Musculoskeletal Drugs Flashcards
(39 cards)
What is the pathways for AA?
What is the starting product?
Where does it go to next?
Start with membrane lipid ( phophatidylinositoly)
lipid—> (Phospholipase A2) –> Arachidonic Acid
What different paths can Arachidonic Acid head down?
What enZs do that?
What drugs inhibit those enzymes?
AA—> (Lipoxygenase)—> Hydorperoxidase ( HPETES) that go to LeukoT
Zieluton inhibits Lipoxygenase
OR
AA–> (COX1 and 2)–> Endoperoxides (PGG2, PGH2)
NSAIDs/aspirin/actaminophen/ COX-2 inhitors block COX1 and 2
What drugs inhibit COX 1 and COX 2?
Corticosteroids
NSAIDS, aspirin, acetominophen, COX-2 inhibitors
Thus can’t make Prostacyclines (PGI2)
Can’t make Prostaglandins (PGE2, PGF2)
Can’t make Thormoboxane (TXA)
What is the Starting point of the AA cycle
What does it genererate?
Via what pathways
Start with lipid membrane —> Phospholipase A2 to AA
Then can head down lipoxygeanse path to make Leukotrienes
OR
Head down the COX1 and 2 path to amke TXA2, Prostaglandins: PGE2, PGF2 and Prostacyclines: PGI2
What drug can inhibit the progression for LTC4, LTD4 and LTE4 which causes
INCREASED bronchial tone
Zarfirlukast and Montelukast block receptor for LCT, LTD and LTE
What is the role of the following:
LTB4:
LTC4, LTD4, LTE4:
LTB4: Neutrophil chemotaxis
LTC4, LTD4, LTE4: Increase bronchial tone (blocked by Zeiluton or Monteclast)
What are the restuls of the following products
Prostacyclin : PGI2
Prostaglandin: PGE2 and PGF2
Thromboxane: TXA
Prostacyclin : PGI2 –> Low plat aggregation, low vascular tone, low bronchial tone, low uterine tone
Prostaglandin: PGE2 and PGF2–> Increased uterine tone and decrease bronchial tone
Thromboxane: TXA: Increase plat aggregation, increase vascular tone, increase bronchial tone
______ is a neutrophil chemotactic agent.
_____ inhibits platelet aggregation and promotes vasodilation.
LTB4
PGI2
what is the mechanism of Acetaminophen?
Where does it act?
What is it used for?
Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
Antipyretic, analgesic, but not anti-inflammatory.
Used instead of aspirin to avoid Reye syndrome in children with viral infection
What drug would we use for child with fever and aches?
What’s it’s mechanims?
Use Acetominophen
irreversible inhibits COX and safer choice over aspirin
What toxicity is associated with Acetominophen?
What organ?
What is the antidote?
Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver.
N-acetylcysteine is antidote—regenerates glutathione.
Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) via acetylation, which decreases synthesis of TXA2 and prostaglandins.
Increased bleeding time. No effect on PT, PTT. A type of NSAID.
Aspirin
What is the difference between low dose, intermediate dose and high dose Aspirin
Low dose (< 300 mg/day): platelet aggregation.
Intermediate dose (300–2400 mg/day): antipyretic and analgesic.
High dose (2400–4000 mg/day): anti-inflammatory.
What is the mechanism of Aspirin?
Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) via acetylation, which increase synthesis of TXA2 and prostaglandins.bleeding time. No effect on PT, PTT. A type of NSAID.
What toxicity is associated with Aspirin?
Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding.
Risk of Reye syndrome in children tr_eated with aspirin for viral in_fection. Causes respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis
What is the mechanism and use of Celcoxib?
Reversibly inhibits specifically the cyclooxygenase (COX) isoform 2,
which is found i_n inflammatory cells and vascular endothelium_ and mediates inflammation and pain; spares COX-1, which helps maintain gastric mucosa.
What pathways in the AA path are spared by Celecoxib?
spares COX-1, which helps maintain gastric mucosa.
Thus, does not have the corrosive effects of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on COX-1.
What are the big effects of aspirin?
Analgesic: central and peripheral action
Antipyrietic: acts in hypothal to lower the set point of temperature control elevated by fever—causes sweating
Anti-inflammatory: INhibits peripheral prostaglandin synthesis
Respiratory stimulation: Direct action on repiratory center thus indirectly increaese CO2 production
This drug can be used for pain relief but doen’st fuck with the gastric mucosa.
What are some risks associated with it?
High risk of thrombophelbeitis because leaves the TXA pathway alone as well as SULFA allergy
Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac.
All are examples of what type of drug and all have what MOA?
NSAIDs
Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis.
These drugs REVERSIBLY inhibit COX 1 and COX2 to block PG synthesis.
What is their use?
What drugs are they?
What is a specific use of Indomethacin?
Use: Antipyretic, analgesic, anti-inflammatory.
Indomethacin is used to close a PDA.
These are NSAIDS: Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac.
Pt experiences chronic low back pain so takes ibuprofen on a daily basis at double the recommended dose..
What is he putting himself at risk for?
Why?
Interstitial nephritis
gastric ulcer (prostaglandins protect gastric mucosa)
renal ischemia (prostaglandins vasodilate afferent arteriole).
What are examples of Bisphosphonates?
How do they work?
Alendronate, other -dronates.
Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity
When would you prescribe Aldeondronate?
What is it’s mechanism?
Osteoporosis, hypercalcemia, Paget disease of bone.
Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity.
