Units 1-2 Flashcards
1
Q
Define absorption:
A
The movement of a drug from its site of administration int the blood
2
Q
When drugs are being absorbed what effects the onset and intensity of effects?
A
The route it is administered because each route has different barriers to absorption
3
Q
What to categories signify the route or medications?
A
- Enteral (via GI tract)
- Parenteral (outside of GI tract via “injection”)
4
Q
Is oral (PO) administration Enteral or Parenteral?
A
Enteral
5
Q
What routes of administration fall under parenteral?
A
- IV
- IM
- Sub Q
6
Q
How are oral drugs absorbed?
A
From intestine, stomach, or both
7
Q
What does P-glycoprotein do in relation to oral administration?
A
-Can effect intestinal absorption by pumping drug back out
8
Q
What are barriers to absorption with oral administration?
A
- layer of epithelial cells that lines GI tract
2. Capillary wall
9
Q
Why is the layer of epithelial cells that lines the GI tract a barrier to oral administration of drug absorption?
A
Drugs absorbed from sites along GI tract must pass through liver before general circulation can occur
10
Q
What are factors that determine the absorption of a drug administered orally?
A
- Solubility and stability of drug
- Gastric and intestinal pH
- Food in gut
- Co-administration of other drugs
- Special coatings on drug preparation
11
Q
What is important about IV drug absorption?
A
-No barrier to absorption
12
Q
What is the only barrier to IM drug absorption?
A
-Capillary wall is only barrier
13
Q
How do Sub Q drug get absorbed?
A
Enters blood by passing through spaces between cells of capillary wall
14
Q
Why is there no barrier to absorption of IV drugs?
A
drug directly in blood stream
15
Q
Is IV drug absorption instantaneous and complete?
A
Yes
16
Q
The water solubility of a drug given IM and blood flow at site of IM injection determine what?
A
Rapid or slow absorption
17
Q
Are there any significant barriers to Sub Q drug absorption?
A
No, similar to IM
18
Q
Solubility of Sub Q drug and blood flow at Sub Q injection site are major determinants of what?
A
Rapid or slow absorption
19
Q
The rate at which a drug undergoes absorption is influenced by what?
A
- Physical and chemical properties of drug itself
- Physiologic and anatomic factors at absorption site
20
Q
What are factors that impact absorption of a drug?
A
- Rate of dissolution
- Surface area
- Blood flow
- Lipid solubility
- pH partitioning
21
Q
How does the rate of dissolution effect drug absorption?
A
Drug must dissolve first, which determines rate of absorption
22
Q
How does surface area effect dug absorption?
A
Larger surface area= faster absorption
23
Q
How does blood flow effect drug absorption?
A
-more blood flow = quicker absorption
24
Q
What is a concentration gradient in relation to drug absorption?
A
Amount of drug outside of the blood and amount drug in blood
25
How does lipid solubility effect the absorption of a drug?
Highly lipid-soluble drugs= quicker absorption
26
Why are lipid soluble drugs absorbed quicker?
Can easily cross membranes
27
Bioavailability is the amount of active drug that what?
Reaches the systemic circulation from its site of administration
28
Can different formulations of the same drug vary bioavailability?
Yes
29
What factors effect the bioavailability of a drug?
- Tablet disintegration time
- Enteric coating of tablet
- Sustained release formulation (can make drug response variable)
30
Small spheres containing drug that release at different times is what type of drug?
Sustained Release (SR) drug
31
Protective coating absorbed in small intestine is what type of drug?
Enteric Coating (EC)
32
Differences in bioavailability occur primarily in what?
Oral preparations (usually too small to lack clinical importance)
33
Differences in bioavailability is the biggest concern with drug that have what?
A small therapeutic range
34
Why do drug with a small therapeutic range have bioavailability concerns?
Small changes can produce significant change in response (toxicity or therapeutic failure)
35
What are factors that impact distribution of a drug?
- Albumin levels
- Blood flow to tissues
- Ability to exit vascular system
- Ability to enter cells
36
Albumin is the main protein used in drug binging which made in the liver, if poor liver function what can happen to distribution of a drug?
Theres not enough albumin for drug to bind to and carry out desired effect
37
How does blood flow to tissued impact drug absorption?
Drugs are carried by blood flow to tissues and organs
38
Why is regional blood flow not typically an issue in drug distribution?
Most tissues are well perfused
39
Why are abscess and tumors a complication in the distribution of drugs?
They have limited blood supply
40
What is a drugs next step after being received from the blood?
Exiting the vascular system
41
Why is exiting the vascular system important for drug distribution?
Most drugs do not produce their effect in the blood need to get to site of action
42
Why is exiting the vascular system important for a drug in order to complete metabolism and excretion?
Yes
43
How do drugs leave the vascular system?
Via capillary beds (typically pass between not through_
44
What is the BBB?
