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Foundations 2 > SM > Flashcards

SM Flashcards

1
Q

What site does a competitive antagonist bind to?

A

Orthosteric site

(SM35a)

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2
Q

How does a competitive antagonist affect efficacy and potency?

A

Efficacy unchanged

Decrease potency

(SM35a)

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3
Q

Where does a noncompetitive antagonist bind?

A

1) Irreversibly to the orthosteric site, or
2) to an allosteric site

(SM35a)

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4
Q

How does a noncompetitive antagonist affect efficacy and potency?

A

Decrease efficacy

Potency unchanged

(SM35a)

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5
Q

When does an uncompetitive antagonist bind?

A

After agonist binds

(SM35a)

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6
Q

How does an uncompetitive antagonist affect efficacy and potency?

A

Decrease efficacy

Increase potency

(SM35a)

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7
Q

Define ED50

A

Median effective dose at which 50% of subjects get the therapeutic effect

(SM35a)

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8
Q

Define LD50

A

Median lethal dose that produces death in 50% of subjects

(SM35a)

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9
Q

Define therapeutic index

A

LD50/ED50 or ED50_toxic/ED50

(SM35a)

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10
Q

What are the two determinants of resting membrane potential?

A

Na+/K+ ATPase

Na+ and K+ leak channels

(SM36a)

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11
Q

What is the Nernst equation?

A

(RT/zF)*ln([ion_out]/[ion_in])

*flip fraction if ion is anion

(SM36a)

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12
Q

What are the types of ion transporting proteins?

A

Channels (voltage-gated, ligand-gated, leak channels)

Pumps

Uniporters, antiporters, symporters

(SM37a)

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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)

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14
Q

Which ion channels are involved in generating action potentials?

A

Voltage-gated Na+ channels

Voltage-gated K+ channels

(SM37a)

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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)

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16
Q

What is the ligand for nicotinic receptors?

A

Acetylcholine

(SM38a 39a)

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17
Q

What is the ligand for 5HT-3 receptors?

A

Serotonin

(SM38a 39a)

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18
Q

What is the ligand for NMDA, AMPA/Kainate receptors?

A

Glutamate

(SM38a 39a)

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19
Q

What is the mechanism of action of Ondansetron (Zofran)?

A

Competitive inhibitor of 5HT-3 receptors

(SM38a 39a)

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20
Q

What is the mechanism of action of benzodiazepines?

A

Allosteric activators of GABA receptors

(SM38a 39a)

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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)

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22
Q

What is the mechanism of action of penicillin?

A

Uncompetitive inhibitor of GABA receptors (open channel blocker)

(SM38a 39a)

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23
Q

What is the mechanism of action of Strychnine?

A

Competitive inhibitor of glycine receptor

(SM38a 39a)

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24
Q

What is the mechanism of action of tetanus toxin?

A

Blocks glycine release from presynaptic cell

(SM38a 39a)

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25
Q

Name the 3 signaling pathways used by GPCRs

A

Membrane delimited

Synthesis of second messengers

Protein phosphorylation

(SM38a 39a)

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26
Q

Describe the MAP Kinase pathway of RTK signaling

A

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)

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27
Q

Describe the PI3 pathway of insulin RTK signaling

A

Insulin binds –> transphosphorylation –> Irs –> PI3 kinase –> Akt (PKB) –> mTOR –> altered protein translation –> increased glucose uptake, glycogen synthesis, fat storage

(SM38a 39a)

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28
Q

How does the JAK/STAT signaling pathway differ from RTK signaling?

A

Receptor has no kinase activity –> need JAK, which has kinase activity

STAT (scaffold) dissociates and dimerizes to alter gene transcription

(SM38a 39a)

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29
Q

What type of signaling do cytokines use?

A

JAK/STAT

(SM38a 39a)

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30
Q

What type of signaling do glucocorticoids use?

A

Cytoplasmic and nuclear receptors

(SM38a 39a)

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31
Q

How does GPCR desensitization occur?

A

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)

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32
Q

What are the 3 membrane delimited effects in GPCR signaling?

A

Activate K+ channels (by beta/gamma)

Inhibit Ca2+ channels (by beta/gamma)

Inhibit adenylyl cyclase (by alpha_i)

(SM38a 39a)

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33
Q

Describe the second messenger pathway of GPCR signaling

A

Activate phospholipase C –> IP3 –> intracellular Ca2+ release –> smooth muscle contraction

(SM38a 39a)

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34
Q

Describe the protein phosphorylation pathway of GPCR signaling

A

Activate adenylyl cyclase –> cAMP –> PKA –> phosphorylation of proteins –> many downstream effects

(SM38a 39a)

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35
Q

What kind of receptors are nicotinic receptors?

A

Excitatory ligand-gated Na+ channels

(SM38a 39a)

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36
Q

What kind of receptors are 5HT-3 receptors?

A

Excitatory serotonin-gated ion channels

(SM38a 39a)

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37
Q

What kind of receptors are GABA receptors?

A

Inhibitory ligand-gated Cl- channels

Main inhibitory receptor in CNS

(SM38a 39a)

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38
Q

What kind of receptors are glycine receptors?

A

Inhibitory ligand-gated Cl- channels

Main inhibitory receptor in spinal cord

(SM38a 39a)

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39
Q

What kind of receptors are NMDA receptors?

A

Excitatory ligand-gated Ca2+ channels

(SM38a 39a)

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40
Q

What are NMDA receptors important for?

A

Learning and memory

(SM38a 39a)

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41
Q

What kind of receptors are AMPA/Kainate receptors?

A

Excitatory ligand-gated Na+ channels

(SM38a 39a)

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42
Q

What is a biased agonist?

A

Agonist which activates one downstream signaling path over another (i.e. favoring either G-protein or beta arrestin pathway for GPCR signaling)

(SM38a 39a)

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43
Q

What is Ondansetron (Zofran) used for?

A

Treat vomiting and nausea

(SM38a 39a)

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44
Q

What are benzodiazepines used for?

