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Fall Pharm > Exam Review 1 > Flashcards

Exam Review 1 Flashcards

1
Q

Pharmacology

A

The study of substances that react with living systems through chemical processes.

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2
Q

Toxicology

A

The branch of pharmacology concerned with the adverse effects of chemicals on living systems

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3
Q

Agonist

A

a substance that binds to a receptor to activate a response (usually the response you would see from the native ligand)

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4
Q

Antagonist

A

a drug that binds to a receptor to prevent the binding of native ligand (inhibits receptor)

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5
Q

Drug

A

Any substance that brings about a change in biological function through chemical processes

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6
Q

Receptor

A

Are proteins where the drug molecule reacts, and plays a regulatory role in the biological system.
(can be: regulatory proteins, enzymes, transport, proteins, structural proteins)

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7
Q

Pharmacogenomics

A

Genetic makeup vs response to drug (the future of pharmacology)

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8
Q

Endogenous

A

“essentially physiology”

ligands inside the body

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9
Q

Exogenous

A

Drugs, toxins, or poisons originating outside the body

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10
Q

Pharmacodynamics

A

the way the drug works on the body

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11
Q

Pharmacokinetics

A

The way the body works on the drug
(Absorption, distribution, metabolism, elimination)
(occasionally L=liberation)

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12
Q

Toxins

A

Biologic

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13
Q

Poisons

A

Typically non-organic

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14
Q

Characteristics that determine interaction between receptor and drug:

A

Appropriate size
Electrical charge
Shape
Atomic composition

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15
Q

Physical nature of drugs

A

solid/liquid/gas

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16
Q

Molecular weight of most drugs:

A

100-1,000 kilodalton (MWU)

Drugs >1,000 MWU can’t readily diffuse and may have to be given directly into the location of action

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17
Q

3 Bond types:

A

Covalent
Electrostatic
Hydrophobic
(see picture on lecture 1 at 1:09:16)

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18
Q

Covalent bonds

A

Drug and receptor are sharing electrons. (Very strong, Less specificity) irreversible

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19
Q

Electrostatic bonds (listed from greater bond strength to lesser bond strength)

A 
Charged molecules (ionic bonds)
Hydrogen bonds (weakly charged bonds)
Van der Waals forces
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20
Q

Hydrophobic interactions

A

Very weak
High specificity
lipid soluble
no charge

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21
Q

Chirality

A

non-superposable on its mirror image

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22
Q

Stereoisomerism

A

Drug with exact same chemical components but are mirror images (have a central carbon)

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23
Q

Amount of drugs we give that are Stereoisomers

A

More than half

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24
Q

Racemic mixture

example

A

a mixture that is equal amounts of left and right hand stereoisomers (R-Ketamine, S-Ketamine)

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25
Q

What is more toxic S or R ketamine?

A

R-Ketamine

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26
Q

Allosteric

A

Bind to a receptor
NOT at active site
Agonist or Antagonist
non-competative

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27
Q

Orthosteric

A

Bind to receptor AT the active site
Agonist or Antagonist
Competitive

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28
Q

Drug concentration response curve:

Bmax

A

Concentration at which maximum receptors are bound

lecture 1 at 1:23:25

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29
Q

Drug concentration response curve:

Kd

A

Concentration at which 1/2 of receptors are bound

lecture 1 at 1:23:25

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30
Q

Drug concentration response curve:

Emax

A

Concentration at which the maximum effect the drug is produce (vary depending on drug)
(Acetaminophen will have lesser Emax than Morphine)(lecture 1 at 1:23:25)

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31
Q

Drug concentration response curve:

EC50

A

Concentration of drug when 50% of effect is seen

lecture 1 at 1:23:25

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32
Q

A low Kd means..

