Exam 1 Flashcards
1
Q
T/F
Covalent bonds are always stronger than ionic bonds.
A
False
2
Q
Which type of bonds are often irreversible by biological systems?
A
Covalent
3
Q
Van der Waals forces are usually associated with
A
Lipid bonding
4
Q
Disulfide bridges are examples of ______ bonding and are found in ____.
A
Covalent; DNA
5
Q
Electrostatic forces are an example of ____ bonding.
A
Ionic
6
Q
T/F
Hydrogen bonding is weaker than ionic bonds.
A
True
7
Q
T/F
Hydrophobic interactions are generally strong.
A
False; they’re weak
8
Q
What bond/interactions exist between lipophilic drugs and lipid component of membrane/receptor?
A
Hydrophobic
9
Q
Most drugs are _____.
A
Weak bases
10
Q
Diffusion thru cell membrane requires _____.
A
Lipid solubility
11
Q
T/F
Drugs that are proteins are best given by mouth.
A
False; stomach acid denatures proteins
12
Q
Pharmacodynamic examines the effect the ____ has on the ____.
A
How the drug affects the body
13
Q
Pharmacodynamics relates ____ and ____.
A
Drug concentration & its effect.
14
Q
Pharmacokinetics relate ____ and ____.
A
Dose & tissue concentration.
15
Q
T/F
All drugs can be mathematically modeled to predict absorption and metabolism.
A
False
16
Q
Acidic Rx in acidic conditions will….
A
Cross the GI mucosa and enters bloodstream.
17
Q
Basic drugs are best absorbed ____.
A
In lower GI tract; below beginning of SM intestine
18
Q
T/F
Drugs with high affinity always give high effect.
A
False; high affinity does not guarantee high effect. It can bind without producing effects.
19
Q
Affinity
A
Level of attraction between compound and receptor.
20
Q
High affinity + low intrinsic activity
A
Competitive antagonist
must have affinity b/c it binds
little/no intrinsic activity b/c it does not stimulate receptor very well
21
Q
What aspect contributes to higher side effects?
A
Low specificity
22
Q
Low affinity drugs have a (higher/lower) KD than high affinity drugs.
A
Higher
23
Q
High affinity drugs occupy _____ receptors at ____ concentrations.
A
High affinity occupies many receptors at low concentrations.
24
Q
More potent drugs have (higher/lower) EC50.
A
Lower EC50
EC50 = concentration that gives half of max effect
Higher potency = lower [ ] needed
25
Which is more potent?
Which has higher efficacy?
A is more potent (more to the left)
B has higher efficacy (reaches higher point on y axis)
26
(T/F)
The action of an agonist at a receptor can also be a side effect.
True
27
Which part of the neuron generates the action potential?
Axon hillock
28
(T/F)
Drug receptors can be found in the cytoplasm and nuclear envelope.
True
29
Digitalis works by
Inhibiting Na/K/ATPase pump of myocytes
30
What are some types of nonspecific acting drugs?
Carbon Monoxide (binds to Hgb)
Alkalinizing drugs
Acidifying drugs
Mannitol (pulls water into urine)
31
Anesthetics mechanism of action
Most effects are receptor mediated.
Alters membrane fluidity, making it less gelatinous and losing membrane pump function.
32
Aminoglycoside antibiotics act on…
What are some examples of aminoglycoside meds?
The ribosome
Impairs bacterial protein production.
gentamicin, amikacin, tobramycin, neomycin, and streptomycin
33
Neuroleptics act in ____ and are used as ____
The CNS
Tranquilizers
34
(T/F)
All drugs exert their effects via receptor-mediated response.
False
Mannitol, methyl cellulose and dextrans are non-receptor mediated drugs.
35
_____ is/are responsible for transduction of biologic signals.
Receptors
36
(T/F)
Enzymes can be drug receptors.
True
37
What drug acts on nucleic acids?
Actinomycin D
38
Altering the ligand structure will affect its
Affinity and/or intrinsic activity (due to required fit for binding site)
39
Examples of drugs that do not act on receptors
Some anesthetics, hypnotics, and sedatives
Alcohols
Osmotically-active drugs
Acidifying/alkalinizing agents
Antiseptics
Mannitol
Methyl cellulose
Dextrans
40
Nonspecific receptors require ____ drug concentrations to produce effect. Specific receptors require ____ .
Nonspecific receptors need high concentrations of drug for effect (milimoles or moles).
Specific needs only low concentration (nano to mili moles).
41
When active, _____ converts ATP to cAMP.
Adenylate cyclase
42
_____________ function as pores, allowing passage of Na into smooth muscle.
Electrotonic gap junctions
43
(T/F)
When part of a motor unit, a muscle fiber can be stimulated individually.
False; they are stimulated as a unit.
44
Propagation vs. diffusion of a charge down the axon
Diffusion is less effective, as the charge would be reduced once it reaches the terminal.
45
Na coming into the neuron _____ voltage.
Increases
46
When K exits the neuron, it restores the more ____ charge.
Negative
47
Local anesthetics work by
Blocking Na channels in the neuron, preventing transmission of the impulse down the axon.
48
Noncompetitive antagonism on a response curve will show as
Flattening curve as more inhibitor is added
49
Positive allosterism is seen on a response curve as
Left shift, similar to increasing potency
50
What happens in positive allosterism?
The ligand increases receptor affinity for agonist.
