Pharmacology Exam 1 - Part 2

Front 1

Through which part of the cell membrane do drugs usually pass?

Back 1

Lipid bilayer

drugs are usually too big to pass through pores and gaps

Front 2

Only ____-soluble drugs can cross the cell membrane by diffusion

Back 2

lipid-soluble

Front 3

Which 2 forms of drug do NOT affect the diffusion gradient?

Back 3

protein bound drug

ionized drug

Front 4

Pharmacokinetic compartmental models

Back 4

one compartment: absorption --> blood --> elimination

two compartment: absorption ---> blood <--> tissues --> elimination

Front 5

5 properties that influence membrane transport by passive difussion

Back 5

size of the drug
degree of ionization
lipid solubuility of non-ionized drug
concentration gradient
surface area

Front 6

How does lipid solubility affect passive diffusion?

Back 6

less polar = more dissolution in mb --> faster transport

if drug is too non-polar, rate of passage diminished (b/c not aqueous)

Front 7

Degree of ionization of a weak acid/base is due to what?

Back 7

pKa of the drug

pH of the medium on each side of the membrane

Front 8

Henderson-Hasselbach Equation

Back 8

pH = pKa + log(A-/HA)

Front 9

For weak acids, at LOW pH...

Back 9

more acid is NON-ionized

therefore, better dissociation across membrane

Front 10

For weak acid, at HIGH pH...

Back 10

more acid is ionized

therefore, less dissociation across membrane

Front 11

drug absorption

Back 11

transfer of drug from site of administration into systemic circulation (plasma)

Front 12

bioavailability

Back 12

fraction of drug dose that reaches plasma

Front 13

before diffusion across lipid membranes, the drug must...

Back 13

dissolve into aqueous solution

Front 14

4 factors affecting rate and extent of absorption depends on

Back 14

blood flow to site of administration
surface area
ionization state of the drug
lipophilicity of the drug

Front 15

Advantages of oral administration

Back 15

relatively safe
convenient
economical
controlled rate of drug release

Front 16

Disadvantages of oral administration

Back 16

GI irritation - nausea
possible destruction of drug by acid or enzymes
complexes w/ substances in Gi tract retard absorption
relatively slow onset not good for emergency use
cannot use in unconscious or uncooperative patient
first pass effect
pathological changes in GI tract physiology or contents may alter absorption
variable absorption - multifactorial

Front 17

Advantages of sublingual administration

Back 17

rapid absorption
eliminate first pass effect
reduce chances of drug destruction by enzymes or acid

Front 18

Disadvantages of sublingual administration

Back 18

drug cannot be given by this route if irritating or has bad taste

Front 19

First pass effect

Back 19

removal of a significant portion of f drug does by metabolism during first pass of the drug through the GI mucosa and liver

thus, only fraction of oral dose reaches peripheral circulation

Front 20

rectal administration advantages

Back 20

can be used in unconscious or uncooperative patients
can be used in vomiting patient
less GI distress
eliminates firest pass effect

Front 21

Rectal administration disadvantages

Back 21

inconvenient

lack of adherence by patient

Front 22

Intravenous administration advantages

Back 22

complete dose in blood
rapid action - suitable for emergency use
controllable rate of administration
larger volumes can be injected i.v. than given SQ or IM

Front 23

i.v. disadvantages

Back 23

not easy for self-medication
can be painful or dangerous
drug myst be water soluble
does is not retrievable once given

Front 24

subcutaneous (s.c.) administration advantages

Back 24

rapid absorption from aqueous solution

can control rate of absorption
- alter blood flow w/ cold, heat, epi
- alter vehicle (oil vs. aqueous)
- use of implants (pellets)

Front 25

intramuscular (i.m.) administration advantages

Back 25

rapid absorption from aqueous solution

can use depot forms for slow absorption
- oil, suspension

Front 26

i.m. disadvantages

Back 26

irritation a slight problem
possible injection into a blood vessel

Front 27

inhalation advantages

Back 27

VERY rapid absorption
rapid onset of action

Front 28

inhalation disadvantages

Back 28

must use aerosol of very fine particle size if drug is not volatile
often causes irritation
hard to control size of dose

Front 29

intrathecal administration advantages

Back 29

ensure entry of drug into CSF and CNS
e.g.: spinal anesthesia

Front 30

intrathecal disadvantages

Back 30

difficult technicque
danger of trauma to nerves
danger of leakage of CSF

Front 31

topical administration advantages

Back 31

local effect w/o systmic effects
controlled release topical patches can provide sustained delivery of drug to systemic circulation (e.g: nitroglycerin)

Front 32

topical admin. disadvantages

Back 32

possibility of absorption into blood of a large amount of drug if mb damaged

drug must be non-irritating

Front 33

most commonly used route of administration

Back 33

oral

Front 34

Properties influencing drug absorption from STOMACH

Back 34

properties of drug
binding of drug to food particles
surface area
blood flow
gastric emptying time

Front 35

Why are oral medications not absorbed in the mouth?

