Anti-inflammatories and Corticosteroids

Question 1

Prostaglandins are produced in almost all tissues and act _____

Answer 1

locally
(they don’t circulate in the blood)

Question 2

Function of Prostaglandins

Answer 2

• Modulate pain, inflammation, and fever
• Control physiologic functions such as acid secretion and mucus production in the GI tract, uterine contractions, and renal blood flow
• Released in allergic and inflammatory processes and direct inflammatory response

Question 3

_____ is the primary precursor of prostaglandins
and is a component of the phospholipids of cell membranes

Answer 3

Arachidonic acid

Question 4

Free arachidonic acid is released from _____

Answer 4

tissue phospholipids by phospholipase A2

Question 5

Prostaglandins are synthesized from
arachidonic acid via the _____

Answer 5

cyclooxygenase pathway

Question 6

COX enzymes functions

Answer 6

COX-1: Responsible for the physiologic production of prostanoids; “housekeeping functions, regulates normal cellular processes
COX-2: Causes elevated production of prostanoids that occur during chronic inflammation and cancer, Expressed in tissue such as brain, kidney, and bone

Question 7

T/F COX-1 and COX-2 have differences
in binding site shape which allow
for selective inhibitors

Answer 7

T

Question 8

NSAIDs (Nonsteroidal Anti-inflammatory Drugs) MOA

Answer 8

● Inhibit the synthesis of prostaglandins
● Primarily inhibit the cyclooxygenase enzymes that catalyze the first step in prostanoid biosynthesis

Question 9

Aspirin is a _____ NSAID

Answer 9

Non-Selective NSAID

Question 10

NSAID analgesic effects:

Answer 10

○ PGE2 sensitizes nerve endings so NSAIDs decrease PGE2 synthesis, which decreases pain sensation
○ Inhibiting COX-2 which is released during inflammation and injury and is thought to cause the analgesic effect

Question 11

NSAIDs lower body temp by impeding ____
synthesis; essentially resetting the thermostat
towards normal

Answer 11

PGE2

Question 12

Non-Selective NSAIDs

Answer 12

● Aspirin (ASA)
● Ibuprofen (Ibu, Motrin, Advil)
● Naproxen (Aleve)
● Diclofenac (Voltaren)
● Ketoprofen (Orudis)
● Piroxicam (Feldene)
● Meloxicam (Mobic)
● Indomethacin (Indocin)
● Ketorolac (Toradol)

Question 13

NSAIDS most important effects

Answer 13

Anti-inflammatory
Analgesic
Antipyretic

Question 14

Contraindications for NSAIDS

Answer 14

● NSAID induced asthma orurticaria
● Aspirin triad
● 3rd Trimester of Pregnancy
● CABG surgery periop use
● Hypersensitivity to NSAIDs

Question 15

Additional contraindication for Indomethacin (NSAID)

Answer 15

Neonatal: renal impairment, active bleeding, necrotizing enterocolitis, congenital heart
disease

Question 16

Additional contraindication for Ketorolac (NSAIDS)

Answer 16

Pre-op major surgery, CABG periop pain, labor
and delivery, coagulation disorders

Question 17

NSAIDS BBWs:

Answer 17

• increase risk of serious and potentially fatal GI adverse events such as bleeding, ulcers, and stomach or intestine perforation
• increase risk of serious and potentially fatal
  cardiovascular thrombotic events, including MI and stroke; contraindicated for CABG perioperative pain

Question 18

____ is an NSAID with indications for more moderate to severe pain

Answer 18

Ketoralac

Question 19

NSAIDs Side Effects (Common)

Answer 19

● Stomach upset
● Dyspepsia
● N/V
● HA
● Dizziness
● Anemia
● Peripheral edema
● Hemorrhage
● Urinary retention
● Cough
● Diarrhea

Question 20

NSAIDs Adverse Reactions (Major):

Answer 20

● GI bleeding
● GI ulcers
● Hemorrhage
● Prolonged bleeding time
● HTN
● MI
● Anaphylaxis
● Nephrotoxicity
● Hepatotoxicity
● Stevens-Johnson syndrome
● Toxic Epidermal Necrolysis

Question 21

Avoid NSAIDs in pts with ____

Answer 21

asthma

Question 22

Why we should Avoid NSAIDs in the 3rd trimester of pregnancy

Answer 22

○ Can cause premature closing of ductus arteriosus
○ Acetaminophen is preferred during pregnancy

Question 23

NSAIDs prevent the synthesis of ___ and ___, which
maintain renal blood flow especially in marginally functioning kidneys

