Quiz 2 Inflammation Flashcards
(216 cards)
1
Q
Innate Immunity
A
- born with
- non-specific
2
Q
Examples of Innate Physical Barriers:
A
- skin, mucus and cilia, stomach acid, tears + saliva
3
Q
What type of cells are INNATE?
A
- WBC..
- neutrophils, eosinophils, basophils, monocytes
4
Q
Acquired immunity aka as..
A
Humoral “blood” immunity
5
Q
Acquired Immunity
A
whereas immune system adapts and remembers specific pathogens for future defense
6
Q
Antigen
A
- a molecule (proteins, sugars) that can provoke the response.
ie.) found on bacteria, viruses, or other foreign substances
7
Q
When B- cell detects an antigen..
A
it gets activated and starts making antibpdoes
8
Q
What are immunoglobulins?
A
- They are antibodies (in the blood)
9
Q
How does immunoglobulin work?
A
-antibodies inactivate invading pathogens + mark them for phagocytic destruction (so that macrophages can eat and destroy them)
10
Q
Immunoglobulin is a biologic… What does it mean?
A
- We do not give it ORALLY
11
Q
Antibody Mediated B- Cell
A
Synthesize ‘antibodies’ – proteins called ‘immunoglobulins’ (in blood)
12
Q
Cell-mediated: T cells
A
*T-cells recognize foreign markers, antigens, and destroy directly + activate phagocytic cells
13
Q
Why is it that T-cells have high viral efficacy?
A
T-cells are especially important in fighting viruses - because viruses hide inside cells, where antibodies can’t reach them
14
Q
Innate Immunity includes:
A
- Physical barriers: skin, mucous membranes
-Cellular Barriers: phagocytes, NK cells, mast cells - Process Barriers: inflammation, cytokines, fever, opsonins
15
Q
Cellular Barriers are includes of:
A
Phagocytes-> eating cells
eg.) macrophages, neutrophil
NK cells : They recognize “abnormal” cells and destroy them without needing antibodies
Mast cells : Release histamine
triggering inflammation to help the immune response
16
Q
Process barriers include of:
A
Inflammation, Cytokines, Fever, Opsonins
17
Q
Inflammation
A
The body’s reaction to injury or infection, causing redness, swelling, heat, and pain.
18
Q
Cytokines
A
signaling proteins that help immune cells communicate
- interferons & interleukins
19
Q
Interferons
A
Help stop viral replication in infected cells
20
Q
Interleukins
A
Help activate other immune cells
21
Q
Complement system
A
A group of proteins (about 50) in the blood that, when activated, work together to fight infections and clear damaged cells
22
Q
Fever
A
Natural response that raises body temp to slow down pathogens and boost immune activity
23
Q
Opsonins
A
Proteins that “tag” bacteria and viruses-> making easier for immune cells to destroy them
24
Q
What are cellular barriers?
A
- involve specific cell types that are directly involved in defending the body against pathogens
25
Adaptive Immunity Cellular Barriers:
- T-cells: memory t-cells, helper t-cells, cytotoxic t-cells
- B-cells antibodies (immunoglobulins)
- B-cells memory
26
Memory T-cells
"Remember" past infections for faster responses in the future.
27
Helper T-cells
Directly kill infected or cancerous cells
28
B cells- antibodies (immunoglobulins)
- activated by an antigen, it produces antibodies (immunoglobulins) that bind to the pathogen.
- These antibodies neutralize the pathogen and mark it for destructio
29
B cells- memory
Memory B-cells "remember" past infections and allow for faster antibody production in the futur
30
Innate immunity: Physical Barriers include:
- Other epithelial linings (protective cell layer) such as digestive, respiratory, urinary
, reproductive tracts
- mucous
- Mucous cell
- Tight junctions
- Entrapped particle
- Basement membrane
- Epithelial cells tied together by tight junctions and supported by fibrous basement membrane
31
Phagocytes-> eating cells
eg.) macrophages, neutrophil
32
NK cells
They recognize "abnormal" cells and destroy them without needing antibodies
33
Mast cells
Release histamine: triggering inflammation to help the immune response
34
What type of tissue is Blood?