A

high drug/receptor affinity

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33
Q

Indirect agonist (mimic)

A

inhibits the molecules responsible for terminating the action of endogenous agonist. (has same effects as agonist but doesn’t bind to the same receptor)

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34
Q

Competitive antagonist

A

Orthosteric

Can be countered by increasing amounts of agonist (surmountable)

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35
Q

Non-competitive antagonist

A

Allosteric

Insurmountable

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36
Q

Irreversible antagonist

A

Can be allosteric or orthosteric
Covalently bind to receptor and do not come off
Not the same as non-competitive
Only way to get rid of it is to get rid of the receptor

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37
Q

Partial agonist

A

Binds to same receptor site as agonist but produces a lower response
Competes with full agonist form binding site

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38
Q

Physiologic antagonism

A

Drugs acting at different receptors to counter effects of each other (example: Epi increases HR at beta1, ACH decreases HR at muscarinic receptor)

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39
Q

Inverse agonist

and example

A

Greater affinity for inactive state of receptor. (no constitute activity) (example: narcan)
(see lecture 2 at 0:20:00)

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40
Q

Factors that determine the duration of a drugs effects:

A
  • As long as the drug stays bound to receptor.
  • Longterm downstream effects last until downstream effectors go away. (If a drug initiates the production of a protein, it will take longer to see effects and longer for response to stop)
  • Receptor is degraded (in covalent bonding)
  • Desensitization
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41
Q

Good receptor properties:

A

Selective

Alteration

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42
Q

Bad receptor properties:

A

“inert binding sites”

drug carriers

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43
Q

Potency

A

Concentration (EC50) or Dose (ED50) of a drug required to produce 50% of that drugs maximal effect

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44
Q

Maximal efficacy

A

Greatest possible response a drug can deliver

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45
Q

Dose-Response curve:

ED50

A

Median Effective Dose

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46
Q

Dose-Response curve:

TD50

A

Median Toxic Dose

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47
Q

Dose-Response curve:

LD50

A

Median Lethal Dose

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48
Q

Therapeutic Index

A

Establishes margin of safety (higher the number the better)
ED50 vs TD50
Animals: LD50/ED50
Humans: TD50/ED50

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49
Q

Idiosyncratic

A

Unusual drug response (we don’t know why one patient responds differently than another)

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50
Q

Possible reasons for idiosyncratic drug response:

A
  • genetic factors
  • hyperactive
  • hypoactive
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51
Q

Tolerance

A

Response changes over course of therapy

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52
Q

Tachyphylaxis

A

Quick tolerance

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53
Q

Chemical Antagonism

and example

A

Administration of opposite charge

example: Protamine (+) and heparin (-

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54
Q

4 causes to variation in drug responsiveness:

A
  • Alteration in concentration of drug that actually reaches receptor (age, weight, sex, disease state, rate of absorption/distribution/clearance)
  • Variation in concentration of endogenous receptor ligand
  • Alteration in number or function of receptors
  • Changes in components of response distal to receptor (largest and most important cause)
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55
Q

Toxic effects

A

Extension of therapeutic effects

Some drugs produce desired and adverse effects at same receptor, others bind to different classes of receptor sites

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56
Q

4 ways of permeation:

A 
Aqueous diffusion
Lipid diffusion
Special carriers
Endocytosis/Exocytosis
(All depend on drug, charge, size)
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57
Q

Aqueous diffusion

A

Diffuse by concentration gradient
Charged drugs through aqueous channels
Molecules can be large (20K-30K MVW)
Larger aqueous compartments (cytosol, Interstitial)

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58
Q

Lipid diffusion

A

Uncharged drugs

Gets into cells/body easily

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59
Q

Special carriers

A

If drug needs to get from one place to another (pumps or special carrier proteins)
Molecules bind to drug and move across barriers.
Active transport or facilitated diffusion.

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60
Q

Endocytosis/Exocytosis

A

Cell swallowing the drug, pulling it into the cell, and pushing it out the other side. (see lecture 2 at 0:56:50)

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61
Q

What will not diffuse through aqueous diffusion?

A

Highly charged molecules

Bound to large proteins (carriers)

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62
Q

What is the most limiting factor for drug permeation?