Answer 23

PGE2 and PGE1

Question 24

T/F Aspirin Only exhibits anti-inflammatory properties at high doses

Answer 24

T

Question 25

Aspirin is An _____ inhibitor of cyclooxygenase activity

Answer 25

irreversible

Question 26

Indications for Aspirin

Answer 26

● Fever ● Reduce risk of CV events → MIs, TIAs, CVAs ● Mild pain

Question 27

Contraindications for Aspirin

Answer 27

● Avoid in pts <20 yrs old with viral infections → Reye syndrome ● Pts with gout ● Pts taking probenecid ● Aspirin Triad (asthma, nasal polyps, aspirin sensitivity) ● GI bleeds/Active PUD ● G6PD Deficiency ● Uncontrolled HTN ● Coagulation disorders

Question 28

Side Effects (Common) for Aspirin:

Answer 28

● GI pain ● Ulcers ● GI bleeding ● N/V ● Dizziness ● Rash ● Tinnitus

Question 29

Adverse Reactions (Major) in Aspirin:

Answer 29

● Hemorrhage ● Reye Syndrome ● Nephrotoxicity ● Anaphylaxis ● Bronchospasm ● Renal failure ● GI perf/ulcer

Question 30

Selective NSAIDS

Answer 30

Celecoxib (Celebrex): Selective to COX-2 inhibitors

Question 31

Celecoxib MOA

Answer 31

MOA: selective for inhibition of COX-2 rather than COX-1 Intended to preserve gastric cytoprotective effects that are mediated by COX-1 while maximizing the anti-inflammatory effects mediated by COX-2

Question 32

Indications for use of Celecoxib

Answer 32

● Approved for the treatment of RA and OA ● Acute mild to moderate pain

Question 33

Contraindications of Celecoxib

Answer 33

● Use caution in pts with sulfonamides allergy or who have had anaphylaxis reactions to aspirin or other NSAIDs ● Avoid in pts with severe hepatic or renal disease

Question 34

Side effects of Celecoxib

Answer 34

HA, dyspepsia, diarrhea, and abdominal pain

Question 35

Corticosteroid Secretion

Answer 35

1. Stress → CRH (corticotropin-releasing hormone) releases from the hypothalamus 2. ACTH (adrenocorticotropic hormone) releases from the anterior pituitary 3. Cortisol releases from the adrenal cortex which inhibits feedback

Question 36

Glucocorticoid Properties

Answer 36

Anti-inflammatory Immunosuppressive Increase resistance to stress

Question 37

Glucocorticoid Properties

Answer 37

- Promote normal intermediary metabolism - Alter blood cell levels

Question 38

______ → acts on distal tubules and collecting ducts, causes reabsorption of sodium, bicarbonate, and water. Also decreases reabsorption of potassium which, with H+, is lost in urine

Answer 38

Aldosterone

Question 39

Glucocorticoids MOA

Answer 39

● Largely unknown ● Influence the inflammatory response by stabilizing mast cell and basophil membranes, resulting in decreased histamine release

Question 40

Short Acting Glucocorticoids

Answer 40

● Hydrocortisone (Cortef) ● Cortisone (Cortone)

Question 41

Intermediate Acting Glucocorticoids

Answer 41

● Prednisone (Sterapred) ● Prednisolone (Orapred) ● Methylprednisolone (Medrol) ● Triamcinolone (Kenalog)

Question 42

Long Acting Glucocorticoids

Answer 42

● Betamethasone (Diprolene) ● Dexamethasone (Decadron) - first line treatment for croup

Question 43

Mineralocorticoids

Answer 43

Fludrocortisone (Florinef)

Question 44

Glucocorticoids Indications

Answer 44

● Inflammatory conditions: RA, skin issues, asthma maintenance control, asthma exacerbations, active inflammatory bowel disease ● Allergies: allergic rhinitis, drug allergic reactions ● Acceleration of lung maturation ● Diagnosis of Cushing syndrome ● Replacement therapy for adrenocortical insufficiency

Question 45

Glucocorticoids side effects

Answer 45

● Increased appetite ● Weight gain ● Emotional disturbances (There is more but these are most common Lauren said)

Question 46

Major Reactions (Major) of Glucocorticoids:

Answer 46

● Adrenal insufficiency ● Anaphylaxis ● Cushing syndrome ● DM ● Seizures ● GI perf ● Hypokalemic alkalosis

Question 47

Follow up/Monitoring of Glucocorticoids:

Answer 47

● Caution in pregnancy ○ Prednisone- preferred, minimizes effects on the fetus ● Caution with abrupt discontinuation of medication ○ May cause adrenal suppression ○ Suggest tapering