Connective tissue
35
Kupffer cells
marcophages located in the liver
36
Blood is made up of:
RBC's WBC's, Platelets, Plasma (liquid; mostly water), Fibrinogen
37
RBCs
Carry oxygen from the lungs to the body
38
WBCs
Fight infections and keep you healthy
39
Platelets
Help blood clot when you get a cut
40
Plasma (liquid)
Carries cells, nutrients, hormones, and waste
41
Fibrinogen (fibers)
Helps blood clot to stop bleeding
*is like a glue that holds the platelet in place
42
What is blood flow's goal?
- perfusion of organs
43
What happens to those cells without direct blood flow? and why is organ perfusion relevant?
- Cells receive their nutrients from blood
- Even those cells that do not have or lack access to blood vessels; can rely on diffusion of from areas with blood flow
44
When blood flow is absent:
- We have necrosis (cell- death)
ie.) Stroke → When a blood vessel in the brain is blocked, brain cells die.
ie.) Heart Attack → When blood flow to the heart is blocked, heart cells die.
45
Different functions of blood?
- Transport of nutrients
-*Waste away from cells (e.g. lactic acid, creatinine, CO2, …)
- *Body temperature regulation
- *Clotting
-*Osmotic pressure – fluid movement (e.g. albumin, …)
- *Protection (immunity e.g. WBC)
46
Lactic acid
waste from muscle activity
47
Creatinine
waste from muscle breakdown, filtered by kidneys
48
Carbon dioxide (CO₂)
waste gas exhaled by lungs
49
Hypothalamus
aka "master regulator"
- critical role in maintaining homeostasis
50
When too hot, what does the hypothalamus tells the brain to do?
- Vasodilate
51
When too cold, what does the hypothalamus tells the brain to do?
- Vasoconstrict, to retain heat when its too cold
52
Clotting; as one of blood's fx?
Platelets and fibrinogen help form blood clots to stop bleeding after injury
53
Osmotic pressure
Osmotic pressure controls how water moves between blood and tissues
54
Albumin
(a protein in blood plasma) helps keep water inside blood vessels so fluids don’t leak into tissues, preventing swelling
55
Blood as: Protection (immunity e.g. WBC)
White blood cells (WBCs) defend against infections.
They attack bacteria, viruses, and other harmful invaders to keep the body healthy
56
Blood is mainly made up of: (2)
- Plasma (55%)
- Cells (45%) aka formed elements
57
Plasma (55% of whole blood volume)
- made mostly of 92% water
- carries nutrients, hormones, waste, and proteins.
- contains blood proteins (albumins, globulins, fibrinogen)
58
Where are blood proteins (such as albumins, globulins) synthesized?
In the liver
59
What type of blood protein is aka as immunoglobulins?
- Globulins
60
Cells aka "formed elements" (45% of whole blood volume)
-*Red (RBC): majority erythrocytes- carry O2 throughout the body
- White (WBC), Platelets (buffer less than 1%)
61
Buffer
- part of "formed elements"
- but it is comprised of leukocytes, and platelets
62
How are RBC and WBCs created?
- Hematopoesis
- occurs at the bone marrow
RBC: erythropoesis
WBC: leukopoeisis
63
what are thrombocytes?
- platelets
64
Which cell are WBC's- monocyte, neutrophil, eosinophil, basophil produced?
Myeloid Stem Cell aka Mast cell (that came from Pluripotent stem cell)
65
Which cell are B- lymphocyte, T-lymphocyte produced from?
- lymphoid stem cell
66
What are monocytes called when they are found in tissues?
Macrophages
66
Pluripotent Stem cell in the bone marrow can turn into 2 different stem cells. What are they?
