Term
| Intact Endothelial Actions to Deter Platelet Activity |
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Definition
1) production of NO -> inhib plat
2) production of PGI2 -> bind plat recep to inhib activation
3) metabolism of ADP to AMP (via CD39 recept) -> no ADP to activate plats |
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Term
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Definition
Made by activated platelets
Binds TXA2 receptor (Gq) on platelet
-> PLC -> PiP2 -> IP3 -> increased Ca++ -> aggregation |
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Term
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Definition
Stored in platelets
Binds P2Y1 (Gq) -> increased Ca++ -> aggreg
Binds P2Y12 (Gi) -> inhibit adenylate cyclase -> decreased cAMP -> aggreg
**must bind both |
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Term
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Definition
a serine protease converted from prothrombin by Factor X
1) cuts fibrinogen -> fibrin
2) cuts N-term of PAR-1 recept on platelet
-> PAR-1 activates itself
PAR-1(Gi) -> decreased cAMP -> aggreg
PAR-1(Gq) -> increased Ca++ -> aggreg |
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Term
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Definition
Activated by:
TXA2&ADP binding platelet -> GPIIIa/IIb receptor appears
fibrinogen binding GPIIIa/IIb -> thrombin protease cleaves
-> becomes fibrin & crosslinks with other plats :) |
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Term
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Definition
Irreversible COX inhibitor
1) decreased TXA2 synth in plats (preferential) -> antiagg
-binds plat in portal vein before metab'd (potent)
-plat enucleated -> must make more plats before more TXA2
2) decreased PGI2 synth in endothelium -> aggreg
-however ASA doesn't reach it until metab
-cells can make more COX |
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Term
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Definition
MOA: block ADP binding site on plat -> anti-agg
ADR: neutropenia, TPP (clotting) |
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Term
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Definition
Ticlid
P2Y12 Antagonist
Worst for neutropenia |
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Term
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Definition
MOA: block ADP binding site on plat -> anti-agg
ADR: neutropenia, TPP (clotting)
Usually loaded dose initially |
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Term
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Definition
Ticlid
P2Y12 Antagonist
Worst for neutropenia |
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Term
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Definition
Plavix --> PRODRUG
M: CYP 2C19 & 3A4 (efficacy decreases with CYPi's)
Irreversible |
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Term
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Definition
Effient --> PRODRUG
M: liver esterase, then CYP
Irreversible |
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Term
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Definition
Brilinta --> Active Drug
Give to CYP-deficient patients |
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Term
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Definition
MOA: blocks fibrinogen binding therefore no crosslinking even if platelet is activated
Uses: prior to angioplasty to prevent clot that would have formed from endothelial disruption |
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Term
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Definition
ReOpro
GPIIb/IIIa Receptor Antagonist |
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Term
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Definition
Aggrastat
GPIIb/IIIa Receptor Antagonist |
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Term
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Definition
Integrilin
GPIIb/IIIa Receptor Antagonist |
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Term
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Definition
PDE3i & adenosine transporter antag -> anti platelet
Uses: stroke only
MOA:
1) blocks adenosine transporter -> more adenosine available EC to bind A2 (Gs) receptor on platelets -> increased cAMP -> antiaggreg
2) inhibit PDE3 -> increased cAMP -> antiaggreg
*also inhib PDE5 -> vasodil |
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Term
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Definition
PDE3i -> anti platelet
Uses: PVD chronic use
MOA: PDE3 inhibitor -> increased cAMP -> antiagg |
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Term
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Definition
PDE3i & "unknown" -> anti platelet
MOA: reduces platelet # by decreasing megakaryocytes arising from stem cells
Uses: thrombocythemia |
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Term
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Definition
IV/(SC rarely)
MOA: inhibits fibrinogen -> fibrin (by less thrombin)
1) factor IIa inhibition via heparin binding AT3; AT3& IIa bind together then bind heparin
2) factor Xa inhibition via heparin binding AT3; AT3 & Xa bind (no direct Xa binding)
OOA: immediate acting |
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Term
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Definition
per unit of activity (due to variation in molecular weight); e.g. amount of hep that will clot 1mL of blood
usually loaded dose initially |
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Term
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Definition
| via PTT; want 2-3x normal clotting time |
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Term
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Definition
inhibits aldosterone -> hyperkalemia
osteoporosis (only w/chronic use)
bleeding
HIT -> reduced number of platelets but remaining platelets activate -> clot formation |
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Term
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Definition
protamine sulfate (basic)
binds free (acidic) heparin to neutralize
dosing: based on estimation of serum heparin;
excess protamine -> anticoagulation effects via fibrinogen inhibition |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
Smallest heparins
MOA: inhibits fibrinogen->fibrin (by less thrombin) |
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Term
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Definition
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Term
LMWHs
Monitoring & Antidote |
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Definition
Monitoring: None (no direct change in Factor IIa)
Antidote: Try protamine (?) |
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Term
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Definition
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Term
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Definition
platelet releases platelet factor 4 ->
heparin binds PF4 -> immune response
Ab binds Hep:PF4 -> Ab:Hep:PF4 binds platelet
-> macrophages eat complexes -> less platelets.