51
What happens in negative allosterism?
Inhibitor decreases affinity for agonist to bind to receptor.
Response curve looks similar to non-competitive antagonism; curve flattens as more inhibitor is added.
52
Fat receives less of what supply?
Water and blood
53
(T/F)
The constituents of ICF and ECF are identical, but vary in quantity.
True
54
Proteins are more abundant in the (ICF/ECF).
ICF
55
Which are mostly in ECF? Which are mostly in ICF?
K
Cl
Na
ECF: Na, Cl
ICF: K
56
ECF is regulated by the ____
Kidneys
57
(T/F)
All cells have a nucleus.
False
RBCs do not have a nucleus.
58
What are the most abundant constituents of lipid membranes?
Proteins and phospholipids
59
How does water enter the cell?
Passive diffusion & aquaporins (proteins that fxn as water channels)
60
T/F
Glucose can readily enter the cell.
False
The membrane is nearly impermeable to ions and glucose.
61
T/F
Steroids can readily pass thru the cell membrane.
True
Fat-soluble substances, such as steroids readily cross the membrane.
62
Gases such as O, CO2, & N pass thru the membrane easily via _____
Diffusion
63
Glucose and amino acids enter the cell thru _______.
Facilitated diffusion
64
How can a cell uptake material without it actually passing thru the membrane?
Endocytosis
65
_____ ions are required to eject neurotransmitters via ____.
Calcium
Exocytosis
66
T/F
The goal of the Na/K/ATPase pump is to reduce the number of ions in the ICF.
True
Must balance the large amount of protein and other intracellular stuff
67
Malignant hyperthermia is linked to a defect in the gene encoding proteins for the ______ receptor, the primary receptor for releasing Ca from the sarcoplasmic reticulum.
Ryanodine
68
The Na/K/ATPase pump, pumps Na and K _____ their gradient.
Against
Requires ATP = active transport = against gradient
69
What is the primary transmembrane transporter for drugs across the BBB?
P-glycoprotein
70
When going against the concentration gradient, a _____ is often needed, which requires ____.
Proteins are often needed, which require ATP
71
Genetic defects in aquaporins may cause which diseases?
Congenital cataracts
Nephrogenic diabetes insipidus
72
T/F
The nucleus of an egg cell has 46 chromosomes.
False
All nucleus have 46 chromosomes, except eggs which have 23
73
Histones
Proteins that cover DNA and regulate transcription
74
What passes thru nuclear pores?
Large mlcls, such as proteins, DNA & RNA
75
What does the nucleolus do?
Synthesize ribosomes
76
________ coordinates movement of chromosomes during cell division.
Centrioles
77
What happens to noncoding genes?
They are transcribed to RNA but not translated into proteins.
78
Mitochondria contain…..
Enzymes and substrates of the Krebs cycle and ETC.
79
Oxidative phosphorylation occurs ______.
In the mitochondria
80
Where are the protons generated through the ETC?
Between the 2 lipid membranes of the mitochondria
81
In the ETC, what drives the conversion from ADP to ATP?
The movement of protons back into the mitochondrial matrix through the inner membrane.
moves: intermembrane space --> thru inner membrane --> mitochondrial matrix
82
What enzyme converts ADP to ATP?
ATP synthase
83
T/F
Mitochondria are always inherited from the mother.
True
Sperm have no mitochondria
84
Ribosomes are mainly composed of ____.
RNA
85
T/F
The rough endoplasmic reticulum lacks ribosomes.
False
The smooth ER lacks ribosomes
86
The sarcoplasmic reticulum is a reservoir for ___.
Calcium
87
Proteins made in the rough ER are sent to _______ where they are stored in __________.
Golgi apparatus
Secretory vesicles
88
_____ vesicles continuously secrete their content. ____ vesicles release their content when a trigger signal is received.
Exocytotic vesicles continuously secrete.
Secretory vesicles secrete when signaled.
89
What makes lysosomes?
Golgi apparatus
90
Regulated secretion in anesthesia includes
Neurotransmitter release
91
Studies what the body does to a drug.
Pharmacokinetics
92
Studies what the drug does to the body.
Pharmacodynamics
93
T/F
Different patients can have similar plasma concentrations of a drug but vary in response.
True
94
Chiral
A center with 3-dimensional asymmetry
95
T/F
Enantiomers can be superimposed on each other if rotated correctly.
False
Enantiomers are non-superimposable mirror images
96
A D enantiomer rotates light in which direction? Is it negative or positive?
D config:
Clockwise
+
Dextrorotatory
97
An L enantiomer rotates light in which direction? Is it negative or positive?
L config:
Counterclockwise
-
Levorotatory
98
Racemic mixture
Contains equal parts of two enantiomers. They cancel each other out. No rotation of light.
99
T/F
Enantiomers usually have identical pharmacological activity.
False
They can have different absorption, distribution, potency, clearance and toxicity.
100
T/F
Enantiomers can antagonize each other’s effects.
True
101
T/F
Systemic therapy can be achieved through topical administration.
True
transdermal patches and some creams/ointments can achieve this
102
T/F
Aerosols penetrate completely to the alveoli.
False
Aerosols are used for localized airway and bronchial tissue.
Gaseous and volatile agents penetrate completely to the alveoli.
103
What is one challenge with rectal administration?
There is an unpredictable volume of water, making absorption unpredictable.
