Intro to pharmacology Flashcards
1
Q
Pharmacokinetics explains what 4 processes?
A
-Absorption
-Distribution
-Metabolism
-Excretion
2
Q
Pharmacogenomics is ____ to the individual and can be determined by genetic testing (this can impact pharmacokinetics)
A
Specific
3
Q
Theoretically, drugs can bind to almost any 3-D target to produce one of what three outcomes?
A
-Turn on a protein (agonist)
-Turn off a protein (antagonist)
-Regulate the function of a protein by how the drug binds
4
Q
Desired effects (as well as adverse effects) occur when drugs bind to selected target molecules, or ____
A
Receptors
5
Q
The binding of a drug to a receptor causes ____ and ____ changes within the body
A
Biological or physiological
6
Q
Receptors are macromolecules that mediate the biochemical or physiological changes that occur when the ____ binds
A
Drug
7
Q
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
A
Normally
8
Q
Receptors are generally what type of molecule?
A
Protein
9
Q
What are the four major levels of the structure of a protein?
A
-Primary (polypeptide chain)
-Secondary (alpha and beta pleated sheets)
-Tertiary (3D structure)
-Quaternary (multiple proteins bound together)
10
Q
Different parts of the protein have different affinities for ____, meaning they will be either hydrophobic or hydrophillic
A
Water
11
Q
The ____ ____ on a receptor is where the drug actually binds
A
Binding site
12
Q
Binding is affected by what types of interaction?
A
-van der Waals forces
-Hydrogen bonding
-Ionic interactions (most common)
-Covalent bonding (rare->usually irreversible and creates an inactivated complex)
13
Q
An example of a drug that binds with covalent bonding is a…
A
Proton pump inhibitor
14
Q
Proton pump inhibitors should only be taken for ___ weeks because of their irreversible mechanism of action
A
8
15
Q
The ____ has the highest absorption of drugs because there is a higher pH, so it is able to ionize drugs
A
Duodenum
16
Q
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
A
Stomach
17
Q
We should stagger giving other drugs ___ hours before or after giving proton pump inhibitors to prevent increased ionization of drugs
A
2
18
Q
_____ can also inhibit drug absorption, which is why dairy is often contraindicated for many drugs (I.e Tetracycline)
A
Calcium
19
Q
____ can also inhibit drug absorption, which explains why women who take birth control have different drug metabolism when they are taking their placebo pills
A
Iron
20
Q
The combination of all the interactions are what gives the drug it’s ____
A
Specificity
21
Q
The favorability of the drug-receptor interaction is the ____ of the drug for the receptor
A
Affinity
22
Q
Binding is rarely caused by just one ____
A
Interaction
23
Q
_____ drug-receptor complexes usually have multiple interactions
A
Stable
24
Q
Drugs commonly are bound to _____, and the unbound drug is what can then go bind to the actual target and become active/effective
A
Albumin
25
Hypoalbuminemia can cause drug ____ since too much of the drug would then become active
Toxicities
26
Affinity is very important in the drug-receptor model because it determines how long a drug will be bound to a ___
Receptor
27
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
28
What are three important factors in the drug-receptor interaction?
-Hydrophobicity
-Ionization state (pKa)
-Conformation and stereochemistry
29
The ____ enantiomer is 4x more potent than the ____ enantiomer due to its ability to bind to the receptor
S; R
30
____ fats are the "bad" fats in butter because they can pack and build up, clogging arteries
Trans
31
Sometimes, drugs will have both ____, and depending on which receptor shape a patient has, one will fit better in one place than another
Stereoisomers
32
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
33
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
34
_____ explains the amount of drug at which the drug produces a therapeutic effect
Potency
35
Warfarin is ___% protein bound, which means that it is bound to albumin in the blood but other proteins can be binding as well
99%
36
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
37
Albumin is made in the ____, so any issues with it can cause decreased albumin production
Liver
38
People awaiting liver transplants will not have good albumin stores, which causes drug concentration to ____, which could lead to bleeding if on Warfarin
Increase
39
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
40
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
41
In some cases, drugs bind to sites that have _____ activity
Enzymatic
42
The ____ ____ is where enzymatic transformation is catalyzed
Active site
43
If a drug inhibits the binding of the normal substrate of the active site, it inhibits the ____ action
Enzymes
44
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
45
Drugs can also bind and change the conformation of the receptor, referred to as ____ ____
Induced fit
46
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
47
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)
48
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
49
_____ 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
50
_____ would be when more receptors are made to make for of the drug active
Upregulation
51
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
52
The structure of a drug can affect its ability to get to the membrane because of the ____ ____
Plasma membrane
53
Highly ____-____ drugs are generally less able to pass through the plasma membrane or they need membrane channels or transporters
Water-soluble
54
Highly _____ drugs cross the membrane easily and have good access to intracellular targets
Lipophilic
55
Rational drug design allows us to gain knowledge of the _____ of the receptor
Structure
56
Rational drug design lets us understand the factors affecting the receptor in order to determine the _____ between the drug and the receptor
Specificity
57
Rational drug design also allows us to increase ____ and decrease ____ by binding more selectively to the receptor
Efficacy; toxicity
58
What are two determinants of drug selectivity?