A

Treat anxiety, produce sleep, reduce muscle spasms

(SM38a 39a)

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45
Q

What is Zolpidem (Ambien) used for?

A

Produce sleep

(SM38a 39a)

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46
Q

What is a common side effect of penicillin?

A

Induce seizures

(SM38a 39a)

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47
Q

What is a common side effect of Strychnine?

A

Excessive spasticity

(SM38a 39a)

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48
Q

What is a common side effect of tetanus toxin?

A

Excessive spasticity

(SM38a 39a)

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49
Q

What kind of receptor do growth factors use?

A

RTKs

(SM38a 39a)

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50
Q

What kind of receptor does insulin use?

A

RTKs

(SM38a 39a)

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51
Q

What type of transport do ABC transporters do?

A

Primary active transport

(SM40a)

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52
Q

What type(s) of transport do SLC transporters use?

A

Secondary active transport

Facilitated diffusion

(SM40a)

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53
Q

What is the direction of transport of ABC transporters?

A

Efflux (out of cell)

(SM40a)

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54
Q

What is the direction of transport of SLC transporters?

A

Influx (into cell)

(SM40a)

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55
Q

What type of transporter is p-glycoprotein?

A

ABC transporter

(SM40a)

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56
Q

What types of transporters are serotonin, norepinephrine, and dopamine reuptake inhibitors?

A

SLC transporters

(SM40a)

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57
Q

What is the safest, most convenient, and most economical route of drug administration?

A

Oral

(SM41a)

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58
Q

What are some cons of oral drug administration?

A

Slow time to effect

Consciousness required

Functional gut required

Limited bioavailability

(SM41a)

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59
Q

What are some pros of rectal drug administration?

A

Good adsorption

No first-pass metabolism

(SM41a)

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60
Q

What are some pros of IV drug administration?

A

100% bioavailability

Rapid onset

Good for emergency situations

Suitable for large volumes

(SM41a)

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61
Q

What are some cons of IV drug administration?

A

Painful

Expensive

Increased risk of bleeding and infection

(SM41a)

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62
Q

What are some pros of intramuscular and subcutaneous drug administration?

A

Rapid onset

No first-pass metabolism

(SM41a)

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63
Q

What is a special application of subcutaneous drug administration?

A

Suitable for insoluble suspensions and implantation of solid pellets

(SM41a)

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64
Q

What is intrathecal drug administration?

A

Injecting drug directly into CSF

(SM41a)

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65
Q

What is bioavailability?

A

Fraction of administered dose of drug that reaches systemic circulation

(SM41a)

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66
Q

What is bioequivalence?

A

Producing same rates and extents of bioavailability and same pharmacokinetics

(SM41a)

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67
Q

What is pharmaceutical equivalence?

A

Containing same active ingredients and identical in strength, dosage form, and route of administration

(SM41a)

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68
Q

What is first-pass metabolism?

A

Metabolism by intestinal epithelium and liver before entering systemic circulation

(SM41a)

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69
Q

What is the formula for apparent volume of distribution?

A

Vd = dose/plasma drug concentration

(SM41a)

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70
Q

What does a high volume of distribution mean?

A

More of the drug has left the blood to other compartments

(SM41a)

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71
Q

Choroid plexus capillaries are _____.

A

Fenestrated

(SM41a)

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72
Q

Choroid plexus epithelial cells have _____.

A

Tight junctions

(SM41a)

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73
Q

Ependymal cells are _____.

A

Leaky

(SM41a)

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74
Q

What is the most abundant drug-binding protein in plasma?

A

Albumin

(SM41a)

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75
Q

What Phase II reaction do all benzodiazepines undergo?

A

Glucuronidation

(SM42a 43a)

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76
Q

What are some substrates for CYP2D6?

A

Opioids (codeine, hydrocodone)

Metoprolol

CNS drugs

(SM42a 43a)

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77
Q

What are some substrates for CYP2C9?

A

NSAIDs (celecoxib, ibuprofen)

Warfarin

(SM42a 43a)

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78
Q

What are some substrates for CYP2C19?

A

Diazepam

Omeprazole

Clopidogrel

(SM42a 43a)

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79
Q

How is acetaminophen metabolized?

A

Glucuronidation, sulfation (normal)

CYP3A4, CYP2E1 (toxic)

(SM42a 43a)

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80
Q

What is the toxic compound produced by acetaminophen metabolism?

A

NAPQI

(SM42a 43a)

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81
Q

What can rescue NAPQI in acetaminophen metabolism?

A

Glutathione

(SM42a 43a)

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82
Q

What are two ways ethanol worsens acetaminophen toxicity?

A

Induce CYP2E1

Reduce glutathione levels

(SM42a 43a)

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83
Q

What is the mechanism of action of Memantine?

A

Uncompetitive inhibitor of NMDA receptor (open channel blocker)

(SM38a 39a)

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84
Q

What is Memantine used for?

A

Treat Alzheimers

(SM38a 39a)

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85
Q

What is the mechanism of action of Fluticasone?

A

Activator of glucocorticoid receptor

(SM38a 39a)

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86
Q

What is Fluticasone used for?

A

Inhibit inflammatory response

(SM38a 39a)

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87
Q

What is the mechanism of action of cocaine?

A

Inhibit norepinephrine and dopamine SLC reuptake transporters

(SM40a)

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88
Q

What is the mechanism of action of ADHD drugs?

A

Inhibit norepinephrine SLC reuptake transporter

(SM40a)

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89
Q

What is the mechanism of action of amphetamines?

A

Inhibitor of dopamine SLC reuptake transporters

(SM40a)

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90
Q

What is the mechanism of action of SSRIs?

A

Inhibit serotonin SLC reuptake transporters

(SM40a)

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91
Q

What is the mechanism of action of Cimetidine?

A

Competitive inhibitor of H2 histamine receptor

(SM42a 43a)

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92
Q

How does Cimetidine impact CYPs?

A

Inhibits many CYPs

(SM42a 43a)

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93
Q

What is Cimetidine used for?

A

Suppress gastric acid secretion

(SM42a 43a)

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94
Q

What is the mechanism of action of Diphenhydramine?

