Term
|
Definition
biologically active and slowly metabolized in vivo
|
|
|
Term
|
Definition
long half life, remain unchanged
chemical stability makes it unsuitable for optimization |
|
|
Term
|
Definition
produce active predictable and controllable in vivo metbaolism
[form nontoxic,inactive metabolite] |
|
|
Term
|
Definition
elimination of toxic metabolites
avoidance
|
|
|
Term
| 7 principles of SOFT DRUGS |
|
Definition
1. similar struct to lead
2. contain metabollically sensitive moiety in lead struct
3. sensitive moiety does not effect physicochemical or steric properties of lead compound
4. built in metabolismis major route for drug deactivation
5. rate of metab is predictable
6. drug metabolites have no other biological activities
7. predicted metabolism does not lead to highly reactive intermediates |
|
|
Term
| 3 steps in the metabloic inactive soft drug approach |
|
Definition
Controllable Metabolism
Activation stage
Predictable metabolism |
|
|
Term
|
Definition
-OH, -NH2,-CH3,-OR
-F,-Cl,Br,-I,-SH,-PH2
-Si3,-SR |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
=C=
=Si=
=N+=
=P+=
=As+=
=Sb+= |
|
|
Term
| nonenzymatic prodrug conversions are indicative of __________ prodrugs |
|
Definition
|
|
Term
| prodrugs and soft drugs are _______ |
|
Definition
|
|
Term
| high proliferation rates and high levlels of certain enzymes are founsd in what type of cells? |
|
Definition
|
|
Term
|
Definition
| antibody-directed enzyme prodrug therapy |
|
|
Term
| antibody-directed enzyme prodrug therapy |
|
Definition
relies on specificity of antibody for site targetting
|
|
|
Term
This drug has high first pass metabolism. Has a hemisuccinate prodrug version to avoid this
[unchanged drug was better intravenous than oral] |
|
Definition
|
|
Term
| This drug is unstable duen to internal nitrogen attacking beta lactam |
|
Definition
|
|
Term
This antipsychotic peaks orally after 2 and 6 hours. ______________
Intramuscular ester prodrug admin lasts for 1 month
______________ |
|
Definition
Haloperidol
Haloperidol Decanoate |
|
|
Term
Bambuterol is converted to _________
it is used as a long acting beta adrenergic aggonist for asthma |
|
Definition
|
|
Term
These two steroids have poor water solubility alone
|
|
Definition
prednisolone (neeeds phosphate)
Methylprednisolone (needs sodium succinate) |
|
|
Term
Fluocinonide to Fluocinonide acetonide
and
Epinephrine to _________ |
|
Definition
Dipivefrin
[for glaucoma] |
|
|
Term
|
Definition
|
|
Term
| Aspirins gastric ulcerogenic activity is reduced by __________________ |
|
Definition
|
|
Term
|
Definition
| inactive compounds converted to active by enzymatic (or nonenzymatic) transformations |
|
|
Term
1.solubility
2.absorption & distribution
3. site specificity
4. formulation
5.instability
6. drug duration
7.toxicity
8.pt acceptibility |
|
Definition
| Factors addressed by Prodrug strategies address |
|
|
Term
| Factors addressed by Prodrug strategies address |
|
Definition
1.solubility
2.absorption & distribution
3. site specificity
4. formulation
5.instability
6. drug duration
7.toxicity
8.pt acceptibility |
|
|
Term
| this antibiotic causes pain upon injection and has bad taste |
|
Definition
| clindamycin (needs phosphate for inj, palmitate for oral) |
|
|
Term
this toxic drug is used as a urinaryt ract antiseptic and is ________________ converted to ______________
[for formulation purposes] |
|
Definition
| methenamine to formaldehyde |
|
|
Term
|
Definition
Carrier linked: contains active linked rx
bioprecursor: metabolized to new rx that is active but metabolized further to THEE active rx |
|
|
Term
bipartate
tripartate
mutual prodrug |
|
Definition
bipartate: one carrier attached
tripartate:one carrier connected to rx thru linker
mutual prodrug: 2 synergistic drugs attached to each other directly or by linker (also called twin drug) |
|
|
Term
| Ideal Drug Carrier will be |
|
Definition
protective
localize site of act
release drug
minimize toxicity
prepared easy
biochemically inert,biodegradeable
stable |
|
|
Term
| Most common func groups in prodrug design |
|
Definition
-COOH
[CARBONATES,ESTERS,AMIDES,CARBAMATES]
-SH
[ETHER,ESTER]
-OH
[ETHER,PHOSPHATE,ESTER]
-PO(OH)2
[PHOSPHATE,ESTER]
-NH
[IMINES,OXIMES,N-MANNICH BASES,CARBAMATES,AMIDES]
-C=O
[OXIMES,IMINES] |
|
|
Term
| THIS GROUOP NOT USUALLY USED AS CARRIER LINKAGE DUE TO HIGH STABILITY |
|
Definition
|
|
Term
N mannich bases inc _____
schiff bases inc_________
Oximes inc
Acetals inc
Oxazolidenones & thioxazolidenones adjust___ |
|
Definition
N mannich bases inc lipophilicity
schiff bases inc lipophilicity
Oximes inc hydrophilicity
Acetals inc lipophilicity
Oxazolidenones & thioxazolidenones adjust lipophilicity |
|
|
Term
| bipartate drugs are innefective. why? |
|
Definition
| they are too labile/stable |
|
|
Term
| tripartate prodrugs cleave spontaneously when... |
|
Definition
| after carrier has been detaached |
|
|
Term
| Bioprecursor prodrug rxns |
|
Definition
Phiosphorylation activation
Oxidative rxn
Reductive activation
Nucleotide activation
Decarboxylation activation |
|
|
Term
| this drug goes thru phosphorylation in cell to affect viruses but leaves normal cells in tact |
|
Definition
|
|
