasodilation and therefore odema
Analgesic and antipyretic
Inhibits prostaglandins and thromboxanes (these are very lipophilic)
What is the active ingredient of aspirin?
Acetyl salicilic acid
What side effects can aspirin have?
Gut irritation, leading to internal bleeding and diarrhea
What is COX1 responsible for?
Normal functioning. Constituitively expressed in most tissue. Responsible for platelet aggregation, renal blood flow and prostaglandins protecting the GI tract
How is COX2 characterised?
inducible and is used in inflammatory cytokines (IL-1 and tumour necrosis factor (TNFα)). Plays a role in renal homeostasis and the CNS
Where is COX3 found?
Brain and kidneys
Least well understood
What is the COX enzyme structure like?
2 identical subunits forming and dimer
Two catalytic sites:
Peroxidase site
Cyclo-oxygenase site
How do the COX1 and COX2 binding sites differ?
COX-1 has Iso523
COX-2 has Val523 which makes a wider channel. This increases its specificity
How does aspirin bind to COX enzymes?
Its acetyl group forms a bond with serine on the cyclo-oxygenase site. This permanently binds to COX, making it a suicide inhibitor.
Aracodonic acid can no longer enter the COX site
What side effects can COX inhibitors have?
Gastric bleeding due to inhibition of prostagladins not secreting stomach acid
Disruption of renal flow due to prostaglandins being inhibited
Liver damage due to phase 1 of metabolism on paracetamol forming a cytotoxic intermediate
How can inhibition of prostaglandins be treated?
Misoprostol (PG analogue)
What are DMARDs used for?
Reducing joint damage, pain and inflammation in individuals with rheumatoid arthritis
How does cyclosporin work as an immunosuppressant?
Decreases T cell proliferation by inhibiting IL-2 synthesis and IL-2 receptor expression
What are the main side effects of cyclosporin?
Most serious side effect is nephrotoxicity
Hepatotoxicity and hypertension can also occur
What is a syndrome developed from chronic prednisolone use?
Cushing’s syndrome
What characterises Cushing’s syndrome?
Hypertension
Cataracts
Poor wound healing
Increased abdominal fat
muscle wasting
How can monoclonal antibodies be used to treat inflammation?
Recognises TNFα and prevents it binding to its receptors
Humanised so that the antibody isn’t rejected
High affinity and selectivity for the target
How does methotrexate treat rheumatoid arthritis?
folic acid antagonist with cytotoxic and immunosuppresant activity.
Which rheumatoid arthritis drug is also used to treat chronic inflammatory bowel disease?
Sulfasulazin
What does cyclosporine bind to in cytokine inhibition?
Calcineurin (dephosphorylates NFKB)
What does glucocorticoid do in cytokine inhibition?
Inhibits NFKB transcription of cytokines