-Cell-type specificity of receptor subtypes
-Cell-type specificity of receptor-effector coupling
59
In general, the more restricted the cell-type distribution, the more ____ the drug will be
Selective
60
In general, the more receptor-effector coupling mechanisms that differ among the cells types targeted, the ____ selective the drug will be
More
61
Beta-blockers have an adrenergic effect by blocking _____ in the sympathetic nervous system; these drugs are selective because they only affect beta 1
Norepinephrine
62
Beta 1 is mainly in the ___ and Beta 2 is mainly in the ____
Heart, lungs
63
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
64
Almost every cell in the body has a ____ receptor, so making a selective thyroid drug is very difficult
Thyroid
65
____ 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
66
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
67
Drugs can bind to ion channels spanning the plasma membrane, causing an alteration in the channel's ____
Conductance
68
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
69
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
70
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
71
Drugs can also inhibit enzymes in the extracellular space without the need to cross the ____ ___
Plasma membrane
72
For a drug to work intracellularly, it must be very _____ since it needs to get through the phospholipid bilayer
Lipophilic
73
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
74
What are three types of transmembrane ion channels?
-Ligand-gated
-Voltage-gated
-Second messenger regulated
75
The plasma membrane acetylcholine receptor is composed of ____ subunits
5
76
In the absence of acetylcholine, the receptor gate is _____, and cations (most importantly, sodium), are unable to traverse the channel
Closed
77
When acetylcholine is bound to both alpha subunits, the channel opens and ____ can pass down its concentration gradient into the cell
Sodium
78
Beta-blockers slow heart rate by blocking ____ channels (they work during phase 2 and phase 4 of the action potential)
Calcium
79
Beta-blockers and calcium blockers together are contraindicated because it reduces _____
Contractility
80
Class I antiarrhythmic blockers extend the whole interval of the contraction and may cause ____ prolongation
QT
81
Antiarrhythmic agents can worse existing arrhythmias by increasing their ____ or ____ or altering the rate of arrhythmias causing new ones
Duration or frequency
82
Transmembrane G protein-coupled receptors are the most ____ class of receptors in humans
Abundant
83
Transmembrane G protein-couple receptors are exposed at the ___ of the cell membrane and traverse through the membrane
Surface
84
Transmembrane G protein-coupled receptors have intracellular regions that activate signaling molecules called ____ ____
G proteins
85
G proteins bind ____ and ____
GTP and GDP
86
A major role for G proteins is to activate the production of ____ ____
Second messengers
87
Unless they bind covalently, the binding of the agonist is not ____
Permanent
88
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
89
Binding of an extracellular ligand (agonist) to a G protein-coupled receptor causes the exchange of ___ for ___ on the alpha subunit
GTP for GDP
90
The beta subunit dissociates from the alpha subunit, which diffuses to interact with ____ proteins
Effector
91
Interaction of the GTP-associated alpha subunit with an effector ____ the effector
Activates
92
In some cases, the ___ subunit can also activate effectors proteins
Beta
93
Depending on the receptor subtype and the specific G-alpha isoform, G-alpha can also ____ the activity of an effector molecule
Inhibit
94
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
95
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
96
Transmembrane receptors have roles in cell...
-Metabolism
-Growth
-Differentiation
97
Intracellular targets can be ____ and have the ability to alter signaling or metabolic molecules
Enzymes
98
Lipophilic drugs can target ____ receptors that affect transcription regulator factors (like steroid hormones)
Cytosolic
99
Lipophilic can also act on cytosolic ____ proteins (antimicrobial and antineoplastic chemotherapy)
Structural
100
Small lipophilic molecules can diffuse through the plasma membrane and bind to intracellular ___ ___
Transcription factors
101
Ligand binding triggers a conformational change in the ____ that leads to transport of the ligand-receptor complex into the nucleus
Receptor
102
In the nucleus, the ligand-receptor complex typically ____
Dimerizes
103
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
104
The target of extracellular enzymes is outside of the ___ ___
Plasma membrane
105
Extracellular enzymes can target enzymes that convert or modify molecules that can influence _____ processes
Physiological
106
One example of a class of drugs that effects extracellular enzymes is...
