Anti-Inflammatories Flashcards
What is inflammation?
A protective response by the body to something harmful.
Pathological inflammation is inflammation that is inappropriate or over-exubrerant
List the clinical signs/symptoms of inflammation
Rubor (Redness)
Calor (Fever)
Tumor (Swelling)
Dolor (Pain)
Loss of function
What are the 2 components of inflammation
Innate non-adaptive immunological response
Adaptive (specific) immunological response
Describe the steps of acute inflammation
A trigger is recognised by the immune cells present in the tissues (PAMPs & DAMPs)
PAMPs and DAMPs bind to the pathogen recognition receptor on sentinel cells.
Following recognition, cells release inflammatory meditators.
Vascular component:
Vasodilation
Increased vascular permeability = oedema
Cellular component:
Recruitment of leukocytes
=Elimination of pathogens
Trigger >
Recognition of immune cells present in the tissue (PAMPs & DAMPs) >
PAMPs & DAMPs bind to the pathogen recognition receptors on sentinel cells >
Following recognition, cells release inflammatory mediators
Vascular component:
Vasodilation
Increased vascular permeability = oedema
Cellular component:
Recruitment of leukocytes
=Elimination of pathogens
Describe the process of leukocyte recruitment
Cytokines (TNF-alpha) are released
Acts on endothelial cells
Expression of adhesion molecules
Immune cells circulating in the blood attach
Immune cells enter into the tissue
Destroy pathogen
What cells are involved in the adaptive immune response
Lymphocytes: B cells, T cells, Antigen presenting cells
Briefly explain the adaptive immune response
Antigen presenting cells (APCs) present the antigen on Major histocompatibility complex (MHC) to T cells.
Co stimulatory signals: CD86/80 on APCs interact with CD28 on T cells
= Activation of T cells
= Activation of other T and B cells (Cytotoxic T cells and B cells)
What are the different classes of anti-inflammatory drugs
NSAIDs
Glucocorticoids
DMARDs: Conventional DMARDs, Biologics, Targeted synthetic DMARDs
Discuss NSAIDs.
MOA
Different classes + examples
NSAID properties
NSAIDs inhibit cyclooxyrgenase enzymes (Isoforms COX1 & COX2)
2 classes of NSAIDs
Non-selective NSAIDs: Aspirin, Ibuprofen
Selective NSAIDs: Celecoxib
NSAIDs have anti-inflammatory, antipyretic and analgesic effects
Discuss glucocorticoids
MOA
Examples
Properties
Side effects
Binds to glucocorticoid receptor > Translocation to the nucleus > Alters gene transcription
Prednisone, cortisone
*Highly anti-inflammatory effects
Rapid onset of action
Long term use is associated with:
High blood pressure
Cushing’s disease
What are DMARDs (its purpose).
State the different types of DMARDs, give an example for each
DMARDs are used to control symptoms and stop/slow the progression of chronic inflammatory diseases.
Types:
Conventional DMARDs i.e. Sulfasalazine
Biologics i.e. Adalimumab
Targeted synthetic DMARDs i.e. Tofacitinib
What are conventional DMARDs?
Small molecules, with non-specific MOA, have anti-proliferative and cytotoxic effects
Affect activation/proliferation of lymphocytes = Immunosuppressive effects
But also affects other rapidly dividing cells = Side effects
E.g. Sulfasalazine, Hydroxychloroquine
What are Biologics
Give an example
Therapeutic agents produced using living organisms or their components (such as cells, proteins, nucleic acids, or tissues).
These drugs are typically large and complex molecules
E.g. Adalimumab, Golilumab, Etanercept
Compare and contrast Biologics and Conventional DMARDs
Biologics:
Highly complex manufacturing process, Difficult to replicate
Large molecules (cannot be administered orally)
More unstable and sensitive to external conditions
csDMARDs:
Easy manufacturing process that is easy to replicate
Small molecules
Stable
What are the different types of bDMARDs +MOA
Anti TNF-alpha therapies:
Binds to TNF-α, preventing cytokine from interacting with cell surface receptors (TNFR1 and TNFR2)
Interleukin inhibitors: Anakinra competitively inhibits the binding of IL-1 to its receptor, preventing the signaling cascade that leads to inflammation.
IL-6 inhibitor: Tocilizumab
Tocilizumab inhibits IL-6 from binding to its receptor, thereby disrupting the signaling pathway and reducing inflammatory processes.
IL-1 inhibitor: Anakinra
Anakinra competitively inhibits the binding of IL-1 to its receptor, preventing the signaling cascade that leads to inflammation.
T-cell activation inhibitors: abatercept
B-cell depletion: Ritixumab
