Exam 2 - Nelson Material Flashcards
How is celexocib related to prostaglandins?
- Selective COX-2 inhibitor –> inhibits formation of prostaglandins from arachidonic acid
- Decreases downstream inflammatory prostaglandins
- Treatment of rheumatoid arthritis
How is latanaprost related to prostaglandins?
- PGF2a analog
- lipophilic so it can penetrate cornea
- decreases production of aqueous humor –> reduces intraocular pressure
- Treatment of ocular hypertension/glaucoma
What is the use and MOA of anakinra?
Interleukin receptor antagonist (IL-IRa)
- competitively inhibits IL-1 from binding and causing inflammation
- used in rheumatoid arthritis to reduce inflammation
What is the use and MOA of etanercept?
Soluble fusion protein
- tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1
- binds to TNF-alpha and “sequesters” it –> leads to decreased inflammation downstream
- used in rheumatoid arthritis
What is the use and MOA of Brilinta (ticagrelor)?
ADP analog
- competitively inhbits ADP from binding to P2y12 receptor in platelets, which would initiate clotting
- used as an anti-thrombotic
What is the use and MOA of aspirin (hemetologic)?
COX-1 inhibitor
- irreversibly inhibits COX-1 by acetylating a serine residue
- inhibits formation of PGH2 (which is converted to TXA2 and initiates clotting)
- used to prevent blood clots in patients at risk
What is the ligand/substrate for the activated GPIIb/IIIa receptor? Why is inhibition therapeutically useful?
- The activated form binds fibrinogen
- When bound, the fibrinogen can form cross-links between platelets via fibrinogen-fibrinogen or fibrinogen-VWF
- Inhibition of fibrinogen prevents cross-links and prevents platelet aggregation
What is the ligand/substrate for COX-2? Why is inhibition therapeutically useful?
- Binds arachadonic acid, converts it to PG-G2
- Implicated in the proinflammatory response and associated with pain
- Inhibition reduces inflammation and pain
What is the ligand/substrate for the P2Y12 receptor? Why is inhibition therapeutically useful?
- Binds ADP and other purines
- A component of ADP-mediated platelet aggregation
- Inhibition leads to less ADP induced platelet-fibrinogen binding and less platelet aggregation
What is the ligand/substrate for xanthine oxidase? Why is inhibition therapeutically useful?
- Oxidizes hypoxanthing to xanthine and uric acid
- Uric acid (in form of sodium urate) can precipitate and form crystals that deposit in joints in gout, leading to inflammation
- Inhibition prevents the formation of the sodium urate and is a treatment for gout
What is the ligand/substrate for COX-1? Why is inhibition therapeutically useful?
- COX-1 converts arachidonic acid –> prostaglandin –> TXA2, which induces platelet aggregation
- Inhibition of COX-1 in platelets lowers TXA2 levels and prevents activation of GPIIb/IIIa, which leads to less platelet aggregation
What is the therapeutic use and MOA of adalimumab (Humira)?
- human MAB specific for TNF-alpha
- prevents TNF-alpha mediated inflammation
How is clopidogrel used and thought to work?
- Oxidation of the thiopene ring yields a ring-open (active) metabolite
- The active metabolite binds to cys 97 of the P2Y12 receptor, which normally binds ADP and induces platelet aggregation
- The covalent bond prevents platelet aggregation
- Used as an anti-thrombolytic
How is tirofiban used and thought to work?
- Competitive antagonist of the GPIIb/IIIa receptor
- Modeled to occupy binding site for Arg-GLy-Asp area of fibrinogen
- Prevents fibrinogen binding, and formation of platelet plug
- Used in acute coronary syndrome, coronary angioplasty