104
T/F
First pass metabolism can be avoided with rectal administration.
False
Drugs absorbed in the lower intestines do not go directly to liver before the heart BUT overall the rectal route is unpredictable so do not expect that it will bypass first pass effect
105
Which route of administration has no absorptive phase?
IV
106
Why give a drug through an artery?
give high concentration to a target tissue
chemo & diagnostics
fewer local irritations
107
Epidural injections are made inside ____ but external to ______.
inside the bony spine but external to the dura matter
108
Max volume for IM injection
5 ml
109
Which absorbs faster into systemic circulation? SubQ or IM?
IM
110
Depot injection
Offers slow absorption of the agent over a prolonged period.
Long term therapy with fewer doses.
Usually prepared in oil.
111
Most drugs cross tissue membranes by _____.
simple lipid diffusion
112
What happens with drugs that are too lipid soluble?
Cannot move out of the membrane once it enters
113
Lipid solubility to water solubility
"oil-to-water partition coefficient"
Predicts how well a drug will cross biological membranes.
Measures the [ ] of each.
Octanol is used b/c its similar to biological membranes.
Larger value = more lipid soluble
114
T/F
Amino acids are neutral at biological pH.
False
they are charged
115
Transport molecules are proteins and can be found ____.
in cell membranes
116
Gases and volatile agents must possess ____ to cross from the alveoli into the blood?
some blood & lipid solubility
117
The blood-to-gas partition coefficient uses the _____ of the agent in each component.
partial pressure
118
What is the driving force to bring gases and volatile agents in the blood?
The higher initial partial pressure of a gas/volatile agent at the alveoli is the driving force for the movement of the molecules into the blood until equilibrium is reached.
119
Tissue-to-blood partition coefficient
Relative solubility of a drug in a tissue compared with the blood.
Determines what tissues Rx enters and to what extent.
120
T/F
Tissue-to-blood partition coefficient can be used to determine effect.
False
Some drugs may enter tissue to a small extent but have great effect.
121
An acidic compound is uncharged in the (protonated/unprotonated) form.
Acidic:
uncharged when protonated
122
A basic compound is uncharged in the (protonated/unprotonated) form.
Basic:
uncharged when unprotonated
123
T/F
Procaine has a slower onset than Lidocaine
True
Lidocaine pKa 7.9
Procaine pKa 8.9
With procaine, it takes longer for the ionized molecules to become unionized.
124
A weak base drug in acidic conditions will be (ionized/not ionized).
Ionized
124
T/F
Onset of a drug is affected by pKa.
True
125
T/F
The thickness of a membrane does not affect rate of diffusion.
False
Thicker membrane = slower diffusion
125
T/F
Diffusion rate can increase if there is a large difference in drug concentrations from one side of the membrane to the other.
True
125
T/F
Drugs that are weak bases absorb well in the stomach.
False
126
Solid dosage forms, such as tablets and capsules must undergo ____ before being absorbed.
dissolution
the process by which solid dosage form breaks into individual molecules/small absorbable particles
127
Acid labile
Easily denatured by acid.
Enteric coating used to protect from stomach so it can be dissolved in small intestine.
128
Acidic drugs in acidic conditions will be (ionized/not ionized).
Not ionized
129
Which type of drug will absorb well in the stomach? Weak acid or weak base?
Weak acid drugs absorb well in the stomach.
130
Passive diffusion requires a drug to be ___.
Passive diffusion requires a drug to be in a lipid soluble form.
131
Most drugs are best absorbed in ______.
Most drugs are best absorbed in the small intestine.
132
What feature of the small intestine increases absorption? What feature might make absorption more difficult?
Microvilli increase the surface area for absorption.
The glycocalyx layer keeps very lipid-soluble drugs from entering epithelium (Large octanol-to-buffer values)
133
Epithelial endocytosis
In GI tract, highly lipid-soluble drugs can bind to fats and be absorbed this way as opposed to passive diffusion.
134
Distribution
after absorption, the drug is transported through the body and crosses into tissues
135
The 2 most common proteins to which drug molecules bind are _____. How strong are these bonds?
albumin
a1-acid glycoproteins
weakly bonded
136
T/F
Only free, unbound drug can cross into tissue and act. Drug bound to protein is unavailable to act.
True
137
T/F
Plasma protein binding can act as a reservoir of drug.
True
Protein binding is an equilibrium. Plasma protein binding can slowly supply additional free drug into plasma as drug plasma levels drop d/t distribution or elimination.
138
T/F
As more drug leaves the plasma into tissues or is excreted, protein-bound drug is released into plasma to restore an equilibrium.
True
139
What methods are able to bring drug into tissues?
passive diffusion
transport protein
endocytotic mechanisms
140
The driving forces for diffusional distribution into a tissue are...... (3)
relative solubility in a given tissue
concentration gradient
rate of blood flow to tissue
141
Redistribution
drug moves from one tissue to another in response to equilibrium shifts
142
As plasma concentration of a drug decreases (distribution or elimination), the drug will....
move back into plasma from tissue to establish equilibrium
143
Highly lipophilic anesthetics exit ____ and redistribute to _____ where they are more soluble, which causes short duration of action.
