Pharm Ch 1

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How does a student develop a "story" about a drug, rather than try to memorize isolated facts about every single drug?

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Biology

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1

How does a student develop a "story" about a drug, rather than try to memorize isolated facts about every single drug?

Associate, Ask, Predict

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2

What does "Associate" mean, regarding a drug's story?

Associate each drug class with info you already know.

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3

What does "Ask" mean, regarding a drug's story?

Ask yourself why some drugs are shots and others are pills, why some are taken 4x and some 2x per day, and why the info is important enough to be in the book.

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4

What does "Predict" mean, regarding a drug's story?

Predict the actions, clinical uses, side effects, and drug interactions based only on its mechanism of action.

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5

What should you envision about a drug?

Envision the course of events that would occur as it enters the body.

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6

What does "formulation" mean?

The drug preparations made by companies that can be administered orally, i.v., or another route.

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7

What are the 5 factors that the drug formulation depends on?

"The barriers the drug can pass. The setting in which the drug will be used. The urgency of the medical situation. The stability of the drug. The first pass effect."

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8

What are barriers that drugs must pass?

Any anatomical structure they must get through in order to reach the bloodstream or target area. IV drugs have no barriers, but pills must pass through the GI tract and the blood vessel wall to get to the blood.

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9

What are some settings in which drugs can be used?

Hospital vs. home

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10

What setting is appropriate to administer an IV?

Hospital

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11

What drugs can be administered in a home setting?

Pills (aspirin)

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12

Why are drug formulations selected based on medical urgency?

The delay before onset of action varies; an IV antibiotic works faster than the same drug administered orally.

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13

How are drug formulations affected by the stability of the drug?

Drugs that are destroyed by acid (such as the proteins found in insulin for diabetics) are not effective if taken orally because of stomach acid

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14

What is the first pass effect?

Oral medicines are absorbed into the portal vein, which goes to the liver before being distributed to the body. The liver deactivates many medicines during this first pass, so they cannot be taken orally.

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15

Name 9 routes of drug administration and their medical abbreviations

Oral (PO) Sublingual, Rectal (PR) Inhalation Topical Transdermal Intravenous (IV) Intramuscular (IM) Subcutaneous (SubQ or SC)"

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16

Which 5 routes of administration are most compatible with drugs that are self-administered?

Oral (PO) sublingual inhalation topical transdermal

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17

What two problems must oral drugs be able to overcome?

Gastric acidity and must permeate the gut lining

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18

Oral drugs are affected by what two things?

Gastric emptying and intestinal motility

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19

What is the key feature that allows a drug to be administered by the sublingual route?

Must have good absorption through the capillary bed under the tongue.

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20

What is the advantage of sublingual drugs over oral drugs?

Gastric acidity and gut-permeability are not needed.

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21

When are rectal drugs mainly used?

For unconscious or vomiting patients or small children.

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22

What is the problem with the rectal route?

Absorption is unreliable

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23

Can topical drugs be administered systematically?

No, they are usually toxic except for topical use

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24

Topical agents can be applied to what parts of the body?

Skin, eyes, nose, vagina, ears

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25

What is a transdermal patch?

The drug is on a patch that is applied to the skin, and it is able to penetrate to the dermis to be absorbed in the blood vessels there. Few drugs are capable of using this route.

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26

What does "parenteral" refer to?

Drugs that are administered in ways other than the gastro-intestinal tract.

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27

What are the 3 advantages of parenteral drugs?

"More rapid absorption More predictable absorption More accurate dose selection"

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28

What are the 4 disadvantages of parenteral drugs?

"Need for strict asepsis Risk of infection Pain Local irritation"

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29

What are the 3 parenteral routes of administration?

"Intravenous (IV) Intramuscular (IM) Subcutaneous (SubQ, SC)"

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30

What are the advantages of IV drugs?

"Rapid onset of action, Useful in emergencies, Useful for unconscious patients"

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31

What is a disadvantage that is unique to IV drugs?

Drug must be soluble in water to be used as an IV drug.

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32

What factor influences the rate of absorption of Intramuscular (IM) and SubQ drugs?

"Oil-based preparations are absorbed slowly Aqueous preparations are absorbed rapidly"

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33

What is a disadvantage that is unique to SubQ drugs?

Only non-irritating drugs can be used.

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34

What is the half-life of a drug?

