Intro to pharmacology Flashcards
Pharmacokinetics explains what 4 processes?
-Absorption
-Distribution
-Metabolism
-Excretion
Pharmacogenomics is ____ to the individual and can be determined by genetic testing (this can impact pharmacokinetics)
Specific
Theoretically, drugs can bind to almost any 3-D target to produce one of what three outcomes?
-Turn on a protein (agonist)
-Turn off a protein (antagonist)
-Regulate the function of a protein by how the drug binds
Desired effects (as well as adverse effects) occur when drugs bind to selected target molecules, or ____
Receptors
The binding of a drug to a receptor causes ____ and ____ changes within the body
Biological or physiological
Receptors are macromolecules that mediate the biochemical or physiological changes that occur when the ____ binds
Drug
A drug cannot make a protein do something it does not ____ do (it just regulates the function)- think about a dimmer switch on a light bulb
Normally
Receptors are generally what type of molecule?
Protein
What are the four major levels of the structure of a protein?
-Primary (polypeptide chain)
-Secondary (alpha and beta pleated sheets)
-Tertiary (3D structure)
-Quaternary (multiple proteins bound together)
Different parts of the protein have different affinities for ____, meaning they will be either hydrophobic or hydrophillic
Water
The ____ ____ on a receptor is where the drug actually binds
Binding site
Binding is affected by what types of interaction?
-van der Waals forces
-Hydrogen bonding
-Ionic interactions (most common)
-Covalent bonding (rare->usually irreversible and creates an inactivated complex)
An example of a drug that binds with covalent bonding is a…
Proton pump inhibitor
Proton pump inhibitors should only be taken for ___ weeks because of their irreversible mechanism of action
8
The ____ has the highest absorption of drugs because there is a higher pH, so it is able to ionize drugs
Duodenum
Proton pump inhibitors raise the pH of the ____, which may cause too much of the drug to become ionized by the time it reaches the duodenum
Stomach
We should stagger giving other drugs ___ hours before or after giving proton pump inhibitors to prevent increased ionization of drugs
2
_____ can also inhibit drug absorption, which is why dairy is often contraindicated for many drugs (I.e Tetracycline)
Calcium
____ can also inhibit drug absorption, which explains why women who take birth control have different drug metabolism when they are taking their placebo pills
Iron
The combination of all the interactions are what gives the drug it’s ____
Specificity
The favorability of the drug-receptor interaction is the ____ of the drug for the receptor
Affinity
Binding is rarely caused by just one ____
Interaction
_____ drug-receptor complexes usually have multiple interactions
Stable
Drugs commonly are bound to _____, and the unbound drug is what can then go bind to the actual target and become active/effective
Albumin
Hypoalbuminemia can cause drug ____ since too much of the drug would then become active
Toxicities
Affinity is very important in the drug-receptor model because it determines how long a drug will be bound to a ___
Receptor
The _____ structure of a drug is what gives the drug its physical and chemical properties that determine how it will bind to a receptor
Molecular
What are three important factors in the drug-receptor interaction?
-Hydrophobicity
-Ionization state (pKa)
-Conformation and stereochemistry
The ____ enantiomer is 4x more potent than the ____ enantiomer due to its ability to bind to the receptor
S; R
____ fats are the “bad” fats in butter because they can pack and build up, clogging arteries
Trans
Sometimes, drugs will have both ____, and depending on which receptor shape a patient has, one will fit better in one place than another
Stereoisomers
Explain the difference between Lexapro and citalopram:
-40 mg dose of citalopram is = to 10 mg dose of Lexapro
-You need less Lexapro because there is nothing there to interfere with the binding
Explain the difference between Albuterol and Xopenex:
-Albuterol is more expensive, but only because it contains other inactive ingredients (you would need 90 mg since 45 mg are inactive)
-Xopenex only contains the active drug (you would only need 45 mg to produce the same exact effect as albuterol)->important to remember that Xopanex has to be stored in foil since it is sensitive to light
_____ explains the amount of drug at which the drug produces a therapeutic effect
Potency
Warfarin is ___% protein bound, which means that it is bound to albumin in the blood but other proteins can be binding as well
99%
Women have a thyroid-binding protein that changes in concentration during ____; this may impact dosage of Levothyroxine if someone is already on it before pregnancy (this is important because if the mother’s thyroid isn’t working, the fetus is at risk)
Pregnancy
Albumin is made in the ____, so any issues with it can cause decreased albumin production
Liver
People awaiting liver transplants will not have good albumin stores, which causes drug concentration to ____, which could lead to bleeding if on Warfarin
Increase
When you give multiple drugs at the same time, it is important to know which has the higher ____, so you know what dose to give (if one has a higher affinity to albumin than the other, the other one will have higher levels in the blood and may cause toxic effects)
Affinity
If you give Levothyroxine (used to treat hypothyroidism) and Warfarin at the same time, what symptoms could you look for in order to determine which one has the higher affinity?
