Chem test 4 Flashcards
the study of how a drug affects the organism
Pharmacodynamics
Pharmacokinetics
the study of how the organism affects the drug
Receptor subtypes include:
Enzymes
Ion Channels
Membrane receptors
Drugs bind due to what chemical interactions
Covalent bonds
Hydrophobic interactions
Electrostatic interactions (intermolecular forces)
Stereospecific interactions (enantiomers)
Affinity is
how well the drug binds to the receptor
how well the drug produces its desired effect is the definition of
Efficacy
term used to compare the relative affinity of competing drugs
Potency
Pharmacodynamics includes the effects of drugs on the body and their:
Site of Action
Mechanism of Action
Receptor Binding
Postreceptor Effects
Chemical Interactions
Pharmacokinetics studies
Helps to better understand the following:
ADME
Drug administration
Therapeutic dosing
Time intervals between drug dosing
Toxic dosing
Absorption rate determines time to
maximal concentration at the receptor to produce peak effect.
how much of the administered drug is actually absorbed. (typically used for oral administration)
Bioavailability
Factors affecting bioavailability include:
molecular weight of the drug
Intestinal motility
Drug stability (especially pH sensitivity)
Drug interactions
Blood flow
Drug formulation
Gastric emptying (food slows this process)
First pass metabolism (typically in the liver)
WISDBFGF
Effectiveness of the movement of the drug throughout the body is influenced by
Blood
Total body water
Extracellular fluids
Lymphatic fluids
Cerebrospinal fluids
Protein-binding
Why is drug solubility important?
Drug solubility properties help determine ability of drug to be distributed to the desired receptor site.
Metabolism is the breakdown of drugs into metabolites, what does this do?
Prodrugs – convert from inactive form to active form
Typically inactivates the drug ahead of excretion
Common processes of metabolism
Hydrolysis (esters, amides, and nitriles)
REDOX reactions (Cytochrome P450 enzymes in the liver)
Most drugs fail during the ________ phase
discovery
what percent of drugs fail in clinical testing?
90%
What is the Lipinski rule of 5?
Violation of more than one “rule” predicts _______
- Hydrogen bond donors (typically amines and alcohols)
- Hydrogen bond acceptors (total number of N, O, and F)
Want less than 10 total donors and acceptors - Molecular weight (MW) max is 500
- Calculated Partition Coefficient (C log P)(a ratio of the solubility of the drug in oil versus water) threshold is 5
a new chemical entity is non-orally available
Low MW drugs with a low cLogP can _____________
easily cross membranes.
Potential drug compounds must have a mix of ____________
hydrophilic and lipophilic groups
what are the Structural alerts – certain functional groups that have been linked to increased toxicity due to their metabolites:
Thiophenes
Aromatic anilines
Polycyclic aromatic hydrocarbons
Aliphatic halides
Nitroaromatics
Drug efficacy is directly related to
the concentration of the drug at its site of action.
Absorption of drugs into the bloodstream is dependent on
the acid/base properties of the drug and the pH at the site of absorption
What happens to transport at high drug concentrations?
transport plateaus due to limited number of transport proteins available
Can lead to competition with structurally similar compounds.
Small Drugs are how many Da?
(< 50 Da)
Lipophilic Drugs are how many Da?
(50 – 500 Da)
Transport and drug distribution is affected by
the size and charge of the drug molecule
What kind of transport is used for small drugs?
bulk flow
What kind of transport is used for lipophilic drugs?
passive transport
What kind of transport is used for ionized drugs?
active transport