- Myeloid Stem Cell: think of BEMN-
- Lymphoid Stem Cells: B and T lymphocytes
67
B-lymphocytes turn into what?
plasma cells (produce large amount of antibodies)
68
Pre B-cells turn into what?
-> develop into B-cells
--> B lymphoblast
--> B lymphocyte: Plasma cell-> produces antibodies
69
Prothymocyte (Pre T- lymphocyte)
T lymphoblast
-->T lymphocyte-> kills infected cells and helps immune response
70
Buffy coat
a thin, white layer between plasma (on top) and red blood cells (on bottom) in a separated blood sample
71
Erythrocytes (red blood cells)
carry oxygen throughout the body.
72
What does RBC contain that binds to O2 and transports it to tissues?
Hemoglobin
73
WBC "leukocytes" are made up of: BEMN
- Basophils
- Eosinophils
-Neutrophils
- Monocytes (becomes macrophaes in the tissue)
74
WBC Characteristics:
- Synthesized from hematopoietic ‘myeloid’ stem cells
- WBCs are part of the immune system and help fight infections, inflammation, and foreign invaders.
- migration & mobility toward stimulus: ‘chemotaxis’
75
Chemotaxis
WBCs move toward an infection or injury by following chemical signals released by damaged cells
76
Describe how migration and mobility towards stimulus is WBC characteristic?
- Migrate out of blood vessels, into tissues: WBCs can leave the bloodstream and enter infected or damaged tissues to fight infections
- Mobile – can flow toward the stimulus; WBCs don’t stay in one place; they move freely in the bloodstream and tissues to attack infections
77
Neutrophils
- the majority of WBC's
- 1st to go to injury site
- highly responsive to bacteria
- ** engulf and digest (break bacteria down using digestive enzymes)
78
How do neutrophils die?
- They apoptosis (self-destruct) after killing 1-10 bacteria
79
What does neutrophils do when they detect an inflammation?
- They release chemicals that attract more WBC's to help fight?
80
What do neutrophils released to attrcat more WBC to help fight?
Prostaglandins: cause inflammation and increases blood flow
Leukotrienes: help guide more immune cells to the infection site
81
Neutrophil Recruitment Pathway
1.)Pathogens entering wound
2.) Macrophage-> They detect the pathogens and release signals to call for more immune cells
3.) Recruitment happens where cytokines is released and alert other WBC's
4.)Extravasation happens:where neutrophil move from the bloodstream into the infected tissue
--> Blood vessels become "leaky" to allow neutrophil to squeeze through and reach the infection in the tissue
5.) Neutrophil: phagocytosize
6.) Tissue repair
82
Mast cell
-Release Histamine and makes BV expand and more permeable
- this allows more neutrophils and immune cells to enter the infected area faster
83
Histamine
- secreted by mast cell
- this increases vessel leakiness= allows more neutrophils to enter the infected area faster
84
Neutrophil
engulf and digest pathogens (using digestive enzymes)
85
CBC (Complete Blood Count)
routine blood test that measures different components of blood (red blood cells, white blood cells, platelets, hemoglobin, etc.)
86
A CBC with Differential
gives a breakdown of different types of WBCs, including bands (immature neutrophils).
87
*Neutrophils
- high especially if theres an infection
*Depletion of mature neutrophils causes immature neutrophil presence: band
88
Lymphocytes
Especially if viruses present
- B-cells (make antibodies) and T-cells (kill infected cells)
89
Eosinophil
Attack allergens & parasites
90
Non-specific markers
-C-reactive protein (pro-inflammatory protein)
- CRP levels increase when there is an infection / injury
91
What is a C-reactive protein?
