SM Flashcards
(410 cards)
1
Q
What site does a competitive antagonist bind to?
A
Orthosteric site
(SM35a)
2
Q
How does a competitive antagonist affect efficacy and potency?
A
Efficacy unchanged
Decrease potency
(SM35a)
3
Q
Where does a noncompetitive antagonist bind?
A
1) Irreversibly to the orthosteric site, or
2) to an allosteric site
(SM35a)
4
Q
How does a noncompetitive antagonist affect efficacy and potency?
A
Decrease efficacy
Potency unchanged
(SM35a)
5
Q
When does an uncompetitive antagonist bind?
A
After agonist binds
(SM35a)
6
Q
How does an uncompetitive antagonist affect efficacy and potency?
A
Decrease efficacy
Increase potency
(SM35a)
7
Q
Define ED50
A
Median effective dose at which 50% of subjects get the therapeutic effect
(SM35a)
8
Q
Define LD50
A
Median lethal dose that produces death in 50% of subjects
(SM35a)
9
Q
Define therapeutic index
A
LD50/ED50 or ED50_toxic/ED50
(SM35a)
10
Q
What are the two determinants of resting membrane potential?
A
Na+/K+ ATPase
Na+ and K+ leak channels
(SM36a)
11
Q
What is the Nernst equation?
A
(RT/zF)*ln([ion_out]/[ion_in])
*flip fraction if ion is anion
(SM36a)
12
Q
What are the types of ion transporting proteins?
A
Channels (voltage-gated, ligand-gated, leak channels)
Pumps
Uniporters, antiporters, symporters
(SM37a)
13
Q
Which ion channels are responsible for setting resting membrane potential?
A
Na+ leak channels
K+ leak channels (inward rectifying, ATP-dependent, twin-pore)
(SM37a)
14
Q
Which ion channels are involved in generating action potentials?
A
Voltage-gated Na+ channels
Voltage-gated K+ channels
(SM37a)
15
Q
What are the 4 large classes of receptors?
A
Ligand-gated ion channels
GPCRs
RTKs, JAK/STATs
Cytoplasmic and nuclear receptors
(SM38a 39a)
16
Q
What is the ligand for nicotinic receptors?
A
Acetylcholine
(SM38a 39a)
17
Q
What is the ligand for 5HT-3 receptors?
A
Serotonin
(SM38a 39a)
18
Q
What is the ligand for NMDA, AMPA/Kainate receptors?
A
Glutamate
(SM38a 39a)
19
Q
What is the mechanism of action of Ondansetron (Zofran)?
A
Competitive inhibitor of 5HT-3 receptors
(SM38a 39a)
20
Q
What is the mechanism of action of benzodiazepines?
A
Allosteric activators of GABA receptors
(SM38a 39a)
21
Q
What is the mechanism of action of Zolpidem (Ambien)?
A
Allosteric activator of GABA receptors (binds to same site as benzodiazepines)
(SM38a 39a)
22
Q
What is the mechanism of action of penicillin?
A
Uncompetitive inhibitor of GABA receptors (open channel blocker)
(SM38a 39a)
23
Q
What is the mechanism of action of Strychnine?
A
Competitive inhibitor of glycine receptor
(SM38a 39a)
24
Q
What is the mechanism of action of tetanus toxin?
A
Blocks glycine release from presynaptic cell
(SM38a 39a)
25
Name the 3 signaling pathways used by GPCRs
Membrane delimited
Synthesis of second messengers
Protein phosphorylation
(SM38a 39a)
26
Describe the MAP Kinase pathway of RTK signaling
Ligand binds --\> RTKs dimerize\* --\> transphosphorylation --\> Grb2 (scaffold) --\> Sos --\> GTP-Ras --\> Raf --\> Mek --\> Erk --\> altered gene transcription
\*Exception: insulin RTKs are already dimerized prior to insulin binding
(SM38a 39a)
27
Describe the PI3 pathway of insulin RTK signaling
Insulin binds --\> transphosphorylation --\> Irs --\> PI3 kinase --\> Akt (PKB) --\> mTOR --\> altered protein translation --\> increased glucose uptake, glycogen synthesis, fat storage
(SM38a 39a)
28
How does the JAK/STAT signaling pathway differ from RTK signaling?
Receptor has no kinase activity --\> need JAK, which has kinase activity
STAT (scaffold) dissociates and dimerizes to alter gene transcription
(SM38a 39a)
29
What type of signaling do cytokines use?
JAK/STAT
(SM38a 39a)
30
What type of signaling do glucocorticoids use?
Cytoplasmic and nuclear receptors
(SM38a 39a)
31
How does GPCR desensitization occur?
GRK phosphorylates GPCR --\> beta arrestins bind --\> GPCR internalized
Can be resensitized after agonist is removed and beta arrestins dissociate
Repeated or prolonged agonist exposure can target GPCRs for lysosomes
(SM38a 39a)
32
What are the 3 membrane delimited effects in GPCR signaling?
Activate K+ channels (by beta/gamma)
Inhibit Ca2+ channels (by beta/gamma)
Inhibit adenylyl cyclase (by alpha\_i)
(SM38a 39a)
33
Describe the second messenger pathway of GPCR signaling
Activate phospholipase C --\> IP3 --\> intracellular Ca2+ release --\> smooth muscle contraction
(SM38a 39a)
34
Describe the protein phosphorylation pathway of GPCR signaling
Activate adenylyl cyclase --\> cAMP --\> PKA --\> phosphorylation of proteins --\> many downstream effects
(SM38a 39a)
35
What kind of receptors are nicotinic receptors?