The amount of time required for the blood concentration of a drug to decrease by 50% after the drug administration has stopped.

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35

What does the distribution half-life reflect?

The rapid decline in plasma drug concentration as a dose of drug is distributed throughout the body.

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36

What is the speed of the elimination half-life of a drug?

It is much slower, reflecting the metabolism and excretion of the drug.

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37

How many half-lives pass before the serum concentration of a drug reaches steady state?

Several

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38

How long do you have to wait before you can draw blood to measure the peak, trough or plasma levels of a drug?

Wait until the 4th or 5th half-life

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39

If the half-life of a drug is 4 hours, how many hours do you have to wait before measuring its level in the blood?

After 4 hours, 50% of the drug will be left in the body (first half-life); it will take four more hours to metabolize 50% of the remaining drug; the body will now have 25% of the original dose remaining. After the 3rd half-life, the body will have 12.5% of the drug left. After the 4th half-life there will be 6.25% left, and 16 hours will have passed. Draw blood at 16-20 hours after drug administration to measure within the 4th - 5th half-life.

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40

How can therapeutic levels of a drug be obtained more rapidly?

By delivering a loading dose followed by maintenance doses.

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41

What is a loading dose?

An initial dose of drug that is higher than subsequent doses.

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42

What is a maintenance dose?

The doses of drug that maintain a steady state plasma concentration in the therapeutic range.

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43

What is a dosing regimen?

Route amount frequency the drug is given

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44

What influences the onset and duration of drug action?

The dosing regimen

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45

What is the onset of a drug?

The amount of time it takes a drug to begin working.

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46

What routes have the fastest and slowest onset?

IV drugs are fastest onset oral drugs are slowest

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47

What is the duration of a drug?

The length of time for which a drug is therapeutic.

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48

What does the duration of a drug usually correspond to?

The half-life of the drug

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49

When would the duration of a drug not correspond to its half-life?

When the drug binds irreversibly to its receptor

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50

What is the duration of a drug dependent upon?

The metabolism and excretion of the drug.

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51

Will increasing the rate of IV infusion decrease the time needed to reach steady state?

No; it always takes 4-5 half-lives of continuous IV infusion to reach steady state.

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52

Will increasing the rate of IV infusion increase the plasma drug concentration at steady state?

Yes (see page 3 in book if you bought it). Instead of administering x-mg per hour, increasing infusion to 2x-mg will result in drug concentration being doubled at steady state (when the graph levels off)

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53

What is the peak and trough of a drug?

When a drug is administered intermittently, there will be peaks (high points of fluctuation) and troughs (low points of fluctuation) See page 3 in book

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54

Are toxic effects most likely to occur during peaks or troughs?

Peaks

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55

Is lack of drug effects more likely to occur during peaks or troughs?

Troughs

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56

Is post-operative pain more likely to return just before a second dose of morphine or midway between the first and second dose?

Just before the second dose

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57

What does pharmacotherapeutic mean?

What the drug is used for

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58

What does pharmacodynamics mean?

How the drug affects the organism

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59

What does pharmacokinetics mean?

How the organism affects the drug (duration of the drug)

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60

What are the 4 phases in pharmacokinetics, in order?

"Absorption Distribution Metabolism Excretion/Clearance"

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61

What are four transport mechanisms that a drug can use to cross membranes?

"Passive diffusion Facilitated diffusion Aqueous channels Active transport"

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62

In which of the four transport mechanisms is energy used?

Active transport

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63

In which of the four transport mechanisms is a carrier protein needed?

"Facilitated diffusion Active transport"

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64

What are the 4 drug-associated factors that influence absorption?

"Ionization state Molecular weight Solubility (water vs lipid soluble) Formulation (solution vs tablet)"

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65

What is the patient-associated factor that influences drug absorption?

Depends on route of administration

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66

Regarding patient-associated factors that influence absorption: What are 3 ways that absorption of oral medicines is affected by the patient?

"The presence of food in the GI tract slow absorption of oral meds. Excess or decreased stomach acidity affects absorption of oral meds. Decreased blood flow to the GI tract slows absorption of oral meds."

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67

What are 3 things that affect drug distribution?

"Membrane permeability Plasma protein binding Depot storage"

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68

For a drug to enter an organ, what must the drug do?

It must permeate all membranes that separate that organ from the site of drug administration.

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69

What is the Blood-Brain Barrier (BBB)?

