Pharmokinetics Flashcards
1
Q
What is the relationship between a drugs dose and the plasma concentration?
A
volume of distribution
2
Q
What two things does volume of distribution assume?
A
- drug distributes instantaneously
2. the drug is not subject to biotransformation or elimination before it fully distributes
3
Q
How would a drug with a low volume of distribution be described?
A
< 0.6mL/kg or < 42L
4
Q
Where do drugs with a low Vd distribute?
A
some or all of the body, but not the fat. “hydrophilic”
5
Q
Does a drug with a low Vd need a larger or smaller dose to achieve a desired plasma concentration?
A
smaller
6
Q
What is one class of a drugs with a low Vd?
A
NMB
7
Q
The ____ the Vd the ___ the loading dose to achieve a desired plasma concentration.
A
higher, higher
8
Q
What is the formula for Vd?
A
Vd= amount of drug / desired plasma concentration
9
Q
What is the formula used to calculate loading dose?
A
IV loading dose = Vd x (desired plasma concentration / bioavailability)
10
Q
How would a drug with a high Vd be described?
A
> 0.6L/kg or > 42L
11
Q
Where do drugs with a high Vd distribute to?
A
into body water and fat. “lipophilic”
12
Q
Do drugs with a higher Vd need a smaller or larger dose to achieve a desired plasma concentration?
A
higher
13
Q
What is an example of drug with a high Vd?
A
propofol
14
Q
How is TBW distributed? TBW = Extracellular= Intracellular= Plasma= Interstitial=
A
TBW = 42L Extracellular= 14L Intracellular= 28L Plasma= 4L Interstitial= 10L
15
Q
What is the volume of plasma that is cleared of drug per unit time?
A
clearance
16
Q
What are the three major clearing organs?
A
liver
kidney
organ independent (Hoffman elimination and ester hydrolysis in plasma)
17
Q
What occurs when the amount of drug entering the body equals the amount being eliminated?
A
steady state
18
Q
How many half lives must occur to reach steady state?
A
5 half lives
19
Q
What is drug clearance directly proportional to?
A
blood flow to clearing organ
extraction ratio
drug dose
20
Q
What is drug clearance inversely related to?
A
half life
drug concentration in the central compartment
21
Q
What describes the alpha phase?
A
distribution of a drug.
22
Q
What occurs during the alpha phase?
A
the drug rapidly distributes from the central compartment (plasma) to the peripheral compartments (tissues)
23
Q
What determines the slope of alpha distribution?
A
Volume of distribution
24
Q
Describe the alpha phase slope of a lipophilic drug.
A
larger volume of distribution, steeper slope
25
What occurs during the beta phase?
eliminiation
26
As a drug is being eliminated from the central compartment and the plasma concentration declines. What will eventually happen?
concentration gradient reverses and drug will redistribute from the tissues back into the central compartment.
27
Does the beta phase slope represent elimination from the central compartment, peripheral, or both?
central
28
What is the speed at which a reaction occurs? "how fast the molecules move b/w compartment"
rate constants
29
Drug transfer from the central to peripheral compartment is K___
K12
30
Drug transfer from the peripheral to central compartment is K___
K21
31
Drug elimination from the body is K___
Ke
32
The time it takes for 50% of the drug to be removed from the body after IV injection
elimination half life
33
The time it takes for 50% of the drug to be removed from the plasma during the elimination phase (beta phase)?
elimination half time
34
Elimination half times is only applicable to what compartment model?
one compartment
35
What is the time required for the plasma concentration to decline by 50% after infusion is stopped?
context sensitive half time
36
What narcotic is quickly metabolized by plasma esterases, and has a context sensitive half time independent of infusion time?
Remifentanil
37
Arrange Fentanyl, Sufentanil, Remifentanil, and Alfentanil from longest to shortest centext sensitive half time.
fentanyl - longest
alfentanil
sufentanil
remifentanil - shortest
38
What ions are weak acids paired with?
sodium, calcium, and magnesium (all positive ions)
39
What ions are weak bases paired with?
chloride, sulfate (all negative)
40
When pKa and pH are the same, what percentage of the drug will be ionized and nonionized?
50%, 50%
41
What does an acidic drug donate?
H+
42
What does a basic drug donate?