Excitatory ligand-gated Na+ channels
(SM38a 39a)
36
What kind of receptors are 5HT-3 receptors?
Excitatory serotonin-gated ion channels
(SM38a 39a)
37
What kind of receptors are GABA receptors?
Inhibitory ligand-gated Cl- channels
Main inhibitory receptor in CNS
(SM38a 39a)
38
What kind of receptors are glycine receptors?
Inhibitory ligand-gated Cl- channels
Main inhibitory receptor in spinal cord
(SM38a 39a)
39
What kind of receptors are NMDA receptors?
Excitatory ligand-gated Ca2+ channels
(SM38a 39a)
40
What are NMDA receptors important for?
Learning and memory
(SM38a 39a)
41
What kind of receptors are AMPA/Kainate receptors?
Excitatory ligand-gated Na+ channels
(SM38a 39a)
42
What is a biased agonist?
Agonist which activates one downstream signaling path over another (i.e. favoring either G-protein or beta arrestin pathway for GPCR signaling)
(SM38a 39a)
43
What is Ondansetron (Zofran) used for?
Treat vomiting and nausea
(SM38a 39a)
44
What are benzodiazepines used for?
Treat anxiety, produce sleep, reduce muscle spasms
(SM38a 39a)
45
What is Zolpidem (Ambien) used for?
Produce sleep
(SM38a 39a)
46
What is a common side effect of penicillin?
Induce seizures
(SM38a 39a)
47
What is a common side effect of Strychnine?
Excessive spasticity
(SM38a 39a)
48
What is a common side effect of tetanus toxin?
Excessive spasticity
(SM38a 39a)
49
What kind of receptor do growth factors use?
RTKs
(SM38a 39a)
50
What kind of receptor does insulin use?
RTKs
(SM38a 39a)
51
What type of transport do ABC transporters do?
Primary active transport
(SM40a)
52
What type(s) of transport do SLC transporters use?
Secondary active transport
Facilitated diffusion
(SM40a)
53
What is the direction of transport of ABC transporters?
Efflux (out of cell)
(SM40a)
54
What is the direction of transport of SLC transporters?
Influx (into cell)
(SM40a)
55
What type of transporter is p-glycoprotein?
ABC transporter
(SM40a)
56
What types of transporters are serotonin, norepinephrine, and dopamine reuptake inhibitors?
SLC transporters
(SM40a)
57
What is the safest, most convenient, and most economical route of drug administration?
Oral
(SM41a)
58
What are some cons of oral drug administration?
Slow time to effect
Consciousness required
Functional gut required
Limited bioavailability
(SM41a)
59
What are some pros of rectal drug administration?
Good adsorption
No first-pass metabolism
(SM41a)
60
What are some pros of IV drug administration?
100% bioavailability
Rapid onset
Good for emergency situations
Suitable for large volumes
(SM41a)
61
What are some cons of IV drug administration?
Painful
Expensive
Increased risk of bleeding and infection
(SM41a)
62
What are some pros of intramuscular and subcutaneous drug administration?
Rapid onset
No first-pass metabolism
(SM41a)
63
What is a special application of subcutaneous drug administration?
Suitable for insoluble suspensions and implantation of solid pellets
(SM41a)
64
What is intrathecal drug administration?
Injecting drug directly into CSF
(SM41a)
65
What is bioavailability?
Fraction of administered dose of drug that reaches systemic circulation
(SM41a)
66
What is bioequivalence?
Producing same rates and extents of bioavailability and same pharmacokinetics
(SM41a)
67
What is pharmaceutical equivalence?
Containing same active ingredients and identical in strength, dosage form, and route of administration
(SM41a)
68
What is first-pass metabolism?
Metabolism by intestinal epithelium and liver before entering systemic circulation
(SM41a)
69
What is the formula for apparent volume of distribution?
Vd = dose/plasma drug concentration
(SM41a)
70
What does a high volume of distribution mean?
More of the drug has left the blood to other compartments
(SM41a)
71
Choroid plexus capillaries are \_\_\_\_\_.
Fenestrated
(SM41a)
72
Choroid plexus epithelial cells have \_\_\_\_\_.
Tight junctions
(SM41a)
73
Ependymal cells are \_\_\_\_\_.
Leaky
(SM41a)
74
What is the most abundant drug-binding protein in plasma?
Albumin
(SM41a)
75
What Phase II reaction do all benzodiazepines undergo?
Glucuronidation
(SM42a 43a)
76
What are some substrates for CYP2D6?
Opioids (codeine, hydrocodone)
Metoprolol
CNS drugs
(SM42a 43a)
77
What are some substrates for CYP2C9?
NSAIDs (celecoxib, ibuprofen)
Warfarin
(SM42a 43a)
78
What are some substrates for CYP2C19?
Diazepam
Omeprazole
Clopidogrel
(SM42a 43a)
79
How is acetaminophen metabolized?
Glucuronidation, sulfation (normal)
CYP3A4, CYP2E1 (toxic)
(SM42a 43a)
80
What is the toxic compound produced by acetaminophen metabolism?
NAPQI
(SM42a 43a)
81
What can rescue NAPQI in acetaminophen metabolism?
Glutathione
(SM42a 43a)
82
What are two ways ethanol worsens acetaminophen toxicity?
Induce CYP2E1
Reduce glutathione levels
(SM42a 43a)
83
What is the mechanism of action of Memantine?
Uncompetitive inhibitor of NMDA receptor (open channel blocker)
(SM38a 39a)
84
What is Memantine used for?
Treat Alzheimers
(SM38a 39a)
85
What is the mechanism of action of Fluticasone?
Activator of glucocorticoid receptor
(SM38a 39a)
86
What is Fluticasone used for?
