Term
| Aspirin: summary of effects |
|
Definition
Inc. BT
No effect on PTT or PT |
|
|
Term
|
Definition
Enters hepatic portal circulation
Most is converted to salicylate (active) by first pass metab, reversibly inhibits body COX1 and COX2
The part that remains ASA in the hepatic portal circulation acetylates the COX1 active site = irreversibly inhibits platelet COX1
These platelets can't ever again synthesize TXA2 (b/c they don't have nuclei) |
|
|
Term
| What happens if ASA gets into the circulation? |
|
Definition
Irreversibly inhibits vascular endothelial cell COX1
But these cells have nuclei and can synthesize new COX1
PGI production resumes in 6-12 hrs |
|
|
Term
| Very large doses of aspirin can ___ |
|
Definition
| Inhibit hepatic synthesis of clotting factors = inc. the PTT |
|
|
Term
| IIb/IIIa-R antagonists (3) |
|
Definition
Abciximab
Eptifibatide
Tirofiban |
|
|
Term
| IIb/IIIa-R antagonists: method of admin, MOA |
|
Definition
IV
Block the IIb/IIIa-R (normally how fibrinogen binds platelets together)
No platelet aggregation (even if caused by another factor like collagen, TXA2, thrombin)
Abciximab: monoclonal Ab, irreversible
Eptifibatide, tirofiban: competitive/reversible |
|
|
Term
| IIb/IIIa-R antagonists: indications, S/E |
|
Definition
PCI
Acute coronary syndrome
Bleeding! |
|
|
Term
| Purinergic/ADP receptor antagonists (2) |
|
Definition
|
|
Term
| Purinergic/ADP receptor antagonists: MOA |
|
Definition
ADP stimulates platelet P2Y1R to activate phospholipase C, resulting in a change in shape
ADP stimulates platelet P2Y12R to inhibit adenyl cyclase (cAMP dec. intracellular [Ca] = inhibits platelet activation/aggregation)
Blockade of either causes inhibition of platelet activation/aggregation
Both drugs block P2Y1R
Clopidogrel: irreversibly blocks the P2Y12R as well |
|
|
Term
| Purinergic/ADP receptor antagonists: indications (5) |
|
Definition
Dec. incidence of MI and stroke in patients w/ CAD (synergy w/ aspirin!)
Treat patients who can't take aspirin (hypersensitivity or who've failed aspirin tx)
Prevent thrombosis in patients w/ previous ischemic stroke
Prevent MI in patients w/ unstable angina
PCI: used w/ aspirin |
|
|
Term
| Purinergic/ADP receptor antagonists: S/E |
|
Definition
Clopidogrel: lower incidence of neutropenia, agranulocytosis
Ticoplidine: neutropenia, agranulocytosis, thrombocytopenia |
|
|
Term
|
Definition
| Releases lipoprotein lipase from capillary endothelial cells = clears the postprandial hyperlipemia caused by chylomicrons high in TG |
|
|
Term
| The main point of anticoagulant therapy is to ___ |
|
Definition
| Prevent the activation of prothrombin (II) to thrombin (IIa) |
|
|
Term
|
Definition
Activated clotting factor "attacks" ATIII and b/c irreversibly bound (suicide inhibition!)
Without heparin, ATIII is a weak inhibitor of activated clotting factors
When heparin binds to ATIII, induces a conformational change making its target more accessible to the activated clotting factor
Once the activated clotting factor is irreversibly bound to ATIII, heparin is released (catalyst!)
Inhibits clotting factors 2, 9, 10, 11, 12
Maintains electronegativity of the damaged vascular wall
Prevents platelet adhesion, aggregation, release reaction |
|
|
Term
|
Definition
Inc. PTT (additive w/ aspirin)
NC PT = warfarin can be tested even in the presence of heparin |
|
|
Term
| Heparin is reversed by ___ |
|
Definition
Protamine sulfate
Binds really well to heparin = prevents heparin interaction w/ ATIII
Given slow IV, immediate effects
Also has anticoagulant activity = don't give too much of it |
|
|
Term
|
Definition
Bind to ATIII
Primarily inhibit Factor 10
Not long enough to bind to both ATIII and IIa simultaneously (as heparin can) = no effect on thrombin! = PTT not inc. |
|
|
Term
| LMW heparin is partially reversed by ___ |
|
Definition
|
|
Term
| Heparin: pharmacokinetics/dynamics |
|
Definition
IV or subcu (NOT p.o.!)