A

Competitive inhibitor of H1 histamine receptor

(SM42a 43a)

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95
Q

What is Diphenhydramine used for?

A

Treat mild allergic reactions

(SM42a 43a)

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96
Q

What is the mechanism of action of methylxanthines?

A

Competitive inhibitor of adenosine receptor

(SM42a 43a)

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97
Q

What is theophylline (methylxanthine) used for?

A

Treat asthma and COPD

(SM42a 43a)

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98
Q

How is codeine metabolized?

A

CYP2D6 (O-dealkylation to morphine)

(SM42a 43a)

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99
Q

Which CYPs exhibit polymorphism?

A

CYP2D6

CYP2C9

CYP2C19

(SM42a 43a)

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100
Q

What are some prodrugs?

A

Codeine

Clopidogrel

Thiopurine

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101
Q

How is hydrocodone metabolized?

A

CYP2D6

(SM42a 43a)

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102
Q

What is the mechanism of action of acetaminophen?

A

COX inhibitor

(SM42a 43a)

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103
Q

What is acetaminophen used for?

A

Reduce pain and fever

(SM42a 43a)

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104
Q

How does beta 1 receptor activity affect the heart?

A

Increase heart rate and contractility

(SM38a 39a)

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105
Q

How does beta 2 receptor activity affect smooth muscle?

A

Relaxes smooth muscle

(SM38a 39a)

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106
Q

What is the mechanism of action of metoprolol?

A

Competitive inhibitor of beta-1 adrenoreceptors

(SM42a 43a)

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107
Q

What is metoprolol used for?

A

Treat hypertension

(SM42a 43a)

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108
Q

What is the mechanism of action of omeprazole?

A

Inhibit proton pump

(SM42a 43a)

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109
Q

What is omeprazole used for?

A

Reduce gastric acid secretion

Treat peptic ulcers and GERD

(SM42a 43a)

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110
Q

How is omeprazole metabolized?

A

CYP3A4, CYP2C19

(SM42a 43a)

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111
Q

What is Clopidogrel used for?

A

Anticoagulation

(SM46a)

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112
Q

How is Clopidogrel metabolized?

A

CYP2C19 (prodrug –> active form)

(SM46a)

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113
Q

What is the mechanism of action of Warfarin?

A

Inhibit VKORC1

(SM46a)

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114
Q

What is Warfarin used for?

A

Anticoagulation

(SM46a)

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115
Q

How is Warfarin metabolized?

A

CYP2C9

(SM46a)

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116
Q

Why is Warfarin monitoring important?

A

Warfarin has narrow therapeutic window (TI ~1)

(SM46a)

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117
Q

How is Warfarin monitored?

A

PT and INR

(SM46a)

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118
Q

What is typical range for therapeutic INR for Warfarin?

A

2-3

(SM46a)

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119
Q

What is the mechanism of action of NSAIDs?

A

COX inhibitor

(SM42a 43a)

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120
Q

How are NSAIDs metabolized?

A

CYP2C9

(SM42a 43a)

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121
Q

How does Probenecid interact with penicillin?

A

Probenecid competes with penicillin for OAT (SLC) transport and increases penicillin half-life in plasma

(SM44a)

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122
Q

How does Ritonavir interact with Tenofovir?

A

Ritonavir inhibits ABC transport of Tenofovir out of renal tubule cells into tubule lumen and leads to Tenofovir toxicity in tubule cells

(SM44a)

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123
Q

How does Probenecid interact with Tenofovir?

A

Probenecid inhibits OAT (SLC) transport of Tenofovir into renal tubule cell from plasma and decreases Tenofovir toxicity in tubule cells

(SM44a)

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124
Q

What is Tacrolimus used for?

A

Immunosuppressant

(SM46a)

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125
Q

How is Tacrolimus metabolized?

A

CYP3A4, CYP3A5

(SM46a)

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126
Q

What is notable about CYP3A5 (i.e. in Tacrolimus metabolism)?

A

CYP3A5 exhibits polymorphism and makes most people poor metabolizers

(SM46a)

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127
Q

What is thiopurine used for?

A

Anti-cancer agent

(SM46a)

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128
Q

What do TPMT poor metabolizers have higher risk of?

A

Bone marrow suppression, sepsis

(SM46a)

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129
Q

How is thiopurine metabolized for activity?

A

It is a prodrug that is converted to thioguanines which have anti-cancer activity

(SM46a)

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130
Q

What is an example of a thiopurine?

A

6-mercapto-purine

(SM46a)

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131
Q

How is thiopurine metabolized for elimination?

A

TPMT

(SM46a)

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132
Q

What is Gefitinib/Erlotibin used for?

A

Anti-cancer agents

(SM46a)

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133
Q

What is the mechanism of action of Gefitinib/Erlotinib?

A

Inhibit hyperactive EGFR

(SM46a)

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134
Q

Where does renal tubular secretion occur?

A

Proximal tubule

(SM44a)

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135
Q

Where does renal reabsorption occur?

A

Distal tubule

(SM44a)

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136
Q

What does OCT transport?

A

Weak bases

(SM44a)

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137
Q

What does OAT transport?

A

Weak acids

(SM44a)

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138
Q

What part of renal elimination accounts for long retention time of lipid soluble drugs?

A

Reabsorption

(SM44a)

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139
Q

What can you do to tubular fluid pH to keep weak acids in urine?

A

Alkalize tubular fluid

(SM44a)

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140
Q

What can you do to tubular fluid pH to keep weak bases in urine?

A

Acidify tubular fluid

(SM44a)

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141
Q

What is the formula for half-life?

A

Half-life = 0.693*Vd/CL

(SM45a)

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142
Q

How are clearance and rate of elimination related?

A

Rate of elimination = CL * plasma drug concentration

(SM45a)

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143
Q

How many half-lives does it take to reach 90% steady state concentration?

A

3.3

(SM45a)

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144
Q

How do you determine maintenance dose?

A

Infusion rate = drug dose/dose interval = Css * CL

(SM45a)

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145
Q

How do you determine loading dose?