Exit the brain and redistribute to body fat
144
The primary organ of metabolism
liver
others:
kidneys, lungs, skin, GI epithelium, plasma
145
Drugs metabolized to less polar forms may lead to.....
build up and toxicity
146
In order to excrete drugs, they must be metabolized into a more ____ form.
polar
147
Phase I metabolism involves mostly _____ reactions.
oxidation-reduction
148
The four types of reactions in Phase I metabolism
hydroxylation
oxidation
reduction
hydrolysis
149
Drugs may be removed from the body by .....
1. kidneys
2. enter the biliary fluid and excrete thru bile
150
T/F
Phase I metabolism is not enzymatic, so its capacity cannot be oversaturated.
False
Phase I metabolism IS enzymatic, so the enzymes can be overwhelmed (too high of a dose or multiple drugs that work the same enzyme). Risk buildup and toxicity.
151
Induction (metabolism)
A drug may increase the number of active enzymes. Shortens the half-life of a drug metabolized by the affected enzyme. Smoking can do this.
152
The goal of metabolism and elimination is to make the drug.....
more water-soluble or at least less lipid soluble
153
Prodrug
A group is added to the drug itself to aid in absorption. This group is metabolized, leaving the active form of the drug.
154
Which phase of metabolism is known as synthetic?
Phase II
155
Which phase of metabolism is characterized by CYPs? What do these do?
Phase I
The cytochrome P450 enzymes ("mixed function oxidase system").
Have a heme group that helps carry out redox reactions.
Mostly hepatic microsomal enzymes (observed via lab technology) & some mitochondrial P450.
156
Mixed function oxidase system
The CYPs!
Phase 1 metabolism
Have a heme group that helps carry out redox reactions.
Mostly hepatic microsomal enzymes (observed via lab technology) & some mitochondrial P450.
157
Which CYP enzymes metabolize most drugs?
1. CYP3A4/5
2. CYP2D6
3. CYP2C8/9
158
Synthetic reactions
Phase II metabolism
attach large polar groups to the molecule being metabolized
159
In hepatocytes, the enzymes for Phase II metabolism are located...
in the cytoplasm and on smooth ER
160
What is the most common reaction in Phase II? What happens?
Glucuronic acid conjugation/ "Glucuronidation"
A sugar group (uridine diphosphoglucuronic acid, UDPGA) is attached
161
Are sugar groups lipid or water soluble?
water soluble
162
Glutathione conjugation
When does it occur?
What happens?
Phase II metabolism
The tripeptide glutathione is attached (makes more water-soluble), eventually producing a mercapturic acid derivative, which can be excreted.
163
What are the synthetic reactions of Phase II metabolism?(7)
Glucuronic acid conjugation/ "Glucuronidation"
Glutathione conjugation
Sulfate conjugation
Glycine conjugation
Glutamate conjugation
Acylation/acetylation
Nonmicrosomal hydrolysis
164
First pass effect
(oral absorption)
Drugs absorbed thru GI enter hepatic portal system to liver, which may highly metabolize the drug before reaching systemic circulation.
ex: lidocaine
165
Bioavailability
amount of drug that reaches systemic circulation after absorption
166
T/F
All drugs are subject to first pass effect.
False
IV and subL don’t
Oral route is mostly affected.
167
Local anesthetics are (strong/weak) (bases/acids).
Weak bases
168
Some examples of ester drug molecules. How are what enzyme helps to metabolize/inactivate them?
plasma esterase or pseudocholinesterase
Succinylcholine
Etomidate
Procaine
169
In the ____, angiotensin I is converted into angiotensin II by _______.
Angiotensin I is converted to angiotensin II in the lungs by angiotensin-converting enzyme.
170
T/F
Metabolism is a form of drug elimination.
True
Metabolizing a drug into a different form (active or not) is a type of drug elimination.
171
T/F
A drug can still be considered in its original form after metabolism, depending on the changes made.
False
Metabolites are not the same as the original drug. The original drug molecule is no longer present in the body.
172
What is the primary excretory organ?
kidneys
173
What conditions must a drug meet to be easily/readily filtered at the glomerulus?
unbound
MW up to 5000 amu
positively charged
174
Where does the reabsorption occur in the kidney?
proximal and distal regions
175
T/F
Weak acids and weak bases are easily excreted via urine.
True
They are somewhat ionized.
Urinary acidifiers can help enhance the excretion of weak base drugs. Urinary alkalinizers enhance the elimination of weak acid drugs.
176
To enhance excretion of weakly acidic drugs via urine, _______ may be given.
Urine alkalinizers
Urinary acidifiers can help enhance the excretion of weak base drugs. Urinary alkalinizers enhance the elimination of weak acid drugs.
177
T/F
Liver cells can secrete drug molecules and metabolites into bile. This requires active transport carriers.
True
178
T/F
Clearance, measured in volume/time, uses volume of the drug.
False
Volume reflects plasma containing the drug, not just the drug itself.
179
What is the goal of pharmacokinetics?
Quantitatively depict ADME and clearance.
Predict the fate of the drug, dosing, and best route.
180
What makes a drug difficult to predict mathematically?
irreversibly acting drugs
drugs that tend to develop tolerance
drugs that act synergistically
181
Drug synergism versus additive effects
Additive effects will give you a sum of the two different meds.
Synergism will have a higher effect than the sum of the two.
182
T/F
Drugs that follow total body water are difficult to predict mathematically.
False
This attribute makes for easier prediction
183
T/F
Intensity of effect is r/t to the concentration of bound drug in plasma.