A

Lipid diffusion because there are many lipid barriers to cross

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63
Q

The number one thing to consider when a drug is crossing a barrier is..

A

..the concentration of the drug on either side of the barrier.

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64
Q

Fick’s Law of Diffusion

A

Relates concentration to variables of diffusion path (how readily a substance will move down a concentration gradient)

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65
Q

pKa and pH

A

pKa is pH at which ionized and unionized concentrations are equal

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66
Q

If pH < pKa, it favors..

ratio will be..

A

Protonated form

ratio will be <1

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67
Q

If pH >pKa, if favors..

ratio will be..

A

Unprotonated form

ratio will be >1

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68
Q

Henderson Hasselbach Equation

A

pH = pKa + log([A-]/[HA])

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69
Q

What does the Henderson Hasselbach equation tell us?

A

Ratio of ionized to unionized.

Relates ionization constant (pKa) to concentration of H+ (pH)

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70
Q

If pH=pKa..

A

..log([A-]/[HA]) = 0

ionized vs unionized are in equilibrium

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71
Q

Weak acids are uncharged when they are..

A

..protonated.

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72
Q

Weak bases are uncharged when they are..

A

..unprotonated

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73
Q

pH of stomach

A

1-1.5

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74
Q

pH of blood

A

7.35-7.45

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75
Q

Where are most drugs filtered?

A

Glomerulus

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76
Q

Weak acids excreted faster in..

A

..alkaline urine

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77
Q

Weak bases excreted faster in..

A

..acidic urine

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78
Q

Receptor affinity..

A

..determines dose

if receptor binds to drug with higher affinity you give less of drug; low affinity, more drug

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79
Q

Receptor selectivity..

A

..varies per drug

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80
Q

Receptors can be activated or blocked by..

A

Agonist or antagonist.

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81
Q

Orphan receptors

A

Receptor without a native ligand or we don’t know what the native ligand is

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82
Q

7 receptor categories by molecular structure:

A
  • Seven-transmembrane receptors (7TM)
  • Ligand gated channels
  • Ion channels
  • Catalytic receptors
  • Nuclear receptors
  • Transporters
  • Enzymes
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83
Q

What is cell signaling?

A

Converting extracellular signals into intracellular responses

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84
Q

Steps in cell signaling:

A 
Signaling molecule released from ligand-->
Binds to receptor-->
Activates signal transduction protein-->
Production of 2nd messengers-->
Activate effector protein
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85
Q

Lag period

A

Ligand binds to a receptor and starts the process of transcription/translation which is a timely process.
(can take 30minutes to several hours)

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86
Q

Persistence

A

How long the drug is going to last.
Protein degradation varies.
(Response can remain for hours to days)

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87
Q

Phosphorylation Cascade

A 
Drug binds to receptor-->
response is to add Phos to a protein which activates protein-->
repeats-->
eventually elicits cell response  
(see lecture 2 at 1:37:16)
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88
Q

Kinase

A

Enzymes within the cell that will add a phosphate group to a specific protein using ATP (require energy)

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89
Q

Phosphorylase

A

Enzyme within the cell that will add a phosphate group to a specific protein using inorganic phosphate thats readily available in the cell (don’t require energy)

90
Q

Phosphatase

A

Enzyme that strips Protein-P of its phosphate

91
Q

Signaling Mechanisms are based on..

A

..Molecular structure (seven superfamilies of receptors)

92
Q

Drug-receptor binding-signaling depends on..

A

..if its intracellular or intercellular

93
Q

G-Protein Coupled Receptor (GPCR) can activate:

A

..hundreds of G-proteins when a ligand is bound to the surface of the receptor.

94
Q

GPCR structure:

A

7 trans-membrane alpha-helices

95
Q

G-protein binding protein:

A 
Guanine nucleotide 
(GDP=inactive)
(GTP=active)
96
Q

GPCR exhibits pleiotropy which means..