ACE inhibitors
107
____ gets converted to Angiotensin I and then II
Renin
108
Renin is released in response to ____ blood pressure
Low
109
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
110
____ is when 2 cells have an area of contact between them
Adhesion
111
Adhesion is required for some functions to occur and is mediated by ____
Receptors
112
What are two examples where adhesion is important?
-Formation of tissue
-Migration of immune cells to a site of imflammation
113
____ or ____ of receptors can lead to cell damage or adverse effects to the body as a whole
Overstimulation or inhibition
114
Over time, the receptors may become ____ to the drug (decreased ability to respond to stimuli)
Desensitized
115
With _____ desensitization, only one type of receptor is diminished but with ____, two or more are diminished
Homologous; heterologous
116
Receptors can also become ____, in which the receptor becomes completely turned off
Inactivated
117
Receptors may also have altered ____ ____, which affects the time before receptors can be stimulated again (Ex: voltage-gated ion channels)
Refractory times
118
Repeated or persistent _____ interaction causes removal of receptors or sites available for interaction
Downregulation
119
With downregulation, ____ sequesters the receptors
Endocytosis
120
Cells can also alter the level of synthesis of receptors, which also regulates the number of receptors available for ____
Binding
121
Not all drugs interact with receptors; what are two examples of drug classes that do not?
-Osmotic diuretics
-Antacids
122
Osmotic diuretics act on ____ ___ to change the osmolarity of nephrons directly
Ion channels
123
Antacids absorb or chemically ____ acid
Neutralize
124
____ explains the effects of a drug on the body
Pharmacodynamics
125
Medications can be used at different ____ for different conditions (Ex: Metoprolol can be used to control blood pressure or heart rate)
Doses
126
____ 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
127
There is a lot of difference in response to psychiatric drugs because of manipulation of _____
Neurotransmitters
128
_____ is tightly controlled; a drug has to get a new steady state to be established
Desensitization
129
_____ is the ability of a drug to produce its effect
Efficacy
130
It is difficult to determine efficacy with ____
Antagonists
131
____ mimic activity that your body normally does
Agonists
132
Antagonists do not really have ____, they just block the activity of an agonist
Efficacy
133
The ____-____ relationship is the relationship between dose (drug concentration) and the patients
Dose-response
134
In general, the response to a drug is proportional to the ____ of receptors that are occupied by the drug
Concentration
135
A ____ Kd indicates a tighter drug-receptor interaction, meaning there is a higher affinity
Lower
136
Kd corresponds to the ligand concentration at which ___% of the receptors are bound by ligand
50%
137
What are the 2 major types of dose-response relationship?
-Graded
-Quantal
138
The graded dose-response relationship explains the effect that various doses have on an ____ and symptoms like heart rate and BP
Individual
139
The quantal dose-response relationship explains the effect of various doses on a ____ (looks at the response to the dose) and looks at things like sleep or no sleep or lives at 6 months or dead at 6 months
Population
140
EC50 is the _____ of a drug, or the concentration at which the drug elicits 50% of its maximal effect
Potency
141
The potency and efficacy of a drug are ____ related
Not
142
We can compare the potency of 2 drugs by comparing the ____ of the 2 drugs
EC50
143
_____ is the maximal response produced by the drug
Emax
144
With quantal dose-response relationships, the responses are defined as ____ or ___ ____ (as opposed to a grades response such as heart rate)
Present or not present
145
What are three important parameters for quantal responses?
-Therapuetic effect (medican effective dose; ED50)
-Adverse effect (toxic effect; TD50)
-Lethal effect (medial lethal dose; LD50)
146
Drug + receptor<_______>Drug-receptor complex
Affinity (k1/k2)
147
Drug-receptor complex <_______> Effect
Efficacy (K3)
148
K1 is the ____ constant, and explains how fast the drug-receptor complex is formed
Association
149
K2 is the _____ constant, and explains how fast the complex comes off of each other
Dissociation
150
The ratio is K1/K2 is the ____
Affinity
151
K3 is where we get our ____ from
Efficacy
152
An ____ is a molecule that binds to a receptor and stabilizes it in a particular conformation (usually the active conformation)
Agonist
153
An ____ is a molecule that inhibits the action of an agonist, but has no effect in the absence of the agonist
Antagonist
154
Antagonists can bind to the active site or the ____ site
Allosteric
155
The binding of an antagonist can be ____ or ____
Reversible or irreversible
156
Antagonists ____ the agonists
Oppose
157
_____ antagonists bind reversibly to the active site of the receptor
Competitive
158
Competitive antagonists maintain receptors in the _____ conformation and block the agonist from binding, but can be pushed off the receptor
Inactive
159
Competitive antagonists reduce _____
Potency
160
Noncompetitive antagonists bind to either the ____ or ____ site
Active or allosteric
161
If noncompetitive antagonists bind to the active site, they bind ____ and can not be competed for by the agonist
Irreversibly
162
What is one example of a non-competitive antagonist?
