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Musculoskeletal

FA complete review part 4 Pharmacology

QuestionAnswer
Which are the anti-inflammatory type of drugs that inhibit Phospholipase A2 in the Arachidonic acid pathway? Glucocorticoids (corticosteroids)
Which enzyme is inhibited by glucocorticoids in the AA pathway? Phospholipase A2
Membrane phospholipids are converted into Arachidonic acid via which enzyme? Phospholipase A2
Leukotriene synthesis stopped by inhibiting which enzyme? 5-Lipoxygenase
Inhibition of 5-lipoxygenase causes the inhibition what type product synthesis? Leukotrienes
What is a common drug that works by inhibiting 5-Lipoxygenase? Zileuton
Which enzyme is inhibited by Zileuton? 5-Lipoxygenase
What process is inhibited with the use of Zileuton? Leukotriene synthesis
Which leukotrienes are inhibited ty Leukotriene receptor antagonists? LTC-4, LTD-4, and LTE-4
What are some common Leukotriene Receptor antagonists? Montelukast and Zafirlukast
LTC4, LTD4, LTE4 cause: Increased bronchial tone
What is the function of LTB4? Incrase neutrophil chemotaxis
Which is precursor of leukotrienes from Arachidonic acid? 5-HPETE
What enzyme converts Arachidonic acid into 5-HPETE? 5-Lipoxygenase
Which Leukotriene (LT) subtype is NOT inhibited by Leukotriene receptor antagonists? LTB-4
What is a common COX-2 only inhibitor? Celecoxib
What is the irreversible COX-1 & COX-2 inhibitors? Aspirin
Which COX is inhibited by Celecoxib? COX-2
List of reversible NSAIDs: - Diclofenac - Ibuprofen - Indomethacin - Ketorolac - Naproxen
What process is inhibited by inhibiting COX? Endoperoxidase synthesis
What are the roles of PGI2? - Decreased platelet aggregation - Decreased vascular tone
Which prostaglandin decreases vascular tone? PGE-1
What are the products of Cyclic endoperoxides? Prostacyclin, Prostaglandins, and Thromboxane
Which prostaglandins work by increased uterine tone? PGE2 and PGF-2 alpha
What is the functions of TXA2? - Increased platelet aggregation - Increased vascular tone
What is the mechanism of action of Acetaminophen? Reversibly inhibits cyclooxygenase, mostly in CNS
Where does acetaminophen has the most efficacy? CNS
What are clinical uses for Acetaminophen? Antipyretic, analgesic, but not anti-inflammatory
True or False. Acetaminophen has no anti-inflammatory properties. True. Acetaminophen is not an anti-inflammatory
What medication should be used instead to aspirin in children to avoid Reye syndrome? Acetaminophen
What does OD on acetaminophen causes? Hepatic necrosis
What is the acetaminophen metabolite? NAPQI
What causes NAPQI? Depletes glutathione and foresm toxic tissue byproducts in liver
What is used to treat acetaminophen overdose? N-acetylcysteine
How does N-acetylcysteine works to treat acetaminophen overdose? Regenerates glutathione
What is MOA of Aspirin? Irreversibly inhibits cyclooxygenase-1/-2, by covalent acetylation leading to decreased synthesis of TXA2 and prostaglandins
What hematologic lab result in increased by the use of Aspirin? Bleeding time
How long do the effects of Aspirin last? Until new platelets are produced
What is the clinical cause for a low dose of Aspirin? Decrease platelet aggregation
What is considered a low dose of aspirin? < 300 mg/day
What is a intermediate dose of aspirin? 300-2,400 mg/day
What is the clinical use of intermediate aspirin dose? Antipyretic and analgesic
What is consider a high dose of Aspirin? 2,400-4,000 mg/day
What is the clinical use of high-dose of Aspirin? Anti-inflammatory
What does toxic doses of Aspirin can provoke? Respiratory alkalosis early, but transition to mixed metabolic acidosis-respiratory alkalosis
What reh the acute adverse effects of Aspirin? Gastric ulceration, tinnitus (CN VII),and allergic reactions
What are some adverse effects of chronic aspirin administration? Acute renal failure, interstitial nephritis, and GI bleeding
What is a severe adverse effect of treating a child's fever with Aspirin? Reye syndrome
Which conditions lead to higher risk to develop allergic reaction to aspirin? Asthma and/or nasal polyps
What is used to treat Aspirin overdose? NaHCO3 (sodium bicarbonate)
What is the acid base profile of Aspirin toxicity? 1st: Respiratory alkalosis (early) 2nd: Transitions to mixed metabolic acidosis <--> Respiratory alkalosis
MOA of Celecoxib Reversibly and selectively inhibits the cyclooxygenase (COX) isoform 2
COX-2 receptors are found in: Inflammatory cells and vascular endothelium and mediates inflammation and pain
Why is Celecoxib used to treat pain in PUD patients? Spares COX-1, which helps maintains gastric mucosa, thus not affect PUD patients
Spares platelet function as TXA2 productions is dependent on COX-1. Drug? Celecoxib
What conditions are often treated with Celecoxib? Rheumatoid arthitirts and Osteoarthritis
What are the significant adverse effects associated with Celecoxib? 1. Increase risk of thrombosis 2. Sulfa allergy
What are some examples of NSAIDs? Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, and piroxicam.
