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N365: Pharmacology in Nursing > Week 2 - Pharmacokinetics > Flashcards

Week 2 - Pharmacokinetics Flashcards

1
Q

To produce its effect, a drug must reach…

A

appropriate concentrations at the site of action

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2
Q

2 Phases of Drug Activity Identified

A
  1. Pharmacokinetics
  2. Pharmacodynamics
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3
Q

Pharmacokinetics

A

Process by which drugs are distributed within the body (drug moving in the body)

Kinesis = movement; They are absorbed, distributed, metabolized (leaving), and excreted (left)

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4
Q

What are the Stages of Pharmacokinetics

A

ADME!

Absorption
Distribution
Metabolism
Excretion

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5
Q

Absorption

A

Stage 1 of Pharmacokinetics

Drug into the blood or lymph

Ends once in the bloodstream

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6
Q

Distribution

A

Stage 2 of Pharmacokinetics

Drug goes from blood to cells and body compartments (ex: liver, bones, etc)

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7
Q

Metabolism

A

“Biotransformation”

Stage 3 of Pharmacokinetics

Alteration of Drug Structure

Direct line to the liver allows for metabolism

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8
Q

Excretion

A

Stage 4 of Pharmacokinetics

Elimination of Drug

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9
Q

Pharmacodynamics

A

process by which drugs influence cell physiology

dynamics - actions - what the drug actually does

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10
Q

Most drugs are absorbed how?

A

From the GI tract, but they can come from IV and topical sites - but in the end everything needs to end up in the bloodstream

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11
Q

What is the main organ for metabolism

A

Liver - others have capabilities but not like this

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12
Q

What can alter metabolism of drugs

A

liver damage from alcohol or hepatitis

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13
Q

What are the 2 major ways of excretion

A

Bile/Stool

Urine through the Kidneys (main one)

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14
Q

Drugs are stuck with __ failure

A

renal

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15
Q

When a drug permeates a cell, it must transverse…

A

the plasma membrane

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16
Q

What are 4 important considerations (chemically) for pharmacokinetics

A

Molecular Size and Shape (Small moves better across membranes)

Solubility - more soluble means easier to combine and move

Degree of Ionization - charged particles do not move across phospholipid bilayer easy

Concentration - things move from high to low

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17
Q

Permeation of cell membranes methods

A

Passive Process
Active Process
Facilitated Transport

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18
Q

Passive Process

A

most common form of permeation - passive diffusion and filtration

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19
Q

Active Process

A

Some drugs are actively moved with energy and a carrier making them harder or more intensive to move through the membrane

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20
Q

Facilitated Process

A

mix of passive and active

carrier mediated with no energy used and movement cannot occur against an electrochemical - required for movements that would be too slow as well like with glucose or insulin (endogenous)

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21
Q

What is the most common process of drug movement across membranes

A

passive diffusion (and filtration)

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22
Q

Diffusion

A

passive process

If the drug is water soluble, it will diffuse with the flow of water

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23
Q

Factors affecting Diffusion

A

Concentration Gradient

Lipid Solubility

Ionization

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24
Q

How does concentration gradient impact diffusion

A

things want to move from high to low until equilibrium is reached

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25
Q

How does lipid solubility impact diffusion

A

the more lipid soluble, the greater and more rapid absorption across the membrane the drug can do (distribution)

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26
Q

How does Ionization impact diffusion

A

If ionized the drug cannot cross the cell membrane as well, and this is related directly to lipid solubility

The opposite of lipid solubility

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27
Q

For Diffusion to occur, what factors would we like to see

A

Low concentration gradient on other side

high lipid solubility

low ionization

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28
Q

How are lipid solubility and ionization related

A

they are in verse of each other

the greater the ionization the less lipid soluble a drug is and vice versa

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29
Q

Most drugs are what kinds of acids and bases? Why?

A

Weak acids and bases because things too strong will cause damage

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30
Q

Weak Acid Drugs

A

tend to be un ionized in acid solution (stomach)

stay themselves in an acidic environment

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31
Q

Weak Base Drugs

A

tends to be un ionized in basic solution (intestine)

stay themselves in a basic environment

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32
Q

What happens to a weak acid in the intestines

A

it will charge/ionize and not move across membranes well - it may even just stay in the area

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33
Q

Filtration

A

simple diffusion but through channels or pores in the membrane rather than across the whole thing

Bulk flow of water will carry dissolved drugs through the channels and this allows for large molecule entrance

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34
Q

If molecules are too big or do not move / distribute well what may be needed?

