Drugs For Treating Inflmmation Flashcards
1
Q
Cardinal Signs of Inflammation
A
- Remember that these are all caused by chemical mediators produced during inflammation.
~ Redness
~ Heat
~ Swelling
~ Pain
~ Functional Loss - Body’s reaction to:
~ Cell death
~ Cell injury
~ Exposure to allergen/pathogen
2
Q
Effects of Bradykinin
A
- Binds to the mast cells found in the connective tissues as well as basophils and platelets in the blood causing a release of histamine.
~ Allergen/Pathogen binding to mast
cell receptors has the same effect. - Causes activation of the enzyme phospholipase A2.
~ Mobilizes arachidonic acid from cell
membranes.
3
Q
Metabolism of Arachidonic Acid
A
- After being mobilized by phospholipase A2, arachidonic acid is metabolized within the cell.
- 2 enzyme pathways metabolize arachidonic acid
~ Cyclooxygenase (COX) - produces
prostaglandins and thromboxanes.
~ Lipoxygenase - produces
leukotrienes.
4
Q
Chemical Mediators of Inflammation
A
- Bradykinin
~ Vasodilation/Increased Vessel
Permeability
> Contributes to Edema/Increased
Heat/Redness
~ Stimulates Pain Receptors - Histamine
~ Vasodilation/Increased Vessel
Permeability
> Contributes to Edema/Increased
Heat/Redness
~ Stimulates Pain Receptors - Prostaglandins
~ Vasodilation/Increased Vessel
Permeability
> Contributes to Edema/Increased
Heat/Redness
~ Stimulates Pain Receptors - Leukotrienes
~ Vasodilation/Increased Vessel
Permeability
> Contributes to Edema/Increased
Heat/Redness
5
Q
NSAIDs and Aspirin
A
- Both affect the COX pathway to exert their drug actions
- COX-1 V. COX-2
~ Two different forms of COX enzyme.
~ Both have similar effects.
> Result in the production of TXs &
PGs
> COX-1 - produced at a constant
level in all cells to maintain
normal levels of TXs & PGs.
> COX-2 - also produced normally,
but production increases in
reaction to injury or infection.
6
Q
NSAIDs Action
A
- Inhibits/binds COX-1 and COX-2 enzymes
- Effects of COX-1/COX-2 Inhibition/Binding
~ Reduces Pain
> Decreased PG Production
~ Reduces Edema Formation
> Decreased PG Production
~ Antipyretic/Reduces Fever
> Decreases PGE2 Production
> Aspirin not used for children
recovering from viral infection as
it can cause Reye’s Syndrome
(abnormal fatty deposits in the
brain: give Ibuprofen instead)
7
Q
Why is Aspirin Separate from NSAIDs?
A
- Aspirin is more selective for the COX-1 enzyme
~ Has all the same effects as the other
NSAIDs, but is also an anti-platelet.
> Interaction between PG-12 and
TXs helps to determine whether
a clot will form.
• Because aspirin is more
selective for COX-1 TX
production is reduced while
PG-12 production is
maintained. - The binding of aspirin to the COX enzyme is irreversible
- PG-I2 is a thinner and TX is a clotter and Aspirin shuts down TX production by inhibiting the COX-1 pathway
8
Q
Is Inflammation fully controlled by inhibition COX-1 and COX-2?
A
- No
~ Bradykinin still being formed.
~ Histamine is still being released.
~ COX-1 & COX-2 are incompletely
inhibited.
~ Binding is reversible with NSAIDs.
~ The lipoxygenase pathway is still
intact.
9
Q
COX-2 Specific NSAIDs
A
- Bextra (discontinued due to deaths)
- Vioxx (discontinued due to deaths)
- Celebrex (needs special approval)
10
Q
Is inhibition of COX-2 a selectively good idea?
A
- Leaves COX-1 intact to meet needs of body and reduce side effects
- Addresses the specific enzyme responsible for the increases in PG that cause unwanted effects associated with inflammation
11
Q
Problem with COX-2 Inhibitors
A
- Interaction between PG-12 and TX determines whether a clot will form.
~ With inhibition of COX-2, PG-12
production is inhibited.
~ Thromboxane is still produced since
COX-1 is not being inhibited.
> With TX able to dominate the
interaction with PG-I2 the blood
tends to clot more readily
12
Q
Combination Aspirin Products: Buffered Aspirin
A
- Aspirin + Buffering Agent
~ Buffering Agent
> Neutralizes Stomach Acid
• Decreases Aspirin Breakdown
in Stomach
• Decreases aspirin absorption
into mucus lining of stomach.
* Decreases stomach
irritation.
} When aspirin is
absorbed PGs are
inhibited which are a
component of the
mucus lining.
} Aspirin forms an
acid in the stomach
tissues.
13
Q
Combination Aspirin Products: Aspirin with Caffeine
A
- Caffeine enhances the analgesic effects especially with headaches.
~ Constricts blood vessels - Elevates Mood
- Common with people who have headaches
14
Q
Aspirin Products Indications
A
- Mild pain
- Fever
- History of Heart Disease
- Inflammatory conditions
15
Q
Aspirin Products Contraindications/Considerations
A
- Not indicated for athletes with muscle or joint injuries. (especially acute due bleeding)
- Presence of lower back pain. (May be due to kidneys = will result in worsening pain)
- Preexisting blood or bleeding disorders (anemia, hemophilia)
- History of ulcer, Gl bleeding or liver disease.