- made by the liver when inflammation is present
92
*Inflammation is an innate (the body’s natural defence), non-specific (happens the same way regardless of the cause) response
True or False
93
A noxious stimuli can be:
- Allergen
- Pathogen (bacteria, viruses, fungi, parasites)
Tissue Injury
Autoimmune disease, Disease process (neoplasm)
94
Tumors can cause inflammation and immune response as the body tries to fight abnormal cells.
Neoplasm
95
What do mast cells do when they detect a harmful stimulants? and what is that response called?
they release "granules" filled with inflammatory chemicals.? Response is called degranulation
96
How does mast cells work?
A noxious stimulus (harmful trigger) activates mast cells-> causing them to release inflammatory mediators.
97
What do primary mast cells secrete?
- histamine
- Prostaglandin
- other pro- inflammatory mediators such as complement system, cytokines, nitric oxide
98
histamine
Causes blood vessels to expand (vasodilation), increases vessel leakiness, leads to swelling, itching, and allergic reactions.
99
Prostaglandin
Cause pain, fever, and inflammation (also involved in muscle contractions, like menstrual cramps
100
Where is prostaglandin produced?
Muscle cell + tissues
101
complement system
- a pro-inflammatory mediator
- A group of proteins that help attack pathogens and enhance the immune response
102
Cytokines
- pro-inflammatory mediator
- Chemical messengers that control inflammation and immune cell movement.
103
–nitric oxide (NO) release
pro-inflammatory mediator
104
What do mast cells release in response to a pathogen to trigger inflammation?
- Histamine
- Bradykinin
- Complement proteins
-Leukotrienes
- Prostaglandins
105
Bradykinin
Increases pain sensitivity and causes blood vessels to widen (vasodilation).
106
Leukotrienes
Increase inflammation, mucus production, and attract white blood cells
107
Vascular permeability (edema)
Blood vessels become "leaky," allowing fluid and immune cells to enter the tissue.
This causes swelling (edema).
108
White blood cells (WBCs) move into the injured tissue to fight infections.
Dead WBCs and bacteria form pus.
Cellular infiltration (pus)
109
what form a barrier to stop further injury.
Thrombosis (clots)
110
From all the pus,that puts pressure—> leads to stimulation of nerve endings True or False
True
111
a little bit of capillary tearing, thrombosis happening (but not to worry too much about (localized or systemic)
Localized Inflammation
112
big problem since there’s clotting everywhere, risk for embolism (clot travelling)
Systemic Inflammation
113
IgE
When an allergen (antigen) enters the body-> binds to IgE on the mast cell
114
Degranulation
release of inflammatory chemicals likes histamine
115
What happens during Hypersensitivity 1?
- Allergen enters the body
- Antigen presenting cell picks up the allergen and presen it to TH cell
- TH Cell: send signals to activate B- cells
- B- cell : produce IgE antibodies that are specific to the allergen
- Mast Cell: when the allergen enters the body again-> it binds to the IgE on mast cells-> triggering mast cell degranulation.
- Mast degranulation : Mast cells release histamine and other inflammatory mediators
leading to allergy symptoms like swelling, itching, runny nose, and difficulty breathing.
116
What is IgE?
- Binds to mast cells and when allergen enters the body again triggers degranulation (release of histamine and other inflammatory mediators)
117
What is igG
- help regulate immune response
- if body produced enough igG- then it can compete with IgE for binsing
118
What happens if IgE dominates?
Mast cells get activated, releasing histamine (causing allergic reactions).
119
What happens if IgG dominates?
-Mast cells stay inactive, preventing allergies
120
What are the 3 stages in Inflammation/ Swelling?
- 1.) Vascular Stage
- 2.) Cellular Stage
- 3.) and 4.) Signaling and Phagocytosis Stages:
121
Vascular Stage
- increase blood flow to the injured area (vasodilation)
- allowing immune cells and proteins to move into tissues (increased vascular permeability)
122
Cellular stage:
WBC migration into tissue (eg.) Neutrophils, Macrophages, NK cells) toward the noxious stimulus via margination (sticking to the blood vessel wall nearby) , transmigration (WBC squeeze through vessel walls into tissues) , chemotaxis (wbc's follow chemical signals to the exact site of injury/ infection)
123
Signalling & Phagocytosis stages:
- Macrophages and mast cells release chemical signals (cytokines, histamine, prostaglandins) that attract more immune cells.