Inhibit inflammatory response
(SM38a 39a)
87
What is the mechanism of action of cocaine?
Inhibit norepinephrine and dopamine SLC reuptake transporters
(SM40a)
88
What is the mechanism of action of ADHD drugs?
Inhibit norepinephrine SLC reuptake transporter
(SM40a)
89
What is the mechanism of action of amphetamines?
Inhibitor of dopamine SLC reuptake transporters
(SM40a)
90
What is the mechanism of action of SSRIs?
Inhibit serotonin SLC reuptake transporters
(SM40a)
91
What is the mechanism of action of Cimetidine?
Competitive inhibitor of H2 histamine receptor
(SM42a 43a)
92
How does Cimetidine impact CYPs?
Inhibits many CYPs
(SM42a 43a)
93
What is Cimetidine used for?
Suppress gastric acid secretion
(SM42a 43a)
94
What is the mechanism of action of Diphenhydramine?
Competitive inhibitor of H1 histamine receptor
(SM42a 43a)
95
What is Diphenhydramine used for?
Treat mild allergic reactions
(SM42a 43a)
96
What is the mechanism of action of methylxanthines?
Competitive inhibitor of adenosine receptor
(SM42a 43a)
97
What is theophylline (methylxanthine) used for?
Treat asthma and COPD
(SM42a 43a)
98
How is codeine metabolized?
CYP2D6 (O-dealkylation to morphine)
(SM42a 43a)
99
Which CYPs exhibit polymorphism?
CYP2D6
CYP2C9
CYP2C19
(SM42a 43a)
100
What are some prodrugs?
Codeine
Clopidogrel
Thiopurine
101
How is hydrocodone metabolized?
CYP2D6
(SM42a 43a)
102
What is the mechanism of action of acetaminophen?
COX inhibitor
(SM42a 43a)
103
What is acetaminophen used for?
Reduce pain and fever
(SM42a 43a)
104
How does beta 1 receptor activity affect the heart?
Increase heart rate and contractility
(SM38a 39a)
105
How does beta 2 receptor activity affect smooth muscle?
Relaxes smooth muscle
(SM38a 39a)
106
What is the mechanism of action of metoprolol?
Competitive inhibitor of beta-1 adrenoreceptors
(SM42a 43a)
107
What is metoprolol used for?
Treat hypertension
(SM42a 43a)
108
What is the mechanism of action of omeprazole?
Inhibit proton pump
(SM42a 43a)
109
What is omeprazole used for?
Reduce gastric acid secretion
Treat peptic ulcers and GERD
(SM42a 43a)
110
How is omeprazole metabolized?
CYP3A4, CYP2C19
(SM42a 43a)
111
What is Clopidogrel used for?
Anticoagulation
(SM46a)
112
How is Clopidogrel metabolized?
CYP2C19 (prodrug --\> active form)
(SM46a)
113
What is the mechanism of action of Warfarin?
Inhibit VKORC1
(SM46a)
114
What is Warfarin used for?
Anticoagulation
(SM46a)
115
How is Warfarin metabolized?
CYP2C9
(SM46a)
116
Why is Warfarin monitoring important?
Warfarin has narrow therapeutic window (TI ~1)
(SM46a)
117
How is Warfarin monitored?
PT and INR
(SM46a)
118
What is typical range for therapeutic INR for Warfarin?
2-3
(SM46a)
119
What is the mechanism of action of NSAIDs?
COX inhibitor
(SM42a 43a)
120
How are NSAIDs metabolized?
CYP2C9
(SM42a 43a)
121
How does Probenecid interact with penicillin?
Probenecid competes with penicillin for OAT (SLC) transport and increases penicillin half-life in plasma
(SM44a)
122
How does Ritonavir interact with Tenofovir?
Ritonavir inhibits ABC transport of Tenofovir out of renal tubule cells into tubule lumen and leads to Tenofovir toxicity in tubule cells
(SM44a)
123
How does Probenecid interact with Tenofovir?
Probenecid inhibits OAT (SLC) transport of Tenofovir into renal tubule cell from plasma and decreases Tenofovir toxicity in tubule cells
(SM44a)
124
What is Tacrolimus used for?
Immunosuppressant
(SM46a)
125
How is Tacrolimus metabolized?
CYP3A4, CYP3A5
(SM46a)
126
What is notable about CYP3A5 (i.e. in Tacrolimus metabolism)?
CYP3A5 exhibits polymorphism and makes most people poor metabolizers
(SM46a)
127
What is thiopurine used for?
Anti-cancer agent
(SM46a)
128
What do TPMT poor metabolizers have higher risk of?
Bone marrow suppression, sepsis
(SM46a)
129
How is thiopurine metabolized for activity?
It is a prodrug that is converted to thioguanines which have anti-cancer activity
(SM46a)
130
What is an example of a thiopurine?
6-mercapto-purine
(SM46a)
131
How is thiopurine metabolized for elimination?
TPMT
(SM46a)
132
What is Gefitinib/Erlotibin used for?
Anti-cancer agents
(SM46a)
133
What is the mechanism of action of Gefitinib/Erlotinib?
Inhibit hyperactive EGFR
(SM46a)
134
Where does renal tubular secretion occur?
Proximal tubule
(SM44a)
135
Where does renal reabsorption occur?
Distal tubule
(SM44a)
136
What does OCT transport?
Weak bases
(SM44a)
137
What does OAT transport?
Weak acids
(SM44a)
138
What part of renal elimination accounts for long retention time of lipid soluble drugs?
Reabsorption
(SM44a)
139
What can you do to tubular fluid pH to keep weak acids in urine?