- Do not use in combination with alcohol.
- Do not use if pregnancy is suspected.
16
Q
Aspirin Products Contraindications/Considerations: Asthma
A
- Due to inhibition of COX pathway. (less PG)
~ Arachidonic acid enters the
lipoxygenase pathway and produces
leukotrienes.
> LTs bind to receptors in the
respiratory tract worsening
Asthma symptoms
• Increased bronchospasm
and mucous production (2
main things that block airway)
17
Q
Aspirin Side Effects
A
- Gastrointestinal Effects
~ Ulceration
~ Gastritis
~ GI Bleeding
~ Causes
> PG inhibition (affects lining)
> Acid production (irritates lining) - Uncontrolled Bleeding
- Nephrotoxicity - Kidney damage as a result of excess exposure to toxins.
~ Toxins come from the metabolization
of Aspirin - Allergic Reactions
~ S&S
> Hives - Raised, Swollen, Red, Itchy
> Edema
> Difficulty Breathing
• Bronchospasm - Rare, but
serous if present
> Rhinitis
> Shock - Reye’s Syndrome
~ Condition following viral infection d
associated with aspirin use
~ Results in generalized brain and liver
dysfunction due to abnormal fatty
deposits
18
Q
NSAIDs Indications
A
- Mild to Moderate Pain
- Fever - use safely w/ children without risk of Reyes
- Inflammatory Conditions
- Not used for those with history of heart disease or stroke.
19
Q
NSAID Side Effects
A
- Most less frequent than with aspirin.
- Gastrointestinal Effects
~ All due to PG inhibition
> Ulceration
> Gastritis
> GI Bleeding - Uncontrolled bleeding
- Nephrotoxicity
- Allergic Reactions
~ S&S
> Hives - Raised, Swollen, Red, Itchy
> Edema
> Difficulty Breathing
• Bronchospasm - Rare, but
serous if present
> Rhinitis
> Shock
~ Individuals with Aspirin allergy often
are allergic to NSAIDs
20
Q
NSAIDs Contraindications/Considerations
A
- Presence of lower back pain.
- Preexisting blood or bleeding disorders (anemia, hemophilia)
- History of ulcer, Gl bleeding or liver disease.
- Asthma
- Caution when use in combination with other salicylates or NSAIDs
- Do not use in combination with alcohol.
~ Deteriorates GI tract
21
Q
Corticosteroids
A
- Hormones produced within the adrenal gland or produced in a laboratory.
~ Types
> Mineralcorticoids
> Glucocorticoids (decreases
Inflammation) - Body naturally makes corticosteroids
22
Q
Corticosteroid Types
A
- Mineralcorticoids
~ Affect mineral/fluid balance in body
> Aldosterone causes the kidney to
reabsorb sodium and excrete
potassium.
• Results in increased fluid
retention. - Glucocorticoids
~ Supresses inflammation
~ Affect glucose and fatty acid levels in
the body.
> Mobilizes amino acids and fatty
acids for energy metabolism. - Where are the stores for amino acids and fatty acids?
~ Proteins and triglycerides - Wherever there’s sodium there’s water = inflammation
23
Q
Glucocorticoid Anti-Inflammatory Mechanisms
A
- Inhibits release of HT
- Inhibits the enzyme that mobilizes arachidonic acid (phospholipase A2)
~ Effects of Inhibition of Phospholipase
A2
> Inhibits Cyclooxygenase Pathway
> Inhibits Lipoxygenase Pathway - Inhibits PG, HT, and LT but leaves BK
24
Q
Corticosteroid Indications
A
- Usually used when NSAIDs aren’t effective or when inflammation is a component of asthma
~ Skin diseases/infections
~ Nasal inflammation
~ Respiratory diseases
~ Orthopedic Injury/condition - If used to often, can break down cartilage and other structures
25
Q
Common Corticosteroid Types
A
- All corticosteroids have mineralcorticosteroid and glucocorticoid effects
- Those that exert mostly mineralcorticoid effects are mineralcorticoids and those that exert mostly glucocorticoid effects are glucocorticoids.
- Ex. Cortisone has more equal mineralcorticoid and glucocorticoid effects while dexamethasone has 25 times stronger glucocorticoid effects and almost no mineralcorticoid effects.
- Common Medications
~ Betamethasone
~ Cortisone
~ Dexamethasone
~ Prednisone
26
Q
Corticosteroid Side Effects
A
- Much more common than NSAIDs and more serious
~ Inhibits Collagen/scar formation
> No or reduced inflammation = no
or reduced movement of cells and
blood plasma into injured tissues
• Reduced movement of plasma
and cells limits materials
necessary for collagen (scar)
formation - Optic
~ Glaucoma (high pressure in eye)
~ Cataracts (abnormal protein deposits
over lens of eye) - Gastrointestinal
- Muscle weakness/wasting (frees up amino acids)
- Increased blood pressure
~ Retains water causing it to go into
circulation = increased BP
27
Q
Corticosteroid Contraindications/Considerations
A
- Immune System Function
~ Suppresses the immune reaction
~ Mask symptoms of infection - Pregnancy
- Corticosteroid use will decrease the amount of natural corticosteroid the body will make
28
Q
General Guidelines for Use
A
- Use prior to activity if used for asthma.
- Healing will be delayed.
~ Athletes receiving intra-articular
injections should not stress the joint
in the short term following the
injection. - Withdraw from long term use must be tapered.
~ Prevent Flare Up
~ Restore Adrenal Function