What is the MOA of NSAIDs? Reversibly inhibit COX-1 and COX-2; blocking prostaglandin synthesis.
What is the clinical use for NSAIDs? Antipyretic, analgesic, anti-inflammatory
What is an specific use for Indomethacin? Close a PDA
Which NSAID is used to close a PDA? Indomethacin
What are the associated adverse effects of NSAIDs? 1. Interstitial nephritis 2. Gastric ulcer 3. Renal ischemia 4. Aplastic anemia
How does usage of NSAIDs for a prolonged time cause a Gastric ulcer? Prostaglandins protect gastric mucosa
Which type of analgesics are contraindicated in persons with PUD or risk of any gastric ulcer? NSAIDs
How does NSAID therapy may cause renal ischemia? Prostaglandin vasodilation afferent arteriole of the nephron
MOA of Leflunomide: Reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis
What are the common uses for Leflunomide? Rheumatoid arthritis and Psoriatic arthritis
Associated adverse effects of Leflunomide: Diarrhea, HTN, Hepatotoxicity, and Teratogenicity
Which enzyme is inhibited by Leflunomide? Dihydroorotate dehydrogenase
Common Bisphosphonates: Alendronate, Ibandronate, Risedronate, and Zoledronate
Pyrophosphate analogs used in bone diseases? Bisphosphonates
MOA of Bisphosphonates: Bind hydroxyapatite in bone, inhibiting osteoclast activity
What are common clinical uses of Bisphosphonates? Osteoporosis, hypercalcemia, Paget disease of bone, metastatic bone disease, and osteogenesis imperfecta
What are the associated adverse effects of Bisphosphonates? 1. Esophagitis 2. Osteonecrosis of jaw 3. Atypical femoral stress fractures
How is Esophagitis due to bisphosphonates intended to prevented? Patients are advised to take with water and remain upright for 30 minutes
What is the mode of action of Teriparatide? Increase osteoblastic activity when administered in pulsatile fashion
Important Recombinant PTH analog used for Osteoporosis. Teriparatide
What is the clinical use of Teriparatide? Osteoporosis; causes increase bone growth compared to antiresorptive therapies
What is the adverse effect of Teriparatide? Increase risk of Osteosarcoma and transient hypercalcemia
What are the chronic gout drugs (preventive)? Probenecid, Allopurinol, Pegloticase, and Febuxostat
List of Acute Gout drugs: 1. NSAIDs 2. Glucocorticoids 3. Colchicine
MOA of Probenecid: Inhibits reabsorption of uric acid in PCT
What is a common adverse of Probenecid? Precipitate uric acid calculi
What are two common Gout (preventive) drugs that inhibit XO? Allopurinol and Febuxostat
What is the mode of action of Allopurinol Competitive inhibitor of XO leading to a decrease conversion of hypoxanthine and xanthine to urate
Other than in Gout, Allopurinol, is also a preventive measure for: Tumor lysis-associated urate nephropathy in Leukemia and lymphoma patients
The use of Allopurinol leads to increase concentrations of: Xanthine oxidase active metabolites, azathioprine, and 6-MP.
High levels of 6-MP and Azathioprine are often seen in patient with long Hx of Gout, because: Allopurinol use
MOA of Febuxostat: Inhibits xanthine oxidase
What is the MOA of Pegloticase? Recombinant uricase catalyzing uric acid to allantoin
What is more water soluble, uric acid or allantoin? Allantoin
Which Gout-treating medication is known to convert uric acid into allantoin? Pegloticase
In which part of the nephron does Probenecid act upon? PCT
What is an added effect of Probenecid? Inhibition of the secretion of penicillin
Which drugs can inhibit (decrease) uric acid excretion/secretion? Diuretics and low-dose salicylates
How does high-dose salicylates help in treating acute gout flares? Inhibit tubular reabsorption of Uric acid
Does high-dose or Low-dose salicylates, help in treating acute gout events? High-dose salicylates
What is the MOA of Colchicine? Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation
To what protein does Colchicine bind in order to work in acute gout? Tubulin
What is the result of Colchicine--Tubulin binding? Microtubule polymerization which leads to impairing neutrophil chemotaxis and degranulation
What type of side effects are associated with Colchicine? GI and Neuromyopathic side effects
List of common TNF-alpha inhibitors: 1. Etanercept 2. Infliximab, 3. Adalimumab, 4. Certolizumab, 5. Golimumab
What is the mechanism of action of Etanercept? TNF-alpha inhibitor
Fusion protein, produced by recombinant DNA Etanercept
What drug is a decoy receptor for TNF-alpha + IgGi Fc? Etanercept
What conditions are often treated with Etanercept? Rheumatoid arthritis, psoriasis, and ankylosing spondylitis
List of Anti-TNF-alpha monoclonal antibody medications: Infliximab, Adalimumab, Certolizumab, and Golimumab
Which conditions are treated with infliximab? Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, and psoriasis
What are the most significant adverse effect of TNF-alpha inhibitors? Predisposition to infection, including reactivation of latent TB and drug-induced lupus.
Created by: rakomi
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