Week 1 Pharmacokinetics Flashcards
(61 cards)
1
Q
What is pharmacokinetics?
A
- branch of pharmacology concerned with the movement of drugs within the body.
- Essentially what the body does to a drug
- Has 4 main properties. AKA the ADME properties
- Absorption
- Distribution
- Metabolism
- Excretion
*your body’s way of taking something you have given it and getting rid of it
2
Q
What is pharmacodynamics?
A
What a drug does to the body
3
Q
What is bioavailability?
A
- relates to absorption
- (F)
- percentage of medication that reaches systemic circulation
- think of F for fraction —— of medication that reaches circulation
- used to figure out oral to IV equivalents
- a percentage of the oral dose that makes it into general circulation
4
Q
What things affect a drugs bioavailability?
A
- dissolution and absorption characteristics (ie:enteric coated, dissolvable tabs)
- route of administration
- stability in GI tract: is it an acid medication or a basic medication?. Where is it going to break down?
- metabolism prior to blood stream: first pass metabolism
5
Q
How does route of administration affect bioavailablitlly?
A
- IV: 100% bioavailablity.
- oral: generally not 100% available
6
Q
Formula to calculate new dose based on changing route and bioavailability
A
New dose = F old x (current dose)/F new
7
Q
What are the routes of administration
A
- oral
- topical
- transdermal: patch, cream
- eye and ear drops
- inhalation
- sublingual/buccal
- injection: IV, IM, SQ, IT
- peripheral vs central
8
Q
Factors to consider with oral administration
A
- gastric pH and contents: when meds are created for oral use, they are tested on people with healthy GI tracts, and not on PPIs, and moves normally. Change in pH can affect absorption
- surface area: people with bowel resection or bariatric surgery
- blood flow: poor blood flow decrease absorption
- GI motility: the longer the med sits in GI tract can increase absorption
- complete GI tract: possible ischemic bowel, decreases absorption
- flora: meds rely on flora for metabolism
9
Q
Consideration for sublingual/buccal administration
A
- bypasses GI tract and drains directly into the vena cava
- very rapid
- meds must be highly lipid soluble and potent
10
Q
What are hydrophilic medications?
A
- AKA water soluble
- more highly ionized. Have either a positive or negative charge.
- like to stay in water bc water carries electrolytes very well.
- generally need a transport molecule or carrier protein to move across membranes
11
Q
What is lipid soluble?
A
- compounds that are less ionized, or less polar are lipid soluble
- they easily move across barriers in the body. They don’t need a transport molecule to move across membranes
12
Q
What is first pass metabolism?
A
- portal circulation is taking the oral medication that has been absorbed from the gut to the liver before reaching systemic circulation
- the liver contains almost all of the metabolizing enzymes
- this does not occur to all P.O. meds
- 90% of an oral medication can be destroyed by the liver before it gets to systemic circulation
13
Q
What are the types of topical administration?
A
- Skin
- Eye
- Inhalation
14
Q
What to consider with skin as site of topical administration
A
- medication needs to be highly lipophilic to pass through the skin membranes
- skin needs to be intact
- temperature can affect rate of absorption
- blood flow: fatty areas have less blood flow, or areas with PVD. More muscular areas have higher blood flow
15
Q
What to consider with topical medications administered to the eye
A
-may become systemic though the nasolacrimal canal
16
Q
What to consider with inhalation route for topical administration
A
- rapid onset due to large surface area
- avoids first pass metabolism
- high amounts of blood flow
- local in site of action
- difficult to control: predicted that less than 20% is actually going where it needs to go.
17
Q
What are the different routes of injectable medications?
A
- IV
- SQ
- IM
18
Q
Things to consider with IV drugs
A
- 100% bioavailability
- potentially immediate
19
Q
Things to consider with sub-Q route of administration
A
- 100% bioavailability
- depending on solution, rates may be slower
- lipophilic, relies on passive diffusion
20
Q
Things to consider with IM medications
A
- 100% bioavailability
- relies on simple passive diffusion, therefor lipophilic
- be sure not to enter directly into blood stream
21
Q
What is volume of distribution?
A
- AKA apparent volume of distribution
- Size of compartment necessary to account for the total amount of drug in the body if it were present through the body at same concentration found in the plasma
- assuming that what you are reading out of peripheral blood is homogenous through the entire body
*average adult plasma has a Vd = 3L
Total body water 0.65L/kg
22
Q
What can volume of distribution be used to calculate?
A
Loading doses
Loading dose = Vd x Cd
Cd; desired concentration
23
Q
How can protein binding affect volume of distribution?
A
- affects the amount of free drug in the body that can actually do things
- affects the amount of free drugs unbound drug: = active
- reversible: they can attach/de-tach
*this is why we get “free-levels” of certain medication to see how much med is actually active
24
Q
What type of protein does acid drugs bind to?
A
Albumin
25
What type of protein does basic drugs bind to?
Alpha 1 acidic glycoprotein
26
If a medication is bound to a protein, is it active?
No, it cannot interact with their receptor, can’t get absorbed somewhere else, or get metabolized
27
How does tissue binding affect the amount of free drug in the body?
