Pharm Flashcards
(133 cards)
1
Q
what is the definition of an acid
A
proton donor, contributes H+ to solution
2
Q
what is the definition of a base?
A
proton acceptor, binds or buffers H+ in solution
3
Q
what is the definition of pH?
A
a measure of the concentration of H+ in a solution
4
Q
definition of strong acids/bases
A
readily dissociate, more ionized than non-ionized
5
Q
definition of weak acid/base
A
does not readily dissociate, strength is determined by its dissociation constant (pKa)
6
Q
what is the pH range of homeostatic plasma?
A
7.34-7.45
7
Q
What are the two buffer systems used to maintain homeostatic plasma pH?
A
Bicarbonate buffer system
non-bicarobonate buffer system
8
Q
definition of open system vs closed system
A
open system= can eliminate acid from the body
closed= hide or bind acid
9
Q
is open or closed systems more powerful and why?
A
open systems are more powerful than closed because closed systems are saturable
10
Q
which buffer system is the most abundant and most important?
A
bicarmonate-carbonic acid buffer system
11
Q
carbonic acid is derived from what? (2)
A
reaction of bicarbonate and H
generated by many cell types specialized to produce acidic or alkaline secretions
12
Q
what are the components of the ubiquitous equation?
A
CO2 and H2O bind together to form carbonic acid which turns into bicarbonate and H
13
Q
what are the two main organs in the bicarbonate-carbonic acid buffer system?
A
lung and kidney
14
Q
what is the role of the lung in the bicarbonate buffer system?
A
CO2 handling through changed in ventilation, sensed by changes in pH
15
Q
How do the lungs increase or decrease pH?
A
increase exhalation of CO2 in response to decrease in pH
decrease in exhalation in response to increased pH
16
Q
what is the role of kidneys in the bicarbonate buffer system?
A
bicarbonate handling through secretion/excretion and reabsorption, regeneration
17
Q
How long do the lungs and kidneys take to respond to changes in pH?
A
lungs= rapid, within minutes kidneys= longer, days
18
Q
what are the three non-bicarbonate buffers?
A
proteins
phosphates
ammonia
19
Q
Where does the non-bicarbonate buffer system takes place? (5)
A
intracellular interstitium cerebrospinal fluid renal tubular filtrate plasma (intravascular)
20
Q
Are membranes more permeable to ionized or non-ionized forms of drugs?
A
non-ionized
21
Q
what are the characteristics of the non-ionized form of a drug? (2)
A
lipid soluble and no electric charges
22
Q
what three things does ionization depend on?
A
whether the drug is a weak acid or weak base
the pKa of the drug
the pH of the medium on either side of the membrane
23
Q
what is the definition of pKa?
A
the pH of the medium at which the dissolved drug is 50% ionized and 50% non-ionized
24
Q
what is the henderson & hasselbalch equation used for?
A
to determine the degree of ionization of the drug based on the pH of the environment
25
what is the definition of absorption of drug?
the transfer of the drug from the site of administration to the systemic circulation
26
Factors affecting drug absorption related to the drug (6)
```
molecular size
lipid solubility
degree of ionization
dissolution in water
concentration at absorptive site
route of administration
```
27
factors affecting drug absorption related to the animal? (5)
```
blood flow
absorptive surface area
connective tissue
species
individual
```
28
how the molecular size of the drug a factor of absorption?
the smaller the molecular size, the faster is penetration through the cell membrane pores
29
how is lipid solubility of a drug a factor of absorption?
the greater the lipid solubility, the greater ability to dissolve in lipid bilayer portion of cell membrane
increase in lipid solubility= increased absorption
30
how is degree of ionization of a drug a factor in absorption?
the more non-ionized the trug, the greater the absorption
| the more ionized the drug, the less absorption will take place
31
how is dissolution of drug in water a factor in absorption?
oral absorption of liquid drugs is faster than solid drugs
| oral absorption of solid drugs depends on their rate of dissolution
32
how is the concentration of the drug at absorptive site a factor in absorption?
the higher the concentration, the faster the absorption
33
how is route of administration a factor in absorption?
inhalation> sublingual>im>sq>enteral
34
how is blood flow a factor of absorption?
