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D&D > Unit 1 Lectures > Flashcards

Unit 1 Lectures Flashcards

1
Q

pharmacotherapeutics

A

dose regimen

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2
Q

pharmacokinetics

A

how plasma concentration changes over time (what the body does to drug)

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3
Q

pharmacodynamics

A

what the drug does to the body

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4
Q

pharmacotherapeutics can use a drug for…(4)

A

prevention, diagnosis, treatment, cure

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5
Q

In a dosage regimen, select drug and dose based on…

A

pharmacodynamics, disease target, drug regulation

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6
Q

In a dosage regimen, select route of administration based on…

A

pharmacokinetics (absorption and distribution)

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7
Q

In a dosage regimen, select dosage frequency based on…

A

pharmacokinetics (metabolism and excretion)

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8
Q

In a dosage regimen, select duration based on…

A

disease pathophysiology

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9
Q

Physiology identifies _________ for drug action

A

potential targets

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10
Q

Pathophysiology determines how the _________ should be _________ in a disease

A

targets, manipulated

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11
Q

bioavailability

A

how much drug reaches a target

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12
Q

volume of distribution

A

what is the drug dose for a desired Cp?

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13
Q

The major organ of metabolism is the ________

A

liver

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14
Q

The major organ of excretion is the _________

A

kidney

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15
Q

Therapeutic uses of drugs act via enhancement or blockade of _______________________

A

normal physiological pathways

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16
Q

Idiosyncratic reactions are adverse drug reactions that occur ____________

A

not at target site (peculiar to an individual, less common, less predictable)

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17
Q

ke is the _____________ and is used to determine __________

A

elimination rate constant (slope of ln Cp vs. time), half-life

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18
Q

factors influencing drug membrane passage (4)

A
  • molecular size
  • concentration
  • lipid solubility
  • degree of ionization
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19
Q

bioavailability equation (F)

A

F = AUC(oral)/AUC(IV)

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20
Q

Bioavailability with oral administration varies based on…

A
  • survival of drug in GI (acidity, digestive enzymes)
  • ability to cross membrane (small, uncharged, lipid soluble)
  • efficiency of metabolism (first pass effect)
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21
Q

Rate of onset of drug effect is determined primarily by…

A

route (rather than individual drug characteristic)

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22
Q

The major equivalency test required for generic drugs is…

A

bioequivalency (therapeutic equivalency)

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23
Q

Generic drugs are bioequivalent to brand name if…

A

rate (Cmax, Tmax) and extent (AUC-bioavailability) of absorption are within set parameters

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24
Q

factors affecting drug absorption

A
  • drug solubility

- rate of dissolution (concentration of drug at site, circulation, area of absorbing surface)

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25
Q

If you take a drug on an empty stomach, you’re protecting the _______

A

drug

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26
Q

Subcutaneous route provides a ____________ rate of absorption

A

slower, more constant

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27
Q

Injection volume of __________ route is more limited than ________ route

A

subcutaneous, intramuscular

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28
Q

Injection of (solution/suspension) provides rapid onset of action

A

solution

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29
Q

The sublingual route of drug administration is useful if the drug is __________________

A

lipid soluble and potent

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30
Q

One advantage of a transdermal patch is that it…

A

avoids first-pass metabolism

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31
Q

With local effects, the response (is/is not) proportional to plasma concentration

A

is not

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32
Q

slow speed of onset of drug effect (4)

A
  • oral
  • intramuscular
  • subcutaneous
  • transdermal
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33
Q

Depo-provera lasts…

A

3 months (IM)

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34
Q

NPH insulin lasts…

A

10-12 hours (SC)

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35
Q

Duragesic lasts…

A

72 hours (transdermal)

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36
Q

Depakote ER (seizures) lasts…

A

24 hours (oral)

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37
Q

Henderson-Hasselbach equation

A

10^pH-pKa = non-protonated/protonated

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38
Q

Henderson-Hasselbach allows prediction of… (2)

A
  • % of total amount of drug that is ionized

- prediction of pH where absorption will be favored

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39
Q

Protein-binding _________ elimination rate, ___________ half-life, and ________ Vd

A

decreases, increases, decreases

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40
Q

protein-binding displacement may be problematic if…(4)

