Week 1: Chapter 2,3,4,5,6,8,9,10 Overview ~ Ray Flashcards
Please add and edit as you see fit :) Week 1 objectives: Differentiate between pharmacodynamics and pharmacokinetics. Recall/employ main concepts of rational drug selection and cost when prescribing. Summarize special drug treatment considerations in pediatric and geriatric patients. Recall mechanisms that cause drug interactions. Recall various herbal therapies and their uses.
What are the stages of drug development? Could you describe each phase?
Preclinical: The drug is targeted, and ingredients are isolated. Medical chemists can create compounds and slightly adjust them to evaluate the perfect combination of properties. Studies are performed on cells, isolated tissues, and organs. Toxicology and safety testing determine the potential risk a compound poses to people and the environment.
Clinical phase I: establishes biological effects (safe dosages and pharmacokinetics) on healthy people at different doses.
Clinical Phase 2: drugs are used to treat diseases in a small number of sick patients. Outcomes are evaluated. <100 people.
Clinical Phase 3: The drug is compared with current medications in the market to evaluate outcomes—larger population group (~1000).
Explain the Dose-Response Curves
The higher the concentration of a drug at its site of action, the more the drug will bind to its receptor and the greater the response will be. With a greater number of drug molecules in the vicinity, more are likely to interact with the receptor and produce a response. Note: far fewer receptors may be needed to produce maximal effect.
IE a graph to show the concentration or dose of a drug in relation to that drugs percent of maximum response.
Explain Graded Response
Biological effects that can be measured continually up to the maximal capacity of the biological system (For example, the use of BP to monitor the effectiveness of Anti-HTNs)
Explain Quantal Response
Quantal Responses: Effects are present or absent. Examples are seizures, pregnancy, or death. NOTE:s can be both. For example, antiseizure medications can be graded by the decrease in seizures, whereas Some medicines can be quantal when there is an absence.
What is potency?
Potency is how much drug is needed to produce a biological response. Describes the difference in concentration of dosage of different drugs required to make the same effect. Higher potency requires less dose/concentration.
What is efficacy? Provide examples.
The maximal effect a drug can produce.
Example: Mild pain relief meds, such as Tylenol, cannot relieve the same pain as Oxy regardless of the dose.
What is intrinsic activity?
the ability of a drug to produce a response ONCE IT HAS OCCUPIED specific receptors.
Some drugs can occupy receptors and provide little to no response. The lower the intrinsic activity the lower efficacy the drug has.
What is Therapeutic Index (TI)? What is the formula?
It is the ratio of the lethal dose to the therapeutic dose. The higher the TI, the safer it is considered.
TI= LD50/ED50
What is Structure-Activity Relationship (SAR)
The correlation of chemical structure with pharmacological activity. Chemical interactions determine a drug’s activity at a particular receptor type, and changes in chemical structure result in changes in pharmacological activity.
What is a receptor?
Receptors are large molecules, usually proteins, that interact with and mediate the action of drugs.
Receptors provide a theoretical framework for understanding and predicting drug actions and the relationship between dose (or concentration) and effect. Also, receptors within the same “superfamily” often share properties.
What are Ion Channel Receptors?
Ion Channel receptors transmit signals across the cell membrane by increasing the flow of ions and altering the electrical potential or separation of charged ions across the membrane. Responses are rapid onset and short duration.
For example, when Acetylcholine (ACh) binds on TWO (2) nicotinic ion receptor sites, the channel opens, and Sodium and Potassium cross the cell membrane to initiate a response.
If you have pro can someone as a pic please
What types of Ion Channel Receptors are there?
ACh (nicotinic)
Gamma-aminobutyric acid (GABA)
Excitatory amino acids (glycine, aspartate, glutamate, etc.).
What are G-protein coulpled receptors? Explain the structure.
G-protein–coupled receptors are proteins that cross the cell membrane seven (7) times, creating a pocket in which drugs can interact. There is a “tail” intracellularly.
What happens when G-proteins are activated?
When a drug is attached to the binding site, the G protein undergoes a conformational change like a “twist”. The G-protein is then released. The, now-activated, G-protein can interact with effector proteins. These effector proteins then make second messengers.
How many subunits are in G-proteins? What are their names?
Alpha, Beta, Gamma.
What is Phosphorylation?
Placing a phosphate group on a protein is a way of marking it for activation or inactivation.
What is a Transmembrane Receptor?
Transmembrane receptors consist of extracellular hormone-binding domain and an intracellular enzyme domains that phosphorylates the amino acid tyrosine
How do transmembrane receptors get activated? What happens?
The hormone binds to the extracellular binding site, the receptor conformation changes, and two receptors bind to each other, activating the enzyme and sustaining the effect. Different receptors catalyze the phosphorylation of tyrosine residues on various downstream signaling proteins.
What are intracellular receptors? what happens when they are activated?
Intracellular receptor resides in the cytoplasm until it binds with a drug that has glucocorticoid activity. Binding of the drug displaces a stabilizing protein and permits the folding of the receptor into its active conformation. The receptor then moves to the nucleus, where it controls the transcription of genes by binding to specific DNA sequences
What are enzymes?
biological molecules that encourage specific chemical reactions in the body.
I think of enzymes as action tasks. Enzymes are the lock, and drug is the key.