Aspirin
163
Aspirin irreversibly inhibits ______
Cyclooxygenase
164
If a noncompetitive antagonist binds to the allosteric site, it prevents the receptor from being activated even if the agonist binds, therefore reducing ____
Efficacy
165
Competitive antagonists are two drugs fighting for the ____ spot
Same
166
Drug ___ can raise the concentration to make the combative one have an advantage
Sitting
167
_____ can bind at the allosteric site and can increase or decreases activity because it changes shape
Benzodiazepines
168
Chemical nonreceptor antagonists modify or sequester the ____ so that it can not bind to the receptor
Agonist
169
Physiological nonreceptor antagonists activate or block a receptor that mediates a physiological response ____ of the agonists
Opposite
170
An example of a nonreceptive physiological antagonist is _____, which blocks sympathetic stimulation
Hyperthyroid
171
When _____ agonists bind to the active site, they only produce a partial response even if all of the receptors are occupied
Partial
172
The dose-response curves of partial agonists plateau at values ____ than those of full agonists
Less
173
A receptor antagonist that binds reversibly is a ____ ____
Competitive antagonist
174
A receptor antagonist that binds irreversibly to the active site is a _____ ____ ____ ____
Noncompetitive active site antagonist
175
Receptor antagonists that bind to the allosteric site, either reversibly or irreversibly, are ____ ____ ___
Noncompetitive allosteric antagonists
176
An agonist alone can increase in ____ and still get up to max effect
Concentration
177
A competitive antagonist reduces the ____ of an agonist without affecting agonist efficacy
Potency
178
A non-competitive antagonist reduces the ____ of an agonist
Efficacy
179
_____ agonists act to nullify the intrinsic activity of unoccupied receptors
Inverse
180
Both inverse agonists and competitive antagonists reduce ___ ___ and full agonist ____
Receptor activity; potency
181
Inverse agonists and competitive antagonists differ in that competitive antagonists have no effect without the presence of an ____, whereas inverse agonists deactivate receptors that are normally active in the absence of an agonist
Agonist
182
An example of an inverse agonist is an _____
Antihistamine
183
____ _____ are present in a situation where max effect is seen before all receptors are occupied
Spare receptors
184
Spare receptors change the dose-response curve to a _____ ____
Noncompetitive antagonist
185
With spare receptors, the max effect may still be achieved in response to ____ concentrations of an antagonist
Low
186
With ____ ____, the drug may only need to block some of the receptors in order to reduce blood pressure
Beta blockers
187
In a system without spare receptors, a noncompetitive antagonist causes ____ to decrease at all concentrations of the antagonist
Efficacy
188
In a system with spare receptors, ____ is decreased but efficacy is unaffected at low concentrations of the antagonist, because a sufficient number of unoccupied receptors is available to generate a maximal response
Potency
189
As increasing concentrations of antagonist bind noncompetitively to more and more receptors, the antagonist eventually occupies all of the ____ receptors, and efficacy is also reduced
Spare
190
The ____ ____ is a range of drug concentrations that deliver a therapeutic response without toxicity, or the drug concentration between the toxic dose and the effective dose
Therapeutic window
191
The ___ ___ is the ratio of TD50/ED50
Therapeutic index
192
A large therapeutic index represents a ____ therapeutic window
Large
193
A small therapeutic index represents a narrow therapeutic window, and these drugs require careful ____ and ____
Dosing and monitoring
194
_____ (ADME) explains what the body does to the drug
Pharmacokinetics
195
What does ADME stand for?
-Absorption
-Distribution
-Metabolism
-Excretion
195
What does ADME stand for?
-Absorption
-Distribution
-Metabolism
-Excretion
196
If drugs are not ____, they will not have any therapeutic effect
Absorbed
197
_____ has an administration requirement of increasing fluid intake by 1.5 liters to prevent bladder crystals, which will not help pain upon urination and other UTI symptoms (many people will stop taking the drug altogether)
Bactrim
198
At all times, free drug in the systemic circulation is in ____ with tissue reservoirs, plasma proteins, and the target site (which usually consists of receptors); only the fraction of the drug that successfully binds to specific receptors will have a pharmacologic effect
Equilibrium
199
What are three barriers that drugs must overcome to reach the target site?