A

a carrier and active transport against the concentration gradient

this can allow large and poorly lipid soluble molecules to move

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35
Q

Absorption is defined as

A

movement of the drug from site of administration into the bloodstream

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36
Q

Important Principle of Pharmacokinetics

A

Drugs must cross cell membranes and many conditions will enhance or impede the process

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37
Q

Pharmaceutical Phase

A

the first step of absorption

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38
Q

Dissolution

A

the initial rate limiting factor of drug therapy and absorption during the pharmaceutical phase

Absorption will depend on drug solubility!!!

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39
Q

Absorption is influenced by what factors

A

Drug solubility

pH

Concentration

Circulation to site of absorption

area of absorbing surface

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40
Q

For absorption we want drugs to be __ soluble

A

lipid

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41
Q

What sort of things can influence drug solubility

A

drug form

local conditions - like in GI if the stomach is full it may slow absorption since they need access to stomach wall

processing can enhance or delay - fillers, buffers, etc - these can make it work longer or be slower

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42
Q

pH differences important to know in the body

A

stomach is acidic - 1 to 2

intestine is alkaline

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43
Q

How does concentration impact absorption

A

high concentrations are absorbed faster than low ones - but we still do not want to give too much

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44
Q

Why is circulation important for drug absorption

A

more blood to carry it off for distribution and more blood in the area

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45
Q

What is one way to increase circulation for drug absorption

A

you could massage the area - like with an analgesic - to activate pressure sensors around the area so it does not hurt as much and also because the circulation to the shot site will make it work faster

this does not apply to drugs like heparin

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46
Q

How does temperature impact absorption

A

heat will increase circulation through vasodilation but cold does the opposite

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47
Q

What is one of the more important determinants of absorption

A

Area of Absorbing Surface

very large SA means a lot of medication can be absorbed

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48
Q

Absorbing surface is determined largely by …

A

ROUTE of administration

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49
Q

what is one the biggest absorbing surfaces

A

the small intestine

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50
Q

What is the typical natural flow of things regarding pharmacokinetic distribution?

A

Typically: GI Tract –> Portal Vein carries it off –> Liver –> Inferior Vena Cava –> Heart (Transportation Hub for the Body) –> General Circulation

not all drugs though

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51
Q

What are the routes of administration

A

Enteral

Parenteral

Percutaneous

Cutaneous

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52
Q

Enteral

A

This means that the route leads to the GI tract so it can be oral, rectal, etc

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53
Q

__ is the most common route of enteral administration

A

oral

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54
Q

Advantages of Enteral/Oral

A

safest (does not have to be clean/sterile)

Most economical (no equipment needed)

Most convenient

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55
Q

Disadvantages of Enteral/Oral

A

GI irritation to emesis (range - some drugs irritate causing NV)

Destruction by digestive enzymes (like insulin)’

Low gastric pH (acidic in stomach)

Irregularities in absorption (gastric bypass would change absorption of the stomach or rectal scarring)

Patient cooperation needed (cannot force)

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56
Q

Why is enteral/rectal usually saved a more “last resort”

A

poor predictability and it irritates the rectum

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57
Q

Parenteral

A

“Outside the GI Tract”

ex; shots, injections, IV

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58
Q

Advantages of Parenteral

A

absorbed in active form (no waiting for breakdown, can go right into the bloodstream)

more rapid and predictable

patient cooperation not necessary (does not need to be awake necessarily)

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59
Q

Disadvantages of Parenteral

A

asepsis must be maintained

pain

patient cannot always self medicate with this

expense - more expensive d/t equipment oftentimes

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60
Q

Forms of Parenteral

A

Subcutaneous

IM

IV

Intrathecal (right to spinal fluid)

(All bypass absorption phase and right to bloodstream)

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61
Q

Parenteral administration bypasses what phase of pharmacokinetics

A

the absorption phase (since it goes straight to blood)