- Neutrophils and macrophages engulf (phagocytose) pathogens and dead cells to clear the infection.
124
Inflammation & Swelling Summary:
- Chemical signals released; capillaries widen and become more permeable.
- Fluid, antimicrobial proteins and clotting from blood move to the site (clotting begins)
- Chemokines released attracts more phagocytic cells (neutrophils and macrophages) to the injury site
- Neutrophils and macrophages phagocytose pathogens, and the tissue heals
125
What are the 2 cells that we have in our body that is part of the innate immune system that release chemical signals and phagocytosis pathogens?
- Neutrophils and Macrophages
126
What does Inflammation cause? (3)
- Swelling (Edema): due to fluid leaking from blood vessels
- Redness and Heat: due to increased blood flow (vasodilation)
- Pain: stimulation of nerve endings
127
What happens if our blood vessels become more permeable?
- It allows for more proteins and fluids to leak into surrounding tissues (swelling/ edema)
128
Inflammation: Histamine Effects in the body:
- Capillary Vasodilation & permeability
- *Stimulation of nerve endings => pain
- Bronchoconstriction: to prevent further entry of the allergen into the respiratory system
- *Tachycardia
- Itching
- Urticaria: hives (red - itch) caused by histamine release
129
Does it matter what type of inflammation do we have? How does this relate to how our innate immune response ?
- The innate immune system triggers inflammation in the same way regardless of the cause (bacteria, injury, etc.)
130
What happens when Histamine and Prostaglandins are released from mast cells:
- Histamine and Prostaglandins released: leukocytes move towards the infection or injury site, capillary become wider and leaky.
- Capillaries dilate (clotting begins): BV expand, more wbc arrive to the area of inflammation, clotting factors stop bleeding and prevent infection from spreading.
- Chemokines released to attract phagocytic cells (phagocytic leukocytes such as macrophages and neutrophils move toward the infection)
- Phagocytes consume pathogen and cell debris
131
What is the primary mediator of sensory stimulated inflammation?
Histamine
132
Where is Histamine stored and What causes it's released/
- stores within mast cells
- released upon mast cell contact with Antigen
133
Histamine has an agonist or antagonist relationship with H1 receptors?
- Agonist; meaning when Histamine bind to H1 receptors; it wil activate inflammatory pathways
134
How does Histamine affect our body?
- Capillary vasodilation & permeability
- Stimulation of nerve endings => pain
- *Bronchoconstriction (contraction of the smooth muscle): to prevent further entry of the allergen into the respiratory system
- *Tachycardia
- *Itching
- *Urticaria (hives, itchy swollen patches)
135
Hypersensitivity ‘allergy
- excessive immune response to a harmless substance (allergen)
- there are 4 different types but Type 1 Hypersensitivity (IgE modulated) is most common
136
Type 1 Hypersensitivity Pathophysiology:
- 1st exposure- allergen (antigen): WBC activation , TH2 signals B-cells to make specific antibodies (IgE type) to be synthesized & secreted.
(the IgE antibodies are preset in tissue and attach to mast cells approx within 1-2 weeks)
- 2nd exposure:– antigen distributes & attaches to the IgE, ‘crosslinking it’ (activate the mast cells)=> then mast cell degranulates quickly & effectively => histamine etc…. Secreted
137
Tx of Hypersensivity will depend on?
- Depend on the severity of the response
138
Allergic Reaction Overview:
1.) Allergen enters the body; B-cells recognize the allergen and activate
2.) B-cells turn into plasma cells and produce specific IgE antibodies against the allergen..
