What does the lipoxygenase pathway of the arachidonic acid pathway yield?
Leukotrienes (remember: L for Lipoxygenase and Leukotrienes)
Which arachidonic acid product is a neutrophil chemotactic agent?
Leukotriene B4 (remember: Neutrophils arrive B4 others)
What effect do leukotrienes C4, D4, and E4 have on the bronchi and the bronchioles?
Bronchoconstriction
What effect do leukotrienes C4, D4, and E4 have on the vasculature?
Vasoconstriction and increase vascular permeability
What effect does prostacyclin (PGI2) have on platelets?
Inhibits platelet aggregation (remember Platelet-Gathering Inhibitor)
What effect does prostacyclin (PGI2) have on the vasculature?
Promotes vasodilation
What is the first step of the arachidonic acid pathway?
Membrane lipids are converted to arachidonic acid by phospholipase A2
Within the arachidonic acid cascade, what two enzymes use arachidonic acid as their substrate?
Lipoxygenase and cyclooxygenase
What drug inhibits the enzyme lipoxygenase?
Zileuton
What are the two mechanisms of action of steroids on the arachidonic acid pathway?
Steroids inhibit the action of phospholipase and inhibit the synthesis of cyclooxygenases
Cyclooxygenase directly converts arachidonic acid into what category of compounds resulting in what two products?
Endoperoxides; prostaglandins G and H
Hydroperoxides are the precursors of what class of arachidonic acid products?
Leukotrienes
Endoperoxides are the precursors of what three arachidonic acid products?
Prostacyclin, prostaglandins, and thromboxane
List two drugs that inhibit leukotrienes from producing an increase in bronchial tone.
Zafirlukast and montelukast
Name three effects of prostacyclin.
Prostacyclin decreases platelet aggregation, causes vasodilation and decreases uterine tone
Name four effects of prostaglandins on the body.
Prostaglandins cause a decrease in vascular tone, increase in pain, increase in uterine tone, increase in temperature
Zileuton inhibits the conversion of _____ to _____.
arachidonic acid to hydroperoxides
Aspirin _____ (reversibly/irreversibly) inhibits cyclooxygenase.
Irreversibly
Aspirin causes a decrease in synthesis of what two products?
Thromboxane and prostaglandins
At what dose does aspirin cause decreased platelet aggregation?
Low-dose; < 300 mg/day
At what dose does aspirin have antipyretic and analgesic properties?
Intermediate dose; 300-2400 mg/day
At what dose does aspirin have antiinflammatory properties?
High dose; 2400-4000 mg/day
What is a common toxicity of aspirin use?
Gastric upset
Chronic use of aspirin can cause what three problems?
Acute renal failure, interstitial nephritis, and upper gastrointestinal bleeding
What syndrome can develop in children with viral illnesses who are given aspirin?
Reyes syndrome
Name four examples of nonsteroidal antiinflammatory drugs.
Ibuprofen, naproxen, indomethacin, and ketorolac
Nonsteroidal antiinflammatory drugs work by reversibly inhibiting what substance?
Cyclooxygenase
Do ibuprofen, naproxen, indomethacin, and ketorolac inhibit cyclooxygenase-1, cyclooxygenase-2, or both?
Both
Nonsteroidal antiinflammatory drugs block the synthesis of what substance?
Prostaglandins
What are the three effects of administration of nonsteroidal antiinflammatory drugs?
They are antipyretics, analgesics, and antiinflammatory agents
Which nonsteroidal antiinflammatory drug is used to close a patent ductus arteriosus?
Indomethacin
What four toxicities are associated with nonsteroidal antiinflammatory drugs?
Renal damage, aplastic anemia, gastrointestinal distress, and ulcers
How do cyclooxygenase-2 inhibitors differ from other nonsteroidal antiinflammatory drugs?
Reversibly inhibit cyclooxygenase-2, found in inflammatory cells and vascular endothelium, mediates inflammation and pain; unlike nonsteroidal antiinflammatory drugs, it spares cyclooxygenase-1
Explain the mechanism by which cyclooxygenase-2 inhibitors help maintain the gastric mucosa.