Alkalize tubular fluid
(SM44a)
140
What can you do to tubular fluid pH to keep weak bases in urine?
Acidify tubular fluid
(SM44a)
141
What is the formula for half-life?
Half-life = 0.693\*Vd/CL
(SM45a)
142
How are clearance and rate of elimination related?
Rate of elimination = CL \* plasma drug concentration
(SM45a)
143
How many half-lives does it take to reach 90% steady state concentration?
3.3
(SM45a)
144
How do you determine maintenance dose?
Infusion rate = drug dose/dose interval = Css \* CL
(SM45a)
145
How do you determine loading dose?
Loading dose = Css \* Vd
(SM45a)
146
What are factors that affect CL (and thus maintenance dose)?
Disease, genetics, drug interactions
(SM45a)
147
What are factors that affect Vd (and thus loading dose)?
Age, weight, sex
(SM45a)
148
What is first-order drug clearance?
Rate of elimination proportional to plasma drug concentration
(SM45a)
149
What is zero-order drug clearance?
Constant rate of elimination
(SM45a)
150
Drug half-life is constant in _____ drug clearance
First-order
(SM45a)
151
Drug half-life is unpredictable in _____ drug clearance
Zero-order
(SM45a)
152
How do most ion channels desensitize?
Conformation change
(SM38a 39a)
153
Which receptor desensitizes in the time course of an action potential?
AMPA receptor
(SM38a 39a)
154
What receptors desensitize on time scale of milliseconds?
Ligand-gated ion channels
(SM38a 39a)
155
What receptors desensitize on time scale of minutes?
GPCRs
(SM38a 39a)
156
What receptors desensitize on time scale of hours?
RTKs
JAK/STAT
Cytoplasmic and nuclear receptors
(SM38a 39a)
157
What are microvilli made of?
Actin filaments
(SM48a)
158
Where are microvilli found?
Intestinal brush border and proximal convoluted tubule of kidney
(SM48a)
159
Where are stereocilia found?
Epididymis and vas deferens
(SM48a)
160
Where are cilia found?
Respiratory tract and female reproductive lining
(SM48a)
161
What are stereocilia made of?
Actin filaments
(SM48a)
162
What are cilia made of?
Microtubules
(SM48a)
163
What proteins form tight junctions?
Claudins and occludins
(SM48a)
164
What proteins form adherens junctions?
Cadherins
(SM48a)
165
What proteins form desmosomes?
Cadherins
(SM48a)
166
What do adherens junctions link?
Actin cytoskeleton
(SM48a)
167
What do desmosomes link?
Intermediate filaments
(SM48a)
168
What proteins form gap junctions?
Connexons
(SM48a)
169
What junctions form the apical junctional complex?
Tight junctions
Adherens junctions
Desmosomes
(SM48a)
170
What do hemidesmosomes link?
Keratin intermediate filaments to type IV collagen
(SM48a)
171
What proteins form hemidesmosomes?
Integrins
(SM48a)
172
What type of epithelium is found in blood vessels?
Simple squamous
(SM48a)
173
What type of epithelium lines lumen of ducts and tubules (i.e. kidney)?
Simple cuboidal
(SM48a)
174
What type of epithelium is found in larger airways of respiratory system?
Pseudostratified
(SM48a)
175
What type of epithelium lines oral cavity?
Stratified squamous
(SM48a)
176
What type of epithelium is skin?
Keratinized stratified squamous
(SM48a)
177
What type of epithelium lines the urinary tract?
Transitional
(SM48a)
178
How does plasma protein binding impact a drug's Vd?
Decrease Vd
(SM45a)
179
How does tissue protein binding impact a drug's Vd?
Increase Vd
(SM45a)
180
What is a classic zero-order drug?
Phenytoin
(SM45a)
181
What is a rule of thumb for drug dosing interval?
Dose every half-life
(SM45a)
182
How does epinephrine affect cardiac muscle?
Increased heart rate and contractility via beta 1 receptor
(SM35a)
183
How does epinephrine affect smooth muscle?
Relax bronchiole smooth muscle via beta 2 receptor
(SM35a)
184
How does epinephrine affect skeletal muscle?
It doesn't
(SM35a)
185
What causes hyperekplexia (familial startle disease)?
Mutated glycine receptors
(SM38a 39a)
186
All receptors on effectors in the autonomic nervous system are \_\_\_\_\_.
GPCRs
(SM38a 39a)
187
What is the fastest form of signaling?
Ligand-gated ion channels
(SM38a 39a)
188
What is the second fastest form of signaling?
GPCR membrane delimited effects
(SM38a 39a)
189
What is the third fastest form of signaling?
Second messenger pathway of GPCR signaling
(SM38a 39a)
190
What subscript typically denotes GPCR membrane delimited effects?
2
(SM38a 39a)
191
What subscript usually denotes GPCR second messenger pathway?
1 or 3
(SM38a 39a)
192
How does PKA phosphorylation affect cardiac and smooth muscle?
Increase heart rate and contractility (beta 1)
Relax smooth muscle (beta 2)
(SM38a 39a)
193
Constitutively active RTKs commonly occur in \_\_\_\_\_.
Cancers
(SM38a 39a)
194
Growth factors typically use the _____ pathway in RTK signaling
Ras/MAP kinase
(SM38a 39a)
195
Describe glucocorticoid signaling
Steroid diffuses through plasma membrane --\> binds to glucocorticoid receptor --\> dissociation of HSP-90 --\> receptors dimerize --\> translocate to nucleus to alter gene transcription --\> inhibit inflammatory response
(SM38a 39a)
196
\_\_\_\_\_ channels desensitize faster than any signaling process
AMPA
(SM38a 39a)
197
\_\_\_\_\_ desensitize very slowly
Positive allosteric modulators
(SM38a 39a)
198
\_\_\_\_\_ can be prescribed for years without desensitization
Zolpidem
(SM38a 39a)
199
How are benzodiazepines (-zolams and -azepams) metabolized?
