1 - Pharmacokinetics Flashcards
(128 cards)
1
Q
What is prescriptive authority?
A
The legal right to prescribe drugs
2
Q
What does it mean to prescribe independently?
What does it mean to prescribe without limitation?
A
- Doesn’t need MD approval
- Can prescribe any meds except schedule 1 drugs
3
Q
What are schedule 1 drugs?
A
Ecstasy, Meth, Heroin, Marijuana, LSD
4
Q
What are the nine essential components of medication educaction?
A
- Name
- Purpose
- Dosing Regimen
- Administration
- Adverse Effects
- Storage
- Lab Testing
- Interactions
- Duration of therapy
5
Q
What are the three purposes of drug monitoring?
A
Determining Therapeutic Dosage
Evaluating medication adequacy
identifying adverse effects
6
Q
What does it mean if a drug has an NTI?
A
It has a narrow therapeutic index
(coumadin, lithium, theophylline)
7
Q
What is the most common nonadherent behavior?
A
Missed a dose (57%)
8
Q
What are the six nonadherent behaviors?
A
- Missed a dose
- Forgot to take a dose
- Didn’t refill in time
- Took less than prescribed
- Didn’t refill at all
- Stopped taking the med
9
Q
What are the four most common reasons for nonadherence?
A
- Forgot (42%)
- Ran Out (34%)
- Away from home (27%)
- Trying to save money (22%)
10
Q
What are the four basic principles of pharmacokinetics
A
Absorption
Distribution
Metabolism
Excretion
11
Q
What is absorption?
A
Drug’s movement from site of administration into the blood
12
Q
What is distribution?
A
Drug’s movement from blood into interstitial space and then into cells
13
Q
What is metabolism?
A
i.e. biotransformation
enzymatically mediated alteration of drug structure
14
Q
What is elimination?
A
The combination of metabolism and excretion
15
Q
What are the three modes by which drugs cross the cell membrane?
Which is most common?
A
Channels/Pores
Transport System
Direction Penetration (Most common)
16
Q
How common is it for drugs to pass through pores or channels?
A
Extremely uncommon
Pores and channels are very specific
17
Q
All transport systems are _____
A
selective
18
Q
What is PGP?
A
AKA P-glycoprotein or multidrug transporter protein
One of the most prolific drug transport proteins
19
Q
Why do most drugs depend on direct penetration to get through membranes?
A
Most drugs are too large to pass through pores/channels
AND
most drugs lack transport systems
20
Q
What kind of drug is most likely to successfully achieve direct penetration?
Why?
A
Lipid soluble drugs
Membranes are composed primarily of lipids, and like dissolves like
21
Q
What are polar molecules?
A
molecules with no net charge but an uneven distribution of electrical charge
Positive and negative charges on the molecule congregate separately, so there is a (+) and (-) end..
TWO POLES
22
Q
Is water polar or nonpolar?
Are lipids polar or nonpolar?
A
Polar
Nonpolar
23
Q
Polar molecules will dissolve in _____ solvents
A
Polar
24
Q
What are ions?
A
Molecules that have a net electrical charge
25
Many drugs are either weak acids or weak bases. Why is that significant?
They can exist in charged and uncharged forms
Weak acids and bases carry electrical charges based on the pH of the medium
26
Acids tend to ionize in _____ media
Bases tend to ionize in ____ media
basic
acidic
27
Drugs that are weak acids are best absorbed in ____ environments
Acidic BECAUSE they remain in a non-ionized form
28
What is pH partitioning or ion trapping?
When a membrane has an acidic side and a basic side, drug molecules will accumulate on the side where the pH most favors their ionization
Acidic drugs accumulate on the alkaline side
Alkaline drugs accumulate on the acidic side
29
What are chemically equivalent drug preparations?
ones that contains the same amount of of the identical chemical compound
30
Preparations are considered equal in bioavailability when:
the drug they contain is absorbed at the same rate and to the same extent
31
What factors affect drug absorption?
1. Rate of dissolution (how quickly it dissolves)
2. Surface area available for absorption (higher in the SI than the stomach, for example)
3. Blood Flow
4. Lipid Solubility
5. pH partitioning
32
As a rule, highly lipid-soluble drugs are absorbed \_\_\_\_\_
more rapidly than drugs with a low lipid solubility
33
How does pH partitioning influence drug absorption?