A

Loading dose = Css * Vd

(SM45a)

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146
Q

What are factors that affect CL (and thus maintenance dose)?

A

Disease, genetics, drug interactions

(SM45a)

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147
Q

What are factors that affect Vd (and thus loading dose)?

A

Age, weight, sex

(SM45a)

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148
Q

What is first-order drug clearance?

A

Rate of elimination proportional to plasma drug concentration

(SM45a)

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149
Q

What is zero-order drug clearance?

A

Constant rate of elimination

(SM45a)

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150
Q

Drug half-life is constant in _____ drug clearance

A

First-order

(SM45a)

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151
Q

Drug half-life is unpredictable in _____ drug clearance

A

Zero-order

(SM45a)

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152
Q

How do most ion channels desensitize?

A

Conformation change

(SM38a 39a)

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153
Q

Which receptor desensitizes in the time course of an action potential?

A

AMPA receptor

(SM38a 39a)

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154
Q

What receptors desensitize on time scale of milliseconds?

A

Ligand-gated ion channels

(SM38a 39a)

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155
Q

What receptors desensitize on time scale of minutes?

A

GPCRs

(SM38a 39a)

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156
Q

What receptors desensitize on time scale of hours?

A

RTKs

JAK/STAT

Cytoplasmic and nuclear receptors

(SM38a 39a)

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157
Q

What are microvilli made of?

A

Actin filaments

(SM48a)

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158
Q

Where are microvilli found?

A

Intestinal brush border and proximal convoluted tubule of kidney

(SM48a)

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159
Q

Where are stereocilia found?

A

Epididymis and vas deferens

(SM48a)

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160
Q

Where are cilia found?

A

Respiratory tract and female reproductive lining

(SM48a)

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161
Q

What are stereocilia made of?

A

Actin filaments

(SM48a)

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162
Q

What are cilia made of?

A

Microtubules

(SM48a)

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163
Q

What proteins form tight junctions?

A

Claudins and occludins

(SM48a)

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164
Q

What proteins form adherens junctions?

A

Cadherins

(SM48a)

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165
Q

What proteins form desmosomes?

A

Cadherins

(SM48a)

166
Q

What do adherens junctions link?

A

Actin cytoskeleton

(SM48a)

167
Q

What do desmosomes link?

A

Intermediate filaments

(SM48a)

168
Q

What proteins form gap junctions?

A

Connexons

(SM48a)

169
Q

What junctions form the apical junctional complex?

A

Tight junctions

Adherens junctions

Desmosomes

(SM48a)

170
Q

What do hemidesmosomes link?

A

Keratin intermediate filaments to type IV collagen

(SM48a)

171
Q

What proteins form hemidesmosomes?

A

Integrins

(SM48a)

172
Q

What type of epithelium is found in blood vessels?

A

Simple squamous

(SM48a)

173
Q

What type of epithelium lines lumen of ducts and tubules (i.e. kidney)?

A

Simple cuboidal

(SM48a)

174
Q

What type of epithelium is found in larger airways of respiratory system?

A

Pseudostratified

(SM48a)

175
Q

What type of epithelium lines oral cavity?

A

Stratified squamous

(SM48a)

176
Q

What type of epithelium is skin?

A

Keratinized stratified squamous

(SM48a)

177
Q

What type of epithelium lines the urinary tract?

A

Transitional

(SM48a)

178
Q

How does plasma protein binding impact a drug’s Vd?

A

Decrease Vd

(SM45a)

179
Q

How does tissue protein binding impact a drug’s Vd?

A

Increase Vd

(SM45a)

180
Q

What is a classic zero-order drug?

A

Phenytoin

(SM45a)

181
Q

What is a rule of thumb for drug dosing interval?

A

Dose every half-life

(SM45a)

182
Q

How does epinephrine affect cardiac muscle?

A

Increased heart rate and contractility via beta 1 receptor

(SM35a)

183
Q

How does epinephrine affect smooth muscle?

A

Relax bronchiole smooth muscle via beta 2 receptor

(SM35a)

184
Q

How does epinephrine affect skeletal muscle?

A

It doesn’t

(SM35a)

185
Q

What causes hyperekplexia (familial startle disease)?

A

Mutated glycine receptors

(SM38a 39a)

186
Q

All receptors on effectors in the autonomic nervous system are _____.

A

GPCRs

(SM38a 39a)

187
Q

What is the fastest form of signaling?

A

Ligand-gated ion channels

(SM38a 39a)

188
Q

What is the second fastest form of signaling?

A

GPCR membrane delimited effects

(SM38a 39a)

189
Q

What is the third fastest form of signaling?

A

Second messenger pathway of GPCR signaling

(SM38a 39a)

190
Q

What subscript typically denotes GPCR membrane delimited effects?

A

2

(SM38a 39a)

191
Q

What subscript usually denotes GPCR second messenger pathway?

A

1 or 3

(SM38a 39a)

192
Q

How does PKA phosphorylation affect cardiac and smooth muscle?

A

Increase heart rate and contractility (beta 1)

Relax smooth muscle (beta 2)

(SM38a 39a)

193
Q

Constitutively active RTKs commonly occur in _____.

A

Cancers

(SM38a 39a)

194
Q

Growth factors typically use the _____ pathway in RTK signaling

A

Ras/MAP kinase

(SM38a 39a)

195
Q

Describe glucocorticoid signaling

A

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
Q

_____ channels desensitize faster than any signaling process

A

AMPA

(SM38a 39a)

197
Q

_____ desensitize very slowly

A

Positive allosteric modulators

(SM38a 39a)

198
Q

_____ can be prescribed for years without desensitization

A

Zolpidem

(SM38a 39a)

199
Q

How are benzodiazepines (-zolams and -azepams) metabolized?

A

CYP3A4* –> glucuronidation

*-azepams also use CYP2C19

(SM42a 43a)

200
Q

How are histamine receptor blockers (Cimetidine, Diphenhydramine) metabolized?

A

CYPs (oxidation)

(SM42a 43a)

201
Q

How are methylxanthines (Caffeine, Theophylline) metabolized?