The brain has protective cells that do not let most drugs through. That limits the number of drugs available to treat brain and spinal cord disorders, including anxiety and convulsions.

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70

What common medicine for anxiety and convulsions can cross the BBB?

Benzodiazepines (valium)

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71

What two areas of the body have membranes that many anti-cancer drugs cannot cross?

Brain and testes

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72

What reduces the amount of free (unbound) drug in the blood?

Plasma proteins that bind to the drugs, such as albumin.

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73

What molecules reach equilibrium between the blood and tissues?

Free (unbound) drugs

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74

How does a decrease in free drug in the serum (because it is bound) affect the target organ?

It causes a decrease in the amount of the drug that can enter the target organ.

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75

What does depot storage mean?

The location in the body where the drug accumulates

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76

What is an example of a lipophilic drug that is a sedative used during surgery?

thiopental

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77

How does the weight of the patient affect lipophilic drugs?

An obese patient will feel the sedation effects of thiopental for a longer time after administration

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78

What is an example of a calcium-binding antibiotic? Where does it accumulate?

Tetracycline; it accumulates in the bones and teeth.

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79

What is the meaning of "apparent" volume of distribution (Vd)?

It is a calculated value that describes the nature of drug distribution.

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80

What does volume distribution (Vd) mean?

The volume that would be required to contain the administered dose if that does was evenly distributed at the concentration measured in plasma.

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81

Where would you predict a drug is located if it has a (Vd) of 3-5 liters?

Since there are only 5 liters of blood in the body, this drug is probably 100% in the plasma

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82

Where would you predict a drug is located if it has a (Vd) of 16 liters?

It is likely distributed in plasma plus interstitial fluid.

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83

Where would you predict a drug is located if it has a (Vd) of 50 liters?

It is likely sequestered in a depot because the body only contains about 40-46 liters of fluid.

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84

What has to happen to most drugs before they can be excreted?

They must be biotransformed, or metabolized

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85

In pharmacology, what does "metabolism" refer to?

Making a drug more polar (water soluble)

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86

When a drug is rendered water soluble, what does it often result in?

It often results in drug inactivation (but not always)

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87

What is a parent drug and a metabolite?

The parent drug is the one that is administered. The metabolite is the one that the body renders water soluble.

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88

Is a metabolite less active or more easily excreted then the parent drug?

Not necessarily

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89

What two things can be transformed by metabolic reactions?

"Active drug → less active or inactive drug Less active or inactive drug→ More active drug"

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90

What is a ProDrug?

An inactive or less-active drug

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91

Drug and toxin metabolism is divided into what two reactions?

Phase I and Phase II

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92

What happens in Phase I reactions?

Drugs are oxidized or reduced (H+ is taken off or added) to make them more polar.

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93

What happens in Phase II reactions?

A Polar group, such as glutathione, is conjugated to the drug, which makes it more polar.

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94

What system in the liver is responsible for the metabolism of most drugs?

The P450 system

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95

How does Phase I occur in the liver?

Cytochrome P450 (absorbs light at 450 nm) is an enzyme in the liver cells. Through the electron transport chain, a drug bound to cytochrome P450 can be oxidized (lose a H+) or reduced (gain a H+). The H+ comes from NADPH.

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96

What happens when a drug enters the body that can be metabolized by P450?

Cytochrome P450 is induced (increases in amount and activity) to handle the chemical load

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97

What happens when a person has been on one drug for a while, and then an additional new drug is administered?

Cytochrome P450 production is increased, which works to inactivate the new drug, and the leftover enzyme will also deactivate more of the old drug. So the effectiveness of the old drug decreases.

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98

What is a common example of P450 induction?

Alcohol tolerance. At first, two drinks make the person tipsy. But when drinking frequently, P450 metabolizes the alcohol faster, so it takes more alcohol to feel the effect.

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99

How does daily alcohol consumption affect the effectiveness of other drugs?

Cytochrome P450 induction has occurred from the alcohol, so the enzyme will degrade other drugs faster than someone who drinks less frequently. So they need a higher dose of medicines.

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100

How is patient safety affected by the percentage of drug that binds to plasma proteins like albumin?

If a drug is mostly bound by albumin, there is very little in free form, which is the form that causes the effect. Giving an additional drug that displaces the first drug from albumin will cause more of the first drug to be in free form, which might be toxic. See picture page 5 of book.

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