OH-
43
What is the process where a molecule gains a positive or negative electron and this molecular charge affects a molecules ability fo diffuse through lipid membranes.
ionization
44
Describe solubility of ionized and non-ionized drugs.
ionized are hydrophilic and lipophobic
| nonionized are hydrophobic and lipophilic
45
Are ionized or nonionized drugs active?
nonionized
46
What type of drugs are more likely to undergo hepatic biotransformation?
nonionized
47
What type of drugs are more likely to undergo renal elimination?
ionized
48
What type of drugs can diffuse across lipid bilayers?
nonionized
49
An acidic drug in a basic solution will be highly ionized or nonionized?
ionized
50
An acidic drug in a acidic solution will be highly ionized or nonionized?
nonionized
51
A basic drug in a acidic solution will be highly ionized or nonionized?
ionized
52
A basic drug in a basic solution will be highly ionized or nonionized?
nonionized
53
What circumstance creates the strongest gradient for passage of LA from mother to fetus?
maternal alkalosis, fetal acidosis
54
What part of a drug can diffuse across the cell membrane?
lipophilic, nonionized
55
What part of a drug can diffuse across the cell membrane?
lipophilic, nonionized
56
Can ionized drugs cross cell membranes?
no
57
What are the three major plasma proteins?
albumin, a1-acid glycoprotein, beta globulin
58
Which plasma proteins bind to basic drugs?
a1-acid glycoprotein and beta globulin
59
What plasma protein binds acidic drugs mainly?
albumin
60
What is the primary determinant of plasma oncotic pressure?
albumin
61
Which plasma protein is a measure of protein synthesis, has a negative charge, and a half life of 2 weeks?
albumin
62
What situations cause a decrease in albumin?
liver disease, renal disease, old age, malnutrition, pregnancy
63
What increases a1-acid glycoprotein?
surgical stress, myocardial infarction, chronic pain, RA, old age
64
What decreases a1-acid glycoprotein?
neonates and pregnancy
65
How is % change of a bound and unbound drug calculated?
% change = (new unbound value - old unbound value) / new unbound value
66
What causes changes in plasma protein binding?
decreased plasma protein content, or competition to binding sites
67
The Vd and plasma protein content have what type of relationship?
inverse
68
Is the metabolism and elimination of highly protein bound drugs slower or faster compared to drugs with decreased protein binding?
slower
69
What order kinetics is described by a drug being eliminated at a rate of 5mg/h?
zero order kinetics
70
When there is more drug than enzyme, the drug is eliminated by which order kinetics?
zero order
71
What drugs undergo zero order kinetics?
aspirin, phenytoin, alcohol, warfarin, heparin, theophylline
72
A drug that is eliminated at a rate of 50%, undergoes which order kinetics?
first order kinetics
73
Is there more enzyme or drug in first order kinetics?
more enzyme. the enzyme metabolizes the drug at a constant fraction
74
What are the three phases of drug reactions?
phase 1: modification
phase 2: conjugation
phase 3: elimination/excretion
75
What are the most common sites of drug metabolism?
liver #1 and plasma
76
The P450 system is located where?
smooth endoplasmic reticulum
77
What types of drug metabolism occurs in the plasma?
Hoffman elimination, hydrolysis reactions,
78
How does metabolism facilitate drug elimination?
metabolism changes a lipid soluble compound into a H20 soluble, inactive byproduct
79
Why does metabolism transform drugs into H2O soluble compounds?
H2O soluble drugs have greater ionization, which decreases Vd, increasing delivery to the kidney for elimination
80
What are the three stages of phase 1 reactions?
oxidation- removes electrons
reduction- adds electrons
hydrolysis- adds H20 to split apart
81
Most phase 1 reactions are carried out by which system?
P450
82
What occurs during conjugation? Phase 2 reactions
H20 is added to the molecule. It becomes highly H20 soluble, inactive and ready for elimination
83
What is enterohepatic circulation?
Drugs like diazepam are excreted in the bile, reactivated in the intestine, then reabsorbed into circulation
84
What do phase 3 reactions require to transport drugs across cell membranes?
ATP dependent carrier proteins
85
86
Which drug has higher efficacy?
| Which drug needs to occupy fewer receptors to cause a response?
Efficacy: A
Response: B
87
Which drug is more potent?
Drug A
88
What drugs undergo perfusion dependent hepatic elimination?
fentanyl, lidocaine, propofol
89
What two drugs undergo capacity dependent elimination?
diazepam and Roc
90
What is the extraction ratio?
how much drug is delivered to clearing organ vs how much is removed by that organ.
91
What does an extraction ratio of 1.0 and 0.5 represent?
