(3) Blood & Inflammation: Anti-inflammatory (3.1-3.2) Flashcards
What is the precursor molecule to prostanoids and leukotrienes?
Arachidonic acid
What enzyme liberates arachidonic acid from the cell membrane?
Phospholipase A2
Which COX enzyme is induced by inflammation?
COX-2
List 2 functions of COX-1
(1) TXA2 ⇒ Platelet aggregation
(2) Gastric cytoprotective prostaglandins
Where is COX-2 expressed?
(1) Vascular endothelial cells
(2) Smooth muscle
List 5 functions of COX-2
(1) PGI2⇒ Vasodilation
(2) Inhibits platelet aggregation
(3) Fever
(4) ↑ Pain sensitivity
(5) ↑ Vascular permeability
Which COX enzyme dilates the renal afferent arteriole?
Both.
Other than Ibuprofen and Aspirin, name 6 non-selective NSAIDs
(1) Diclofenac
(2) Ketorolac
(3) Indomethacin
(4) Meloxicam
(5) Piroxicam
(6) Naproxen
Adverse Effects (7) : Non-selective NSAIDs
(1) GI erosions
(2) Bleeding
(3) ↓ Na+ excretion ⇒ ↑ BP
(4) Interstitial nephritis
(5) Renal papillary necrosis
(6) Aplastic anemia
(7) Hypoaldosteronism
* (Bleeding often presents as GI bleed)*
Specifically, what type of kidney damage can occur due to NSAID induced vasoconstriction?
Renal papillary necrosis
(Medulla is already hypoxic ∴ ↑ Sensitivity ischemia ⇒ PAPILLARY necrosis)
What psychiatric drug’s concentration can be increased by NSAIDs?
Li+
Which NSAID most commonly causes aplastic anemia?
Indomethacin
MOA: Aspirin
IRREVERSIBLY acetylates COX-1 and COX-2
What NSAID is used in Kawasaki’s disease?
Aspirin
(Notable as ASA is usually avoided due to Reyes syndrome)
Name 2 signs/symptoms of Reye’s syndrome
(1) Encephalopathy
(2) Liver dysfunction
Name 3 signs of aspirin toxicity
(1) Metabolic acidosis
(2) Respiratory alkalosis
(3) Tinnitus
* (+ Hyperthermia. Tinnitus presents first)*
Treatment: Aspirin toxicity
(1) Charcoal
(2) NaHCO3
Contraindications (2) : NSAIDs
(1) Kidney ischemia
(2) Pregnancy
* (i.e., ACE inhibitors ⇒ ↓ renal perfusion. Also, remember they antagonize the effects of loop diuretics)*
Name 2 COX-2 selective antagonists
(1) Celecoxib
(2) Acetaminophen
Name one reason Celecoxib is better and one reason it’s worse than other NSAIDs
(1) Positive: Minimal GI damage
(2) Negative: ↑ Risk of cardiovascular damage
Which COX inhibitor is a sulfa drug?
Celecoxib
MOA: Acetaminophen toxicity
Consumption of GS-SH
⇒ ↑ NAPQI
⇒ Free radical liver damage
(⇒ Centrilobular liver necrosis)
Treatment: Acetaminophen toxicity
(1) Charcoal
(2) N-acetyl-cysteine
Why is N-acetyl-cysteine used for Acetaminophen toxicity?
Restores GSH
(GSH - glutathione)
Gout is caused by the build-up of:
Uric acid
What is uric acid derived from?
Purines
What enzyme converts hypoxanthine to uric acid?
Xanthine oxidase
Name 3 classes of drugs used in the acute treatment of gout
(1) NSAIDs (Indomethacin)
(2) Glucocorticoids
(3) Colchicine
MOA: Colchicine
Inhibits polymerization of microtubules
(∝ Vinca alkaloids and Griseofulvin)
What cell does Colchicine inhibit when used in treatment of gout?
Neutrophils
Describe the crystals of pseudogout
(1) Rhomboid
(2) Positively birefringent
Name 2 drugs used to treat chronic gout due to uric acid overproduction
(1) Allopurinol
(2) Febuxostat
Indications (3) : Allopurinol
(1) Gout
(2) Tumor lysis syndrome
(3) Lesch-Nyhan syndrome
What type of cancer most commonly causes tumor lysis syndrome?
(1) Lymphoma
(2) Acute lymphoblastic leukemia (ALL)
What drug class is notable for its interaction with Allopurinol?
Purine analogs
Adverse Effects (2) : Allopurinol
(1) Steven-Johnson syndrome
(2) DRESS syndrome
Treatment (3) : Gout (in under-excreters)
(1) Probenecid
(2) HIGH DOSE Aspirin
(3) Pegloticase
Adverse Effect: Probenecid (in treatment of gout)
⇒ Renal stones
What drug used to treat gout is notable for increasing the serum levels of several antibiotics?
Probenicid
Name a Sulfa drug used to treat gout
Probenicid
MOA: Pegloticase
Converts uric acid ⇒ Allantoin
Adverse Effects (2) : Pegloticase
(1) Hemolytic anemia (G6PD)
(2) Anaphylaxis
Name a drug used to treat gout which is only administered IV
Pegloticase
