Pharmacology Basics Flashcards
What does pharmacodynamics include?
Site of action
mechanism of action
receptor binding
post-receptor effects
chemical interactions
What can affect pharmacodynamics?
Diseases
Age
Drug-drug interactions
What are the different receptor subtypes?
Enzymes
Ion channels
Membrane receptors
What allows drugs to bind?
Chemical Interaction:
Electrostatic (H+ bonding)
hydrophobic
covalent
stereospecific
What are the 3 drug properties?
Affinity
Efficacy
Potency
What is drug affinity?
How well the drug binds to the receptor
What is drug efficacy?
How well the drug produces the desired effect
What is potency?
Term used to compare the relative affinity of competing drugs
What are the catagories of drugs?
Agonist
Antagonist
What are the different types of antagonists?
Competitive- reversible
non competitive- irreversible binding or binds allosterically
What is an allosteric antagonist?
diminish the agonists ability to bind to a different receptor
What affects the ability of a drug to give its desired effects?
Concentration
What are some of the parenteral routes?
IV
IM
SQ
Inhalation
What does absorption rate determine?
Time to max concentration at the receptor to produce peak effect
What factors affect bioavailability?
Molecular weight of the drug
Drug formulation
Drug stability (especially pH sensitivity)
First pass metabolism (typically in the liver)
Blood flow
Gastric emptying (food slows this process)
Intestinal motility
Drug interactions
What influences drug distribution?
Blood
Total body water
Extracellular fluids
Lymphatic fluids
Cerebrospinal fluids
Protein-binding
What properties help determine that ability of a drug to be distributed to the desired receptor site?
Drug solubility properties
What does hydrolysis break down?
esters, amides, nitriles
What uses REDEOX reactions for metabolism?
CYP450 enzymes in the liver
How are most drugs excreted?
Kidneys
When do most drugs fail?
Discovery phase
what percent of drugs fail in clinical testing?
90%
What is Lipinski Rule of 5 used for?
Used as a tool to measure a new chemical entity (NCE) potential bioavailability
What is Lipinski Rule based on?
Hydrogen bond donors (typically amines and alcohols)
Hydrogen bond acceptors (total number of N, O) <10 total
Molecular weight (MW) <500
Calculated Partition Coefficient (cLogP) <5
What does violation of two of lipinski rules indicate?
Predicts a new chemical entity (NCE) in non-orally available
Which structural groups have been linked with increased toxicity?
Aromatic anilines
Nitroaromatics
Aliphatic halides
Polycyclic aromatic hydrocarbons
Thiophenes
Which type of molecules can use passive transport?
Small Drugs (< 50 Da)
Lipophilic Drugs (50 – 500 Da)
Which drugs use active transport?
Ionized Drugs (> 50 Da)
greater the level of ionization the slower it is to cross into the membrane (less in unionized form)
What does Da stand for?
grams/mol
Why do we use Da when talking about proteins?
because proteins are so large
What happens to active transport at high drug concentrations?
Transport plateaus due to limited number of transport proteins available
aromatic anilines
Nitroaromatics
Usually convert to aniline via metabolism
Aliphatic Halides
Bad because they like to form covalent bonds
Halide adjacent to CH2
Polycyclic aromatic hydrocarbons
more then 2 benzene rings (napthalene is fine)
cancer causing
Thiophenes
Like to oxidize to toxic metabolites
What kind of bonding do we want in drug molecules?
Hydrogen bonding: increases drug affinity for receptor
What does it mean in regards to affinity if a drug has no H+ bonds?
Low affinity
How many years does it take to get a drug from start to market?
13 years
What are the 2 main reasons why drugs fail?
1) Pharmacokinetic stage (preclinical)
2) Lack of efficacy (need too much of drug to get desired response)
What is LD50?
lethal dose in 50%
tested on animals
mg drug/ kg of body weight
violation of more than ______ lipinski rule makes it a poor drug candidate?
1
What is a cLOGp greater than 1?
Fat soluble compounds
(log >1 is actually 10)
What is cLOGp less than 1?
More water soluble compounds
What happens to a drug with increasing cLOGp?
More it struggles to be distributed in the body
What are fluorines added to molecules for?
Prevent metabolism of compounds
What does low % ionization mean?
more drug being absorbed