A

..several downstream effects are possible

97
Q

Steps of activating GPCR:

A

Ligand binds to receptor–>
Activates G-protein which dislodges GDP and binds to GTP–>
G-protein activates 2nd enzyme–>
Activates cellular response–>
G-protein becomes inactive and strips iP off GTP becoming GDP–>
G-protein goes back to receptor

98
Q

GPCR: Fast response

A

Metabotropic ion channels (G-protein activates and opens ion channel)
(undergoes rapid desensitization)

99
Q

GPCR: Slow response

A

Transcription factor activation

100
Q

Second messengers:

A 
cAMP
cGMP
Calcium
DAG
IP3
101
Q

Adenylyl cyclase –>

A

Increases cAMP

102
Q

Adenylyl cyclase K+ channels–>

A

Decreases cAMP

Change in membrane potential

103
Q

Phospholipase C–>

A

Increases IP3 and DAG

104
Q

cGMP phosphodiesterase–>

A

Decreases cGMP

105
Q

Catalytic cell-surface receptors:

location and activation

A

Membrane bound

Ligand activated

106
Q

Catalytic cell-surface receptors:

Examples

A

Tyrosine Kinase
Tyrosine Phosphatase
Serine/Threonine Kinase
Guanylate cyclase

107
Q

Catalytic cell-surface receptors do not have to activate another enzyme because..

A

..they are enzymes and have enzymatic activity directly associated with them.

108
Q

Receptor Tyrosine Kinase (RTKs) ligands are..

A

..Growth factors and adhesions

109
Q

We typically want to activate or inhibit RTK?

A

Inhibit

110
Q

Dimerization

A

It takes two molecules (two monomers) to come together to form a dimer, which activates the signal of a RTK

111
Q

How is the dimer of a RTK activated?

A

The tyrosine has to be phosphorylated by ATP

112
Q

Voltage gated ion channels

A

Opening depends on the resting membrane potential

selective for ions

113
Q

Voltage gated ion channels are found in..

A

..excitable cells (neurons, muscle, endocrine)

114
Q

Closed ion channel

A

Activation gate closed

Inactivation gate open

115
Q

Active ion channel

A

Activation gate open

Inactivation gate open

116
Q

Inactive ion channel

A

Activation gate open

Inactivation gate closed

117
Q

Deactivated ion channel

A

Activation gate closed

Inactivation gate closed

118
Q

Ionotropic Ligand-gated ion channels

A

A ligand binds and the channel opens.

When a ligand is not bound, the channel is closed.

119
Q

Ionotropic Ligand-gated ion channel: Cys-loop

A

Excitatory: ACh
Inhibitory: GABA

120
Q

Metabotropic ion channels

A

Ligand doesn’t directly bind to receptor.
Ligand binds to GPCR which sends 2nd messenger to activate Metabotropic channel.
(see lecture 3 at 1:13:35)

121
Q

How do gasses get into cell?

A

Direct crossing

see lecture 3 at 1:14:27

122
Q

Goal of rational dosing:

A

To achieve desired beneficial effect with minimal adverse effects.

123
Q

Volume of Distribution (Vd)

A

Amount of drug in body to concentration in blood (does it stay in the blood, or leave the blood)
Vd= (amount of drug in body/concentration)

124
Q

Blood volumes:

Whole blood

A
  1. 08L/kg

5. 6L per 70kg person

125
Q

Blood volumes:

Plasma

A
  1. 04 L/kg

2. 8L per 70kg person

126
Q

What is meant by a high Vd?

A

The drug leaves the blood and goes elsewhere.