-Hyperthyroid symptoms (insensitivity to heat, bulging eyes, irritation, jitters, increased color)
-Bleeding
In some cases, drugs bind to sites that have _____ activity
Enzymatic
The ____ ____ is where enzymatic transformation is catalyzed
Active site
If a drug inhibits the binding of the normal substrate of the active site, it inhibits the ____ action
Enzymes
In some cases, the drug does not bind to the active site; in these cases, the drug may change the ___ of the receptor to increase or decrease substrate binding
Shape
Drugs can also bind and change the conformation of the receptor, referred to as ____ ____
Induced fit
Omega 3s are “bad” substrates when it comes to lowering cholesterol, so the function of the enzyme is blocked; you need ____ mg of EHA and HDA to affect cholesterol levels
1000
What are three things that could result from an induced fit binding?
-Closes the active site
-Opens the active site
-Desensitizes the active site (inactivated)
An example of a drug that desensitizes is ____; once on a certain dose for some time, more pain receptors will be made and less of those receptors will be blocked by the drug, leading to a need to increase the dose
Opioids
_____ is when the drug (or receptor?) gets pulled into the cell instead of remaining active on the surface; eventually, lysosomes will clear the drug from the inside of the cell
Downregulation
_____ would be when more receptors are made to make for of the drug active
Upregulation
A drug like ____ stabilizes the inactive receptors so that if more histamine comes, it can’t become active, therefore preventing upcoming symptoms (this is why you should take the drug before you have any allergy symptoms)
Allegra
The structure of a drug can affect its ability to get to the membrane because of the ____ ____
Plasma membrane
Highly ____-____ drugs are generally less able to pass through the plasma membrane or they need membrane channels or transporters
Water-soluble
Highly _____ drugs cross the membrane easily and have good access to intracellular targets
Lipophilic
Rational drug design allows us to gain knowledge of the _____ of the receptor
Structure
Rational drug design lets us understand the factors affecting the receptor in order to determine the _____ between the drug and the receptor
Specificity
Rational drug design also allows us to increase ____ and decrease ____ by binding more selectively to the receptor
Efficacy; toxicity
What are two determinants of drug selectivity?
-Cell-type specificity of receptor subtypes
-Cell-type specificity of receptor-effector coupling
In general, the more restricted the cell-type distribution, the more ____ the drug will be
Selective
In general, the more receptor-effector coupling mechanisms that differ among the cells types targeted, the ____ selective the drug will be
More
Beta-blockers have an adrenergic effect by blocking _____ in the sympathetic nervous system; these drugs are selective because they only affect beta 1
Norepinephrine
Beta 1 is mainly in the ___ and Beta 2 is mainly in the ____
Heart, lungs
If someone is taking too much _____ for hypertension, it becomes less selective and instead of only working on beta 1 in the heart, it becomes less selective and affects beta 2 in the lungs, possibly inducing an asthma attack
Metoprolol
Almost every cell in the body has a ____ receptor, so making a selective thyroid drug is very difficult
Thyroid
____ can be used to treat central nervous system conditions which cause overactivity; if this gets into the CNS, it reduces activity of norepinephrine which in excess, can cause depressive symptoms
Propranolol
What are some examples of drug receptors?
