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Pharmacology > Principles of Pharmacology > Flashcards

Principles of Pharmacology Flashcards

1
Q

What is the study of drugs?

A

pharmacology

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2
Q

What is the study of drugs in human?

A

clinical pharmacology

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3
Q

What is pharmacokinetics?

A

what the body does to drug before it gets to site of action (what happens to the drug)

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4
Q

What is pharmacodynamics?

A

what the drug does to the body when it gets to site of action (what happens to the body) - physical response

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5
Q

What is the easiest place to measure what is going on with a drug?

A

bloodstream

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6
Q

What is the movement of a drug from the site of administration into plasma (time we take medication until it gets to blood stream)

A

absorption

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7
Q

What is the process of drug movement throughout the body?

A

distribution

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8
Q

What is the biotransformation of a chemical (a drug) into another chemical (metabolite)? (drug is changing by an enzyme system)

A

metabolism

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9
Q

What is the irreversible loss of a drug (or metabolites)?

A

excretion, or elimination

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10
Q

What is the acronym that describes pharmacokinetics and what does it stand for?

A

ADME
A: absorption
D: distribution
M: metabolism
E: excretion or elimination

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11
Q

What does absorption require?

A

crossing a biological barrier

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12
Q

Absorption, and therefore bioavailability, is determined by what factors?

A
  • drug characteristics (weight, solubility)
  • patient factors (muscle mass, renal and liver function, gut function)
  • ability to cross membranes
    **passive diffusion
    **facilitated diffusion
    **active transport
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13
Q

What describes drugs moving between “compartments” such as bloodstream, fat, muscle, etc?

A

distribution

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14
Q

What are some physical factors that determine the rate and extend of distribution?

A
  • cardiac output
  • regional blood flow
  • capillary permeability (inflammation, lesions)
  • tissue volume
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15
Q

If a patient has low cardiac output, describe the quickness of medication travel throughout the body?

A

slow, low travel of medications

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16
Q

Areas of less blood flow may receive what?

A

not as much drug

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17
Q

What describes how much drug we can get into a space?

A

tissue volume

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18
Q

Movement of dug between compartments is determined by what factors?

A
  • drug characteristics (weight, solubility)
  • membrane permeability
  • binding
    **plasma protein binding
    **tissue binding
    **fat storage
    **bone uptake
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19
Q

The body uses what to help prevent substances from getting into certain areas to protect it from substantial harm?

A

membrane permeability

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20
Q

What are different barriers in the body that drugs would need to cross?

A
  • blood-brain barrier (protect brain)
  • blood-placental barrier (protect fetus)
  • blood-testes barrier
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21
Q

Why is membrane permeability an important concept to consider when treating infectious illnesses?

A
  • just because drug is effective against a specific organism does not mean it will be able to reach the site of infection
  • presence of inflammation can increase permeability of a normally impermeable membrane allowing drug to penetrate (meningitis)
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22
Q

When you have inflammation of the meninges, what increases, and what decreases?

A

permeability increases, protection decreases

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23
Q

What is the issue with plasma protein binding?

A

drugs bind to proteins instead of the receptors to induce a response, so it becomes stuck to the protein and cannot become “free” to bind to its site of action

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24
Q

What is a saturable system due to there being only so many binding sites so competition can occur?

A

plasma protein binding

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25
Q

If two highly bound drugs are given together, what can happen?

A

one may displace the other resulting in toxicity (due to more drug in blood)

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26
Q

Competition between drugs with the same site of action is only clinically relevant when?

A

when the drugs are more than 90% protein bound

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27
Q

Albumin is the primary circulating protein that binds what?

A

acidic drugs

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28
Q

alpha1-acid glycoproteins bind what?

A

basic drugs

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29
Q

Why do you need to watch for disease states, such as dementia, where albumin levels are decreased?

A
  • albumin levels decrease with age
  • decrease in levels may lead to greater drug effects in the elderly - drug toxicity
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30
Q

What describes when drugs may concentrate in tissues serving as a reservoir that slowly releases drug over time?

A

tissue binding

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31
Q

What can tissue binding lead to?

A

increased concentration in some tissues which can lead to localized tissue (gentamicin)

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32
Q

What describes when lipid soluble drugs may be sequestered in adipose tissue such as oral contraceptives moving into fat spaces?

A

fat storage

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33
Q

Why do drugs stay in adipose tissues when they are sequestered there?

A

there is poor blood flow to fat

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34
Q

What can be an issue in obese patients?

A

storage of drugs in adipose tissue (fat storage)

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35
Q

What describes when drugs can be absorbed onto bone crystal surface and continue to leach out over time?

A

bone uptake

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36
Q

What situations can bone uptake of drugs be beneficial in?

A

in cases where the drugs incorporation in bone allows for stabilization of bone matrix

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37
Q

Bone uptake is harmful when considering tetracyclines, lead and radium why?