Cyclooxygenase-2 inhibitors do not affect the cyclooxygenase-1 enzymes that produce the prostaglandins that protect the gastric mucosa
What are the two clinical indications for using cyclooxygenase-2 inhibitors?
To treat rheumatoid arthritis and osteoarthritis
Individuals with an allergy to _____ should avoid taking cyclooxygenase-2 inhibitors.
Sulfa
There is an increased risk of _____ when taking cyclooxygenase-2 inhibitors.
Thrombosis
Acetaminophen reversibly inhibits what substance in the central nervous system?
Cyclooxygenase
Acetaminophen has antipyretic and analgesic activities but lacks what other property that is common to nonsteroidal antiinflammatory drugs?
Antiinflammatory properties
What are the physiologic effects of an acetaminophen overdose?
Hepatic necrosis
Acetaminophens metabolite depletes what reducing substance in hepatic cells?
Glutathione
What is the antidote to acetaminophen toxicity?
N-acetylcysteine; regenerates glutathione depleted by acetaminophen overdose
True or False? Acetaminophen has antiinflammatory activity.
False; acetaminophen is an nonsteroidal antiinflammatory drug without antiinflammatory activity
Aspirin is a Nonsteroidal Antiinflammatory Drug with what additional activity?
Antiplatelet activity
Name four bisphosphonates.
Etidronate, pamidronate, alendronate, and risedronate
What is the mechanism of action of bisphosphonates?
Inhibit osteoclastic activity
Name three clinical indications for use of bisphosphonates.
Malignancy-associated hypercalcemia, Pagets disease of bone, postmenopausal osteoporosis
Name the three major toxicities of bisphosphonates.
Corrosive esophagitis, nausea, and diarrhea
Is colchicine used to treat chronic gout or acute gout?
Acute gout
Which medication used for gout depolymerizes microtubules, thereby impairing leukocyte chemotaxis and degranulation?
Colchicine
Colchicine has adverse effects related to which organ system, especially when taken orally?
The gastrointestinal system
Which medication is used more often to treat acute gout because it causes less toxicity than colchicine?
Indomethacin
Is probenecid used to treat chronic gout or acute gout?
Chronic gout
Which medication for gout inhibits the reabsorption of uric acid and the secretion of penicillin?
Probenecid
Is allopurinol used to treat chronic gout or acute gout?
Chronic gout
Which treatment for gout inhibits xanthine oxidase, which decreases the conversion of xanthine oxidase into uric acid?
Allopurinol
Which treatment for gout inhibits xanthine oxidase and is used to prevent tumor-lysis-associated urate nephropathy in individuals with lymphomas and leukemias?
Allopurinol
Allopurinol causes increased serum levels of which drugs if taken concurrently?
Azathioprine and 6-MP; both normally metabolized by xanthine oxidase, which is inhibited by allopurinol
What drug should not be used to treat gout?
Salicylates, which depress uric acid clearance
What substance is converted to uric acid for excretion from the body? What are the intermediates?
Purines; hypoxanthine and xanthine
Which two reactions are inhibited by allopurinol and catalyzed by xanthine oxidase?
Conversion of hypoxanthine to xanthine and conversion of xanthine to uric acid
Which two drugs inhibit the tubular reabsorption of uric acid?
Probenecid and high-dose salicylates
Which two drugs inhibit the tubular secretion of uric acid?
Diuretics and low-dose salicylates
List three clinical uses for etanercept.
Rheumatoid arthritis, psoriasis, and ankylosing spondylitis
A patient with Crohn’s disease presents for treatment with infliximab. What infection does the physician worry about reactivating?
Latent tuberculosis
List three clinical uses for infliximab.
Crohn’s disease, rheumatoid arthritis, and ankylosing spondylitis
Name the drug with the following mechanism: directly binds tumor necrosis factor receptor sites.
Adalimumab
List three clinical uses for adalimumab.
Rheumatoid arthritis, psoriasis, and ankylosing spondylitis
Name the drug with the following mechanism: recombinant form of human tumor necrosis factor receptor that binds tumor necrosis factor.
Etanercept (remember: EtanerCEPT is a TNF decoy reCEPTor)