What is full agonist
drugs that produce receptor stimulation and conformation change every time they are bonded. they do not need all the available receptors to produce maximum effect.
what are antagonists
Drugs that occupy a receptor without stimulating them and prevent other molecules from occupying the same site to produce a response.
what are the two types of antagonists (explain both)
Competitive: compete for the same binding site. Drugs can overcome antagonistic effects with higher concentrations of competing agonists.
Non-competitive: antagonist irreversibly bind somewhere else in the enzyme, changing it and making it unusable. Increasing drug does not increase effectiveness.
what are partial agonists?
Bind to receptors but when they occupy the receptor sites, they stimulate only some of the receptors. They trigger a lower maximal response than a full agonist. This is sometimes called intrinsic activity
What is pharmacokinetics
The absorption, distribution through the body, metabolism, and excretion of drugs
What is absorption?
The way in which medications are presented to the body
What is bioavailability? Which route has the highest bioavailability?
The percentage of the admin dose that enters the bloodstream (regardless of route).
IV admin has the highest bioavailability as it goes straight into circulation and skips first pass.
What is peak blood levels?
The highest concentration of drug in the body. Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side effects. IV push leads to the highest peak blood levels.
What is distribution?
the process of drugs moving throughout the body.
What are properties that affect distribution?
Molecule size, charge, pH (ionization), chemical structure, transport systems.
When does passive diffusion occur most readily?
When drugs are small and uncharged and have the right balance between water and lipid solubility, preferring lipophilic molecules.
What is the Henderson-Hasselbalch equation
pH=pKa + log([A-]/[HA])
A- (ionized) HA = non-ionized
how is pH defined
-log[H+]
what is pKa?
The acid dissociation constant (pKa) is the pH at which a drug is half charged and half uncharged. it is a FIXED property
What is passive diffusion?
Passive diffusion is a process through which drugs cross some type of biological barrier, such as a cell membrane or a layer of cells, based on the concentration difference between the two sides of the barrier. passive diffusion proceeds until the concentration of un-ionized drug is the same on both sides. As a result, pH differences can cause more drugs to accumulate based on the fraction of un-ionized and ionized molecules. This is called ion trapping.
what are plasma proteins?
Proteins are made in the liver, and drugs can bind to them. Albumin is the most common.
Others: alpha-1-acid glycoprotein, cortisol-binding globulin, sex hormone–binding globulin, and lipoprotein
What happens when drugs are bonded to plasma proteins? (aka why is it importaint)
They can freely circulate the blood system. (plasma proteins are the Ubers). They also protect the drug from metabolism/excretion. However, it prevents the interaction of drug molecules with their site of action. Can make a blood level of a drug appear high when it is actually not active.
what are transporters?
Membrane proteins that facilitate the movement of molecules across the cell membranes. They are directional (influx/efflux).
examples:
MRCP1, P-glycoprotein
What does a non-competitive or irreversible antagonist do to the dose response curve?
Lowers the max efficacy of the drug, it will not be able to reach same ED100
what are metabolites
drugs that are chemically altered by enzymes
what is metabolism?
Process of changing one chemical into another, usually using or creating energy.
what is first-pass metabolism?
metabolism by the liver following oral administration
Who is the MPV of metabolism?
The P450 enzyme family 😎
What is phase I of metabolism
nonsynthetic reactions.
Oxidation, reduction, and hydrolysis reactions.
They unmask polar groups, which improves water solubility and prepares drug molecules for further metabolic reactions.
They are either eliminated or go to phase II
What is phase II of metabolism?
Synthetic or conjugation reactions.
Metabolites are linked/conjugated to highly polar molecules, making them water-soluble.
What is drug selectivity?
Ratio for the drug amount or concentration producing undesired effects to the concentration producing the desired effect. How many times would a therapeutic dose have to be given to undesired effects.
Example. If a drug produces desired effect at one tablet and no undesired effects, but you will see undesired effects at 5 tablets, the selectivity ratio is 5.
What are the differences between Brand and Generic drugs?
Have same active ingredient but differ the inactive ingredients, fillers, capsules or coloring. There is usually variations in the rate of absorption due to differences in the time it takes to break down and dissolve.
What is a single nucleotide polymorphism (SNPs)
Minor mutations in proteins that can result in metabolic activity changes.
Can charged/ ionized molecules can passively diffuse through a cell membrane?
No, uncharged or unionized molecules are more lipid soluable and more readily pass through the cell membrane.
What are the most important CYP subfamilies?
CYP3A4, CYP2D6
what is competition?
when two drugs are metabolized by the same enzyme. Often the enzyme can metabolize both drugs, but sometimes one drug will be preferentially metabolized, delaying the metabolism and extending the half-life of the competing drug.
What is first order metabolism?
Metabolism is related to drug concentration so that a fixed FRACTION of a drug is metabolized per hour.
characterized by half-life. (elimination per hr is dependent on drug concentration). Exponential.
1st half-life: 50%
two half-life: 75%
third half-life: 87.5%
Can G-couple protein receptors have a rebound effect?
Yes, receptors can be desensitized or number downregulated with stimulation. This can limit the amount of time a drug can be given and can cause a rebound effect when abruptly stopped.
What is zero-order metabolism?
Metabolize a constant amount of drug each hour regardless of dose in body. Linear.
What are prodrugs?
Drugs that rely on metabolism to become active.
what is enzyme induction?
When some drugs increase the expression of drug-metabolizing enzymes
What is Excretion?
the process in which drugs are transferred from inside the body to outside the body.