False
Free drug
184
Pros of synergism
Less anesthetic required
lower doses of each drug
lower risk of toxicity
Ex: Versed in pre-op working synergistically with anesthetics d/t its CNA depressive effects
185
Fick's Law
larger molecules are more difficult/slower to diffuse/absorb
memory tip: "big Fick energy"
186
T/F
Drugs only need to be lipid soluble to be absorbed.
False
High lipid solubility may prevent a drug from crossing the glycocalyx
187
Why should you not apply topical creams to abraded skin?
It will absorb faster than formulated to do so, creating a higher concentration in plasma. Risk of increased side effects.
188
PO medications take how long for effect?
~40 mins
189
T/F
Topical medications do not require lipid solubility.
False
they do!
190
What drugs absorb best in the stomach? Acids or bases?
Acids
Acidic drug in acid = keeps its proton/H = uncharged = cross lipid bilayer
191
Which will absorb faster: IM or subQ injection? Why?
IM
higher blood flow
192
T/F
Irritating agents can be given IM or subQ, as long as they are given slowly.
False
IV: Irritating drugs are okay if given slowly
IM/subQ: no irritating agents
193
T/F
The blood brain barrier can be bypassed through fluid channels.
False
The BBB does not have fluid channel entry. But we can bypass the BBB using intrathecal drug administration.
194
T/F
Chemo drugs can be given arterially.
True
Doesn't sound like a great idea but it is lol.
Allows targeted treatment of cancerous tissue; remaining drug is diluted in veins.
195
What does the blue dot tell us?
What does the purple highlighted region tell us?
Blue dot = peak of drug concentration
At this point, drug absorption rate = elimination rate
Purple line = elimination is occurring faster than absorption
196
When does elimination begin?
immediately after administration
197
Which order of kinetics removes drug at a constant rate, maxing out the enzymes?
Zero order
Your enzymes: I'm doing the best I can, ma'am. I can go **zero** percent faster.
198
Which order of kinetics removes drugs at a rate dependent on the plasma concentration?
First Order
199
The duration of action is the time spent...
above minimum effective dose
200
Therapeutic window is the area between....
BELOW the minimum effective concentration for adverse response
ABOVE the minimum effective concentration for desired dose
201
Distribution
movement of drug out of plasma to site of action (tissue)
202
T/F
Aqueous channels allow passive diffusion of small, water-soluble drugs.
True
203
Facilitated diffusion vs. Active transport
Facilitated diffusion: moves HI to LO; don't need ATP
Active transport: moves LO to HI; needs ATP
204
T/F
A longer carbon chain increased water solubility.
False
Longer carbon chain = nonpolar = increased lipid solubility & character
205
What is Octanol/buffer partition coeffecient?
measures lipid solubility; higher values = higher lipid solubility
BUT, very high values can inhibit absorption
206
T/F
Very high lipid solubility can inhibit absorption.
True
Cannot cross glycocalyx, a sugar layer outside membrane.
207
In what conditions are basic drugs charged?
Basic drugs are charged in acidic conditions.
208
Basic drugs are unprotonated in which conditions?
basic conditions
209
When are acidic drugs protonated? Are they ionized or unionized in this scenario?
in acidic conditions; nonionized/uncharged
210
T/F
The BBB is an example of a gap junction.
False
Its an example of a tight junction
211
T/F
Amino acids can quickly cross into CSF even though they are charged at body pH.
True
carrier proteins make this possible
212
T/F
Very lipid-soluble drugs accumulate in CSF quickly.
True
they easily go from plasma into the brain
213
Which feature of the lungs allows drugs to quickly move into the alveolar space?
transient fenestrae (fenestrations) make the lungs more permeable
214
What parts of the body feature fenestrations? What significance is this to ADME?
* lungs and capillaries (this includes the gomerulus)
* increases absorption
215
T/F
Eyedrops are considered topical medication.
True
216
Most of the body's water is located (inside/outside) the cells.
inside
217
Most extracellular fluid is located....
in between cells
most ECF is interstitial
218
Blood is mostly composed of...
plasma
219
Drugs that follow _____ tend to distribute well.
Total body water
220
T/F
Metabolites are the inactive form of drugs.
False
Metabolites can be active or inactive.
221
T/F
Drugs can travel to tissue depots, where they exert their effects.
False
Drugs can bind to tissue depots, but they do not act there.
222
T/F
Any change to a drug is considered a metabolite.
True
223
T/F
Protein-drug binding is a strong bond.
False
it is weak; drug can dissociate from protein, especially in response to bound drug to free drug equillibrium
224
Volume of Distribution
What does it tell us?
Common values and their interpretation?
Volume of Distribution: where the drug goes
5 L = stays in plasma
10-12 L = concentrated in ECF
1500 L = moves rapidly out of plasma into the tissues
225
T/F
Volume of distribution should reflect the actual total body fluid volume.
False
Values can far exceed normal body fluid volume
Ex: 1500 L, which means the drug travels out of the vascular compartment
226
What is K1 and K2?
K1 = rate of association
K2 = rate of dissociation
one = ON
two = OFF
K2 --->✌🏼 the drug is peacing out
227
We would expect IV doses to rapidly decrease in concentration because...
IV drugs rapidly mix
228
Which of the following holds drugs the longest?
Vessel rich group
Vessel poor group
Muscles
None of these are correct
vessel poor group holds drugs the longest
229
Once we stop administering the drug, concentrations will first drop in the:
Vessel rich group
Vessel poor group
Muscles
None of these are correct
Vessel rich group
230
Which phase of metabolism focuses on adding groups?