Back 35

Despite thin epithelium and rich vascularity, the surface area is small and the medication is not in the mouth long enough.

Front 36

drug absorption in the small intestine

Back 36

luminal pH becomes progressively more alkaline (from 4-5 all the way to 8 in the lower ileum)

GI flora may inactivates some drugs, reducing absorption

drug transit is slow compared to stomach

Front 37

what organ presents the largest GI surface area for absorption?

Back 37

small intestine

Front 38

4 factors that influence absorption from the small intestine

Back 38

properties of drug
binding of drug to food particles
surface area
blood flow

Front 39

pH in stomach favors absorption by diffusion of ____ ______

Back 39

weak acids

Front 40

3 factors favoring absorption of weak acid from the small intestine

Back 40

large surface area

high blood flow

pH in the blood favors the ionized form (ion trapping)

Front 41

dissolution of drug into GI fluids can be REDUCED by _____ or ____

Back 41

COATING particles with wax or other water-insoluble material

EMBEDDING drug in matrix

Front 42

parenteral sites of absorption

Back 42

non-GI sites

Front 43

2 factors affeccting rate of entry into capillaries

Back 43

hydrophobicity of drug

capillary drug flow

Front 44

What causes delayed or erratic absorption following IM injection?

Back 44

drugs that are salts of poorly soluble acids and bases

Front 45

example of poorly soluble acid drug

Back 45

phenytoin (anticonvulsant drug)

dissolves only at pH 12

Front 46

What happens when phenytoin is injected IM?

Back 46

tissue fluids act as buffers --> decrease pH

shifts equilibrium of drug toward precipitate form (HA)

Front 47

3 functions of prolonged release dosage forms

Back 47

reduce frequency of dosing

maintain more uniform plasma drug concentrations

may improve patient adherence

Front 48

prolonged release dosage is especially good for drugs with...

Back 48

short duration of effect

Front 49

prolonged release doses usually maintain therapeutic levels for up to ____ (time)

Back 49

12 hours

Front 50

means by which prolonged release dosages forms are created

Back 50

coating with wax or other water-insoluble substances

embedding in matrix

Front 51

3 forms of non-intravenous, parenteral perparations that provide sustained blood levels (prolonged release)

Back 51

insoluble salts injected IM
- provide activity for several weeks
- e.g.: fluphenzaine deconoate

suspensions in non-aqueous vehicles
- e.g.: crystalline insulin

procaine salt of penicillin in jected IM

Front 52

effect of oil containing aluminum stearate as a vehicle

Back 52

as in procaine salt of penicillin suspension

oil prevents contact of the salt with aqueous medium, retarding dissolution

aluminum stearate increases the viscosity of the suspension, also delaying dissolution

Front 53

Body water

Back 53

For 70 kg man,

Total body water: (60% body weight; 42 liters)

Intracellular fluid (40% of body weight; 28 liters)

Interstitial fluids (16% body weight; 11 liters)

Plasma (4% body weight; 3 liters)

Front 54

Extracellular fluid

Back 54

20% body weight - 14 liters

Front 55

Pathway from plasma to inside cells, including barriers

Back 55

Plasma --> capillary walls --> interstitial fluid --> cell membrane --> intracellular fluid

Front 56

Which are more permeable, capillary walls or cell membranes. Why?

Back 56

Capillary walls - they have pores

Front 57

Primary plasma protein to bind drugs

Back 57

albumin

Front 58

What effect does plasma protein binding have on drug distrubution?

Back 58

significant reduction

Front 59

what effect does plasma protein binding have on drug absorption? Why?

Back 59

Enhances drug absorption

free drug diffuses into plasma down its gradient - protein plasma binding increases gradient (decresses plasma conc. of free drug)

Front 60

When is movement of a drug across membranes not reduced by plasma protein binding?

Back 60

when the drug is actively transported

Front 61

why are infants highly sensitive to centrally-acting drugs like morphine?

Back 61

blood brain barrier relatively permeable in infants

Front 62

disease state that alters permeability of BBB

Back 62

inflammation (e.g.: meningitis)

Front 63

besides diffusion across BBB, another way drugs gain access to brain tissue

Back 63

active transport through choroid plexus

Front 64

differential distribution

Back 64

concentration of drug is not uniform from tissue to tissue

Front 65

factors that determine differential of drug distribution

Back 65

binding of drugs to plasma proteins in tissue
storage of drugs by body fat
BBB
active transport in the liver, kidney, etc.

Front 66

Is the site of drug action the site at which the drug concentration highest in the body?