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62
Q

Percutaneous

A

absorption from mucous membranes, sub lingual, or inhaled

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63
Q

Forms of percutaneous administration

A

pulmonary (gas/volatile drugs inhaled)

sub lingual (under tongue)

buccal (cheek)

other - vaginal, GU, nasal, eye ear

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64
Q

Cutaneous

A

administration via skin absorption

there is a good lipid barrier on skin so its poorly absorbed but if the skin is broken it could cause toxic dosage

skin is thick and stokes many types of drugs

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65
Q

Why are Children and Topical Meds Tricky

A
  1. Large skin surface in relation to body weight (lots of skin = more absorption)
  2. Thin dermis and epidermis leading to greater permeability (not fully developed skin barriers yet either - the child may get it faster and at a greater extent)
  3. Minimal lipid surface film (which blocks absorption usually)
  4. Skin is v prone to irritation
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66
Q

Nurses need to know when medications are formulated for what?

A

long acting or delayed release effects - these meds should not be crushed or broken as it removes the delay effect and leads to large amounts being delivered at once

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67
Q

Delayed Response

A

technically, refers to drugs w coatings that delay their release until after passing through the stomach

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68
Q

Extended Release

A

refers to those medications that have effects for a longer interval than an instant release for of that medication

69
Q

What are some examples of suffixes in drug names that may indicate delayed response or extended release

A

CR - controlled Delivery
CR - controlled release
ER - extended release
LA - long acting
SA-sustained action
SR- sustained release
XL = “extra” long
XR = “extended” release

70
Q

Regarding controlled response and extended release suffixes what is the problem?

A

there is no standard interpretation so one cannot easily know whether a medication has a specific effect interval and what that might be

71
Q

Distribution

A

Drugs now in the bloodstream and moving throughout the body

72
Q

How is the pattern of drug distribution done?

A

it is principally determined by blood flow and has 2 phases once in the bloodstream

73
Q

2 Phases of Distribution

A

Initial Phase
Second Phase

74
Q

Initial Phase

A

first phase of distribution that reflect cardiac output and regional blood flow

Heart, liver, kidney, brain (highly perfused organ) all receive most of the drug during the first few minutes after absorption - and because the body wants to protect itself above other things, the medication will get to those areas faster due to high blood flow they all have

75
Q

Second Phase

A

second phase of distribution

muscle, viscera, skin, and fat all receive drugs (slower than the others) and it may take several minutes to hours after drug absorption until equilibrium is reached

It is limited by blood flow, and involves far larger fractions of body mass - these “not as important” parts are slower acting/distribution to these areas as a result.

76
Q

What factors superimposed onto the patterns of blood flow determine rate of drug diffusion?

A
  1. If the drug is lipid INSOLUBLE - it will penetrate poorly and restrict distribution
  2. Drug Binding
  3. Drugs may accumulate
  4. pH (pH partitioning and ion trapping)
77
Q

What are some special areas of drug distribution

A

CNS
Placenta
Breast Milk
Drug Reservoi

78
Q

How is the CNS a special area of drug distribution

A

drugs move across endothelial membrane and perivascular cell membrane - blood brain barrier

special connective tissue (glia) will favor LIPID SOLUBLE DRUGS - so the drugs either need to be this way or have a brain catheter insertion

79
Q

How is placenta a special area of drug distribution

A

it is NOT a barrier, it has the same cell membranes as anywhere else, so drugs can get to the baby very easily - so all drugs for pregnant women must be cleared

80
Q

How is Breast Milk a special area of drug distribution

A

It has a lipid membrane (breast) so things can cross into the milk and the pH of the milk leads to weak bases having greater concen. here than in plasma

81
Q

What is the pH of breast milk compared to plasma

A

pH milk - 6.6 (weak acid)

plasma - 7.35 to 7.45 average

82
Q

Why do weak bases accumulate in greater concentration in breast milk

A

the weak acidic pH of the milk neutralized with weak base drugs and causes some particles to become charged making it hard to get back across the membrane - so then its trapped and gets to the infant

(weak acid can leave and not become trapped)

83
Q

Drug Reservoirs

A

body compartments in which drug accumulates (stored)

ex: Plasma Proteins, Cell Reservoirs

84
Q

How do plasma proteins act as drug reservoirs

A

the drug attaches to proteins like albumin - but is usually reversible

when attached they do not leave the bloodstream but become undone and then can leave