CYP3A4\* --\> glucuronidation
\*-azepams also use CYP2C19
(SM42a 43a)
200
How are histamine receptor blockers (Cimetidine, Diphenhydramine) metabolized?
CYPs (oxidation)
(SM42a 43a)
201
How are methylxanthines (Caffeine, Theophylline) metabolized?
CYPs (dealkylation)
(SM42a 43a)
202
Furanocoumarins in grapefruit juice inhibit \_\_\_\_\_
CYP3A4
(SM42a 43a)
203
Does substrate shape matter for CYP3A4?
No, very large active site
(SM42a 43a)
204
How is metoprolol metabolized?
CYP2D6
(SM42a 43a)
205
How are opioids (codeine, hydrocodone) metabolized?
CYP2D6
(SM42a 43a)
206
How are many CNS drugs metabolized?
CYP2D6
(SM42a 43a)
207
How is omeprazole metabolized?
CYP2C19
(SM42a 43a)
208
How is clopidogrel metabolized?
CYP2C19
(SM42a 43a)
209
How are NSAIDs metabolized?
CYP2C9
(SM42a 43a)
210
What is the mechanism of action of tetrodotoxin?
Blocks voltage-gated Na+ channels in nerve and muscle
(SM37a)
211
What is the mechanism of action of local anesthetics?
Block inactivated voltage-gated Na+ channels
(SM37a)
212
What is the mechanism of action of minoxidil?
Activate K\_ATP channels in vascular smooth muscle
(SM37a)
213
What is minoxidil used for?
Treat hypertension
(SM37a)
214
What is the mechanism of sulfonylurea?
Inhibit K\_ATP channels in pancreatic beta cells
(SM37a)
215
What is sulfonylurea used for?
Treat diabetes
(SM37a)
216
What happens if you inhibit HERG K+ channel?
Can increase risk of arrhythmia by prolonging QT interval too much
(SM37a)
217
Why was terfenadine withdrawn?
It blocked HERG K+ channels, making it pro-arrhythmic
(SM37a)
218
Cl- is _____ in developing neurons and _____ in mature neurons
High; low
(SM36a)
219
CYP3A4 can be found in _____ and in \_\_\_\_\_
Intestinal epithelium; liver
(SM41a)
220
St. John's wort induces \_\_\_\_\_
CYP3A4, CYP2C9, CYP2C19, CYP2E1
(SM42a 43a)
221
Gingko induces \_\_\_\_\_
CYP3A4, CYP2C9, CYP2C19
(SM42a 43a)
222
Echinacea induces \_\_\_\_\_
CYP3A4
(SM42a 43a)
223
What is the formula for renal clearance?
Renal clearance = urine concentration \* urine flow rate / plasma concentration
(SM44a)
224
\_\_\_\_\_ are not filtered well at glomerulus
Large anionic molecules
(SM44a)
225
Normal GFR is \_\_\_\_\_
125 mL/min or 180 L/day
(SM44a)
226
Digoxin, lithium carbonate, allopurinol, and antibiotics are commonly eliminated via \_\_\_\_\_
Kidneys
(SM44a)
227
Cimetidine, ceftazimide, digoxin, cisplatin, indinavir, quinidine, and verapamil are transported by _____ in the kidneys
OCTs
(SM44a)
228
Penicillin, probenecid, aspirin, furosemide, thiazides, ibuprofen, and statins are transported by _____ in the kidneys
OATs
(SM44a)
229
Methamphetamine is a _____ that is better excreted in _____ urine
Weak base; acidic
(SM44a)
230
Phenobarbital is a _____ that is best excreted in _____ urine
Weak acid; alkaline
(SM44a)
231
What is the formula for hepatic clearance?
Hepatic clearance = hepatic flow \* extraction ratio
Extraction ratio = (C\_in - C\_out)/C\_in
(SM44a)
232
High extraction drugs are sensitive to \_\_\_\_\_
Liver blood flow
(SM44a)
233
Low extraction drugs are sensitive to \_\_\_\_\_
Intrinsic hepatic metabolism and protein binding
(SM44a)
234
Morphine, lidocaine, propranolol, verapamil, propofol, and ketamine are \_\_\_\_\_(high/low) extraction drugs
High
(SM44a)
235
Digoxin, diazepam, valproic acid, tolbutamide, cimetidine, and phenytoin are \_\_\_\_\_(high/low) extraction drugs
Low
(SM44a)
236
What can statins cause at high levels?
Myotoxicity (due to impaired SLCs)
(SM44a)
237
Digoxin, morphine, and estradiol are commonly recycled via \_\_\_\_\_
Enterohepatic cycle
(SM44a)
238
\_\_\_\_\_ forms spinal cord segments below S2 and comes from _____ germ layer
Caudal eminence; mesoderm
(SM49a 54a)
239
What are the layers of the meninges, from outermost to innermost?
Dura mater, arachnoid, pia mater
(SM49a 54a)
240
CSF is in the _____ space
Subarachnoid
(SM49a 54a)
241
What suspends the spinal cord in the subarachnoid space?
Denticulate ligaments (part of pia mater)
(SM49a 54a)
242
Where does the subarachnoid space terminate?
S1 vertebrae
(SM49a 54a)
243
What anchors the bottom of the spinal cord?