Phase II (synthetic/anabolic)
231
T/F
Most tissues metabolize and eliminate drugs to some degree.
True
232
Primary reactions of Phase I include all of the following except:
Hydration
Hydrolysis
Oxidation
Reduction
Hydration
"Hydro O.R."
Hydrolysis
Oxidation
Reduction
233
Grapefruit juice inhibits which enzyme?
CYP3A4/5
234
Which enzyme metabolizes opioids?
CYP3A4/5
also:
local anesth.
benzos
1/2 of the drugs we handle
235
The ____ group allows CYP enzymes to...
heme
transfer e-'s; perform redox reactions
236
T/F
Hydrolysis usually occurs in the liver.
False
usually in plasma/tissues
237
T/F
Cholinesterase is an example of a CYP enzyme.
False
it is considered a non-cytochrome enzyme
238
CYPs are used in Phase ___ metabolism.
Phase ___ uses many transferase enzymes.
CYPs are phase I
transferases are phase II
239
How does mucomyst reverse Tylenol toxicity?
It repletes the enzyme that metabolizes Tylenol, glutathione
240
What are some limitations of Phase II metabolism?
precursors are required for the synthesis/anabolic reactions
If precursors are exhausted, Phase II metab stops
241
What happens in these reactions?
Is this Phase I or II?
Phase I
242
Is this an oxidation or reduction reaction?
Reduction (phase II)
Nitro group ---> amine group
243
What happens in glucuronidation?
A sugar group is added to a molecule, making it more water-soluble
GLUCurONidation ---> glucose on
244
What groups can be added to a drug to aid in elimination? What phase does this occur in?
Phase II
Can add:
Acetyl (from acetylCoA)
Sulfate (SO4)
Glutathione (amino acid)
Glucose/sugar group
245
In nonmicrosomal hydrolysis, Cholinesterase breaks a _____ bond to form a ____ group.
breaks ester bond
hydroxy group formed (OH)
246
What ultimately decides proper dosing?
Relationship between drug [ ] and effect.
(Pharmacodynamics)
247
What kinda of drug is propanolol?
B-adrenergic antagonist
Proved that receptors exist
248
Do osmotic laxatives act on a receptor?
No
249
Receptor Structures (4)
Can be single protein or multiple protein subunits
Types:
Ligand Gated Ion Channels/Ionophores
Metabophores
G-protein Couples Receptors
Intracellular Receptors (steroid receptors)
250
KA
Association constant
Equals Kon/Koff
Higher value = higher affinity
251
KD
Equilibrium dissociation constant
[ ] @ which 50% of the receptors are occupied
Equal to 1/KA (or: K off/ K on)
252
Brownian Motion
Drug molecules move in this way
random movement displayed by small particles that are suspended in fluids
253
Who dis
Relative affinity constant
shows rate of binding and release
D= drug [ ]
R= free receptor [ ]
DR= [ ] drug-occupied receptors
254
T/F
High-affinity drugs act on the receptor for long periods of time.
False
Even high-affinity drugs may interact with a receptor briefly. Long duration of action is not guaranteed.
255
Intrinsic activity
describes the effect the ligand has when it interacts with the receptor
256
T/F
A low affinity drug may still illicit effects if the intrinsic activity is very high.
False
a drug with a high level of intrinsic activity but low affinity may not elicit much of a response.
257
(In a dose-response curve) Once a critical number of receptors are occupied, increasing the dose will increase the response. The increase in response is described as ______.
logarithmic
258
(In a dose-response curve) What is happening when increasing the dose does not increase the response?
maximal response has been reached; the tissue cannot produce a greater response
259
pH and receptor shape
pH changes can change receptor shape; the receptor protein may be become charged or uncharged
260
Endogenous benzos
endozepines
P.S. they need to get to workin' cuz ya girl is ANXIOUS
261
What does it take to be a good agonist?
good affinity
good intrinsic activity
262
Partial agonists have good affinity & their intrinsic activity is (higher/lower) than the endogenous compound.
Lower
partial agonist:
good affinity
lower instrinsic activity than the endogenous
263
What receptor does buprenorphine act on?
Mu receptor
264
Buprenorphine vs Morphine
Which has higher agonist effect?
Which is the partial agonist?
Morphine
(Buprenorphine is a partial agonist)
265
Fentanyl is about _____ times more potent than morphine at the _____ receptor, making it a superagonist.
100x
Mu opioid receptor
266
Physiologic agonist
definition & example
produce same bodily effects but use a different receptor system & mechanism
Ketamine and propofol are physiologic agonists.
Ketamine acts on NMDA receptors. Propofol acts on GABA(A) receptor complex.
Both produce loss of consciousness.
**NMDA: N-methyl-D-aspartate
267
Coagonists
definition & example
Certain agonists need help of another agonist to produce effects. These are called coagonists.
Glycine & Glutamate
some NMDA receptors must bind with both
**NMDA: N-methyl-D-aspartate
268
Isoproterenol vs. Albuterol
Which is selective?
Which is non-selective?
Isoproterenol: nonselective Beta-adrenergic 1 & 2 agonist
Albuterol: selective Beta 2 agonist
269
Law of Mass Action
greater [ ] of drug around receptor = greater chance receptor will be occupied
Memory tip: If there's a MASSive crowd of drug, there will be ACTION
270
How can we use competitive antagonists and agonists to control effects? Think of Vecuronium, acetylcholine and neostigmine.
