Mnpc Test 3

Front 1

Remifentanil

Back 1

Rapidly inactivated opioid analgesic
Soft drug

Front 2

Prodrug solution for solubility

Back 2

add polar or charged groups to incr water solubility

Front 3

Prodrug solution for oral absorption
.........and distribution

Back 3

incr lipophilicity
......incr/decr serum prot binding. an incr will lead to a decr in metabolism rate

Front 4

Prodrug solution to increase half life

Back 4

decrease clearance, decrease metabolism/inactivation

Front 5

prodrug solution to improve formulation
prodrug solution to improve stability

Back 5

change physical properties
in general improves shelf life and stability in gut

Front 6

prodrug solution for increased BBB penetration or access to other difficult targets
solution for site specificity
solution for patient acceptability

Back 6

There are general things you can do with drugs to alter them to prodrugs with these properties

Front 7

basic groups on an ester serve what purpose in the prodrug?

Back 7

increase pKa

Front 8

acetamide group

Back 8

NOT a prodrug--usually stable to amidases

Front 9

imine prodrug

Back 9

often too labile to spontaneous (non-enz) hydrolysis
hydrolyzed to amine and aldehyde

Front 10

ketals and acetals

Back 10

the result of a ketone/aldehyde reacting with a diol
non-enzymatic hydrolysis reverses

Front 11

heparin

Back 11

40 monosachcarides
12,000-14,000 = MW
specific sequence that binds antithrombin, a serpin
full length heparin chains can bind both thrombin and antithrombin, bringing them together and 1000xgreater inactivation.
2nd, when binds antithrombin, antithrombin conformationally changes and facilitates interaction with serine proteases.

Front 12

antithrombin

Back 12

inhibits many coag factors (they are serine proteases)
cleaves an arg-ser peptide and forms a 1:1 inactive complex

Front 13

LMWH

Back 13

preferential to factor 10a
heparin depolymerized by:
benzylation followed by alkaline hydrolysis=Enoxaparin
nitrous acid depolymerization=Dalteparin
peroxidative cleavage=Ardeparin

Front 14

Danaproid

Back 14

mix of non-heparin LMW glycosaminoglycans
reduced cross sensitivity compared to heparins (no HIT)

Front 15

possible advantages of LMWHs

Back 15

fewer effects on platelets & less action on thrombin=less bleeding probs
less nonspecific binding to plasma proteins and endothelial cells + smaller size=incr bioavailability
more predictable resp & less interpt variability
incr duration of anti-factor Xa
decr risk of immune sensitization
decr risk of thrombocytopenia

Front 16

synthetic pentasaccharides

Back 16

Fondaparinux
bind and activate antithrombin

Front 17

bivalirudin

Back 17

20 a.a. peptide, smaller than hirudin, designed based on the pep seq of hirudin
directly inhib thrombin by specifically binding both to catalytic site and anion-binding exosite of circulating and clot-bound thrombin
reversible, competitive manner slowly cleaved by thrombin

Front 18

argatroban

Back 18

phe-pro-arg peptidomimetic-this is where thrombin cleaves fibrinogen.
competitive

Front 19

hirudins and argatroban

Back 19

direct inhibitors of thrombin: block fibrinogen to fibrin and activation of other coag factors; also blocked is platelet agg and protein C

Front 20

direct inhibitors of Xa

Back 20

the "xaban"s--new

Front 21

Rivaroxaban

Back 21

inhibits Xa in the prothrombinase complex
highly selective, oral, rapid onset
interrupts intrinsic and extrinsic
no effect on thrombin or platelets
diff properties than LMWH but therapeutically similar

Front 22

Vitamin K antagonists

Back 22

Coumarins & Indanediones, oral

Front 23

Coumarins

Back 23

block gamma-carboxylation of glutamate residues in prothrombin and factors 2, 7, 9, 10, and the anticoag prot C.

Front 24

thrombolytic drugs

Back 24

given IV to quickly dissolve clots by proteolytic cleavage *plasmin
Alteplase, Reteplase, Urokinase, Streptokinase

Front 25

Alteplase

Reteplase

Back 25

recombinant tPA, fibrin-bound plasminogen->plasmin

mutant tPA w/ 1st 172 a.a.'s removed: longer t1/2 b/c reduced hepatic elim

Front 26

Urokinase

Back 26

protease that directly activates plasminogen to plasmin to then convert fibrin to fibrinogen
NOT selective for fibrin bound plasminogen.DIRECTLY acts on plasminogen
does not show antigenicity that is possible with streptokinase

Front 27

streptokinase

Back 27

thrombolytic enz-->proteolytic dissolution of fibrin. forms 1:1 complex w/ plasminogen in 23 min.
Nonspecific fibrin b/c complex also degrades fibrinogen and other coag factors.

Front 28

Anistreplase

Back 28

anisoylated plasmin streptokinase activator complex. In VITRO prep of plasmin-streptokinase complex where the active site of the complex has a p-anisoylated lysine residue

Front 29

Coagulants (hemostatics)

Back 29

Vitamin K
Protamine
Amino Caproic Acid

Front 30

Thromboxane A2

Back 30

eicosanoid that induces platelet agg and is potent vasoconstrictor. ASA inhibits this production by inhibiting the COX enz IRREVERSIBLY.

Front 31

ASA+Dipyridamole=Aggrenox=combined, additive antiplatelet effects.

Back 31

Dipyridamole=antiplatelet drug that inhibits PDE3. (also adenosine uptake antagonist-->block of platelet adenylate cyclase)
ASA acetyl gp ends up on Ser 529

Front 32

Cilostazol

Back 32

inhibit PDE3 activity and suppress degradation of cAMP

Front 33

Ticlopidine and Clopidogrel: inhibitors of ADP-mediated platelet agg

Back 33

irreversible inhibitors of GPIIb/IIIa complex via modification of the platelet ADP receptor.
oral & req metabolic conversion to active metabolite

Front 34

Direct GPIIb/IIIa antagonists

Back 34

Abciximab
Tirofiban
Eptifibatatide

Front 35

Epifibatide

Back 35

RGD tripeptide seq
rigid cyclic structure-->incr stability
blocks fibrinogen-GPIIb/IIIa interactions resulting in inhibition of platelet agg
Big effort to discover oral RGD-likes

Front 36

Abciximab :)

Back 36

the Fab fragment of a monoclonal Ab that binds to the GPIIb/IIIa complex on the platelet surface

Front 37

Tirofiban (looser form of Epifibatide)

Back 37

competitively binds to RGD binding sites in GP complex and inhibits fibrinogen-GP complex interactions and blocks platelet agg.