Inflammation #3 (Murnane) Flashcards Preview

Musculoskeletal Disorders and Pain Management > Inflammation #3 (Murnane) > Flashcards

Flashcards in Inflammation #3 (Murnane) Deck (69):
1

T/F OA is an IRREVERSIBLE, DEGENERATIVE, "wear and tear" arthritis

TRUE

(OA is not an auto immune disease and it is not related to antibodies)

2

OA may reflect excessive release of enzymes that break down ________

articular cartilage

(this cartilage is then replaced by badly aligned or overworked joints)

3

Where is articular cartilage located?

between the end of the bone and synovial fluid

4

When does synovitis (swelling or irritation of joints) occur in OA

late OA

5

T/F NSAID should be used instead of steroids in patients with OA

TRUE;
steroids exacerbate bone resorption

6

Steroids are the most....

profoundly anti-inflammatory substance

7

OA process causes (4)

-hyaline cartilage breakdown
-bone remodeling
-osteophyte formation
-synovial inflammation

8

What are CARDINAL SYMPTOMS of OA? (6)

-ACUTE PAIN
-stiffness
-Joint tenderness, enlargement, deformity
-limitation of motion
-radiological findings (joint space narrow)
-NO SPECIFIC LAB FINDINGS in plasma

9

Although inflammation was once though NOT to be involved in OA, it is now considered one of the main contributors, why?

due to proinflammatory cytokines

10

What is the #1 risk factor for OA?

age

11

osteophytes are also known as? what is the purpose of osteophytes?

bone spurs. osteophytes are produced in an attempt to STABILIZE THE JOINT due to bone overgrowth

12

T/F Inflammation in OA is systemic

FALSE; local

13

T/F If you WERE to test the synovial fluid of a patient with OA, there would be cytokines present

TRUE, however this method is not used routinely

14

What joints are commonly affected by OA?

joints that are used a lot or bear weight (hip, knee, foot, spine, etc)

15

Osteoarthritis of the spine is caused by?

slow deterioration of the disks between the bones that make up the backbone

16

T/F OA is a HETEROGENOUS DISEASE and 2 of the MAJOR symptoms are ACUTE PAIN and INFLAMMATION

TRUE

17

What is FIRST LINE therapy for the treatment of OA?

NSAIDS

18

What pharmacological activities does Tylenol have? (2)

-analgesic
-antipyretic

19

What is a major side effect of Tylenol?

hepatotoxicity due to overdose

20

Describe the analgesic activity of COX inhibitors (4)

1. pain occurs
2. pain mediators (i.e. PGE2) signal
3. increase in growth factors through signaling (i.e. EP)--> increase in transcription/translation of TRPV1 (trafficking or phosphorylation)
4. pain is desensitized

21

antipyretic effects of APAP:
APAP and NSAIDS inhibits PGE2 production by COX-2 in the _______ in response to circulating _____

hypothalamus; cytokines

22

What are the major and minor metabolisms of APAP?

major (conjugation)
minor (P450 enzyme)

23

Why is the P450 enzyme considered the minor way for metabolism of APAP?

it produces a HIGHLY reactive intermediate (NAPQI) which can build up in the liver (hepatotoxicity)

24

T/F High doses of APA require cytochrome P450 for metabolism.

TRUE; leading to formation of highly reactive intermediates (e.g., NAPQI), which damage the liver by depleting its antioxidant glutathione

25

Which NSAID is the ONLY one that IRREVERSIBLY binds to COX?

aspirin

26

COX-1 induces homeostatic functions; while COX-2 induces

inflammation

27

Why can COX-2 increase its expression at the site of inflammation?

b/c it is induced by cytokines via NfKb pathway

28

What is a cell derived mediator?

prostaglandin

29

What is a plasma-derived mediator? (3)

-kinin system
-clotting system
-complement system

30

NSAID block what types of mediators?

PLASMA derived (prostaglandins) and CELL derived mediators (kinin, clotting, complement systems)

31

Prostacyclin synthase is found primarily in _______, while thromboxane synthase is found ONLY in _____

endothelial cells; platelets

32

Prostacyclin synthase cause (2)......., while Thromboxane synthase causes (2).....

-prostacyclin--> vasoDILATION and inhibit platelet aggregation

-thomboxane-->vasoCONSTRICTION and promote platelet aggregation

33

What is the anti-platelet dose for ASA?