85
Q

Protein bind

A

reversible often times

It is when a drug can come off of a protein bind eventually to be moved

86
Q

Free Drug

A

active drug not bound to anything

this is the thing that can be used - bound drug cannot be used

87
Q

Why does child and infant albumin levels matter with drug dosing

A

infant albumin doesnt bind well and children have low albumin, so there is less binding occurring which can cause toxic amounts all at once - so they need to lower the dose when low protein levels exist

88
Q

Cellular Reservoirs

A

Drug accumulation in muscle and other cells - some areas include adipose tissue and fat, bones, transcellular

89
Q

Why is fat relatively stable as a drug reservoir

A

it has lower blood flow (lower distribution) and has affinity for certain drugs (ex: psychotropics)

90
Q

What sort of drugs have a higher affinity to bind to bone reservoirs

A

heavy metals like lead and radium

tetracycline

91
Q

Metabolism / Biotransformation

A

mechanism by which drugs are altered structurally (biotransformed) usually to facilitate excretion from the body

92
Q

The ultimate goal for metabolism is

A

make the drug WATER soluble so it can be excreted via kidney

93
Q

Kidneys excrete ___ soluble compounds

A

water

94
Q

Metabolism can make things more ___ and ___

A

potent and powerful

95
Q

What are the two things metabolism can cause a drug to become

A

less toxic - detoxification

more toxic - biotoxification

96
Q

Metabolism most often occurs in …

A

the liver - but some occurs in renal, blood plasma, and intestinal mucosa

97
Q

CYPs

A

metabolizing enzymes - 75% of drug metabolism occurs in this group

major enzymes in the liver for metabolism

Most drugs undergo deactivation by them, either directly or by facilitated excretion from the body - but there are some compounds bioactivated by CYPs forming active compounds

98
Q

Metabolites

A

compounds derived from original drug

usually less lipid soluble and more polar which embraces secretion

many have pharm activity and may be similar or different from parent drug

end product or by product of the liver

99
Q

Do metabolites have function

A

yes they sometimes can and some drugs are planned for becoming metabolites to do the action

100
Q

Factors that Influence Biotransformation/Metabolism

A
  1. Age - both extremes have decreased activity (1-64 ok range)
  2. Disease pathology - especially liver issues from ETOH, hep, and hepatotoxic meds
  3. Concomitant Drug Therapy
101
Q

Concomitant drug therapy

A

drugs enhancing or inhibiting one another (their metabolism)

ex; Drug B speeds up Drug A metabolism but Drug C lowers metabolism

102
Q

Patterns of Metabolism

A
  1. Hepatic Metabolism
  2. First Pass Metabolism
103
Q

Hepatic Metabolism

A

most drugs undergo this once absorbed, are distributed to sites of action THEN undergo metabolic changes when returned in blood through the liver

104
Q

First Pass Metabolism

A

all drugs absorbed from GI tract go to the portal system and liver BEFORE systemic circulation - if some are taken up and metabolized the first time through it is first pass elimination or metabolism and the drug could be completely inactivated this way (ex: nitroglycerin)

105
Q

What are the 2 ways to overcome First pass metabolism

A
  1. Different route bypassing liver
  2. give a high dose and some will get through
106
Q

Why does nitroglycerin get through despite its high first pass

A

because we give it sublingually so it goes right into the bloodstream and bypasses the first pass liver (this is not oral administration though)

107
Q

Metabolism is most located…

A

in the hepatic Endoplasmic reticulum

108
Q

Microsomal Portion of the Liver

A

the Hepatic ER of the liver where most metabolism occurs

109
Q

Microsomal System v Nonmicrosomal Liver

A

Microsomal - conjugation and most oxidation, some reduction and hydrolysis

Nonmicrosomal - mainly reduction and hydrolysis

110
Q

Research has shown that metabolism by the microsomal system can be depressed or stimulated by…

A

disease, drugs, foods, chemicals, etc

111
Q

How does Depressed metabolism come about

A

by conditions that have a neg. effect on hepatic fxn like starvation, jaundice, CO poisoning. - Anything that can damage the liver

diseases of renal, liver, or severe cardiac

by some drugs when administered simultaneously (ex: drug A stops Bs metabolism)