t1/2 inc. w/ dose
Cleared by reticuloendothelial system
Should be measured every 6 hours and infusion rate adjusted until desired steady state inc. in PTT is observed
Given every 8-12 hrs subcu for long-term treatment |
|
|
Term
|
Definition
| Inc. PTT 1.5-2x normal value |
|
|
Term
| Why would one b/c resistant to heparin? (4) |
|
Definition
Inc. heparin clearance, like in PEm
Genetic ATIII def.
Acquired ATIII def. like nephrotic syndrome, hepatic cirrhosis, DIC
Acute phase proteins released in response to inflamm bind heparin and inactivate it |
|
|
Term
|
Definition
Prophylaxis for postop DVT, PCI
Tx DVT, PEm
Unstable angina
Anticoag for IV cath, hemodialysis, cardiopulmonary bypass
DOC for prego anticoag b/c not teratogenic!!! |
|
|
Term
| LMW heparin: indications (4) |
|
Definition
Prophylaxis of postop DVT
Ischemic stroke
Acute coronary syndrome
Hemodialysis anticoag |
|
|
Term
| Heparin: S/E (same for LMW but less) |
|
Definition
Bleeding
Reversible HIT, thrombosis, limb loss, death (IgG binds to platelet-heparin complex, elicits platelet activation, clotting)
-Monitor platelet count during tx
Osteoporosis, fractures w/ continuous tx
Inhibition of aldosterone synthesis causing slight elevation of plasma K (issue if the patient is taking an ACEI) |
|
|
Term
| Advantages of LMW heparin over heparin (6) |
|
Definition
Kinetics not altered by binding to plasma proteins, acute phase proteins, endothelial cells, macrophages = less resistance
Inc. F, longer t1/2
Cleared by the kidney
Fewer antiheparin Ab formed = less HIT
Dec. length of postop hospitalization b/c can administer the drug at home
When given subcu q12h or qd they produce a predictable, reproduccible anticoag effect w/o the need for laboratory monitoring of hemostasis
(EXPENSIVE, though!) |
|
|
Term
| Heparin alternatives (if HIT occurs) |
|
Definition
Argatroban
Fondaparinux
Lepirudin |
|
|
Term
|
Definition
Synthetic pentasacch that mimic the heparin site that binds ATIII
Indirectly inhibits Factor 10 via ATIII |
|
|
Term
| Fondaparinux: method of admin, pharmacokinetics/dynamics |
|
Definition
Subcu
F = 1.0
t/12 = 17-24h (inc. w/ renal dysfxn)
No effect on PTT or PT |
|
|
Term
| Fondaparinux: effects, indications |
|
Definition
Produces a predictable, stable antithrombotic effect
Superior to LMW heparins for tx of acute coronary syndromes (same risk reduction but less bleeding, re-infarct, morbidity/mortality) |
|
|
Term
| A point-of-care assay for Factor 10 activity is necessary to monitor the effects of... |
|
Definition
| LMW heparins and fondaparinux |
|
|
Term
|
Definition
Direct inhibitor of free and clot-bound thrombin = doesn't require ATIII
Inhibits thrombin-induced platelet activation and aggregation
Essentially irreversible |
|
|
Term
| Lepirudin: method of admin, pharmacokinetics/dynamics |
|
Definition
IV
t/12 = 1.3 hrs (inc. in patients w/ renal failure)
Inc. PTT to 1.5-2.5x normal value
NC PT |
|
|
Term
| What is the antidote to argatroban, fondaparinux, and lepirudin? |
|
Definition
|
|
Term
|
Definition
Direct, competitive (reversible) inhibitor of thrombin
Inhibits soluble, fibrin-bound, and clot-bound thrombin
Inhibits platelet aggregation and TXA2 release |
|
|
Term
| Argatroban: method of admin, pharmacokinetics/dynamics |
|
Definition
IV
t1/2 = 40-50 min
Predictable dose-response curve
Inc. PTT 1.5-3x normal value
Slightly inc. PT, potentiated w/ warfarin
NC BT |
|
|
Term
|
Definition
|
|
Term
| Warfarin is unique b/c it's the only ___ |
|
Definition
|
|
Term
|
Definition
Inhibits vitK epoxide reductase = no reduced vitK available to catalyze gamma carboxylation of Factors 2, 7 9, 10
(Carboxylation is necessary for Factors to be able to bind Ca and activate) |
|
|
Term
| Warfarin: pharmacokinetics/dynamics |
|
Definition
99% bound to plasma proteins, drug-drug interactions involve displacement from the plasma proteins
Metab CYP
See the effects first in Factor 7 (shortest t1/2) and so measure warfarin's efficacy via PT/INR
INR inc. 2-3x normal values (>4 = bleeding)
Only overdose w/ warfarin causes it to affect PTT
Works only in vivo! |
|
|
Term
| Phytonadione: MOA, method of admin, pharmacokinetics |
|
Definition
Phytonadione = reduced vitK
IV, subcu, or p.o.
