Pharmacokinetics Flashcards
1
Q
pharmacokinetics
A
what the body does to the drug
2
Q
pharmacokinetic properties
A
ADME
3
Q
how to get the drug into the body, where/how a drug is administered
A
absorption
4
Q
factors affecting drug absorption
A
- pH
- blood flow
- surface area
- contact time
- presence of transporter proteins
5
Q
partially ionizes/charges in water
A
weak acid
6
Q
partially takes a H+ from water
A
weak base
7
Q
uncharged drug passes through membranes more readily
A
true
8
Q
increased blood flow =
A
increased absorption
9
Q
increased surface area =
A
increased absorption
10
Q
increased contact time =
A
increased absorption
11
Q
increased transporter proteins =
A
decreased absorption
12
Q
drug formulations
A
how a company manufactures drugs, dependent on barriers, setting, stability, first pass effect
13
Q
Routes of administration
A
rate and efficiency of absorption differs based on ROA
14
Q
enteral
A
by mouth, safest/most common
15
Q
parenteral
A
directly into systemic circulation
16
Q
other
A
neither oral or parental
17
Q
enteral
A
oral, sublingual, buccal,
18
Q
other
A
inhalation/nasal, intrathecal/intraventricular, topical, transdermal, rectal
19
Q
parenteral
A
IM, IV, SubQ
20
Q
enteric coated
A
chemical envelope that protects drug from stomach acid/if irritable. allows drug to reach intestines
21
Q
extended release
A
coating that control drug release
22
Q
factors affecting oral absorption
A
physiologic variability, areas with different pH, gastric emptying, first pass metabolism, bioavailability
23
Q
gastric emptyign rate
A
rate which stomach empties into small intestines
24
Q
first pass metabolism
A
blood supply draining GI passes through liver before reaching systemic circulation, results in less unchanged drug entering systemic circulation
25
prodrug
administering an inactive form of the drug to be activated by naturally occurring enzymes in the body (metabolism)
26
advantage of prodrug
protection, solubility, lipophilicity, site selective, avoid first pass metabolism effect
27
bioavailability
rate/extend at which administered drug reaches systemic circulation
28
PO bioavailability
solution > suspension > capsule > tablet > coated tablet > extended release
29
low bioavailability =
poor absorption in GI
30
IV results in
100% bioavailability
31
can drugs have equivalent bioavailability
yes
32
sublingual
placed under tongue, unionized, highly lipid soluble, potent agent, rapid absorption
33
rectal administration
suppository/enema, for pts unable to tolerate meds, absorption highly variable, systemic/local effect, defication terminates drug exposure
34
inhalation
oral/nasal, administered as gas/aerosol, fast action, may irritate lung tissue (albuterol)
35
topical administration
application direct to membrane or skin, local or systemic effect, many dosage forms (nalaxone, eye drops, creams)
36
transdermal administration
patch containing drug applied to skin, continuous/long acting, lipophilic, pt skin characteristics affect rate
37
intramuscular
directly to muscle, rapid absorption of aqueous solution, pain @ site, volume restriction
38
subcutaneous
loose tissue injection, slow and constant absorption, volume restrictions
39
IV
most common parenteral route, 100% bioavail, greater risk of adverse effects
40
4 mechanisms of passage of drugs across membranes
1. passive diffusion
2. facilitated diffusion
3. active transport
4. endo/exocytosis
41
drug distribution
drug leaves blood stream and enters into interstitum and tissues
42
drug distribution is dependent on
blood flow, capillary permeability, drug binding to proteins/tissues, lipohilicity, volume of distribution
43
blood flow
rate of drug diffusion into tissue is primary function of blood flow
44
brain/heart/liver/kidney
highly vascular
45
central compartments
rapid distribution 1st, diffuse 1st
46
peripheral compartments
slower distribution, 2nd to diffuse
47
capillary permeability
determined by structure (leaky v tight) and chemical nature (ionized/polar vs lipid soluble)
48
continuous capillary (tight)
skin, muscle, lung, CNS
49
fenestrated capillary (semi)
exocrine glands, renal glomeruli, intestinal mucosa
50
sinusoid capillary
liver, spleen, bone marrow
51
blood brain barrier
contains tight junctions, must pass as lipid soluble and active transport. Ionized/polar cannot pass thru BBB
52
ion trapping
occurs when pH of 2 water compartments differ, weak acids/bases concentrate in the compartments which they are most highly ionized. once ionized they cannot cross membranes
53
plasma protein binding
reversible, determines extent of drugs distribution/elimination rate, only free drug can leave circulation
54
when drug levels are too high, plasma protein binding sites are
saturated
55
binding does not prevent drug from reaching site of action but lessens rate at which it occurs. T/F?
true
56
lipophilicity
lipophilic drugs readily move across biologic membranes, hydrophilic drugs do not readily penetrate cell membranes
57
volume of distrubution
measure of the apparent space in the body available to contain a drug
58
volume of distribution is useful for caclulating the loading dose of a drug
true
59
volume of distribution
relates amount of drug in the body to concentration of drug in blood / plasma
60
plasma vol, ECF vol, total body water vol
3L, 15L, 40L
61
Vd
Total amount (dose) of drug / blood or plasma concentration
62
low molecular weight, low protein binding, high tissue binding, high membrane permeability, lipophilic, un-ionized
high Vd
63
high molecular weight, high protein binding, low tissue binding, low membrane permeability, lipophobic, ionized
low Vd
64
excretion 3 major routes
hepatic metabolism, biliary excretion, urinary excretion
65
sites of drug metabolism
kidneys/liver/GI tract
66
kidney drug metabolism
eliminates small molecules, polar, fully ionized at physiologic pH
67
liver drug metabolism
primary organ, biotransformation of drug molecules
68
other sites of drug metabolism
GI (most important extrahepatic site)
69
metabolism phase 1
makes the drug more polar by introducing polar functional groups, catalyzed by cytochrome P450
70
metabolism phase 2
phase 1 products that were not able to be eliminiated rapidly undergo conjugation
71
cytochrome P450
oxidations catalyzed by iron containing proteins located in liver and GI, has relative specificity
72
factors affecting CYP450 isoenzymes
age, disease states, genetics, environmental factors, exposure to drugs/chemicals
73
CYP 450 induction
↑metabolism = ↓ drug concentration
lose therapeutic effect
can increase toxicity
St Johns wort
74
CYP450 inhibition
↓ metabolism = ↑ drug concentration
Ex. -azole antifungals
75
poor metabolizers
lack a gene to produce the CYP450 isoenzyme
76
drug excretion (3 processes)
glomerular filtration, tubular secretion, tubular reabsorption
77
drug must be polar/nonpolar and fully ionized/unionized to be excreted in urine
POLAR, FULLY IONIZED
78
glomerular filtration
produce protein free ultra filtrate that will become urine. protein bound drug and large molecule not filtered
79
tubular secretion
energy consuming secretion from capillaries to renal tubule. potential target of drug action
80
tubular reabsorption
drug concentration inceases as moves through tubule, reabsorb unionized drugs into blood stream
81
urinary pH
impacts rate of excretion, pH may be adjusted, ionized excreted in urine
82
weak base excreted at low pH
true
83
weak acids excreted at high pH
true
84
clearance
estimates amount of drug cleared per unit time, total clearance estimates all mechaisms of drug elimination
85
excretion
fecal route, tylenol vs ibuprofen, etc
