Pharmacodynamics Flashcards
(171 cards)
1
Q
What is pharmacodynamics?
A
How a drug affects the body. There are two types: physiological PD and molecular PD.
2
Q
What does physiological pharmacodynamics entail?
A
Includes agonists, antagonists, partial agonist, efficacy, potency, and side effects.
3
Q
What does molecular pharmacodynamics entail?
A
Includes receptor types, affinity, competitive and non-competitive antagonists, inverse agonists, and allosteric inhibitors.
4
Q
The following graph represents what?
A
The pharmacodynamic effect of insulin on glucose after eating high carb meal.
5
Q
What is the ED50?
A
The halfway point of dose-response curves. It is also the effective dose that gives 50% of the response.
6
Q
What does the curved line on a dose-response curve mean?
A
The bottom line near the x-axis is the lowest dose of the drug that exerts a tiny bit of effect. The top part of the line that has flattened out again is where there is no longer a stronger effect even when more drug is added.
7
Q
What is efficacy?
A
Efficacy describes the maximal level of response a drug can produce.
8
Q
Which drug has the least efficacy, and which drug has the most?
A
The blue line is the least efficacious, and the red line is the most efficacious.
9
Q
What is potency?
A
The potency of a drug reflects its affinity for its receptor.
10
Q
Which drug is more potent? And which one has the lower ED 50?
A
Drug A is more potent than drug B. Drug A has a lower ED50 than drug B.
11
Q
What are partial agonists?
A
These drugs bind and activate a receptor but only have partial efficacy at the receptor.
12
Q
This dose-response curve shows a curve of a ______ agonist and a _______ agonist.
A
Full; partial
13
Q
How is the therapeutic index found in graphs and mathematically?
A
In a graph, the therapeutic index is the range between the ED50 and LD50 (lethal dose). Mathematically, TI can be calculated by dividing the LD50 log conc by the ED50 log conc.
14
Q
What is the maximum tolerated dose (MTD)?
A
How much drug can be given before intolerable side effects take place.
15
Q
What is an agonist?
A
A drug that binds and produces a signal.
16
Q
What are the dose-response curves for a full agonist, partial agonist, antagonist, and inverse agonist?
A
Full agonist is the full curve
Partial agonist is partial curve
Antagonist is a straight line
inverse agonist is negative curve
17
Q
How does typical agonist binding work?
A
Agonist binds to a receptor which causes downstream signalling which can eventually target proteins inside the cell called effectors. Ultimate targets of receptors tend to be transcription factors which instill long-term change.
18
Q
A drug HB increases heartrate by 20% over baseline when the dose is 200 mg. But a new drug called HBX increases heart rate by 20% in a 50 mg dose. Which of the following is changed in HBX? (ED50, efficacy, or side effects)
A
ED50
19
Q
A drug HB increases heartrate by 20% over baseline when the dose is 200 mg. But a new drug called HBX increases heart rate by 20% in a 50 mg dose. Which of the following is HBX? (agonist, effector, partial agonist, or receptor).
A
Agonist
20
Q
A drug HB increases heart rate by 20% over baseline when the dose is 200 mg. But a new drug called HBY increases the heart rate by 8% in a 50 mg dose- its ED50. Which of the following is HBY? (agonist, effector, partial agonist, receptor).
A
Partial agonist
21
Q
A drug HB increases heartrate by 20% over baseline when the dose is 200 mg. But a new drug called HBY increases the heart rate by 8% in a 50 mg dose- its ED50. What is the relationship between HBY relative to HB? (higher, lower, or the same affinity).
A
?
22
Q
What is Kd?
A
Kd is the equilibrium dissociation constant. It is that unique concentration of a drug that will occupy 50% of the total receptor population. Affinity and Kd are often used interchangeably.
23
Q
How are affinity and Kd related?
A
If affinity decreases than Kd increases. The bigger the Kd, the less likely the drug-receptor dimer complex forms.
If affinity increases, than Kd decreases. The lower the Kd, the more likely the drug-receptor dimer complex forms.
24
Q
What does K1 and K-1 mean in the affinity equation?
A
K1 is the rate at which the drug binds/associates with the receptor.
K-1 is the ease at which the drug dissociates from its receptor.
25
What are the drivers of drug affinity?