-Physical (route to enter the body)
-Chemical (acidic environment)
-Biological (blood-brain barrier, placental barrier, cell membrane)
200
A biological membrane is the ___ ___, which has a hydrophilic surface with a hydrophobic core
Lipid bilayer
201
_____ is a drug used for rheumatoid arthritis; it has a problem with accumulating and can become toxic because it is designed to inhibit the metabolism
Methotrexate
202
____ ____ is not active until in the body and cannot be used when taking methotrexate
Folic acid
203
An obese person may need a higher dose to have any therapeutic effect, but may have ____ effects later on
Toxic
204
A ___-___ is the amount of time it takes for half of the drug to be removed from blood
Half-life
205
Half-life does not stay constant; it has a direct effect on the availability of the drug to cause _____ effect
Therapeutic
206
If you increase the time between doses, there is more to for ____
Clearance
207
____ is a drug that has reduced clearance; it induced an arrhythmia and extended QT interval; all statins will increase QT
Amantadine
208
The hydrophobic core of biological membranes presents the major barrier to drug ____
Transport
209
What type of drugs can cross the membrane via passive diffusion?
-Nonpolar
-Lipophilic
-Unionized
210
Other larger polar drugs need help via ____ ____ or ____ ____
Facilitated diffusion or active transport
211
The _____ enzyme system is responsible for the metabolism of drugs and there is variability between people in how they absorb drugs
CYP450
212
______ can have toxic effects at large doses due to specific metabolites; within 8-10 hours, it can destroy the liver and cause the need for a transplant
Acetaminophen
213
The rate of diffusion depends on the ____ ____, which is explained by Fick's Law
Concentration gradient
214
Fick's law applies when there are no _____, meaning that the drug is small, unionized, and lipophilic
Complications
215
The drug will diffuse along the concentration gradient until _____ is reached (molecules moving in = those moving out)
Equilibrium
216
____ ____ can occur when an unionized drug crosses the membrane, but due to the conditions of the environment on the other side, the molecule becomes trapped
pH (ion) trapping
217
The amount of trapped drug is determined by the ____ (dissociation constant) of the drug and the pH of the environment
pKa
218
What is an example of a type of drug that participates in ion trapping?
NSAIDs
219
When taken for extended periods of time, NSAIDs can cause ___ ___ due to ion trapping (the pH of the lining of the stomach is less acidic which causes the drug to become ionized and get stuck in the lining of the stomach
Peptic ulcers
220
NSAIDs block _____ which blocks prostaglandin secretion; the charged drug erodes away at the mucosal barrier and causes peptic ulcers (we can give proton pump inhibitors, but then we lose the benefits of having an acidic environment in the stomach
Cyclooxygenase
221
____ ____ might prevent absorption of drugs into the stomach lining, but a downside is that the rest of the drug might not be absorbed as well
Enteric coating
222
The blood-brain barrier has ___ ____ that do not allow most drugs to pass by passive diffusion
Tight junctions
223
Drugs need to be small and lipophilic or use existing ____ ____ in the blood-brain barrier to pass through
Transport proteins
224
Hydrophilic drugs can pass if they target facilitated or active ____ ___ of the blood-brain barrier
Transport proteins
225
We can also infuse drugs directly into the ____ ____ to avoid the blood-brain barrier
Cerebrospinal fluid
226
_____ is the amount of drug available to the target organ
Bioavailability
227
We can also explain bioavailability as the quantity of a drug reaching the systemic ____ divided by the quantity of drug administered (only applied to drugs that reach their target site by systemic circulation
Circulation
228
The ___ ___ ____ is the concentration in the blood the drug needs to be at in order to be effective
Minimal effective concentration
229
The therapeutic window is between the ____ and ____
MTC (minimal toxic concentration) and MEC (minimal effective concentration)
230
When figuring out dosing and timing of doses, we need to see how long it takes for drugs to reach maximal _____; we want to give a second dose at the point when the concentration reaches the minimal effective concentration
Concentration
231
An IV drug is ____ available in the circulation and then distributed to other body compartments and eliminated by first-order kinetics
Immediately
232
Any other route of administration (oral, subcutaneous, IM) demonstrate ____ entry of the drug into the blood and must also take into account the bioavailability of the drug
Slower
233
If a drug has 100% bioavailability, the total amount of drug reaching the systemic circulation will be the same for all routes of drug administration, but non-IV routes will require a longer period od time to reach a maximal _____ of drug in the plasma
Concentration
234
If the bioavailability of an oral, subcutaneous, or IM dosage form is less than 100%, then the dose of the drug would have to be ____ in order for the total amount of drug reaching the systemic circulation to be the same as that of an intravenous dose
Increased
235
____ is the simplest of drug routes, but exposes the drug to harsh acidic and basic environments that can limit absorption
Enteral
236
After absorption, enteral drugs go to the liver where they experience the ____ ____ ____ where the liver enzymes metabolize a fraction of the drug, reducing the drug concentration systemically available
First pass effect
237
With _____ administration of drugs, the drug is delivered directly into the systemic circulation or tissue space
Parenteral
238
Examples of parenteral drug administration routes:
-Subcutaneous
-Intermuscular
-Intervenous
-Intrathecal (into the CNS)
239
Drugs can also be administered into mucus membranes like...