Absorption is enhanced with the difference between the pH of the plasma and the pH at the site of administration is such that drug molecules will have a greater tendency to be ionized in the plasma
If the plasma is more basic than the site of administration, and the medication is a weak acid, the medication is more likely to ionize and get “trapped” in the plasma
34
What three factors determine drug distribution?
1. Blood flow to tissues
2. Ability of a drug to exit the vascular system
3. Ability of a drug to enter cells
35
Since most tissues are well perfused, distribution is seldom a limiting factor for drug delivery. When is this not true?
Abscesses and Tumors
An abscess has no internal blood vessels, so ABX can't reach it. That's why they have to be drained.
Solid Tumors have a limited blood supply on the INSIDE. Can make chemo therapy minimally effective
36
Why is it so easy for drugs to pass through capillaries?
Where is this not true?
They simply pass through the pores in the capillary walls in between capillary cells (rather than through them)
The brain and the placenta
37
Only drugs that are ____ or ____ can cross the Blood Brain Barrier
Lipid soluble
have a transport system
38
Why is the blood brain barrier so impermeable to most drugs?
Tight cell junctions
PGP pumps drug back into the blood from capillary cells, limiting the amount that can get through to the brain
39
Why are newborns so susceptible to medications with CNS toxicity?
The BBB is not fully developed at birth
40
Most drugs cross the placenta via \_\_\_\_\_\_\_
simple diffusion
41
What kind of drugs pass easily from the maternal bloodstream into fetal blood supply?
lipid soluble, non-ionized compounds
42
What kind of drugs have a hard time passing through the placental membrane?
compounds that are ionized, highly polar, or protein bound
drugs that are substrates for the PGP transporter (which pumps the drug back out into maternal circulation)
43
What is the most important protein drugs may bind to?
Albumin
44
What determines the percentage of drug molecules that circulate bound to albumin?
The strength of the attraction between albumin and the drug
45
How does albumin contribute to drug interactions?
Each albumin only has a few binding sites
Drugs that bind with albumin compete for these sites and can displace one another
Giving one drug with a high affinity for albumin may decrease the albumin binding of another drug, dramatically increasing its free concentration and effect
46
Where does most drug metabolism take place?
The liver
47
Most drug metabolism that takes place in the liver is performed by:
the p450 system
48
What is cytochrome p450?
It is NOT a single molecule! It is a group of 12 closely related CYP enzyme families
49
Which p450 families metabolize drugs?
CYP1
CYP2
CYP3
50
If three p450 families metabolize drugs, what do the other 9 do?
metabolize endogenous compounds (steroids, fatty acids, etc)
51
What are the six functions/consequences of drug metabolism?
1. Enables renal excretion
2. Drug inactivation
3. increased therapeutic action
4. activation of prodrugs
5. increased or decreased toxicity
52
What is the most important consequence of drug metabolism?
promotion of renal excretion
lipid soluble drugs have to metabolized into hydrophilic forms before the kidneys can excrete them
53
what is the most common end result of drug metabolism?
inactivation
54
Give an example of metabolism that causes increased therapeutic action
Codeine is metabolized into morphine, which is much, much more analgesic
55
What is a prodrug?
A drug that is pharmacologically inactive until it is metabolized into its active form in the body
56
What are some advantages to prodrugs?
a drug that can't ordinarily cross the BBB can be administered as a lipid-soluble prodrug that is converted to the active form once inside the CNS
57
What is an example of increased toxicity from metabolism?
It's actually the metabolites of tylenol that are lethal to the liver, not the tylenol itself
58
What factors influence the rate of drug metabolism?
Age
Induction and Inhibition of Enzymes
First-Pass Effect
Nutritional Status
Competition between drugs
59
Drugs that are metabolized by P450 hepatic enzymes are called \_\_\_\_\_\_
p450 substrates
60
Drugs that increase the rate of drug metabolism are \_\_\_\_\_
p450 inducers
61
Drugs that decrease the rate of drug metabolism are \_\_\_\_\_\_
p450 inhibitors
62
How do drugs that are p450 inducers effect metabolism?
act on the liver to stimulate enzyme synthesis
Decreases the amount of active drug and plasma levels fall
63
What is the first-pass effect?
the rapid hepatic inactivation of certain ORAL drugs
64
Why is first-pass effect only a factor with oral medications?