(IgE antibodies circulate in the blood; preparing for the next exposure)
3.) Mast Cell: IgE antibodies then attach to IgE receptor on the mast cell; ready to respond if allergen enters the body again.
4.) If allergen binds to IgE antibodies n mast cells (cross linking), leads to mast cell degranulation and the release of Histamine
5.) Histamine and other chemicals: is our allergic reaction
139
Antihistamines
block H1 receptors-> stop histamine from causing allergic reactions
140
When is Antihistamine used?
-treat allergies, hives, and cold symptoms
141
1st Generation of Histamine
- Cross BBB; cause drowsiness
142
Benadryl: 1st or 2nd gen of Histamine?
1st generation
143
blocks H1 receptor?
Anti- histamine
144
What is special about Cetirizine?
- non-drowsy
-On set: 10-20 mins and duration is 24hrs
145
binds to H1 receptor>?
Histamine
146
147
What is special about Cetirizine?
- non-drowsy
-On set: 10-20 mins and duration is 24hrs
148
Other systems involved, bronchoconstriction and tachycardia., What is your tx?
Dx: Anaphylaxis
-
Tx: Anti- histamine and life saving drugs (Epinephrine esp if going to shock)
149
More systems involved in allergies, eyes red, urticaria, but no VS change. What is your tx?
- Anti-histamine and monitor (we monitor because allergies can progress)
150
Localized Allergy; usually in one area. What is your tx?
Benadryl Cream
151
Localized Allergy; usually in one area. What is your tx?
Benadryl Cream
152
The same situation with a cat and other systems involved but now we see diffused urticaria throughout, difficulty breathing (bronchocnstriction) and tachycardia?
- There is VS change!
- Diagnosis: Anaphylaxis
Tx: Antihistamine + life saving drugs
- Systemic allergic reaction is life threatening
153
Patient comes to a friend’s house, the friend has a cat.
*Within 15 minutes, starts to have s&s:
Watery eyes (epiphora)
Itchy eyes (allergic conjunctivitis)
Runny nose (rhinorrhea)
Sneezing
Slightly itchy skin throughout (pruritus)
Localized or Systemic?, What is your tx?
- We see more systems involved (eyes, nose, skin)
- Systemic, non-life threatening
- Tx: Anti-histamine & monitor
154
S&S: localized urticaria (hives), pruritus (itching at the contact site); no change to VS; no other deficits noted
Localized or Systemic Allergy? What is your tx?
Localized; since there is no change to VS, system involved is only skin
Tx: Benadryl cream
155
In whats ways we can test for allergic reaction?
- Topical and Superficial injection; where they adminster the allergen
156
How does allergy de-sensitization (immunotherapy) work?
- long term tx
- low amounts of allergen-serum given IM over many months/ years
- **we see immune system shifts from TH2 dominant (IgE) to a more controlled TH1 & T-reg response**
- The TH1 activate B- cell that forms IgG instead of IgE
- We like IgG because it aids to suppression of the immune system's overreaction to allergies.
157
How does IgG help in suppression of the immune system to overreaction to allergies?
- IgG competes with IgE; when given IgG during immunotherapy- we have more igG than IgE hence this allows for the binding of IgG to mast cells first before the IgE.
- Once IgG has formed a complex with antigen; antigen and IgE cross linking will not happen.
- no cross linking happens= no mat cell activation--> no histamine release and no allergic reaction.
158
IgG
= suppression of immune system
159
what triggers production of IgG?
TH1 that activates B-cell to make IgG
160
What triggers production of IgE?
Th2 reponse
161
What happens when the physical and chemical barriers are breached?
1.) Tissue damage cause release of vasoactive (histamine, protaglandins) and chemotactic (cytokines, complement proteins) attract immune cells to the injury site --> trigger a local increase in blood flow and capillary permeability
2.) Permeable capillaries allow an influx of fluid (exudate-> contains antibodies, complement proteins, phagocytes) and cells
3.) Phagocytes migrate to site of inflammation
4.) Phagocytes and antibacterial exudate (fluid full of infection-fighting substances) destroy bacteria
162
What releases Arachidonic acid?