-Sublingual
-Ocular
-Pulmonary
-Nasal
-Rectal
240
Advantages of administrating drugs into mucous membranes:
-Rapid absorption
-Convenience
-Avoid harsh GI 1st pass effect
241
Transdermal drugs are absorbed through the skin; these drugs must be highly ____
Lipophilic
242
Transdermal drugs are good for drugs that need to be ____ and ____ administered
Slowly and continuously
243
The duration of action and peak plasma concentration of a drug can be affected markedly by the drug's ____ ____
Absorption rate
244
What are three factors that affect absorption of drugs?
-Blood flow (greatest effect)
-Surface area
-High/rapid dose
245
If someone has a damaged intestinal tract and poor blood flow, this would cause erratic and non-predictable ____ rates
Absorption
246
The volume of distribution is equal to...
Dose/ (drug concentration in plasma)
247
The volume of distribution can be manipulated to find the ____ ____
Loading dose
248
The loading dose is equal to the (volume of distribution X concentration steady state)/_____
Bioavailability
249
What are factors that affect the volume of distribution?
-Tissue distributed to (muscle, adipose, hepatic)
-Volume or mass of the tissue
-Number of binding sites in tissues
-Protein binding-proteins can bind (inactive) to a large percentage of a drug and only a small percentage of a drug and only a small percentage remains free (active)
250
A drug that has a higher volume of distribution than another equally potent drug will take a ____ initial dose to reach a therapeutic concentration
Higher
251
Coadministration of other drugs can affect the percentage of _____ drug
Bound
252
_____ is one of the most netgatively charged ions, so it can not get across the placenta, making it safe during pregnancy
Heparin
253
A drug that is bound to albumin or other plasma proteins cannot diffuse from the ____ ____ into the surrounding tissues
Vascular space
254
Drugs that do not bind to plasma proteins appreciably diffuse ___ into tissues
Readily
255
Drugs that do not bind to plasma proteins have a ____ level of binding to the site of action and a high rate of elimination
High
256
Drugs that exhibit high levels of binding to plasma proteins require a ____ total plasma drug concentration of free, unbound drug in the circulation (otherwise, only a small fraction of the drug can diffuse into the extravascular space and only a small percentage of the receptors are occupied
High
257
Most drugs are distributed ____ from the systemic circulation to other compartments in the body; this accounts for the sharp decrease in plasma drug concentration after an IV bolus, this decline continues, but not nearly as fast because drug from tissues can diffuse back into blood as drug is eliminated
Rapidly
258
Immediately after intravenous administration of a drug, the plasma concentration rapidly ____ as the drug distributes from the vascular compartment to other body compartments
Declines
259
The ____ plays the biggest role in drug metabolism, but the GI system, lungs, skin, and kidneys also play important roles
Liver
260
Hepatic enzymes can chemically modify a variety of substituents on drug molecules in a process called ____ which can make the drugs inactive or facilitate its elimination
Biotransformation
261
What are the two types of biotransformation?
-Phase I (oxidation/reduction reactions)
-Phase II (conjugation/hydrolysis reactions)
262
Oxidative/reduction reactions are facilitated mostly through the ____; some prodrugs take advantage of this metabolism
CYP450
263
Conjugation/hydrolysis reactions hydrolyze or conjugate a drug to a large polar molecule to inactivate or to enhance _____
Solubility
264
What are the most common substances to add to cause conjugation/hydrolysis reactions?
-Gluconate
-Sulfate
-Glutathione
-Acetate
265
Most drugs are excreted through ____ (most common) or ____ (less common) excretion
Renal; biliary
266
Other than renal and biliary, other drugs can be eliminated in...
-Feces
-Respiratory
-Dermal
267
Renal blood flow makes up ____% of systemic blood flow
25
268
The rate of elimination through the kidneys depends on...