Filum terminale (part of pia mater)
(SM49a 54a)
244
The _____ are dorsal and ventral roots descending from the spinal cord to the appropriate level of exit from vertebral column
Cauda equina
(SM49a 54a)
245
Vagus nerve is cranial nerve \_\_\_\_\_
X
(SM49a 54a)
246
Where do sympathetic neurons leave spinal cord from?
T1 to L2
(SM49a 54a)
247
Where do parasympathetic neurons leave spinal cord from?
Cranial and sacral regions
(SM49a 54a)
248
What splanchnic nerves pass through the diaphragm?
Thoracic and lumbar
(SM49a 54a)
249
What does somatopleure give rise to?
Somatic nervous system
(SM49a 54a)
250
What does splanchnopleure give rise to?
Autonomic nervous system
(SM49a 54a)
251
All _____ have visceral sensory nerves traveling with them
Autonomic nerves
(SM49a 54a)
252
Where does spinal cord end in adults?
L1 vertebrae (right below it)
(SM49a 54a)
253
What is ECM made of?
Fibers: collagen, elastin
Ground substance: GAGs, proteglycans, glycoproteins
(SM50a)
254
Where is loose connective tissue found?
Superficial fascia
(SM50a)
255
What is dense irregular connective tissue made of?
Woven collagen fibers in a matrix with some elastin
(SM50a)
256
What is dense irregular connective tissue good at?
Resisting multidirectional impact
(SM50a)
257
Where is dense irregular connective tissue found?
Dermis, joints, fascia
(SM50a)
258
What is dense regular connective tissue made of?
Parallel collagen fibers
(SM50a)
259
What is dense regular connective tissue good at?
Resisting tension
(SM50a)
260
What is reticular connective tissue made of?
Very fine type III collagen
(SM50a)
261
Where is reticular connective tissue found?
Stroma of lymphathic and hematopoietic organs
(SM50a)
262
What is adipose (connective tissue) good at?
Storing energy, providing insulation, protection
(SM50a)
263
What cell type produces most of ECM components?
Fibroblasts/myofibroblasts
(SM50a)
264
Where is dense regular connection tissue found?
Tendons
(SM50a)
265
What is required to assemble collagen fibers?
Vitamin C
(SM50a)
266
What is required to assemble elastin fibers?
Fibrillin
(SM50a)
267
Density is used to refer to what images?
X-ray
(SM51a)
268
What are the 5 x-ray densities from blackest to whitest?
Air
Fat
Soft tissue, liquid
Bone, calcium
Metal, contrast
(SM51a)
269
Echogenicity is used to refer to what images?
Ultrasound
(SM51a)
270
Intensity is used to refer to what images?
MRI
(SM51a)
271
What imaging modalities do not use ionizing radiation?
Ultrasound and MRI
(SM51a)
272
What can ultrasound not penetrate?
Air and bone
(SM51a)
273
What is ultrasound useful for?
Evaluating solid organs, guiding biopsies, evaluating blood flow
(SM51a)
274
What are examples of conditionally dividing cells?
Liver and kidney cells
(SM52a)
275
What are examples of non-dividing cells?
Muscle cells and neurons
(SM52a)
276
Physiologic stimuli for cellular morphologic changes are often mediated by what?
Hormones
(SM52a)
277
What is a physiologic example of hypertrophy during pregnancy?
Growth of uterus
(SM52a)
278
What is a physiologic example of hyperplasia during pregnancy?
Proliferation of breast tissue
(SM52a)
279
What is a physiologic example of metaplasia?
Cervix during menarche
(SM52a)
280
What is a pathologic example of metaplasia in the esophagus?
Barrett's Esophagus
(SM52a)
281
What is a pathologic example of metaplasia in the lungs?
Columnar to squamous metaplasia in smoker
(SM52a)
282
What is a carcinoma?
Malignant epithelial neoplasm
(SM52a)
283
What is a sarcoma?
Malignant mesenchymal neoplasm
(SM52a)
284
What is a lymphoma?
Malignant lymphatic neoplasm
(SM52a)
285
What is a melanoma?
Malignant melanocytic neoplasm
(SM52a)
286
What does the prefix adeno mean?
Derived from glandular tissue
(SM52a)
287
What does the prefix leiomyo mean?
Derived from smooth muscle
(SM52a)
288
What does the prefix rhabdomyo mean?
Derived from skeletal muscle
(SM52a)
289
What intercellular junction form spot welds?
Desmosomes (macula adherens)
(SM48a)
290
What is mesothelium?
Epithelium that lines the pleurae, peritoneum, and pericardium
(SM48a)
291
For cancer, what does grading refer to?
Degree of histologic differentiation
(SM52a)
292
For cancer, what does staging refer to?
Extent of tumor spread, including size of primary tumor, lymph node involvement, and distant metastatic spread
(SM52a)
293
What are the two things that make up a blastocyst?
Trophoblast and inner cell mass
(SM59a 60a)
294
What three things do the inner cell mass give rise to?
Amnion, embryonic disc, and yolk sac
(SM59a 60a)
295
What three layers make up the chorion?
Syntrophoblast, cytotrophoblast, and extraembryonic mesoderm
(SM59a 60a)
296
What two layers make up the amnion proper?
Ectoderm and extraembryonic mesoderm
(SM59a 60a)
297
What two layers make up the yolk sac proper?
Endoderm and extraembryonic mesoderm
(SM59a 60a)
298
What can too little amniotic fluid indicate?
Renal agenesis
(SM59a 60a)
299
What can excess amniotic fluid indicate?
Anencephaly or tracheoesophageal fistula
(SM59a 60a)
300
What layer of the chorion is in direct contact with maternal blood?