127
Q

Clearance

A

Ability of body to eliminate drug
Predicts rate of elimination in relation to drug concentration.
(Constant)

128
Q

Rate of elimination

A

RofE = CL x C

129
Q

First-order elimination

A

Applies to most drugs (low doses)

Clearance is constant, rate of elimination varies with concentration

130
Q

Zero order of elimination

A

Occurs when body’s ability to eliminate a drug has reached its maximum capability (high doses)
(Rate of elimination is constant, clearance varies with concentration)

131
Q

Capacity-Limited Elimination

A

Starts as 1st order, turns into zero order

132
Q

Flow dependent elimination

A

Some drugs are highly sensitive to 1st pass metabolism
“high extraction drugs”
depends on blood flow through the organ

133
Q

Organ clearance

A

tells us the clearance of a particular organ

Blood flow x extortion ratio

134
Q

Half-life (T1/2)

A

Time required to change drug in body to 1/2 of dose

T1/2= (0.7xVd)/CL

135
Q

How many half lives does it take to get to target concentration in steady state?

A

4

it also takes 4 to eliminate it after stopping drug

136
Q

Why will true half life often be greater than calculated?

A

Because the calculation is based off of healthy test subjects

137
Q

Accumulation

A

building up levels of drug in the body more than target concentration and will continue until dosing stops

138
Q

Dosing in intervals

A

If you give a second dose shorter than 4 half lives, then the concentration in the blood will go up

139
Q

Bioavailability (F)

A

The fraction of unchanged drug reaching systemic circulation (percentage)
*remember if you are calculating using F, convert the % to a decimal

140
Q

Biotransformation

A

the alteration of a drug before reaching systemic circulation. Some drugs become inactive after altered, some become active after altered.

141
Q

First-pass elimination

A

Just because there is a high absorption doesn’t mean there is a high bioavailability.
Liver can filter out many drugs leaving less to enter systemic circulation

142
Q

Maintenance Dose

A

Maintain steady state of drug by giving just enough to replace eliminated drug

143
Q

Dosing rate for steady state

A 
Dosing rate (SS)= Rate of elimination(ss) 
OR
Dosing rate(SS)= CL X Target Concentration
144
Q

Important Dosing rate for steady state if bioavailability is 100%

A 
Dosing rate(SS)= Rate of elimination(ss) 
OR
Dosing rate(SS)= CL X Target Concentration
145
Q

Important Dosing rate if bioavailability is less than 100% (like PO drug)

A

Dosing rate = (CL X TC)/F

146
Q

Important Intermittent maintenance dosing

A

Maintenance dose = Dosing rate X dosing interval
OR
md=[(CLxTC)/F] x interval

147
Q

when do we give loading dose?

A

When we need to reach target concentration quickly

148
Q

Loading dose equation

A

LD = Vd x TC

149
Q

How do you administer loading doses for potentially toxic drugs?

A

slowly. They need time for distribution into compartments

150
Q

When calculating a dose for a patient, if the drug has a high Vd, do we use actually body weight or ideal body weight?

A

Actual body weight because the drug mostly leaves the blood and goes into the fatty tissue.

151
Q

Why do we have to use Ideal Body Weight (IBW) when dosing an obese patient with a drug that is not lipid soluble?

A

Because if you use actual body weight then you are giving a higher amount of drug and this drug will not diffuse into fatty tissue, therefore the dose will stay in circulation and you can reach toxic side effects faster.

152
Q

IBW for men

A

52 + (1.9kg x inches over 5ft)

153
Q

IBW for women

A

49 + (1.7kg x inches over 5ft)

154
Q

Hepatic Clearance

A

Product of blood flow (Q) and Extraction (E)

extraction is drug specific

155
Q

3 primary considerations of hepatic clearance:

A

1) Hepatic blood flow
2) Plasma-drug binding (albumin)
3) Biotransformation mechanisms

156
Q

Hepatic blood flow (if drug was give PO)

A

GI–> Local veins–> hepatic portal vein–> sinusoids–> hepatic vein–> vena cava–> systemic circulation

157
Q

Hepatic artery flow (If drug was give IV)

A

Systemic circulation–> hepatic artery–> sinusoids–> hepatic vein–> vena cava–> systemic circulation

158
Q

Two different types of reactions in the liver:

A

Phase 1 and Phase 2

159
Q

Phase 1 reactions:

A

Convert drug to more polar metabolite. (usually to make it more water soluble)
More readily excreted, less likely to cross barriers.
Lipophilic becomes hydrophilic.