Back 66

Not necessarily

Front 67

targeted drugs

Back 67

designed to achieve high concentrations at site of action

Front 68

redistribution of drugs

Back 68

initial distribution of drugs often follows distribution of blood flow to organs

later, drugs may redistriubte according to affinity for various tissues

Front 69

example of drug that redistributes

Back 69

thiopental

Front 70

Describe thiopental distribution

Back 70

lipid-soluble barbituate used as ultra-short acting general anesthetic

duration of action after i.v. administration = 30 minutes

initial distribution to organs that are rapidly perfused (brain, kidney)

redistributes to muscle and adipose tissues, lowering brain concentration

Front 71

Volume of distribution definition

Back 71

relationship btw drug dose and plasma concentration immediately after administration

Front 72

apparent volume of distribution (Vd) =

Back 72

Vd = A/Cp,

A = does of drug administered
Cp = plasma concentration of drug following distribution and before elimination

Front 73

Vd is the volume of fluid that would be required to...

Back 73

contain the drug at the same concentration as in plasma

Front 74

pharmacokinetics

Back 74

characterization of the amount or concentration of drug in the body over time

Front 75

What determines the magnitude of the pharmacologic response?

Back 75

drug concentration at the receptor site

Front 76

since it isusually impossible to measure concentration at receptor site, ____ is used as a surrogate

Back 76

plasma drug concentration

Front 77

permissible range

Back 77

values between minimum effective conc. and maximum effective conc.

Front 78

maximum effective concentration

Back 78

above which toxicity occurs

Front 79

3 factors influencing maximum effective concentration

Back 79

potency of drug
magnitude of desired response
concentration at which toxicity occurs

Front 80

stated drug concentrations usually represent...

Back 80

total (protein-bound + free) drug in plasma

Front 81

can free, unbound drug be measured?

Back 81

yes

Front 82

compartmental pharmacokinetic modeling

Back 82

body viewed as having various compartments into which a drug distributes at various rates

Front 83

simplest compartmental pharmacokinetic model

Back 83

one-compartment model:

body as single compartment from which drug elimination takes place

Front 84

assumption in one compartment model

effect of assumption

Back 84

drug enters the blood and RAPIDLY equilibrates with tissues

ergo, the rate at which the plasma concentration changes reflects the rate at which the concentrations change in tissues

Front 85

describe brain, liver, plasma graphs of drug conc. as a function of time

Back 85

all inverse relationships - parallel with each other

plasma conc > liver conc. > brain conc

Front 86

Is Vd regarded as a constant or a variable for any given drug?

Back 86

constant

Front 87

Proportional relationship between volume of distribution and fraction of total drug in the body that resides in tissues

Back 87

The larger the value of Vd, the greater the fraction in tissues

Front 88

Drug eliminiation is usually a ___-order process

Back 88

first-order process

Front 89

rate of drug elimination =

Back 89

Rate = dCp/dT = Ke* Cp

Cp = plasma conc.
T=time
Ke = elimination constant

Front 90

Describe effect of plasma concentration on elimination

Back 90

If concentration in plasma high, drug elimination is fast

If low, elimination is slow

i.e.: first-order kinetics: a CONSTANT FRACTION is eliminated per unit time

Front 91

How do you linearize a first-order relationship?

Back 91

ln(Cp) vs. time

Front 92

in first-order kinetics, half-life (t1/2) is ____

Back 92

a constant (0.693/Ke)

Front 93

Ke is _____ly proportional to the drug half life

Back 93

inversely

Front 94

What do the two phases of drug disappearance reflect?

Back 94

distribution
elimination

Front 95

shape of alpha phase of drug distribution

Back 95

alpha phase - distribution - inverse curve of ln(Cp) vs. time

beta phase - elimination - decreasing linear of ln(Cp) vs. time

Front 96

What needs to be done to calculate Vd in a two compartment model?

Back 96

to obtain initial Cp, need to extrapolate elimination (linear) phase back to t = 0

Front 97

zero-order kinetics, aka:

Back 97

saturation kinetics:

elimination occurs at a constant rate, independent of drug plasma concentration

Front 98

why do zero-order trends arise in pharmacokinetics?

Back 98

b/c elimination processes become saturated with relatively high amounts of drug

Front 99

Are t1/2 and Ke used to describe zero-order kinetics?

Back 99

no (not constant)

Front 100

In zero-order kinetics, the rate of decline of drug in the body =

Back 100

-dA/dT = Ko (constant)

not proportional to the amount in the body

Front 101

example of drug that exhibits zero-order kinetics at saturation levels and than transitions to first-order

Back 101

salicylate

Front 102

measure used to quantify the elimination process

Back 102

total body clearance, aka: plasma clearance

Front 103

total body clearance - definition

Back 103

volume of plasma that is completely cleared of a substance per unit time by all elimination mechanisms combined

Front 104

What measure answers the question, "How fast is a drug eliminated from the body?"