Takes a while for effects to manifest (24 hrs for full effect)
Repeated doses necessary for warfarin OD |
|
|
Term
| Warfarin is reversed by ___ (3) |
|
Definition
Factor 9 concentrate (also has lots of 2, 7, 10)
FFP (immediate)
Phytonadione |
|
|
Term
|
Definition
Prego category X (affects fetal bone mineralization, CNS, hemorrhage)
Bleeding
Cutaneous necrosis |
|
|
Term
| Warfarin: indications (2) |
|
Definition
Prophylaxis of postop DVT
Prophylaxis of thromboembolus in patients w/ afib, prosthetic heart valves, rheumatic mitral valve disease, unstable angina |
|
|
Term
|
Definition
|
|
Term
|
Definition
Alteplase
Streptokinase
tPA |
|
|
Term
|
Definition
Serine protease binds exposed lysine residues on fibrin (plasminogen dose too)
Amino terminus lysine binding site binding to fibrin augments rate of cleavage of plasminogen to form plasmin
Plasmin degrades the fibrin, normally effect is small and systemic fibrinolysis doesn't occur
Injection of alteplase overwhelms PAI and specificity of plasmin for thrombic fibrin is lost
Systemic fibronolysis from degradation of Factors 5, 8, and fibrinogen |
|
|
Term
|
Definition
Binds at carboxy terminus of plasminogen
Conformation change exposing the protease site
Cleaves plasminogen to form plasmin
Attacks thrombic fibrin or circulating clotting Factors 5, 8, fibrinogen
(Larger doses may be necessary in someone w/ Ab against prior Strep infxn) |
|
|
Term
| Fibrinolytics: pharmacokinetics |
|
Definition
Short t1/2!
Alteplase = 5-10 min
Streptokinase = 40-80 min |
|
|
Term
| Fibrinolytics: indications |
|
Definition
Establish reperfusion of coronary vessels post MI (PCI is superior, though!)
-Enhanced by cotx w/:
--UFH/LMWH
--Aspirin and clopidogrel
--B-blocker: dec. infarct size, myocardial ischemia, prevents re-infarct and fatal ventricular dysrhythmias
--ACEI: dec. preload and afterload = inc. CO, dec. infarct size, prevents dysrhythmias
--Nitrate: dec. preload and infarct size
PEm
DVTs
Ischemic stroke |
|
|
Term
|
Definition
| Bleeding! Inc. w/ heparin |
|
|
Term
| Aminocaproic acid: MOA, indications |
|
Definition
Lysine analog
Occupies the lysin binding sites of tPA, alteplase, plasminogen, plasmin
Prevent them from binding to thrombic fibrin
Prevent fibrinolytic tx-induced bleeding and extracorporeal circulation of blood |
|
|
Term
|
Definition
|
|
Term
| How does morphine help in the treatment of MI? |
|
Definition
Alters response to pain and inhibits baroreflex
Dec. sympathetic activity
Dec. preload and afterload = inc. SV
Dec. HR and automaticity
Dec. cardiac O2 demand |
|
|
Term
| Thrombus is held together by ___, which is dissolved by ___ when ___. |
|
Definition
Cross-linked fibrin net
Plasmin
Vascular repair is complete |
|
|
Term
| tPA is released from ___ while plasminogen is synthesized in ___ and found in ___ |
|
Definition
Vascular endothelial cells
Liver, plasma |
|
|
Term
| tPA and plasminogen bind to ___ in fibrin via their ___ |
|
Definition
Lysine
Amino-terminus lysine binding sites |
|
|
Term
| When bound to ___, TPA activates ___ |
|
Definition
Fibrin
Plasminogen to form plasmin |
|
|
Term
| tPA normally cuases the proteolytic activity of plasmin to be ___, but plasmin is ___ and will also attack ___ |
|
Definition
Clot specific
Not necessarily specific for fibrin
Factors 5, 8, fibrinogen |
|
|
Term
| Plasma tPA doesn't normally activate circulating plasminogen b/c ___ and b/c any circulating tPA-created plasmin ___ |
|
Definition
Plasma PAI1 and PAI2 inhibit tPA
Is inhibited by a2antiplasmin directly and by a2antiplasmin lysine binding site binding to fibrin and thereby blocking the binding of plasminogen or plasmin to fibrin = protects the thrombus from degradation before vascular repair has been completed |