-> Remaining platelets activate & clot |
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Term
fondaparinux
MOA, admin, dosing, ADR, monitoring, antidote |
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Definition
Arixtra
Synthetic LMWH
MOA: Factor Xa inhibitor via LMWH template action
Admin: SC
Dosing: by pt weight
ADR: decreased HIT, bleeding risk
Monitoring: None
Antidote: None |
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Term
rivaroxiban
Name, Class, Admin |
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Definition
Xarelto PO
Factor Xa inhibitor |
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Term
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Definition
| directly binds Xa to inhibit |
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Term
rivaroxiban
Antidote & Distribution |
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Definition
Antidote: none
Distrib: strongly PPB -> thus dialysis won't help in an overdose because there exists a reservoir |
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Term
| Factor Xa Inhibitors: List them |
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Definition
| fondaparinux & rivaroxiban |
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Term
| Direct Thrombin Inhibitors: List them |
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Definition
| desirudin, bivalirudin, argatroban, dabigatran |
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Term
Direct Thrombin Inhibitors
MOA, Discovery, ADR, Antidote |
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Definition
MOA: Bind Thrombin (Factor IIa) itself
Discovery: Leech saliva
ADR: very much decrease in HIT; switch pt to DTI if experiencing HIT
Antidote: none |
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Term
desirudin, bivalirudin
metab |
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Definition
Direct Thrombin Inhibitors IV
metab: renal excretion |
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Term
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Definition
Direct Thrombin Inhibitor IV
metab: CYP450 in liver |
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Term
dabigatran
metab, dosing, ADRs |
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Definition
Direct Thrombin Inhibitor PO
metab: renal excretion
dosing: BID
ADR: GERD |
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Term
warfarin
Name, MOA, Dosing |
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Definition
Coumadin
MOA: Vitamin K Reductase Inhibition
-> blocks return of Vitamin K to reduced form; thus it stays oxidized & final step of clot factor synthesis (coupled with oxidation of Vitamin K) is inhibited
-> ultimately less fibrinogen -> fibrin
Dosing: PO QD; based on Cyp2C9 & VCORC1 genomics |
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Term
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Definition
Vitamin-K Containing Foods -> decreased effect
2C9 Inhibitors -> raise warfarin -> increased effect
2C9 Inducers (St. John's Wort) -> decrease warfarin -> decreased effect
Cephalosporins -> kill GIT bacteria -> decreased K -> increased effect
Other PPBs -> displace warfarin -> increased free warfarin -> increased effect |
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Term
warfarin
antidote, metab, distrib, monitoring |
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Definition
Antidote: Vitamin K (delayed eff)
Metab: CYP 2C9
Distrib: 99% PPB
Monitoring: INR 2-3 |
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Term
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Definition
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Term
| Physiologic Thrombolytic Action |
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Definition
Plasminogen circulates in plasma; cut by TPA (a serine protease found on endothelial cells) into plasmin
-> plasmin (serine protease) breaks up fibrin within a clot -> clot dissolves without fibrin crosslinks |
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Term
| Fibrinolytic Drugs: List them (3) |
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Definition
Streptokinase
Urokinase
TPAs: Activase, Retavase, TNKase |
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Term
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Definition
Fibrinolytic
MOA: converts more plasminogen -> plasmin
ADR: hypersensitivity (made from strep bacteria) & activation of bradykinin -> vasodilation & hypoTN; bleeding |
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Term
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Definition
Fibrinolytic
ADR: hypersensitivity (made from neonatal kidney cells) -> fever & hypoTN; bleeding |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
rh TPA Fibrinolytic selectivity
@physiologic & pharmacologic doses |
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Definition
Plasminogen can exist in clots & in circulation
@ physiologic dose: selective to clot-plasminogen
@ pharmacologic dose: activates all plasminogen -> bleed risk |
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Term
Hemostatics: List them (2)
& Indications |
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Definition
tranexamic acid & aminocaproic acid
Indications: excess bleeding, OD fibrinolytic, topical during surgery, mouthwash after dental surgery, tablet for heavy periods |