112
Q

Depressed Metabolism =

A

drug levels rise in the body/blood

113
Q

What sort of things stimulate metabolism

A

CNS depressants - barbiturate’s (“downers”)

Xanthines

Pesticides

Food Preservatives

Food Dyes

Some other specific drugs

114
Q

Non microsomal rxns are primarily in the liver, but…

A

some can be in plasma and other tissues

115
Q

What is the major means of Excretion

A

Renal - often excretion route is the kidney

Some does leave via milk, stool, exhalation, and such but most is via urine

116
Q

The kidney likes excreting ___ and ___ substances

A

ionized and lipid soluble

for absorption/distribution it was wanted unionized and lipid soluble

117
Q

___ is needed for Excretion

A

transformation (metabolism)

118
Q

What are some other routes of excretion

A

feces (oral ingested drugs unabsorbed)

bile - minor route

milk (important d/t effect on infant, not excretion amount)

exhalation (mainly for anesthesia and vapors and ETOH)

insignificant loss - sweat saliva tears hair

119
Q

What sort of things should be metabolized before secretion and what things largely stay unchanged

A

change - lipid soluble unionized

little change - water soluble ionized

120
Q

Renal pH

A

4.6-8.2

121
Q

If a drug ionized in urine…

A

then it will NOT be reabsorbed

122
Q

What ways can we change urine pH to aid excretion

A

increase pH to alkaline levels with NaHCO3 (ionizes weak acids) or decrease pH with Vit C (ionize weak bases)

123
Q

Most drugs leave the body through ___ secretion

A

tubular secretion (active transports 4/5 drugs)

124
Q

MEC

A

Minimum Effective Concentration

Smallest amount of drug in the body for effect

125
Q

MTC

A

maximum therapeutic concentration

highest amount we want in bloodstream for effect but not be toxic

126
Q

Therapeutic Range

A

area between MEC and MTC

127
Q

How long is the lag between onset time of effect for oral meds

A

about 30 minutes - 1 hour

128
Q

C Max

A

maximum concentration for a dose of medication

129
Q

Once a curve drops below MEC…

A

there is no longer an effect, BUT there is still drug in the body

130
Q

Onset of Action

A

point when MEC is reached

131
Q

When the initial drug dose is given what occurs?

A

plasma level rises (then they drop off after peak)

132
Q

Half Life

A

amount of time for PLASMA level concentrations to decreased to 50% of the original concentration

133
Q

Rate of Elimination =

A

Half Life

134
Q

How does half life work over time with 10 mg of a drug with a half life of 3 hours given at 9 am

A

5 mg left at noon

2.5 by 3 pm

etc

135
Q

Effects of drugs are essentially eliminated by the end of ___ half lives

A

4

136
Q

Initial Loading Dose

A

A larger dose of the drug given to bring level to minimal rapidly - then in increments afterward there is maintenance to keep levels in therapeutic range

ex:” Digoxin has 1 mg initial loading dose but doses after are .25 mg

137
Q

Pharmacodynamic Phase

A

what the drug does to the body, not how it moves but what it does

138
Q

Phamacokinetics are effects of __ on __

A

body on drugs

139
Q

Pharmacodynamics are effects of ___ on ___

A

drugs on body

140
Q

The effects of drugs occur when…

A

the medication reaches the target cell and the therapeutic effect occurs

141
Q

3 General Properties of Drugs

A
  1. Drugs do not confer any NEW functions of a tissue or organ - they only MODIFY existing function
  2. Drugs in general exert MULTIPLE actions rather than a single effect
  3. Drug action is a result of physiochemical interaction between the drug and functionally important molecules in the body
142
Q

3 Theories of Drug Action

A

Receptor Theory

Drug Enzyme Interaction Theory

Non Specific theory

143
Q

What are the 3 main ideas of how drug actions produce effects

A
  1. selectively combine with specific cellular sites (receptors)
  2. interacting with body systems (probably enzyme)
  3. non-specific
144
Q

Most drugs follow what theory of drug action

A

Receptor Theory - that selectively combining with specific cellular sites (receptors) produces effects

145
Q

Receptor Theory

A

Drug interacts at a site of action w/ receptor (specialized macromolecule) –> interaction stimulates a series of events that give rise to observed effect

ex: heart tissue has receptors –> drug comes in (ex: Beta 1 receptor) and acts on this receptor to increase contraction force and BP and speed