Tissue damage
163
Arachidonic Acid is essential in which?
starts the inflammatory process
164
Who does Arachidonic Acid work with in order to produce different kinds of PG's?
COX 1 and COX2
165
COX 1(at rest)
- increase platelet aggregation
166
COX 2 (at rest)
( increase pain and inflammation)
167
Non- Selective Inhibitors COX- 1
- decrease platelet aggregation (does the opposite of what it does at rest)
168
Non-Selective Inhibitors COX-2
- decrease pain and inflammation ( does the opposite of what it does at rest))
169
Selective COX-2 Inhibitors:
-only inhibit COX 2 (pain and inflammation) but it spares COX-1 hence; we are at risk for clots
170
- selective COX-2 inhibitor
- very good with pain and inflammation but risk for clots
- Celecoxib
171
Non- Selective COX inhibitors
Aspirin, Ibuprofen
172
How does Non-selective COX inhibitors work?
- Inhibit COX 1 and COX2
- decrease platelet aggregation (COX1)
- decrease pain and inflammation (COX 2)
173
Released from injured cells
activates pain receptors (nociceptors)
K+ ions
174
What travels to the brain and cause hypothalamus to increase body temp?
Pyrogens
175
What increases blood vessel permeability?
Histamine
176
Does Opiates reduce inflammation?
- They do not reduce inflammation; but block pain signals in the brain and spinal cord
177
Aside from COX 1 and COX 2 working along with AA; what else does it do?
-Aside from synthesizing prostaglandins
- It also plays a role in further prostaglandin differentiation
178
COX 1 location and function (platelet aggregation)
- present in all tissues
- protects:
gastric mucosa supports kidney function, and promotes platelet aggregation
179
COX 2 location and function (pain and inflammation)
- present at sites of tissue injury
(normally inactive-->activated during inflammation)
- mediates inflammation,
- sensitizes pain receptors
- mediates fever in the brain
180
What drug class does Non- Selective COX Inhibitors and Selective COX iInhibitors fall under?
NSAID
- Non- Steroidal Anti- Inflammatory Drugs
181
NSAID effects:
-Anti inflammatory
- Analgesic
- Anti pyretic
182
Celecoxib (Celebrex)
- only prescription
- "black box" bc of CV warning
- since its a selective COX 2 inhibitor; there is a risk for clots
183
Why is Celecoxib (Celebrex), a COX 2 inhibitor is not the first choice of NSAID when treating pain?
- risk forc clots since it is a Selective COX 2 inhibitor
184
Non- Selective Cox Inhibitors Drugs:
Acetylsalicylic acid (Aspirin aka ASA)
*+ Enteric-coated ASA (ECASA)
*Ibuprofen (Advil, Motrin)
*Ibuprofen-like:
*Voltaren (Diclofenac)
*Naproxen (Aleve, Naprosyn)
*Ketorolac (Toradol)
*Indomethacin
185
Why is Aspirin contraindicated in children?
Reye's Syndrome:
-Fulminant Hepatitis (sudden and severe failure)
- Cerebral Edema: brain swelling + somnolence (drowsy) and confusion
186
How to treat Aspirin overdose?
- Aspirin is an acidic drug
- IN excretion: Acidic drug in basic environment
- We will need to alkanize the urine to better enhance excretion of Aspirin
187
Tx for soft tissue injury (due to twisted sprained ankle)?
NSAIDS:
- ibuprofen (PO), Voltaren cream
- and ICE, ELEVATE, REST
188
HPA Axis?