1 means 100% delivered in cleared
| 0.5 means 50% of drug delivered is cleared
92
What two factors determine hepatic clearance?
blood flow and extraction ratio
93
What extraction ratio signifies flow limited extraction?
ER > 0.7
94
What extraction ratio signifies capacity limited extraction?
ER < 0.3
95
What does an ER > 0.7 mean?
clearance is dependent on liver BLOOD FLOW
96
What does an ER < 0.3 mean?
clearance is dependent on the livers ability to extraction drug from the blood.
97
What has a significant impact on hepatic clearance if the drug has a ER < 0.3?
enzyme activity and protein binding
98
What drugs have an ER < 0.3 so they are enzyme dependent?
Rocuronium, Diazepam, Lorazepam, Methadone, Thiopental, Theophylline, Phenytoin
99
What are examples of drugs with an intermediate ER?
Versed, Vec, Alfentanil, methohexital
100
What are drugs with a ER > 0.7, blood flow dependent elimination?
Fentanyl, Sufentanil, Morphine, Meperidine, Naloxone, Ketamine, Propofol, Lidocaine, Bupivacaine, Metoprolol, Propranolol, Alprenolol, Nifedipine, Diltiazem, Verapamil
101
What is the most important mechanism of drug biotransformation in the body?
P450 enzymes
102
Where are P450 enzymes located?
hepatocyte smooth ER. Also lungs, skin, kidneys, adrenal gland, and GI tract.
103
What is the most important cytochrome P450 enzyme?
CYP 3A4
104
What are the three effects of enzyme inducers?
increase clearance, decrease plasma levels, may need higher doses.
105
What are examples of enzyme inducers?
tobacco, barbiturates, ethanol, phenytoin, rifampin carbamazepine
106
What do enzyme inhibitors do?
compete for binding sites on an enzyme and reduce clearance.
107
What are the three effects of enzyme inhibitors?
decrease clearance, increase plasma levels, need smaller doses.
108
What are examples of enzyme inhibitors?
grapefruit juice, cimetidine, omeprazole, isoniazid, SSRI's, erythromycin, ketoconazole
109
What are examples of drugs that undergo metabolism by CYP 3A4?
Fentanyl, Alfentanil, Sufentanil, Methadone
Midazolam, Diazepam
Lidocaine, Bupivacaine, Ropivacaine
110
What are examples of drugs that undergo metabolism by CYP 2D6?
codeine, oxycodone, hydrocodone
111
What are examples of drugs that undergo metabolism by CYP 1A2?
Theophylline
112
What are some CYP 3A4 inhibitors and inducers?
inducers: phenytoin, carbamazepine, dexamethasone
inhibitors: isoniazid, SSRI's, Quinidine
113
What are some CYP 1A2 inhibitors and inducers?
inducers: tobacco, cannabis, ethanol
inhibitors: erythromycin, ciprofloxacin
114
What type of drugs are excreted unchanged?
hydrophilic
115
What type of drugs must undergo biotransformation before they can be eliminated?
lipophilic
116
What drugs are freely filtered at the glomerulus?
those not bound to proteins
117
What are the organic anion transporters?
furosemide, thiazide diuretics, & penicillin
118
What are the organic cation transporters?
morphine, meperidine, & dopamine
119
What determines whether drugs are excreted in the urine or reabsorbed into peritubular capillaries?
urine pH
120
How does the pH of the urine determine reabsorption and excretion of drugs?
acidic urine reabsorbs acidic drugs, eliminated basic drugs
| basic urine reabsorbs basic drugs, eliminated acidic drugs
121
What medications acidify urine and leads to elimination of basic drugs?
ammonium chloride and cranberry juice
122
What medications will alkalinize urine and eliminate acidic drugs?
sodium bicarbonate and acetazolamide
123
What are the three main metabolic pathways in the plasma?
pseudocholinesterase, nonspecific esterases, alkaline phosphatase
124
What metabolic pathway does not involve enzymes?
Hoffman elimination
125
Pseudocholinesterase deficiency extends the duration of action of what three drugs?
succinylcholine, mivicurium, and ester LA's (1 "i" in their name)
126
What drugs undergo metabolism by nonspecific esterases?
remifentanil, esmolol, etomidate, atracurium
127
What drug undergoes metabolism by nonspecific esterases and hepatic metabolism?
etomidate
128
What drug undergoes metabolism by nonspecific esterases and Hoffman elimination?
atracurium
129
What medication is converted to a prodrug by alkaline phosphatase?
fospropofol
