Module 10: Pharmacology Basics Flashcards
Test 4
What is the difference between Pharmacology, pharmacodynamics, and pharmacokinetics?
Pharmacology: interactions between a drug & organism
pharmacodynamics: how the drug affects the organism
pharmacokinetics: how the organism affects the drug (ADME)
What are 3 things that can affect pharmacodynamics?
- disease/disorder
- age
- drug interactions
What are the receptor subtypes? Main one?
Enzyme (main)
Ion channel
membrane receptor
How do drugs bind to receptors?
Intermolecular forces (electrostatic interactions)
Hydrophobic interactions
Covalent bonds (Intramolecular forces)
Sterospecific interactions
SICH of this…
Covalent bonds are normally _____ therefore we try to avoid them
irreversible
Why are sterospecific interactions important?
some receptors are antiomer specific while some allow multiple stereoisomers. some receptors will illicit a negative effect if bound with a different stereoisomer.
Drugs act as a _______
ligand
What are 4 drug properties that we look at? Describe them. Do we like for them to be low or high?
- Affinity: How well the drug binds to the receptor
- Specificity: How specific the drug is to that receptor
- Efficacy: how well the drug produces desired effects
- Potency: compare drugs to see which has a higher affinity/specificity/efficacy
- We want all of these things to be high
What are the 2 types of drugs and their subtypes?
Agonist
Antagonist: Competitive & noncompetitive (irreversible)
What does allosteric mean?
Outside of active site
What does ADMET stand for?
Absorption
Distribution
Metabolism
Excretion
Toxicity
________ of the drug at the _________ affects the ability of the drug to give its desired effects
concentration
active site
ADMET refers to Pharmaco_____
kinetics
What is LD50?
Lethal dosing to kill 50% of population in animals
T/F: Water has an LD50
T
Everything has an LD50
What are 4 things Pharmacokinetics help us understand?
- Drug administration
- therapeutic dosing
- time intervals between drug dosing
- toxic dosing
What is the unit measurement in toxic dosing?
mg/kg
What is fentanyl’s LD50?
Very low
0.2 mg/kg
This means a very small amount can kill you
The lower the LD50, the easier it is to kill a person with a small dose!!! This is why people wear gloves when there could be a possible exposure to fentanyl
Explain ADME
Absorption: getting drug into the body
Distribution: getting the drug to the place where it needs to work (site of action)
Metabolism: Most metabolized in the liver by enzyme P450
Excretion: Leaving the body by means of mostly urine or feces
What type of reactions are used in the liver for metabolism? What enzyme is used?
REDOX
Cytochrome P450
What are all the ways a drug can be exreted from the body? What are the 2 most common ways?
Urine
Bile
Feces
Sweat
Saliva
What happens if we dont properly excrete drugs from the body?
Toxic build up
What are the methods of drug administration?
Enteral (oral)
Parenteral (non-oral)
–IM
–SQ
–IV
–Inhalation
–Topical
Which method of drug administration bypasses the 1st pass effect?
IV, IM, SQ
Which method of drug administration is the fastest?
IV
Which method of drug administration is most effected by the 1st pass effect?
PO
Which method of drug administration are effected by the 1st pass effect?
PO
Inhalation
________ rate will determine how long it takes to see peak effects
absorption
What does bioavailability refer to?
How much of the administered drug is actually absorbed. Typically in PO & topical
Describe what taking a medication on an empty stomach does vs with food
W/ food: slows down absorption
w/o food: drug absorbed more rapidly
What does ionized mean?
Able to dissociate when dissolved in water
An ionized drug is ______ soluble in water
More
T/F: A drug that is less water soluble is more easily distributed through the body
F
more water soluble
How do you make a drug more water soluble?
Adding more polar groups
Ionization of the drug
Although making a drug more polar/ionized will help it be distributed through the body more, why dont we want to do this TOO much?
having the drug be too polar or too charged will make it harder for it to cross the cell membranes.
What happens to drugs and prodrugs in the liver?
Prodrugs: actives
drugs: inactives or activated metabolites
What are the 2 reactions that take place during metabolism?
Hydrolysis
REDOX
What helps prevent toxic buildup and promotes the removal of metabolites in the body?
Excretion
How many years does it take for a drug to make it to market?
13 years
What are the top 2 reasons why drugs fail during clinical testing? What percentage is it?
Pharmacokinetics and lack of efficacy
69%
Where do most drugs fail at?
Discovery phase
How long is the preclinical phase?
1 year
How long is the discovery phase?
4.5 years
Describe the Lipinski Rule of 5
-Occurs in preclinical
-Want to ensure drug compounds follow these 5 basic rules
-Used as a tool to measure a NCE’s (new chemical entity) bioavailability
What are the Lipinski’s Rule of 5
- Less than 10 Hydrogen donors/acceptors
- Molecular wt less than 500
- Calculated partition coefficient (cLogP) <5
What is Calculated partition Coefficient (cLogP)?
ratio that measures the solubility of oil vs water
Want to be <5
What are hydrogen bond donors?
-NH
-OH
What are hydrogen bond acceptors?
NOF
-N
-O
-F
T/F: -NH is both a good hydrogen bond donor & acceptor
T
Why do we want the hydrogen bond donors/acceptors to be less than 10 in the Lipinski’s Rule of 5?
It increases polarity which decreases membrane premeability
Describe a hydrogen bond
Specialized dipole-dipole interaction
Increases affinity of a drug to a receptor
What increases a drug’s affinity to a receptor?
Hydrogen bonds
What part of an amino acid is able to undergo hydrogen bonding?
Side chains
Potential drugs must have both _______ and ______ groups
Hydrophilic
Lipophilic
Which structural groups have been linked to increased toxicity due to their metabolites?
Aromatic anilines
Nitroaromatics
Aliphatic halides
Polycyclic armomatic hydrocarbons
Thiophens
What does Nitroaromatics metabolize into?
Armomatic aniline
What happens when you metabolize aliphatic halides?
Covalent bonds
Polycyclic aromatic hydrocarbons are ________
Cancer causing
Thiophens oxidize into_______
toxic metabolites
T/F: Size & charge of the drug effect permeability
T
What are we going to need if we have a big, charged drug?
Active transport protein
What are the 2 types of transport? Describe them
Active: Requires energy (ATP)
-Across a gradient
-AT high drug concentration, transport plateaus
Passive: high concentration to low concentration
-drug needs to be low wt, and uncharged
What is Da?
Dalton
Unit of measurement
Grams/Mol
What is a small drug? What does this mean?
< 501 Dalton
Uses passive transport
What functional groups does Hydrolysis include?
Esters
Amides
Nitriles