|
|
Term
| PAI1, PAI2, a2antiplasmin also protect ___ |
|
Definition
|
|
Term
| Because of their low mass relative to other blood cells, platelet are shunted to the outermost layer of laminar flow and have lots of spontaneous interactions w/ the endothelium. Platelets don't adhere to a healthy endothelium for 5 reasons. |
|
Definition
1. Adhesion is prevented by the thick glycocalyx that covers all endothelial cells
2. NO is continually synthesized/released by the endothelial cells and inhibits adhesion/activation/secretion/aggregation as well as relaxes vascular smooth muscle (most important local factor affecting platelets!!!)
3. Endothelial cell COX1 produces PGI which inhibits platelet fxn and relaxes vascular smooth muscle
4. Endothelial cells also release ectoADPase, which destroys platelet-released ADP = limits thrombus formation, stabilization, growth
5. ATIII binds to endothelial surface GAGs and inhibits thrombin and Factor 10a (interaction enhanced by endothelial surface thrombomodulin, which binds to thrombin and lessens its ability to activate platelets, Factors 5 and 13, and bind fibrinogen)
6. Endothelial cells also release TFPI, which inhibits Factor 10a in the TF/7a/10a complex |
|
|
Term
| PGI: induction and effects |
|
Definition
Not a circulating hormone: synthesized and secreted in response to biochemical (thrombin, ADP) or mechanical (shear stress, vascular damage) stimuli
Doesn't prevent platelet adhesion
Instead it inhibits aggregation and returns platelets to "resting"
Latter causes dispersal of aggregates = prevents growing a thrombus |
|
|
Term
|
Definition
| Act synergistically to discourage platelet aggregation and thrombus growth after endothelial injury |
|
|
Term
| Platelets adhere to exposed vWF on endothelial cells (from damage) via ___ and to collagen via ___. This activates ___. Subsequent interaction b/t ___. |
|
Definition
GP1bR
GPV1R
Platelets, resulting in a conformational change from a disk to a ball = inc. SA in contact with the wall
Platelets, endothelial cell integrinR, and fibrinogen makes an irreversible bond and the platelets flatten over the injured site |
|
|
Term
| Platelets secrete/expose ___, which promote platelet aggregation and formation of a hemostatic plug (15) |
|
Definition
Fibrinogen
Fibronectin
vWF
Thrombospondin
Vitronectin
P-selectin
GPIIb/IIIa
Growth factors
Chemokines (PF4)
Cytokine-like factors (IL1B, CD40ligand, B-thromboglobulation)
Factors 5, 11
PAI1
Plasminogen
Protein S |
|
|
Term
| vWF, P-selectin, fibronectin, thombospondin, plasminogen secretion from a-granules ___ |
|
Definition
| Enhances adhesion and promotes cell-cell interactions b/t platelets |
|
|
Term
| ADP and 5HT release from dense granules ___ |
|
Definition
| Promotes recruitment of additional platelets |
|
|
Term
| Inc. free cytosolic Ca activates ___ |
|
Definition
PLA2 thereby liberating AA, COX1, TXA2 synthase
Produce TXA2, which VC, activates platelets, and works w/ ADP to further recruit platelets |
|
|
Term
| DAG activates PKC, which ___ |
|
Definition
Inc. affinity of GPIIb/IIIa receptor for fibrinogen
Cross link platelets to form aggregates/plugs |
|
|
Term
| Formation of a platelet plug/white clot is followed by... |
|
Definition
Activation of the intrinsic clotting cascade
Platelet exposure to collagen causes PhtdSer in the platelet cell membrane to migrate to the outer surface
Serves as the organizing surface for partial proteolysis and sequential activation of the clotting sequence |
|
|
Term
| Activated thrombin converts ___ and activates ___, which ___ |
|
Definition
