1 - Intro to Pharm of Inflammation Flashcards
What is the importance of inflammation?
It provides self-protection to rid organism of initial cause of injury (mocrobes, toxins) and the consequences of the injury (necrotic cells).
Starts the healing process.
What negative things can result from inflammation?
Can be inappropriately triggered or poorly controlled.
Can cause tissue injury in disorders.
Underlie life-threatening hypersensitivity reactions.
__________ drugs would ideally control the harmful effects of inflammation, yet not interfere with its beneficial effects.
Anti-inflammatory drugs
What is the physiological response to ACUTE inflammation?
Vasodilation, increase in vascular permeability, accumulation of inflammatory cells.
Describe acute inflammation? What is the main characteristic? What are the main cell type involved?
Rapid onset (minutes) Short duration (hours-days)
Main characteristic is edema.
Main cell types: leukocytes, predominantly neutrophils (PMNs).
What triggers inflammation?
Infection and microbial toxins.
Tissue necrosis
Foreign bodies
Describe chronic inflammation? What is the main characteristic? What is the main cell type?
Prolonged duration (weeks to months)
Main characteristic: fibrosis
Main cell type: monocyte.
What can initiate chronic inflammation?
Immune-mediated inflammatory diseases: RA, MS, inflam bowel disease, allergic disease, asthma.
Prolonged exposure to potentially toxic agents, either exogenous or endogenous.
What is the cycle of chronic inflammation?
Propagation of the disease typically occurs as a result of an autoimmune response, inducing a self-amplifying cycle of damage.
Once a chronic disease is established, flares are frequent.
Inflammation is a _____ _____ response to foreign invaders and necrotic tissue, but it is itself capable of causing _____ _____.
Defensive host response
tissue damage
In most cases inflammation resolves without intervention, but harmful effects can require treatment with drugs. What are examples of harmful side effects?
Release of enzymes that digest normal tissues - collagenases in severe arthritis.
Edema/swelling that can obstruct airways/brain swelling.
Pain.
What is the mediator theory?
Signs and symptoms of inflammation are caused by the release of chemicals.
______ can be effective targets to treat inflammation.
Mediators.
What is histamine and what are it’s functions? What is a known therapeutic agent associated with it?
Biogenic amine that causes increased vascular permeability and pain.
Antihistamine/H1 receptor antagonist blocks histamine.
What is bradykinin?
A peptide that’s 9 amino acids long.
Increases vascular permeability and causes pain.
What is the physiological response of the complement system? Where are they found?
Made in the liver and circulate in the blood.
Chemotaxis, promote release of mediators from PMNs, and increase vascular permeability.
What is the acute phase reaction? What is acute phase protein?
Reaction: Response to injury, local inflammatory cells secrete cytokines that cause the liver to increase or decrease production of various proteins.
Acute phase protein is one whose plasma concentration changes from baseline by at least 25% during inflammation.
Which acute phase reactant is an inflammation marker that is associated with increased risk of diabetes, hypertension, and CV disease when it’s at high levels?
C-reactive protein (CRP) a plasma protein that’s a pentameric shape protein (25 kDa).
What are the five cardinal signs of inflammation?
Heat, swelling, redness, pain, and loss of function.
What are key cytokines that interact with specific receptors to induce gene expression through activation of TFs such as NFkB and AP-1?
TNF-alpha: causes fever
IL-1: causes fibroblast and lymphocyte proliferation and fever.
Fever caused by increase COX and lipoxygenase activity.
Induction of collagenase causes fibrosis.
What to drugs block TNF-alpha ?
Etanercept
Inflixamab
What drug released during injury has an anti-inflammatory effect and is released in response to methotrexate treatment?
Adenosine - a purine nucleoside formed from the breakdown of ATP.
What is the name of glycoproteins on the cell surface that mediate contact beteeen two cells or between cells and the EC matrix? What drug targets these for anti-platelet therapy in heart disease?
Cell Adhesion Molecules (CAMs) - a family of proteins including Ig-like CAMs, integrins, selectins, and cadherins.
Abciximab
What mediators are responsible for the intracellular killing of bacteria by neutrophils and have endogenous antioxidant mechanisms to control the effect of free radicals? What drug can target these?
Oxygen-derived free radicals: superoxides and hydroxyl radicals.
Targeted by antioxidents such as VitC and VitE, although there has been limited success in clinical trials.