A

Because these things hang out in the bone and can cause damage over time

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38
Q

An example where a drug is given IV and concentrates in the kidneys and leads to kidney damage is an example of what?

A

tissue binding

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39
Q

What is an imaginary volume of fluid that would be required to contain the amount of drug present in the body at the same concentration as the plasma?

A

volume of distribution

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40
Q

What is Vd?

A

volume of distribution

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41
Q

What is Cpo?

A

plasma concentration at time it enters bdoy

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42
Q

How do you find volume of distribution?

A

amount of drug in body (dose) divided by plasma concentration (Cpo)

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43
Q

What is the underlying assumption of volume of distribution?

A

that there is a uniform distribution throughout the body, but we know that is not true

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44
Q

What can calculating Vd tell us?

A

what body compartment the drug is distributed in

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45
Q

Total body water accounts for how much of an adults weight?

A

60%

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46
Q

Intracellular fluid accounts for how much of an adults weight?

A

35%

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47
Q

Extracellular fluid accounts for how much of an adults weight?

A

25%

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48
Q

Interstitial fluid accounts for how much of an adults weight?

A

21%

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49
Q

Plasma accounts for how much of an adults weight?

A

4%

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50
Q

Volume of distribution says we can hold so much fluid, but sometimes we can’t, what does this mean, if Vd is greater than total body weight?

A

This means that some of the drug we injected has gone somewhere else, so blood levels have decreased

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51
Q

What is the pattern of how drugs move through the body compartments?

A

plasma/blood -> extracellular -> tissue/fat or intracellular

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52
Q

What can tell you where the drug goes, so how much is in the blood or out of the blood?

A

volume of distribution

53
Q

How many phases to metabolism are there?

A

2:
- phase I
- phase II

54
Q

What phase of metabolism is cytochrome drive, CYP450, and is found in the smooth endoplasmic reticulum?

A

phase I

55
Q

What phase of metabolism is non-synthetic, so it is not breaking anything down, and includes things such as oxidation, reduction, and hydrolysis?

A

phase I

56
Q

What are the enzymes involved in phase I of metabolism?

A
  • 1A2
  • 2B6
  • 2C8
  • 2C9
  • 2D6
  • 2E1
  • 3A4
  • 3A5
57
Q

What is the most common enzyme in phase I metabolism responsible for over 60% of cytochrome activity (drug breakdown) and is located in the liver and gut as well?

A

CYP3A4

58
Q

What are some reasons as to why phase I metabolism is not the same in all individuals?

A
  • age creases phase I reactions by 30% or more
  • some cytochromes may be deficient in certain populations (genetic polymorphisms)
  • some disease states have altered cytochrome functioning
59
Q

What can be substrates, inducers, and inhibitors?

A

drugs

60
Q

What are metabolized by the system (enzyme works on it)?

A

substrate

61
Q

What increases the activity of the system so metabolizing ability is increased (more of enzyme is activated)?

A

inducer

62
Q

What decreases the activity of the system so there is a decreased ability to metabolize substances (enzyme doesn’t do its function)?

A

inhibitor

63
Q

If inducers of an enzyme are given, what happens?

A

more of the drug is going to be destroyed by enzymes, so the effect of the drug will decrease

64
Q

If inhibitors of an enzyme are given, what happens?

A

more of the drug will build up since there aren’t as many enzymes, which can lead to toxicity

65
Q

What is a prodrug?

A

a substance that is put into the body and is inactive until it gets broken down by cytochrome and converted into something else

66
Q

What may be exploited to transform a prodrug into an active substance?

A

cytochrome system

67
Q

What % of caucasians have 2C19 and 2D6 cytochrome deficiencies?

A

respectively:
- 3-5%
- 6-10%

68
Q

What % of asians have 2C19 and 2D6 cytochrome deficiencies?

A

respectively:
- 12-23%
- 1%

69
Q

What % of african americans have a 2D6 cytochrome deficiency?

A

2-5%

70
Q

If you have polymorphisms, are older, or are taking an inhibitor, what may be useless?

A

prodrugs because enzyme won’t be able to break it down so drug will remain in its inactive state

71
Q

What phase of metabolism includes synthetic reactions and create more polar compounds allowing for excretion?

A

phase II

72
Q

What occurs in phase II metabolism where endogenous chemical groups are attached to drug molecules via covalent bonds?

A

conjugation

73
Q

What are glucuronidation, acetylation, sulfation apart of?

A

phase II of metabolism

74
Q

Where does phase II metabolism occur?

A

cytosol

75
Q

What has no effect of phase II metabolism reactions?

A

aging; but newborns cannot readily glucuronidate compounds

76
Q

What is the most common enzyme deficiency in adults?

A

G6PD

77
Q

What prevents some drugs from being metabolized leading to hemolysis, anemia, and possible jaundice (due to excess hemoglobin destruction)?

A

G6PD deficiency

78
Q

G6PD deficiency has its highest prevalence in what descent?

