Pharmacology Flashcards
(27 cards)
Initial enzyme-substrate interactions in active sites are typically ________
Non covalent (H-bonding, VDW, hyrdophobic, electrostatic)
Active site excludes ______
bulk solvent which would reduce cat.
Species Specificity (differential)
The likeliness of a drug to attack enzyme isoform in one species while leaving the host alone
Two fundamental phenomena behind drug resistance
- reduced intracellular concentration of drug
2. changes in drug target
A flexible drug avoids
Drug resistance
What mechanisms may cause reduced intracelluar concentration of a drug?
Drug inactivation, Prevention of drug uptake, Drug efflux
What mechanisms are classisfied as target-based mechanisms
Altered drug target (receptor mutates), Bypassing metabolic requirements, insensitivity to apoptosis
Activation of the receptor to signal as a result of binding
Agonists
Drugs that bind to a receptor and block agonist from binding
antagonists
Bind to an active receptor and turn it to an inactive/tense for
inverse agonist
Pro-drug
utilizes a specific enzyme to transform inactive molecule to active form in vivo.
Why use a pro-drug?
When absorption/cell permeation or manufacturing are issues. Also, used to target specific tissues
Pharmacodynamic DDI
a drug-drug interaction that occurs at the receptor [additive, synergistic, antagonistic] (e.g. competitive inhibitor)
Pharmacokinectic DDI
Affects the metabolism, absorption, excretion, or distribution of the drug.
Suicide Inhibitors
bind covalently to the enzyme and reders it ineffective.
Two phases of drug metabolism
(1) reactions (Redox, hydrolysis) to increase aqueous solubility accerates elimination
(2) reactions conjugate drug or metabolite to an endogenous substrate (acetice acid, amino acid, etc.)
PM
poor metabolizers
EM
extensive metabolizers
IM
intermediate metabolizers
Acute drug toxicity will most likely affect what organs?
liver, kidney, brain, heart
Between an inhibitor and an inducer, which effects would be seen first?
Inhibitor. Inducer must bind to a promoter and upregulate protein synthesis at a target gene. (exception - suicide inhibitor)
Ligand-Receptor binding creates
Hyperbolic saturation binding curve
Enzyme Reaction creates
Hyperbolic Michaelis-Menten Plot
Positive cooperativity
refers to ligand-receptor, increases binding aff. of OTHER SUBUNITS