Syntrophoblast
(SM59a 60a)
301
What weeks cover the blastocyst period?
1-2
(SM59a 60a)
302
What weeks cover the embryo period?
3-8
(SM59a 60a)
303
What weeks cover the fetal period?
8-term
(SM59a 60a)
304
What is gastrulation?
Formation of intraembryonic mesoderm and elongation of embryonic disc
(SM59a 60a)
305
What does the primitive knot give rise to?
Notochord (midline of mesoderm)
(SM59a 60a)
306
What does the primitive streak give rise to?
Intraembryonic mesoderm (except notocord)
(SM59a 60a)
307
What does lateral plate mesoderm give rise to (embryo)?
Intraembryonic coelom
(SM59a 60a)
308
What two germ layers are in somatopleure?
Ectoderm and mesoderm
(SM59a 60a)
309
What two germ layers are in splanchnopleure?
Endoderm and mesoderm
(SM59a 60a)
310
What two things does septum transversum give rise to?
Diaphragm and liver stroma
(SM59a 60a)
311
What week does blastocyst implantation occur?
2
(SM59a 60a)
312
What week do you get the formation of amnion proper, yolk sac proper, and chorion?
2
(SM59a 60a)
313
What week does gastrulation occur?
3
(SM59a 60a)
314
What week does gastrula change shape from disc to cylinder?
4
(SM59a 60a)
315
What week do somatopleure and splanchnopleure form?
4
(SM59a 60a)
316
What week does septum transversum form?
4-8
(SM59a 60a)
317
What week do you get GI organ buds and limb buds?
4-8
(SM59a 60a)
318
What does somatopleure become?
Lateral and ventral body wall
(SM59a 60a)
319
What does splanchnopleure become?
Visceral structure, including gut tube walls and mesenteries
(SM59a 60a)
320
What do you call the two sheets of visceral peritoneum that suspend gut tube from body wall?
Mesenteries
(SM59a 60a)
321
How many amions and yolk sacs do monozygotic twins have?
2
(SM59a 60a)
322
How many chorion and placenta do monozygotic twins have?
1
(SM59a 60a)
323
What is reperfusion injury?
Explosive onset of necrosis during reperfusion of ischemic organs due to sudden generation of ROS
(SM53a)
324
What is karyolysis?
Nuclei fading and disappearing
(SM53a)
325
What is karyorrhexis?
Nuclei fragmentation
(SM53a)
326
What is pyknosis?
Nuclear shrinkage and increased basophilia (darker)
(SM53a)
327
Are karyolysis, karyorrhexis, and pyknosis associated with reversible or irreversible cellular injury?
Irreversible
(SM53a)
328
Does apoptosis or necrosis use caspases?
Apoptosis
(SM53a)
329
Is cytoplasmic blebbing associated with apoptosis or necrosis?
Apoptosis
(SM53a)
330
Is cell swelling associated with apoptosis or necrosis?
Necrosis
(SM53a)
331
Is cell shrinkage associated with apoptosis or necrosis?
Apoptosis
(SM53a)
332
Is chromatin condensation associated with apoptosis or necrosis?
Apoptosis
(SM53a)
333
Is inflammation associated with apoptosis or necrosis?
Necrosis
(SM53a)
334
Is nuclear swelling and lysis associated with apoptosis or necrosis?
Necrosis
(SM53a)
335
Is energy required for apoptosis or necrosis?
Apoptosis
(SM53a)
336
Is protein synthesis required for apoptosis or necrosis?
Apoptosis
(SM53a)
337
Is apoptosis or necrosis energy dependent?
Apoptosis
(SM53a)
338
Is de novo transcription associated with apoptosis or necrosis?
Apoptosis
(SM53a)
339
Is a DNA fragmentation ladder associated with apoptosis or necrosis?
Apoptosis
(SM53a)
340
Is random DNA degradation associated with apoptosis or necrosis?
Necrosis
(SM53a)
341
What type of necrosis is associated with cell outlines with missing nuclei?
Coagulative
(SM53a)
342
What type of necrosis is often found in brain?
Liquefactive
(SM53a)
343
What type of necrosis is commonly associated with tuberculosis and looks like dry cheese?
Caseous
(SM53a)
344
What type of necrosis is almost exclusively found in adipose tissue contiguous with pancreas?
Fat
(SM53a)
345
What type of necrosis is associated with immune reactions in blood vessels?
Fibrinoid
(SM53a)
346
What type of necrosis is commonly localized to lower limb soft tissues?
Gangrenous
(SM53a)
347
How does decreased ATP production affect pH?
Decreases pH
(SM53a)
348
What is required to open mitochondrial transitional pore?
Ca2+
(SM53a)
349
What organelle can leak apoptotic proteins?
Mitochondria
(SM53a)
350
What is the effect of Mg2+ and polyvalent cations on voltage-gated Ca2+ channels?
Competitive inhibitor
(SM57a)
351
How do Mg2+ and polyvalent cations affect neurotransmission?
Reduce neurotransmitter release
(SM57a)
352
What is the mechanism of action of botulinum toxin A?
Cleave SNAP-25
(SM57a)
353
What is botulinum toxin A used for?
Treat spasticity
(SM57a)
354
What is the mechanism of action of rocuronium and vercuronium?
Competitive inhibitor of nicotinic receptors
(SM57a)
355
Are rocuronium and vercuronium depolarizing or non-depolarizing?
Non-depolarizing
(SM57a)
356
What are rocuronium and vercuronium used for?
Relax neuromuscular junction for surgery
(SM57a)
357
What is the mechanism of action of succinylcholine?