Blood brain barrier
45
What is the name for unique capillaries in CNS?
BBB
46
Is the placenta a absolute barrier to drug distribution in the fetus?
No
47
Is protein binding important for a drug to leave the vascular system,?
Yes
48
What does BBB do?
Protect certain drug from effecting CNS
49
Why most some drugs enter cells during distribution?
To reach site of action
50
Why must all drugs enter cells during distribution at some point?
To undergo metabolism and excretion
51
The factors that allow drugs to enter cells are same as what allows them to cross membranes, what are these factors?
- Lipid solubility
- Presence of transport system
- Or both
52
Many drugs do produce their action by binding with receptors on external surfaces of a cell and do not need to do what?
Cross the cell membrane to act
53
Is the liver one of the most important organs for protein making?
Yes
54
What is the most common/important protein?
Albumin
55
What is the name of the protein that is a large molecule which is forced to remain in the blood stream?
Albumin
56
Does albumin impact drug distribution?
Yes
57
Can drugs make reversible bonds with various proteins/
Yes
58
Can drugs be bound or unbound?
Yes
59
Even though drug can bind to albumin, only what will occur?
Only some drugs will be bound at any moment
60
What does the percentage of drug molecules that are bound depend on?
Strength of attraction between albumin and the drug
61
What is a consequence of protein binding?
Restriction of drug distribution
62
Drugs bound to albumin can't do what?
Leave bloodstream
63
Because when drugs are bound to albumin they can't leave the blood stream, what does this prolong and increase?
- Distribution phase is prolonged
| - drug half-life increases
64
Protein binding can also be a source for what?
Drug interactions
65
Because each albumin only have a few binding sites, this can be a source for what?
Drug interaction of unbound drugs?
66
Drugs competing for binding sites can be a source for what?
Drug interactions
67
Why can competition of protein binding cause potential for drug interactions?
When competing drugs may displace each other and cause serum drug levels to rise
68
Can competition for binding sites increase intensity f drug responses?
Yes
69
The rise of plasma drug levels can cause what?
Drug toxicity
70
What decreased bioavailability, resulting in less ADRs and drug toxicity risk?
Increased protein binding?
71
What increases bioavailability, resulting in more risk of ADRs and drug toxicity?
Decreased protein binding
72
How does the BBB protect the body?
It has tight junction between cells and CNS (making hard to easily pass through)
73
How can drug get around the BBB?
- Be lipid soluble to pass through cell wall
| - or be able to use existing transport system
74
Receptors are special chemical sites in the body that most drugs do what with?
Interact to produce effect
75
Can many cellular components be considered drug receptors?
Yes
76
Is binding to a receptor usually reversible?
Yes
77
When a drug binds to a receptor it will do what?
Mimic or block body's regulatory molecules
78
Do drugs help the body help itself?
Yes
79
Because drugs can only mimic or block its own regulatory molecules, this means what?
Drugs can't give cells new function
80
The enzymatic alteration of drug structure is called what?
Drug metabolism
81
Drug metabolism most often takes place where?
Liver
82
Hepatic Drug-Metabolizing Enzyme works through what?
Hepatic microsomal enzyme system/ P450 system
83
The hepatic microsomal enzyme system/P450 system is capable of what?
Catalyzing a wide variety of drug reactions
84
What does P450 refer to?
Cytochrome
85
Cytochrome P450 is a key component of what?
The hepatic microsomal enzyme system/P450 system
86
Drug metabolism does not always result in breakdown of a drug, it can also result in what?
Formation of a large parent drug
87
The time required for the amount of drug in the body to decrease by 50% is called what?
Serum half-life
88
What does the serum half-life determine?
Dosing intervals
89
A short-half life means what?
Drug leaves quickly
90
A long half-life means what?
Drug leaves slowly
91
Explain Morphine if it has a half-life of 3 hours:
- body stores morphine will decrease by 50% in 3 hours regardless of how much in body
- 50mg would equal 25mg in 3 hours
92
When the liver metabolizes drugs to such an extent that only a small amount of active drug emerges is called what?
First pass effect
93
Does the first pass effect decrease therapeutic effect?
Yes
94
What may need to be changed in relation to the first pass effect on a drugs therapeutic effect?
Dose may need to be increased
95
The "first pass" through the liver can cause rapid inactivation of some oral drugs which does what?
Greatly reduces the availability of the drug
| ex: drug may be need to be 1-2mg IV, 4mg IM, and 10mg Oral
96
Does the first pass effect have an impact in drug bioavailability?
Yes
97
The first pass effect may cause a too low of drug dose to not produce therapeutic effects why?
Not enough drug made it ti bloodstream to produce desired response
98
What labs are we concerned about related to drug metabolism?