A
  • displaced drug has narrow therapeutic index
  • displaced drug is started in high dose
  • Vd of displaced drug is small
  • response to drug occurs more rapidly than redistribution
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41
Q

Vd represents the relationship between ___________ and ____________

A

dose of a drug, resulting Cp

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42
Q

Vd equation

A

Vd = dose (amt drug in body)/Cp (concentration drug in plasma)

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43
Q

drugs highly bound to plasma

A

warfarin, heparin

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44
Q

drugs highly water soluble (don’t enter cells, found in extracellular water)

A

gentamicin, ibuprofin

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45
Q

drugs that freely enter cells (total body water)

A

lithium, ethanol

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46
Q

drugs highly lipid-soluble sequestered at tissue sites

A

amitriptyline, fluoxetine

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47
Q

Vd varies between patients based on… (3)

A
  • body composition (fat vs. lean)
  • body size
  • changes in protein binding
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48
Q

Loading Dose equation

A

LD = Cp (desired) x Vd

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49
Q

phase I reaction types

A
  • oxidations
  • hydrolysis
  • reductions
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50
Q

phase II reaction types

A

conjugations

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51
Q

phase I enzymes

A
  • CYP450
  • esterases-amidases
  • reductases
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52
Q

phase II enzymes

A

transferases

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53
Q

phase I and II genetic polymorphisms are (significant/insignificant)

A

significant

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54
Q

phase I induce-inhibit

A

significant

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55
Q

phase II induce-inhibit

A

possible-less

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56
Q

phase I and II development patterns

A

variable

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57
Q

phase I age changes

A

decrease in 1/3

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58
Q

phase II age changes

A

minimal

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59
Q

phase I saturability

A

minimal

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60
Q

phase II saturability

A

substantial

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61
Q

T/F: There is cytochrome P450 development in neonates

A

true

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62
Q

Drugs that are metabolized by the __________ system are usually highly lipid-soluble

A

CYP450

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63
Q

Drugs metabolized by the CYP450 system are usually metabolized in the ___________________

A

smooth ER

64
Q

CYP3A4

A

major; gastric mucosa but not large intestine

65
Q

CYP2E1

A

turns acetaminophen into a metabolite that destroys liver

66
Q

CYP2D6

A

metabolite of opioids, antipsychotics; genetic polymorphisms

67
Q

CYP2C9

A

warfarin

68
Q

The amplichip test detects polymorphisms in __________ and ___________

A

CYP2D6, CYP2C19

69
Q

Caucasians tend to be _________ poor-metabolizers which Asians tend to be ___________ poor-metabolizers

A

CYP2D6, CYP2C19

70
Q

Some examples of CYP450-dependent phase I oxidations are…

A
  • aromatic hydroxylations
  • aliphatic hydroxylations
  • oxidative dealkylation
71
Q

Some examples of CYP450-independent phase I oxidations are…

A
  • monoamine oxidase

- dehydrogenases (alcohol, aldehyde)

72
Q

Phase I reductions

A
  • azo
  • nitro (can produce toxic intermediates)
  • carbonyl
73
Q

Valacyclovir undergoes phase ___ __________

A

phase I hydrolysis

74
Q

The products of phase II conjugations are often…

A

highly water-soluble, readily excreted

75
Q

Hydrolysis by bacterial B-glucuronidase can lead to ____________

A

enterohepatic recirculation

76
Q

Characteristics of N-acetylation (Phase II conjugation)

A
  • some products are less water-soluble

- marked genetic variation

77
Q

Alcohol dehydrogenation is a ______________

A

non-P450 oxidation

78
Q

The mechanism of induction of drug metabolism is mainly due to _________________

A

increased synthesis of enzyme production (and some decreased turnover)

79
Q

Which phase enzymes are more prone to inhibition?

A

phase I

80
Q

Drug interactions effects are most obvious when…

A

drugs are given orally (via first-pass effect)

81
Q

Rifampin interacts with _____________ because it ___________ clearance, thus altering ____

A

oral contraceptives, increases, Cp (decreased, unplanned pregnancy)

82
Q

Erythromycin interacts with _________ because it ___________ clearance, thus altering ____

A

lipitor, decreases, Cp (increased, myopathy)

83
Q

Saturation is less likely to occur with ____________ than ___________

A

renal excretory process, metabolism

84
Q

P-glycoprotein transporters in the GI tract _________________

A

decrease oral absorption

85
Q

P-glycoprotein transporters in the liver-kidney _________________

A

enhance biliary and renal excretion

86
Q

P-glycoprotein transporters in the blood-brain barrier _________________

A

limit distribution of drugs

87
Q

Adult levels of glucuronyl transferases are reached by age ____

A

3-4

88
Q

What is the best documented and clinically most important mechanism of drug-drug interaction?