-Filtration
-Secretion
-Reabsorption
269
____ can link onto a metabolite or drug to escort it out of the body
Conjugates
270
Drugs can be filtered at the renal ____
Glomerulus
271
Drugs will then be secreted into the ____ ____ of the kidney
Proximal tubule
272
Drugs can then be reabsorbed from the tubular lumen and transported back into the blood as the ____ ____ develops or excreted in the urine
Concentration gradient
273
The relative balance of filtration, secretion, and reabsorption rates determines the kinetics of drug ____ by the kidney
Elimination
274
What three things can cause a drug to be excreted more rapidly?
-Enhancing blood flow
-Increasing GFR
-Decreasing plasma protein binding
275
Although reabsorption can decrease the elimination rate of a drug, many drugs exhibit ____ ____ in the distal tubule and are therefore efficiently excreted in the urine
pH trapping
276
For drugs that are dependent on the kidney for elimination, compromised renal function can result in ____ plasma drug concentrations, and the dose and frequency of the drug administration must be altered accordingly
Higher
277
Drugs can be reabsorbed because the bile duct enters the GI tract in the ____, and drugs must pass through the small and large intestines before being eliminated
Duodenum
278
With ____ ___, drugs get reabsorbed in the GI and retained in the portal and then system circulation
Enterohepatic circulation
279
Digoxin is renal cleared, but if someone can't get the drug excreted, the concentration would be too high and this could ____ heart rate
Decrease
280
Digitoxin has the same effect as digoxin but it is ____ eliminated instead of renaly eliminated
Hepatically
281
Drug _____ is the parameter that limits the time a drug has at its molecular, cellular, and organ targets
Clearance
282
The rate of elimination of the drug from the body is relative to the ____ of drug in the plasma
Concentration
283
Metabolism and excretion can be thought of as _____ mechanisms
Clearance
284
Most drugs demonstrate ___-____ kinetics; this means that the amount of drug that is eliminated in a given amount of time is directly proportional to the concentration at that time (constant half-life)
First-order
285
Some drugs demonstrate ____-___ kinetics, or saturation; this means that once saturated, the amount of drug eliminated stays constant regardless of the drug concentration in circulation (this can result in toxic or lethal effects)
Zero-order
286
What are two drugs that demonstrate zero-order kinetics?
-Phenytoin
-Ethanol
287
With zero-order kinetics, there is not nearly enough enzymes to ____ half of the drug in a given period of time
Metabolize
288
The half-life of a drug is the amount of time over which the drug concentration in the plasma decreases to ___ of its original value
1/2
289
If the volume of distribution goes up, the half life goes ____
Up
290
If the volume of distribution stays the same and the clearance goes down, the half life will go ____
Up
291
If the volume of distribution goes down and the clearance stays the same, the half life will go ____
Down
292
The half-life of Chloroquine is...
1 week
293
The half-life of amiodarone is...
1 month
294
What are three things that affect volume of distribution?
-Aging: decreased muscle mass and distribution
-Obesity: increased adipose and distribution
-Pathological fluid: increased distribution
295
What are 6 things that can affect the clearance of a drug?
-P450 induction: increased metabolism
-P450 inhibition: decreased metabolism
-Cardiac failure: decreased clearance
-Hepatic failure: decreased clearance
-Renal failure: decreased clearance
296
_____ explains when you get more work capability in a specific CYP family of enzymes (upregulation, on the other hand, is when you get increased production of enzymes)
Induction
297
_____ is when a drug induces its own metabolism
Autoinduction
298
The therapeutic dosing goal is to maintain peak plasma concentrations below the ____ concentration and above the ____ effective concentration
Toxic; minimum
299
____ ____ is reached after 4-5 half-lives for most drugs
Steady state
300
____ is an anticoagulant that may have less risk of bleeding at the correct dose, but at toxic doses, there is a much higher risk of deadly bleeding than with Warfarin
Zaralto
301
Can you just double the dose and increase the time between doses for the same effect?
No (due to half-life principles)
302
The first several doses of a drug are typically _____ as the drug equilibrates to its stead-state concentration
Subtherapeutic
303
If the initial (_____) dose is larger than the maintenance dose, the drug reaches therapeutic concentrations more rapidly
Loading
304
The magnitude of the loading dose is determined by the ____ of the drug
Vd
305
Excessive maintenance doses or dosing frequency results in drug _____ and toxicity
Accumulation
306
Insufficient maintenance doses or dosing frequency results in subtherapeutic ___-___ drug concentrations
Steady-state
307
_____ is the process by which the body alters drugs
Biotransformation
308
Drugs can be changed in what 4 ways?