Add competitive antagonist to decrease normal effects (vecuronium)
Add agonist to compete away the competitive antagonist.
Scenario:
Vecuronium (competitive antag) blocks acetylcholine (endogenous agonist) @ neuromuscular nicotinic receptor.
Compete away Vec using more agonist.
Neostigmine increases agonist (acetylcholine) by decreasing its metabolism.
271
Which drug can reverse Vecuronium?
Neostigmine
It decreases the metabolism of acetylcholine.
More ACh
ACh competes with Vecuronium (comp. antag)
Reversal of Vecuronium
272
Noncompetitive antagonism can occur by 2 mechanisms. What are they?
1. Binds irreversibly
2. Allosteric inhibition: binds to allosteric site & changes receptor conformation (agonist may no longer be able to bind). This can reverse when [ ] of antagonist decreases.
273
Irreversible inhibitor of alpha adrenergic receptors
phenoxybenzamine
274
T/F
Irreversible antagonism
Antagonistic effects will stop if the concentration of the antagonist decreases.
False
Even if antagonist [ ] around receptor decreases, effects of antagonism will continue.
275
T/F
Allosteric inhibition may stop if concentration of the allosteric antagonist decreases.
True
Unlike irreversible antagonism, it's not necessarily irreversible.
As the concentration of the allosteric antagonist decreases, the
receptor complex may return to its previous conformation
and function normally
276
Example of allosteric inhibition
In certain neuronal pathways in the spinal cord,
-Glycine binds with its receptors to inhibit the pathway
-Allosteric binding of strychnine decreases the affinity of glycine for its site (glycine receptor complex)
-Increased stimulation of the pathway (convulsions)
In this case, strychnine is an allosteric inhibitor.
277
Allosteric potentiation
definition & example
is it agonism or antagonism?
Ligand binds to the allosteric site and increases the affinity of normal agonist for the receptor.
Benzo's and some anesthetics increase GABA's affinity for its receptor.
It's a form of Agonism
278
Inverse agonist vs. antagonist
Inverse agonists:
-appear as if antagonist was given.
-can reverse with competitive antagonist
Cannot reverse antagonist in this way.
279
Partial agonist
gives less effect than normal agonist
appears as if we gave antagonist
280
Agonist/antagonist
definition & example
ligand acts as an agonist at certain receptors, but as an antagonist in others
Nalbuphine:
antagonist @ M-opioid receptor
agonist @ K-opioid receptor
281
Up-regulation
definition and resulting effects
Can increase number of receptors in reponse to lack of normal stimulation.
Ex: Destroy nerve leading to receptor zone on a muscle cell = no ACh.
Cell senses missing ACh & increases number of ACh receptors.
Result:
Cell becomes hypersensitive to agonist
Can be overstimulated
Cell injury/death
282
Down regulation
definition
how does this apply to medication management?
Can decrease number of receptors due to excessive stimulation.
Prolonged use of a medication should not be stopped suddenly as this will cause inadequate receptor stimulation. Taper off.
283
How is down regulation related to tolerance?
Some drugs may cause tolerance by down-regulation.
Less receptors = more drug needed for effect
284
T/F
Morphine tolerance is mainly due to down-regulation.
False
This is not the only way morphine tolerance develops.
285
T/F
The inward rectifier potassium channel is always open.
True
286
Ionophores
Aka Ligand-gated ion channels
5 protein subunit
in active state, span entire cell membrane
ligand binding will open or close (induces opposite state)
may require >1 molecule @ >1 site
respond to NT's and ions
287
Most ligand-gated ion channels are activated by ______ which include...
Neurotransmitters
ACh
glycine
GABA
glutamic acid
serotonin
288
Metabophores
transmembrane receptors
external binding site
internal enzyme component
ligand modifies intracellular enzyme component
take part in conversion of GTP to cGMP
289
Neuromuscular nicotinic ACh receptors are located on ______ muscle.
skeletal
290
Describe the ACh activity at the neuromuscular junction that initiates muscle contractions.
1. ACh released from somatic cholinergic nerve terminals
2. binds to two receptor sites on the nicotinic receptor (postsynaptic membrane)
3. stimulates an allosteric change in the pentameric receptor complex
4. complex opens ion channel
5. Na ions enter the cell
6. This initiates local depolarization, which can initiate muscle contraction
(skeletal muscle @ NMJ)
291
cGMP is a (primary/secondary) messenger. Its purpose is to....
secondary
trigger additional biochemical processes
292
G-protein coupled receptors
large transmembrane protein
7 transmembrane loops
extracellular binding site
detects specific ligands in ECF & initiate intracellular response
293
G-protein coupled receptors vs. metabophore
metabophore: directly link enzymatic fxn to ligand interaction
G protein: initiates series of changes that may eventually lead to control of a specific enzyme
(Metabophores are more direct in their enzymatic control)
294
Which receptor family is the most common type of receptor found on cell membranes?
G-protein coupled receptor family
295
The G-protein complex is located (inside/outside) of the cell membrane.