A

inhibition or induction of metabolism of the drug

89
Q

Rate of elimination of first order kinetics is proportional to ______________

A

plasma concentration (constant %/time eliminated)

90
Q

With half-life, a constant __________ is eliminated per unit time and is ___________ of the total amount of drug present

A

fraction, independent

*half-life is the same regardless of Cp

91
Q

equation for clearance

A 
CL = Vd x ke
CL = (maintenance dose/tau)/Cp(ss)
92
Q

Clearance

A
  • volume of plasma that is completely cleared in a given period of time
  • proportionality constant that makes Cp(ss) equal to rate of administration
93
Q

The half-life of a drug depends on ______________

A

CL (inversely proportional) and Vd (directly proportional)

94
Q

(Free drug/protein-bound drug) can be metabolized

A

free drug

95
Q

The time it takes to reach steady state is independent of ___________

A

drug dosage

96
Q

The time it takes to reach steady state depends entirely on ___________

A

half-life

97
Q

Loading dose equation

A

LD = Cp x Vd

98
Q

tau

A

time between doses

99
Q

Steady state level depends on __________

A

MD/tau

100
Q

fold-fluctuations

A

2^n (n=tau/half-life)

101
Q

More _________ in a dosing interval means greater fluctuation

A

half-lives, not hours

102
Q

The amount of fluctuation in Cp that can be tolerated by a drug is determined by its _________________

A

therapeutic index

103
Q

Saturation is more likely to occur with __________ than _________ processes

A

hepatic metabolic, renal excretory

104
Q

When giving a single dose, what equation do you use to determine plasma concentration?

A

Cp = dose/Vd

105
Q

Steady-state is proportional to …

A

dose/dosage interval

106
Q

Fluctuations are proportional to …

A

dosage interval/(t(1/2))

107
Q

Types of protein receptors (4)

A
  • hormone and neurotransmitter
  • receptor, voltage-gated ion channel
  • enzymes
  • transport proteins
108
Q

What 3 factors determine binding affinity to a receptor?

A

size, shape, electrical charge

109
Q

What effect does a pharmacologic antagonist have in the absence of agonist?

A

none

110
Q

Potency depends on … (2)

A
  • affinity (Kd) of receptors for binding drug

- efficiency of drug-receptor complex to generate response

111
Q

The power of a drug to bring about a response is related to …

A

Emax

112
Q

Physiological antagonists act on ______________

A

a different receptor than agonist

113
Q

What happens to EC50, Emax, and potency with competitive, reversible inhibitors?

A
  • EC50 increases
  • Emax unchanged (surmountable)
  • potency decreases
114
Q

What happens to EC50, Emax, and potency with noncompetitive inhibitors?

A
  • EC50 unchanged
  • Emax reduced
  • potency unchanged
115
Q

Quantal dose-response curves can provide information on dose __________ but not dose ___________

A

potency, efficacy

116
Q

Idiosyncratic drug reactions

A

genetically-determined abnormal response to drug (unpredictable)

117
Q

Pharmacokinetic drug interactions can result in…

A
  • elevated drug concentrations (toxicity)

- decreased plasma concentrations (sub therapeutic)

118
Q

Pharmacodynamic drug interactions can result in…

A
  • pharmacologic enhancement or antagonism via same drug target
  • physiologic enhancement or antagonism via different effector system
119
Q

What is an indirect pharmacodynamic effect?

A

pharmacologic effect of one drug indirectly affects second

120
Q

Half-life may be (prolonged/shortened) with toxicity

A

prolonged

121
Q

When poisoned, how do you decrease absorption?

A
  • gastric lavage
  • emesis
  • activated charcoal
  • whole-bowl irrigation
  • cathartics
122
Q

When poisoned, how do you enhance elimination?