When drugs are absorbed through the gut, they go through portal circulation before they enter the systemic circulation
65
Drugs that undergo rapid hepatic metabolism often must be given \_\_\_\_\_\_
parenterally, in order to avoid the first-pass effect
66
Why does nutritional status effect drug metabolism?
drug-metabolizing enzymes require a lot of cofactors which are mostly obtained via nutrition
Without them, drug metabolism is impaired
67
What is enterohepatic recirculation?
When a drug is absorbed through the gut, is transported to the liver via portal circulation, the liver transports it into the bile duct, and it returns to the duodenum. Then the process repeats.
68
Which drugs are effected by enterohepatic recirculation?
Drugs that have undergone glucuronidation (a process that coverts lipid soluble drugs to water soluble drugs by binding them to glucuronic acid)
It causes these drugs to be present in the body much longer than they otherwise would
69
What are the 6 modes of excretion?
1. Urine
2. Bile
3. Sweat
4. Saliva
5. Breast Milk
6. Exhalation
70
Which organ accounts for the majority of drug excretion?
Kidneys
71
What factors modify renal drug excretion?
1. pH dependent ionization
2. competition for active tubular transport
3. Age
72
Which drugs undergo passive tubular reabsorption?
ONLY lipid soluble drugs
73
Why can manipulating urinary pH change excretion?
Drugs that are ionized at the pH of urine will ionize within the tubule and will not reabsorb
If you alter the urine's pH to promote ionization of the drug, it will be excreted much more effectively
This has been used to promote excretion of poisons and medications that have been taken in toxic doses
74
If you give two drugs that have the same active excretion system, what will happen?
The excretion time of each will be delayed because they're competing for excretion
75
Which drugs are most likely to pass into breast milk?
The same principles apply here as for any other membrane:
Lipid soluble drugs pass easily
Drugs that are polar, ionized, or protein bound do not
76
What does a plasma drug level tell us?
It tells us the amount of drug in the blood, but NOT the amount of drug at the site of action
We know from experience that there is a direct correlation between therapeutic and toxic responses and the amount of drug present in plasma
We know which plasma drug concentration are highly predictive of therapeutic and toxic responses
77
What are the two plasma drug levels?
1. minimum effective concentration
2. toxic concentration
78
What is minimum effective concentration?
the plasma drug level less than which therapeutic effects will not occur
79
The therapeutic range falls between ____ and \_\_\_
MEC and Toxic Concentration
80
Which is more dangerous, a narrow therapeutic range or a wide therapeutic range?
Narrow
81
The latent period of a drug (between administration and onset of effects) is determined by:
the rate of absorption
82
The duration of a drug is determined by:
metabolism and excretion
83
What is drug half life?
the time required for the amount of drug in the body to decrease by 50%
84
Does every drug have a half life?
No. Some drugs (like ethanol) leave the body at a constant rate, regardless of how much is present
85
What causes a plateau in drug levels, even when successive doses are administered?
Eventually the amount of drug eliminated between doses equals the dose administered, and the average drug level remains constant
86
When a drug is administered repeatedly in the same dose, when will a plateau be reached?
After four half lives
87
How does the size of the dose impact the time required to reach a plateau?
As long as the dose is constant, the plateau time will always be four half lives, regardless of the size of the dose
88
What are three techniques that can be used to reduce fluctuations in drug levels?
Continuous infusion
Administer a depot preparation (slow release)
Reduce both the size of dose and dose interval
89
What is the purpose of a loading dose?
To reach a plateau in less than four half lives
90
What is pharmacodynamics?
the effects of drugs and the molecular mechanisms that cause those effects
91
Dose-response curves reveal two characteristic properties of drugs:
1. maximal efficacy
2. Relative Potency
92
What is maximal efficacy?
the height of the dose-response curve
the largest effect that a drug can produce
93
What is relative potency?
the amount of the drug that must be given to elicit an effect
the relative position of the dose-response curve along the x (dose) axis
94
How are efficacy and potency related?
They aren't!
Potency and efficacy are completely independent. Drug A can be more effective than Drug B even though Drug B may be more potent
95
Pharmacologically, what is the definition of a receptor?
any macromolecule in a cell to which a drug binds to produce its effects
96
What's the relationship between selectivity and side effects?
The more selective a drug, the fewer side effects
97
Describe Simple Occupancy Theory
1. The intensity of response to a drug is proportional to the number of receptors occupied by that drug
2. Maximal response occurs when all available receptors have been occupied
98
What are some shortcomings with the simple occupancy theory?