75-325 mg Daily

34

T/F COX stimulation INCREASES GP IIb/IIIa expression

TRUE; GP IIb/ IIIa allows for cross linking of platelets

35

During first pass metabolism, ASA is broken down into?

salicylates

first pass metabolism: occurs in the liver

36

Prior to first pass effect, ASA travels in the ________ where it has access to platelets

hepatic portal vein, if ASA binds there platelet can no longer resynthesizes COX b/c they do not have nuclei

37

T/F Higher doses of ASA could escape 1st pass metabolism

TRUE

38

T/F If you "knock out" thromboxane, you can still synthesize prostacyclin and cause vasodilation AND inhibit platelet aggregation

TRUE b/c the prostacyclin pathway can only be inhibited at high doses of aspirin

39

What are 2 major side effects of PROPIONIC ACID and ACETIC ACID NSAID (i.e. ibuprofen, diclofenac)?

-gastric ulcers
-increased bleeding

40

What is the first inflammatory mediator response?

the release of cytokines from neutrophils

41

What are the DIRECT and INDIRECT ways that you can evaluate COX selectivity?

DIRECT
-in VITRO (in cells, bacteria, etc) direct inhibition of COX-1 and COX-2
-in VIVO (in humans) by measuring the ability of the drug to interfere with synthesis of PGs

INDIRECT
-in VIVO by evaluating pharmacological effect

42

Potency vs. Efficacy

-potency: the concentration or amount of the drug required to produce a defined effect
-efficacy: the therapeutic effectiveness of the drug in humans

43

What is the normal function of PGE2 synthesis? (2)

-replenish the GI tract epithelium
-supports secretion of mucus and bicarbonates

44

NSAIDs (primarily w/ COX-1 inhibitory activity) can inhibit PGE2, which causes what to happen? (2)

-an INCREASE in acid release
-DECREASE in mucosal bood flow epithelial cell proliferation

45

Mucous injury can occur from NSAIDs due to (2)

-physiochemical disruption of the gastric mucosa
-prolonged inhibition of gastric mucosal protection

46

COX-1 is mediates the "house keeping" functions and is ________ expressed in most cells, however COX-2 can be ______ in most cells and mediates acute, transient actions

constitutively; induced

47

Selectively inhibiting COX-2, inhibits ______ synthase. What does this cause?

prostacyclin, so you longer have the cardiovascular protection instead Thromboxane synthase induces PLATELET AGGREGATION and VASOCONSTRICTION

48

T/F Activity of BOTH COX-1 and COX-2 are required to produce adequate levels of PROSTACYCLIN to counterbalance the affects of thromboxane

TRUE

49

T/F Drugs that contain Capsaicin deplete the sensory nerve endings of neuropeptides

TRUE

50

Capsaicin _______ stimulates TRPV1 receptors

DIRECTLY

51

Where are neuropeptides (substance P; calcitonin) synthesized?

in the cell bodies of sensory neurons

52

T/F Substance P (neuropeptide) functions as a neurotransmitter AND neuromodulator

TRUE

53

What is an ANTIDROMIC AP?

an action potential that travels back towards the nerve ending rather than towards the spinal cord

54

Capsaicin inhibits ______

substance P

55

What is the ALTERNATIVE 1st line therapy for OA patients?

Tramadol (Ultram)

56

What is the MOA of Tramadol?

Weak Mu agonist with NET and SERT blocking activity

57

What is the endogenous ligand for Mu receptors?

endorphins

58

What part of the brain are Mu receptors (most dense)? (2)

-brainstem
-midbrain

59

Mu receptors function as an _____ and produces _____

analgesic; euphoria

60

Which neurotransmitters are pain INDUCING? (3)

-glutamate
-substance P
-CGRP (calcitonin gene related peptide)

61

Which neurotransmitters are pain REDUCING? (5)

-5-HT
-NE
-Endogenous opioids
-Glycine
-GABA

62

What transporters do Tramadol work on? (3)

-SERT
-NE
-post synaptic opioid receptors (Mu)

63

Glucocorticoids (steroids) has profounding anti-inflammatory effects because?

they prevent synthesis and release of cytokines

they also decrease proliferation of lymphocytes and macrophages

64

What is the MOA of glucocorticoid?

modulate gene expression

65

What is a LONG TERM effect of using steroids?

Cushing Syndrome

66

What are clinical uses for glucocorticoids? (3)

-effective anti-inflammatory
-allergic response
-organ replacement surgeries

67

What are supplements that can be used to treat OA? (2)

-glucosamine
-chondroitin sulfate

68

T/F Duloxetine is a SNRI-serotonin norepinephrine reuptake inhibitor like tramadol

TRUE

69

What are possible effects of steroids? (7)

-increase blood glucose
-decrease protein synthesis
-sodium reabsorption
-fluid retention
-weight gain
-hypertension
-suppression of the HPA axis
AND lots of other (view slide 121 and 122)