Back 104

total body clearance

Front 105

total body clearance =

Back 105

total body clearance = Vd*Ke = Vd*(0.693/t1/2)

Front 106

In first order kinetics, does clearance change as plasma drug concentration declines?

Back 106

NO

only the amount of drug in that volume

Front 107

half life of a drug due to renal excretion can be calculated if what two things are known?

Back 107

renal clearance
Vd

Front 108

renal clearance =

Back 108

excretion rate/Cp (units = L/hr)

Front 109

shape of plasma concentration vs time curve after an oral dose depends on relative rates of ____ & ____ of the drug

Back 109

absorption and elimination of the drug

Front 110

Is Ka a constant or a variable for each drug?

Back 110

variable

Front 111

Given that Ke is fixed, but Ka is variable:

When the absorption of an orally given drug is slower, the Ka is ____, the peak plasma concentration will be ____ and the time until the peak Cp will be ____

Back 111

When the absorption of an orally given drug is SLOWER, the Ka is low, the peak plasma concentration will be LESS and the time until the peak Cp occurs will be LATER

Front 112

GIven that Ke is fixed, but Ka is variable:

Although plasma concentrations are lower for a smaller dose, is the shape of the curve for Cp vs. time altered?

Back 112

no

Front 113

If Ka is fixed and Ke is varied:

If the elimination process decreases when absorption is constant, the peak plasma concentrations will be ____ and the duration of action will be _____

Back 113

If the elimination process decreases when absorption is constant, the peak plasma concentrations will be GREATER and the duration oaction will be LONGER

Front 114

Bioavailability = what calculus derived value?

Back 114

Integration of the curve Cp. vs. time

Front 115

The integration of the curve Cp vs. time

abbreviation
directly proportional to...

Back 115

AUC is directly proportional to the amount of drug that reaches the systemic circulation

Front 116

Bioavailability followin a non-i.v. administration is calculated...

Back 116

Bioavail = AUC(oral)/AUC(i.v.)

Front 117

consideration when patients switch medication from one manufacturer to another, even for the same drug product

Back 117

formulation can influence bioavailability - varies widely

Front 118

The drug in the body reaches a steady-state level when the rate of ____ equals the rate of _____

Back 118

rate of absorption equals the rate of elimination

Front 119

Given first-order kinetics, the amount of drug in body at steady state =

Back 119

amount at steady state = Kad/ke

Kad = rate of drug administration
(i.e.: zero-order "absorption"constant)

ke = first order elimination constant

Front 120

Given first order kinetics, steady state plasma concentration =

Back 120

plasma concentration = (Kad/Ke)/Vd = Kad/clearance

Front 121

time to reach 90% of the steady-state plasma concentration =

Back 121

t = 3.3 * t1/2

Front 122

time to reach 95% of steady state plasma concentration =

Back 122

t = 5*t1/2

Front 123

True or False: Een if each dose is absorbed as a first -order process (e.g.: oral administration), the overall effect of a constant dosing schedule approximates zero-order administration

Back 123

True

Front 124

plasma concentration = (amount of drug in body)/(volume of distribution)

Back 124

plasma concentration = (amount of drug in body)/(volume of distribution)

Front 125

proper maintenance dose =

Back 125

dose = Vd*(Cp(elimination) - Cp(maintenance))

Front 126

dosage interval is dependent on ____

Back 126

permissible range of fluctuation and the biological half-life of the drug

Front 127

rage of fluctuation of Cp as percent of CpE vs. dosing interval

values for 10%, 50% and 90% CpE

Back 127

10% CpE --> 1/1*t/12

50% --> t/12

90% --> 3.3*t1/2

Front 128

Purpose of loading dose

Back 128

rapid establishment of effective therapeutic plasma concentration

i.e.: steady state level can be achieved in one administration

Front 129

loading dose =

Back 129

loading dose = CpE * Vd

Front 130

Halving both the dose and the dosage interval has what effect on plasma concentration?

Back 130

reduces the amount of fluctuation but leaves mean steady state level unchanged

Front 131

equation for calculating steady state plasma level of drug given by i.v.

Back 131

Cp = (infusion rate)/(total clearance)

Front 132

What happens when drug elimination follows zero order kinetics and the drug is being administered at a rate greater than the rate of elmination?

Back 132

drug will accumulate indefinitely

Front 133

will plateau level occur when drug eliminiation follows zero-order kinetics and the administration is greater than the rate of elimination?

Back 133

No; because drug is eliminated at a rate which does nOT increase in proportion to plasma concentration

Front 134

result of indefinite drug accumulation

Back 134

toxicity

Front 135

True or false: some drugs follow first order kinetics at low doses, but zero order kinetics at higher doses

Back 135

True (zero order kinetics represent saturation kinetics)