Fibrinogen to water-soluble fibrin
Factor 13, which cross-links the fibrin to form a "fishing net" of water insoluble fibrin
"Catches" RBCs to form the red clot, contracts |
|
|
Term
| After vascular repair has occurred ___ |
|
Definition
| Thrombus is dissolved via tPA and plasmin |
|
|
Term
|
Definition
Endothelial cell activation, dysfxn, and injury
Phenotypic transformation
Normal antithrombotic properties of the endothelium are lost
Now express multiple adhesion molecules, secrete inflammatory messengers, create a prothrombotic environment |
|
|
Term
| Inappropriately expressed endothelial adhesion molecules lead to... |
|
Definition
Invasion of the intima by monocytes and Th1s
Produce a fatty streak of foam cells
Covered by a fibrous cap of organized ECM (collagen) and vascular smooth muscle cells |
|
|
Term
| Unstable atherosclerotic plaques have... |
|
Definition
A thin fibrous cap
Few smooth muscle cells
Large lipid pool w/ debris
Lots of inflamm cells
Especially at shoulder of plaque! (Where plaque meets normal vessel wall = interface b/t cap and lipid core) |
|
|
Term
| Two mechanisms leading to plaque disruption and coronary artery thrombosis are... |
|
Definition
Overt plaque rupture
Superficial rupture of the endothelium |
|
|
Term
| Plaque rupture is preveded by... |
|
Definition
Thinning of the fibrous cap via oxLDL, reactive oxygen species, IL1B, TNFa, IFNg
Apoptosis of smooth muscle cells
ECM no longer being synthesized and is actually being degraded by matrix metalloproteinases |
|
|
Term
| MMPs (matrix metalloproteinases) are induced and activated by... |
|
Definition
Reactive oxygen species
IL1B
TNFa
CD40ligand
NFKBligand
PGE2
oxLDL |
|
|
Term
| CD40ligand strongly induces the expression of ___, which ___ |
|
Definition
TF by macrophages/foam cells in lipid core
When exposed to blood + Factor 7 activates Factor 7 |
|
|
Term
| TF requires ___ to fxn at its maximal catalytic rate. But TF released from the lipid core during plaque rupture ___ |
|
Definition
Phospholipids esp. PhtdSer
Doesn't require activated platelets to form thrombin, PhtdSer serves as the phospholipid surface for assembly |
|
|
Term
| ___ + ___ are the key initiators of thrombosis after plaque rupture |
|
Definition
|
|
Term
| Collagens are potent activators of ___ even in the absence of ___ |
|
Definition
|
|
Term
| Plasma EPI is inc. during ___ and is also a potent inducer of ___ |
|
Definition
|
|
Term
|
Definition
Busulfan
Carboplatin
Carmustine (BCNU)
Chlorambucil
Cisplatin
Cyclophosphamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Temozolamide
Thiotepa |
|
|
Term
|
Definition
5FU
6MP
6TG
Azacitidine
Capecitabine
Cytarabine (araC)
Gemcitabine
Methotrexate |
|
|
Term
| Antibiotic (antineoplastic) drug list, S/E |
|
Definition
Bleomycin
Dactinomycin
Doxorubicin
MitomycinC
Usually myelosuppression (not bleomycin!) |
|
|
Term
| Epipodophyllotoxic drug list |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Miscellaneous cancer drug list |
|
Definition
|
|
Term
| Cancer is characterized by... |
|
Definition
Uncontrolled cell proliferation including decreased apoptosis
decreased differentiation
invasion
metastasis |
|
|
Term
|
Definition
| Rapidly dividing cells including normal, noncancerous cells (GI, hair) |
|
|
Term
|
Definition
G0: resting, differentiation
G1: getting ready for DNA synthesis (synthesizing necessary compounds), 18-30h
S: DNA replication and repair (doubling of chromosomes), 16-20h
G2: getting ready for mitosis (synthesizing necessary compounds), 2-10h
M: mitosis, 30min-1h |
|
|
Term
| Cell cycle nonspecific (CCNS) drug characteristics |
|
Definition