Different bonding types (ionic bonds, hydrogen bonds, van der waals forces, etc)
26
In classic occupation theory, the _______ equals the _________.
ED50; Kd
27
Erbitux/cetuximab is an antibdoy that binds and inhibits epidermal growth factor receptor (EGFR). Erbitux has a Kd of 0.2 nM. it has few cross-reactions with other kinases. Erlotinib is a small molecule that inhibits EGR. It has a Kd of 0.4 microM. It has a Kd for other kinases in 0.09-0.4 microM range. Which drugs binds EGFR with greater affinity?
Erbitux binds EGFR with higher affinity because its Kd value is smaller than that of Erlotinib.
28
What are antagonists?
Antagonist binds to receptors and deactivates it. It also blocks the agonist from working.
29
What are competitive antagonists?
Antagonists that bind in a reversbile manner to the receptor and prevent agonist action.
30
What happens graphically when an antagonist is introduced to ligand A and its receptor?
Adding antagonist will shift the curve to the right. Adding antagonist requires a greater concentration of ligand to achieve an effect.
31
What is IC50?
IC50 is the inhibitor concentration decreasing the activity of the agonist by half.
32
According to the graph, which ligand is the full agonist? The partial agonist? and the antagonist?
Isoproterenol is the full agonist.
Clenbuterol is the partial agonist.
Propronolol is the antagonist.
33
What does ibuprofen target?
Ibuprofen targets the activity of cyclooxygenase I and II (COX I and II). These enzymes cleave arachidonic acid to prostaglandins.
34
What is Ki?
Ki is the affinity of the inhibitor for the receptor. Low Ki means a more potent inhibitor while high Ki means less potent inhibitor.
35
How do you calculate the concentration of an agonist required to produce an effect in the presence of a competitive antagonist?
C'/C= 1 + ([I]/Ki)
36
What are two important features of a curve to describe enzymatic reactions?
Vmax and Km
37
What is Vmax?
Maximum velocity of an enzymatic reaction.
38
What is Km?
Substrate concentration when the Vmax is at half.
39
Tofacitinib (Xeljanz) inhibited the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50 of 406, 56, and 1377 nM. Does that mean tofacitinib is more or less active against 1/3 or 2/2?
The lower the IC50, the more potent the drug. This means that tofacitinib is more active against JAK1/JAK3.
40
What happens to Vmax and Km if a non-competitive inhibitor is added?
Vmax is decreased while Km stays the same. Vmax decreases because the binding of non-competitive inhibitors lowers the concentration of binding sites. Km stays the same because the binding site for the substrate is still available for binding.
41
What happens to Vmax and Km if an uncompetitive inhibitor is added?
Km stays the same, but Vmax is lower.
42
What happens to Vmax and Km if a competitive inhibitor is added?
Vmax stays the same while Km is increased. Km is increased because more substrate will be needed to achieve 1/2 vmax. Eventually we can reach the same Vmax.
43
What are irreversible receptor antagonists?
These bind to receptors, and when they do in the presence of an agonist, a blockade cannot be overcome due to the loss of active receptors.
44
What are the neurons called that produce acetylcholine (Ach)?
Cholinergic neurons
45
What is acetylcholine synthesized from?
Acetyl CoA and Coline
46
What is the function of the bacteria Clostridium Botulinum?
Blocks release of Ach by blocking the pre-synaptic release into the synaptic cleft. This bacteria is used in botox, which typically stays localized.
47
What is the interaction between tetanus and Ach?
Tetanus toxin is produced by Clostridium Tetani, and it blocks the release of Ach from a pre-synaptic area like botox.
48
What is Acetylcholine broken down into?
Acetate and Choline
49
What enzyme breaks down Acetylcholine?
Acetylcholinesterase
50
What are the main functions of Acetylcholine?
Salivation, tears, urination, defecation, and decreased heartbeat
51
What is the function of a drug like Donepezil (Aracept)?
Selectively and reversibly inhibits the acetylcholinesterase enzyme that typically breaks down Ach. Used to treat Parkinson's and Alziehmers.
52
What is the shorthand for acetylcholine/ cholinergic receptors?
AchR
53
What were the symptoms of Alexei Navalny, who was poisoned with a drug called Novichok?