-Transmembrane ion channel (common)
-Transmembrane linked to intracellular G protein (common)
-Transmembrane with enzymatic cytosolic domain
-Extracellular enzyme
-Adhesion
Drugs can bind to ion channels spanning the plasma membrane, causing an alteration in the channel’s ____
Conductance
Heptahelical receptors spanning the plasma membrane are functionally coupled to intracellular ___ proteins; drugs can influence the actions of these receptors by binding to the extracellular domain of a transmembrane region of the receptor
G
Drugs can bind to the extracellular domain of a transmembrane receptor and cause a change in signaling within the cell by activating or inhibiting an enzymatic ____ ____ of the same receptor molecule
Intracellular domain
Drugs can diffuse through the plasma membrane and bind to cytoplasmic or nuclear receptors; this is often the pathway used by ____ drugs that bind to steroid hormone receptors
Lipophilic
Drugs can also inhibit enzymes in the extracellular space without the need to cross the ____ ___
Plasma membrane
For a drug to work intracellularly, it must be very _____ since it needs to get through the phospholipid bilayer
Lipophilic
Xeljanz is a ____ inhibitor that works to inhibit messages internally (think about ringing a doorbell but nobody comes to answer the door); this means that the autoimmune system creates inflammatory cells but they don’t have any harmful effects on the joints
Jak
What are three types of transmembrane ion channels?
-Ligand-gated
-Voltage-gated
-Second messenger regulated
The plasma membrane acetylcholine receptor is composed of ____ subunits
5
In the absence of acetylcholine, the receptor gate is _____, and cations (most importantly, sodium), are unable to traverse the channel
Closed
When acetylcholine is bound to both alpha subunits, the channel opens and ____ can pass down its concentration gradient into the cell
Sodium
Beta-blockers slow heart rate by blocking ____ channels (they work during phase 2 and phase 4 of the action potential)
Calcium
Beta-blockers and calcium blockers together are contraindicated because it reduces _____
Contractility
Class I antiarrhythmic blockers extend the whole interval of the contraction and may cause ____ prolongation
QT
Antiarrhythmic agents can worse existing arrhythmias by increasing their ____ or ____ or altering the rate of arrhythmias causing new ones
Duration or frequency
Transmembrane G protein-coupled receptors are the most ____ class of receptors in humans
Abundant
Transmembrane G protein-couple receptors are exposed at the ___ of the cell membrane and traverse through the membrane
Surface
Transmembrane G protein-coupled receptors have intracellular regions that activate signaling molecules called ____ ____
G proteins
G proteins bind ____ and ____
GTP and GDP
A major role for G proteins is to activate the production of ____ ____
Second messengers
Unless they bind covalently, the binding of the agonist is not ____
Permanent
In the resting state, the alpha and beta subunits of a G protein are associated with one another, and ____ is bound to the alpha subunit
GDP
Binding of an extracellular ligand (agonist) to a G protein-coupled receptor causes the exchange of ___ for ___ on the alpha subunit
GTP for GDP
The beta subunit dissociates from the alpha subunit, which diffuses to interact with ____ proteins
Effector
Interaction of the GTP-associated alpha subunit with an effector ____ the effector
Activates
In some cases, the ___ subunit can also activate effectors proteins
Beta
Depending on the receptor subtype and the specific G-alpha isoform, G-alpha can also ____ the activity of an effector molecule
Inhibit
The alpha subunit possesses intrinsic ____ activity, which leads to the hydrolysis of GTP to GDP, leading to the reassociation of the alpha subunit with the beta subunit and the cycle can begin again
GTPase
What are the 5 types of transmembrane receptors with enzymatic systolic domains?