Hypothalamic-Pituitary-Adrenal Axis
- How your body responds to stress by releasing cortisol
189
Hypothalamus (detects stress) and releases:
Corticotropin releasing hormone (CRH)
- CRH then travels to Anterior Pituitary
190
Anterior Pituitary (below the brain)
- Once CRH gets to Anterior Pituitary
- It releases Adrenocorticotropic Hormone (ACTH)
191
Adrenal Cortex (top of the kidneys)
- ACTH is released into the adrenal cortex.
- It then releases cortisol (stress hormone)
192
Where is cortisol released?
Adrenal Cortex
193
Where is ACTH hormone released?
Anterior Pituitary
194
HPA Axis hormones released:
Corticotropin Releasing Hormone (CRH)--> Adrenocorticotropin hormone (ACTH)--> Cortisol
- Hypothalamus--> Anterior Pituitary-> Adrenal Cortex
195
Glucocorticoid
steroidal (synthetic) drugs (mimic or modify natural hormones)
196
Which part of the HPA Axis produces glucocorticoid?
Adrenal cortex
197
Glucocorticoid molecular characteritsics, enzymes, metabolism
- Glucocorticoid are:
- lipophilic
- nuclear receptor binding
- some are prodrugs
198
Glucocorticoid as an Endogenous substance (not synthetic)
- stimulates gluconeogenesis: making glucose from proteins and fats to raise blood glucose
- stimulates protein
degradation: break down of proteins for energy
- facilitates lipolysis :breakdown of fat stores for energy
199
How is Glucocorticoid related to inflammation?
- Inhibits prostaglandin synthesis (COX-2): reduce swelling and pain
- Suppress Histamine release: reduce allergic reaction
- Suppression of Phagocytes/ Lymphocytes: lowers immune activity
200
Glucocorticoid as a drug
- HIGH EFFICACY FOR TISSUE INFLAMMATION.
- think how it inhibits COX2
- suppress Histamine
- lowers immune system (suppression of phagocytes/ lymphocytes)
201
Glucocorticoid Drugs:
*Hydrocortisone, Cortisone
*Prednisone, Prednisolone
*Methylprednisolone
*Dexamethasone
202
Hydrocortisone
Glucocorticoid
203
Cortisone
Glucocorticoid
204
Prednisone
Glucocorticoid
205
Prednisolone
Glucocorticoid
206
Methylprednisolone
Glucocorticoid
207
Dexamethasone
Glucocorticoid
208
What are DMARD?
disease-modifying anti-rheumatic drugs
209
Where is DMARD the main primary tx?
- used in Rheumatoid Arthritis to reduce joint damage
210
Is glucocorticoid a DMARD?
No, but they have "DMARD- like" effect because they protect joints by reducing inflammation and damage
211
Glucocorticoid therapeutic effects
- Affects multiple systems in the body-> not just joints
- Important for growth (in utero for liver + gut maturation)
- Stops insulin from being used properly
-Anti allergic (suppresses Histamine)
-Anti inflammtory effect and immunosuppression (reduced pain, swelling, stiffness and physical disability)
- Helps blood vessel work properly and reduces permeability (histamine suppuression)
212
Glucocorticoids Adverse Effects: (Part 1)
- risk for infection (suppression of phagocytes/ lymphocytes)
- myopathy(muscle weakness)
- osteonecrosis/osteoporosis
- mood changes/ anxiety, depression, even psychosis
- long term use can suppress natural cortisol production
213
Glucocorticoids Adverse Effects: (Part 2)
- Metabolism:
- weight gain/ obesity
- fluid retention/edema
-cushing syndrome
- impaired glucose metabolism
- insulin resistance + beta cell dysfunction
- stomach; gastric ulcer if taken with NSAID
- Hirsutism (excess hair growth) and skin thinning
- eyes (cataract and glaucoma)
- increased CV risk
214
Cushing syndrome
cause of chronic use of glucocorticoid
S &S:
- moon face, buffalo hump (fat on upper back), high blood sugar and skin thinning
215