Novichok blocks the breakdown of Ach, so it accumulates in the body. This causes extreme GIT cramping, diarrhea, salivation, and tears.
54
What is one receptor type that acetylcholine can bind to?
Acetylcholine/ cholenergic receptors
55
What are the two types of acetylcholine/cholinergic receptors?
1. Metabotropic muscarinic receptors
2. Ionotropic nicotinic receptors
56
How does the ionotropic nicotinic receptors work?
The nAchR is also an ion channel for the flow of K+ and Na+. In the closed state, there is a higher concentration of Na+ extracellularly and, therefore, lower inside the cell. There is higher K+ intracellularly and less outside the cell. When the agonist (Ach) binds, the receptor opens, and Na+ flows into the cell while K+ flows out of the cell.
Na+ flow creates a membrane potential that is the basis of sense, learning, and memory.
57
Are different acetylcholine receptors fast or slow?
These receptors are fast! Milliseconds type fast
58
What is the effect of black widow toxin on Ach release?
Black widow spider toxin induces the release of Ach increasing overall body concentrations.
59
Can the ionotropic nicotinic receptor only accept Ach as a ligand?
No, the nAchR has several other binding sites for other types of ligands.
60
Which of the inhibitors, A or B, is a competitive inhibitor?
B is the competitive inhibitor.
61
Imagine that someone develops a new version of ibuprofen called X-1000 and has a Ki 1000 times lowers than the current ibuprofen. Does that mean the new drug is more active or less active than the old one?
A lower Ki means a potent inhibitor so the new drug, X-1000, is more active than the old one.
62
Imagine that someone develops a new version of ibuprofen called X-1000 and has a Ki 1000 times lowers than the current ibuprofen. If someone mistook X-1000 for the original, could they reverse the effect by taking the same dose of the original ibuprofen?
No, because X-1000 is still more potent than the original ibuprofen and would beat out the original in its ability to be more potent.
63
Imagine someone was given a drug that inhibited Ach breakdown. What would be the effect?
They would have excess Ach hanging out in the synaptic cleft that would continue to bind and cause an increase in crying, urination, hypersalivation, defecation, and decrease heart rate.
64
What is the main medication used as an inhibitor of the Ach receptor?
Atropine
65
What can bind and inhibit the Ach receptor?
Glucocorticoids
66
Nicotine can affect nAchR's everywhere including post-synaptically (__________) and pre-synaptically (_________).
altering signalling; increasing Ach release
67
Why does smoking make people happy?
Both nicotine and ethanol stimulate dopamine release which sets of the dopamine reward pathway.
68
What is desensitization?
This is when receptors often stop responding to ligands over time. It can be due to conformational change, receptors being internalized, or degraded.
69
What is the drug Chantix/ Varenicline?
High-affinity partial agonist of the nAchR. This medication works by being so strong that if a cigarette is smoked after this drug is taken, there will be no effect from the nicotine because it is not as strong.
70
What would be the use of a low-affinity partial agonist of the nAchR?
It would be used for those trying to quit smoking.
71
In nicotine poisoning, is the pathway depressed or overstimulated?
It is overstimulated
72
What do you think would be the effect of botulinum toxin? Would an acetylcholinesterase inhibitor make things better or worse?
Botulinum toxin blocks the release of Ach into the synaptic cleft. It seems like an inhibitor of the enzyme that breaks it down would be a good idea so any Ach left over before the bite could still be able to bind to its receptors.
73
What are the symptoms of nicotine poisoning?
Red hot skin, drolling, dizziness, nausea, respiratory depression, headaches, vomiting, low blood pressure, and possible seizures.
74
What type of receptor is the acetylcholine muscarinic receptor?
A G-protein coupled receptor
75
What are the symptoms of muscarinic receptor overstimulation?
SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI cramps, and emesis
76
What are the symptoms of nicotinic receptor overstimulation?
WTF: weakness, twitching, fasciculation, high blood pressure, and paralysis
77
How many types of mAchR are there?
There are 5. They all can bind Ach and are all GPCRs.
78
What are G-protein coupled receptors?
These receptors span the cell membrane. It has an outside part that ligands bind to that converts it to the 'on' state, where the alpha subunit releases GDP and GTP replaces it.
79
The M1, M3, and M5 mAchR all have subunit ________ and are ________.