A
  • inhibit toxication or enhance detoxication (give antidote)
  • hemodialysis
  • manipulate urine pH
123
Q

(Ipecac/activated charcoal) must be given before (ipecac/activated charcoal)

A

ipecac, activated charcoal

124
Q

What is the most rapid and complete method of emptying the stomach?

A

gastric lavage

125
Q

How does activated charcoal work to treat toxicity?

A

binds drug in gut to limit absorption (ion-trapping in stomach)

126
Q

When should magnesium citrate or sulfate be avoided?

A
  • renal disease

- poisoning with nephrotoxic agents

127
Q

When should sodium sulfate be avoided?

A

-CHF
-hypertension
(systemic Na+ absorption leads to edema)

128
Q

methanol toxication

A

methanol, alcohol dehydrogenase, formic acid, retinal damage

-inhibit alcohol dehydrogenase with ethanol (substrate and competitive inhibitor)

129
Q

ethylene glycol toxication

A

ethylene glycol, alcohol dehydrogenase, oxalic acid, acute renal failure
-inhibit alcohol dehydrogenase with fomepizole (specific inhibitor)

130
Q

How does hemodialysis inhibit toxication?

A

removes parent compounds/metabolites

-best for toxins with small Vd and low protein-binding capacity

131
Q

Acetaminophen is normally eliminated by (Phase I/Phase II) mechanism

A

phase II (gets saturated with toxic dose)

132
Q

What is the treatment for acetaminophen toxication?

A

gastric lavage, supportive therapy, N-acetylcysteine (replenishes GSH)

133
Q

Treatment for methanol and ethylene glycol toxication act by…

A

inhibiting toxication

134
Q

Treatment for acetaminophen toxicity acts by…

A

enhancing detoxication

135
Q

Hemodialysis, hemoperfusion , chelation of heavy metals, and forced diuresis act by…

A

enhancing elimination

136
Q

What enzyme is responsible for producing the hepatotoxic metabolite of acetaminophen?

A

CYP2E1

137
Q

Pre-clinical testing

A

5-8 years

  • acute-chronic toxicity in rodent and non-rodent species
  • determine safe dosage range for humans
138
Q

Phase I drug trial

A

2-10 years

  • Is it safe? toxicity
  • pharmacokinetics: absorption, half-life, elimination-metabolism
139
Q

Phase II drug trial

A

2 years

  • Does it work in patients?
  • safety and efficacy, final dosing and regimens
140
Q

Phase III drug trials

A

3 years

  • Does it work double blind?
  • efficacy measured against established therapy
141
Q

Phase IV

A

-post-marketing surveillance (include omitted study groups, document low-incidence drug effects

142
Q

Patents expire ____ years after application

A

20

143
Q

What is the difference between pharmaceutical equivalence, bioequivalence, and therapeutic equivalence>?

A
  • pharmaceutical equivalence: drug formulation (ingredients, dose, route of administration, strength)
  • bioequivalence: drug molecules
  • therapeutic equivalence: therapeutic effect
144
Q

Bioequivalence

A

rate (Cp max, Tmax) and extent (bioavailability) that active ingredient is absorbed and becomes available

145
Q

What is considered a supplement? (4)

A

vitamins, minerals, amino acids*, herbal medicine

*molecular entity and safe dosage range known

146
Q

Which drug studies involve testing safety?

A

Phase I, II, and III

147
Q

Which are required for determining generic drug equivalence with brand names?
therapeutic equivalence, pharmaceutical equivalence, bioequivalence

A

Pharmaceutical equivalence, bioequivalence

148
Q

Criteria for classifying drugs with abuse potential

A

medical use, physical/physiological dependence, abuse potential

149
Q

When are drugs required to go through cells as opposed to between? (3)

A

absorption into small intestine, blood-brain barrier, kidneys

150
Q

Rate of absorption of a drug is estimated as ________

A

peak Cp (Cmax) or time to attain peak Cp (Tmax)

151
Q

_____________ route of administration can only be used with potent drugs

A

Transdermal

152
Q

Cp vs. time graphs determine ___________

A

pharmacokinetics

153
Q

What type of phase II conjugation does morphine undergo?

A

glucuronidation

154
Q

What type of phase II conjugation does acetaminophen undergo?

A

sulfate conjugation

155
Q

____________ is the only factor that will keep a drug from being filtered at the glomerulus

A

protein binding

D&D (3 decks)

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