Alkylating agents (guanine N7, O6) = intercalate/cross-link DNA (if have 2 reactive groups) or make ssDNA breaks (if have 1 reactive group), misreading of DNA and inhibition of synthesis of everything,
Kills G1 and S cells best b/c nucleotides become unpaired and are susceptible to alkylation
Toxicity expressed as cells enter S
Can kill at any phase (works in G0 due to the background DNA repair)
Killing is dose/concentration dependent = give in 1 big dose (like gentamicin) |
|
|
Term
| Radiation "works" because... |
|
Definition
Normal cells can efficiently and effectively repair the damage overnight
Cancer cells can't repair the damage as quickly or as well |
|
|
Term
| Doxorubicin: CCNS/CCS, class, MOA |
|
Definition
CCNS
Antibiotic (anthracycline)
Intercalates, inhibits TopoII, DNA strand scission = single and double strand breaks, cells die in G2 |
|
|
Term
| CCNS drug list (most are alkylating agents) |
|
Definition
Busulfan
Carboplatin
Carmustine (BCNU)
Chlorambucil
Cisplatin
Cyclophosphamide
Dactinomycin
Doxorubicin
Lomustine (CCNU)
Mechlorethamine
Melphalan
MitomycinC
Procarbazine
Temozolamide
Thiotepa
Topotecan |
|
|
Term
| Cell cycle specific (CCS) drug characteristics |
|
Definition
Kill in specific phases of cell cycle (obvi)
Killing is time/exposure dependent = regular, small doses (like PCN)
Most effective in hematologic cancers and tumors with lots of cells in the "growth fraction" |
|
|
Term
| G1 phase drugs and phys. effects |
|
Definition
Corticosteroids
Suppress mitosis, cause apoptosis in non-dividing cells |
|
|
Term
|
Definition
Antimetabolites = structural analogs of naturally occuring basis for DNA/RNA synthesis = 5FU, 6MP, 6TG, azacitidine, capecitabine, cytarabine, gemcitabine, hydroxyurea, methotrexate
Usually myelosuppressive |
|
|
Term
| 5FU, capecitabine: CCNS/CCS, class, MOA |
|
Definition
CCS S phase
Antimetabolite
Inhibits thymidylate synthase |
|
|
Term
| 6MP, 6TG: CCNS/CCS, class, MOA |
|
Definition
CCS S phase
Antimetabolite
Inhibits purine (A, G) synthesis |
|
|
Term
| Methotrexate: CCNS/CCS, class, MOA |
|
Definition
CCS S phase
Antimetabolite
Inhibits DHF reductase |
|
|
Term
| Cytarabine: CCNS/CCS, class, MOA |
|
Definition
CCS S phase
Antimetabolite
Inhibits DNA polymerase |
|
|
Term
| Azacitidine: CCNS/CCS, class, MOA |
|
Definition
CCS S phase
Antimetabolite
Incorporated into DNA, RNA |
|
|
Term
| Hydroxyurea: CCNS/CCS, class, MOA |
|
Definition
CCS S phase
Antimetabolite
Inhibits ribonucleotide reductase |
|
|
Term
|
Definition
|
|
Term
| Bleomycin: CCNS/CCS, class, MOA |
|
Definition
CCS G2 phase
Antibiotic
O2 free radicals fragment DNA, cells accumulate in G2 |
|
|
Term
| Etoposide: CCNS/CCS, class, MOA |
|
Definition
CCS G2 phase
Epipodophyllotoxin
Stabilizes the topoisomerase II-DNA bond, topoII is inhibited, dsDNA breaks remain (b/c topoII also rejoins dsDNA) |
|
|
Term
| Late G2(/early M) phase drug list |
|
Definition
| Vinca alkaloids/"spindle poisons" = vinblastine, vincristine |
|
|
Term
| Vincristine, vinblastine: CCNS/CCS, class, MOA |
|
Definition
CCS late G2(/early M) phase
Vinca alkaloid/"spindle poison"
Bind to tubulin, prevent microtubule assembly, mitotic filaments can't form, cells arrest in late G2 |
|
|
Term
|
Definition
Paclitaxel
(Vinblastine
Vincristine) |
|
|
Term
| Paclitaxel: CCNS/CCS, class, MOA |
|
Definition
CCS M phase
Taxane
Enhances polymerization of tubulin, promotes microtubule assembly and stabilizes them against depolymerization, loss of dynamic instability, anaphase can't happen, mitotic arrest
Phosphorylates BCL2, turns it off, restores apoptosis |
|
|
Term
| Normal rapidly proliferating tissues, S/E from chemo collateral damage |
|
Definition
Bone marrow: myelosuppression