A

African, Asian, and Mediterranean descent

79
Q

What is slow acetylation and what can it lead to?

A

slow to breakdown drugs that are acetylated; can lead to toxicity

80
Q

What is fast acetylation and what can it lead to?

A

drugs acetylated are metabolized too quickly and can lead to therapeutic failure

81
Q

What describes when drugs taken orally and absorbed from the GI tract into portal vein are delivered directly to the liver where they may be metabolized before entering systemic circulation?

A

firs-pass effect

82
Q

What results in only a fraction of the original dose being available (decreased bioavailability)?

A

first-pass effect

83
Q

Because of phase I effects, older patients are started on what doses?

A

lower doses

84
Q

What is the best indicator to know if someone has a genetic alteration in metabolism rate?

A

monitoring patient’s response

85
Q

What may be metabolized prior to elimination or may be excreted as unchanged drug?

A

drugs

86
Q

What are the primary pathways of elimination of drug?

A
  • urine
  • feces
87
Q

What are some additional pathways of drug elimination?

A
  • respiratory
  • breast milk
  • secretions
88
Q

What are the renal pathways of elimination of drugs?

A
  • glomerular filtration
  • tubular secretion
  • tubular reabsorption
89
Q

What is important in glomerular filtration?

A

renal perfusion (blood flow - kidneys need to be receiving blood properly)

90
Q

In what type of renal elimination occurs when drugs must bind to a carrier and may compete for the carrier impairing secretion and therefore elimination?

A

tubular secretion

91
Q

What type of renal elimination depends on ionization of drug (acidity/basicity) and has the possibility that drugs in urine can be taken back up?

A

tubular reabsorption

92
Q

Acidic drugs are excreted faster in what type of urine?

A

alkaline urine

93
Q

Basic drugs are excreted in what type of urine?

A

acidic urine

94
Q

What happens in biliary/fecal elimination?

A
  • some drugs actively secreted into bile
  • reabsorption may occur once in the intestine
95
Q

What is it called when reabsorption of a drug occurs in the intestines?

A

enterohepatic recycling

96
Q

What odes enterohepatic recycling do to a drug?

A

increases the half life of the drug

97
Q

What is a common process for bile salts?

A

enterohepatic recycling

98
Q

What is one of the most important routes of clearance and is often used to determine drug doses?

A

renal clearance

99
Q

What is an estimate of the GFR (glomerular filtration rate)?

A

CrCl

100
Q

What does glomerular filtration rate tell us?

A

how well the glomerulars work/how healthy the kidneys are

101
Q

Why do we use creatinine to measure glomerular filtration rate?

A

because it is not secreted or absorbed

102
Q

Renal filtration only filters what type of drugs?

A

only free drugs; bound drugs cannot do anything and cannot be filtered

103
Q

Renal reabsorption favors what?

A

lipid soluble drugs

104
Q

What do some drugs utilize to be actively secreted into the urine?

A

transporters

105
Q

What is the primary route of drugs?

A

kidneys

106
Q

What describes the volume of plasma cleared of drug per unit time?

A

clearance

107
Q

How can you determine clearance?

A

rate of elimination/concentration

108
Q

What is used in the calculations of half-life (t1/2) and steady-state (Css)?

A

clearance

109
Q

What is proportionate to volume distribution of drugs?

A

clearance

110
Q

What is important for determining half-life?

A

clearance

111
Q

Where is drug metabolism via enzymes occurring primarily?

A

in the liver

112
Q

What describes as plasma concentration increases, the drug metabolism increases?

A

first order kinetics

113
Q

In what order kinetics is rate proportional to concentration?

A

first order kinetics

114
Q

Most drugs go through what order kinetics?

A

first order kinetics

115
Q

What is there a lower chance of in first order kinetics and why?

A

lower chance of overdose because there is a low saturation risk

116
Q

What is Vmax?

A

maximum metabolic activity

117
Q

What order kinetics has enzymes that can be saturated?

A

zero order kinetics

118
Q

What describes as plasma concentration increases, drug metabolism stays constant?

A

zero order kinetics

119
Q

What is the problem with zero order kinetics?

A

more drug is entering the system than being metabolized, can lead to toxicity

120
Q

In what order kinetics is rate independent of concentration?

A

zero order kinetics

121
Q

Constant rate of elimination is related to?

A

zero order kinetics

122
Q

In zero order elimination, what happens to half-life as concentration decreases?

A

half-life decreases

123
Q

In first order elimination, what happens to half-life as concentration decreases?

A

half-life remains constant

124
Q

What is t1/2?

A

time to metabolize half of the drug

125
Q

Knowing rate of elimination can help with what?

A

dosing

126
Q

How many half-lives of a drug are associated with 90% of the drug being gone?

A

3.3 half-lives

127
Q

In what order eliminations can enzymes metabolize drug more efficiently?

A

first order elimination

128
Q

What order elimination takes longer?

A

zero order elimination

Pharmacology (13 decks)

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