Gq; excitatory
80
The M2 and M4 mAchr all have subunit ________ and are _________.
Gi; inhibitory
81
Ach triggers ________________ to cleave PI-4,5-biphosphate into __________ and _____________.
Phospholipase C
1,4,5-triphosphate (IP3); diacylglycerol
82
What is the function of IP3 and diacylglycerol?
IP3 raises intracellular Ca+ levels by releasing it from the lumen of the ER. Ca+ then activates protein kinase C.
83
What is cAMP?
This is cyclic adenosine monophosphate.
84
What is the simplest target of cAMP?
cAMP-dependent protein kinase (PKA). It activates the transcription factor cAMP- dependent response element binding protein (CREB), which is important in learning and memory.
85
Is cAMP stable or unstable?
It is unstable and metabolized back to AMP.
86
What is the cAMP downstream pathway?
Adenylyl cyclase is activated by a g-protein coupled receptor, which converts ATP to cAMP. cAMP targets PKA, which can phosphorylate CREB, a DNA element that binds to drive transcription and is important in cognition.
87
What enzyme break cAMP down into ATP?
Cyclic AMP phosphodiasterase
88
What type of receptor is involved in vision?
G-protein coupled receptors
89
What are two ways to inactivate G-protein coupled receptors?
1. Phosphorylation by a kinase that blocks interactions with G proteins
2. Arrestin binds and blocks signalling and promotes the internalization of the receptor.
90
How are GCPRs and ion channels different?
GCPRs act through intermediates while ion channels have rapid responses.
91
Between the nAchR and mAchR receptors, which is the fastest?
nAchR is faster because it is an ion channel
92
Between the nAchR and mAchR receptors, which gets the pyramid scheme award for the most amplified signal?
mAchR.
93
Anti-muscarinics are linked to ________ loss.
Cognitive
94
How does caffeine work in the brain?
As we stay awake, adenosine enters the synapse and binds to GPCR called A1. Stimulation gradually decreases wakefulness. Caffeine antagonizes adenosine binding to A1, which stimulates the central nervous system.
95
What effect does caffeine have on smooth muscle?
Vasoconstriction of vessels increases blood pressure but causes vasodilation in smooth muscles in the gut.
96
How does cannabinoid receptor signalling work?
THC binds to GPCR called the CB1 receptor.
97
Anandamide binds to CB1 with 78 nM affinity. THC binds to CB1 with 10nM affinity and CB2 at 24 nM. EGCG is in green tea and binds with a 34 uM affinity. Which of these ligands has the greatest affinity?
The THC that binds to CB1
98
Someone is taking an antagonist of the nicotine acetylcholine receptor. Which of the following responses might they have? (elevated blood pressure, muscle relaxation, rapid heartbeat, or twitching)
Muscle Relaxation
99
Which of the following conditions might someone have if they are taking an antagonist of the M1 muscarinic receptor? (slow heartbeat, seasonal allergies, constipation, motion sickness).
Motion sickness
100
What is a tyrosine kinase receptor?
Span the plasma membrane. Has two distinct domains; extracellular domain for ligand binding and intracellular kinase domain for enzymatic reaction.
101
What is a kinase in the most basic sense?
Kinase are enzymes that phosphorylate by taking a phosphate from ATP.
102
What is EGFR? What is the ligand that binds it?
Epidermal Growth Factor Receptor. EGF/ epidermal growth factor binds that receptor.
103
The EGFR signalling system is important in ________ and ___________.
Cancer; development
104
Describe the EGFR signalling pathway.
EGF binds, and the extracellular domain undergoes a conformational change where the receptor folds around the ligand. Another EGFR receptor bound to EGF homodimerizes with the original to become a single compound. Then the intracellular kinase domain becomes active, and the dimer pair phosphorylates each other on tyrosine. These new phosph-tyrosines are docking sites for other proteins. This is a growth-promoting pathway. Docked proteins can trigger downstream signalling or cause EGFR to be endocytosed back into the cell through the protein called clathrin. Once endocytosed, the kinase intracellular end is now the extracellular portion which can keep signalling.
105
What type of receptor is EGFR?
Tyrosine kinase receptor
106
What are the main functions of EGF?
Proliferation, survival, and gene expression
107
What is the drug Cetuximab?
