Corticosteroids Flashcards
(33 cards)
What is inflammation?
- Very generally speaking, inflammation is the immune response to an irritant
- The irritant might be a germ, but it could be a foreign object as a splinter in your finger
What is the purpose of inflammation?
- The inflammatory response is a defence mechanism to protect from injury and infection
- To localize and eliminate the injurious agent and to remove damaged tissue components so that the body can begin to heal
Acute vs Chronic inflammation?
- An inflammatory response that lasts only a few days is called acute inflammation, while a response of long duration is referred to as chronic inflammation
What are some inflammation associated diseases? (6)
- Diabetes mellites
- Inflammatory breast cancer
- Pulmonary diseases, asthma
- Arthritis and autoimmune disease
- Inflammatory bowel disease
- Cardiovascular disease
When can inflammation be bad, asthma, arthritis?
- Asthma, asthmatic bronchioles are much more inflamed than normal and cause restricted air flow, inhale corticosteroids
- Arthritis, inflammation of the joints, injection of corticosteroids
What are corticosteroids?
Corticosteroids: class of drugs that lowers inflammation and immune system activity in the body (shut down whole immune system)
What symptoms do corticosteroids treat?
corticosteroids ease swelling, itching, redness, and allergic reactions, doctors often prescribe them to help treat diseases like asthma, arthritis
What is a steroid?
A steroid is a biologically active organic compound with 4 rings arranged in a specific molecular configuration
What are steroids 2 main functions?
- Important components of cell membranes which can alter membrane fluidity (made from cholesterol)
- Are signaling molecules
What are the two kinds of corticosteroids?
Corticosteroids – refers to both glucocorticoids and mineralocorticoids but is often used as a synonym for “glucocorticoid”
What does the adrenal gland produce?
The adrenal gland produces cortisol, corticosteroids, aldosterone
How does stress signal produce corticosteroids?
A signal (stress, illness, hypoglycemia, hemorrhage) tells the brain to produce the hormone (CRH) in the hypothalamus
CRH acts on the pituitary gland to produce ACTH
ACTH acts on the adrenal gland to produce corticosteroids
Corticotropin-releasing hormone (CRH)
Arginine vasopressin (AVP)
Adrenocorticotropic Hormone (ACTH)
What does ACTH do?
ACTH: goes into the adrenal gland and regulates glucocorticoid synthesis
ACTH increases the delivery of cholesterol to the inner mitochondrial membrane (of cells in the adrenal gland)
Increases transcription of steroidogenic enzymes
(need cholesterol to produce glucocorticoids)
ACTH regulates glucocorticoid synthesis in the zonae fasciculata/reticularis
Cortisol synthesis?
Starting with cholesterol, the 2 main enzymes used are CYP17 and CYP11B1
Negative feedback of glucocorticoids?
Too much glucocorticoids – negative feedback
Signals to hypothalamus to stop producing CRH
Turns off pathway
Steroid hormone receptors?
- Are generally intracellular receptors (cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days
glucocorticoid signaling:
chaperones bind to it and bring It into the cell – nucleus
Anti-inflammatory Effects of Glucocorticoids?
- Changes in cell proliferation, survival, differentiation, migration
- Decrease pro-inflammatory cytokines, interleukins, prostaglandins
- Can affect cell growth, adverse effect in kids, need to make sure its localized affect, asthma
Effects of glucocorticoid on inflammatory cells?
- Stops degradation of mast cells, stops recruitment of other cells to stop proliferation of other immune cells
- Corticosteroids inhibit immune “signals”
Metabolic effects of glucocorticoids?
Generally transcriptional activation
- Metabolic – increase glucose to protect the brain and heart (fight or flight)
- Increase blood glucose by:
o Increasing glycogen breakdown (glycogenolysis)
o Increasing glucose synthesis (gluconeogenesis)
o Decreasing fat deposits (increased lipolysis)
o Increased protein catabolism and decreased synthesis
(CBG) corticosteroid-Binding globulin?
- Transports glucocorticoids in the blood and thereby modulates the tissue availability of these hormones
- Basically, binding to CBG helps transport the hormone but inflammation, stress, induced release of molecules like elastase releases the steroid from the complex
- When giving someone a glucocorticoid the CBG binding, and loss of bioavailability needs to be considered
- Absence of CBG – less availability
Pharmacokinetics of glucocorticoids?
- Glucocorticoids are administered through most routes, but local administration is preferred to minimize adverse effects associated with systematic actions
- Circulating cortisol is 80%-90% bound to plasma proteins with high affinity to corticosteroid-binding globulin (CBG, transcortin), 5%-10% loosely bound to albumin, and 3%-10% as the free, active fraction
- (lipid base transported in blood, CBG binding protein, CBG in blood, glucocorticoids release by adrenal gland, can bind to CBG, can move anywhere)
- CBG can also bind synthetic glucocorticoids such as prednisone and prednisolone, but not dexamethasone, resulting in almost `00% of plasma dexamethasone bioactive
glucocorticoids absorption in the GI tract, the skin?
- Most glucocorticoids are absorbed rapidly and readily from the GI tract and from synovial and conjunctival spaces because of their lipophilic character, but they are absorbed very slowly through the skin
Increased estrogen effect on cortisol and CBG?
- Elevated concentrations of estrogen, such as occurs in pregnancy, contraceptive use, or hormone replacement therapy, increase the biosynthesis of CBG in the liver, requiring increased plasma cortisol concentrations to maintain an appropriate bioactive fraction
What is the circadian rhythm?
Circadian rhythm is the name given to your body’s 24-hour internal clock
Glucocorticoids are regulated by circadian rhythm
At different times of the day, you can have more or less glucocorticoids
If you give more corticosteroids when levels are already elevated, this has a different effect on the body