absorption of a drug from a particular site is related to blood flow to that site. increased blood flow- increased drug absorption
35
what three factors can modify blood flow?
drugs
physological factors
disease
36
what can increase flood flow and absorption?
heat or massage of intramuscular injection site
37
what are the two simulations related to flood flow?
sympathetic-fight or flight
| parasympathetic- rest and digest
38
what parts of the body increase/decrease blood flow during sympathetic stimulation?
increases skeletal muscles
| decrease GI tract and subcutaneous tissue
39
what parts of the body increase/decrease blood flow during parasympathetic stimulation?
decrease skeletal muscles
| increase GI tract
40
how is absorbing surface area a factor in drug absorption?
the greater the area available, the more efficiently absorption will occur
41
how is connective tissue a factor in drug absorption?
presence of connective tissue will decrease absorption
42
what is the main site of absorption for eternally administered drugs, why and what does it depend on?
the upper part of the small intestines
extensive surface area and rich blood supply
rate of absorption depends on rate of gastric emptying
43
what two factors can modify the rate of gastric emptying, and how?
drugs and disease
| affect blood flow, affect GI activity, other material in GI tract can absorb drug particles
44
what is the rate-limiting step for oral absorption?
dissolution- drugs must disintegrate before they can dissolve and be absorbed
45
what is the first-pass effect?
drugs absorbed from GI tract and distribute first to the liver for metabolism
some drugs will be metabolized before distribution to other tissues
high first pass metabolism= less distribution
46
definition of distribution of drugs
the transport of drugs from the plasma to the tissues (site of action, site of storage, site of metabolism, site of excretion)
47
what are the 5 factors related to the drug that affect drug distribution?
```
lipid solubility
degree of ionization
concentration gradient
plasma protein binding
affinity for certain issues
```
48
what are the 4 factors related to the animal that affect drug distribution?
blood flow
species/individual differences
plasma protein binding
tissue barriers
49
acidic/basic drugs bind to what proteins int he plasma?
acid- albumin
| basic- acid alpha-glycoproteins and lipoproteins
50
Some drugs bind to what in the plasma?
globulins (hormones, steroids)
51
is plasma protein binding reversible or irreversible?
reversible
52
how does plasma protein binding affect the half-life of the drug?
prolongs the half-life= how long the drug stays around in the bloodstream
53
what state is the drug when it is bound?
inactive- can't be distributed, metabolized or excreted by glomerular filtration
54
what does the rate of binding depend on?
the amount of drug
55
what can binding be modified by?
the disease- decreased protein or changes in the binding affinity
56
what does drug competing for the same binding site result in?
displacement of one of the drugs= increase the amount of free drug in circulation.
the drug may cause potentiation of another drug and can lead to toxicity
57
what is the rate of tissue perfusion relative to the mass of the tissue affect?
distribution of drug to that tissue?
58
what are 5 highly perfused tissues?
```
brain
liver
kidney
glands
heart
```
59
what are 2 moderately perfused tissues?
muscle
| skin
60
what are 2 poorly perfused tissues?
bone
| adipose tissue
61
what are three factors that can alter blood flow and how?
physiologic factors- stress (fight or flight)
drugs- vasosonstriction/ vasodialation)
disease- reduced blood flow to liver/kidney, blood clot
62
what are 7 parts of the body with unique tissue barriers to drug movement?
```
brain
eye
testicles
placental
mammary gland
prostate
synovial joints
```
63
what are the 4 properties of the Blood-brain barrier?
comprised of tight capillary endothelial junctions
further sealed off by glial cells
active transport mechanisms for removal of organic acids or bases
constant flow of CSF into venous drainage (flushing)
64
what are two categories of factors affecting the BBB
age
| physiological features
65
how does age affect the BBB
younger= greater drug movement due to incomplete BBB
66
what are 5 examples of physiological factors that affect the BBB
```
inflammation
allergic reaction
severe hypotension or hypoxia
high doses of organic solvents
high doses or heavy metals
```
67
definition of redistribution of drugs
the movement of drugs from the tissues back to the bloodstream, and sometimes to other tissues
68
definition of metabolism of drugs
the chamical alteration of the drug molecule by the cells of the animal
69
what are the two main effects of drug biotransformation?