A drug that binds the extracellular domain on EGR prevents the binding of EGF—preventing binding stops dimerization and activation.
108
What is the classification of the drug Cetuximab?
It is a monoclonal antibody.
109
How does a lab produce monoclonal antibodies?
An antigen is injected into a mouse, so it produces an antibody. The plasma cells that make the antibodies in the mice are extracted and squished and then combined with tumour cells to form a hybridoma. Hybridomas are immortal and continue producing the identical monoclonal antibody from the original antibody from the mouse.
110
What does the monoclonal antibody ending -omab mean?
Murine monoclonal antibody (0% human)
111
What does the monoclonal antibody ending -ximab mean?
Chimeric monoclonal antibody (65% human)
112
What does the monoclonal antibody ending -zumab mean?
Humanized monoclonal antibody (90% human)
113
What does the monoclonal antibody ending -umab mean?
Fully human monoclonal antibody (100% human)
114
What type of monoclonal antibody is Cetuximab?
Chimeric monoclonal antibody
115
Why is cancer so hard to treat?
Let's say a tumor is growing due to EGFR being highly expressed. The tumor continues to grow when EGF binds. Tumor is treated with Cetaximub, and growth stops. Over time though, selective pressure for mutation is the RAS system can reactivate protein, and the tumor continues to grow even in the presence of Cetuximab. MET is another tyrosine kinase receptor for growth signalling when EGFR is disabled.
116
How does the insulin signalling pathway work?
Insulin receptor autophosphorylates itself, creating binding sites for downstream proteins that are then also phosphorylated. The RAS and AKT pathways are activated. AKT activation transports the GLUT4 transporter to the cell membrane, where glucose is brought into the cell.
117
What type of receptor is the insulin receptor?
Disulfide cross-linked receptor
118
You are developing an opiate called OPI. It has no effect until a dose of 10 micrograms is used, and OPI has no further effects at doses above 100 micrograms. The midpoint of the curve is 50 micrograms. What is the term for the 100 microgram dose? (efficacy, IC50, KD, potency)
Efficacy
119
You are developing an opiate called OPI. It has no effect until a dose of 10 micrograms is used, and OPI has no further effects at doses above 100 micrograms. The midpoint of the curve is 50 micrograms. You prepare a second compound called OPI-X. It has the same max effect as OPI, but the minimum dose produces a measurable effect is 1 microgram, and the midpoint of the curve is 8 micrograms. What measure of OPI-X is greater than the original OPI? (antagonism, efficacy, KD, potency)
Potency
120
In clinical testing, the midpoint of OPI-X activity in relieving pain is at an 8-microgram dose. In animals, we know that the analogous lethal dose is 400 micrograms. What term is represented by the value of 400/8=50? (efficacy, maximum tolerated dose, potency, therapeutic index)
Theraputic index
121
You are working in a lab testing the hypothesis that a nerve growth factor called BDNK binds to a receptor called TrkA, which activates the receptor to signal through a kinase called AKT, which activates a transcription factor called forkhead. You treat cells that express TrkA with an antibody to TrkA that blocks BDNF binding. Then you add BDNF. What would happen to the activity of AKT?
The activity of AKT will be inhibited since BDNF cannot bind to TrkA.
122
Epinephrine binds to its receptors through three types of bonds. Nitrogen from an ionic bond with amino acids on the receptor. Two hydroxyl groups from hydrogen bond with amino acids on the receptor, and the phenyl group forms van der Waals interactions with a receptor amino acid. The chemistry is not important, but the bonds are. If you made a new form of epinephrine that lacked nitrogen, how would the Kd of this new ligand change for the same receptor?
The affinity for its receptor would decrease so the KD value would increase.
123
For an agonist and receptor system, the formation of a complex is reflected by their concentration like this: Which of the following represents the Kd?
K-1/K1
124
Epinephrine, when administered intravenously, can produce an increase in heart rate of 300 bpm (relative to a resting pulse of 70 bpm), the maximal response obtainable. A second drug XYZ causes a heart rate of 70 bpm, while the combination of epinephrine and XYZ is 70 bpm. Which of the following best categorizes drug XYZ? (partial agonist, competitive antagonist, full agonist, inverse agonist)
Competitive antagonist
125
Epinephrine, when administered intravenously, can produce an increase in heart rate of 300 bpm (relative to a resting pulse of 70 bpm), the maximal response obtainable. A second drug ABC causes a heart rate of 50 bpm, while the combination of the epinephrine plus ABC is 50 bpm. Which is the following represents drug ABC?