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Term
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Definition
Lysteda
Hemostatic
MOA: inhibit plasminogen -> plasmin |
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Term
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Definition
Hemostatic
MOA: inhibit plasmin binding to fibrin |
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Term
| PGE2 Receptors (4) & Activity |
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Definition
Brain: 1) pain sensation; 2) thermoregulation: establish fever
Stomach: mucin production
Nerve endings: locally sensitize nocireceptors (pain)
Blood Vessels: local vasodilation -> swelling, pain, redness |
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Term
| COX Action & Isozyme Locations |
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Definition
converts free arachidonic acid -> PGH2 intermediate;
COXi -> inhibit TXA2, PGE2, PGI2
COX1: everywhere
COX2: kidney & brain; inducible in areas of inflammation
[COX3: possibly CNS?] |
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Term
COXis
Goal, Indications, additional benefit |
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Definition
Goal: inhibit PGE2
Indications: antipyretic, antiinflammatory, analgesic
Add.Ben: decreased colon polyps -> decreased colon cancer |
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Term
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Definition
| Aspirin, Non-acetylated salicylates, NSAIDs |
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Term
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Definition
1) Ulcer due to PGE2 inhibition (increases mucin normally)
2) Bleeding due to TXA2 inhibition
3) Nephrotoxicity due to PGE2 inhibition (keeps renal artery dilated normally to maintain GFR) -> increased fluid retention & increased BP
4) Hypersensitivity due to increased arachidonic acid available to 5-lipoxygenase -> leukotrienes. If Patient has high 5-lipoxygenase levels genomically (pt usually will have asthma or nasal polyps). -> bronchocon, angioedema, itching
5) Nausea, Vomiting, Dizziness
6) Dermatitis, SJS (d/c immediately if rash appears)
7) Closing of ductus arteriosis b/w mom&baby due to PGE2 inhibition (PGE2 keeps it dilated normally); C.I. in pregnancy
*admin indomethacin IV to newborn to close |
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Term
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Definition
| irreversible inhibition of COX1&COX2 via acetylation |
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Term
| Aspirin ADRs (in addition to COXi ADRs) (4) |
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Definition
1) gastric upset due to acidic nature
2) Reye's Syndrome (encephalopathy & ARF); occurs w/age <12, flu-like s/sx, ASA. C.I. ages < 16.
3) Salicylism (tinnitis, sweating, increased respiration to clear acid, death by respiratory failure) due to high blood levels.
4) Interaction w/NSAIDs: decreased anti-TXA2 effect. For ASA to work, it must irrev bind COX1 in plat; if coadmin w/NSAID, NSAID will compete and reversibly bind. Thus dose a few hours apart. |
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Term
| Non-Acetylated Salicylates: List them (3) |
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Definition
| diflunisal, salsalate, choline magnesium trisalicylate |
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Term
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Definition
Dolobid
non-acetylated salicylate |
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Term
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Definition
Disalcid
non-acetylated salicylate |
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Term
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Definition
Trilisate
non-acetylated salicylate |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
Toradol
NSAID
**much better analgesic effects; used acutely |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
Celebrex
COX2 selective inhibitor (to protect from ulcers by not inhibiting COX1)
**Black Box Warning: MI/Stroke
C.I. in history of MI, risk factors MI, atherosclerosis |
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Term
| COX2 selectivity -> Withdrawn Drugs -> What hapd? |
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Definition
| due to selectivity -> inhibit epithelium's protective ability to secrete PGI2 via COX2 (upregulated) to keep atherosclerotic vessel dilated -> too much TXA2 from COX1 of platelet in comparison -> too clotty¬ anticlotty enough -> stroke/MI |
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Term
acetaminophen
indications, pt who can use, ADR, antidote |
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Definition
Indications: analgesic, antipyretic, [not anti-inflamm]
Pt: pregnancy, prior MI, atherosclerosis, children, HTN, renal insufficiency
MOA: proposed: COX3i in brain -> less PGE2 in brain -> decreased pain sensation, decreased fever induction
ADRs: large doses -> more reactive metabolite -> reacts with glutathiones -> liver cells die
Antidote: cause emesis; admin N-acetyl cysteine to neutralize metabolite w/in 12-24 hours |
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Term
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Definition
increased serum uric acid (low solubility) precipitation; created by purine metabolism by xanthine oxidase.