-Tyrosine kinase (largest group)
-Tyrosine phosphatases
-Tyrosine kinase-associated receptors
-Receptor serine/theronine kinases
-Receptor Guanylyl cyclases
Transmembrane receptors have roles in cell…
-Metabolism
-Growth
-Differentiation
Intracellular targets can be ____ and have the ability to alter signaling or metabolic molecules
Enzymes
Lipophilic drugs can target ____ receptors that affect transcription regulator factors (like steroid hormones)
Cytosolic
Lipophilic can also act on cytosolic ____ proteins (antimicrobial and antineoplastic chemotherapy)
Structural
Small lipophilic molecules can diffuse through the plasma membrane and bind to intracellular ___ ___
Transcription factors
Ligand binding triggers a conformational change in the ____ that leads to transport of the ligand-receptor complex into the nucleus
Receptor
In the nucleus, the ligand-receptor complex typically ____
Dimerizes
The dimerized ligand-receptor complex binds to ____ and then may recruit coactivators or corepressors; these complexes alter the rate of gene transcription, leading to a change (either up or down) in cellular protein expression
DNA
The target of extracellular enzymes is outside of the ___ ___
Plasma membrane
Extracellular enzymes can target enzymes that convert or modify molecules that can influence _____ processes
Physiological
One example of a class of drugs that effects extracellular enzymes is…
ACE inhibitors
____ gets converted to Angiotensin I and then II
Renin
Renin is released in response to ____ blood pressure
Low
ACE metabolizes ____, so when ACE is blocked, it accumulates; this causes irritation in the lung tissue that causes a dry, unproductive cough which can decrease the quality of sleep and induce insomnia
Bradykinin
____ is when 2 cells have an area of contact between them
Adhesion
Adhesion is required for some functions to occur and is mediated by ____
Receptors
What are two examples where adhesion is important?
-Formation of tissue
-Migration of immune cells to a site of imflammation
____ or ____ of receptors can lead to cell damage or adverse effects to the body as a whole
Overstimulation or inhibition
Over time, the receptors may become ____ to the drug (decreased ability to respond to stimuli)
Desensitized
With _____ desensitization, only one type of receptor is diminished but with ____, two or more are diminished
Homologous; heterologous
Receptors can also become ____, in which the receptor becomes completely turned off
Inactivated
Receptors may also have altered ____ ____, which affects the time before receptors can be stimulated again (Ex: voltage-gated ion channels)
Refractory times
Repeated or persistent _____ interaction causes removal of receptors or sites available for interaction
Downregulation
With downregulation, ____ sequesters the receptors
Endocytosis
Cells can also alter the level of synthesis of receptors, which also regulates the number of receptors available for ____
Binding
Not all drugs interact with receptors; what are two examples of drug classes that do not?
-Osmotic diuretics
-Antacids
Osmotic diuretics act on ____ ___ to change the osmolarity of nephrons directly
Ion channels
Antacids absorb or chemically ____ acid
Neutralize
____ explains the effects of a drug on the body
Pharmacodynamics
Medications can be used at different ____ for different conditions (Ex: Metoprolol can be used to control blood pressure or heart rate)
Doses
____ is an alpha 2 agonist that is used when someone is agitated after being under anesthesia; it reduces norepinephrine availability which can induce sleep
Precedex
There is a lot of difference in response to psychiatric drugs because of manipulation of _____
Neurotransmitters
_____ is tightly controlled; a drug has to get a new steady state to be established
Desensitization
_____ is the ability of a drug to produce its effect
Efficacy
It is difficult to determine efficacy with ____
Antagonists
____ mimic activity that your body normally does
Agonists
Antagonists do not really have ____, they just block the activity of an agonist
Efficacy
The ____-____ relationship is the relationship between dose (drug concentration) and the patients
Dose-response
In general, the response to a drug is proportional to the ____ of receptors that are occupied by the drug
Concentration
A ____ Kd indicates a tighter drug-receptor interaction, meaning there is a higher affinity
Lower
Kd corresponds to the ligand concentration at which ___% of the receptors are bound by ligand
50%
What are the 2 major types of dose-response relationship?
-Graded
-Quantal