A

CYPs (dealkylation)

(SM42a 43a)

202
Q

Furanocoumarins in grapefruit juice inhibit _____

A

CYP3A4

(SM42a 43a)

203
Q

Does substrate shape matter for CYP3A4?

A

No, very large active site

(SM42a 43a)

204
Q

How is metoprolol metabolized?

A

CYP2D6

(SM42a 43a)

205
Q

How are opioids (codeine, hydrocodone) metabolized?

A

CYP2D6

(SM42a 43a)

206
Q

How are many CNS drugs metabolized?

A

CYP2D6

(SM42a 43a)

207
Q

How is omeprazole metabolized?

A

CYP2C19

(SM42a 43a)

208
Q

How is clopidogrel metabolized?

A

CYP2C19

(SM42a 43a)

209
Q

How are NSAIDs metabolized?

A

CYP2C9

(SM42a 43a)

210
Q

What is the mechanism of action of tetrodotoxin?

A

Blocks voltage-gated Na+ channels in nerve and muscle

(SM37a)

211
Q

What is the mechanism of action of local anesthetics?

A

Block inactivated voltage-gated Na+ channels

(SM37a)

212
Q

What is the mechanism of action of minoxidil?

A

Activate K_ATP channels in vascular smooth muscle

(SM37a)

213
Q

What is minoxidil used for?

A

Treat hypertension

(SM37a)

214
Q

What is the mechanism of sulfonylurea?

A

Inhibit K_ATP channels in pancreatic beta cells

(SM37a)

215
Q

What is sulfonylurea used for?

A

Treat diabetes

(SM37a)

216
Q

What happens if you inhibit HERG K+ channel?

A

Can increase risk of arrhythmia by prolonging QT interval too much

(SM37a)

217
Q

Why was terfenadine withdrawn?

A

It blocked HERG K+ channels, making it pro-arrhythmic

(SM37a)

218
Q

Cl- is _____ in developing neurons and _____ in mature neurons

A

High; low

(SM36a)

219
Q

CYP3A4 can be found in _____ and in _____

A

Intestinal epithelium; liver

(SM41a)

220
Q

St. John’s wort induces _____

A

CYP3A4, CYP2C9, CYP2C19, CYP2E1

(SM42a 43a)

221
Q

Gingko induces _____

A

CYP3A4, CYP2C9, CYP2C19

(SM42a 43a)

222
Q

Echinacea induces _____

A

CYP3A4

(SM42a 43a)

223
Q

What is the formula for renal clearance?

A

Renal clearance = urine concentration * urine flow rate / plasma concentration

(SM44a)

224
Q

_____ are not filtered well at glomerulus

A

Large anionic molecules

(SM44a)

225
Q

Normal GFR is _____

A

125 mL/min or 180 L/day

(SM44a)

226
Q

Digoxin, lithium carbonate, allopurinol, and antibiotics are commonly eliminated via _____

A

Kidneys

(SM44a)

227
Q

Cimetidine, ceftazimide, digoxin, cisplatin, indinavir, quinidine, and verapamil are transported by _____ in the kidneys

A

OCTs

(SM44a)

228
Q

Penicillin, probenecid, aspirin, furosemide, thiazides, ibuprofen, and statins are transported by _____ in the kidneys

A

OATs

(SM44a)

229
Q

Methamphetamine is a _____ that is better excreted in _____ urine

A

Weak base; acidic

(SM44a)

230
Q

Phenobarbital is a _____ that is best excreted in _____ urine

A

Weak acid; alkaline

(SM44a)

231
Q

What is the formula for hepatic clearance?

A

Hepatic clearance = hepatic flow * extraction ratio

Extraction ratio = (C_in - C_out)/C_in

(SM44a)

232
Q

High extraction drugs are sensitive to _____

A

Liver blood flow

(SM44a)

233
Q

Low extraction drugs are sensitive to _____

A

Intrinsic hepatic metabolism and protein binding

(SM44a)

234
Q

Morphine, lidocaine, propranolol, verapamil, propofol, and ketamine are _____(high/low) extraction drugs

A

High

(SM44a)

235
Q

Digoxin, diazepam, valproic acid, tolbutamide, cimetidine, and phenytoin are _____(high/low) extraction drugs

A

Low

(SM44a)

236
Q

What can statins cause at high levels?

A

Myotoxicity (due to impaired SLCs)

(SM44a)

237
Q

Digoxin, morphine, and estradiol are commonly recycled via _____

A

Enterohepatic cycle

(SM44a)

238
Q

_____ forms spinal cord segments below S2 and comes from _____ germ layer

A

Caudal eminence; mesoderm

(SM49a 54a)

239
Q

What are the layers of the meninges, from outermost to innermost?

A

Dura mater, arachnoid, pia mater

(SM49a 54a)

240
Q

CSF is in the _____ space

A

Subarachnoid

(SM49a 54a)

241
Q

What suspends the spinal cord in the subarachnoid space?

A

Denticulate ligaments (part of pia mater)

(SM49a 54a)

242
Q

Where does the subarachnoid space terminate?

A

S1 vertebrae

(SM49a 54a)

243
Q

What anchors the bottom of the spinal cord?

A

Filum terminale (part of pia mater)

(SM49a 54a)

244
Q

The _____ are dorsal and ventral roots descending from the spinal cord to the appropriate level of exit from vertebral column

A

Cauda equina

(SM49a 54a)

245
Q

Vagus nerve is cranial nerve _____

A

X

(SM49a 54a)

246
Q

Where do sympathetic neurons leave spinal cord from?

A

T1 to L2

(SM49a 54a)

247
Q

Where do parasympathetic neurons leave spinal cord from?

A

Cranial and sacral regions

(SM49a 54a)

248
Q

What splanchnic nerves pass through the diaphragm?

A

Thoracic and lumbar

(SM49a 54a)

249
Q

What does somatopleure give rise to?

A

Somatic nervous system

(SM49a 54a)

250
Q

What does splanchnopleure give rise to?