- AST
- ALT (very liver specific)
- Alkaline phospatase
- Bilirubin
- GGT
99
Is cytochrome p450 system a single molecular entity?
No
100
Is the cytochrome P450 system a group of 12 closely related enzyme families?
Yes
101
3 of the cytochrome p450 enzyme families do what?
Metabolize drugs (CYP1, CYP2, CYP3)
102
CYP1, CYP2, and CYP3 are each composed of multiple form that only do what?
Metabolize certain drugs
103
What do the other 9 enzyme families of the cytochrome p450 family do?
metabolize endogenous compounds (steroids, fattty acids, etc)
104
Taking multiple drugs with the same metabolizing enzyme a decrease dose or what will happen?
bioavailability will increase and possibly cause drug toxicity
105
Drugs that act on the liver to increase rates of drug metabolism are called what?
inducers (enzyme induction)
106
What consequences of inducers?
- they can also increase their own rate of metabolism
| - can accelerate metabolism of other drugs
107
Drugs that act on liver to decrease rates of drug metabolism are called what?
Inhibitors (enzyme inhibition)
108
What are consequences of inhibitors?
-Slower metabolism= increase active drug accumulation; and can lead to increase risk of ADRs and toxicity
109
What is excretion of a drug?
Removal of drug from the body
110
What is excretion of a drug carried out through?
- Urine
- Sweat, saliva (small amount)
- Breast milk
- Bile
- Expired Air (anesthetics)
111
Are most drugs excreted through the kidneys?
Yes
112
What facilitates the removal of a drug through the kidneys?
- Glomerular filtration
- Passive tubular transport
- Active tubular secretion
113
What labs are we concerned about in relation to excretion (renal function)?
- GFR
- BUN
- Creatinine
- I & O's
114
Drug receptors change in response to what?
Inhibition and activation
115
Continuous exposure of a receptor to a drug causes what with time?
Desensitized or refractory "down regulation"
116
What does a receptor being desensitized or refractory "down regulation" mean?
Receptor becomes less responsive
117
Continuous exposure of a receptor to an antagonist causes what?
hypersensitivity
118
Does an "empty stomach" require fasting?
No
119
What does take a drug on a empty stomach mean?
-1 hour before meal
or
-2 hours after a meal
120
May a drug need to be taken on an empty stomach due to acidity needs?
Yes
121
Do some drugs need to be taken on a empty stomach due to possible drug/food interactions?
Yes
122
What does the range of plasma drug levels which fall between the MEC and the toxic concentration signify?
The therapeutic index of that drug
123
What does MEC mean?
minimum effective concentration
124
When there is enough drug present to produce therapeutic responses but not so many as to cause toxicity, what is this achieving?
Plasma drug level in a therapeutic range
125
How is therapeutic range calculated?
By ratio of drugs LD50 to its ED50
126
The average lethal dose in 50% of the animals treated is called the what?
LD50
127
The median effective dose that produces a specific effect in 505 of population is called what?
ED50
128
TD divided by Ed equals what?
Therapeutic dose
129
The smaller the therapeutic dose number the more what?
Dangerous the drug is
130
A drug with a wider/larger therapeutic index means what?
Safer the drug is
131
A drug with a smaller/more narrow therapeutic index means what?
Less safe the drug is
132
A nurse who is aware of drugs with narrow therapeutic range which are most likely to require intervention for drug related complications, can focus on what?
Additional attention need to monitor these patients for S/S of toxicity
133
What a drug-drug risk of interaction directly proportionate to?
number of drugs and individual is taking
134
For safety how should you monitor drugs with a narrow therapeutic range?
check labs for serum drug levels
135
The more drugs a person is taking puts them at more risk for what?
- drug toxicity
| - drugs that decrease effectiveness of each other
136
When the combined effect of two drugs exceeds the expected additive effect of each the drugs administered independently , then one drug is said to be what over the other?
Potentiative
137
When a drug decreased the metabolism of other drugs what are they called?
Inhibitory drugs (sometimes desired)
138
A medication that mimics the action of the signal ligand by binding to and activating a receptor is called a what?
Agonist
139
A medication that typically binds to a receptor without activating them, which instead decreased the receptors ability to be activated by other agonists is called a what?
Antagonist
140
What are 3 ideal drug properties?
- Effectiveness (most important)
- Safety
- Selectivity
141
When a drug produces a response for which it was given means the drug has what?
Effectiveness
142
When a drug can't produce harm even at high doses and for prolonged periods, means the drug is what?
Safe
143
In regards to safety do all drugs have benefits and risks?
Yes
144
When a drug produces only the response for which it was given means the drug is what?
Selective
145
Is complete drug selectivity possible?
No all drugs have side effects
146
What are other ideal properties of a drug?
- Reversible action
- Predictability
- Ease of administration
- Freedom of drug interactions
- Low cost
- Chemical stability
- Simple generic name
