Anti-inflammatories and Corticosteroids Flashcards
Prostaglandins are produced in almost all tissues and act _____
locally
(they don’t circulate in the blood)
Function of Prostaglandins
- 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
_____ is the primary precursor of prostaglandins
and is a component of the phospholipids of cell membranes
Arachidonic acid
Free arachidonic acid is released from _____
tissue phospholipids by phospholipase A2
Prostaglandins are synthesized from
arachidonic acid via the _____
cyclooxygenase pathway
COX enzymes functions
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
T/F COX-1 and COX-2 have differences
in binding site shape which allow
for selective inhibitors
T
NSAIDs (Nonsteroidal Anti-inflammatory Drugs) MOA
● Inhibit the synthesis of prostaglandins
● Primarily inhibit the cyclooxygenase enzymes that catalyze the first step in prostanoid biosynthesis
Aspirin is a _____ NSAID
Non-Selective NSAID
NSAID analgesic effects:
○ 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
NSAIDs lower body temp by impeding ____
synthesis; essentially resetting the thermostat
towards normal
PGE2
Non-Selective NSAIDs
● Aspirin (ASA)
● Ibuprofen (Ibu, Motrin, Advil)
● Naproxen (Aleve)
● Diclofenac (Voltaren)
● Ketoprofen (Orudis)
● Piroxicam (Feldene)
● Meloxicam (Mobic)
● Indomethacin (Indocin)
● Ketorolac (Toradol)
NSAIDS most important effects
Anti-inflammatory
Analgesic
Antipyretic
Contraindications for NSAIDS
● NSAID induced asthma orurticaria
● Aspirin triad
● 3rd Trimester of Pregnancy
● CABG surgery periop use
● Hypersensitivity to NSAIDs
Additional contraindication for Indomethacin (NSAID)
Neonatal: renal impairment, active bleeding, necrotizing enterocolitis, congenital heart
disease
Additional contraindication for Ketorolac (NSAIDS)
Pre-op major surgery, CABG periop pain, labor
and delivery, coagulation disorders
NSAIDS BBWs:
- 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
____ is an NSAID with indications for more moderate to severe pain
Ketoralac
NSAIDs Side Effects (Common)
● Stomach upset
● Dyspepsia
● N/V
● HA
● Dizziness
● Anemia
● Peripheral edema
● Hemorrhage
● Urinary retention
● Cough
● Diarrhea
NSAIDs Adverse Reactions (Major):
● GI bleeding
● GI ulcers
● Hemorrhage
● Prolonged bleeding time
● HTN
● MI
● Anaphylaxis
● Nephrotoxicity
● Hepatotoxicity
● Stevens-Johnson syndrome
● Toxic Epidermal Necrolysis
Avoid NSAIDs in pts with ____
asthma
Why we should Avoid NSAIDs in the 3rd trimester of pregnancy
○ Can cause premature closing of ductus arteriosus
○ Acetaminophen is preferred during pregnancy
NSAIDs prevent the synthesis of ___ and ___, which
maintain renal blood flow especially in marginally functioning kidneys
PGE2 and PGE1
T/F Aspirin Only exhibits anti-inflammatory properties at high doses
T
Aspirin is An _____ inhibitor of cyclooxygenase activity
irreversible
Indications for Aspirin
● Fever
● Reduce risk of CV events → MIs, TIAs, CVAs
● Mild pain
Contraindications for Aspirin
● 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
Side Effects (Common) for Aspirin:
● GI pain
● Ulcers
● GI bleeding
● N/V
● Dizziness
● Rash
● Tinnitus
Adverse Reactions (Major) in Aspirin:
● Hemorrhage
● Reye Syndrome
● Nephrotoxicity
● Anaphylaxis
● Bronchospasm
● Renal failure
● GI perf/ulcer
Selective NSAIDS
Celecoxib (Celebrex): Selective to COX-2 inhibitors
Celecoxib MOA
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
Indications for use of Celecoxib
● Approved for the treatment of RA and OA
● Acute mild to moderate pain
Contraindications of Celecoxib
● 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
Side effects of Celecoxib
HA, dyspepsia, diarrhea, and abdominal pain
Corticosteroid Secretion
- Stress → CRH (corticotropin-releasing hormone) releases from the hypothalamus
- ACTH (adrenocorticotropic
hormone) releases from the anterior pituitary - Cortisol releases from the adrenal cortex which inhibits feedback
Glucocorticoid Properties
Anti-inflammatory
Immunosuppressive
Increase resistance to stress
Glucocorticoid Properties
- Promote normal intermediary metabolism
- Alter blood cell levels
______ → 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
Aldosterone
Glucocorticoids MOA
● Largely unknown
● Influence the inflammatory response by stabilizing mast cell
and basophil membranes, resulting in decreased histamine
release
Short Acting Glucocorticoids
● Hydrocortisone (Cortef)
● Cortisone (Cortone)
Intermediate Acting Glucocorticoids
● Prednisone (Sterapred)
● Prednisolone (Orapred)
● Methylprednisolone (Medrol)
● Triamcinolone (Kenalog)
Long Acting Glucocorticoids
● Betamethasone (Diprolene)
● Dexamethasone (Decadron) - first line treatment for croup
Mineralocorticoids
Fludrocortisone (Florinef)
Glucocorticoids Indications
● 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
Glucocorticoids side effects
● Increased appetite
● Weight gain
● Emotional disturbances
(There is more but these are most common Lauren said)
Major Reactions (Major) of Glucocorticoids:
● Adrenal insufficiency
● Anaphylaxis
● Cushing syndrome
● DM
● Seizures
● GI perf
● Hypokalemic alkalosis
Follow up/Monitoring of Glucocorticoids:
● Caution in pregnancy
○ Prednisone- preferred, minimizes effects on the fetus
● Caution with abrupt discontinuation of medication
○ May cause adrenal suppression
○ Suggest tapering