GI mucosa: n/v, stomatitis
Hair follicles: alopecia (regrowth), post-radiation therapy (no regrowth)
Ovary/testis: amenorrhea/azoospermia |
|
|
Term
| Myelosuppression consequences |
|
Definition
Anemia
Hemorrhage
Infections, fever
Leukopenia (neutropenia) |
|
|
Term
| Drug for myelosuppressive anemia |
|
Definition
|
|
Term
| Drug for myelosuppressive hemorrhage |
|
Definition
|
|
Term
| Oprelvekin (IL11): class, MOA |
|
Definition
Myelosuppression tx
Megakaryocyte growth factor to counter thrombocytopenic hemorrhage |
|
|
Term
|
Definition
Myelosuppression tx
Granulocyte-CSF to counter leukopenic/neutropenic infection |
|
|
Term
|
Definition
Myelosuppression tx
Granulocyte-macrophage-CSF to counter leukopenic/neutropenic infection |
|
|
Term
|
Definition
Neutrophil count <1000
Recovery can be rapid (14-21 days) or delayed (50+ days) |
|
|
Term
| Leucovorin (rescue): class, MOA |
|
Definition
Methotrexate myelosuppression tx
Normal cells take up the drug and use it for THF synthesis, tumor cells can't take it up |
|
|
Term
|
Definition
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| Doxorubicin (anthracyclines) |
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| Drugs toxic to skin, nails |
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Definition
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Carmustine
Cisplatin
Mechlorethamine
MitomycinC
Thiotepa |
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Term
| p.o. alkylating agents (BuChCy LoMe PrTe) |
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Definition
Busulfan
Chlorambucil
Cyclophosphamide
Lomustine
Melphalan
Procarbazine
Temozolamide |
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Term
| Alkylating agent toxicity |
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Definition
Dose-limiting: myelo- and immunosuppresion
N/V within 30-60min of tx (pretreat with 5HT3 blockers)
Secondary leukemias (AML)
Amenorrhea/azoospermia
Hepatic veno-occlusive disease (HVOD, b/c obliterates small hepatic vein branches), portal htn, esophageal varices, rupture, internal bleeding, death
PF with busulfan, chlorambucil, melphalam, nitirosureas = carmustine and lomustine |
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Term
| Drugs used to tx heme-onc and solid tumors (usually in combination with other drugs) |
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Definition
| Alkylating agents = busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, lomustine, mechlorethamine, mephalan, procarbazine, temozolamide, thiotepa |
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Term
| Cyclophosphamide toxicity |
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Definition
Myelo-, immunosuppression (used in organ transplantation)
n/v
Non-hemorrhagic and hemorrhagic cystitis (b/c concentrates in urine so need adequate hydration/urination)
SIADH (b/c of the hydration/urination) |
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Term
Hematuria but no WBCs in the urine
I should be thinking... |
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Definition
| Cyclophosphamide toxicity |
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Definition
Injected into urinary bladder to tx superficial bladder cancers, the peritoneal cavity, and the CSF to tx CNS metastases
(BCG = bovine TB also used for the superficial bladder cancers b/c stimulates the immune system to come and fight the cancer) |
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Term
| Busulfan: application, method of admin, S/E |
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Definition
Kill bone marrow for marrow transplant
p.o.