Inverse agonist
126
Referring figure 1 shows a graph of a dose-response curve of agonist A1. Draw a curve for a related drug that has 50% of the efficacy of A1 with 2 x greater affinity of A1 for the same receptor.
127
Refer to figure 3. The blue line shows an increase in the rate of an enzymatic reaction when increasing doses of a substrate are added. The dashed red line shows the 50% point of the blue curve. Plot a line analogous to the solid line indicating the same reaction if a non-competitive inhibitor was added.
Non-competitive inhibitors will decrease Vmax while not affecting the Km
128
How does nicotine function at synapses?
It activates an ionic channel
129
Which of the following best explains why smoking is addictive?
Nicotine increases dopamine release
130
What are type 1 nuclear receptors?
Steriod receptors
131
How does ligand binding work with steroid receptors?
In the resting state, the steroid receptor is bound by a chaperone in the cytoplasm. Ligand passes through the cell membrane and into the cytoplasm, where it binds the receptor. The new ligand/receptor complex separates from the chaperone and moves into the nuclear membrane. It will then bind to the specific sequence of DNA to act as a transcription factor.
132
How does the timing of a steroid receptor event compare with the tyrosine kinase receptor event?
This process of altering gene expression takes much longer than the tyrosine kinase phosphorylation effects.
133
How does estrogen binding to its steroid receptor work?
Estrogen binds as all steroids do to steroid receptors. Estrogen and its receptor acting as a transcription factor can turn many genes off and on.
134
What is Ethinyl estradiol?
Typically used birth control acting as an agonist for the estrogen receptor.
135
What is Tamoxifen?
Common antagonist for the estrogen receptor used for treating estrogen-dependent breast cancer.
136
What type of receptors are type 2 nuclear receptors?
Thyroid receptors
137
How do thyroid receptors signal?
Thyroid receptors stay bound to specific DNA sequences. When there is no ligand present, it binds a corepressor protein. When a ligand binds, the receptor switches partners to a coactivator and turns ON gene expression.
138
What is the drug use for Levothyroxine?
Used to treat low thyroid because the drug can replace the thyroid hormone the body is not making.
139
What are the symptoms and diagnosing criteria for major depressive disorder?
SIGECAPS
S- sleep disturbances
I- Interest decreased
G- Guilt
E- Energy decreased
C- concentration problems
A- appetite/ weight changes
P- Psychomotor agitation
S- Suicidial ideations
Symptoms are 2 weeks of depressed mood followed by loss of interest plus 3 of the following; fatigue, changes in weight, sleep, motor skills, guilt, loss of concentration, and thoughts of suicide.
140
What are the 3 types of monoamines?
Dopamine, norepinephrine, and serotonin
141
What name is synonymous with serotonin?
5-HT
142
Most serotonin receptors are ___________, but 5-HT3 is an ___________ channel that opens in response to serotonin binding.
GPCR; ion
143
The serotonin transporter removes serotonin from synaptic space where the enzyme ________ __________ degrades it.
Monoamine Oxidase
144
What are monoamine oxidase inhibitors (MAO inhibitors)?
They stop the breakdown of all monoamines by inhibiting the enzyme that degrades them.
145
What are monoamine oxidase inhibitors (MAO inhibitors)?
They stop the breakdown of all monoamines by inhibiting the enzyme that degrades them.
146
What are tricyclic antidepressants?
They inhibit all monoamine transporters. They stop serotonin reuptake as well as dopamine and norepinephrine.
147
What kind of drug is Amitriptyline?
Tricyclic Antidepressant
148
What other receptors do tricyclic antidepressants inhibit and activate?
Adrenergic receptors (catecholamines bind) are activated, muscarinic receptors (Ach bind) are inhibited, and histamine H1 receptor is inhibited (histamine binds).
149
What effects do activation of adrenergic receptors and inhibition of muscarinic and histamine receptors have on the body?