According to the theory, two drugs that act on the same receptor should produce the same maximal effect, but they don't
one drug can have higher maximal efficacy than another, even though they target the same receptor
99
Modified Occupancy Theory ascribes two qualities to drugs:
1. Affinity (strength of attraction between a drug and its receptor - potency)
2. Intrinsic Activity (ability of a drug to activate a receptor upon binding - maximal efficacy)
100
When drugs bind to receptors, they can do one of two things:
1. mimic the action of endogenous regulatory molecules
2. block the action of endogenous regulatory molecules
101
What are agonists?
Drugs that mimic the actions of endogenous regulators
102
What are antagonists?
Drugs that block the actions of endogenous regulators
103
What are partial agonists?
mimic actions of endogenous regulatory molecules, but produce weaker responses
104
Agonists are molecules that \_\_\_\_\_\_
activate receptors
105
Antagonists produce their effects by:
preventing receptor activation
106
How do antagonists effect receptor function?
They pretty much don't
They just stop it from being activated. If activated, it will still function just the same
107
If you give an antagonist but there is no agonist present, what will happen?
Absolutely nothing
If the receptor isn't being activated by an agonist, the blocking effect won't have any consequences
If you gave someone narcan who wasn't actively high, nothing would happen
108
Are most antagonists competitive or noncompetitive?
competitive
109
What's another word for non-competitive antagonists?
Insurmountable
110
If a non-competitive antagonist is given and binds to a receptor, why does the dose still have limited effect?
Cells are constantly breaking down and replacing receptors. That drug's decreasing effectiveness will depend on the break down of the receptors, not the breakdown of plasma levels
111
What is unique about partial agonists?
They can act as antagonists and agonists
ex: pentazocine and meperidine (when pentazocine is given alone, it acts as an agonist on opioid receptors and produces mild pain relief. If given with meperidine, it antagonizes the binding of meperidine and prevents it from exert its greater intrinsic activity)
112
What are some drugs that don't interact with receptors?
Antacids, antiseptics, saline laxatives, chelating agents
All of these work through simple physical or chemical interactions and don't involve any kind of cellular receptor
113
What is the ED50?
average effective dose
Dose required to produce a defined therapeutic response in 50% of the population
114
What is LD50?
Lethal dose in 50% of the population
115
What is the therapeutic index?
A measure of the drug's safety
ratio of the drug's LD50 to its ED50
A large therapeutic index = relatively safe
Small therapeutic index = relatively unsafe
116
In order for a drug to be truly safe, what must be true?
the highest dose required to produce therapeutic effects must be substantially lower than the lowest dose required to produce death
117
When two drugs interact, there are three possible outcomes:
1. Intensification (either increased therapeutic or adverse effects)
2. Reduction (either reduced therapeutic or reduced adverse effects)
3. Creation of a Unique Response (effects that do not occur when one or the other is used alone)
118
Drugs interact through four mechanisms:
1. Direct chemical or physical interactions (IV compatibility)
2. Pharmacokinetic Interactions (altered absorption, distribution, protein binding, pH etc)
3. Pharmacodynamic Interactions (effecting the same receptor)
4. Combined Toxicity
119
Why does giving bicarb help with aspirin toxicity?
when the extracellular space becomes more basic, acidic drugs (such as aspirin) are drawn from within the cells and into the extracellular space. Once there, they are ionized and trapped from re-entering the cell
120
Some drugs increase the metabolism of other drugs, and others decrease the metabolism of other drugs. How?
Inducing synthesis or inhibiting drug-metabolizing enzymes (primarily P450 enzymes)
121
What is the primary function of PGP?
transporting a wide variety of drugs OUT OF CELLS
122
Most of the drugs that induce P450 have what effect on PGP?
Usually the same. Drugs that induce or inhibit P450 have the same effect on PGP
123
What effect on other drugs would a PCP inducing drug have?
Reduced Absorption
Reduced Fetal Drug Exposure
Reduced brain drug exposure
Increased drug elimination
124
Grapefruit raises drug levels mainly by inhibiting:
intestinal CYP3A4 metabolism of many drugs
125
Grapefruit pretty much never affects IV medications. Why?
Because it only effects intestinal CYP3A, almost never in the liver
126
Patients taking MAOIs MUST avoid foods that contain:
tyrosine (aged cheese, yeast extracts, Chianti)
127
Most drug-food interactions concern drug _____ or drug ____ and very rarely drug \_\_\_\_\_
absorption or metabolism
action
128
What is an example of a food that cause decreased drug action?
Leafy greens (high in Vit K) and coumadin