Bronze hyperpigmentation, HVOD, PF, pseudo-Addison's |
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Term
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Definition
Carmustine
Lomustine
Temozolamide for primary and secondary, doesn't need bioactivation
All of these cross the BBB |
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Term
| Procarbazine: CCNS/CCS, class, MOA, method of admin |
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Definition
CCNS
Alkylating agent
Inhibits synthesis of everything, causes chromosomal breaks
p.o. |
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Term
| Cisplatin, carboplatin: method of admin, S/E |
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Definition
IV
n/v! (have to pretreat with 5HT3 blocker + dexamethasone)
Nephrotoxic, more so than carboplatin! (Peri-admin saline to decrease this)
High-frequency hearing loss
Sensory neuropathy |
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Term
| If something is super-emetic, that's because it... |
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Definition
| Kills enterochromafin cells, release 5HT3, serotonin syndrome |
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Term
| Gold standard for anti-emesis |
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Definition
| Dexamethasone but don't know why |
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Term
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Definition
Myelosuppression (rescued with leucovorin)
Nephrotoxic: excreted unchanged, sulfa drugs/NSAIDs/COX2 inhibitors decrease its renal clearance, insoluble in acidic urine so large doses can cause ppt in renal tubules (prevent with hydration and alkaline urine)
Other: mucositis, hemorrhagic enteritis, transient increase in LFTs (chronic tx small doses for arthritis can lead to hepatic fibrosis)
Intrathecal injection cause cause arachnoiditis = stiff neck, headache, fever |
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Term
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Definition
Antimetabolites (not methotrexate) = 5FU, azacitidine, capecitabine, cytarabine, gemcitabine
Usually myelosuppression (not cytarabine!) |
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Term
| 5FU: application, MOA, method of admin, S/E |
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Definition
Actinic keratoses, basal cell cancers
Its metabolite FdUMP irreversibly inhibits thymidylate synthetase, lack of thymidylate, blocks DNA synthesis
Topical, IV
Myelosuppression, photosensitivitiy, hyperpigmentation, diarrhea, hand-foot syndrome (eryhtematous desquamation) |
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Term
| Capecitabine: MOA, method of admin, S/E |
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Definition
Converted to 5FU by cells' thymidine phosphorylase (>>>in tumor cells)
Oral
Less toxic than IV 5FU |
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Term
| Cytarabine: application, MOA, method of admin, S/E |
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Definition
AML
Incorporated into DNA/RNA, inhibits DNA pol
IV, subcu
Conjunctivitis, jaundice, reversible cerebellar toxicity |
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Term
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Definition
Inhibits DNA methyltransferase, no methylation to turn off tumor suppressor genes = tumor suppressor genes stay on
Myelosuppression |
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Term
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Definition
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Term
| 6MP, 6TG: MOA, method of admin, S/E |
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Definition
HGPRT converts it to active form, inhibit purine nucleotide pathway enzymes, inhibit synthesis of everything
p.o.
Myelosuppression
6MP: allopurinol inhibition of xanthine oxidase inhibits degradation of 6MP |
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Term
| Bleomycin: method of admin, S/E |
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Definition
| IV, IM, subcu No myelosuppression! Pulmonary fibrosis Lethal ananphylaxis, esp. in lymphoma pt |
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Term
| Dactinomycin: MOA, method of admin, S/E |
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Definition
Intercalates in DNA, RNA synthesis can't proceed
IV
Myelo- and immunosuppresion, radiation "recall" |
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Term
| Doxorubicin: application, S/E |
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Definition
Carcinomas, sarcomas, heme cancers
Chronic heart failure, cumulative dose-related
Short-term myelosuppression |
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Term
| Etopside: method of admin, S/E |
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Definition
IV
Dose-limiting myelosuppresion, anaphylaxis, secondary leukemias |
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Term
| Topotecan: CCNS/CCS, class, MOA |
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Definition
CCNS
Camptothecin
Inhibit topoI, DNA damage |
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Term
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Definition
| Myelosuppression, some diarrhea |
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Term
| Vincristine, vinblastine: method of admin, S/E |
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Definition
IV
Vincris: dose-limiting neurotoxicity: loss of tendon reflexes, paresthesias, autonomic dysfunction
Little myelosuppression!
Vinblas: dose-limiting myelosuppression |
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Definition
| Myelosuppression, peripheral neuropathy, myalgias |
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Term
| Hydroxyurea: application, method of admin, S/E |
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Definition
SCD: turns on HbF gene
p.o.
Myelosuppression |
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