-Active drug to inactive drug
-Active drug to active or reactive (toxic metabolite)
-Inactive prodrug to active drug
-Unexcretable drug to excretable
309
Metabolites of drugs can be either ____ or ____
Pharmacological or toxicological
310
One example of a conjugation reaction is ____, which takes acetaminophen metabolites out of the body
Glutathione
311
CYP450 reactions involve a set of ____/_____ steps in which an iron moiety in the P450 enzyme acts as an electron carrier to transfer electrons from NADPH to oxygen; the reduced oxygen is then transferred to the drug, resulting in an additional -OH group on the now-oxidized drug
Oxidation/reduction
312
The addition of the -OH group results in increased drug hydrophilicity and an increased rate of drug _____
Excretion
313
_____ ____, a sugar, is the most common group that is conjugated to drugs; the addition of these moieties makes the resulting drug metabolite more hydrophilic and often enhances drug excretion
Glucuronic acid
314
After oral administration, drug is absorbed in the GI and gets transported through the portal vein to the liver; the liver metabolizes drugs and therefore drugs get metabolized before ever reaching the ____ circulation (known as the first pass effect)
Systemic
315
The bioavailability of oral lidocaine is only ___%
3
316
What are examples of key molecules that help facilitate the transport of drugs into the cells?
-P-glycoprotein (key in intestine)
-OATP
-OCT (important in 1st pass effect and statin metabolism)
-OAT (important for renal secretion of antibiotics and NSAIDs)
317
____ of drug-metabolizing enzymes will decrease drug concentration
Induction
318
_____ of drug-metabolizing enzymes will increase drug concentration
Inhibition
319
Rates of biotransformation ___ greatly between patient to patient
Vary
320
____ is the study of genetic variability of drug metabolism
Pharmacogenomics
321
Certain populations have ____ or ____ in their metabolizing enzymes, which can greatly affect drug kinetics for those patients
Polymorphisms or mutations
322
What types of things can cause variability in how people metabolize drugs?
-Slow metabolizers
-Fast metabolizers
-Race and ethnicity
-Age and gender
-Diet and environment
323
___-___ interactions increase when 2 or more drugs are administered that require metabolism via the same enzymes
Drug-drug
324
Two drugs may compete for the same enzyme and reduce the overall ____ of the drugs; this can also increase the concentration of one or both drugs and increase the risk of adverse effects
Metabolism
325
Any disease of the ____ can have an impact of CYP450 enzymes (hepatitis, cirrhosis, cancer)
Liver
326
Cardiac diseases can often _____ metabolism of drugs
Decrease
327
____ disease can increase or decrease the metabolism of drugs
Thyroid
328
Unintended effects of a drug are considered ____ effects or ____ effects
Side/adverse
329
Mechanisms of drug toxicity:
-"On-target": adverse effects, the drug is on the right receptor, but may be wrong concentration, incorrect tissue, or suboptimal kinetics
-"Off-target": adverse effects, drug on the wrong receptor
-Production of toxic metabolites
-Production of a harmful immune response
-Idiosyncratic response
330
Four types of harmful immune responses:
-Type I: reaction mediated by IgE antibodies
-Type II: cytotoxic reaction mediated by IgG or IgM antibodies
-Type III: reaction mediated by immune complexes
-Type IV: delayed reaction mediated by cellular response
331
Drug toxicity occurs when the drug is recognized as foreign by the ____ ____
Immune system
332
Most small molecules can't trigger an immune response, but drugs covalently bind to proteins and then this molecule, known as a ____, can then trigger an immune response
Hapten
333
With an _____ toxicity, there is no obvious mechanism known
Idiosyncratic
334
Drug ____ can happen when the dose isn't kept between the therapeutic efficacy and toxicity
Overdose
335
Drug-drug interactions can be due to...
-Enzyme metabolism
-Activation by both drugs on the same pathway
-Herbs
336
Drug-drug interactions can be either good; you may want to delay metabolism with drugs like ____ and ____
Penicillin and Probenecid
337
Drug-drug interactions can also be bad because sometimes drugs can actively complement each other like how ___ and ____ can cause severe hypotension when taken together
Nitroglycerine and Viagra
338
Pathology of drug toxicity:
-Can be parent drug (unmetabolized)
-Mostly metabolites that react with proteins, DNA, and oxidative defense molecules
-Can be acute or chronic
-May not be known before hand and only found out about after drug has been on the market for a while
339
_____ is a complex process that causes normal cells to transform into a neoplastic cell that expands
Carcinogenesis
340
Carcinogenesis causes ____ damage or mutations
DNA
341
____ is the induction of birth defects in the fetus, usually caused by drugs called teratogens
Teratogenesis
342
What classes of drugs are fine for pregnancy?
A, B, C
343
Class ___ drugs are contraindicated during pregnancy, and an example is ACE inhibitors
X