Inside
296
Activation of the G-protein complex & following events
1. Ligand binds to the extracellular site
2. conformational change triggers substitution of GTP on the G-protein in place of GDP
3. activates the G-protein complex
4. G-protein separates from the transmembrane protein
5. G-protein migrates & interacts with effector macromolecules (activating/inhibiting them)
6. Hydrolysis of G-protein: converts GTP to GDP & deactivates the effector molecule.
7. G-protein complex recombines with the transmembrane protein
Repeats
297
Internal effectors activated/inhibited by G-protein subunits include....
phospholipase C
adenylyl cyclase
phosphodiesterase
298
The Beta-adrengeric receptors are are what type of receptor?
G-protein coupled
note the transmembrane loops (7)
299
Beta-adrenergic receptors must be stimulated by an (antag/agonist) to activate adenylyl cyclase, which catalyzes the conversion of ___ to ___.
Beta-adrenergic receptor + agonist = ATP into cAMP
300
Where are steroid receptors?
intracellular
301
How do steroids enter the cell?
passive diffusion
302
What happens once steroids enter the cell?
1. binds to a specific inactive protein complex.
2. inactivating protein dissociates from the complex.
3. Complex now active!
4. activated complex goes to nucleus
5. forms a dimer with another activate receptor complex.
6. binds to specific regions of DNA.
7. increase/decrease transcription of specific genes into RNA for translation into proteins.
303
receptor-mediated ion channel Interactions vs. steroid
receptor-induced effects
ion channel interactions: nearly instantaneous in response
steroid receptor–induced effects: slower &
last longer due to the lag time for protein synthesis
304
T/F
Without energy, transport proteins cannot work.
False
transporters may or may not need energy
305
SSRI's, such as fluoxetine, act on the transport protein ____, which is responsible for serotonin reuptake.
SERT
(SERT sounds similar to SERoTonin)
306
Ammonium chloride (increases/decreases) the pH of urine.
decreases
307
Ammonium chloride can increase elimination of (acidic/basic) compounds.
basic
it makes urine more acidic, and helps excrete the basic
308
General anesthetics appear to elicit their effects by...
still unclear but....
increasing inhibitory signals or decreasing excitatory signals in the brain &/or spinal cord
physical properties + multiple receptor zone effects
309
Agents that work on the ______ complex increase inhibitory pathways.
GABA(A) ionophoric
complex.
310
The GABA(A) ionophoric
complex opens and allows _____ ions to enter the cell.
Cl
311
How do cells become hyperpolarized?
increasing negative charge (ex: chloride ion influx) lowers the local intracellular voltage
makes cell more resistant to depolarization.
312
Agents that allosterically potentiate GABA binding to its receptor site
Many of the general anesthetic agents including:
barbiturates
propofol
etomidate
isoflurane
desflurane
sevoflurane
313
Influx of Cl- into the cell causes increased (excitatory/inhibitory) activity.
inhibitory
314
Non-neuronal receptors
located throughout body cells (ex – ADP receptors on platelets, insulin receptors, LDL receptors)
315
Atropine
what does it do?
agonist or antagonist?
Atropine blocks muscarinic ACh receptors
antagonist
316
Whats going on here?
potentiation
or
positive allosterism
317
noncompetitive antagonsim
or
negative allosterism
318
Total body water accounts for __% of body mass.
60%
319
Intracellular fluids accounts for ___% of body mass.
40%
320
Extracellular fluid accounts for ___% of body mass.
20%
321
Interstitial fluid accounts for __% of body mass.
15%
322
The body contains about ___L of plasma.
3
323
T/F
Sublingual drugs are subject to first pass effect.
False
Oral route is though
sublingual or buccal route of administration permits a rapid onset of drug effect because this blood bypasses the liver
324
What kind of drug is vecuronium?
competitive antagonist @ neuromuscular nicotinic receptors (blocks ACh)
325
Acetylcholine released from _____ nerve terminals at the synapse binds to two receptor sites on the ____ receptor.
somatic cholinergic
nicotinic
326
Neuromuscular nicotinic acetylcholine receptor1 is located on _____ muscle at the neuromuscular junction.
skeletal
327
Which anesthetic agents appear to act by decreasing excitatory signaling through NMDA glutamate receptors and nicotinic acetylcholine receptors in the brain or spinal cord?
nitrous oxide, xenon, ketamine
328
2 receptors that ACh binds to
muscarinic (G-protein coupled)
nicotinic (ionotropic)
329
Drugs administered into the proximal rectum are absorbed into the ___ veins and transported via the portal venous system to the liver.
superior hemorrhoidal
330
Butorphanol is a (full/partial) agonist.
partial
331
Partial agonist + full agonist = what effect?
Example
partial reversal of agonist
Butorphanol (partial) + Fentanyl (full) = Partial reversal of Fentanyl
High dose opioid users may withdraw!
332
Protein binding
Acidic drugs bind to ___. Basic drugs bind to ___.
acidic --> albumin
basic --> alpha 1 glycoprotein
333
T/F
The G-protein coupled receptor is a muscarinic receptor.
True
G-protein = muscarinic
ionotropic= nicotinic
334
Ka
dissociation constant of an acid
335
uptake of particulate matter (bacteria, damaged cells) by cells
phagocytosis
336
uptake of materials in solution in the extracellular fluid
pinocytosis
337
How can enterohepatic recycling affect half-life?
can greatly extend half life
"attached glucuronide group is removed, releasing the original drug molecule. If this molecule is reabsorbed into the body, the duration of effect of the drug may be increased "
338