A

Autonomic nervous system

(SM49a 54a)

251
Q

All _____ have visceral sensory nerves traveling with them

A

Autonomic nerves

(SM49a 54a)

252
Q

Where does spinal cord end in adults?

A

L1 vertebrae (right below it)

(SM49a 54a)

253
Q

What is ECM made of?

A

Fibers: collagen, elastin

Ground substance: GAGs, proteglycans, glycoproteins

(SM50a)

254
Q

Where is loose connective tissue found?

A

Superficial fascia

(SM50a)

255
Q

What is dense irregular connective tissue made of?

A

Woven collagen fibers in a matrix with some elastin

(SM50a)

256
Q

What is dense irregular connective tissue good at?

A

Resisting multidirectional impact

(SM50a)

257
Q

Where is dense irregular connective tissue found?

A

Dermis, joints, fascia

(SM50a)

258
Q

What is dense regular connective tissue made of?

A

Parallel collagen fibers

(SM50a)

259
Q

What is dense regular connective tissue good at?

A

Resisting tension

(SM50a)

260
Q

What is reticular connective tissue made of?

A

Very fine type III collagen

(SM50a)

261
Q

Where is reticular connective tissue found?

A

Stroma of lymphathic and hematopoietic organs

(SM50a)

262
Q

What is adipose (connective tissue) good at?

A

Storing energy, providing insulation, protection

(SM50a)

263
Q

What cell type produces most of ECM components?

A

Fibroblasts/myofibroblasts

(SM50a)

264
Q

Where is dense regular connection tissue found?

A

Tendons

(SM50a)

265
Q

What is required to assemble collagen fibers?

A

Vitamin C

(SM50a)

266
Q

What is required to assemble elastin fibers?

A

Fibrillin

(SM50a)

267
Q

Density is used to refer to what images?

A

X-ray

(SM51a)

268
Q

What are the 5 x-ray densities from blackest to whitest?

A

Air

Fat

Soft tissue, liquid

Bone, calcium

Metal, contrast

(SM51a)

269
Q

Echogenicity is used to refer to what images?

A

Ultrasound

(SM51a)

270
Q

Intensity is used to refer to what images?

A

MRI

(SM51a)

271
Q

What imaging modalities do not use ionizing radiation?

A

Ultrasound and MRI

(SM51a)

272
Q

What can ultrasound not penetrate?

A

Air and bone

(SM51a)

273
Q

What is ultrasound useful for?

A

Evaluating solid organs, guiding biopsies, evaluating blood flow

(SM51a)

274
Q

What are examples of conditionally dividing cells?

A

Liver and kidney cells

(SM52a)

275
Q

What are examples of non-dividing cells?

A

Muscle cells and neurons

(SM52a)

276
Q

Physiologic stimuli for cellular morphologic changes are often mediated by what?

A

Hormones

(SM52a)

277
Q

What is a physiologic example of hypertrophy during pregnancy?

A

Growth of uterus

(SM52a)

278
Q

What is a physiologic example of hyperplasia during pregnancy?

A

Proliferation of breast tissue

(SM52a)

279
Q

What is a physiologic example of metaplasia?

A

Cervix during menarche

(SM52a)

280
Q

What is a pathologic example of metaplasia in the esophagus?

A

Barrett’s Esophagus

(SM52a)

281
Q

What is a pathologic example of metaplasia in the lungs?

A

Columnar to squamous metaplasia in smoker

(SM52a)

282
Q

What is a carcinoma?

A

Malignant epithelial neoplasm

(SM52a)

283
Q

What is a sarcoma?

A

Malignant mesenchymal neoplasm

(SM52a)

284
Q

What is a lymphoma?

A

Malignant lymphatic neoplasm

(SM52a)

285
Q

What is a melanoma?

A

Malignant melanocytic neoplasm

(SM52a)

286
Q

What does the prefix adeno mean?

A

Derived from glandular tissue

(SM52a)

287
Q

What does the prefix leiomyo mean?

A

Derived from smooth muscle

(SM52a)

288
Q

What does the prefix rhabdomyo mean?

A

Derived from skeletal muscle

(SM52a)

289
Q

What intercellular junction form spot welds?

A

Desmosomes (macula adherens)

(SM48a)

290
Q

What is mesothelium?

A

Epithelium that lines the pleurae, peritoneum, and pericardium

(SM48a)

291
Q

For cancer, what does grading refer to?

A

Degree of histologic differentiation

(SM52a)

292
Q

For cancer, what does staging refer to?

A

Extent of tumor spread, including size of primary tumor, lymph node involvement, and distant metastatic spread

(SM52a)

293
Q

What are the two things that make up a blastocyst?

A

Trophoblast and inner cell mass

(SM59a 60a)

294
Q

What three things do the inner cell mass give rise to?

A

Amnion, embryonic disc, and yolk sac

(SM59a 60a)

295
Q

What three layers make up the chorion?

A

Syntrophoblast, cytotrophoblast, and extraembryonic mesoderm

(SM59a 60a)

296
Q

What two layers make up the amnion proper?

A

Ectoderm and extraembryonic mesoderm

(SM59a 60a)

297
Q

What two layers make up the yolk sac proper?

A

Endoderm and extraembryonic mesoderm

(SM59a 60a)

298
Q

What can too little amniotic fluid indicate?

A

Renal agenesis

(SM59a 60a)

299
Q

What can excess amniotic fluid indicate?

A

Anencephaly or tracheoesophageal fistula

(SM59a 60a)

300
Q

What layer of the chorion is in direct contact with maternal blood?

A

Syntrophoblast

(SM59a 60a)

301
Q

What weeks cover the blastocyst period?

A

1-2

(SM59a 60a)

302
Q

What weeks cover the embryo period?

A

3-8

(SM59a 60a)

303
Q

What weeks cover the fetal period?

A

8-term

(SM59a 60a)

304
Q

What is gastrulation?

A

Formation of intraembryonic mesoderm and elongation of embryonic disc

(SM59a 60a)

305
Q

What does the primitive knot give rise to?

A

Notochord (midline of mesoderm)

(SM59a 60a)

306
Q

What does the primitive streak give rise to?

