Pharmacology - Anti Inflammatory Drugs Flashcards
What are the 4 class of anti-inflammatory drugs?
1) Corticosteroids
2) Topical Agents
3) NSAIDs
4) Monoclonal Antibodies
Cortisol is responsible for the redistribution of what?
Neutrophils (moves to plasma and then can’t get out), lymphocytes, monocytes, eosinophils, and basophils
What does cortisol cause a decrease in the release from macrophages?
Decreases release of TNFa, IL1, metalloproteinase, and plasminogen factor
What does cortisol cause a decrease in synthesis of?
- A decrease in synthesis of prostaglandins, leukotrienes, thromboxane, and histamines from mast cells.
What Cox does cortisol decrease the expression of?
- It decreases the expression of COX2
What are 4 synthetic corticosteroids?
1) Prednisone
2) Triamcinolone
3) Dextametasone
4) Fludrocortisone
How are synthetic corticosteroids different from natural corticosteroids?
- Higher affinity for mineral corticoids and glucocorticoid receptors
- Protein binding affinity, rate of elimination, and metabolic products.
Basically it prolongs it
What corticosteroid has the highest salt-retaining activity and is essentially equivalent to aldosterone?
- Fludrocortisone
What drugs have the highest anti inflammatory activity?
- Betamethasone, Desamethasone, and Fludrocortisone.
What are the clinical indication for use of corticosteroids?
- Arthritis (Osteoarthritis, Rheumatoid arthritis, and Psoriatic arthritis)
- Bursitis and tenosynovitis
- Asthma
- Temporal arteritis (Giant cell arteritis)
- Dermatitis
- Inflammatory bowel disease (chrohn’s and UC)
What are the adverse effects of corticosteroids?
What are some contraindication?
- Na+ retention and hypertension.
- Hypokalemia
- Osteoporosis
- Infections
- Hyperglycemia, glycosuria, and peptic ulcers
- Contraindications: peptic ulcers, hypertension, osteoporosis, and heart failure
Why is use of glucocosteroids assist in infection spread?
- due to immune system supression.
Why do NSAIDs cause kidney failure?
- Because of lower levels of prostacyclin in the afferent arterioles.
What 3 classes to NSAIDs fall into?
- Anti-inflammatory, anti-pyretic, and analgesics
What are some adverse affects with long term NSAID use.
-Increase in bleeding time, dyspepsia, subepithelial damage and hemorrhage, GASTRIC MUCOSAL EROSION, FRANK ULCERATION, and GASTRIC MUCOSAL NECROSIS
What is NSAIDs effects on the blood vessels?
- decrease the blood vessels’ sensitivity to bradykinin and histamine
What are the 3 traditional classifications of NSAIDs
- Aspirin and other traditional NSAIDs
- Acetaminophen
- COX2 - selective
In the Mode of action for Aspirin, what is irreversible inhibited and what does that lead to?
- COX1 and COX2 are irreversible inhibited leading to inhibition of prostaglandins, thromboxanes, and prostacyclins.
In the mode of action of aspirin what effect is there on energy production?
decrease in NADPH oxidase which is responsible for neutrophil oxidative burst (aka energy to engulf stuff)
Aspirin inhibition of this leads to increased aspirin-triggered lipoxins?
-COX2
What are aspirins clinical uses?
- decreases incidence of transient ischemic attacks
- unstable angina and coronary artery thrombosis
- ANALGESIC: synergistic with opioids and has been used in combination with morphine, etc. against cancer pain.
What are some adverse effects of Aspirin use?
- AIRWAY HYPERACTIVITY in asthmatic patients. Susceptible patients may also be reactive to indomethacin, naproxen, mefenamate, and phenylbutazone.
- REYE syndrome: may affect certain children under a certain age.
What NSAIDs are members of the propionic acid derivatives?
-IBUPROFEN, naproxen, ketoprofen, flurbiprofen
What are some clinical uses for propionic acid derivatives?
- Ibuprofen for arthritis
- a. spondylitis, gout, primary dysmenorrhea
Why would naproxen be favored over aspirin?
- Naproxen has a half-life 20x greater than aspirin. **
- Naproxen directly inhibits leukocyte function
- Causes less severe adverse effects than aspirin.
What are members of the acetic acid derivative class of NSAIDs?
INDOMETHACIN, sulindac, etodolac, diclofenac, and ketorolac
What is the mode of action of acetic acid derivatives?
- decreases the availability of arachidonic acid in addition to COX inhibition–> other eicosanoids are affected
What is Indometacin a direct inhibitor of. What is its clinical use?
- direct inhibitor of neutrophil motility***, but is less tolerated.
- Used in promoting closure of patent ductus arteriosus.***
What is Diclofenac mode of action? What is its main clinical use?
- decreases intrcellular concentration of arachidonic acid
- used widely in renal stone-associated pain
What is Ketorolac’s main clinical use?
- Strong analgesic properties, used in post-surgical patients.
What drugs are part of Fenamate derivatives?
What does it antagonize?
Compare it to aspirin?
What are it’s uses?
- mefenamate and meclofenamate
- Antagonize prostanoid receptors
- Less anti-inflammatory activity and higher adverse effects than aspirin
- Mefenamate- primary dysmenorrhea
- Meclofenamate - used for arthritis
What is piroxicam’s clinical use?
What does it inhibit?
- As efficacious as aspirin, naproxen, and ibuprofen against arthritis and is tolerated better.
- Inhibits collagenase, proteoglycanase, and oxidative burst
What is the use of Nabumetone?
- A prodrug that is more selective for COX2 and has less GI disturbances
What is the difference of Acetaminophen and other NSAID?
- unlike other NSAIDS acetaminophen is devoid of anti-inflammatory activity, but has a lower toxicity profile.
What is acetaminophen’s clinical efficacy?
Comparable analgesic and antipyretic effects as other NSAIDs
What type of toxicity might result from acetaminophen overuse?
May cause kidney and liver toxicities. The CYP 2E1 and CYP3A4 mediate toxicity via release of N-Acetyl-benzoquinone imine.
What is Celecoxib’s efficacy in treating clinical issues?
- similar efficacy in treating osteoarthritis, rheumatoid arthritis, primary dysmenorrhea but causes less GI side effects than other NSAIDs.
- also approved for familial adenomatous polyposis
What are the toxicity dangers from celecoxib?
- Higher risk of cardiovascular toxicity (heart attack and stroke)** than other NSAIDS
Name 3 types of drugs that are antibodies against TNFa?
- Adalimumab (RA)***, Etanercept (RA and psoriatic arthritis), and Infliximab (RA, UC, and Crohn’s, ankylosing spondylitis, and psoriatic arthritis). They work by suppressing IL-1, IL-6, and adhesion molecules involved in leukocytes migration (lymphoma risk)
What is the MOA and the clinical use of Abatacept?
- blocks T-cell activation with subsequence decrease in TNFa. It is approved for use in patient with sever resistant rheumatoid arthritis.
Glance over D-F
s
If patient has ankylosing spondylitis what treaments are available?
Short term - prostaglandin
Long term - Don’t use corticosteroids