  • basically drugs just bind to specific receptors
146
Q

How can binding to a receptor lead to causing an effect

A
  1. causing permeability of membrane to be altered and allowing ionic movement
  2. stimulating an organ response
  3. causing the release of stimulating substances
147
Q

Drug Enzyme Interaction Theory

A

Provision of substrate material - drug combines with enzymes by virtue of structural resemblance to an enzymatic substrate molecule

this can either block normal enzymatic action or result in production of other substances with unique biochemical properties

148
Q

Antimetabolites

A

drugs which resemble enzyme substrate and bind to the enzyme as a result

149
Q

Non Specific theory

A

Partially Physiochemical theory

Drugs demonstrate no structural specificity such as receptor affinity; presumably act by more general effects on cell membranes and processes

May penetrate cells or accumulate in cell membranes where they interfere (by physiological and chemical means) with some cell function of fundamental metabolic process

150
Q

Receptor

A

Specialized macromolecule with which a drug interacts

May be cell or substance

Interaction stimulates a series of events that give rise to the observed effect (get something to happen or stop)

151
Q

Affinity

A

propensity of drug to be found at a given receptor site (Most likely drug is at or going to that certain site)

some dont have high affinity for where they should be though!

152
Q

Efficacy

A

drugs ability to initiate biological activity as a result of binding with receptor (how effective the drug is )

153
Q

Agonist (Action)

A

a drug which causes effects as a result of direct STIMULATION of the functional properties of the receptor with which it interacts (where you can actually cause an effect)

ex: Morphine is an opioid agonist/narcotic agonist - it makes opioid things happen suich as relieve pain, sedate, dilate blood vessels, etc - it makes actions happen

154
Q

Antagonis

A

Inhibits the action

drug which causes effects by INHIBITION of actions of specific agonists

ex: Narcan/Naloxone is an opioid antagonist - it stops opioid action - it will go in and bump opioids off receptors then sit there and take up the space to prevent rebinding

155
Q

Antagonist and Agonist interactions are usually ____, and based on ___

A

reversible, concentration

156
Q

Competitive Antagonist

A

has an affinity for the same receptor site as an agonist

competition site inhibits the action of the agonist

It will block action at “normal” concentrations, but if the agonist concentration is high it may override the antagonist

It is usually reversible and which ever is in higher amount will live on the receptor reversibly

157
Q

Non Competitive Antagonist

A

combines with a receptor mechanism and inactivates the receptor itself so the agonist cannot be effective regardless of concentration

This is considered irreversible and nearly so

158
Q

What is preferable for people: non competitive or competitive antagonists and why?

A

Competitive antagonists because they are reversible

We do not want to put non competitive irreversible things in the body - this is how pesticides work

159
Q

Partial Agonists (Agonist-Antagonist)

A

Have affinity and some efficacy but may antagonize the action of other drugs that have greater efficacy

Some efficacy but impacts other drugs too - the mid way drugs

Some opioids are A-A and are medium effectiveness with less abuse potential

160
Q

Bioavailability

A

percentage of active medication absorbed

how much the drug took that is actually available in the body for use

ex: levodopa only 2% is available to the body / brain

161
Q

Potency

A

amount of drug needed to cause an effect

162
Q

Highly potent drugs need ___ doses to cause effects

A

smaller doses to cause effect

163
Q

Weakly potent drugs need ___ doses to cause effects

A

larger doses to cause effect

164
Q

Is potency how strong a medication is?

A

NO

It means how much is needed to cause effect

ex: 1 mg of Dilaudid is potent but Morphine needs 15 mg to cause effect

165
Q

Your patient works the night shift and often cannot sleep during the day. This is an example of what kind of variable ?

health status

environment

life span and gender

lifestyle and diet and habits

A

Lifestyle Diet and Habits

166
Q

Absorption of Enteral drugs occur most frequently where?

A

Small intestine (absorption not administration)

167
Q

Why is the onset of action rapid after IM injection?

A

muscles have great blood supply so it gets to the bloodstream very fast

168
Q

Which of the following is most likely to be affected by ischemia?

Absorption

Distribution

Metabolism

Excretion

A

Distribution (ischemia is reduced blood flow)

N365: Pharmacology in Nursing (15 decks)

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