Competitive inhibitor of nicotinic receptors
(SM57a)
358
Is succinylcholine depolarizing or non-depolarizing?
Depolarizing
(SM57a)
359
What is succinylcholine used for?
Relax neuromuscular junction for surgery
(SM57a)
360
What is the mechanism of action of neostigmine?
Inhibit cholinesterase
(SM57a)
361
What is neostigmine used for?
Speed recovery from non-depolarizing block after surgery and treat myasthenia gravis
(SM57a)
362
What is the mechanism of action of atropine?
Competitive inhibitor of muscarinic receptors
(SM57a)
363
What is atropine used for?
Increase HR during spinal anesthesia
(SM57a)
364
What is the mechanism of action of ipratropium and tiotropium?
Competitive inhibitor of muscarinic receptors
(SM57a)
365
What are ipratropium and tiotropium used for?
Treat asthma and COPD
(SM57a)
366
What is the mechanism of action of phenylephrine?
Agonist of alpha-1 adrenoreceptors
(SM57a)
367
What is phenylephrine used for?
Increase blood pressure and decrease nasal congestion
(SM57a)
368
What can exogenous norepinephrine and epinephrine be used for?
Treat hypotension
(SM57a)
369
What is the mechanism of action of exogenous norepinephrine and epinephrine?
Agonist of alpha-1 adrenoreceptors
(SM57a)
370
What is the mechanism of action of albuterol?
Agonist of beta-2 adrenoreceptors
(SM57a)
371
What is albuterol used for?
Open airways (rescue inhaler)
(SM57a)
372
What are formeterol and salmeterol used for?
Open airways (long lasting)
(SM57a)
373
What is the mechanism of action of propranolol?
Competitive inhibitor of beta-1 (and beta-2) adrenoreceptors
(SM57a)
374
What is the mechanism of action of metaprolol?
Competitive inhibitor of beta-1 adrenoreceptors
(SM57a)
375
What are propranolol and metaprolol used for?
Treat arrhythmias and hypertension
(SM57a)
376
You should never give (propranolol/metaprolol) to asthmatics
Propranolol
(SM57a)
377
What signaling pathway do alpha-1 adrenoreceptors use?
Phospholipase C --\> smooth muscle contraction
(SM57a)
378
What adrenoreceptor is responsible for sympathetic tone?
Alpha-1
(SM57a)
379
What signaling pathway do beta-1 adrenoreceptors use?
cAMP --\> increase HR and heart contractility
(SM57a)
380
What signaling pathway do beta-2 adrenoreceptors use?
cAMP --\> relax smooth muscle
(SM57a)
381
What signaling pathway do alpha-2 adrenoreceptors use?
Membrane delimited inhibitory effects
(SM57a)
382
What signaling pathway do muscarinic receptors in the heart use?
Activate K+ channels
(SM57a)
383
What signaling pathway do muscarinic receptors in the airways use?
Phospholipase C --\> smooth muscle contraction
(SM57a)
384
The (vagus/phrenic) nerve runs posterior to the root of lung
Vagus
(Lab 2)
385
The (vagus/phrenic) nerve runs anterior to root of lung
Phrenic
(Lab 2)
386
What three branches come off the aortic arch?
Brachiocephalic trunk
Left common carotid artery
Left subclavian artery
(Lab 2)
387
What two branches feed into superior vena cava?
Right brachiocephalic vein
Left brachiocephalic vein
(Lab 2)
388
Which nerve runs along trachea and esophagus?
Vagus
(Lab 2)
389
Where does phrenic nerve leave from?
Ventral rami of cervical spinal nerves 3-5
(Lab 2)
390
What does the notochord do?
Induce neural plate formation
(SM59a 60a)
391
What does paraxial column mesoderm give rise to?
Somites
(SM59a 60a)
392
What does intermediate column mesoderm give rise to?
Kidneys and gonads
(SM59a 60a)
393
What does lateral plate mesoderm give rise to (adult)?
Pleura, peritoneum, and connective tissue of organs and body wall
(SM59a 60a)
394
What genes establish anterior-posterior axis in embryo?
HOX genes
(SM61a)
395
3' HOX genes are expressed (earlier/later) than 5' HOX genes
Earlier
(SM61a)
396
3' HOX genes end more (anteriorly/posteriorly) than 5' HOX genes
Anteriorly
(SM61a)
397
What results from HOX-D13 mutations?
Polysyndactyly
(SM61a)
398
What genes establish dorsal-ventral neural tube axis in embryo?
Shh
(SM61a)
399
What results from Shh mutations?
Holoprosencephaly (abnormal septation in brain)
(SM61a)
400
What results from Patched mutations?
Basal cell nevus syndrome (skull/rib abnormalities and cancer predisposition)
(SM61a)
401
What results from GLI3 mutations?
Cephalopolysyndactyly, polysyndactyly
(SM61a)
402
What is the fate of medial dermamyotomes?
Back musculature and skin
(SM61a)
403
What is the fate of lateral dermamyotomes?
Lateral and ventral body wall musculature and skin
(SM61a)
404
What is the fate of sclerotomes?
Ribs and vertebral bodies
(SM61a)
405
What genes establish anterior-posterior limb axis?
Shh
(SM61a)
406
What is ascites?
Fluid accumulation in peritoneal cavity
(SM62a)
407
Pleural cavities become separated from pericardial cavity by growth of what?
Pleuropericardial folds
(SM62a)
408
What is the epicardium?
Visceral layer of pericardium
(SM62a)
409
What does the gut tube give rise to?
Trachea, lungs, digestive organs
(SM62a)
410
Is the charged or uncharged form of a drug more easily absorbed?
Uncharged
(SM40a)
