Lecture 6: Pharmacokinetics Pt 1 Flashcards
(88 cards)
1
Q
what is the end goal of pharmacokinetics
A
getting rid of the drug
2
Q
what does ADME stand for
A
absorption, distribution, metabolism, excretion
3
Q
what does the area under the curve for amount of drug in blood x time show
A
overall drug exposure: plasma concentration of the drug from the time it’s taken to the time it’s eliminated
4
Q
what is Cmax
A
highest concentration of drug in blood
5
Q
what is t1/2
A
half life
6
Q
what is half life
A
time at which drug has lost half its maximum concentration
7
Q
what is Cmin
A
lowest concentration of drug in blood
8
Q
what does the concentration x time plot for drug show
A
plasma concentration of the drug from the time its taken to the time its eliminated
9
Q
types of ocular delivery
A
drops, bioadhesives
10
Q
types of buccal delivery
A
mucoadhesive, spray
11
Q
types of sublingual delivery
A
tablets
12
Q
types of oral delivery
A
capsule, pill
13
Q
method of IV delivery
A
injection
14
Q
types of intramuscular delivery
A
depot
15
Q
types of subcutaneous delivery
A
depot, implant
16
Q
types of transdermal delivery
A
patch, cream, spray
17
Q
types of pulmonary/nasal delivery
A
aerosol, spray
18
Q
types of vaginal/rectal delivery
A
gel, suppository
19
Q
which method of administration is the fastest
A
IV
20
Q
which admin methods bypass 1st pass liver metabolism
A
IV, intranasal, transdermal
21
Q
disadvantages of IV route
A
painful; chance of infection
22
Q
example of intranasal drug
A
naloxone
23
Q
which admin method bypasses the blood brain barrier
A
intranasal
24
Q
how fast does intranasal administration act
A
minutes
25
disadvantage of intranasal admin
limited absorption
26
benefits of oral administration
convenient & non-invasive
27
how long does it take for oral admin to act
minutes (>30)
28
disadvantages of oral admin
many 🫣
29
where is subcutaneous method administered
into cutis layer of the skin, below dermis & epidermis
30
characteristics of absorption via subcutaneous administration
slow, sustained absorption
31
disadvantages of subcutaneous administration
irritation & pain at site of injection
- rate of absorption is difficult to control
32
technique for transdermal administration
delivered through skin, administered via patch/ointment/microneedles
33
disadvantages of transdermal admin
skin irritation, need low molecular weight, slow
34
absorption definition
the process of movement of drug molecules from the site of admin to systemic circulation
- a drug is only absorbed when it has entered blood
35
mechanisms of absorption
- passive diffusion
- carrier-mediated transport (eg active & facilitated diffusion)
- nonspecific drug transporter (eg p-glycoproteins)
36
function of p-glycoproteins
ATP-dependent efflux pump; looks for foreign objects & kicks them out of the cell
- found in BBB
37
1st pass metabolism function
starts to degrade drug before it can be absorbed
- oral or enteral administration may have hindered absorption in the GI tract
38
what organ is involved in first pass metabolism
liver
39
characteristics of bupropion metabolism
undergoes hepatic metabolism by CYP2B6; even though it gets significantly metabolized the metabolite is still active & readily absorbed
40
characteristics of codeine metabolism
prodrug; weakly binds MORs, so needs conversion into morphine by CYP2D6 to produce effects
41
bioavailability formula
(concentration following non-IV dose)/(concentration following IV dose)
42
bioavailability definition
the fraction of the dose which reaches systemic circulation intact
43
what is IV bioavailability
100%
44
absolute bioavailability
compares 1 non-IV route w/ IV route
45
relative bioavailability
compares one non-IV route w/ another
46
distribution definition
the process of movement of drug molecules from systemic circulation to tissues or organs
47
what is distribution dependent on
vascular permeability, blood flow, pH, plasma protein binding, and lipid solubility
48
volume of distribution
apparent volume a drug disperses into to produce the observed plasma concentration
49
why is plasma concentration a good proxy for measuring distribution
we cannot sample from all compartments in the body, but we can sample bloodstream
50
what does high Vd mean
drug wants to leave the plasma & enter compartments
51
what does low Vd mean
drug wants to stay in plasma
52
what are examples of drugs w/ low Vd
heparin & insulin
53
heparin function
blood anticoagulant
54
insulin fxn
regulates blood sugar levels
55
why do we want heparin & insulin to have low Vd
we want the drugs to stay in the plasma or interstitial fluid where they can exert their effects
56
examples of drugs w/ high Vd
morphine, propranolol
57
morphine function
opioid analgesic
- works on spinal cord & brain
58
propranolol function
beta blocker to treat hypertension
- works on brain to inhibit sympathetic stimulation of the heart
59
why do we want morphine & propranolol to have a high Vd
we want these drugs to be distributed to the tissues where they act
60
how does molecular size affect drug's Vd
larger molecules are harder to passively diffuse out of the central compartment & have smaller Vd
61
how does molecular charge affect drug's Vd
highly ionized molecules will have higher water solubility & may be trapped in the central compartment by electrostatic factors which keep them bound to proteins w/ corresponding charge
62
how does PkA affect Vd
determines degree of ionization & therefore influences lipid solubility
63
how does lipid solubility affect Vd
highly lipid-soluble drugs will have the highest Vd bc of the low fat content of the bloodstream
64
how does water solubility affect Vd
highly water soluble drugs have difficulty penetrating lipid bilayer membranes & tend to have smaller Vds, being limited to extracellular water
65
how does patient pH affect Vd
pH interacts w/ the drug's pKa to influence the degree of lipid solubility
- also influences degree of protein binding
66
how does patient's body water volume affect Vd
dehydrated patients have drug levels concentrated in the plasma
- all dissolved substances are concentrated by loss of water
67
how does patient's protein levels affect Vd
for highly protein-bound drugs, lower serum protein levels will result in a higher free (unbound) drug fraction
68
how does patient's drug displacement affect Vd
drugs are displaced from their protein & tissue binding sites by the effects of pH or by competition from other drugs/substances
- displaced drugs may redistribute into plasma, decreasing calculated Vd
69
major types of proteins in the plasma
albumin, globulins, fibrinogens
70
albumin function
major component of osmotic pressure of plasma
71
globulin function
antibodies (immunoglobin) & transport proteins
72
fibrinogens function
blood clotting
73
ionization properties of drugs
most are weak electrolytes & only partially dissociate into ions when in water
- only nonionized species will be able to permeate across biological barriers
74
where do ionized drugs stay in the body
in the blood; more water soluble
75
acidic drugs bioavailability
higher oral bioavailability
76
acidic drugs clearance
poorer hepatic clearance
77
acidic drugs protein binding
higher
78
acidic drugs Vd
smaller
79
acidic drugs absorption
absorbed better in the stomach
80
basic drugs protein binding
higher
81
basic drugs Vd
larger
82
basic drugs CNS penetration
better
83
general properties of basic drugs
receptor promiscuity (ie decreased selectivity), sequestered in acidic organelles (including mitochondria)
84
lipophilic definition
easier to cross barrier (plasma membrane)
85
distribution characteristics of molecules w/ high lipid solubility
distribute into highly vascular, lipid-rich areas
- redistribute into fat cells, where they can remain for a long time
86
hydrophilic drug characteristics
highly soluble in aqueous, polar media
87
lipophilic drugs characteristics
soluble in fats & non-polar solution
88
what is the rate of distribution dependent on
diffusion characteristics of the drug & rate of delivery to tissues