A

Intraembryonic mesoderm (except notocord)

(SM59a 60a)

307
Q

What does lateral plate mesoderm give rise to (embryo)?

A

Intraembryonic coelom

(SM59a 60a)

308
Q

What two germ layers are in somatopleure?

A

Ectoderm and mesoderm

(SM59a 60a)

309
Q

What two germ layers are in splanchnopleure?

A

Endoderm and mesoderm

(SM59a 60a)

310
Q

What two things does septum transversum give rise to?

A

Diaphragm and liver stroma

(SM59a 60a)

311
Q

What week does blastocyst implantation occur?

A

2

(SM59a 60a)

312
Q

What week do you get the formation of amnion proper, yolk sac proper, and chorion?

A

2

(SM59a 60a)

313
Q

What week does gastrulation occur?

A

3

(SM59a 60a)

314
Q

What week does gastrula change shape from disc to cylinder?

A

4

(SM59a 60a)

315
Q

What week do somatopleure and splanchnopleure form?

A

4

(SM59a 60a)

316
Q

What week does septum transversum form?

A

4-8

(SM59a 60a)

317
Q

What week do you get GI organ buds and limb buds?

A

4-8

(SM59a 60a)

318
Q

What does somatopleure become?

A

Lateral and ventral body wall

(SM59a 60a)

319
Q

What does splanchnopleure become?

A

Visceral structure, including gut tube walls and mesenteries

(SM59a 60a)

320
Q

What do you call the two sheets of visceral peritoneum that suspend gut tube from body wall?

A

Mesenteries

(SM59a 60a)

321
Q

How many amions and yolk sacs do monozygotic twins have?

A

2

(SM59a 60a)

322
Q

How many chorion and placenta do monozygotic twins have?

A

1

(SM59a 60a)

323
Q

What is reperfusion injury?

A

Explosive onset of necrosis during reperfusion of ischemic organs due to sudden generation of ROS

(SM53a)

324
Q

What is karyolysis?

A

Nuclei fading and disappearing

(SM53a)

325
Q

What is karyorrhexis?

A

Nuclei fragmentation

(SM53a)

326
Q

What is pyknosis?

A

Nuclear shrinkage and increased basophilia (darker)

(SM53a)

327
Q

Are karyolysis, karyorrhexis, and pyknosis associated with reversible or irreversible cellular injury?

A

Irreversible

(SM53a)

328
Q

Does apoptosis or necrosis use caspases?

A

Apoptosis

(SM53a)

329
Q

Is cytoplasmic blebbing associated with apoptosis or necrosis?

A

Apoptosis

(SM53a)

330
Q

Is cell swelling associated with apoptosis or necrosis?

A

Necrosis

(SM53a)

331
Q

Is cell shrinkage associated with apoptosis or necrosis?

A

Apoptosis

(SM53a)

332
Q

Is chromatin condensation associated with apoptosis or necrosis?

A

Apoptosis

(SM53a)

333
Q

Is inflammation associated with apoptosis or necrosis?

A

Necrosis

(SM53a)

334
Q

Is nuclear swelling and lysis associated with apoptosis or necrosis?

A

Necrosis

(SM53a)

335
Q

Is energy required for apoptosis or necrosis?

A

Apoptosis

(SM53a)

336
Q

Is protein synthesis required for apoptosis or necrosis?

A

Apoptosis

(SM53a)

337
Q

Is apoptosis or necrosis energy dependent?

A

Apoptosis

(SM53a)

338
Q

Is de novo transcription associated with apoptosis or necrosis?

A

Apoptosis

(SM53a)

339
Q

Is a DNA fragmentation ladder associated with apoptosis or necrosis?

A

Apoptosis

(SM53a)

340
Q

Is random DNA degradation associated with apoptosis or necrosis?

A

Necrosis

(SM53a)

341
Q

What type of necrosis is associated with cell outlines with missing nuclei?

A

Coagulative

(SM53a)

342
Q

What type of necrosis is often found in brain?

A

Liquefactive

(SM53a)

343
Q

What type of necrosis is commonly associated with tuberculosis and looks like dry cheese?

A

Caseous

(SM53a)

344
Q

What type of necrosis is almost exclusively found in adipose tissue contiguous with pancreas?

A

Fat

(SM53a)

345
Q

What type of necrosis is associated with immune reactions in blood vessels?

A

Fibrinoid

(SM53a)

346
Q

What type of necrosis is commonly localized to lower limb soft tissues?

A

Gangrenous

(SM53a)

347
Q

How does decreased ATP production affect pH?

A

Decreases pH

(SM53a)

348
Q

What is required to open mitochondrial transitional pore?

A

Ca2+

(SM53a)

349
Q

What organelle can leak apoptotic proteins?

A

Mitochondria

(SM53a)

350
Q

What is the effect of Mg2+ and polyvalent cations on voltage-gated Ca2+ channels?

A

Competitive inhibitor

(SM57a)

351
Q

How do Mg2+ and polyvalent cations affect neurotransmission?

A

Reduce neurotransmitter release

(SM57a)

352
Q

What is the mechanism of action of botulinum toxin A?

A

Cleave SNAP-25

(SM57a)

353
Q

What is botulinum toxin A used for?

A

Treat spasticity

(SM57a)

354
Q

What is the mechanism of action of rocuronium and vercuronium?

A

Competitive inhibitor of nicotinic receptors

(SM57a)

355
Q

Are rocuronium and vercuronium depolarizing or non-depolarizing?

A

Non-depolarizing

(SM57a)

356
Q

What are rocuronium and vercuronium used for?

A

Relax neuromuscular junction for surgery

(SM57a)

357
Q

What is the mechanism of action of succinylcholine?

A

Competitive inhibitor of nicotinic receptors

(SM57a)

358
Q

Is succinylcholine depolarizing or non-depolarizing?

A

Depolarizing

(SM57a)

359
Q

What is succinylcholine used for?

A

Relax neuromuscular junction for surgery

(SM57a)

360
Q

What is the mechanism of action of neostigmine?