change in physicochemical properties of the drug
| change in pharmacologic activity
70
what is the change in physicochemical properties of the drug?
the metabolite may be more water soluble, more polar and more ionized
71
what are the two types of change in pharmacologic activity?
bioinactivation (detoxification)
| bioactivation
72
what is bioinactivation?
conversion of a parent drug to an inactive metabolite
73
what are two examples of bioactivation?
conversion of a prodrug into an active drug
| conversion of a non-toxic substance to a toxic one (lethal synthesis)
74
what is the main site of biotransformation, and where can it occur in (6)?
liver
| smooth ER, hepatocyte cytoplasm, mitochondria, lysosomes, nuclear envelope, plasma membrane
75
what other tissues can be the site of biotransformation? (7)
nervous tissue, kidney, GI epithelium, lungs, skin, plasma
76
What do enzymes lack for hepatic drug metabolism, and what are the enzymes called (2)?
specificity
| microsomal enzymes, cytochrome P450
77
what kind of reactions are enzymatic reactions and how can enzymes be affected by other drugs?
saturable reactions
drugs can compete for the same enzyme
enzymes can be induced or inhibited
78
what 4 types pf reactions does microsomal enzymes cause?
oxidation, reduction, hydrolysis, conjugation to glucuronic acid
79
what are the two categories of metabolic reactions, and what are examples of their reactions?
phase 1 reactions (nonsynthetic)= oxidation, reduction, hydrolysis
phase 2 reaction (synthetic)= conjugation
80
what are cats deficient in?
phase 2 glucoronidation
81
definition of oxidation
the loss of one or more electrons by a substance (gain O2 or remove H)
82
definition of reduction
the gain of one or more electrons by a substance (gain H or remove O2)
83
definition of hydrolysis
the splitting of a molecule into fragments by the addition of water
84
what is the most common biotransformation reaction?
oxidation
85
what are two types of oxidation reactions, and where do they occur?
microsomal in SER
| non-microsomal in cytoplasm or mitochondria
86
definition of conjugation reactions
combination of a drug or its metabolite with an endogenour substance
87
where is conjugation deficient?
neonate and lacking in cats
88
what are three characteristics of metabolite conjugates?
inactive, water soluble, and non-toxic
89
what is the most common example of conjugation?
glucuronic acid (glucuronidation)- microsomal
90
species differences in metabolism of drugs (6)
cats are deficient in glucuronyl transferases
dogs deficient in acetylating enzymes
ruminants have less plasma pseudocholinesterase
ruminants and horses have high levels of oxidative enzymes
pigs are deficient in sulfate conjugating enzymes
birds lack oxidative enzymes
91
what are the criteria and result of hepatic first-pass metabolism?
criteria: drug must go to liver before systemic circulation and be metabolized, must have a high hepatic extraction ratio
result: decrease in oral bioavailability
92
definition of enzyme inducer
drugs that stimulate the liver to produce more metabolic enzymes
93
is enzyme induction reversible or irreversible and what does it lead to?
reversible
| may lead to tolerance or drug-drug interactions
94
what are 5 examples of drug enzyme inducers?
```
phebobarbital,
phenybutazone,
griseofulvin,
rifampin
chlorinated hydrocarbon insecticides
```
95
definition of enzyme inhibitor?
drugs that inhibit liver production of metabolic enzymes
96
what can enzyme inhibition lead to and what are 3 examples of inhibitors?
may lead to drug-drug interactions
chloramphenicol
cimetidine
ketoconazole
97
how does distribution and storage affect metabolism of drugs?
decreased distribution= decreased metabolism
| increased storage= decreased metabolism
98
definition of excretion of drugs
the removal or clearance of the drug from the body
99
what are 9 routes of drug excretion?
```
renal
hepatic and biliary
feces
milk
semen
sweat
saliva
hair/feathers
expired air
```
100
what 3 things does renal excretion depend on and what does the sum of them equal?
glomerlular filtration rate (GFR)
active tubular secretion
passive tubular reabsorption
sum= total renal excretion
101
what are the 4 factors affecting glomerular filtration?