Crystals trigger immune response -> kill WBC -> inflamm contents spilled everywhere -> local inflammatory attack. |
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Term
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Definition
1) Tissue: tophaceous
2) Urine: urolithiasis
3) Joints: GOUT |
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Term
| Three Routes for Uric Acid in Blood |
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Definition
1) Filtered by glomerulus
2) Secreted into prox tubule by organic acid transporters
3) Reabsorbed by prox tubule back into blood |
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Term
| Two Causes for Hyperuricemia |
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Definition
1) overproducer (genomic enz diffs)
2) underexcreter (secretion into prox tubule is competed with by other acidic drugs -- diuretics, aspirin, niacin) |
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Term
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Definition
1) NSAIDs
2) Corticosteroids
3) Cochicine |
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Term
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Definition
Colchrys
Acute Gout Drug
MOA: inhibit WBC activity (give w/in 48hr of attack); prevent further WBC coming & lysing
ADR: severe neutropenia & bone marrow suppression |
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Term
Colchicine
Admin, Excret, Coadmin w/NSAID? |
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Definition
Admin: 1 tab q2hr until no s/sx, max dose, diarrhea.
Excret: unchanged in kidney -> lower dose for renal insuff
Coadmin w/NSAID-> nephrotox risk -> NSAID decreases GFR -> increases colchicine -> decreases WBC |
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Term
| Chronic Drug Classes for Gout (3) |
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Definition
| XOis, Uricosurics, recombinant uricase |
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Term
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Definition
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Term
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Definition
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Term
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Definition
*for overproducers & underexcreters
ADR: hypersensitivity
DDI: azothiaprene(prodrug), 6-MP(active) [purines for RA] -> compete w/XO -> buildup of 6-MP -> fatal immunosupp
Metab: renal; decrease dose for renal insuff |
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Term
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Definition
**for underexcreters
MOA: prevent reabsorption of uric acid
ADR: urolithiasis due to more uric acid in kidney
DDI: antibiotics -> uricosuric inhibits Abx secretion -> Abx buildup (just lower the Abx dose) |
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Term
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Definition
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Term
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Definition
*for severe cases of gout
recombinant uricase
MOA: breaks down uric acid into soluble allantoin |
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Term
| NSAID-Exacerbated Respiratory Dz |
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Definition
By inhibiting COX2, more substrate available for 5-lipoxygenase -> leukotrienes.
Pt w/genomic high amts of 5-lipoxygenase & LTC4 synthase get worse bronchocon, runny nose |
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Term
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Definition
| bind WBC receptors -> WBC chemotaxis |
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Term
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Definition
| bind sm.musc. receptors -> bronchocon, vessel permeab (runny nose), WBC chemotaxis |
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Term
Leukotriene Receptor Antagonists
MOA, Effects, Indications, ADRs |
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Definition
MOA: Block LTC4/LTD4/LTE4 binding @ cysteinyl LT Recep
Effs: decreased bronchocon/runny nose
Use: chronic asthma
ADR: increased risk of upper resp infexn due to inhib of wbc chemotaxis |
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Term
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Definition
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Term
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Definition
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Term
5-lipoxygenase inhibitors
MOA, ADR, Pt Response |
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Definition
MOA: block LT synthesis
ADR: increased hepatox
*Not a first-line drug because it doesn't work in all pt due to genomic diffs in 5-lipoxygenase |
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