Inhibition of muscarinic receptors causes cramps and nausea. Inhibiting histamine receptors causes drowsiness. Activating adrenergic receptors causes increased blood pressure.
150
What are SSRIs?
Selective Serotonin Reuptake Inhibitors
151
What is the function of SSRIs?
Inhibit the reuptake of serotonin by acting on the serotonin transporter.
152
Where are the majority of serotonin receptors in the body?
90% in the GIT, 8% in platelets and 1-2% in CNS.
153
What does serotonin regulate?
Mood, sleep, cognition, and appetite
154
What type of drug is Zoloft/Sertraline?
SSRI. This drug also has no dose-response benefit. It has NO affinity for muscarinic, adrenergic, and histamine receptors.
155
Why do SSRIs have many side effects even though it only targets one type of transporter?
It has many side effects because there are serotonin receptors all over the body that will be affected by the intake of an SSRI.
156
Based on the picture, which of these inhibitors is more active at inhibiting dopamine reuptake?
Sertraline. This is because it has the lowest Ki value meaning it has the highest affinity to inhibit the receptor.
157
Why does it take a long time for SSRIs to work?
It is hypothesized that antidepressants increase serotonin levels which elevates brain-derived neurotrophic factor (BDNF), which increases neuronal branching and survival. Leads to better neuronal health.
158
Someone in your profession wants to treat depression with a monoclonal antibody that inhibits the serotonin transporter SLC6A4 with a high affinity and efficacy. What would be the pros and cons of this versus sertraline?
Monoclonal antibodies inhibiting the serotonin transporter would cause increased levels of serotonin in the synapse, which would cause increased binding and serotonin overload.
159
What are SNRIs?
Serotonin Norepinephrine reuptake inhibitors
160
What type of drug is Duloxetine/Cymbalta?
SNRI
161
After activation, how does the muscarinic acetylcholine receptor return to its inactive 'off' state?
GTP is hydrolyzed and proteins bound to the receptor change conformation.
162
Cannabinoids such as delta-9-THC act on the CB2 cannabinoid receptor. Which of the following proteins is most likely to down-regulate CB2 receptor signalling? (adenylate cyclase, arrestin, CREB, inositol 3-phosphate)
Arrestin
163
Some countries allegedly used cholinesterase inhibitors as 'nerve agents'. If someone took a toxic dose of a cholinesterase inhibitor, answer whether the following would be useful/ not useful as a treatment and briefly explain why. (nicotine, acetylcholine, antimuscarinic drug).
Nicotine- not useful. The system is already over-stimulated with Ach
Acetylcholine- not useful. The system is already over-stimulated with Ach.
Antimuscarinic drug- useful. this should alleviate some of the symptoms of excess Ach.
164
Which of the following statement best represents the mechanism of action of caffeine?
It inhibits adenosine signalling through its receptor.
165
Which of the following best describes the identity and mechanism of Cetuximab?
A chimeric monoclonal antibody that inhibits EGF binding to its receptor.
166
You are part of a research group studying the insulin receptor. One group member makes a monoclonal antibody that locks the insulin receptor in the activated conformation. If the antibody were to be used therapeutically, which of the following side effects would be most likely a direct consequence of using the antibody?
Hypoglycemia
167
Which of the following best represents the role of estrogen receptor (ER) in regulating the expression of its target?
Estrogen receptor directly increases and decreases RNA levels of many target genes.
168
Several techniques can be used to indicate whether a protein is in the nucleus or cytoplasm. If you were to use one of these techniques on a sample from tissue that produces the thyroid receptor but is not exposed to thyroid hormone, which option best describes the location of the thyroid hormone receptor?
In the nucleus, it is bound to a co-repressor.
169
Based on what you know about the thyroid hormone receptor, which of the following best represents the side effects of the thyroid hormone receptor agonist Levothyroxine?
Hyperactivity and weight loss
170
Which of the following inhibits both monoamine transporters and multiple receptors? (antimuscarinics, SNRIs, SSRIs, or tricyclic antidepressants)
Tricyclic antidepressants
171
SSRIs like Sertraline have a diverse range of side effects, including GI, tremors, and sexual side effects. How can one drug cause such a diverse range of side effects?
Serotonin receptors are everywhere in the body, especially in the gut and blood vessels. Sertraline will affect all of these receptors.