Fat is a reservoir for lipid soluble drugs
*where the medication likes to be is important to remember when drawing level
28
What is membrane permeability?
In order to enter an organ, a drug must permeate all membranes that separate the organ from the site of drug administration
- if its a hydrophilic med it will need a transport molecule or carrier protein.
- membranes have a lipid by-layer. Must be lipophilic to pass through
29
How do medications the cross blood brain barrier?
- Have very tight junctions
- not easy to move through without help or being highly lipophilic
- when inflamed with infection like meningitis, it opens up more
30
What protein will limit the placental transfer of medication?
P-glycoproteins
31
What medications will a fetus be exposed to due to placental transfer?
Fetus is exposed to nearly all medications a mother takes
32
Is fetal plasma more acidic or basic?
- acidic
| - it will trap basic drugs
33
What are P-glycoproteins
- family of transport molecules in lipid by-layers
- requires ATP or energy molecule
- found all over, including blood brain barrier
- important at for medication interactions and drug resistance
34
What are the types of way drug transport occurs across membranes?
```
Passive diffusion
-no energy
-no carrier
Facilitated diffusion
-no energy
-yes carrier
Aqueous channels
-no energy
-no carrier
Active transport
-yes energy
-yes carrier
```
35
What is passive diffusion?
Don’t need energy or a carrier
Lipophilic, nonionic, small molecules will pass through a membrane
36
What is facilitated diffusion?
Doesn’t need energy, but may need a carrier.
Drug will bind to a carrier and get moved through the lipid bi-layer
37
What are aqueous channels?
Water moves through these, and sometimes small hydrophilic drugs will pass through with them
38
What is active transport?
Need energy and need a carrier molecule to pass through
Closed channels, but will open up with something like ATP
39
What is metabolism?
The entire purpose of metabolism is to take a large molecule and make it more ionized, more hydrophilic, more water-loving, more small, to keep in blood stream to be eliminated though kidneys.
40
What are prodrugs?
When when an inactive medication is metabolized by the body to produce an active drug.
More rare
41
What are metabolites?
A product of metabolism
Some times you give an active molecule then metabolites inactive
Can have active:active
Inactive: active
Active : inactive
42
What is phase I metabolism?
Trying to break down and expose ionized group so that will stay in the blood
Generally lose activity, rare instances preserved
Then often hydrolysis or ester lined for rapid elimination thru kidneys
43
What is phase II metabolism?
If not hydrophilic enough, sometimes will add on a compound.
This will make it more easily eliminated
44
Where are most of the enzymes located that break down medications?
The liver
Can also be in GI tract, kidney, lung
45
What is Cytochrome P450?
-the most common enzymes that break down medications
Aka CyPs
These are phase I type reactions
Trying to take molecule and make more ionized, polar, more hydrophilic
46
What are substrates?
Is a drug that is metabolized by an enzyme system
47
What is inhibition of enzymes?
Will keep the enzyme from working properly
-ability to increase amount of parent compound
48
What is induction of enzymes?
Will enhance the capability of the enzyme
- the ability to quickly metabolize the parent compound
49
What leads to drug interactions?
When medications inhibit or induction of enzymes
This will either speed up or slow down metabolism.
Inhibition is more frequent than induction
If meditation inhibits the enzyme that metabolizes another medication, there will be more of that second medication active in the system
50
What other factors affect metabolism?
- genetics
- environmental, diet
- disease factors
- liver disease, heart failure, sepsis
- age and sex
- when young, CYP enzymes haven’t developed, when old they fail
51
What are pharmacogenetics?
Can see CYP enzymes and how they act
Some people have alleles or enzymes that affect how people react to medications
52
What is the process of elimination?
If the medication is small enough or hydrophilic enough, it may be excreted unchanged.
It can be eliminated unchanged, a metabolite, or unchanged
53
Is it easier to eliminate polar/hydrophilic compounds, or lipophilic compounds?
It’s easier to eliminate hydrophilic compounds
54
A bulk of medications rely of this order for elimination?
The kidney
Eliminate a lot of medications through urine
55
What are the 3 processes to renal elimination?
- glomerular filtration
- unbound medication
- active tubular secretion
- can be brought into kidney by transport proteins
- passive tubular reabsorption
- week acids and bases via concentration gradients
56
What are routes of elimination?
- renal
- biliary and fecal
- sweat, saliva, and tears
- lungs
57
What are first order kinetics?
A percentage is coming out with each half life or interval
Comes down on a gradient
58
What are zero order kinetics?
Medications are preceded a specific amount over time
More linear, easier to predict
59
What is half life?
How much time it takes for concentration of a medication in blood stream to halve
Use an elimination rate to find this
60
What is elimination rate?
Used to determine half life of a mediation
```
Elimination rate (k):
-fraction or % of the total amount of a drug in the body removed per unit of time
```
61
What do we use the half-life of medications for?
- estimate the time to steady state
- need 5 half-lives to get to steady state
- estimate the time to eliminate the medication from the body
- predict non-steady state plasma levels
- predict steady state from a non-steady state level
- determine dosing intervals