160
Q

Phase 1 reactions include:

A

Oxidation, reduction, dehydrogenation, hydrolysis

161
Q

Most drugs are usually activated or inactivated by Phase 1:

A

Inactivated

162
Q

What do Phase 2 reactions do?

A

Add larger conjugate to endogenous substrate.

163
Q

Phase 1:

Oxidation enzyme:

A

Cytochrome P450

164
Q

Phase 1:

Hydrolysis enzymes:

A

Esters and Amides

165
Q

Cytochrome P450

A

Enzyme in Oxidation.
Responsible for the metabolism of 2/3 of non-antibiotic drugs.
Mostly in Liver

166
Q

How does oxidation with Cytochrome P450 work?

A

The lipophilic drug binds to Cytochrome P450–> through a series of oxidation reduction reactions the drug becomes oxidized–> an -OH group is added to the drug and the enzyme is recycled

167
Q

Specificity of Cytochrome P450:

A

Very low

168
Q

Important types of Cytochrome P450s:

A

CYP3A4 (metabolizes 50% of drugs)
CYP2D6
CYP2B6

169
Q

P450 Induction

A

some drugs enhance synthesis of P450 and inhibit degradation
(Decreases drug effect if metabolism deactivates drug)
(Increases drug effect if metabolism activates drug)

170
Q

P450 Inhibition

A

Decreases or inhibits P450

171
Q

Hydrolysis

A

Phase 1
means “break water”
occurs throughout body

172
Q

Carboxylesterases

A

Phase 1

Hydrolysis of both esters and amides

173
Q

Carboxylesterase

2 main isoforms:

A

hCE1 and hCE2

174
Q

Example of drugs effected by carboxylesterase

A

Cocaine, meperidine (demerol), heroin

175
Q

Cholinesterase

A

Phase 1
Acetylcholinesterase (enzyme at NMJ)
Hydrolysis of Succinylcholine

176
Q

Types of Phase 2 reactions:

A 
Glucuronidation
Acetylation
Glutathione conjugation
Glycine conjugation
Sulfation
Methylation
Water conjugation
177
Q

Glucuronidation (UGTs)

A

Phase 2
Attaches a glucuronic acid to a Phenol, alcohol, carboxyl, or sulfhydryl group.
Increases aqueous solubility
Increases urine excretion

178
Q

Where does glucuronidation happen?

A

Primarily in the liver

179
Q

Propofol undergoes phase 2 reaction with what enzyme?

A

UGT1A9

180
Q

Opioids undergo phase 2 reaction with what enzyme?

A

UGT2B7

181
Q

Glucuronidate does what to morphine?

A

Makes it more potent

182
Q

Glutathione-S-transferase (GST)

A

Phase 2
Important in Detoxification like tylenol
(can Increase toxicity)
Increases water solubility

183
Q

Glutathione-S-transferase (GST) is located?

A

All over the body

184
Q

Example of drug broken down by GST?

A

Sevoflurane

Toxic metabolite- compound A

185
Q

Acetaminophen is inactivated by..

A

Phase 2 reactions

186
Q

What happens in Acetaminophen overdose?

A

If you give too much Acetaminophen you overwhelm phase 2 reactions, therefore phase 1 reactions (CYP450)can further detoxify them. Phase 1 reactions will still build up toxic metabolites which are degrade by glutathione. Glutathione get used up rapidly so if you don’t give them more, then liver cell death occurs.