A

Inhibit cholinesterase

(SM57a)

361
Q

What is neostigmine used for?

A

Speed recovery from non-depolarizing block after surgery and treat myasthenia gravis

(SM57a)

362
Q

What is the mechanism of action of atropine?

A

Competitive inhibitor of muscarinic receptors

(SM57a)

363
Q

What is atropine used for?

A

Increase HR during spinal anesthesia

(SM57a)

364
Q

What is the mechanism of action of ipratropium and tiotropium?

A

Competitive inhibitor of muscarinic receptors

(SM57a)

365
Q

What are ipratropium and tiotropium used for?

A

Treat asthma and COPD

(SM57a)

366
Q

What is the mechanism of action of phenylephrine?

A

Agonist of alpha-1 adrenoreceptors

(SM57a)

367
Q

What is phenylephrine used for?

A

Increase blood pressure and decrease nasal congestion

(SM57a)

368
Q

What can exogenous norepinephrine and epinephrine be used for?

A

Treat hypotension

(SM57a)

369
Q

What is the mechanism of action of exogenous norepinephrine and epinephrine?

A

Agonist of alpha-1 adrenoreceptors

(SM57a)

370
Q

What is the mechanism of action of albuterol?

A

Agonist of beta-2 adrenoreceptors

(SM57a)

371
Q

What is albuterol used for?

A

Open airways (rescue inhaler)

(SM57a)

372
Q

What are formeterol and salmeterol used for?

A

Open airways (long lasting)

(SM57a)

373
Q

What is the mechanism of action of propranolol?

A

Competitive inhibitor of beta-1 (and beta-2) adrenoreceptors

(SM57a)

374
Q

What is the mechanism of action of metaprolol?

A

Competitive inhibitor of beta-1 adrenoreceptors

(SM57a)

375
Q

What are propranolol and metaprolol used for?

A

Treat arrhythmias and hypertension

(SM57a)

376
Q

You should never give (propranolol/metaprolol) to asthmatics

A

Propranolol

(SM57a)

377
Q

What signaling pathway do alpha-1 adrenoreceptors use?

A

Phospholipase C –> smooth muscle contraction

(SM57a)

378
Q

What adrenoreceptor is responsible for sympathetic tone?

A

Alpha-1

(SM57a)

379
Q

What signaling pathway do beta-1 adrenoreceptors use?

A

cAMP –> increase HR and heart contractility

(SM57a)

380
Q

What signaling pathway do beta-2 adrenoreceptors use?

A

cAMP –> relax smooth muscle

(SM57a)

381
Q

What signaling pathway do alpha-2 adrenoreceptors use?

A

Membrane delimited inhibitory effects

(SM57a)

382
Q

What signaling pathway do muscarinic receptors in the heart use?

A

Activate K+ channels

(SM57a)

383
Q

What signaling pathway do muscarinic receptors in the airways use?

A

Phospholipase C –> smooth muscle contraction

(SM57a)

384
Q

The (vagus/phrenic) nerve runs posterior to the root of lung

A

Vagus

(Lab 2)

385
Q

The (vagus/phrenic) nerve runs anterior to root of lung

A

Phrenic

(Lab 2)

386
Q

What three branches come off the aortic arch?

A

Brachiocephalic trunk

Left common carotid artery

Left subclavian artery

(Lab 2)

387
Q

What two branches feed into superior vena cava?

A

Right brachiocephalic vein

Left brachiocephalic vein

(Lab 2)

388
Q

Which nerve runs along trachea and esophagus?

A

Vagus

(Lab 2)

389
Q

Where does phrenic nerve leave from?

A

Ventral rami of cervical spinal nerves 3-5

(Lab 2)

390
Q

What does the notochord do?

A

Induce neural plate formation

(SM59a 60a)

391
Q

What does paraxial column mesoderm give rise to?

A

Somites

(SM59a 60a)

392
Q

What does intermediate column mesoderm give rise to?

A

Kidneys and gonads

(SM59a 60a)

393
Q

What does lateral plate mesoderm give rise to (adult)?

A

Pleura, peritoneum, and connective tissue of organs and body wall

(SM59a 60a)

394
Q

What genes establish anterior-posterior axis in embryo?

A

HOX genes

(SM61a)

395
Q

3’ HOX genes are expressed (earlier/later) than 5’ HOX genes

A

Earlier

(SM61a)

396
Q

3’ HOX genes end more (anteriorly/posteriorly) than 5’ HOX genes

A

Anteriorly

(SM61a)

397
Q

What results from HOX-D13 mutations?

A

Polysyndactyly

(SM61a)

398
Q

What genes establish dorsal-ventral neural tube axis in embryo?

A

Shh

(SM61a)

399
Q

What results from Shh mutations?

A

Holoprosencephaly (abnormal septation in brain)

(SM61a)

400
Q

What results from Patched mutations?

A

Basal cell nevus syndrome (skull/rib abnormalities and cancer predisposition)

(SM61a)

401
Q

What results from GLI3 mutations?

A

Cephalopolysyndactyly, polysyndactyly

(SM61a)

402
Q

What is the fate of medial dermamyotomes?

A

Back musculature and skin

(SM61a)

403
Q

What is the fate of lateral dermamyotomes?

A

Lateral and ventral body wall musculature and skin

(SM61a)

404
Q

What is the fate of sclerotomes?

A

Ribs and vertebral bodies

(SM61a)

405
Q

What genes establish anterior-posterior limb axis?

A

Shh

(SM61a)

406
Q

What is ascites?

A

Fluid accumulation in peritoneal cavity

(SM62a)

407
Q

Pleural cavities become separated from pericardial cavity by growth of what?

A

Pleuropericardial folds

(SM62a)

408
Q

What is the epicardium?

A

Visceral layer of pericardium

(SM62a)

409
Q

What does the gut tube give rise to?

A

Trachea, lungs, digestive organs

(SM62a)

410
Q

Is the charged or uncharged form of a drug more easily absorbed?

A

Uncharged

(SM40a)

Foundations 2 (1 decks)

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