GFR- blood pressure
molecular size small= filtered
molecular charge pos charger= filtered
plasma protein binding- unbound= filtered
102
what are the three factors affecting active tubular secretion?
proximal convoluted tubule (PCT)
organic cation transporters (OTCs)
organic antion transporters (OATs)
103
what are 6 factors affecting passive tubular reabsorption?
proximal and distal convoluted tubules (PCT & DCT)
physochemical properties of the drug
degree of ionization
acidification of the urine pH enhances renal excretion of basic drugs
Alkinization of urine excreted acidic drugs
fluid therapy and diuretics
104
what is the second most important organ for excretion of drugs?
liver
105
what is enterohepatic recirculation and what does it do to the half-life of a drug?
conjugates lipophilic compounds excreted in bile can be hydrolyzed in the intestines, then converts them back into lipid soluble free drug, which can be reabsorbed in the intestines
prolongs the half-life
106
what are other routes of drug excretion? (6)
```
feces
milk
semen
saliva
eggs
expired air
```
107
what is the definition of pharmacokinetics?
the mathematical description of the plasma concentration-time course
108
what is the clinical importance of pharmacokinetics and what are 4 factors with it?
Dosage regimen
| dosage, route of administration, frequency, duration of administration
109
what are the 3 factors for optimal dosage regimen?
effective
nontoxic
without prolonged drug residues in the tissues of food animals
110
what is the definition of systemic bioavailabilty?
the fraction of the dose which reaches the systemic circulation intact (%F)
111
what is the concept of compartments and what are the 4 compartments?
tissues and organs for which the rates of uptake and subsequent clearance of a drug are similar
blood, tissue, fat, 3rd spaces
112
what is the one-compartment model
all tissues and organs which the drug penetrates behave as if they were in ready equilibrium with the blood
113
what is the two-compartment model and what are the two compartments?
the log curve is a biphasic with a distribution phase and an elimination phase
central and peripheral compartment
114
what is the rate of distribution estimated by?
the distribution phase half-time in the two compartment model
115
what is the extent of distribution measured by?
apparent volume of distribution
116
what is the definition of volume of distribution?
the volume of fluid which would be required to contain the amount of drug in the body if it were uniformly distributed, and the concentration i that fluid was equal to the concentration in the plasma
117
what does a small Vd imply?
the drug is not being distributed to all tissues of the body- remain mostly in the plasma
118
what does a large Vd imply?
the drug is preferentially distributed somewhere outside of the bloodstream (more than one compartment)
119
how is drug elimination measured?
by half-life of total body clearance
120
what is the definition of half-life?
the time required for the body to eliminate 1/2 of the drug it contains
121
elimination of most drugs follow what?
1st order kinetics
122
what is 1st order kinetics?
the rate of removal of the drug from the plasma is proportional to the concentration present at a given time
constant percentage of drug is eliminated per unit time
123
what is zero-order kinetics?
the rate of elimination remains constant regardless of the amount of drug in the body
a constant amount of drug is eliminated per unit time
124
what are 2 examples of drugs that follow zero-order kinetics?
aspirin in cats
| phenybutazone in dogs and horses
125
how many half-lives does it take to almost completely eliminate a drug?
5
126
what is steady state concentration?
the plasma concentration of drug when the maintenance rate of drug administration is equal to the rate of elimination
127
definition of plasma clearance
the volume of plasma cleared of the drug per unit time
128
definition of renal clearance
the volume of plasma cleared of the drug by the kidneys per unit time
129
definition of total body clearance
rate of drug elimination from the body, by all routes, relative to the concentration of the drug in plasma
130
what is the relationship between total body clearance with Vd and with Half-life?
inc Vd= dec clearance
| inc Half-life = dec clearance
131
definition of extraction ratio
the fraction of the drug removed from the perfused body by an organ
132
What is the meaning of the extraction ration when it is 0 and when it is 1?
```
0= no drug is taken out
1= all the drug is taken out
```
133
what are 4 drug examples that have high hepatic extraction ratio, and what happens if these drugs are given orally?
```
lidocane
propaholol
diazepam
nitroglycerin
these drugs will have high first-pass metaboilsm
```