187
Q

Antidote for Acetaminophen

A

N-acetylcysteine

It replenishes glutathione if given within 8 hours of overdose

188
Q

Other factors that can effect metabolism:

A

Diet, Environment (smoking), Age, Sex (males metabolize faster), Disease state, genetics

189
Q

Pro-drug

A

Needs metabolism to work

190
Q

Pro-drug given to poor metabolizer

A

Poor efficacy

Possible accumulation of pro-drug

191
Q

Active drug given to poor metabolizer

A

Good efficacy
Accumulation of drug can produce adverse reactions
May need lower dose

192
Q

Pro-drug given to ultra-rapid metabolizer

A

good efficacy, rapid effect

193
Q

Active drug given to ultra-rapid metabolizer

A

Poor efficacy

Need greater dose or slow release formulation

194
Q

Genetic analysis allows:

A
  • More rapid determination of stable therapeutic dose.
  • Better prediction of dose than clinical methods alone.
  • Genetic testing now recommended/required by FDA
195
Q

TPMT mutation

A

6-MP is an active drug that is detoxified by TPMT. If there is a TPMT deficiency or mutation it will result in toxic metabolites more quickly (my way to remember: Troubled People Make Toxins)

196
Q

Warfarin is metabolized by:

A

CYP2C9 (Carol Your Patient in room 2’s Coumadin level is 9)

197
Q

To get Herceptin treatment for breast cancer you must be positive for what protein?

A

HER2 over expression

198
Q

Parameters affecting Passive diffusion:

A
  • Molecular weight (larger it is, harder to cross barrier)
  • pKa (Charged vs uncharged due to pH)
  • lipid solubility
  • plasma protein
199
Q

Solute Carrier Proteins (SLC)

A

15-30% of all membrane proteins

High specificity

200
Q

Drug Efflux transporters

A

Proteins that pump drugs out of cells.
It is a cell survival mechanism.
Broad substrate specificity.

201
Q

ATP-Binding Cassette

A

ABC transporters

Multidrug resistant protein

202
Q

ABC gene families

A

A-G and over 50 genes

203
Q

ABC A1

A

Cholesterol efflux

204
Q

ABC B1

A

(Broadest substrate specificity)
Antineoplastics, HIV protease inhibitor, antibiotics, antidepressants, antieplileptics, and opioids.
(Wide distribution)
GI, Kidney, Liver, testes
Critical in maintenance of Blood-brain barrier

205
Q

ABC B1 Loperamid effects

A

Antidiarrheal

no CNS effects because it is bound to ABC B1 in GI and not absorbed into the blood

206
Q

ABC B1 Fentanyl effects

A

Koreans have significantly altered efflux therefore fentanyl will not work as well

207
Q

ABCC

A

Largest class
ubiquitous
Antineoplastic efflux

208
Q

ABCG2

A

Breast cancer resistant protein
Antineoplastic, toxins, food-borne carcinogens
Folate transport

209
Q

Non-ABC drug efflux transporters

A

SLC21
(OATPs)
passive transport gradients
some function for drug Influx

210
Q

Blood brain barrier is made up of:

A

Physical barrier and transport barrier

211
Q

In the blood brain barrier, transporters are mainly pumping..

A

..into blood.

212
Q

Blood-CSF barrier

A

Fewer effluxes

some drugs can get into brain easier from CSF than from blood except antineoplastics

213
Q

GI tract transporter pump..

A

..into intestine cell, then into blood.

214
Q

Liver transporter pump..

A

..into hepatocyte, then into bile.

215
Q

Placenta transporters pump..

A

..back into maternal circulation.

216
Q

IND

A

Investigational New Drug

217
Q

NDA

A

New Drug Applicaiton

218
Q

Phase 1 clinical testing:

A

20-100 healthy volunteers
Dosing, Safety, ADME
Can be in patients if high risk

219
Q

Phase 2 clinical testing:

A

100-200 patients
Double-blind
efficacy

220
Q

Phase 4 clinical testing:

A

1000s patients
Market formulation
route

221
Q

GRASE

A

Generally Recognized As Safe and Effective

222
Q

St. John’s Wort

A

Claims: Depression
Issues: induce CYPs
others: MAOI (serotonin syndrome, malignant hyperthermia)

Fall Pharm (8 decks)

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